Shenyang Medical College

Cancer stem cells (CSCs) are a subpopulation of tumor cells that possess unique self-renewal activity and mediate tumor initiation and propagation. The PI3K/Akt/mTOR signaling pathway can be considered as a master regulator for cancer. More and more recent studies have shown the links between PI3K/Akt/mTOR signaling pathway and CSC biology. Herein, we provide a comprehensive review on the role of signaling components upstream and downstream of PI3K/Akt/mTOR signaling in CSC. In addition, we also summarize various classes of small molecule inhibitors of PI3K/Akt/mTOR signaling pathway and their clinical potential in CSC. Overall, the current available data suggest that the PI3K/Akt/mTOR signaling pathway could be a promising target for development of CSC-target drugs.

Although intradendritic protein synthesis has been documented in adult neurons, the question of whether axons actively synthesize proteins remains controversial. Adult sensory neurons that are conditioned by axonal crush can rapidly extend processes in vitro by regulating the translation of existing mRNAs (Twiss et al., 2000). These regenerating processes contain axonal but not dendritic proteins. Here we show that these axonal processes of adult sensory neurons cultured after conditioning injury contain ribosomal proteins, translational initiation factors, and rRNA. Pure preparations of regenerating axons separated from the DRG cell bodies can actively synthesize proteins in vitro and contain ribosome-bound beta-actin and neurofilament mRNAs. Blocking protein synthesis in these regenerating sensory axons causes a rapid retraction of their growth cones when communication with the cell body is blocked by axotomy or colchicine treatment. These findings indicate that axons of adult mammalian neurons can synthesize proteins and suggest that, under some circumstances, intra-axonal translation contributes to structural integrity of the growth cone in regenerating axons. By immunofluorescence, translation factors, ribosomal proteins, and rRNA were also detected in motor axons of ventral spinal roots analyzed after 7 d in vivo after a peripheral axonal crush injury. Thus, adult motor neurons are also likely capable of intra-axonal protein synthesis in vivo after axonal injury.

Chemokines, which have chemotactic abilities, are comprised of a family of small cytokines with 8-10 kilodaltons. Chemokines work in immune cells by trafficking and regulating cell proliferation, migration, activation, differentiation, and homing. CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1, also known as CXCL12), which has been found to be expressed in more than 23 different types of cancers. Recently, the SDF-1/CXCR-4 signaling pathway has emerged as a potential therapeutic target for human tumor because of its critical role in tumor initiation and progression by activating multiple signaling pathways, such as ERK1/2, ras, p38 MAPK, PLC/ MAPK, and SAPK/ JNK, as well as regulating cancer stem cells. CXCL12/CXCR4 antagonists have been produced, which have shown encouraging results in anti-cancer activity. Here, we provide a brief overview of the CXCL12/CXCR4 axis as a molecular target for cancer treatment. We also review the potential utility of targeting CXCL12/CXCR4 axis in combination of immunotherapy and/or chemotherapy based on up-to-date literature and ongoing research progress.

Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

Ultraviolet (UV) irradiation induces excessive accumulations of elastic fibers in animal and human skin. Collagen is damaged and glycosaminoglycans are vastly increased. Formerly considered an irreversible change, we recently showed, post-irradiation, that a band of normal connective tissue was laid down subepidermally . Because of its ability to stimulate fibroblasts and enhance healing of wounds, we thought it likely that retinoic acid (RA) would promote the formation of this subepidermal zone of reconstruction. Hairless mice were irradiated for 10 weeks with Westinghouse FS20 sunlamps for a total UV dose of 7 J/cm2. Then, 0.05% RA was applied for 5 and 10 weeks. Observations were made by light and electron microscopy. In contrast to controls treated with vehicle, the reconstruction zone was significantly wider in RA-treated mice. The enhanced repair was dose related. Histochemically and ultrastructurally, collagen was normal, fibroblasts were numerous and in a configuration of high metabolic activity.

