FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.

Pontocerebellar hypoplasia (PCH) is a group of rare neurodevelopmental disorders with limited diagnostic and therapeutic options. Mutations in WDR11, a subunit of the FAM91A1 complex, have been found in patients with PCH-like symptoms; however, definitive evidence that the mutations are causal is still lacking. Here, we show that depletion of FAM91A1 results in developmental defects in zebrafish similar to that of TBC1D23, an established PCH gene. FAM91A1 and TBC1D23 directly interact with each other and cooperate to regulate endosome-to-Golgi trafficking of KIAA0319L, a protein known to regulate axonal growth. Crystal structure of the FAM91A1-TBC1D23 complex reveals that TBC1D23 binds to a conserved surface on FAM91A1 by assuming a Z-shaped conformation. More importantly, the interaction between FAM91A1 and TBC1D23 can be used to predict the risk of certain TBC1D23-associated mutations to PCH. Collectively, our study provides a molecular basis for the interaction between TBC1D23 and FAM91A1 and suggests that disrupted endosomal trafficking underlies multiple PCH subtypes.

Cathepsin V is correlated with the prognosis and tumor microenvironment in liver cancer.

Recent studies have shown that high cell cycle activity negatively correlates with antitumor immunity in certain cancer types. However, a similar correlation has not been proven in liver cancer. We downloaded transcriptomic profiles of the cancer genome atlas-liver hepatocellular carcinoma (TCGA-LIHC) and assessed the cell cycle distribution of samples using single sample gene set enrichment analysis (ssGSEA), termed the cell cycle score (CCS). We obtained cell cycle-related differentially expressed prognostic genes and identified CENPA, CDC20, and CTSV using LASSO regression. We studied the effect of CTSV on clinical features and immune alterations in liver cancer based on TCGA-LIHC data. In vitro and in vivo experiments were performed to validate the role of CTSV in liver cancer using liver cancer cell lines and tissues. We found that the CCS closely correlated with the clinical features and prognosis of patients in TCGA-LIHC. Analysis of differentially expressed genes (DEGs), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression identified cathepsin V (CTSV) with prognostic significance in LIHC. Importantly, single-gene survival analysis of CTSV using microarray and sequencing data indicated that high levels of CTSV expression correlated with an unfavorable prognosis in various cancers. Gene set enrichment analysis revealed that high CTSV expression closely correlated with decreased expression of metabolic genes and increased expression of cell cycle genes. Furthermore, difference and correlation analyses of the relationship between CTSV expression and immune infiltrates, determined using CIBERSORT and TIMER algorithms, revealed that CTSV expression correlated with macrophages and CD4+ T cells. In vitro and in vivo experiments revealed that knockdown of CTSV inhibited liver cancer cells proliferation. Immunohistochemical staining showed that high CTSV expression correlated with macrophage infiltration in liver cancer tissues, predicted a poor prognosis, and is associated with the effectiveness of hepatocellular carcinoma treatment. In couclusion, CTSV is a novel cell cycle-associated gene with clinical significance in HCC.

Asymmetric synthesis of (R)-baclofen and (3S,4S)-tetflupyrolimet via "on water" organocatalytic addition reactions: a tip on catalyst screening.

This work demonstrates asymmetric synthesis of the GABA derivative (R)-baclofen and a new herbicidal mode-of-action inhibitor (3S,4S)-tetflupyrolimet featuring low loading (0.5 mol%) organocatalytic addition reactions of dithiomalonates to nitrostyrenes under "on water" conditions. Importantly, we observed that increasing the hydrophobicity of the catalyst does not guarantee improved catalytic performance under "on water" conditions and the trends in the catalytic efficiency of different HBD catalysts under "on water" conditions (with hydrophobic additives) align more closely with those observed in pure hydrophobic organic solvents. These findings propose a valuable tip for screening organocatalysts in developing asymmetric hydrogen-bonding catalysis under "on water" conditions.

Access to 2-pyridinones comprising enaminonitriles via AgOAc promoted cascade reactions of thioesters with aminomethylene malononitriles.

