Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Recent progress in SERS monitoring of photocatalytic reactions.

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique renowned for its ultra-high sensitivity. Extensive research in SERS has led to the development of a wide range of SERS substrates, including plasmonic metals, semiconductors, metal organic frameworks, and their assemblies. Some of these materials are also excellent photocatalysts, and by taking advantage of their bifunctional characteristics, the photocatalytic processes that occur on their surface can be monitored in situ via SERS. This provides us with unique opportunities to gain valuable insights into the intricate details of the photocatalytic processes that are challenging to access using other techniques. In this review, we highlight key development in in situ and/or real-time SERS-tracking of photocatalytic reactions. We begin by providing a brief account of recent developments in SERS substrates, followed by discussions on how SERS can be used to elucidate crucial aspects of photocatalytic processes, including: (1) the influence of the surrounding media on charge carrier extraction; (2) the direction of charge carrier transfer; (3) the pathway of photocatalytic activation; and (4) differentiation between the effects of photo-thermal and energetic electrons. Additionally, we discuss the benefits of tip-enhanced Raman spectroscopy (TERS) due to the ability to achieve high-spatial-resolution measurements. Finally, we address major challenges and propose potential directions for the future of SERS monitoring of photocatalytic reactions. By leveraging the capabilities of SERS, we can uncover new insights into photocatalytic processes, paving the way for advancements in sustainable energy and environmental remediation.

Engineering Spatially Adjacent Redox Sites with Synergistic Spin Polarization Effect to Boost Photocatalytic CO2 Methanation.

The integration of oxidation and reduction half-reactions to amplify their synergy presents a considerable challenge in CO2 photoconversion. Addressing this challenge requires the construction of spatially adjacent redox sites while suppressing charge recombination at these sites. This study introduces an innovative approach that utilizes spatial synergy to enable synergistic redox reactions within atomic proximity and employs spin polarization to inhibit charge recombination. We incorporate Mn into Co3O4 as a catalyst, in which Mn sites tend to enrich holes as water activation sites, while adjacent Co sites preferentially capture electrons to activate CO2, forming a spatial synergy. The direct H transfer from H2O at Mn sites facilitates the formation of *COOH on adjacent Co sites with remarkably favorable thermodynamic energy. Notably, the incorporation of Mn induces spin polarization in the system, significantly suppressing the recombination of photogenerated charges at redox sites. This effect is further enhanced by applying an external magnetic field. By synergizing spatial synergy and spin polarization, Mn/Co3O4 exhibits a CH4 production rate of 23.4 µmol g-1 h-1 from CO2 photoreduction, showcasing a 28.8 times enhancement over Co3O4. This study first introduces spin polarization to address charge recombination issues at spatially adjacent redox sites, offering novel insights for synergistic redox photocatalytic systems.

SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic Nanomaterials.

ConspectusWhen the size of materials is reduced, their volume decreases much faster than their surface area, which in the most extreme case leads to 2D nanomaterials which are "all surface". Since atoms at the surface have free energies, electronic states, and mobility which are very different from bulk atoms, nanomaterials that have large surface-to-volume ratios can display remarkable new properties compared to their bulk counterparts. More generally, the surface is where nanomaterials interact with their environment, which in turn places surface chemistry at the heart of catalysis, nanotechnology, and sensing applications. Understanding and utilizing nanosurfaces are not possible without appropriate spectroscopic and microscopic characterization techniques. An emerging technique in this area is surface-enhanced Raman spectroscopy (SERS), which utilizes the interaction between plasmonic nanoparticles and light to enhance the Raman signals of molecules near the nanoparticles' surfaces. SERS has the great advantage that it can provide detailed in situ information on surface orientation and binding between molecules and the nanosurface. A long-standing dilemma that has limited the applications of SERS in surface chemistry studies is the choice between surface-accessibility and plasmonic activity. More specifically, the synthesis of metal nanomaterials with strong plasmonic and SERS-enhancing properties typically involves the use of strongly adsorbing modifier molecules, but these modifiers also passivate the surface of the product material, which prevents the general application of SERS in the analysis of weaker molecule-metal interactions.In this Account, we discuss our efforts in the development of modifier-free synthetic approaches to synthesize surface-accessible, plasmonic nanomaterials for SERS. We start by discussing the definition of "modifiers" and "surface-accessibility", especially in the context of surface chemistry studies in SERS. As a general rule of thumb, the chemical ligands on surface-accessible nanomaterials should be easily displaceable by a wide range of target molecules relevant to potential applications. We then introduce modifier-free approaches for the bottom-up synthesis of colloidal nanoparticles, which are the basic building blocks for nanotechnology. Following this, we introduce modifier-free interfacial self-assembly approaches developed by our group that allow the creation of multidimensional plasmonic nanoparticle arrays from different types of nanoparticle-building blocks. These multidimensional arrays can be further combined with different types of functional materials to form surface-accessible multifunctional hybrid plasmonic materials. Finally, we demonstrate applications for surface-accessible nanomaterials as plasmonic substrates for SERS studies of surface chemistry. Importantly, our studies revealed that the removal of modifiers led to not only significantly enhanced properties but also the observation of new surface chemistry phenomena that had been previously overlooked or misunderstood in the literature. Realizing the current limitations of modifier-based approaches provides new perspectives in manipulating molecule-metal interactions in nanotechnology and can have significant implications in the design and synthesis of the next generation of nanomaterials.

