Emergent Chirality and Hyperuniformity in an Active Mixture with Nonreciprocal Interactions.

We investigate collective dynamics in a binary mixture of programmable robots in experiments and simulations. While robots of the same species align their motion direction, interaction between species is distinctly nonreciprocal: species A aligns with B and species B antialigns with A. This nonreciprocal interaction gives rise to the emergence of collective chiral motion that can be stabilized by limiting the robot angular speed to be below a threshold. Within the chiral phase, increasing the robot density or extending the range of local repulsive interactions can drive the system through an absorbing-active transition. At the transition point, the robots exhibit a remarkable capacity for self-organization, forming disordered hyperuniform states.

Immobilization of recombinant Trametes versicolor aflatoxin B1-degrading enzyme (TV-AFB1D) with montmorillonite for absorption and in situ degradation of aflatoxin B1.

Aflatoxin B1 is a highly carcinogenic and teratogenic substance mainly produced by toxin-producing strains such as Aspergillus flavus and Aspergillus parasitic. The efficient decomposition of aflatoxin is an important means to reduce its harm to humans and livestock. In this study, Trametes versicolor aflatoxin B1-degrading enzyme (TV-AFB1D) was recombinantly expressed in Bacillus subtilis (B. subtilis) 168. MMT-CTAB-AFB1D complex was prepared by the immobilization of TV-AFB1D and montmorillonite (MMT) by cross-linking glutaraldehyde. The results indicated that TV-AFB1D could recombinantly express in engineered B. subtilis 168 with a size of approximately 77 kDa. The immobilization efficiency of MMT-CTAB-AFB1D reached 98.63% when the concentration of glutaraldehyde was 5% (v/v). The relative activity of TV-AFB1D decreased to 72.36% after reusing for 10 times. The content of AFB1 in MMT-CTAB-AFB1D-AFB1 decreased to 1.1 µg/g from the initial 5.6 µg/g after incubation at 50 °C for 6 h. The amount of 80.4% AFB1 in the MMT-CTAB-AFB1D-AFB1 complex was degraded by in situ catalytic degradation. Thus, the strategy of combining adsorption and in situ degradation could effectively reduce the content of AFB1 residue in the MMT-CTAB-AFB1D complex.

Epidemiological study of multi-site WMSDs in the footwear industry in China.

Objectives. This study aimed to identify the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) in Chinese footwear industry workers from 2018 to 2020 and explore the possible influencing factors of WMSDs. Methods. 7106 subjects from 26 large shoe factories in China were investigated using the epidemiological cross-sectional survey method by using the Nordic musculoskeletal questionnaire (NMQ). Results. The total prevalence of WMSDs in the study subjects was 36.8% (2616/7106). Among them, the prevalence of multi-site WMSDs was 26.1% (1858/7106). The proportion of multi-site WMSDs involving two sites was the largest (31.38%). In addition, the results showed that the risk factors of multi-site WMSDs were gender, marital status, long current job experience, poor health, poor working posture, etc. Conclusions. The prevalence of WMSDs was high in the Chinese footwear industry. Based on the results, therefore, it seems necessary to improve work posture, work organization and workenvironment to prevent WMSDs.

Robust All-Solid-State Lithium Metal Batteries Enabled by a Composite Lithium Anode with Improved Bulk Li Diffusion Kinetics Properties.

All-solid-state batteries (ASSBs) with a Li metal anode are expected to be one of the most promising energy storage systems to achieve high energy density. However, the interfacial instability between the Li metal anode and solid-state electrolyte (SSE) limits the rate capability and cycling stability of ASSBs. The main issue is the formation of voids at the Li/SSE interface during Li stripping due to the slow diffusion of Li within the bulk Li metal, then increasing internal cell resistance and inducing the formation of lithium dendrites. To address these issues, a composite Li anode (LAO) composed by Li-Ag alloy and Li2O is constructed by mixing the stoichiometric metal Li and Ag2O directly. LAO anode is capable of improving bulk Li diffusion kinetics and inhibiting the formation of interfacial voids effectively, achieving a high critical current density over 1.5 mA cm-2 and long stable cycling over 1000 h at 1 mA cm-2. The ASSBs, employing LAO as the anode, Li6PS5Cl as the SSE, and LiCoO2 as the cathode, exhibit superior rate capability and stable cycling over 4000 cycles at 5 C. Moreover, ASSBs can operate stably with a high LiCoO2 loading of 17.8 mg cm-2 for more than 100 cycles at 0.2 C.