The facile synthesis of 2-pyridinones containing enaminonitriles from thioesters with aminomethylene malononitriles is achieved through an AgOAc-promoted acylation/cyclization/tautomerization cascade reaction. Control experiments reveal that AgOAc acts as a versatile promoter, activating both thioester and cyano groups while also serving as a Brønsted base in the cascade sequence. Moreover, 2-pyridinones were transformed into biologically significant 2-pyridinone-fused 2-pyrimidones with intriguing fluorescence emission properties.

Metabolites of Clostridium leptum fermenting flaxseed polysaccharide alleviate obesity in rats.

Obesity is a chronic metabolic disease. Our previous research found flaxseed polysaccharide (FP) has an anti-obesity effect, and its anti-obesity effect possibly depends on Clostridium leptum (C. leptum). However, whether the strain takes the role and how it works is still being determined. Here, FP was fermented in vitro by C. leptum and its metabolites were analyzed. Subsequently, the FP fermentation broth of C. leptum (FPF) was given to the obese pseudo sterile rats. The results showed FPF was rich in various metabolites, among which the top ten in relative expression abundance were 3 beta-hydroxy-5-cholestenoate, 7,8-dihydro-3b,6a-dihydroxy-alpha-ionol 9-glucoside, Valyl-Serine, 2-amino-4-[(2-hydroxy-1-oxopropyl)amino]butanoic acid, Agavoside B, glycylproline, lycopersiconolide, armillaritin, Isoleucyl-Hydroxyproline and norethindrone acetate. After intervention with FPF, the weight, abdominal fat ratio, and total fat ratio of rats were significantly reduced and the lipid metabolism of them has been improved. This effect may be achieved by up regulating glucagon-like peptide-1 and adiponectin and further activating the AMP-activated protein kinase signaling pathway. This is the first experimental proof that FP exerts its anti-obesity effects through metabolites from C. leptum fermenting FP, not FP itself and the bacterial cells (debris) of C. leptum. It is also the first demonstration that FPF has a significant anti-obesity effect.

PCSK9 aggravated carotid artery stenosis in ApoE-/- mice by promoting the expression of tissue factors in endothelial cells via the TLR4/NF-κB pathway.

Atherosclerosis, a chronic inflammatory disease, is the most relevant cause of carotid artery stenosis. Vascular endothelial cells (ECs) play a significant role in the development of atherosclerosis. In this chronic inflammatory environment, we aimed to investigate whether PCSK9 could mitigate atherosclerosis progression by reducing tissue factor expression in ECs via in vivo and in vitro assays. In vivo, we investigated the effect of PCSK9 inhibition on preventing atherosclerotic lesion formation in ApoE-/- mice fed a western diet. The results showed that inhibiting PCSK9 could significantly downregulate the protein expression of tissue factor (TF) in ECs to reduce the area of atherosclerotic plaques. In vitro, we incubated human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). We found that LPS-induced TF elevation was suppressed by a PCSK9 inhibitor at both the mRNA and protein levels and that the TLR4/NF-κB pathway was also suppressed by a PCSK9 inhibitor. With respect to plasma samples from patients with carotid artery stenosis, we also demonstrated that the expression of TF was positively correlated with that of PCSK9. Thus, in addition to regulating lipid metabolism, the regulation of endothelial cell TF expression through the TLR4/NF-κB pathway may be a potential mechanism of PCSK9 in promoting atherosclerotic carotid stenosis.

The circadian rhythm: A new target of natural products that can protect against diseases of the metabolic system, cardiovascular system, and nervous system.

