Nanjing Medical University

Autophagy is an important intracellular degradative process that delivers cytoplasmic proteins to lysosome for degradation. Dysfunction of autophagy is implicated in several human diseases, such as neurodegenerative diseases, infectious diseases, and cancers. Autophagy-related proteins are constitutively expressed in the eye. Increasing studies have revealed that abnormal autophagy is an important pathological feature of several ocular diseases. Pharmacological manipulation of autophagy may provide an alternative therapeutic target for some ocular diseases. In this manuscript, we reviewed the relevant progress about the role of autophagy in the pathogenesis of ocular diseases.

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

OBJECTIVE: To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China. METHODS: Nationwide case series of 2135 pediatric patients with COVID-19 reported to the Chinese Center for Disease Control and Prevention from January 16, 2020, to February 8, 2020, were included. The epidemic curves were constructed by key dates of disease onset and case diagnosis. Onset-to-diagnosis curves were constructed by fitting a log-normal distribution to data on both onset and diagnosis dates. RESULTS: There were 728 (34.1%) laboratory-confirmed cases and 1407 (65.9%) suspected cases. The median age of all patients was 7 years (interquartile range: 2-13 years), and 1208 case patients (56.6%) were boys. More than 90% of all patients had asymptomatic, mild, or moderate cases. The median time from illness onset to diagnoses was 2 days (range: 0-42 days). There was a rapid increase of disease at the early stage of the epidemic, and then there was a gradual and steady decrease. The disease rapidly spread from Hubei province to surrounding provinces over time. More children were infected in Hubei province than any other province. CONCLUSIONS: Children of all ages appeared susceptible to COVID-19, and there was no significant sex difference. Although clinical manifestations of children's COVID-19 cases were generally less severe than those of adult patients, young children, particularly infants, were vulnerable to infection. The distribution of children's COVID-19 cases varied with time and space, and most of the cases were concentrated in Hubei province and surrounding areas. Furthermore, this study provides strong evidence of human-to-human transmission.

BACKGROUND/AIMS: There is little published data on the role of FOXP3 in gastric cancer. METHODS: FOXP3 expression and localization in gastric cancer tissues and cells were examined by immunohistochemistry, RT-PCR, flow cytometry, western blot, and laser confocal microscopy. CCK8, plate clone, wound healing, and transwell insert assays were performed for gastric cancer cells. Potential molecules and signaling pathways were screened using high-throughput transcriptome sequencing. RESULTS: FOXP3 expression in gastric cancer tissues was higher than that in para-carcinoma tissues. It was restricted to the cytoplasm of para-carcinoma tissues, but was observed in the cytoplasm or/and nuclei of gastric cancer tissues. FOXP3 expression was positively correlated with pathological grading, and was detected in gastric cancer and GES-1 cells, where it was expressed in the cytoplasm alone, or in both the cytoplasm and the nucleus. FOXP3 overexpression promoted cell proliferation, migration, and invasion, while FOXP3 knockdown suppressed these effects. Furthermore, RT-PCR and ELISA confirmed that FOXP3 upregulation resulted in increased TGF-β expression and secretion in gastric cancer cells. CONCLUSION: FOXP3 expression was associated with degree of gastric cancer differentiation. In addition, upregulated and ectopic tumoral FOXP3 can promote gastric cancer proliferation, migration, and invasion, partly through the TGF-β pathway.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and found that serotonin receptor 5-HT2A is the sole molecular target for feeding inhibition by metitepine. These results highlight the conservation of molecular mechanisms controlling appetite and provide a method for unbiased whole-organism drug screens to identify novel drugs and molecular pathways modulating food intake.

AIM: Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy. METHODS: Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms. RESULTS: Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux. CONCLUSION: Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.

BACKGROUND: Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. METHODS: After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. RESULTS: Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. CONCLUSIONS: Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

BACKGROUND: Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD. SUBJECT AND METHOD: 932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores. RESULT: The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p = <0.001), miR-155 (OR, 1.520; 95 % CI, 1.132-2.042, p = 0.005), and miR-130a (OR, 1.943; 95% CI, 1.410-2.678, p = <0.001) were potential risk factors for CHD. Moreover, miR-130a (OR, 2.405; 95 % CI, 1.691-3.421, p = <0.001) remained independently associated with the risk of CHD after adjusting for potential confounding factors. The analysis of the possible positive/negative associations between miR-221, miR-155 and miR-130awere conducted. A positive association between miR-130a and miR-155 was found (SI = 1.60, SIM = 1.21 and AP = 0.22), and in these groups, the proportion of CHD attributable to the interaction between miR-130a and miR-155 was as high as 22 %. A negative interaction was found between miR-221 and miR-130a (SI = 0.68, SIM = 0.60 and AP = 0.27). CONCLUSION: Plasma levels of miR-221, miR-130a and miR-155 decreased in patients with CHD, and miR-130a may be an independent predictor for CHD.

