Chungnam National University

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

<h3>Importance</h3> Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. <h3>Objective</h3> To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. <h3>Evidence Review</h3> We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. <h3>Findings</h3> In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). <h3>Conclusions and Relevance</h3> The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

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.

Oilseed rape (Brassica napus L.) was formed ~7500 years ago by hybridization between B. rapa and B. oleracea, followed by chromosome doubling, a process known as allopolyploidy. Together with more ancient polyploidizations, this conferred an aggregate 72× genome multiplication since the origin of angiosperms and high gene content. We examined the B. napus genome and the consequences of its recent duplication. The constituent An and Cn subgenomes are engaged in subtle structural, functional, and epigenetic cross-talk, with abundant homeologous exchanges. Incipient gene loss and expression divergence have begun. Selection in B. napus oilseed types has accelerated the loss of glucosinolate genes, while preserving expansion of oil biosynthesis genes. These processes provide insights into allopolyploid evolution and its relationship with crop domestication and improvement.

The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All of the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 deg2 of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include the measured abundances of 15 different elements for each star. In total, SDSS-III added 5200 deg2 of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 deg2; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Melanogenesis is a process to synthesize melanin, which is a primary responsible for the pigmentation of human skin, eye and hair. Although numerous enzymatic catalyzed and chemical reactions are involved in melanogenesis process, the enzymes such as tyrosinase and tyrosinase-related protein-1 (TRP-1) and TRP-2 played a major role in melanin synthesis. Specifically, tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin synthesis, and the downregulation of tyrosinase is the most prominent approach for the development of melanogenesis inhibitors. Therefore, numerous inhibitors that target tyrosinase have been developed in recent years. The review focuses on the recent discovery of tyrosinase inhibitors that are directly involved in the inhibition of tyrosinase catalytic activity and functionality from all sources, including laboratory synthetic methods, natural products, virtual screening and structure-based molecular docking studies.

Among the recent developments in metal-organic frameworks (MOFs), porous layered coordination polymers (CPs) have garnered attention due to their modular nature and tunable structures. These factors enable a number of properties and applications, including gas and guest sorption, storage and separation of gases and small molecules, catalysis, luminescence, sensing, magnetism, and energy storage and conversion. Among MOFs, two-dimensional (2D) compounds are also known as 2D CPs or 2D MOFs. Since the discovery of graphene in 2004, 2D materials have also been widely studied. Several 2D MOFs are suitable for exfoliation as ultrathin nanosheets similar to graphene and other 2D materials, making these layered structures useful and unique for various technological applications. Furthermore, these layered structures have fascinating topological networks and entanglements. This review provides an overview of different aspects of 2D MOF layered architectures such as topology, interpenetration, structural transformations, properties, and applications.