BACKGROUND: The treatment of metabolic system, cardiovascular system, and nervous system diseases remains to be explored. In the internal environment of organisms, the metabolism of substances such as carbohydrates, lipids and proteins (including biohormones and enzymes) exhibit a certain circadian rhythm to maintain the energy supply and material cycle needed for the normal activities of organisms. As a key factor for the health of organisms, the circadian rhythm can be disrupted by pathological conditions, and this disruption accelerates the progression of diseases and results in a vicious cycle. The current treatments targeting the circadian rhythm for the treatment of metabolic system, cardiovascular system, and nervous system diseases have certain limitations, and the identification of safer and more effective circadian rhythm regulators is needed. AIM OF THE REVIEW: To systematically assess the possibility of using the biological clock as a natural product target for disease intervention, this work reviews a range of evidence on the potential effectiveness of natural products targeting the circadian rhythm to protect against diseases of the metabolic system, cardiovascular system, and nervous system. This manuscript focuses on how natural products restore normal function by affecting the amplitude of the expression of circadian factors, sleep/wake cycles and the structure of the gut microbiota. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: This work proposes that the circadian rhythm, which is regulated by the amplitude of the expression of circadian rhythm-related factors and the sleep/wake cycle, is crucial for diseases of the metabolic system, cardiovascular system and nervous system and is a new target for slowing the progression of diseases through the use of natural products. This manuscript provides a reference for the molecular modeling of natural products that target the circadian rhythm and provides a new perspective for the time-targeted action of drugs.

Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed non-insulin-resistant rats.

Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.

Effects of plant natural products on metabolic-associated fatty liver disease and the underlying mechanisms: a narrative review with a focus on the modulation of the gut microbiota.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.

SwinGar: Spectrum-Inspired Neural Dynamic Deformation for Free-Swinging Garments.

Our work presents a novel spectrum-inspired learning-based approach for generating clothing deformations with dynamic effects and personalized details. Existing methods in the field of clothing animation are limited to either static behavior or specific network models for individual garments, which hinders their applicability in real-world scenarios where diverse animated garments are required. Our proposed method overcomes these limitations by providing a unified framework that predicts dynamic behavior for different garments with arbitrary topology and looseness, resulting in versatile and realistic deformations. First, we observe that the problem of bias towards low frequency always hampers supervised learning and leads to overly smooth deformations. To address this issue, we introduce a frequency-control strategy from a spectral perspective that enhances the generation of high-frequency details of the deformation. In addition, to make the network highly generalizable and able to learn various clothing deformations effectively, we propose a spectral descriptor to achieve a generalized description of the global shape information. Building on the above strategies, we develop a dynamic clothing deformation estimator that integrates graph attention mechanisms with long short-term memory. The estimator takes as input expressive features from garments and human bodies, allowing it to automatically output continuous deformations for diverse clothing types, independent of mesh topology or vertex count. Finally, we present a neural collision handling method to further enhance the realism of garments. Our experimental results demonstrate the effectiveness of our approach on a variety of free-swinging garments and its superiority over state-of-the-art methods.

GAC-SleepNet: A dual-structured sleep staging method based on graph structure and Euclidean structure.

Sleep staging is a precondition for the diagnosis and treatment of sleep disorders. However, how to fully exploit the relationship between spatial features of the brain and sleep stages is an important task. Many current classical algorithms only extract the characteristic information of the brain in the Euclidean space without considering other spatial structures. In this study, a sleep staging network named GAC-SleepNet is designed. GAC-SleepNet uses the characteristic information in the dual structure of the graph structure and the Euclidean structure for the classification of sleep stages. In the graph structure, this study uses a graph convolutional neural network to learn the deep features of each sleep stage and converts the features in the topological structure into feature vectors by a multilayer perceptron. In the Euclidean structure, this study uses convolutional neural networks to learn the temporal features of sleep information and combine attention mechanism to portray the connection between different sleep periods and EEG signals, while enhancing the description of global features to avoid local optima. In this study, the performance of the proposed network is evaluated on two public datasets. The experimental results show that the dual spatial structure captures more adequate and comprehensive information about sleep features and shows advancement in terms of different evaluation metrics.

The impact of microbially modified metabolites associated with obesity and bariatric surgery on antitumor immunity.