Exploring mRNA translation strategies for hypoxia adaptation across distantly related metazoans.

Adaptation to variations in oxygen concentration is a conserved mechanism in all metazoans. Extensive studies have been focused on the roles of hypoxia-inducible factors (HIFs) in response to hypoxia. However, HIF1α is not conserved in all animals, and HIF2α and HIF3α are only observed in vertebrates. In this review, we discuss mechanisms enabling three cross-species to adapt to hypoxic conditions. Using transcriptomic data of hypoxia-induced genes from distantly related metazoans, we analyzed the enrichment and conservation of mRNA determinants such as transcript, CDS, 5'UTR and 3'UTR size. We found that long genes are enriched in hypoxia-induced transcripts and might be translated in a 3'UTR-dependent manner. We hope our work can provide a new direction on investigating alternative mechanisms for mRNA translation under hypoxia.

Many studies have focused on a group of proteins called hypoxia-inducible factors (HIFs) that help animals adapt to different oxygen concentrations, but not all animals have the same HIF proteins. This means that some genes involved in oxygen adaptation work differently in different animals. In this review, we look at three different species and how they adapt to low oxygen levels, with a special focus on how genes are used to make proteins. We used information from these species to see if certain features of genes (like their size) are important for adaptation. We found that in response to low oxygen, longer genes become more active and may use a specific part of the gene to make proteins. However, some common features thought to be important for gene activity in low oxygen were not found to be significant. This research gives us new directions to explore how genes make proteins in low-oxygen conditions, which is important for understanding how animals survive in changing environments.

Enoxaparin sodium bone cement plays an anti-inflammatory immunomodulatory role by inducing the polarization of M2 macrophages.

OBJECTIVE: The implantation of PMMA bone cement results in an immune response and the release of PMMA bone cement particles causes an inflammatory cascade. Our study discovered that ES-PMMA bone cement can induce M2 polarization of macrophages, which has an anti-inflammatory immunomodulatory effect. We also delved into the molecular mechanisms that underlie this process. METHODS: In this study, we designed and prepared samples of bone cement. These included PMMA bone cement samples and ES-PMMA bone cement samples, which were implanted into the back muscles of rats. At 3, 7, and 14 days after the operation, we removed the bone cement and a small amount of surrounding tissue. We then performed immunohistochemistry and immunofluorescence to observe the polarization of macrophages and the expression of related inflammatory factors in the surrounding tissues. The RAW264.7 cells were exposed to lipopolysaccharide (LPS) for 24 h to establish the macrophage inflammation model. Then, each group was treated with enoxaparin sodium medium, PMMA bone cement extract medium, and ES-PMMA bone cement extract medium, respectively, and cultured for another 24 h. We collected cells from each group and used flow cytometry to detect the expressions of CD86 and CD206 in macrophages. Additionally, we performed RT-qPCR to determine the mRNA levels of three markers of M1 macrophages (TNF-α, IL-6, iNOS) and two M2 macrophage markers (Arg-1, IL-10). Furthermore, we analyzed the expression of TLR4, p-NF-κB p65, and NF-κB p65 through Western blotting. RESULTS: The immunofluorescence results indicate that the ES-PMMA group exhibited an upregulation of CD206, an M2 marker, and a downregulation of CD86, an M1 marker, in comparison to the PMMA group. Additionally, the immunohistochemistry results revealed that the levels of IL-6 and TNF-α expression were lower in the ES-PMMA group than in the PMMA group, while the expression level of IL-10 was higher in the ES-PMMA group. Flow cytometry and RT-qPCR analyses revealed that the expression of M1-type macrophage marker CD86 was significantly elevated in the LPS group compared to the NC group. Additionally, M1-type macrophage-related cytokines TNF-α, IL-6, and iNOS were also found to be increased. However, in the LPS + ES group, the expression levels of CD86, TNF-α, IL-6, and iNOS were decreased, while the expression of M2-type macrophage markers CD206 and M2-type macrophage-related cytokines (IL-10, Arg-1) were increased compared to the LPS group. In comparison to the LPS + PMMA group, the LPS + ES-PMMA group demonstrated a down-regulation of CD86, TNF-α, IL-6, and iNOS expression levels, while increasing the expression levels of CD206, IL-10, and Arg-1. Western blotting results revealed a significant decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 in the LPS + ES group when compared to the LPS group. Additionally, the LPS + ES-PMMA group exhibited a decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 levels when compared to the LPS + PMMA group. CONCLUSION: ES-PMMA bone cement is more effective than PMMA bone cement in down-regulating the expression of the TLR4/NF-κB signaling pathway. Additionally, it induces macrophages to polarize towards the M2 phenotype, making it a crucial player in anti-inflammatory immune regulation.