Environmental and economic concerns surrounding restrictions on glyphosate use in corn.

Since the commercialization of transgenic glyphosate-tolerant (GT) crops in the mid-1990s, glyphosate has become the dominant herbicide to control weeds in corn, soybean, and other crops in the United States and elsewhere. However, recent public concerns over its potential carcinogenicity in humans have generated calls for glyphosate-restricting policies. Should a policy to restrict glyphosate use, such as a glyphosate tax, be implemented? The decision involves two types of tradeoffs: human health and environmental (HH-E) impacts versus market economic impacts, and the use of glyphosate versus alternative herbicides, where the alternatives potentially have more serious adverse HH-E effects. Accounting for farmers' weed management choices, we provide empirical evaluation of the HH-E welfare and market economic welfare effects of a glyphosate use restriction policy on US corn production. Under a glyphosate tax, farmers would substitute glyphosate for a combination of other herbicides. Should a 10% glyphosate tax be imposed, then the most conservative welfare estimate is a net HH-E welfare gain with a monetized value of US$6 million per annum but also a net market economic loss of US$98 million per annum in the United States, which translates into a net loss in social welfare. This result of overall welfare loss is robust to a wide range of tax rates considered, from 10 to 50%, and to multiple scenarios of glyphosate's HH-E effects, which are the primary sources of uncertainties about glyphosate's effects.

SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

Comparative analysis of SARS-CoV-2 Omicron BA.2.12.1 and BA.5.2 variants.

The initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BA.1 and BA.2, are being progressively displaced by BA.5 in many countries. To provide insight on the replacement of BA.2 by BA.5 as the dominant SARS-CoV-2 variant, we performed a comparative analysis of Omicron BA.2.12.1 and BA.5.2 variants in cell culture and hamster models. We found that BA.5.2 exhibited enhanced replicative kinetics over BA.2.12.1 in vitro and in vivo, which is evidenced by the dominant BA.5.2 viral genome detected at different time points, regardless of immune selection pressure with vaccine-induced serum antibodies. Utilizing reverse genetics, we constructed a mutant SARS-CoV-2 carrying spike F486V substitution, which is an uncharacterized mutation that concurrently discriminates Omicron BA.5.2 from BA.2.12.1 variant. We noticed that the 486th residue does not confer viral replication advantage to the virus. We also found that 486V displayed generally reduced immune evasion capacity when compared with its predecessor, 486F. However, the surge of fitness in BA.5.2 over BA.2.12.1 was not due to stand-alone F486V substitution but as a result of the combination of multiple mutations. Our study upholds the urgency for continuous monitoring of SARS-CoV-2 Omicron variants with enhanced replication fitness.

LED lighting area recognition for visible light positioning based on convolutional neural network in the industrial internet of things.

In the industrial environment, the positioning of mobile terminals plays an important role in production scheduling. Visible light positioning (VLP) based on a CMOS image sensor has been widely considered as a promising indoor positioning technology. However, the existing VLP technology still faces many challenges, such as modulation and decoding schemes, and strict synchronization requirements. In this paper, a visible light area recognition framework based on convolutional neural network (CNN) is proposed, where the training data is the LED images acquired by the image sensor. The mobile terminal positioning can be realized from the perspective of recognition without modulating LED. The experimental results show that the mean accuracy of the optimal CNN model is as high as 100% for the two-class and the four-class area recognitions, and is more than 95% for the eight-class area recognition. These results are obviously superior to other traditional recognition algorithms. More importantly, the model has high robustness and universality, which can be applied to various types of LED lights.

RIS-aided dynamically adaptive wide field-of-view receiver for visible light communication in industrial internet of things.