Blood-brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates the pharmacotherapy for CNS disorders as the most chemical drugs and biopharmaceuticals have been impeded to enter the brain. Insufficient drug delivery into the brain leads to low therapeutic efficacy as well as aggravated side effects due to the accumulation in other organs and tissues. Recent breakthrough in materials science and nanotechnology provides a library of advanced materials with customized structure and property serving as a powerful toolkit for targeted drug delivery. In-depth research in the field of anatomical and pathological study on brain and BBB further facilitates the development of brain-targeted strategies for enhanced BBB crossing. In this review, the physiological structure and different cells contributing to this barrier are summarized. Various emerging strategies for permeability regulation and BBB crossing including passive transcytosis, intranasal administration, ligands conjugation, membrane coating, stimuli-triggered BBB disruption, and other strategies to overcome BBB obstacle are highlighted. Versatile drug delivery systems ranging from organic, inorganic, and biologics-derived materials with their synthesis procedures and unique physio-chemical properties are summarized and analyzed. This review aims to provide an up-to-date and comprehensive guideline for researchers in diverse fields, offering perspectives on further development of brain-targeted drug delivery system.

Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. The application and development of hybrid nanoparticles, which incorporates the combined properties of different nanoparticles, has led this type of drug-carrier system to the next level. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. In this review, we discuss the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.

This article updates the guidance published in 2015 for authors submitting papers to British Journal of Pharmacology (Curtis et al., 2015) and is intended to provide the rubric for peer review. Thus, it is directed towards authors, reviewers and editors. Explanations for many of the requirements were outlined previously and are not restated here. The new guidelines are intended to replace those published previously. The guidelines have been simplified for ease of understanding by authors, to make it more straightforward for peer reviewers to check compliance and to facilitate the curation of the journal's efforts to improve standards.

Competing endogenous RNAs (ceRNAs) are transcripts that can regulate each other at post-transcription level by competing for shared miRNAs. CeRNA networks link the function of protein-coding mRNAs with that of non-coding RNAs such as microRNA, long non-coding RNA, pseudogenic RNA and circular RNA. Given that any transcripts harbouring miRNA response element can theoretically function as ceRNAs, they may represent a widespread form of post-transcriptional regulation of gene expression in both physiology and pathology. CeRNA activity is influenced by multiple factors such as the abundance and subcellular localisation of ceRNA components, binding affinity of miRNAs to their sponges, RNA editing, RNA secondary structures and RNA-binding proteins. Aberrations in these factors may deregulate ceRNA networks and thus lead to human diseases including cancer. In this review, we introduce the mechanisms and molecular bases of ceRNA networks, discuss their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay. At last, we discuss the limitations of current ceRNA theory, propose possible directions and envision the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets.

Ferroptosis is an intracellular iron-dependent form of cell death that is distinct from apoptosis, necrosis, and autophagy. Extensive studies suggest that ferroptosis plays a pivotal role in tumor suppression, thus providing new opportunities for cancer therapy. The development of resistance to cancer therapy remains a major challenge. A number of preclinical and clinical studies have focused on overcoming drug resistance. Intriguingly, ferroptosis has been correlated with cancer therapy resistance, and inducing ferroptosis has been demonstrated to reverse drug resistance. Herein, we provide a detailed description of the mechanisms of ferroptosis and the therapeutic role of regulating ferroptosis in reversing the resistance of cancer to common therapies, such as chemotherapy, targeted therapy and immunotherapy. We discuss the prospect and challenge of regulating ferroptosis as a therapeutic strategy for reversing cancer therapy resistance and expect that our review could provide some references for further studies.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991–2018. Across all study countries, we find that 37.0% (range 20.5–76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change. Current and future climate change is expected to impact human health, both indirectly and directly, through increasing temperatures. Climate change has already had an impact and is responsible for 37% of warm-season heat-related deaths between 1991 and 2018, with increases in mortality observed globally.