Thermotolerance improvement of engineered Saccharomyces cerevisiae ERG5 Delta ERG4 Delta ERG3 Delta, molecular mechanism, and its application in corn ethanol production.

BACKGROUND: The thermotolerant yeast is beneficial in terms of efficiency improvement of processes and reduction of costs, while Saccharomyces cerevisiae does not efficiently grow and ferment at high-temperature conditions. The sterol composition alteration from ergosterol to fecosterol in the cell membrane of S. cerevisiae affects the thermotolerant capability. RESULTS: In this study, S. cerevisiae ERG5, ERG4, and ERG3 were knocked out using the CRISPR-Cas9 approach to impact the gene expression involved in ergosterol synthesis. The highest thermotolerant strain was S. cerevisiae ERG5ΔERG4ΔERG3Δ, which produced 22.1 g/L ethanol at 37 °C using the initial glucose concentration of 50 g/L with an increase by 9.4% compared with the wild type (20.2 g/L). The ethanol concentration of 9.4 g/L was produced at 42 ℃, which was 2.85-fold of the wild-type strain (3.3 g/L). The molecular mechanism of engineered S. cerevisiae at the RNA level was analyzed using the transcriptomics method. The simultaneous deletion of S. cerevisiae ERG5, ERG4, and ERG3 caused 278 up-regulated genes and 1892 down-regulated genes in comparison with the wild-type strain. KEGG pathway analysis indicated that the up-regulated genes relevant to ergosterol metabolism were ERG1, ERG11, and ERG5, while the down-regulated genes were ERG9 and ERG26. S. cerevisiae ERG5ΔERG4ΔERG3Δ produced 41.6 g/L of ethanol at 37 °C with 107.7 g/L of corn liquefied glucose as carbon source. CONCLUSION: Simultaneous deletion of ERG5, ERG4, and ERG3 resulted in the thermotolerance improvement of S. cerevisiae ERG5ΔERG4ΔERG3Δ with cell viability improvement by 1.19-fold at 42 °C via modification of steroid metabolic pathway. S. cerevisiae ERG5ΔERG4ΔERG3Δ could effectively produce ethanol at 37 °C using corn liquefied glucose as carbon source. Therefore, S. cerevisiae ERG5ΔERG4ΔERG3Δ had potential in ethanol production at a large scale under supra-optimal temperature.

Hexaindium Heptasulfide/Nitrogen and Sulfur Co-Doped Carbon Hollow Microspindles with Ultrahigh-Rate Sodium Storage through Stable Conversion and Alloying Reactions.

Group IIIA-VA metal sulfides (GMSs) have attracted increasing attention because of their unique Na-storage mechanisms through combined conversion and alloying reactions, thus delivering large theoretical capacities and low working potentials. However, Na+ diffusion within GMSs anodes leads to severe volume change, generally representing a fundamental limitation to rate capability and cycling stability. Here, monodispersed In6 S7 /nitrogen and sulfur co-doped carbon hollow microspindles (In6 S7 /NSC HMS) are produced by morphology-preserved thermal sulfurization of spindle-like and porous indium-based metal organic frameworks. The resulting In6 S7 /NSC HMS anode exhibits theoretical-value-close specific capacity (546.2 mAh g-1 at 0.1 A g-1 ), ultrahigh rate capability (267.5 mAh g-1 at 30.0 A g-1 ), high initial coulombic efficiency (≈93.5%), and ≈92.6% capacity retention after 4000 cycles. This kinetically favored In6 S7 /NSC HMS anode fills up the kinetics gap with a capacitive porous carbon cathode, enabling a sodium-ion capacitor to deliver an ultrahigh energy density of 136.3 Wh kg-1 and a maximum power density of 47.5 kW kg-1 . The in situ/ex situ analytical techniques and theoretical calculation both show that the robust and fast Na+ charge storage of In6 S7 /NSC HMS arises from the multi-electron redox mechanism, buffered volume expansion, negligible morphological change, and surface-controlled solid-state Na+ transport.

Prevalence status and associated factors of wrist postural injury in the Chinese occupational population.

