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Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe 3 O 4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe 3 O 4 @ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe 3 O 4 @ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe 3 O 4 @ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe 3 O 4 @ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe 3 O 4 @ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Background: Prostate cancer (PCa) is the most common non-cutaneous malignancy in men globally. Sappan lignum , which exists in the heartwood of Caesalpinia sappan L., has antitumor effects; however, its exact mechanism of action remains unclear. This study elucidated the underlying mechanisms of Sappan lignum in PCa through network pharmacology approaches and molecular docking techniques. Moreover, the therapeutic effects of Sappan lignum on PCa were verified through in vitro experiments., Methods: The constituent ingredients of Sappan lignum were retrieved from the HERB database. Active plant-derived compounds of Sappan lignum were screened based on gastrointestinal absorption and gastric drug properties. Disease targets for PCa were screened using unpaired and paired case datasets from the Gene Expression Omnibus. Intersection targets were used for gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Core targets were identified through topological analysis parameters and their clinical relevance was validated through The Cancer Genome Atlas database. The affinity between the phytochemicals of Sappan lignum and core proteins was verified using the molecular docking technique. Validation experiments confirmed the significant potential of Sappan lignum in treating PCa., Results: Twenty-one plant-derived compounds of Sappan lignum and 821 differentially expressed genes associated with PCa were collected. Among 32 intersection targets, 8 were screened according to topological parameters. KEGG analysis indicated that the antitumor effects of Sappan lignum on PCa were primarily associated with the p53 pathway. The molecular docking technique demonstrated a strong affinity between 3-deoxysappanchalcone (3-DSC) and core proteins, particularly cyclin B1 (CCNB1). CCNB1 expression correlated with clinicopathological features in patients with PCa. Experimental results revealed that 3-DSC exhibited anti-proliferative, anti-migratory, and pro-apoptotic effects on 22RV1 and DU145 cells while also causing G2/M phase cell cycle arrest, potentially through modulating the p53/p21/CDC2/CCNB1 pathway., Conclusion: This research highlights the promising therapeutic potential of Sappan lignum in treating PCa, with a particular focus on targeting the p53 pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Jiang, Zhang, Sun, Zhang, Xu, Huang and Wan.)

Today, pathogenic microorganisms are increasingly developing resistance to conventional drugs, necessitating the exploration of alternative strategies. In addressing this challenge, nano-based antibacterial agents offer a promising avenue of research. In the present study, we used an extract of Moringa oleifera , a widely recognized edible and medicinal plant, to synthesize biogenetic tellurium nanoparticles (Bio-TeNPs). Transmission electron microscopy, scanning electron microscopy, and dynamic light scattering analyses revealed that the obtained Bio-TeNPs had diameters between 20 and 50 nm, and zeta potential values of 23.7 ± 3.3 mV. Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy revealed that the Bio-TeNPs consisted primarily of Te(0), along with some organic constituents. Remarkably, these Bio-TeNPs exhibited potent antibacterial activity against a spectrum of pathogens, including Escherichia coli , Klebsiella pneumoniae , Shigella dysenteriae , Salmonella typhimurium , Streptococcus pneumoniae , and Streptococcus agalactiae . In addition, findings from growth curve experiments, live/dead cell staining, and scanning electron microscopy observations of cell morphology demonstrated that Bio-TeNPs at a concentration of 0.07 mg/mL effectively disrupted E . coli and K . pneumoniae cells, leading to cell rupture or shrinkage. The biofilm inhibition rates of 0.7 mg/mL Bio-TeNPs against E . coli and K . pneumoniae reached 92% and 90%, respectively. In addition, 7 mg/mL Bio-TeNPs effectively eradicated E . coli from the surfaces of glass slides, with a 100% clearance rate. These outcomes underscore the exceptional antibacterial efficacy of Bio-TeNPs and highlight their potential as promising nanomaterials for combating bacterial infections.