N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m6A-selective ‘reader’ proteins of the YTH family, which incorporate m6A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m6A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m6A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m6A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.

Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

The BJP has been and remains an active advocate of the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010a) that were established by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in 2010. The ARRIVE guidelines need no introduction and we will not rehearse the arguments in depth here, other than to restate that the lack of key in vivo experimental details has been identified as a major contributing factor to the poor reproducibility of pre-clinical research. This fact was the primary driver for establishment by the NC3Rs of the first version of the ARRIVE guidelines. ARRIVE provided a 20-point checklist, specifying all of the experimental details (procedures and fixed factors) that should be included in manuscripts for proper reporting of animal research. The guidelines were rapidly endorsed internationally by funding bodies, universities, learned societies and, importantly, Life Science journals. Currently there are 1,046 journals endorsing ARRIVE including BJP, which was one of the original six influential journals that published the guidelines in full in 2010 (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010b). However, ARRIVE has not had the effect that was originally hoped for, despite this widespread support and endorsement. In 2016 and in 2018 assessments of adherence of articles published in endorsing journals identified a lack of engagement. As an example, one systematic review of reports of studies investigating acute lung injury revealed that, of the items expected for ARRIVE compliance, only 45% of those advised for inclusion in the Methods, and only 29% of those for inclusion in the Results section, were present (Avey et al., 2016). Moreover, formal endorsement of the ARRIVE guidelines by journals did not necessarily improve compliance (Leung, Rousseau-Blass, Beauchamp, & Pang, 2018). Such disappointing reports of outcome triggered a reappraisal of the guidelines led by the NC3Rs who, in 2018, established a new, international Working Group to review and update the ARRIVE guidelines to generate ARRIVE 2.0 (Percie du Sert et al., 2018). As with the team of experts brought together to establish the first iteration of ARRIVE, the Editor in Chief of the BJP is a member of the new team that was assembled. As such, the BJP has been well-placed to influence the content, testing and final publication of both iterations of the guidelines. In 2015, the BJP published an editorial reporting findings from a survey of compliance with ARRIVE in articles published in 2014 in two issues of the journal (McGrath & Lilley, 2015). The results were not as had been hoped for, as was also evident from assessments elsewhere, and revealed scope for improving compliance in respect of both the design of the (animal) experiments and the description of experimental procedures. To help remedy this problem, a checklist was developed that provided an aide memoire of the details of the animals and research procedures that should be reported in manuscripts submitted to the journal. A further editorial focussed on experimental design and data analysis (Curtis et al., 2018) for all types of experimental data published in the journal, including those emanating from experiments with animals, was also published. A key issue with many of the studies reported in BJP prior to this related to inadequate experimental design and inappropriate statistical analysis. At the same time, the Instructions to Authors were revised, to include the new rubric, and the editorial scrutiny of these aspects of the peer review process was tightened up. As a further prompt, in 2016, authors were required to make a Declaration as part of the submission process, to confirm that their manuscript was ARRIVE compliant. In addition to these measures, two new 'specialist' editors were appointed: a Design & Analysis Advisor and a Consulting Editor in ARRIVE Guidelines and Animal Welfare. The brief of the latter was to monitor ARRIVE compliance in BJP publications and to assist Senior Editors with their appraisal of manuscripts. All these changes still remain in place with the addition of a Consulting Editor in Statistical Analysis to ensure that the research reports match BJP criteria and so qualify for publication. ARRIVE 2.0 together with an 'Explanation and Elaboration' document was loaded onto the NC3Rs website in July 2019 as a preprint (i.e., before peer review (Percie du Sert et al., 2019)), and is now published in full in PLOS Biology (Percie du Sert et al., 2020), with simultaneous publication in several international journals, including this issue of the BJP (Percie du Sert et al., 2020). In preparation for the publication of the new guidelines we conducted surveys assessing compliance to ARRIVE in the BJP over 4 years, the results of which can be seen in Table 1. These data together with the July 2019 preprint of ARRIVE 2.0 were discussed extensively by the Senior Editorial Board of the BJP in December 2019. This editorial explains the ensuing changes in the journal's editorial policy as a result of those discussions and how they relate to ARRIVE 2.0. The principle of full disclosure lies at the heart of what we expect from authors wishing to publish in the BJP and in support of this principle is the absence of a word restriction for the Methods section. Judging from articles surveyed, between July 2014 and October 