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star–black hole mergers. We infer the binary neutron star merger rate to be between 10 and <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:mn>1700</a:mn><a:mtext> </a:mtext><a:mtext> </a:mtext><a:msup><a:mrow><a:mi>Gpc</a:mi></a:mrow><a:mrow><a:mo>−</a:mo><a:mn>3</a:mn></a:mrow></a:msup><a:mtext> </a:mtext><a:msup><a:mrow><a:mi>yr</a:mi></a:mrow><a:mrow><a:mo>−</a:mo><a:mn>1</a:mn></a:mrow></a:msup></a:mrow></a:math> and the neutron star–black hole merger rate to be between 7.8 and <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mrow><c:mn>140</c:mn><c:mtext> </c:mtext><c:mtext> </c:mtext><c:msup><c:mrow><c:mi>Gpc</c:mi></c:mrow><c:mrow><c:mo>−</c:mo><c:mn>3</c:mn></c:mrow></c:msup><c:mtext> </c:mtext><c:msup><c:mrow><c:mi>yr</c:mi></c:mrow><c:mrow><c:mo>−</c:mo><c:mn>1</c:mn></c:mrow></c:msup></c:mrow></c:math>, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" display="inline"><e:mrow><e:mn>44</e:mn><e:mtext> </e:mtext><e:mtext> </e:mtext><e:msup><e:mrow><e:mi>Gpc</e:mi></e:mrow><e:mrow><e:mo>−</e:mo><e:mn>3</e:mn></e:mrow></e:msup><e:mtext> </e:mtext><e:msup><e:mrow><e:mi>yr</e:mi></e:mrow><e:mrow><e:mo>−</e:mo><e:mn>1</e:mn></e:mrow></e:msup></e:mrow></e:math> at a fiducial redshift (<g:math xmlns:g="http://www.w3.org/1998/Math/MathML" display="inline"><g:mi>z</g:mi><g:mo>=</g:mo><g:mn>0.2</g:mn></g:math>). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" display="inline"><i:mo stretchy="false">(</i:mo><i:mn>1</i:mn><i:mo>+</i:mo><i:mi>z</i:mi><i:msup><i:mo stretchy="false">)</i:mo><i:mi>κ</i:mi></i:msup></i:math> with <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" display="inline"><m:mi>κ</m:mi><m:mo>=</m:mo><m:mn>2.</m:mn><m:msubsup><m:mn>9</m:mn><m:mrow><m:mo>−</m:mo><m:mn>1.8</m:mn></m:mrow><m:mrow><m:mo>+</m:mo><m:mn>1.7</m:mn></m:mrow></m:msubsup></m:math> for <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" display="inline"><o:mi>z</o:mi><o:mo>≲</o:mo><o:mn>1</o:mn></o:math>. Using both binary neutron star and neutron star–black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" display="inline"><q:msubsup><q:mn>1.2</q:mn><q:mrow><q:mo>−</q:mo><q:mn>0.2</q:mn></q:mrow><q:mrow><q:mo>+</q:mo><q:mn>0.1</q:mn></q:mrow></q:msubsup></q:math> to <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" display="inline"><s:msubsup><s:mn>2.0</s:mn><s:mrow><s:mo>−</s:mo><s:mn>0.3</s:mn></s:mrow><s:mrow><s:mo>+</s:mo><s:mn>0.3</s:mn></s:mrow></s:msubsup><s:msub><s:mi>M</s:mi><s:mo stretchy="false">⊙</s:mo></s:msub></s:math>. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of <v:math xmlns:v="http://www.w3.org/1998/Math/MathML" display="inline"><v:msubsup><v:mn>8.3</v:mn><v:mrow><v:mo>−</v:mo><v:mn>0.5</v:mn></v:mrow><v:mrow><v:mo>+</v:mo><v:mn>0.3</v:mn></v:mrow></v:msubsup></v:math> and <x:math xmlns:x="http://www.w3.org/1998/Math/MathML" display="inline"><x:msubsup><x:mn>27.9</x:mn><x:mrow><x:mo>−</x:mo><x:mn>1.8</x:mn></x:mrow><x:mrow><x:mo>+</x:mo><x:mn>1.9</x:mn></x:mrow></x:msubsup><x:msub><x:mi>M</x:mi><x:mo stretchy="false">⊙</x:mo></x:msub></x:math>. While we continue to find that the mass distribution of a binary’s more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately <ab:math xmlns:ab="http://www.w3.org/1998/Math/MathML" display="inline"><ab:mn>60</ab:mn><ab:msub><ab:mi>M</ab:mi><ab:mo stretchy="false">⊙</ab:mo></ab:msub></ab:math>, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below <db:math xmlns:db="http://www.w3.org/1998/Math/MathML" display="inline"><db:msub><db:mi>χ</db:mi><db:mi>i</db:mi></db:msub><db:mo>≈</db:mo><db:mn>0.25</db:mn></db:math>. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum. Published by the American Physical Society 2023

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and triggering of pyroptosis, which is of paramount importance in a variety of physiological and pathological conditions. Over the past decade, considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing (Signal 1) and assembly (Signal 2) involved in NLRP3 inflammasome activation. Recently, a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels. In this review, we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions, posttranslational modifications, and spatiotemporal regulation of the NLRP3 inflammasome machinery. We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly. A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.

Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 (10-15%) fatalities in 2003. The causative agent of SARS has been identified as a novel human coronavirus (SARS-CoV), and its viral protease, SARS-CoV 3CL(pro), has been shown to be essential for replication and has hence been recognized as a potent drug target for SARS infection. Currently, there is no effective treatment for this epidemic despite the intensive research that has been undertaken since 2003 (over 3500 publications). This perspective focuses on the status of various efficacious anti-SARS-CoV 3CL(pro) chemotherapies discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, natural products, and virtual screening. We describe here mainly peptidomimetic and small molecule inhibitors of SARS-CoV 3CL(pro). Attempts have been made to provide a complete description of the structural features and binding modes of these inhibitors under many conditions.

We present images, integrated photometry, surface-brightness and color profiles for a total of 1034 nearby galaxies recently observed by the GALEX satellite in its far-ultraviolet (FUV; 1516A) and near-ultraviolet (NUV; 2267A) bands. (...) This data set has been complemented with archival optical, near-infrared, and far-infrared fluxes and colors. We find that the integrated (FUV-K) color provides robust discrimination between elliptical and spiral/irregular galaxies and also among spiral galaxies of different sub-types. Elliptical galaxies with brighter K-band luminosities (i.e. more massive) are redder in (NUV-K) color but bluer in (FUV-NUV) than less massive ellipticals. In the case of the spiral/irregular galaxies our analysis shows the presence of a relatively tight correlation between the (FUV-NUV) color and the total infrared-to-UV ratio. The correlation found between (FUV-NUV) color and K-band luminosity (with lower luminosity objects being bluer than more luminous ones) can be explained as due to an increase in the dust content with galaxy luminosity. The images in this Atlas along with the profiles and integrated properties are publicly available through a dedicated web page at http://nedwww.ipac.caltech.edu/level5/GALEX_Atlas/

Despite the recent attention focused on the roles of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of type 2 diabetes, little is known about the ex vivo profile of inflammasome activation in type 2 diabetic patients. In this study, we investigated patterns of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) from drug-naïve patients with newly diagnosed type 2 diabetes. Type 2 diabetic subjects had significantly increased mRNA and protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and proinflammatory cytokines in MDMs cultured with autologous sera compared with healthy controls. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals). Mitochondrial reactive oxygen species and NLRP3 were required for IL-1β synthesis in MDMs. Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1β in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation. Taken together, these data suggest that NLRP3 inflammasome activation is elevated in myeloid cells from type 2 diabetic patients and that antidiabetic treatment with metformin contributes to modulation of inflammasome activation in type 2 diabetes.

Studies of bone and the immune system have converged in recent years under the banner of osteoimmunology. The immune system is spawned in the bone marrow reservoir, and investigators now recognize that important niches also exist there for memory lymphocytes. At the same time, various factors produced during immune responses are capable of profoundly affecting regulation of bone. Mechanisms have evolved to prevent excessive interference by the immune system with bone homeostasis, yet pathologic bone loss is a common sequela associated with autoimmunity and cancer. There are also developmental links, or parallels, between bone and the immune system. Cells that regulate bone turnover share a common precursor with inflammatory immune cells and may restrict themselves anatomically, in part by utilizing a signaling network analogous to lymphocyte costimulation. Efforts are currently under way to further characterize how these two organ systems overlap and to develop therapeutic strategies that benefit from this understanding.

A capacitive deionization process utilizing flow-electrodes (FCDI) was designed and evaluated for use in seawater desalination. The FCDI cell exhibited excellent removal efficiency (95%) with respect to an aqueous NaCl solution (salt concentration: 32.1 g L−1), demonstrating that the FCDI process could effectively overcome the limitations of typical CDI processes.