Arsenic (As) is a groundwater contaminant of global concern. The degradation of dissolved organic matter (DOM) can provide a reducing environment for As release. However, the interaction of DOM with local microbial communities and how different sources and types of DOM influence the biotransformation of As in aquifers is uncertain. This study used optical spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), metagenomics, and structural equation modeling (SEM) to demonstrate the how the biotransformation of As in aquifers is promoted. The results indicated that the DOM in high-As groundwater is dominated by highly unsaturated low-oxygen(O) compounds that are quite humic and stable. Metagenomics analysis indicated Acinetobacter, Pseudoxanthomonas, and Pseudomonas predominate in high-As environments; these genera all contain As detoxification genes and are members of the same phylum (Proteobacteria). SEM analyses indicated the presence of Proteobacteria is positively related to highly unsaturated low-O compounds in the groundwater and conditions that promote arsenite release. The results illustrate how the biogeochemical transformation of As in groundwater systems is affected by DOM from different sources and with different characteristics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xianjun xie reports financial support was provided by China University of Geosciences. Xianjun xie reports a relationship with China University of Geosciences that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Although the prognosis of advanced schistosomiasis patients has significantly improved, the impact of historical disease conditions on life expectancy remains unclear., Methods: Utilizing data from an advanced schistosomiasis cohort (n=10 362) from 2008 to 2019 in Hunan, China, we examined five historical disease conditions: times of praziquantel treatment, the history of ascites, splenectomy, upper gastrointestinal bleeding (UGIB) and hepatic coma. Using latent class analysis, participants were categorized into three groups: Group 1 (characterized by no risk conditions), Group 2 (had ≤3 times of praziquantel treatment without UGIB history) and Group 3 (had UGIB history). Life expectancies were calculated using the life table method., Results: At the age of 45 y, patients with ≤3 times of praziquantel treatment, a history of ascites, UGIB, hepatic coma and those without splenectomy exhibited lower life expectancies. Groups 1, 2 and 3 had estimated life expectancies of 32.32, 26.76 and 25.38 y, respectively. Compared with Group 1, women in Group 3 experienced greater life expectancy loss than those in Group 2, with the difference narrowing with age., Conclusions: Based on the consideration of overall physical conditions, tailored treatment and healthcare, along with public health interventions targeting diverse populations, could mitigate the prevalence of poor disease conditions and premature deaths., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Xiatianwu is a traditional Chinese medicine. This study investigates the function of Xiatianwu in treating HCC through database analyses and in vitro experiments. The active ingredients of Xiatianwu were identified from TCMSP and HERB databases and their targets were predicted by Swiss TargetPrediction. The HCC dataset was screened using the GEO database, and the differentially expressed genes between HCC and non-tumor liver tissues were analyzed to identify overlapping targets with Xiatianwu. The intersecting targets underwent enrichment analysis using R software to elucidate the molecular mechanisms of Xiatianwu against HCC. Core targets were identified using the PPI network and MCODE algorithm. Clinical relevance and disease prognosis in HCC were verified using the TCGA database. Meanwhile, binding affinities among components and targets were validated with molecular docking. Finally, the anti-HCC efficacy of the active ingredient was validated in vitro. Our findings revealed that eight active ingredients of Xiatianwu interacted with 11 key targets, providing anti-HCC efficacy. Molecular docking indicated that bicuculline and fumarine exhibited superior binding abilities. Bicuculline, a representative ingredient of Xiatianwu, was chosen for in vitro validation. Results demonstrated that bicuculline, in a dose-dependent manner inhibited HCC cell viability, reduced migration, suppressed the G0/M cell cycle, and decreased core protein expression. Xiatianwu demonstrates significant potential for clinical application in treating HCC. Bicuculline, a key active ingredient of Xiatianwu, exerts anti-HCC effects by inhibiting the cell cycle., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The rumen plays an essential role in the physiology and production of agriculturally important ruminants such as cattle. Functions of the rumen include fermentation, absorption, metabolism, and protection. Cattle are, however, not born with a functional rumen, and the rumen undergoes considerable changes in size, histology, physiology, and transcriptome from birth to adulthood. In this review, we discuss these changes in detail, the factors that affect these changes, and the potential molecular and cellular mechanisms that mediate these changes. The introduction of solid feed to the rumen is essential for rumen growth and functional development in post-weaning calves. Increasing evidence suggests that solid feed stimulates rumen growth and functional development through butyric acid and other volatile fatty acids (VFAs) produced by microbial fermentation of feed in the rumen and that VFAs stimulate rumen growth and functional development through hormones such as insulin and insulin-like growth factor I (IGF-I) or through direct actions on energy production, chromatin modification, and gene expression. Given the role of the rumen in ruminant physiology and performance, it is important to further study the cellular, molecular, genomic, and epigenomic mechanisms that control rumen growth and development in postnatal ruminants. A better understanding of these mechanisms could lead to the development of novel strategies to enhance the growth and development of the rumen and thereby the productivity and health of cattle and other agriculturally important ruminants.

Background: Satellite cells are myogenic precursor cells in adult skeletal muscle and play a crucial role in skeletal muscle regeneration, maintenance, and growth. Like embryonic myoblasts, satellite cells have the ability to proliferate, differentiate, and fuse to form multinucleated myofibers. In this study, we aimed to identify additional transcription factors that control gene expression during bovine satellite cell proliferation and differentiation., Results: Using chromatin immunoprecipitation followed by sequencing, we identified 56,973 and 54,470 genomic regions marked with both the histone modifications H3K4me1 and H3K27ac, which were considered active enhancers, and 50,956 and 59,174 genomic regions marked with H3K27me3, which were considered repressed enhancers, in proliferating and differentiating bovine satellite cells, respectively. In addition, we identified 1,216 and 1,171 super-enhancers in proliferating and differentiating bovine satellite cells, respectively. Analyzing these enhancers showed that in proliferating bovine satellite cells, active enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation whereas repressed enhancers were associated with genes essential for myoblast differentiation, and that in differentiating satellite cells, active enhancers were associated with genes essential for myoblast differentiation or muscle contraction whereas repressed enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation. Active enhancers in proliferating bovine satellite cells were enriched with binding sites for many transcription factors such as MYF5 and the AP-1 family transcription factors; active enhancers in differentiating bovine satellite cells were enriched with binding sites for many transcription factors such as MYOG and TFAP4; and repressed enhancers in both proliferating and differentiating bovine satellite cells were enriched with binding sites for NF-kB, ZEB-1, and several other transcription factors. The role of TFAP4 in satellite cell or myoblast differentiation was previously unknown, and through gene knockdown and overexpression, we experimentally validated a critical role for TFAP4 in the differentiation and fusion of bovine satellite cells into myofibers., Conclusions: Satellite cell proliferation and differentiation are controlled by many transcription factors such as AP-1, TFAP4, NF-kB, and ZEB-1 whose roles in these processes were previously unknown in addition to those transcription factors such as MYF5 and MYOG whose roles in these processes are widely known., (© 2024. The Author(s).)