2019, most authors are conscientious about compliance with our 'Instructions to Authors' in respect of confirming ethical approval of the research, specifying the source, species and strain of animals and the inclusion of a statement on the translational relevance of the research study (Table 1). However, a general observation is that, although many manuscripts include lengthy details of the molecular biological or biochemical techniques that were used in the study, when experiments involved the use of animals, both the design of experiments and the description of the experimental procedures are often inadequately detailed making reproducibility challenging. Reporting of the method for killing animals has improved over the years but is still inconsistent, despite the need for manuscripts to be clear about when and how animals were killed. Information on housing and husbandry is often provided but, again, the level of detail is highly variable. Important elements, such as stocking density, configuration of group-housed animals (in respect of littermates, genotypes, or randomised mixed-caging, for example) provision of food (including, ideally, the composition of the laboratory diet) and water and environmental enrichment are not always disclosed, despite increasing recognition that these factors can affect the research findings (Finney et al., 2020; Reardon, 2016). The poor reporting of the provision of analgesia in the surgical context is particularly worrying. Of course, a lack of any mention of analgesia in the manuscript does not mean that none was provided; there could also be a strong scientific justification for withholding analgesia in some experiments. However, that did not apply to any of the manuscripts that were reviewed: in all those cases, analgesia could and should have been provided. Two options were considered by the Senior Editorial Board in December 2019: (i) endorse ARRIVE 2.0 guidelines and adopt them verbatim as official BJP policy or (ii) endorse ARRIVE 2.0 but devise our own reporting policy, which would be particularly relevant for pharmacologists. In considering the results of our surveys and the content of the ARRIVE 2.0 preprint, the Board decided on the latter approach. Authors should be reassured that nothing major has changed in practice. This journal has always taken inspiration from ARRIVE, while adopting a 'bespoke' approach to the reporting of the types of animal research carried out by pharmacologists. Authors should also note that requirements in respect of experimental design and analysis in articles published in BJP have not changed at all and can be found at: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14153 (Curtis et al., 2018). That said, we strongly advise authors to use the NC3Rs Experimental Design Assistant (https://www.nc3rs.org.uk/experimental-design-assistant-eda) (Percie du Sert et al., 2017) when planning the experimental design and the data analysis of their work. The most striking change in the updated ARRIVE guidelines is the subdivision of the original checklist into two tables/checklists: the 'Essential 10' and the 'Recommended set'. The former focuses mainly on aspects of the experimental design that are essential for reducing bias (subjective or systematic), whereas the latter deals with points that pertain to the factors that authors are advised to disclose in order to enable others to replicate the experiment. Our current guidelines for experimental design and statistical analysis address many of the 'Essential 10', and for our modified approach we concentrate on many of the items in the 'Recommended set'. Our updated'BJP Declaration of Transparency and Scientific Rigour: Checklist for Animal Experimentation' is shown in Table 2, along with indicators of how each element connects with ARRIVE 2.0. These amendments do not challenge the importance of either version of ARRIVE. On the contrary, we strongly recommend that all authors read ARRIVE 2.0 (Percie du Sert, Hurst, et al., 2020) and familiarise themselves with the complementary 'Explanation and Elaboration' document (Percie du Sert et al., 2020). Essential 8 Essential 9 Recommended Recommended 12 Recommended 14 Recommended 15 Recommended 16 In terms of the details that should be included in every manuscript submitted to the BJP, the new checklist for reporting animal research will consist of the following six mandatory elements (see also Table 2): Details of the source, species, strain, sex, age and/or weight range of the animals used in the study must be given. A comprehensive account of the experimental procedure with particular attention to the use of any pharmacologically active agents at any stage of the study, including: anaesthesia, analgesia, antibiotics or any veterinary treatment administered for welfare purposes. Authors should also confirm that, for all surgical procedures, precautions to ensure aseptic conditions were applied throughout. Details of post-surgical analgesia and care of the animals should be provided, as should any procedures for monitoring the animals during post-operative recovery: e.g., the frequency and duration of the observations, temperature control etc. If analgesia cannot be given, this needs to be justified scientifically. A statement to confirm that the animals were killed by an individual trained to do this procedure, together with a description of how and when animals are killed, must also be included. In this context, authors should bear in mind that only certain methods for humane killing are permitted in the UK (and other countries governed by Directive 2010/63/EU) and these are stringently regulated. As a consequence, it might not be possible to consider a manuscript for publication in this journal if euthanasia has