Objective: This study investigated the prevalence of wrist injuries in 15 industries and different types of work in China. Study on the associated factors of wrist injuries provides a scientific basis for prevention and treatment of wrist diseases in occupational workers. Methods: A cross-sectional study of musculoskeletal symptoms of related practitioners in 15 industries, including automobile manufacturing, was conducted to retrieve worker demographic information, working wrist posture, and pain conditions. Multivariable binary logistic regression analyses were performed to identify factors associated with work-related musculoskeletal disorders (WMSDs). Results: The prevalence of wrist injuries among the study population was 13.2%. Toy manufacturing, animal husbandry, automobile manufacturing, shoe manufacturing, and biopharmaceutical manufacturing had the highest wrist injury rates at 29.1, 19.1, 14.9, 14.9, and 14.0%, respectively. Among the types of jobs, enamel workers (63.0%), butchers (43.6%), combers (32.5%), welders (31.3%), and scaffolders (26.5%) had the highest prevalence rates. Based on the final multivariate logistic regression analysis: female [odds ratios (OR) = 1.24; 95% confidence interval (CI), 1.15-1.35], 6-10 years of service (OR = 1.11; 95% CI, 1.03-1.18), >10 years of service (OR = 1.15; 95% CI, 1.06-1.25), frequent upward and downward flexion in wrist posture at work (OR = 1.81; 95% CI, 1.84-2.11), and frequent wrist placement on the edge of angular objects increased the OR of injury (OR = 1.52; 95% CI, 1.44-1.61). Need to squeeze objects tightly while working (OR = 1.72; 95% CI, 1.57-1.89), prolonged wrist flexion (OR = 1.86; 95% CI, 1.75-1.97), and work hand position above the shoulder for prolonged periods (OR = 1.11; 95% CI, 1.04-1.19) also suggested the relationship between these factors and the higher prevalence of wrist injury in the workers. The associated factor was physical activity (OR = 0.86; 95% CI, 0.80-0.94). Conclusion: This study suggested the relationship between these factors and the higher prevalence of wrist injury in the toy manufacturing, animal husbandry, automobile manufacturing, and shoe-making industries, enamel workers, butchers, and combers. And are work types that require special attention. Females, working age, physical activity, and abnormal posture of the wrist were factors significantly associated with WMSDs.

Shoulder work-related musculoskeletal disorders and related factors of workers in 15 industries of China: a cross-sectional study.

BACKGROUND: Changes in modern industrial production practices can easily lead to shoulder work-related musculoskeletal disorders (WMSD). The current reports on shoulder WMSD are limited to some industries are less well studied, and the sample size is usually small. This study aimed to describe the prevalence and severity of shoulder WMSD in a large sample of Chinese workers from 15 industries, analyze the possible correlations with sociodemographic and work-related variables, and compare the differences between industries. METHODS: A cross-sectional study was conducted among a sample of 55,749 participants from 252 enterprises in 15 industries throughout China. A Chinese version of the musculoskeletal disease questionnaire was used to collect the demographic factors, shoulder symptoms in past 12 months, and work-related factors including posture-related factors, repetition, vibration, work organization, job control, and environmental factors as independent variables. Descriptive statistics were used, and the binary logistic regression analysis was performed to explore the association between shoulder WMSD and potential demographic and work-related factors. RESULTS: Nearly 35.5% of participants reported shoulder pain and discomfort in the previous 12 months. Biopharmaceutical manufacturing (56.2%), medical services (54.4%), and aviation services (50.1%) were the three industries with the highest prevalence of shoulder WMSD. The pain score of aviation services workers was the highest. The related factors for shoulder WMSD varied among the different industries. CONCLUSION: Our study found a relatively high prevalence of shoulder WMSD in China. There were large differences in the prevalence of shoulder WMSD among industries, and the related factors were particular to each industry. Such information is useful to help occupational health practitioners and policymakers conduct preventive programs to reduce shoulder disorders in these working populations.

Characterization of a Trametes versicolor aflatoxin B1-degrading enzyme (TV-AFB1D) and its application in the AFB1 degradation of contaminated rice in situ.