Intramuscular fat, also referred to as marbling fat, is the white fat deposited within skeletal muscle tissue. The content of intramuscular fat in the skeletal muscle, particularly the longissimus dorsi muscle, of cattle is a critical determinant of beef quality and value. In this review, we summarize the process of intramuscular fat development and growth, the factors that affect this process, and the molecular and epigenetic mechanisms that mediate this process in cattle. Compared to other species, cattle have a remarkable ability to accumulate intramuscular fat, partly attributed to the abundance of sources of fatty acids for synthesizing triglycerides. Compared to other adipose depots such as subcutaneous fat, intramuscular fat develops later and grows more slowly. The commitment and differentiation of adipose precursor cells into adipocytes as well as the maturation of adipocytes are crucial steps in intramuscular fat development and growth in cattle. Each of these steps is controlled by various factors, underscoring the complexity of the regulatory network governing adipogenesis in the skeletal muscle. These factors include genetics, epigenetics, nutrition (including maternal nutrition), rumen microbiome, vitamins, hormones, weaning age, slaughter age, slaughter weight, and stress. Many of these factors seem to affect intramuscular fat deposition through the transcriptional or epigenetic regulation of genes directly involved in the development and growth of intramuscular fat. A better understanding of the molecular and cellular mechanisms by which intramuscular fat develops and grows in cattle will help us develop more effective strategies to optimize intramuscular fat deposition in cattle, thereby maximizing the quality and value of beef meat.

Background: The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues., Results: A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network., Conclusions: These validated results show significant improvement over current bovine genome annotations., (© The Author(s) 2024. Published by Oxford University Press GigaScience.)

Background: Huaier ( Trametes robiniophila Murr), a traditional Chinese medicine, is widely used in China as a complementary and alternative therapy to treat hepatocellular carcinoma (HCC). Past studies have shown that Huaier can arrest the cell cycle, promote apoptosis and inhibit the proliferation of cancer cells. However, how it regulates the metabolism of HCC is still unclear., Objective: This study explores the metabolic-related function of Huaier in treating HCC with an in-silico approach., Methods: A network pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of metabolic reprogramming in HCC with Huaier. The compounds of Huaier were obtained from public databases. Oral bioavailability and drug likeness were screened using the TCMSP platform. The differential gene expressions between HCC and non-tumor tissue were calculated and used to find the overlap from the targets of Huaier. The enrichment analysis of the overlapped targets by Metascape helped filter out the metabolism-related targets of Huaier in treating HCC. Protein-protein interaction (PPI) network construction and topological screening revealed the hub nodes. The prognosis and clinical correlation of these targets were validated from the cancer genome atlas (TCGA) database, and the interactions between the hub nodes and active ingredients were validated by molecular docking., Results: The results showed that Peroxyergosterol, Daucosterol, and Kaempferol were the primary active compounds of Huaier involved in the metabolic reprogramming of HCC. The top 6 metabolic targets included AKR1C3, CYP1A1, CYP3A4, CYP1A2, CYP17A1, and HSD11B1. The decreased expression of CYP3A4 and increased expression of AKR1C3 were related to the poor overall survival of HCC patients. The molecular docking validated that Peroxyergosterol and Kaempferol exhibited the potential to modulate CYP3A4 and AKR1C3 from a computational perspective., Conclusion: This study provided a workflow for understanding the mechanism of Huaier in regulating the metabolic reprogramming of HCC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Dysregulated iron homeostasis underlies diverse pathologies, from ischemia-reperfusion injury to epithelial-mesenchymal transition and drug-tolerant "persister" cancer cell states. Here, we introduce ferrous iron-activatable luciferin-1 (FeAL-1), a small-molecule probe for bioluminescent imaging of the labile iron pool (LIP) in luciferase-expressing cells and animals. We find that FeAL-1 detects LIP fluctuations in cells after iron supplementation, depletion, or treatment with hepcidin, the master regulator of systemic iron in mammalian physiology. Utilizing FeAL-1 and a dual-luciferase reporter system, we quantify LIP in mouse liver and three different orthotopic pancreatic ductal adenocarcinoma tumors. We observed up to a 10-fold increase in FeAL-1 bioluminescent signal in xenograft tumors as compared to healthy liver, the major organ of iron storage in mammals. Treating mice with hepcidin further elevated hepatic LIP, as predicted. These studies reveal a therapeutic index between tumoral and hepatic LIP and suggest an approach to sensitize tumors toward LIP-activated therapeutics., Competing Interests: Declaration of interests E.A.C. and A.R.R. are co-founders and consultants to Tatara Therapeutics., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2-5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