Antibody-drug conjugates (ADCs) represent a novel class of biopharmaceuticals comprising monoclonal antibodies covalently conjugated to cytotoxic agents via engineered chemical linkers. This combination enables targeted delivery of cytotoxic agents to tumor site through recognizing target antigens by antibody while minimizing off-target effects on healthy tissues. Clinically, ADCs overcome the limitations of traditional chemotherapy, which lacks target specificity, and enhance the therapeutic efficacy of monoclonal antibodies, providing higher efficacy and fewer toxicity anti-tumor biopharmaceuticals. ADCs have ushered in a new era of targeted cancer therapy, with 15 drugs currently approved for clinical use. Additionally, ADCs are being investigated as potential therapeutic candidates for autoimmune diseases, persistent bacterial infections, and other challenging indications. Despite their therapeutic benefits, the development and application of ADCs face significant challenges, including antibody immunogenicity, linker instability, and inadequate control over the release of cytotoxic agent. How can ADCs be designed to be safer and more efficient? What is the future development direction of ADCs? This review provides a comprehensive overview of ADCs, summarizing the structural and functional characteristics of the three core components, antibody, linker, and payload. Furthermore, we systematically assess the advancements and challenges associated with the 15 approved ADCs in cancer therapy, while also exploring the future directions and ongoing challenges. We hope that this work will provide valuable insights into the design and optimization of next-generation ADCs for wider clinical applications.

This is a meta-analysis of the pooled prevalence of sleep disturbances and its associated factors in Chinese university students. English (PubMed, PsycINFO, Embase) and Chinese (SinoMed, Wan Fang Database and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from inception until 16 August 2016. The prevalence of sleep disturbances was pooled using random-effects model. Altogether 76 studies involving 112 939 university students were included. The overall pooled prevalence of sleep disturbances was 25.7% (95% CI: 22.5-28.9%). When using the screening scales Pittsburgh Sleep Quality Index, Athens Insomnia Scale and Self-Rating Sleeping State Scale, and the diagnostic criteria of the Chinese Classification of Mental Disorders (Second Edition), the pooled prevalence of sleep disturbances was 24.1% (95% CI: 21.0-27.5%) and 18.1% (95% CI: 16.4-20.0%), respectively. The percentages of students dissatisfied with sleep quality and those suffering from insomnia symptoms were 20.3% (95% CI: 13.0-30.3%) and 23.6% (95% CI: 18.9-29.0%), respectively. Subgroup analyses revealed that medical students were more vulnerable to sleep disturbances than other student groups. There was no significant difference between males and females, and across geographic locations. Sleep disturbances are common in Chinese university students. Appropriate strategies for prevention and treatment of sleep disturbances in this population need greater attention.

BACKGROUND: Improvement of quality of life has been one of goals in health care for people living with bladder cancer. Meanwhile, positive psycho-social variables in oncology field have increasingly received attention. However, the assessment of quality of life of bladder cancer patients and the integrative effects of positive psycho-social variables has limited reporting. The aim of this study was to assess quality of life as well as the integrative effects of social support, hope and resilience on quality of life among Chinese bladder cancer patients. METHODS: A cross-sectional study was conducted at the First Hospital of China Medical University in Liaoning Province, China. A total of 365 bladder cancer patients eligible for this study completed questionnaires on demographic variables, FACT-BL, Perceived Social Support Scale, Adult Hope Scale, and Resilience Scale-14 during July 2013 to July 2014. RESULTS: The average score of FACT-BL was 87.60 ± 16.27 (Mean ± SD). Hierarchical regression analyses indicated that social support, hope and resilience as a whole accounted for 30.3 % variance of quality of life. Under standardized estimate (β) sequence, social support, hope and resilience significantly and positively associated with quality of life, respectively. CONCLUSIONS: Quality of life for bladder cancer patients was at a low level in China, which should receive more attention in Chinese medical institutions. More importantly, efforts to increase social support, hope and resilience might be useful to support the quality of life among Chinese bladder cancer patients.