In the current visible light communication (VLC) system, a condenser lens is generally used in the front of receiver to achieve a higher data rate, making an extremely narrow field-of-view for the receiver. With the spread of Industrial Internet of Things (IIoT), the communication between mobile terminals is urgently required. A wide-range detecting method for VLC system in IIoT scenario is asked. In this paper, a novel self-adaptive wide-FoV receiver involving reconfigurable intelligent surfaces (RIS) is proposed. The effective detecting range of the receiver can be expanded by dynamically adjusting the incident light directions with the assistance of RIS. Based on the maximum arrived flux criterion, the mathematical model is established and the optimized RIS parameter tuning algorithm is presented. The feasibility and validity of the method are verified by simulation. The results show that the tolerable transceiver offset can be increased to 2∼4 times as the conventional receiver.

KIF2C is a prognostic biomarker associated with immune cell infiltration in breast cancer.

BACKGROUND: The kinesin-13 family member 2C (KIF2C) is a versatile protein participating in many biological processes. KIF2C is frequently up-regulated in multiple types of cancer and is associated with cancer development. However, the role of KIF2C in immune cell infiltration of tumor microenvironment and immunotherapy in breast cancer remains unclear. METHODS: The expression of KIF2C was analyzed using Tumor Immune Estimation Resource (TIMER) database and further verified by immunohistochemical staining in human breast cancer tissues. The correlation between KIF2C expression and clinical parameters, the impact of KIF2C on clinical prognosis and independent prognostic factors were analyzed by using TCGA database, the Kaplan-Meier plotter, and Univariate and multivariate Cox analyses, respectively. The nomograms were constructed according to independent prognostic factors and validated with C-index, calibration curves, ROC curves, and decision curve analysis. A gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms of KIF2C. The degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA (ssGSEA). The Tumor mutational burden and Tumor Immune Dysfunction and Rejection (TIDE) were used to analyze immunotherapeutic efficiency. Finally, the KIF2C-related competing endogenous RNA (ceRNA) network was constructed to predict the putative regulatory mechanisms of KIF2C. RESULTS: KIF2C was remarkably up-regulated in 18 different types of cancers, including breast cancer. Kaplan-Meier survival analysis showed that high KIF2C expression was associated with poor overall survival (OS). KIF2C expression was associated with clinical parameters such as age, TMN stage, T status, and molecular subtypes. We identified age, stage, estrogen receptor (ER) and KIF2C expression as OS-related independent prognosis factors for breast cancer. An OS-related nomogram was developed based on these independent prognosis factors and displayed good predicting ability for OS of breast cancer patients. Finally, our results revealed that KIF2C was significantly related to immune cell infiltration, tumor mutational burden, and immunotherapy in patients with breast cancer. CONCLUSION: KIF2C was overexpressed in breast cancer and was positively correlated with immune cell infiltration and immunotherapy response. Therefore, KIF2C can serve as a potential biomarker for prognosis and immunotherapy in breast cancer.

Exploiting the LSPR effect for an enhanced photocatalytic hydrogen evolution reaction.

Incorporation of plasmonic metals is one of the most widely adopted strategies for improving the photocatalytic hydrogen evolution reaction (HER) activity of semiconductor photocatalysts. This article summarizes recent advances in the development of plasmonic metal-semiconductor photocatalysts and four localized surface plasmon resonance (LSPR) driven mechanisms by which plasmonic metal nanoparticles can contribute to enhancement of HER activity. In addition, principles for maximizing the contribution of these LSPR driven mechanisms are highlighted to provide insights for future design of plasmonic metal-semiconductor photocatalysts with enhanced HER activity.

Association between diabetes complicated with comorbidities and frailty in older adults: A cross-sectional study.