Background and Aim: Microbiome-targeted therapies (MTTs) are considered as promising interventions for cirrhosis, but the impact of gut microbiome modulation on liver function and disease severity has not been fully assessed. We comprehensively evaluated the efficacy of MTTs in patients with liver cirrhosis., Methods: Data from randomized controlled trials were collected through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov from inception to February 20, 2023. Clinical outcomes were pooled and expressed in terms of risk ratios or mean differences (MD). Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A trial sequential analysis was applied to calculate the required information size and evaluate the credibility of the meta-analysis results., Results: Twenty-one studies with a total of 1699 cirrhotic patients were included for meta-analysis. MTTs were associated with a significant reduction in aspartate aminotransferase (MD, -3.62; 95% CI, -6.59 to -0.65), the risk of hepatic encephalopathy (risk ratio = 0.56, 95% CI: 0.46 to 0.68), model for end-stage liver disease score (MD, -0.90; 95% CI, -1.17 to -0.11), ammonia (MD, -11.86; 95% CI, -16.39 to -7.33), and endotoxin (MD, -0.14; 95% CI, -0.23 to -0.04). The trial sequential analysis yielded reliable results of these outcomes. No effects were observed on the changes of other hepatic function indicators., Conclusion: MTTs appeared to be associated with a slowed deterioration in liver cirrhosis, which could provide reference for clinicians in treatment of cirrhotic patients based on their conditions., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Oncomelania hupensis is the sole intermediate host of Schistosoma japonicum. Its emergence and recurrence pose a constant challenge to the elimination of schistosomiasis in China. It is important to accurately predict the snail distribution for schistosomiasis prevention and control., Methods: Data describing the distribution of O. hupensis in 2016 was obtained from the Yunnan Institute of Endemic Disease Control and Prevention. Eight machine learning algorithms, including eXtreme Gradient Boosting (XGB), support vector machine (SVM), random forest (RF), generalized boosting model (GBM), neural network (NN), classification and regression trees (CART), k-nearest neighbors (KNN), and generalized additive model (GAM), were employed to explore the impacts of climatic, geographical, and socioeconomic variables on the distribution of suitable areas for O. hupensis. Predictions of the distribution of suitable areas for O. hupensis were made for various periods (2030s, 2050s, and 2070s) under different climate scenarios (SSP126, SSP245, SSP370, and SSP585)., Results: The RF model exhibited the best performance (AUC: 0.991, sensitivity: 0.982, specificity: 0.995, kappa: 0.942) and the CART model performed the worst (AUC: 0.884, sensitivity: 0.922, specificity: 0.943, kappa: 0.829). Based on the RF model, the top six important variables were as follows: Bio15 (precipitation seasonality) (33.6%), average annual precipitation (25.2%), Bio2 (mean diurnal temperature range) (21.7%), Bio19 (precipitation of the coldest quarter) (14.5%), population density (13.5%), and night light index (11.1%). The results demonstrated that the overall suitable habitats for O. hupensis were predominantly distributed in the schistosomiasis-endemic areas located in northwestern Yunnan Province under the current climate situation and were predicted to expand north- and westward due to climate change., Conclusions: This study showed that the prediction of the current distribution of O. hupensis corresponded well with the actual records. Furthermore, our study provided compelling evidence that the geographical distribution of snails was projected to expand toward the north and west of Yunnan Province in the coming decades, indicating that the distribution of snails is driven by climate factors. Our findings will be of great significance for formulating effective strategies for snail control., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Snail abundance varies spatially and temporally. Few studies have elucidated the different effects of the determinants affecting snail density between upstream and downstream areas of the Three Gorges Dam (TGD). We therefore investigated the differential drivers of changes in snail density in these areas, as well as the spatial-temporal effects of these changes., Methods: A snail survey was conducted at 200 sites over a 5-year period to monitor dynamic changes in snail abundance within the Yangtze River basin. Data on corresponding variables that might affect snail abundance, such as meteorology, vegetation, terrain and economy, were collected from multiple data sources. A Bayesian spatial-temporal modeling framework was constructed to explore the differential determinants driving the change in snail density and the spatial-temporal effects of the change., Results: Volatility in snail density was unambiguously detected in the downstream area of the TGD, while a small increment in volatility was detected in the upstream area. Regarding the downstream area of the TGD, snail density was positively associated with the average minimum temperature in January of the same year, the annual Normalized Difference Vegetation Index (NDVI) of the previous year and the second, third and fourth quartile, respectively, of average annual relative humidity of the previous year. Snail density was negatively associated with the average maximum temperature in July of the previous year and annual nighttime light of the previous year. An approximately inverted "U" curve of relative risk was detected among sites with a greater average annual ground surface temperature in the previous year. Regarding the upstream area, snail density was positively associated with NDVI and with the second, third and fourth quartile, respectively, of total precipitation of the previous year. Snail density was negatively associated with slope., Conclusions: This study demonstrated a rebound in snail density between 2015 and 2019. In particular, temperature, humidity, vegetation and human activity were the main drivers affecting snail abundance in the downstream area of the TGD, while precipitation, slope and vegetation were the main drivers affecting snail abundance in the upstream area. These findings can assist authorities to develop and perform more precise strategies for surveys and control of snail populations., (© 2023. The Author(s).)

Background: Schistosomiasis is of great public health concern with a wide distribution and multiple determinants. Due to the advances in schistosomiasis elimination and the need for precision prevention and control, identifying determinants at a fine scale is urgent and necessary, especially for resource deployment in practice. Our study aimed to identify the determinants for the seropositive rate of schistosomiasis at the village level and to explore their spatial variations in local space., Methodology: The seropositive rates of schistosomiasis were collected from 1714 villages or communities in Human Province, and six spatial regression models including ordinary least squares (OLS), spatial lag model (SLM), spatial error model (SEM), geographically weighted regression (GWR), robust GWR (RGWR) and multiscale GWR (MGWR) were used to fit the data., Principal/findings: MGWR was the best-fitting model (R2: 0.821, AICc:2727.092). Overall, the nearest distance from the river had the highest mean negative correlation, followed by proportion of households using well water and the annual average daytime surface temperature. The proportions of unmodified toilets showed the highest mean positive correlation, followed by the snail infested area, and the number of cattle. In spatial variability, the regression coefficients for the nearest distance from the river, annual average daytime surface temperature and the proportion of unmodified toilets were significant in all villages or communities and varied little in local space. The other significant determinants differed substantially in local space and had significance ratios ranging from 41% to 70%, including the number of cattle, the snail infested area and the proportion of households using well water., Conclusions/significance: Our study shows that MGWR was well performed for the spatial variability of schistosomiasis in Hunan province. The spatial variability was different for different determinants. The findings for the determinants for the seropositive rate and mapped variability for some key determinants at the village level can be used for developing precision intervention measure for schistosomiasis control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The inhibitory effect of growth hormone (GH) on adipose tissue growth is well known, but the underlying mechanism is not fully understood. In this study, we determined the possibility that GH inhibits adipose tissue growth by inhibiting adipogenesis, the process of formation of adipocytes from stem cells, in the lit/lit mice. The lit/lit mice are GH deficient because of a spontaneous mutation to the GH releasing hormone receptor (ghrhr) gene, and they have more subcutaneous fat despite being smaller than the lit/+ mice at the same age. We found that cells of the stromal vascular fraction (SVF) of subcutaneous fat from the lit/lit mice had greater adipogenic potential than those from the lit/+ mice, as evidenced by forming greater numbers of lipid droplets-containing adipocytes and having greater expression of adipocyte marker genes during induced adipocyte differentiation in culture. However, addition of GH to the culture did not reverse the superior adipogenic potential of subcutaneous SVF from the lit/lit mice. Through florescence-activated cell sorting and quantification of mRNAs of preadipocyte markers, including CD34, CD29, Sca-1, CD24, Pref-1, and PPARγ, we found that subcutaneous SVF from the lit/lit mice contained more preadipocytes than that from the lit/+ mice. These results support the notion that GH inhibits adipose tissue growth in mice at least in part by inhibiting adipogenesis. Furthermore, these results suggest that GH inhibits adipogenesis in mice not by inhibiting the terminal differentiation of preadipocytes into adipocytes, rather by inhibiting the formation of preadipocytes from stem cells or the recruitment of stem cells to the fat depot., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Jia, Tan and Jiang.)