Recent decades have witnessed the fast and impressive development of nanocarriers as a drug delivery system. Considering the safety, delivery efficiency and stability of nanocarriers, there are many obstacles in accomplishing successful clinical translation of these nanocarrier-based drug delivery systems. The gap has urged drug delivery scientists to develop innovative nanocarriers with high compatibility, stability and longer circulation time. Exosomes are nanometer-sized, lipid-bilayer-enclosed extracellular vesicles secreted by many types of cells. Exosomes serving as versatile drug vehicles have attracted increasing attention due to their inherent ability of shuttling proteins, lipids and genes among cells and their natural affinity to target cells. Attractive features of exosomes, such as nanoscopic size, low immunogenicity, high biocompatibility, encapsulation of various cargoes and the ability to overcome biological barriers, distinguish them from other nanocarriers. To date, exosome-based nanocarriers delivering small molecule drugs as well as bioactive macromolecules have been developed for the treatment of many prevalent and obstinate diseases including cancer, CNS disorders and some other degenerative diseases. Exosome-based nanocarriers have a huge prospect in overcoming many hindrances encountered in drug and gene delivery. This review highlights the advances as well as challenges of exosome-based nanocarriers as drug vehicles. Special focus has been placed on the advantages of exosomes in delivering various cargoes and in treating obstinate diseases, aiming to offer new insights for exploring exosomes in the field of drug delivery.

Using the presence or absence of 63 variable restriction endonuclease (RE) sites selected from 225 sites with six REs, genomic polymorphism of 242 herpes simplex virus type 1 (HSV-1) strains from six countries (Japan, Korea, China, Sweden, U.S.A. and Kenya) was quantitatively analysed. Twenty-five of the 63 sites were found to differ between Korean and Kenyan strains. In contrast, only three and six sites were found to differ between isolates from Sweden and the U.S.A. and between those from Korea and China, respectively, suggesting that they are closely related to each other. In this way, characterization of 63 sites enabled us to categorize 186 distinct HSV-1 genotypes from 242 individuals. Some strains from Japan, Korea and China shared the same genotypes, indicating that they are phylogenetically closely related. Many significant correlation coefficients (magnitude of > 0.42; P < 0.01) between pairs of sites were found in isolates from the three Asian countries (Japan, Korea and China) as well as in those from Sweden and the U.S.A., suggesting that HSV-1 strains from within the same ethnic groups are evolutionarily closer. The average number of nucleotide substitutions per nucleotide, as defined by nucleotide diversity (pi), was estimated for HSV-1 genomes within (pi x or pi y) and between (pi xy) countries. On the basis of 225 sites, nucleotide diversity for Kenyan isolates was 0.0056, almost three times higher than that for Korean isolates, implying that Kenyan HSV-1 genomes are much more diverse than those from Korea. In addition, the diversity between HSV-1 isolates from different countries (pi xy) was highest between isolates from the three Asian countries and Kenya (0.0075 to 0.0081) and lowest among those from the three Asian countries (0.0032 to 0.0040). The mutation rate (lambda) for HSV-1 was estimated to be 3.5 x 10(-8)/site/year. All these findings show that the evolution of HSV-1 may be host-dependent and very slow.

BACKGROUND: College life represents a key transitional period in the life of young adults that is marked by increased social engagement; living habits acquired during this period have implications on the future life of college students. Therefore, investigation of the determinants of health status of college students is a key imperative; however, there is limited evidence on the study of concomitant effects of physical activity (PA), sedentary time (ST), and sleep duration on the health-related quality of life (HRQOL) of college students. METHODS: This cross-sectional survey was conducted at a medical university in Shenyang in Northeast China in 2017. The study group comprised 926 undergraduate students. Data were collected by a self-administered questionnaire. PA, ST, sleep duration, and HRQOL were measured using the international physical activity questionnaire (IPAQ)-Long Form and the Chinese version of the 12-Item Short-Form Health Survey (SF-12). The association of PA, ST, and sleep duration with the HRQOL was examined using independent t-test, Pearson Chi-squared test, and multivariate linear regression analysis. RESULTS: After adjusting for potential confounding factors, students who reported high PA had significantly higher physical component summary (PCS) score in the total study population and among female students than those who reported low PA, whereas students who reported moderate PA had significantly higher PCS score only among female students (P < 0.05). In the total study population and among male students, students who slept for ≥9 h/day had significantly higher mental component summary (MCS) score than those who slept for 7-< 8 h/day, whereas among only male students, those who slept for 8-< 9 h/day had significantly higher MCS score (P < 0.05). The interaction term between ST and PA was not statistically significant. CONCLUSIONS: PA and sufficient sleep duration had a positive impact on the HRQOL of college students; however, ST was not associated with HRQOL and there was no interaction between the impact of ST and PA on the HRQOL of college students. Increasing PA and promoting adequate sleep duration are key health promotion strategies for college students.