Obesity is strongly associated with the occurrence and development of many types of cancers. Patients with obesity and cancer present with features of a disordered gut microbiota and metabolism, which may inhibit the physiological immune response to tumors and possibly damage immune cells in the tumor microenvironment. In recent years, bariatric surgery has become increasingly common and is recognized as an effective strategy for long-term weight loss; furthermore, bariatric surgery can induce favorable changes in the gut microbiota. Some studies have found that microbial metabolites, such as short-chain fatty acids (SCFAs), inosine bile acids and spermidine, play an important role in anticancer immunity. In this review, we describe the changes in microbial metabolites initiated by bariatric surgery and discuss the effects of these metabolites on anticancer immunity. This review attempts to clarify the relationship between alterations in microbial metabolites due to bariatric surgery and the effectiveness of cancer treatment. Furthermore, this review seeks to provide strategies for the development of microbial metabolites mimicking the benefits of bariatric surgery with the aim of improving therapeutic outcomes in cancer patients who have not received bariatric surgery.

Hua-Tan-Sheng-Jing Decoction Treats Obesity With Oligoasthenozoospermia by Up-Regulating the PI3K-AKT and Down-Regulating the JNK MAPK Signaling Pathways: At the Crossroad of Obesity and Oligoasthenozoospermia.

Background: Oligoasthenozoospermia is the leading cause of male infertility, seriously affecting men's health and increasing the societal medical burden. In recent years, obesity-related oligoasthenozoospermia has attracted increased attention from researchers to find a cure. This study aimed to evaluate the efficacy of Hua-Tan-Sheng-Jing decoction (HTSJD) in treating obesity with oligoasthenozoospermia, determine its active ingredients and identify its mechanism of action. Methods: The ingredients of HTSJD were determined by combining the ultra-performance liquid chromatography with mass spectrometry (UPLC-MS/MS) and systems pharmacology approach. The common pathogenesis of obesity and oligoasthenozoospermia and the potential mechanism of HTSJD against obesity with oligoasthenozoospermia were obtained through target fishing, network construction, and enrichment analyses. Further, molecular docking of the key ingredients with the upstream receptors of the key signaling pathways of the potential mechanism was used to predict their affinity. Finally, high-fat-induced obesity with oligoasthenozoospermia rat model was constructed to determine the effects of HTSJD on semen concentration, sperm motility, body weight, and serum lipid metabolism. The key proteins were validated by immunohistochemistry (IHC). Results: A total of 70 effective components and 847 potential targets of HTSJD (H targets) were identified, of which 743 were common targets related to obesity and oligoasthenozoospermia (O-O targets) mainly enriched in the pathways related to inflammation, oxidative stress and hormone regulation. Finally, 143 common targets (H-O-O targets) for HTSJD against obesity with oligoasthenozoospermia were obtained. Combining the hub genes and the results of Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of H-O-O targets, PI3K-AKT and MAPK signaling pathways were identified as the key pathways. Molecular docking results showed that Diosgenin, Kaempferol, Quercetin, Hederagenin, Isorhamnetin may act on the related pathways by docking EGFR, IGF1R and INSR. The animal-based in vivo experiments confirmed that HTSJD improves the sperm quality of high-fat diet-fed rats by reducing their body weight and blood lipid levels, influencing the PI3K-AKT and MAPK signaling pathways and altering the corresponding protein expressions. Conclusion: HTSJD treats obesity with oligoasthenozoospermia by up-regulating the PI3K-AKT signaling pathway and down-regulating the MAPK signaling pathway, which are at the crossroad of obesity and oligoasthenozoospermia.

Obese Individuals With and Without Phlegm-Dampness Constitution Show Different Gut Microbial Composition Associated With Risk of Metabolic Disorders.