Objectives: In this study, we aimed to study the rate of autoantibodies against type I interferons (IFNs) in patients with COVID-19 and analyze its dependence on severity of infection and some other variables., Methods: A systemic review with the search terms: "COVID-19" or "SARS-CoV-2" and "autoantibodies" or "autoantibody" and "IFN" or "interferon" for the period 20 December 2019 to 15 August 2022 was carried out using PubMed, Embase, Cochrane, and Web of Science. R 4.2.1 software was used for meta-analysis of the published results. Pooled risk ratios and 95% confidence intervals (CIs) were calculated., Results: We identified eight studies involving 7729 patients, of whom 5097 (66%) had severe COVID-19 and 2632 (34%) had mild or moderate symptoms. The positive rate of anti-type-I-IFN-autoantibodies in the total dataset was 5% (95% CI, 3-8%), but reached 10% (95% CI, 7-14%) in those with severe infection. The most common subtypes were anti-IFN-α (89%) and anti-IFN-ω (77%). The overall prevalence in male patients was 5% (95% CI, 4-6%), and in female patients 2% (95% CI, 1-3%)., Conclusion: Severe COVID-19 is associated with high rates of autoantibodies against type-I-IFN and more so in male than female patients., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The area of Oncomelania hupensis snail remains around 3.6 billion m 2 , with newly emerging and reemergent habitats continuing to appear in recent years. This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam (TGD)., Methods: Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance. Meta-analysis was conducted to estimate the snail density. Joinpoint model was used to identify the changing trend and inflection point. Inverse distance weighted interpolation (IDW) was used to determine the spatial distribution of recent snail density., Results: A total of 3777 snail survey sites with a precise location of village or beach were identified. For the downstream area, snail density peaked in 1998 (1.635/0.11 m 2 , 95% CI: 1.220, 2.189) and fluctuated at a relatively high level before 2003, then declined steadily from 2003 to 2012. Snail density maintained lower than 0.150/0.11 m 2 between 2012 and 2019. Joinpoint model identified the inflection of 2003, and a significant decreasing trend from 2003 to 2012 with an annual percentage change (APC) being - 20.56% (95% CI: - 24.15, - 16.80). For the upstream area, snail density peaked in 2005 (0.760/0.11 m 2 , 95% CI: 0.479, 1.207) and was generally greater than 0.300/0.11 m 2 before 2005. Snail density was generally lower than 0.150/0.11 m 2 after 2011. Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being - 6.05% (95% CI: - 7.97, - 7.09), and no inflection was identified. IDW showed the areas with a high snail density existed in Poyang Lake, Dongting Lake, Jianghan Plain, and the Anhui branch of the Yangtze River between 2015 and 2019., Conclusions: Snail density exhibited a fluctuating downward trend in the Yangtze River basin. In the downstream area, the operation of TGD accelerated the decline of snail density during the first decade period, then snail density fluctuated at a relatively low level. There still exists local areas with a high snail density. Long-term control and monitoring of snails need to be insisted on and strengthened., (© 2023. The Author(s).)

Culex tritaeniorhynchus is the primary vector of Japanese encephalitis (JE) and has a wide global distribution. However, the current and future geographic distribution maps of Cx. tritaeniorhynchus in global are still incomplete. Our study aims to predict the potential distribution of Cx. tritaeniorhynchus in current and future conditions to provide a guideline for the formation and implementation of vector control strategies all over the world. We collected and screened the information on the occurrence of Cx. tritaeniorhynchus by searching the literature and online databases and used ten algorithms to investigate its global distribution and impact factors. Cx. tritaeniorhynchus had been detected in 41 countries from 5 continents. The final ensemble model (TSS = 0.864 and AUC = 0.982) indicated that human footprint was the most important factor for the occurrence of Cx. tritaeniorhynchus . The tropics and subtropics, including southeastern Asia, Central Africa, southeastern North America and eastern South America, showed high habitat suitability for Cx. tritaeniorhynchus . Cx. tritaeniorhynchus is predicted to have a wider distribution in all the continents, especially in Western Europe and South America in the future under two extreme emission scenarios (SSP5-8.5 and SSP1-2.6). Targeted strategies for the control and prevention of Cx. tritaeniorhynchus should be further strengthened.