BACKGROUND AND PURPOSE: Information has been sparse on the comparison of pulse pressure (PP) and mean arterial pressure (MAP) in relation to ischemic stroke among patients with uncontrolled hypertension. The present study examined the relation among PP, MAP, and ischemic stroke in uncontrolled hypertensive subjects in China. METHODS: A total of 6104 uncontrolled hypertensive subjects aged > or = 35 years were screened with a stratified cluster multistage sampling scheme in Fuxin county of Liaoning province of China, of which 317 had ischemic stroke. RESULTS: After multivariable adjustment for age, gender, and other confounders, individuals with the highest quartile of PP and MAP had ORs for ischemic stroke of 1.479 (95% CI: 1.027 to 2.130) and 2.000 (95% CI: 1.373 to 2.914) with the lowest quartile as the reference. Adjusted ORs for ischemic stroke were 1.306 for MAP and 1.118 for PP with an increment of 1 SD, respectively. Ischemic stroke prediction of PP was annihilated when PP and MAP were entered in a single model. In patients aged < 65 years, on a continuous scale using receive operating characteristics curve, ischemic stroke was predicted by PP (P=0.001) and MAP (P<0.001). The area under the curve of PP (0.570, 95% CI: 0.531 to 0.609) differed from the area under the curve of MAP (0.633, 95% CI: 0.597 to 0.669; P<0.05). Among patients aged > or = 65 years, presence of ischemic stroke was only predicted by MAP. CONCLUSIONS: PP and MAP were both associated with ischemic stroke. Ischemic stroke prediction of PP depended on MAP. On a continuous scale, MAP better predicted ischemic stroke than PP did in diagnostic accuracy.

The production of metrnl, a novel adipomyokine, is induced upon exercise in adipose tissue and skeletal muscle. In this study, we investigated the anti-inflammatory and antipyroptotic effects of exercise-induced metrnl producted in rats in vitro and in vivo. Forty Sprague-Dawley rats were divided randomly into five groups: control (CG), osteoarthritis (OA) with sedentary lifestyle (OAG), OA with low intensity exercise (OAL), OA with moderate intensity exercise (OAM), and OA with high intensity exercise (OAH). The correlation between the level of metrnl and OA degree was detected using ELISA, X-ray imaging, histology, and immunohistochemistry in vivo. Primary chondrocytes were preincubated with recombinant metrnl before interleukin-1β administration to verify the anti-inflammatory and antipyroptotic effects of metrnl. Western blotting and quantitative reverse transcription (qRT)-PCR were used to evaluate the differences in protein and mRNA expression between groups, respectively. Reactive oxygen species (ROS) assay, immunofluorescence, transmission electron microscopy (TEM), and flow cytometry were used to evaluate morphological changes and pyroptosis in chondrocytes. In the moderate-intensity treadmill exercise group, the severity of OA showed maximum relief and the metrnl levels had the most significant increase. Metrnl exerted its anti-inflammatory effect through the suppression of the PI3K/Akt/NF-κB pathway in IL-1β-induced OA chondrocytes, which was accompanied with the recovery of collagen II expression and the attenuation of MMP13 and ADAMTS5. Moreover, metrnl ameliorated chondrocyte pyroptosis by inhibiting the activation of the nod-like receptor protein-3/caspase-1/gasdermin D cascade. In conclusion, moderate-intensity exercise improves inflammation and pyroptosis by increasing metrnl release, which inhibits the PI3K/Akt/NF-κB and further NLRP3/caspase-1/GSDMD signaling pathways.