Background: Obesity is conventionally considered a risk factor for multiple metabolic diseases, such as dyslipidemia, type 2 diabetes, hypertension, and cardiovascular disease (CVD). However, not every obese patient will progress to metabolic disease. Phlegm-dampness constitution (PDC), one of the nine TCM constitutions, is considered a high-risk factor for obesity and its complications. Alterations in the gut microbiota have been shown to drive the development and progression of obesity and metabolic disease, however, key microbial changes in obese patients with PDC have a higher risk for metabolic disorders remain elusive. Methods: We carried out fecal 16S rRNA gene sequencing in the present study, including 30 obese subjects with PDC (PDC), 30 individuals without PDC (non-PDC), and 30 healthy controls with balanced constitution (BC). Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt. Results: Obese individuals with PDC had higher BMI, waist circumference, hip circumference, and altered composition of their gut microbiota compared to non-PDC obese individuals. At the phylum level, the gut microbiota was characterized by increased abundance of Bacteroidetes and decreased levels of Firmicutes and Firmicutes/Bacteroidetes ratio. At the genus level, Faecalibacterium, producing short-chain fatty acid, achieving anti-inflammatory effects and strengthening intestinal barrier functions, was depleted in the PDC group, instead, Prevotella was enriched. Most PDC-associated bacteria had a stronger correlation with clinical indicators of metabolic disorders rather than more severe obesity. The PICRUSt analysis demonstrated 70 significantly different microbiome community functions between the two groups, which were mainly involved in carbohydrate and amino acid metabolism, such as promoting Arachidonic acid metabolism, mineral absorption, and Lipopolysaccharide biosynthesis, reducing Arginine and proline metabolism, flavone and flavonol biosynthesis, Glycolysis/Gluconeogenesis, and primary bile acid biosynthesis. Furthermore, a disease classifier based on microbiota was constructed to accurately discriminate PDC individuals from all obese people. Conclusion: Our study shows that obese individuals with PDC can be distinguished from non-PDC obese individuals based on gut microbial characteristics. The composition of the gut microbiome altered in obese with PDC may be responsible for their high risk of metabolic diseases.

Traditional Chinese Medicine Constitution Identification Based on Objective Facial and Tongue Features: A Delphi Study and a Diagnostic Nomogram for Blood Stasis Constitution.

Objective: The aim of this study was to systematically summarize and form an expert consensus on the theoretical experience of tongue and facial features for the identification of nine types of traditional Chinese medicine (TCM) constitution. Additionally, we sought to explore the feasibility of TCM constitution identification through objective tongue and facial features. Methods: We used Delphi method to investigate the opinions of experts on facial and tongue feature items for identifying TCM constitution. We developed and validated a diagnostic nomogram for blood stasis constitution (BSC) based on objective facial and tongue features to demonstrate the reliability of expert consultation. Results: Eleven experts participated in two rounds of expert consultation. The recovery rates of the two rounds of expert consultation were 100.0% and 90.9%. After the first round, 39 items were screened out from 147 initial items, and 2 items were supplemented by experts. In the second round, 7 items were eliminated, leaving 34 items for 8 types of TCM constitution. The coefficient of variation in the first round was 0.11-0.49 for the 147 items and 0.11-0.29 for the included items. The coefficient of variation in the second round was 0.10-0.27 for the 41 items and 0.10-0.20 for the included items. The W value was 0.548 (P < 0.001) in the first round and 0.240 (P < 0.001) in the second round. Based on expert consultation, we selected BSC as an example and developed and validated a diagnostic nomogram consisting of six indicators: sex, hair volume, lip color-dark purple, susceptibility-facial pigmentation/chloasma/ecchymosis, zygomatic texture-red blood streaks, and sublingual vein-varicose and dark purple. The nomogram showed good discrimination (AUC: 0.917 [95% confidence interval [CI], 0.877-0.956] for the primary dataset, 0.902 [95% CI, 0.828-0.976] for the validation dataset) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion: This is the first study to systematically summarize the existing knowledge and clinical experience to form an expert consensus on the tongue and facial features of nine types of TCM constitution. Our results will provide important prior knowledge and expert experience for future constitution identification research. Based on expert consultation, this study presents a nomogram for BSC that incorporates objective facial and tongue features, which can be conveniently used to facilitate the individualized identification of BSC.

Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells.