Background: Few studies have investigated the change in life expectancy (LE) and the healthy lifespan among patients with advanced schistosomiasis. This study was to evaluate the LE and healthy life expectancy (HLE) for patients and assess the mechanism responsible for the LE inequality., Methods: We utilized data from a dynamic advanced schistosomiasis cohort (10,362 patients) for the period from January 2008 to December 2019 in Hunan Province, China, to calculate the LEs of patients, and made a comparison with that of general population (19,642 schistosomiasis-free individuals) in the schistosomiasis endemic areas. LEs were estimated from 15 years of age by constructing period life tables. Arriaga's decomposition method was applied to quantify the influence of the age structure on the difference in LE. HLE for advanced schistosomiasis patients was calculated by using Sullivan method with age-specific disability weight. The LE and HLE were calculated for both males and females to perform further analyses on gender gap., Results: The estimated LE for advanced schistosomiasis patients aged 15-19 was 49.51 years (48.86 years for males and 51.07 years for females), which was 20.14 years lower compared with general population (69.65 years), and the LE gap between patients and general population decreased with age. The largest age-specific mortality contribution to the gap (32.06%) occurred at age 80-84 years. Women had a lower LE and HLE than men at age ≥ 60 years (both gender gaps in LE and HLE < 0). For advanced schistosomiasis patients, the gender gap in LE was largely attributed to the difference in mortality among those under the age of 55; the age-specific mortality in women exerted positive influence on the gap at age 25-64 and 75-79 years, with the contribution rate ranging from 0.59% to 57.02%, and made the negative contribution at other age groups., Conclusions: The LE of advanced schistosomiasis patients was still much lower compared with general population. Strengthened prevention strategies and targeted treatments are needed to reduce morbidity and mortality due to advanced schistosomiasis, especially for younger population and elderly female patients., (© 2023. The Author(s).)

The inhibitory effect of growth hormone (GH) on adipose tissue growth and the stimulatory effect of GH on lipolysis are well known, but the mechanisms underlying these effects are not completely understood. In this study, we revisited the effects of GH on adipose tissue growth and lipolysis in the lit/lit mouse model. The lit/lit mice are GH deficient because of a mutation in the GH releasing hormone receptor gene. We found that the lit/lit mice had more subcutaneous fat and larger adipocytes than their heterozygous lit/+ littermates and that these differences were partially reversed by 4-week GH injection. We also found that GH injection to the lit/lit mice caused the mature adipose tissue and adipocytes to reduce in size. These results demonstrate that GH inhibits adipose tissue growth at least in part by stimulating lipolysis. To determine the mechanism by which GH stimulates lipolysis, we cultured adipose tissue explants and adipocytes derived from lit/lit mice with GH and/or isoproterenol, an agonist of the beta-adrenergic receptors. These experiments showed that whereas isoproterenol, expectedly, stimulated potent lipolysis, GH, surprisingly, had no effect on basal lipolysis or isoproterenol-induced lipolysis in adipose tissue explants or adipocytes. We also found that both isoproterenol-induced lipolysis and phosphorylation of hormone-sensitive lipase were not different between lit/lit and lit/+ mice. Taken together, these results support the conclusion that GH has lipolytic effect in mice but argue against the notion that GH stimulates lipolysis by directly acting on adipocytes or by enhancing β-adrenergic receptors-mediated lipolysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao and Jiang.)

Importance: Early recognition of metabolic bone disease (MBD) in infants is necessary but difficult; an appropriate tool to screen infants at risk of developing MBD is needed., Objectives: To develop a predictive model for neonates at risk for MBD in the prenatal and postnatal periods and detect the pivotal exposed factors in each period., Design, Setting, and Participants: A diagnostic study was conducted from January 1, 2012, to December 31, 2021, in Shanghai, China. A total of 10 801 pregnant women (singleton pregnancy, followed up until 1 month after parturition) and their infants (n = 10 801) were included. An artificial neural network (ANN) framework was used to build 5 predictive models with different exposures from prenatal to postnatal periods. The receiver operating characteristic curve was used to evaluate the model performance. The importance of each feature was examined and ranked., Results: Of the 10 801 Chinese women who participated in the study (mean [SD] age, 29.7 [3.9] years), 7104 (65.8%) were local residents, 1001 (9.3%) had uterine scarring, and 138 (1.3%) gave birth to an infant with MBD. Among the 5 ANN models, model 1 (significant prenatal and postnatal factors) showed the highest AUC of 0.981 (95% CI, 0.970-0.992), followed by model 5 (postnatal factors; AUC, 0.977; 95% CI, 0.966-0.988), model 4 (all prenatal factors; AUC, 0.850; 95% CI, 0.785-0.915), model 3 (gestational complications or comorbidities and medication use; AUC, 0.808; 95% CI, 0.726-0.891), and model 2 (maternal nutritional conditions; AUC, 0.647; 95% CI, 0.571-0.723). Birth weight, maternal age at pregnancy, and neonatal disorders (anemia, respiratory distress syndrome, and septicemia) were the most important model 1 characteristics for predicting infants at risk of MBD; among these characteristics, extremely low birth weight (importance, 50.5%) was the most powerful factor. The use of magnesium sulfate during pregnancy (model 4: importance, 21.2%) was the most significant predictor of MBD risk in the prenatal period., Conclusions and Relevance: In this diagnostic study, ANN appeared to be a simple and efficient tool for identifying neonates at risk for MBD. Combining prenatal and postnatal factors or using postnatal exposures alone provided the most precise prediction. Extremely low birth weight was the most significant predictive factor, whereas magnesium sulfate use during pregnancy could be an important bellwether for MBD before delivery.

This study explored the environmental determinants of different months on snail density measured in April at different types of snail habitats (marshlands, inner embankments, and hills) by considering spatial effects. Data were gathered from surveys on snails that were conducted in Hunan Province in April 2016, and information was collected on environmental variables. To investigate the environmental factors influencing snail density in various types of snail habitats, the ordinary least square model, spatial lag model, and spatial error model were all used. The environmental determinants for snail density showed different effects in the three types of snail habitats. In marshlands, snail density measured in April was associated positively with the normalized difference vegetation index (NDVI) and was associated negatively with flooding duration and annual hours of sunshine. Extreme temperatures correlated strongly to snail density measured in April (P < 0.05). In areas inside embankments, snail density measured in April increased with a decreased distance between snail habitat and the nearest river (P < 0.05). In hills, extreme heat, annual hours of sunshine, NDVI in September, and annual average land surface temperature (LST) were associated negatively with snail density measured in April, whereas index of moisture (IM) was associated positively with snail density measured in April (P < 0.05). The effects of LST and hours of sunshine on snail density measured in April varied with months of the year in the three different types of snail habitats (P < 0.05). Our study might provide a theoretical foundation for preventing snail transmission and subsequent spread of schistosomiasis.