been carried out using a procedure that is regarded as unacceptable in the UK.One notable change to our policy is that whenever welfare assessments, or other precautions, were necessary during any stage of the research, these must now be reported, together with a clear definition of humane end-points. We acknowledge that these aspects of experimental conduct may well be implemented routinely in individual laboratories but, hitherto, they have not been perceived as an essential aspect of the research report. We want authors to include this information, as a matter of course, not least because other researchers in the field would find it important and helpful. Full details of the specific animal model that was used and the scientific justification for the choice of that model in the context of achieving the research objectives should be provided. This aspect of the report can be challenging, but we hope to encourage authors to be conservative and realistic when claiming to have used an animal 'model' of a complex human disorder (see next section). A statement to confirm that the research reported in the manuscript obtained local ethical approval is essential. BJP seeks to publish research on animals that conforms to standards upheld in the UK. Some elements should always be included, for example: type of housing, type of cage (open or individually ventilated) stocking density, food and water provision, bedding material, environmental enrichment, lighting regimen. For fish, details of the tank and the number of fish in each one should be included. Information on other elements should be included if they are crucial for the study or if they could affect the experimental results: e.g., the time of day the study took place, nature of handling/capture. The configuration of animals within cages should also be specified for instance, mixed or separate housing of genetically-altered/wildtypes or disease-susceptible/normal animals should be provided. Any welfare-related assessments, measurements and interventions that were carried out before, during, or after the study, especially if these were intended to ameliorate or limit the harms to the animals (e.g., humane end-points) must be reported. Another change is that both ARRIVE 2.0 and our revised BJP Declaration have removed the obligation to report any advance in the 3Rs (Replacement, Reduction and Refinement) that has emerged from the research. This is partly because compliance with this has been negligible. Nevertheless, the BJP Senior Editorial Board recognises the importance of the 3Rs as part of the ethical framework for all research that uses animals and so we encourage authors to include this information whenever their findings have made a useful contribution to any of the 3Rs. The ARRIVE 2.0 guidelines are certainly viewed as an important step in helping to address the problem of poor reproducibility and translation of research findings in the biomedical sciences. However, successful translation also depends on a sound rationale for the research. So far, the attempts to improve reproducibility have somewhat overshadowed the growing scepticism about the validity of 'animal models' of some human disorders. In many cases, the creation of an animal model in order to carry out experiments, which would not be permitted in humans, is an entirely reasonable objective. That would be the case for human disorders that have an established link with a single genetic abnormality, such as cystic fibrosis, Down syndrome and hypertrophic cardiomyopathy. Even in cases where a specific genetic mutation is a common, but not invariable, cause of the disorder (e.g., Fragile X syndrome, amyotrophic lateral sclerosis), it is still reasonable to back-translate the mutation to create an animal model to investigate the underlying biological abnormalities and potential treatments. Few people would argue that those research findings are not instructive or that the description of the animal as a 'model' of the human disorder is scientifically unjustified. Even when there is no such clear causal link, it is valid to describe an animal as a 'model' when it expresses an abnormality that is convincingly analogous to the diagnostic biomarker(s) in humans. Examples of these would include: neoplasia, Cushing's/Addison's disease, diabetes, skin pigmentation diseases, myasthenia gravis. Even though treatment strategies that are effective in the animals often do not translate into humans, it is still reasonable to regard them as 'models' of the human condition and such research has contributed a great deal to our understanding of the illnesses. It is far more difficult to be confident about the validity of animal models of complex, multifactorial human illnesses, which can comprise a mixture of any of several pathological, physiological and behavioural abnormalities, which can be primary or secondary features of the illness. These would include conditions such as: hypertension, heart failure, renal failure, metabolic syndrome, neurological and psychiatric disorders. In all these cases, the profile and/or severity of the underlying problems can differ substantially from patient to patient, but still meet the criteria for the same broad clinical diagnosis. In such cases, we hope to encourage authors to be more cautious about claims that their 'animal model' is analogous to the human condition. This is especially important for 'models' that are based on evidence from procedures that are normally used as drug screens to predict therapeutic efficacy in humans (see, for example: Stanford, 2017). In such cases, authors should justify their assumption that the abnormality that is being evaluated in the baseline condition (i.e, with no experimental intervention such as drug