AIM: Irritable bowel syndrome (IBS) is a multifactorial functional bowel disorder characterized by disruption of the intestinal barrier. Circulating exosomal microRNAs (miRNAs) are involved in regulating epithelial barrier function, and upregulation of miR-148b-5p has been detected in IBS. However, whether exosomal miR-148-5p is involved in the IBS pathogenesis remains unclear. This study was aimed at investigating the relationship of exosomal miR-148-5p with colonic epithelial permeability. METHODS: Exosomes were isolated from the serum of IBS patients and healthy controls. HT-29 cells were cultured with the IBS-derived serum exosomes (IBS-exo). Exosome uptake assay was used to evaluate whether the IBS-exo could be absorbed by HT-29 cells. FITC-Dextran flux and transepithelial/endothelial electrical resistance were measured to evaluate epithelial permeability. A luciferase reporter assay was used to determine whether the regulator of G protein signaling- (RGS-) 2 is a target gene of miR-148b-5p. RESULTS: miR-148b-5p was obviously elevated in the IBS-exo compared to the control-exo. Upregulation of miR-148b-5p was observed in the HT-29 cells cultured with IBS-exo. Exposure to IBS-exo increased cell permeability and decreased RGS2 expression. The IBS-exo-induced alterations were obviously reversed by interfering with the miR-148b-5p expression. Mimicking the IBS-exo treatment, miR-148b-5p overexpression increased cell permeability and downregulated RGS2 expression, which were abrogated by overexpressing RGS2. The luciferase reporter assay revealed that RGS2 was a direct target of miR-148b-5p. CONCLUSIONS: Serum-derived exosomes from IBS patients increase colonic epithelial permeability via miR-148b-5p/RGS2 signaling.

Effect of Knowledge/Practice of COVID-19 Prevention Measures on Return-to-Work Concerns; Attitudes About the Efficacy of Traditional Chinese Medicine: Survey on Supermarket Staff in Huanggang, China.

Objective: The objective of this study was to investigate how knowledge and practice of coronavirus disease 2019 (COVID-19) prevention measures affected concerns about returning to work among supermarket staff. Attitudes about the ability of traditional Chinese medicine (TCM) to prevent COVID-19 were also assessed. Methods: A cross-sectional study was conducted in Huanggang, Hubei Province, China from April 23 to 25, 2020. Participants were invited to fill out an electronic questionnaire on their cell phones. Results: The results showed that from 2,309 valid questionnaires, 61.5% of participants were concerned about resuming work. Major concerns included asymptomatic infection (85.01%) and employees gathering in the workplace (78.96%). Multivariate logistic regression indicated that the female gender, having school-aged children and pregnancy were risk factors for being concerned about resuming work, while good knowledge and practice of preventive measures were protective factors. Knowledge and practice of preventive measures were positively correlated. Among preventive measures, the highest percentage of participants knew about wearing masks and washing hands. Meanwhile, 65.8% of participants expressed confidence in the ability of TCM to prevent COVID-19, where 74 and 51.3% thought there was a need and a strong need, respectively, for preventive TCM-based products. Among them, 71.5% preferred oral granules. Regarding TCM as a COVID-19 preventative, most were interested in information about safety and efficacy. Conclusion: These findings suggested that promoting knowledge and practices regarding COVID-19 prevention can help alleviate concerns about returning to work. Meanwhile, TCM can feasibly be accepted to diversify COVID-19 prevention methods. Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2000031955.

COVID-19 Knowledge/Practices, Mental Status, and Return-To-Work Concerns Among Healthcare Workers in Huangzhou District, Huanggang City, China.