Myoblast differentiation is a complex process whereby the mononuclear muscle precursor cells myoblasts express skeletal-muscle-specific genes and fuse with each other to form multinucleated myotubes. The objective of this study was to identify potentially novel mechanisms that mediate myoblast differentiation. We first compared transcriptomes in C2C12 myoblasts before and 6 days after induction of myogenic differentiation by RNA-seq. This analysis identified 11,046 differentially expressed genes, of which 5615 and 5431 genes were upregulated and downregulated, respectively, from before differentiation to differentiation. Functional enrichment analyses revealed that the upregulated genes were associated with skeletal muscle contraction, autophagy, and sarcomeres while the downregulated genes were associated with ribonucleoprotein complex biogenesis, mRNA processing, ribosomes, and other biological processes or cellular components. Western blot analyses showed an increased conversion of LC3-I to LC3-II protein during myoblast differentiation, further demonstrating the upregulation of autophagy during myoblast differentiation. Blocking the autophagic flux in C2C12 cells with chloroquine inhibited the expression of skeletal-muscle-specific genes and the formation of myotubes, confirming a positive role for autophagy in myoblast differentiation and fusion.

Tellurite [Te(IV)] is a high-toxicity metalloid. In this study, a fungus with high Te(IV) resistance was isolated. Strain AB1 could efficiently reduce highly toxic Te(IV) to less toxic Te(0). The reduced products formed rod-shaped biogenetic Te(0) nanoparticles (Bio-TeNPs) intracellularly. Further TEM-element mapping, FTIR, and XPS analysis showed that the extracted Bio-TeNPs ranged from 100 to 500 nm and consisted of Te(0), proteins, lipids, aromatic compounds, and carbohydrates. Moreover, Bio-TeNPs exhibited excellent antibacterial ability against Shigella dysenteriae , Escherichia coli , Enterobacter sakazakii , and Salmonella typhimurium according to inhibition zone tests. Further growth and live/dead staining experiments showed that E . coli and S . typhimurium were significantly inhibited by Bio-TeNPs, and cells were broken or shriveled after treatment with Bio-TeNPs based on SEM observation. Additionally, the antioxidant and cytotoxicity tests showed that the Bio-TeNPs exhibited excellent antioxidant capacity with no cytotoxicity. All these results suggested that strain AB1 showed great potential in bioremediation and Bio-TeNPs were excellent antibacterial nanomaterials with no cytotoxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ao, He, Lv, Tu, Tan, Jiang, Shi, Li, Hou, Hu and Xia.)

Background: Microbiome-targeted therapies (MTTs), including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), have been proposed as a potential treatment for cirrhosis via modulation of gut microbiome, while the impact of gut microflora alteration on liver function in cirrhosis trajectory is unclear, and no related systematic review has been published. We aim to comprehensively assess the effects of MTTs in patients with liver cirrhosis., Methods: We will search databases of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) with no time restriction. Only randomized controlled trials published in English will be included. Two independent reviewers will be responsible for study identification and selection, data extraction, and risk of bias assessment, with discrepancies resolved by consensus or referral to a third author. Heterogeneity of studies will be examined using Cochrane Q-test and I 2 statistics. The data will be pooled using either a fixed- or random-effects model based on I 2 statistics. The results will be presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). We will perform subgroup analysis on the type of MTTs and assess the reporting biases. Sensitivity analysis will be conducted to test the stability of each outcome result., Discussion: There is no current study about the role of MTTs in developing the liver function, and the therapeutic effects of MTTs are inconsistent. By investigating the liver-specific indicators when treating with multiple MTTs on course of cirrhosis, our findings will give more conclusive and stronger evidence about the efficacy of MTTs and provide new insight into the action mechanisms of these MTTs., Systematic Review Registration: PROSPERO CRD42021253198., (© 2022. The Author(s).)

Previous studies have suggested that air pollutant exposure is related to tuberculosis (TB) risk, but results have not been consistent. This study evaluated the relation between daily air pollutant exposure and TB incidence in Shanghai from 2014 to 2019. Overall, there were four pollutants that were positively related to the risk of new TB cases. After a 5 μg/m 3 increase, the maximum lag-specific and cumulative relative risk (RR) of SO 2 were 1.081, (95% CI: 1.035-1.129, lag: 3 days) and 1.616 (95% CI: 1.119-2.333, lag: 0-13 days), while for NO 2 , they were 1.061 (95% CI: 1.015-1.11, lag: 4 days) and 1.8 (95% CI: 1.113-2.91, lag: 0-15 days). As for PM 2.5 , with a 50 μg/m 3 increase, the lag-specific and cumulative RR were 1.064 (95% CI: 1-1.132, lag: 6 days) and 3.101 (95% CI: 1.096-8.777, lag: 0-21 days), while for CO, the lag-specific RR was 1.03 (95% CI: 1.005-1.057, lag: 8 days) and the cumulative RR was 1.436 (95% CI: 1.004-2.053, lag: 0-16 days) with a 100 μg/m 3 increase. The associations tended to be stronger in male and elderly patients and differed with seasons. Air pollutant exposure may be a risk factor for TB incidence.