treatment or genetic alteration) is a valid model of the human illness or a particular aspects of that illness. On the other hand, we want to discourage non-committal descriptions such as 'cirrhosis-like', 'epilepsy-like' or 'autism-like', or vague terms, such as 'asthma' instead of 'respiratory allergy'. Instead, our aim is to encourage authors to be precise about the extent to which aspect(s) of the human disorder are expressed in the animal model, and also to acknowledge its limitations. Where these questions have been very well analysed for any particular model, it is appropriate for authors to cite the relevant literature explaining why the animal model is appropriate. We believe this is timely advice because there is burgeoning interest in research of 'endophenotypes' in which a specific aspect of an animal's normal/abnormal physiology or behaviour can be mapped onto an underlying genetic mutation or physiological system (e.g., neuronal network, or other physiological feedback loop) – and which are often not confined to a single human disorder. This approach further acknowledges that some human illnesses are better regarded as assemblies of endophenotypes, rather than unitary disorders. Obviously, the definition of an endophenotype also needs scrupulous validation, but this change of mindset will be essential for successful progress in stratified and personalised medicine. A final point, addressed only indirectly by ARRIVE 2.0, concerns the validity of some research procedures that are used to produce the 'model' (see: Stanford, 2020). Examples include some experimental interventions to induce end-stage heart failure, or the use of environmental stressors that are intended to alter the physiology and/or behaviour of the animals. Examples include the use of environmental stressors, such as electric shocks or a series of unpredictable stressors that change from day to day, sometimes for several weeks. In most cases, the individual stressors are mild and can arguably be regarded as analogous to challenges faced by some humans and which impair their mental health, but this is not always the case. Some of these experiments involve prolonged bouts of stressors, which would be regarded as severe, especially when their cumulative harm is taken into account. In such cases, the BJP will require authors to provide assurance that the severity and duration of the aversive stimuli was the minimum required to meet the scientific objectives of the study, particularly when using a series of unpredictable stressors, for instance. Also, in order to underpin the validity of such animal 'models', authors should include a statement to clarify the ways in which the aversive stimuli used in the research are relevant to the manifestation of the disorder of interest, which is being modelled in the animals. In response to the publication of the revised ARRIVE guidelines (ARRIVE 2.0), the Senior Editorial Board of this journal has revised the policy on reporting of animal research. The primary principle remains the same as before, which is to encourage full disclosure of all relevant information and to expect to see evidence for high standards of animal welfare. It is important to remember that this is not simply for the benefit of the animals. High standards of experimental design, reporting and animal welfare are crucial if the research is to be reproducible and translatable. In that context, we encourage authors to read Drummond and Vowler (2013). The BJP has, for some time, taken the view that the prevailing standards expected by the regulatory framework in the UK should be reflected in the journal's publications. For example, studies of proprietary tobacco products are not permitted in the UK and the BJP will not publish them. Similarly, death as an endpoint, in non-regulatory studies would not normally be acceptable (with the exception of studies of anti-cancer and certain antimicrobial drugs, for example), but when current regulatory guidelines still mandate mortality endpoints, we expect humane endpoints to be described fully and implemented. Some experiments that involve procedures that would be regarded as 'severe' but can, nonetheless, be scientifically justified. However, the justification for some such procedures might not be clear. In most of these cases, a discussion between the editor(s) and the authors would seek to confirm whether or not there was a robust justification for using such procedures, or humane endpoints, regardless of any local ethical approval for the study. If this turns out to be the case, the manuscript may be published. Finally, raising the standard of research reporting will certainly help to improve reproducibility but, to improve translation will also require a more realistic, evidence-based appraisal of the validity of the experimental procedures and research 'models'. To that end, we want to encourage authors to consider the extent to which the models they have investigated really do offer insight into the causes, pathology and treatment of multifactorial human disorders. In cases where there is any doubt, authors should be assured that more modest objectives and clarity about the specific features of the disorder that have been 'modelled' would attract even more confidence and scientific merit. The authors declare no conflicts of interest.

Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1β. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. Hence, we provided an overview of morphological and molecular characteristics of pyroptosis. We also focus on mechanism of regulating pyroptosis in tumor cells as well as the potential roles of pyroptosis in cancer to explore potential diagnostic markers in cancers contributing to the prevention and treatment in cancers.