Objective: This study investigated the COVID-19-prevention knowledge and practices of healthcare workers (HCWs), their psychological states concerning the return to work, and their trust and requirements in using traditional Chinese medicine (TCM) to prevent and treat COVID-19. It is hoped that the study can serve as a reference for policy making during the resumption of work in other countries or regions experiencing similar situations. Methods: This study comprised a quantitative cross-sectional online survey design. Purposive sampling and Cluster sampling were used to recruit all HCWs working in public hospitals in Huangzhou District, Huanggang City, Hubei Province, China. From April 23 to May 14, 2020, surveys were sent electronically to all 13 public hospitals in this area. Results: In total, 2,079 responses were received and 2,050 completed forms were included. After analysis, 47.9 and 46.6% of HCWs indicated that they possessed very good knowledge or good knowledge of preventative measures, respectively. Multivariable log-binomial regression indicated that male, tertiary hospital, medical staff, and undergraduate/postgraduate qualification were associated with good knowledge. Good knowledge was also well-correlated with good practice (OR: 3.277; 95% CI: 2.734-3.928; P < 0.01). 59.8% of HCWs reported worries about resuming work; especially asymptomatic infections. The Self-Rating Anxiety Scale (SAS) indicated that 10.8% of participants had mild anxiety, 1.5% moderate anxiety, and 0.1% severe anxiety. Female, divorced/widowed, and working in a high risk hospital (the Huangzhou District People's Hospital was used for throat swab examinations of returning workers) were risk factors for concerns about resuming work and anxiety symptoms. However, good preventive knowledge was a protective factor for anxiety. HCWs' trust in using TCM to treat COVID-19 was significantly higher than their trust in using TCM for prevention (P < 0.001). Regarding preferences for preventative TCM products, oral TCM granules were the most preferred (62.4%). HCWs also indicated they wanted to know more about the clinical efficacy, applicable population, and adverse reactions of preventative TCM products (89.3, 81.1, and 81.4%, respectively). Conclusion: While HCWs had good knowledge of COVID-19 preventative measures, this did not eliminate the psychological impact of resumption of work. Promotion of COVID-19 prevention knowledge reduces the risk of infection, and alleviates the worries and anxiety symptoms of HCWs about resuming work (especially in administrative staff, those with low education, and those working in primary hospitals). Additional psychological support is required for female HCWs, divorced/widowed HCWs, and those working in high-risk hospitals. Finally, systematic trials of preventative TCM products are recommended.

Group visualization of class-discriminative features.

Research explaining the behavior of convolutional neural networks (CNNs) has gained a lot of attention over the past few years. Although many visualization methods have been proposed to explain network predictions, most fail to provide clear correlations between the target output and the features extracted by convolutional layers. In this work, we define a concept, i.e., class-discriminative feature groups, to specify features that are extracted by groups of convolutional kernels correlated with a particular image class. We propose a detection method to detect class-discriminative feature groups and a visualization method to highlight image regions correlated with particular output and to interpret class-discriminative feature groups intuitively. The experiments showed that the proposed method can disentangle features based on image classes and shed light on what feature groups are extracted from which regions of the image. We also applied this method to visualize "lost" features in adversarial samples and features in an image containing a non-class object to demonstrate its ability to debug why the network failed or succeeded.

Guar gum different from Ganoderma lucidum polysaccharide in alleviating colorectal cancer based on omics analysis.

It is unclear if guar gum can alleviate colorectal cancer (CRC). We evaluated the effect of guar gum (unmodified) on the mortality, colon status, serous tumor necrosis factor-alpha (TNF-α) concentration, and gut microbial and colonic epithelial cell gene expression profiles in CRC mice and performed omics analyses to compare these with those of Ganoderma lucidum polysaccharide (GLP), whose main component is ß-glucan (>90%). We found that guar gum had a CRC alleviating effect. However, it showed a 20% higher mortality rate, shorter colon length, worse colon status, larger number and size of tumors, higher concentration of serous TNF-α and upregulation of epithelial cell genes (Il10, Cytl1, Igkv7-33, Ighv1-14, Igfbp6 and Foxd3) compared to that of GLP. The higher relative abundance of Akkermansia, the alteration of microbial metabolic pathways, especially those involving chaperones and folding catalysts, fatty acid biosynthesis, glycerophospholipid metabolism, glycolysis/gluconeogenesis, lipid biosynthesis and pyruvate metabolism, and the upregulation of specific genes (Mcpt2, Mcpt9, Des and Sostdc1) were also determined in animals fed a guar gum diet. The results suggested that the alleviating effect of guar gum (an inexpensive polysaccharide) on CRC was inferior to that of GLP (a more expensive polysaccharide). This could potentially be attributed to the increased presence of Akkermansia, the alteration of 10 microbial metabolic pathways and the upregulation of 4 epithelial cell genes.