BACKGROUND: Hypoxic tumor microenvironment and maintenance of stemness contribute to drug resistance in breast cancer. However, whether Hypoxia-inducible factor-2α (HIF-2α) in hypoxic tumor microenvironment mediates conversion to a stem cell phenotype and chemoresistance of breast tumors has not been elucidated. METHODS: The mRNA and protein expressions of HIF-1α, HIF-2α, Wnt and Notch pathway were determined using qRT-PCR and western blot. Cell viability and renew ability were assessed by MTT, Flow cytometric analysis and soft agar colony formation. RESULTS: In our study, acute hypoxia (6-12 h) briefly increased HIF-1α expression, while chronic hypoxia (48 h) continuously enhanced HIF-2α expression and induced the resistance of breast cancer cells to Paclitaxel (PTX). Furthermore, HIF-2α overexpression induced a stem cell phenotype, the resistance to PTX and enhanced protein expression of stem cell markers, c-Myc, OCT4 and Nanog. Most importantly, Wnt and Notch signaling, but not including Shh, pathways were both activated by HIF-2α overexpression. Dickkopf-1 (DKK-1), a Wnt pathway inhibitor, and L685,458, an inhibitor of the Notch pathway, reversed the resistance to PTX and stem phenotype conversion induced by HIF-2α overexpression. In addition, HIF-2α overexpression enhanced tumorigenicity and resistance of xenograft tumors to PTX, increased activation of the Wnt and Notch pathways and induced a stem cell phenotype in vivo. CONCLUSION: In conclusion, HIF-2α promoted stem phenotype conversion and induced resistance to PTX by activating Wnt and Notch pathways.

BACKGROUND: Depression is a major public health problem that affects both individuals and society. Previous studies report that university teachers are particularly susceptible to high levels of occupational stress and depressive symptoms. The aims of this study were to explore the association between occupational stress and depressive symptoms in a group of university teachers, and assess the mediating role of psychological capital between these variables. METHODS: A cross-sectional study was performed between November 2013 and January 2014. Teachers from six universities were randomly sampled in Shenyang. The Center for Epidemiologic Studies Depression Scale, effort-reward imbalance scale, and psychological capital questionnaire (PCQ-24), as well as questions about demographic and working factors, were administered in questionnaires distributed to 1,500 university teachers. Completed questionnaires were received from 1,210 participants. Hierarchical linear regression analysis was used to examine the mediating role of psychological capital. RESULTS: In the present study, 58.9% (95% CI (Confidence Intervals): 56.1% to 61.7%) of university teachers had a CES-D score equal to or above the cut-off of 16. Both effort-reward ratio (ERR) and scores of over-commitment were positively associated with depressive symptoms, whereas psychological capital was negatively associated with depressive symptoms among university teachers. Psychological capital partially mediated the relationship between occupational stress and depressive symptoms. CONCLUSIONS: Among Chinese university teachers, occupational stress may be a risk factor for depressive symptoms, whereas psychological capital might be protective against depressive symptoms. Our results suggest that college administrators could support the development of psychological capital in their staff to alleviate depressive symptoms.

Abstract In addition to genomic mutations, RNA editing is another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editing contributes to different types of human diseases, including cancers. Here we report that peptides generated as a consequence of RNA editing are indeed naturally presented by human leukocyte antigen (HLA) molecules. We provide evidence that effector CD8 + T cells specific for edited peptides derived from cyclin I are present in human tumours and attack tumour cells that are presenting these epitopes. We show that subpopulations of cancer patients have increased peptide levels and that levels of edited RNA correlate with peptide copy numbers. These findings demonstrate that RNA editing extends the classes of HLA presented self-antigens and that these antigens can be recognised by the immune system.

BACKGROUND: Infertility-related stress can seriously impact the fertility quality of life (QoL) of infertile women. Resilience, as a coping resource, can effectively combat psychological stress. This study aimed to evaluate the fertility QoL of infertile women and to examine whether resilience moderates the association of infertility-related stress with fertility QoL. METHODS: This cross-sectional study was conducted in northeast of China from December 2017 to February 2018. Out of 559 women outpatients with infertility, 498 (89.1%) completed self-reported questionnaires including the FertiQoL Scale, Fertility Problem Inventory (FPI) and Connor-Davidson Resilience Scale (CD-RISC). Hierarchical multiple regression analysis and simple slope analysis were applied to explore the influencing factors related to fertility QoL as well as to examine the moderating effect of resilience on the association of infertility-related stress with fertility QoL. RESULTS: The mean FertiQoL score was 64.54 ± 16.90 among the participants. Household monthly income and causes of infertility were significantly related to fertility QoL. In addition, infertility-related stress was negatively related to fertility QoL, and resilience was positively associated with fertility QoL, explaining 36.3% of the variance. Resilience moderated the association of infertility-related stress with fertility QoL. Specifically, the effect of infertility-related stress on fertility QoL varied by low(1 SD below the mean, B = - 0.496, β = - 0.714, P < 0.001), mean (B = - 0.293, β = - 0.422, P < 0.001) and high (1 SD above the mean, B = - 0.090, β = - 0.130, P < 0.001) levels of resilience. The higher resilience was, the weaker the effect of infertility-related stress on fertility QoL was. CONCLUSIONS: Overall, women with infertility in China had relatively low FertiQoL scores. Resilience influenced the association of infertility-related stress with fertility QoL. Infertile patients' psychological status must be addressed and adequate resilience-based interventions such as mindfulness-based skills should be provided to improve fertility QoL of women with infertility.