Aflatoxin B1 (AFB1) contaminates rice during harvest or storage and causes a considerable risk to human and animal health. In this study, Trametes versicolor AFB1-degrading enzyme (TV-AFB1D) gene recombinantly expressed in engineered E. coli BL21 (DE3) and Saccharomyces cerevisiae. The TV-AFB1D enzymatic characteristics and AFB1 degradation efficiency in contaminated rice were investigated. Results showed that the size of recombinant TV-AFB1D expressing in E. coli BL21 (DE3) and S. cerevisiae was appropriately 77 KDa. The kinetic equation of TV-AFB1D was y = 0.01671x + 1.80756 (R 2 = 0.994, Km = 9.24 mM, and Vmax = 553.23 mM/min). The Kcat and Kcat/Km values of TV-AFB1D were 0.07392 (s-1) and 8 M-1 s-1, respectively. The AFB1 concentration of contaminated rice decreased from 100 µg/ml to 32.6 µg/ml after treatment at 32°C for 5 h under the catabolism of TV-AFB1D. S. cerevisiae engineered strains carrying aldehyde oxidase 1 (AOX1) and Cauliflower mosaic virus 35 S (CaMV 35 S) promoters caused the residual AFB1 contents, respectively, decreased to 3.4 and 2.9 µg/g from the initial AFB1 content of 7.4 µg/g after 24 h of fermentation using AFB1-contaminated rice as substrate. The AFB1 degradation rates of S. cerevisiae engineered strains carrying AOX1 and CaMV promoters were 54 and 61%, respectively. Engineered S. cerevisiae strains integrated with TV-AFB1D expression cassettes were developed to simultaneously degrade AFB1 and produce ethanol using AFB1-contaminated rice as substrate. Thus, TV-AFB1D has significant application potential in the AFB1 decomposition from contaminated agricultural products.

Prevalence and risk factors analysis for low back pain among occupational groups in key industries of China.

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.

CRISPR-Cas9 Approach Constructed Engineered Saccharomyces cerevisiae with the Deletion of GPD2, FPS1, and ADH2 to Enhance the Production of Ethanol.

Bioethanol plays an important value in renewable liquid fuel. The excessive accumulation of glycerol and organic acids caused the decrease of ethanol content in the process of industrial ethanol production. In this study, the CRISPR-Cas9 approach was used to construct S. cerevisiae engineering strains by the deletion of GPD2, FPS1, and ADH2 for the improvement of ethanol production. RNA sequencing and transcriptome analysis were used to investigate the effect of gene deletion on gene expression. The results indicated that engineered S. cerevisiae SCGFA by the simultaneous deletion of GPD2, FPS1, and ADH2 produced 23.1 g/L ethanol, which increased by 0.18% in comparison with the wild-type strain with 50 g/L of glucose as substrate. SCGFA strain exhibited the ethanol conversion rate of 0.462 g per g of glucose. In addition, the contents of glycerol, lactic acid, acetic acid, and succinic acid in SCGFA decreased by 22.7, 12.7, 8.1, 19.9, and 20.7% compared with the wild-type strain, respectively. The up-regulated gene enrichment showed glycolysis, fatty acid, and carbon metabolism could affect the ethanol production of SCGFA according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Therefore, the engineering strain SCGFA had great potential in the production of bioethanol.

Incidence and Risk Factors of the Upper-Limb Musculoskeletal Disorders Among Occupational Groups in Key Industries - China, 2018-2021.

What is already known about this topic?: The burden of illness and economic losses due to upper-limb work-related musculoskeletal disorders (UL-WMSDs) is high; thus, they have become a major global public health problem. At present, the epidemiological characteristics of UL-WMSDs in China's occupational population are still unknown. What is added by this report?: The incidence of UL-WMSDs among key occupational groups in China is 22.5%, with distinct occupational characteristics. What are the implications for public health practice?: This study has primarily determined the occurrence and potential risk factors of UL-WMSDs in key industries in China and provided data support for recommending prevention and control of the occurrence of such diseases in key industries in China, and in facilitating the addition into the China's List of Legal Occupational Diseases.

Transition-metal-free, one-pot synthesis of benzoxaboroles from o-bromobenzaldehydes via visible-light-promoted borylation.

A novel and simple one-pot stepwise method to synthesize benzoxaboroles was demonstrated. This step-by-step synthetic method includes photocatalytic boronization with phenothiazine as a photocatalyst and sequential water-induced reduction in the presence of bis(pinacolato)diboron. A series of o-bromobenzaldehydes were well-tolerated under the standard conditions. In addition, this method has been successfully applied in the synthesis of the anti-tuberculosis candidate drug GSK 3036656 and anti-fungal drug tavaborole.