AIMS AND OBJECTIVES: This study investigated the relationship between frailty and diabetes complicated with comorbidities. BACKGROUND: Frailty is a common geriatric syndrome, and older adults with diabetes are prone to frailty. Patients with diabetes and comorbidities might be at increased risk of developing frailty. DESIGN: A multicenter cross-sectional study. METHODS: A cross-sectional study was conducted to identify older patients with diabetes and comorbidities in the internal medicine departments of five tertiary general hospitals in Sichuan Province, China, from March 2020 to June 2021. We used the FRAIL scale to identify frailty, and multinomial logistic regression was used to compare sociodemographic characteristics and comorbidities of frail or pre-frail participants with robust participants. The STROBE checklist was used for this cross-sectional study. RESULTS: A total of 1652 patients (883 males, 53.5%) were included, and the prevalence of frailty was 26.5%. Multinomial logistic regression analysis revealed that compared with robust patients, diabetic patients with hypertension, coronary heart disease, chronic cardiac failure, COPD, cerebrovascular diseases, osteoarticular diseases, chronic renal diseases, chronic gastrointestinal diseases and cancer were more likely to be frail. In addition, patients who engaged in less exercise, presented more comorbidities, were older and had lower education levels, were more prone to frailty. CONCLUSION: There was a clear correlation between diabetes complicated with comorbidities and the development of frailty. Appropriate personalised care levels for patients with diabetes and comorbidities, and early screening for frailty might reduce the prevalence of frailty in these patients. RELEVANCE TO CLINICAL PRACTICE: This study provided information for healthcare providers to identify circumstances that increase the risk of frailty and more effectively support patients with diabetes and comorbidities.

Comparison of bacterial community structure in PM2.5 during hazy and non-hazy periods in Guilin, South China.

In recent years, significant efforts have been made to study changes in the levels of air pollutants at regional and urban scales, and changes in bioaerosols during air pollution events have attracted increasing attention. In this study, the bacterial structure of PM2.5 was analysed under different environmental conditions during hazy and non-hazy periods in Guilin. A total of 32 PM2.5 samples were collected in December 2020 and July 2021, and the microbial community structures were analysed using high-throughput sequencing methods. The results show that air pollution and climate change alter the species distribution and community diversity of bacteria in PM2.5, particularly Sphingomonas and Pseudomonas. The structure of the bacterial community composition is related to diurnal variation, vertical height, and urban area and their interactions with various environmental factors. This is a comprehensive study that characterises the variability of bacteria associated with PM2.5 in a variety of environments, highlighting the impacts of environmental effects on the atmospheric microbial community. The results will contribute to our understanding of haze trends in China, particularly the relationship between bioaerosol communities and the urban environment. Supplementary Information: The online version contains supplementary material available at 10.1007/s10453-022-09777-0.

Production of single-cycle infectious SARS-CoV-2 through a trans-complemented replicon.

Single-cycle infectious virus can elicit close-to-natural immune response and memory. One approach to generate single-cycle severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is through deletion of structural genes such as spike (S) and nucleocapsid (N). Transcomplementation of the resulting ΔS or ΔN virus through enforced expression of S or N protein in the cells gives rise to a live but unproductive virus. In this study, ΔS and ΔN BAC clones were constructed and their live virions were rescued by transient expression of S and N proteins from the ancestral and the Omicron strains. ΔS and ΔN virions were visualized by transmission electron microscopy. Virion production of ΔS was more efficient than that of ΔN. The coated S protein from ΔS was delivered to infected cells in which the expression of N protein was also robust. In contrast, expression of neither S nor N was detected in ΔN-infected cells. ΔS underwent viral RNA replication, induced type I interferon (IFN) response, but did not form plaques. Despite RNA replication in cells, ΔS infection did not produce viral progeny in culture supernatant. Interestingly, viral RNA replication was not further enhanced upon overexpression of S protein. Taken together, our work provides a versatile platform for development of single-cycle vaccines for SARS-CoV-2.

Promotion of Phenol Electro-oxidation by Oxygen Evolution Reaction on an Active Electrode for Efficient Pollution Control and Hydrogen Evolution.

We report an electrolysis system using NiFe layered double hydroxide/CoMoO4/nickel foam (NFLDH/CMO/NF) as the anode and CMO/NF as the cathode for simultaneous phenol electro-oxidation and water electrolysis. This system shows high performance for both phenol degradation and hydrogen evolution. We demonstrate that the degradation rate of phenol on the active anode is governed by the mass transfer rate at a low phenol concentration (0.5-2 mM) and by the electro-oxidation rate at a high phenol concentration (5 mM). The anodic oxygen evolution reaction (OER) can promote the phenol degradation through enhanced mass transfer efficiency. More importantly, the common deactivation issue of phenol electro-oxidation on the inert anode can be eliminated by the high OER activity of the active anode. The constructed full electrolytic cell only needs a low potential of 1.498 V to achieve 10 mA/cm2 for water electrolysis. The reported promotion effect of phenol degradation by OER as well as the improved anode resistance to deactivation offer new insights into efficient and robust waste-to-resource electrolysis system for water treatment.

Selective Removal of Phenolic Compounds by Peroxydisulfate Activation: Inherent Role of Hydrophobicity and Interface ROS.