Ensemble-averaged statistics at constant phase of the turbulent near-wake flow (Reynolds number ≈ 21400 around a square cylinder have been obtained from two-component laser-Doppler measurements. Phase was defined with reference to a signal taken from a pressure sensor located at the midpoint of a cylinder sidewall. The distinction is drawn between the near wake where the shed vortices are ‘mature’ and distinct and a base region where the vortices grow to maturity and are then shed. Differences in length and velocity scales and vortex celerities between the flow around a square cylinder and the more frequently studied flow around a circular cylinder are discussed. Scaling arguments based on the circulation discharged into the near wake are proposed to explain the differences. The relationship between flow topology and turbulence is also considered with vorticity saddles and streamline saddles being distinguished. While general agreement with previous studies of flow around a circular cylinder is found with regard to essential flow features in the near wake, some previously overlooked details are highlighted, e.g. the possibility of high Reynolds shear stresses in regions of peak vorticity, or asymmetries near the streamline saddle. The base region is examined in more detail than in previous studies, and vorticity saddles, zero-vorticity points, and streamline saddles are observed to differ in importance at different stages of the shedding process.

Long-chain unsaturated fatty acids, such as linoleic acid, show antibacterial activity and are the key ingredients of antimicrobial food additives and some antibacterial herbs. However, the precise mechanism for this antimicrobial activity remains unclear. We found that linoleic acid inhibited bacterial enoyl-acyl carrier protein reductase (FabI), an essential component of bacterial fatty acid synthesis, which has served as a promising target for antibacterial drugs. Additional unsaturated fatty acids including palmitoleic acid, oleic acid, linolenic acid, and arachidonic acid also exhibited the inhibition of FabI. However, neither the saturated form (stearic acid) nor the methyl ester of linoleic acid inhibited FabI. These FabI-inhibitory activities of various fatty acids and their derivatives very well correlated with the inhibition of fatty acid biosynthesis using [(14)C] acetate incorporation assay, and importantly, also correlated with antibacterial activity. Furthermore, the supplementation with exogenous fatty acids reversed the antibacterial effect of linoleic acid, which showing that it target fatty acid synthesis. Our data demonstrate for the first time that the antibacterial action of unsaturated fatty acids is mediated by the inhibition of fatty acid synthesis.

We report the observation of gravitational waves from two compact binary coalescences in LIGO's and Virgo's third observing run with properties consistent with neutron star-black hole (NSBH) binaries. The two events are named GW200105_162426 and GW200115_042309, abbreviated as GW200105 and GW200115; the first was observed by LIGO Livingston and Virgo and the second by all three LIGO-Virgo detectors. The source of GW200105 has component masses, whereas the source of GW200115 has component masses and (all measurements quoted at the 90% credible level). The probability that the secondary's mass is below the maximal mass of a neutron star is 89%-96% and 87%-98%, respectively, for GW200105 and GW200115, with the ranges arising from different astrophysical assumptions. The source luminosity distances are and, respectively. The magnitude of the primary spin of GW200105 is less than 0.23 at the 90% credible level, and its orientation is unconstrained. For GW200115, the primary spin has a negative spin projection onto the orbital angular momentum at 88% probability. We are unable to constrain the spin or tidal deformation of the secondary component for either event. We infer an NSBH merger rate density of when assuming that GW200105 and GW200115 are representative of the NSBH population or under the assumption of a broader distribution of component masses. © 2021. The Author(s). Published by the American Astronomical Society.

During viral infection, virus-derived cytosolic nucleic acids are recognized by host intracellular specific sensors. The efficacy of this recognition system is crucial for triggering innate host defenses, which then stimulate more specific adaptive immune responses against the virus. Recent studies show that signal transduction pathways activated by sensing proteins are positively or negatively regulated by many modulators to maintain host immune homeostasis. However, viruses have evolved several strategies to counteract/evade host immune reactions. These systems involve viral proteins that interact with host sensor proteins and prevent them from detecting the viral genome or from initiating immune signaling. In this review, we discuss key regulators of cytosolic sensor proteins and viral proteins based on experimental evidence.