Epidemiological Data of Work-Related Musculoskeletal Disorders - China, 2018-2020.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: In recent decades, work-related musculoskeletal disorders (WMSDs) have become increasingly prominent and have become an important issue that is of universal concern and an urgent need to be solved in all countries of the world. WHAT IS ADDED BY THIS REPORT?: The top three industries or occupational groups with the highest standardized prevalence rate of WMSDs were flight attendants, medical staff, and vegetable greenhouses in that order. Women workers were 1.5 times more likely to suffer from WMSDs than men workers. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study has found the prevalence and distribution characteristics of WMSDs in key industries in China. It is urgent to draw up relevant measures to prevent and control occupational populations with WMSDs.

Cucurbitane-Type Triterpene Glycosides from Momordica charantia and Their α-Glucosidase Inhibitory Activities.

Ten cucurbitane-type triterpene glycosides, including five new compounds named charantosides H (1), J (2), K (3), momorcharacoside A (4), goyaglycoside-L (5), and five known compounds (6-10), were isolated from the EtOAc extract of Momordica charantia fruits. The chemical structures of these compounds were identified by 1D and 2D NMR and HRESIMS spectroscopic analyses. Configurations of new compounds were determined by ROESY correlations and comparison of their 13C NMR data with literature reported values. All compounds were evaluated for their inhibition against α-glucosidase, in which compounds 2, 5, 7, 8, 9 showed moderate inhibitory activities with IC50 values ranging from 28.40 to 63.26 µM comparing with the positive control (acarbose, IC50 87.65 ± 6.51 µM).

Virtual Screening and Optimization of Novel mTOR Inhibitors for Radiosensitization of Hepatocellular Carcinoma.

BACKGROUND: Radiotherapy has an ameliorative effect on a wide variety of tumors, but hepatocellular carcinoma (HCC) is insensitive to this treatment. Overactivated mammalian target of rapamycin (mTOR) plays an important part in the resistance of HCC to radiotherapy; thus, mTOR inhibitors have potential as novel radiosensitizers to enhance the efficacy of radiotherapy for HCC. METHODS: A lead compound was found based on pharmacophore modeling and molecular docking, and optimized according to the differences between the ATP-binding pockets of mTOR and PI3K. The radiosensitizing effect of the optimized compound (2a) was confirmed by colony formation assays and DNA double-strand break assays in vitro. The discovery and preclinical characteristics of this compound are described. RESULTS: The key amino acid residues in mTOR were identified, and a precise virtual screening model was constructed. Compound 2a, with a 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine scaffold, exhibited promising potency against mTOR (mTOR IC50=7.1 nmol/L (nM)) with 126-fold selectivity over PI3Kα. Moreover, 2a significantly enhanced the sensitivity of HCC to radiotherapy in vitro in a dose-dependent manner. CONCLUSION: A new class of selective mTOR inhibitors was developed and their radiosensitization effects were confirmed. This study also provides a basis for developing mTOR-specific inhibitors for use as radiosensitizers for HCC radiotherapy.

NMR-based Structural Classification, Identification, and Quantification of Triterpenoids from Edible Mushroom Ganoderma resinaceum.

Ganoderma mushrooms have been widely used as functional food in China, Japan, and Korea. Ganoderma triterpenoids are deemed to be the main functional constituents. The structures of Ganoderma triterpenoids are complex but quite similar, which makes their analyses markedly limited. In this study, we developed a general 2D NMR method to differentiate Ganoderma triterpenoids, which classifies them into six types (A-F). Then, by the NMR-based isolation of A-F type triterpenoids from the fruiting bodies of G. resinaceum, four new compounds (1-4) and eight known compounds (5-12) were obtained. Moreover, combined with spiking experiments in 1D and 2D NMR spectra, compounds 5, 7, and 8, which belong to triterpenoids of A and B types, were identified. At the end, to achieve a more extensive application for this NMR method, a qNMR method for the absolute quantification of 5, 7, and 8 in the gross triterpenoids from G. resinaceum was set up. The results showed that this NMR method is reliable for the NMR-guided isolation and quantification of triterpenoids in G. resinaceum.

Investigation on Work-Related Musculoskeletal Disorders - China, 2018-2019.

What is already known about this topic? Work-related musculoskeletal disorders (WMSDs) have a high prevalence and seriously harmful, which has attracted extensive attention in various countries in the world. Currently, the occurrence and rules of WMSDs in key industries are not known in China. What is added by this report? The prevalence of WMSDs is relatively high among professional populations in key industries in China, with the most commonly affected body parts concentrated in neck, shoulders, and low back and increasing with age and working years. What are the implications for public health practice? This study determined the prevalence and distribution characteristics of WMSDs in key industries in China and provided scientific evidence to recommend for inclusion of WMSDs in the new revision of the list of occupational diseases in China.