Selective removal of organic pollutants by advanced oxidation methods has been receiving increasing attention for environmental remediation. In this study, a novel catalyst, which can selectively oxidize phenolic compounds (PCs) based on their hydrophobicity, composed of metal-organic-framework-derived Fe/Fe3O4 and three-dimensional reduced graphene oxide (rGOF) is designed for peroxydisulfate (PDS) activation. This heterogeneous PDS activation system can completely degrade hydrophobic PCs within 30 min. By investigating the hydrophobic properties of eight representative PCs, a positive correlation between the hydrophobicity of PC and the reaction kinetics is reported for the first time. The selective removal stems from the strong interaction between highly hydrophobic PCs and the catalyst. Moreover, the mechanism investigation shows that the degradation reaction is triggered by interface reactive oxygen species (ROS). Our study reveals that the selective degradation of organic pollutants by PDS activation depends on the hydrophilic and hydrophobic properties of the pollutant and catalyst. The reported results provide new insights into a highly selective and efficient PDS activation system for organic pollutant removal.

Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV-infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-ß expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-ß expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-ß induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.

Research on the frailty status and adverse outcomes of elderly patients with multimorbidity.

BACKGROUND: As patients age, the frailty of those with multimorbidity increases, often resulting in adverse health outcomes. The current study investigated the frailty status and the factors which influence it in elderly patients with multimorbidity in Chinese hospitals. The relationship between the frailty of patients with multimorbidity and adverse outcomes was explored. METHODS: The current prospective cohort study investigated inpatients in the internal medicine department of 5 tertiary hospitals in Sichuan Province, China. A total of 3836 elderly patients with multimorbidity were enrolled. Frailty was assessed using the FRAIL scale and adverse outcome events occurring during hospitalization were tracked. Descriptive statistics and logistic regressions were used for data analysis. RESULTS: The prevalence of frailty was 27.2% and of pre-frailty, 58.9%. Logistic regression analysis showed that increasing age, low BMI, low education level, lack of exercise, multiple types of medications and multiple numbers of chronic diseases were the main risk factors for frailty in elderly patients with multimorbidity (OR values: 1.020, 1.469, 2.350, 2.836, 1.156 and 1.308, respectively). The incidence of adverse outcomes was 13.9% among the cohort with the most common being deep vein thrombosis (42.4%), followed by pressure injury (38.8%). Regression analysis showed a significant correlation of frailty with adverse outcome (OR: 1.496; p < 0.01). CONCLUSIONS: The prevalence of frailty and pre-frailty in hospitalized elderly patients with multimorbidity was high. Increasing age, low BMI, low education level, lack of exercise, multiple types of medications and multiple numbers of chronic diseases were factors which influenced frailty and frailty was an important factor in the occurrence of adverse outcomes. The most common adverse outcome of elderly multimorbidity patients during hospitalization was deep vein thrombosis.

Molecular genetic survey and forensic characterization of Chinese Mongolians via the 47 autosomal insertion/deletion marker.

The Mongolians are mainly distributed in the modern state of Mongolia, China, Russia, and other countries. While the historic and archaeological records of the rise and fall of the Mongol Empire are well documented, little has been known about the genetic legacy of modern Mongolian populations. Here, 611 Mongolian individuals from Hohhot, Hulunbuir, and Ordos of China were genotyped via the 47 Insertion/Deletion markers. Forensically statistical parameters indicated that this InDel system could be applied to forensic investigation in Mongolian populations. The comprehensive population comparisons indicated that targeted Mongolian populations are a homogeneous population, which kept close genetic proximity with geographically northern East Asians. The findings of the model-based clustering analysis revealed a southern East Asian-specific ancestral component, which was maximized in Hainan Li, and Mongolian populations harbored relatively less Hainan Li-related ancestry and more northern East Asian-related ancestry compared with reference Tai-Kadai, Austroasiatic and Sinitic people.

Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-mediated ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). SARS-CoV and its ORF3a protein were found to be potent activators of pro-IL-1ß gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro-IL-1ß transcription through activation of NF-κB, which was mediated by TRAF3-dependent ubiquitination and processing of p105. ORF3a-induced elevation of IL-1ß secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3-dependent K63-linked ubiquitination of ASC was more pronounced in SARS-CoV-infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS-CoV ORF3a protein activates NF-κB and the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of p105 and ASC.-Siu, K.-L., Yuen, K.-S., Castaño-Rodriguez, C., Ye, Z.-W., Yeung, M.-L., Fung, S.-Y., Yuan, S., Chan, C.-P., Yuen, K.-Y., Enjuanes, L., Jin, D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.