BACKGROUND: Maternal body mass index is linked to short- and long-term unfavorable health outcomes both for child and mother. We conducted a systematic review and meta-analysis of population-based cohort studies to evaluate maternal BMI and the risk of harmful neonatal outcomes in China. METHODS: Six databases identified 2454 articles; 46 met the inclusion criteria for this study. The dichotomous data on maternal BMI and harmful neonatal outcomes were extracted. Pooled statistics (odds ratios, ORs) were derived from Stata/SE, ver. 12.0. Sensitivity analyses assessed the robustness of the results. Meta-regression and subgroup meta-analyses explored heterogeneity. RESULTS: The meta-analysis revealed that compared with normal BMI, high maternal BMI is associated with fetal overgrowth, defined as macrosomia ≥4000 g (OR 1.91, 95% CI 1.75-2.09); birth weight ≥ 90% for gestational age (OR 1.88, 95% CI 1.64-2.15); and increased risk of premature birth (OR 1.38, 95% CI 1.25-2.52) and neonatal asphyxia (OR 1.74, 95% CI 1.39-2.17). Maternal underweight increased the risk of low birth weight (OR 1.61, 95% CI 1.33-1.93) and small for gestational age (OR 1.75, 95% CI 1.51-2.02). CONCLUSIONS: Raised as well as low pre-pregnancy BMI is associated with adverse neonatal outcomes. Management of weight during pregnancy might help reduce their adverse neonatal outcomes in future intervention studies or programmes.

Photocatalytic hydrogen (H2) evolution is an appealing and promising means for productive solar-to-chemical energy conversion. g-C3N4(CN) is an exciting semiconductor, but its undesirable pristine activity seriously limited the potential for large-scale application. Herein, we, for the first time, demonstrated that the low-cost nickel boride (Ni3B)/nickel hydroxide (Ni(OH)2) is an ecofriendly hybrid cocatalyst for remarkably boosting visible-light H2 evolution over CN. The maximum H2 evolution rate of CN–3%Ni3B–2%Ni(OH)2 reaches 352.43 μmol g–1 h–1, with an apparent quantum efficiency of 0.70% at 405 nm, which is much higher than that of pure CN, only 0.1 μmol g–1 h–1. In the cycling experiment, the ternary CN–3%Ni3B–2%Ni(OH)2 shows relatively high stability in the triethanolamine solution. More importantly, the promoted charge separation and reduced overpotential were demonstrated to be responsible for the significantly boosted visible-light H2 generation over CN nanosheet-based photocatalysts due to the loading of Ni3B/Ni(OH)2 cocatalyst. It is believed that this study will provide a suitable strategy to rationally design a low-cost, facile-fabrication, and ecofriendly cocatalyst for efficient visible-light hydrogen evolution of CN nanosheet-based photocatalysts.

Abstract Purpose: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. Experimental Design: To characterize the immune microenvironment in HCC, IHC staining was performed for CD8-positive T lymphocytes, PD-1–positive, and LAG-3–positive lymphocytes, CD163-positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. Results: Expression of CD8 was reduced in tumor, and expression of CD163 was reduced at the tumor interface. Positive clusters of PD-L1 expression were identified in 24 of 29 cases (83%), and positive expression of LAG-3 on tumor-infiltrating lymphocytes was identified in 19 of 29 cases (65%). The expression of both PD-L1 and LAG-3 was increased in tumor relative to liver background. No association between viral status or other clinicopathologic features and expression of any of the IHC markers investigated was noted. Conclusions: LAG-3 and PD-L1, two inhibitory molecules implicated in CD8 T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC. Clin Cancer Res; 23(23); 7333–9. ©2017 AACR.