KRAS mutations drive a quarter of cancer mortality, and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at the doses needed to adequately extinguish RAS/RAF/MAPK signaling in the tumor cell. We found that oncogenic KRAS signaling induced ferrous iron (Fe2+) accumulation early in and throughout mutant KRAS-mediated transformation. We converted an FDA-approved MEK inhibitor into a ferrous iron-activatable drug conjugate (FeADC) and achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor-bearing animals, with tumor-selective drug activation, producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation, and FeADCs hold promise for improving the treatment of KRAS-driven solid tumors., Competing Interests: Disclosures: R.K. Muir reported a patent to WO2019/005977 issued. S.C. Behr reported grants from CTT, and personal fees from AAA Novartis and Genvivo outside the submitted work. J. Korkola reported “other” from Convergent Genomics outside the submitted work. M.J. Evans reported a patent to Trioxolane Agents (PCT/US2018/039768) pending. E.A. Collisson reported grants from Astra Zeneca and Bayer outside the submitted work. E.A. Collisson and A.R. Renslo are cofounders of Tatara and have an ownership interest in the company. A.R. Renslo reported personal fees from Tatara Therapeutics outside the submitted work; in addition, A.R. Renslo had a patent number 10,287,312 issued, a patent number 10,662,215 issued, a patent number 11,014,955 issued, and a patent number 11,072,594 issued. No other disclosures were reported., (© 2022 Jiang et al.)

The occurrence of microorganisms has been confirmed in the tumor microenvironment (TME) of many different organs. Microorganisms (e.g., phage, virus, bacteria, fungi, and protozoa) present in TME modulate TME to inhibit or promote tumor growth in species-dependent manners due to the special physiological and pathological features of each microorganism. Such microorganism-TME interactions have recently been emulated to turn microorganisms into powerful cancer theranostic agents. To facilitate scientists to explore microorganisms-TME interactions further to develop improved cancer theranostics, here we critically review the characteristics of different microorganisms that can be found in TME, their interactions with TME, and their current applications in cancer diagnosis and therapy. Clinical trials of using microorganisms for cancer theranostics are also summarized and discussed. Moreover, the emerging technology of whole-metagenome sequencing that can be employed to precisely determine microbiota spectra is described. Such technology enables scientists to gain an in-depth understanding of the species and distributions of microorganisms in TME. Therefore, scientists now have new tools to identify microorganisms (either naturally present in or introduced into TME) that can be used as effective probes, monitors, vaccines, or drugs for potentially advancing cancer theranostics to clinical applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: This systematic review aimed to document and describe how and when to assess patients' expectancies to acupuncture and the relationship between patients' expectancies and clinical effects. Materials and Methods: Three English databases, including PubMed, Cochrane Central Register of Controlled Trials, and EMBASE, and four Chinese databases, including the Chinese Biomedicine Literature Database, Chinese Journal Full-text Database, Chinese Scientific Journal Full-text Database, and Wanfang Database, were searched up to February 2020. Studies involving patients' expectancies to acupuncture were included. Based on the detailed situations of patients' expectancies, we made a standardized data extraction table that included the basic information of articles, study design details, and measurement of expectations. Based on the data, a descriptive analysis was performed, covering the characteristics of studies, measuring methods of expectations and the relationship between patients' expectancies and clinical effects. Methodology quality assessment was also performed by the risk of bias and the standards for reporting interventions in controlled trials of acupuncture. Results: There were 61 randomized controlled trials included in our analysis. The number of articles increased gradually over time and grew significantly after 2008. About half of trials focused on pain alleviation. Expectancies were measured before the treatment ( N  = 43), after the treatment ( N  = 3), and both before and after the treatment ( N  = 10), and five studies did not mention it. The measurement of expectancies used self-made questionnaires or scales ( N  = 27), the Acupuncture Expectations Scale ( N  = 6), and other scales ( N  = 11), while 17 studies did not describe what scale they used. The used questionnaires or scales mostly tried to ascertain the strength of confidence that acupuncture would help. Patients' expectancies and clinical effects were relevant in 19 studies, irrelevant in 21 studies, and were not mentioned in 21 studies. Conclusions: Patients' expectations to acupuncture have received increasing attention in recent years, but there is still no recognized measurement time and methods. It is critical to develop questions and answers regarding patients' expectations with better discrimination and reliability to accurately assess expectations and to explore the relationship between patients' expectations and acupuncture outcomes in future trials.

Background and Aims: Patients with pancreatic ductal adenocarcinoma (PDA) have not yet benefitted from the revolution in cancer immunotherapy due in large part to a dominantly immunosuppressive tumor microenvironment. MEK inhibition combined with autophagy inhibition leads to transient tumor responses in some patients with PDA. We examined the functional effects of combined MEK and autophagy inhibition on the PDA immune microenvironment and the synergy of combined inhibition of MEK and autophagy with CD40 agonism (aCD40) against PDA using immunocompetent model systems., Methods: We implanted immunologically "cold" murine PDA cells orthotopically in wide type C57BL/6J mice. We administered combinations of inhibitors of MEK1/2, inhibitors of autophagy, and aCD40 and measured anticancer efficacy and immune sequelae using mass cytometry and multiplexed immunofluorescence imaging analysis to characterize the tumor microenvironment. We also used human and mouse PDA cell lines and human macrophages in vitro to perform functional assays to elucidate the cellular effects induced by the treatments., Results: We find that coinhibition of MEK (using cobimetinib) and autophagy (using mefloquine), but not either treatment alone, activates the STING/type I interferon pathway in tumor cells that in turn activates paracrine tumor associated macrophages toward an immunogenic M1-like phenotype. This switch is further augmented by aCD40. Triple therapy (cobimetinib + mefloquine + aCD40) achieved cytotoxic T-cell activation in an immunologically "cold" mouse PDA model, leading to enhanced antitumor immunity., Conclusions: MEK and autophagy coinhibition coupled with aCD40 invokes immune repolarization and is an attractive therapeutic approach for PDA immunotherapy development., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Satellite cells are the myogenic precursor cells in adult skeletal muscle. The objective of this study was to identify enhancers and transcription factors that regulate gene expression during the differentiation of bovine satellite cells into myotubes., Results: Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to identify genomic regions where lysine 27 of H3 histone is acetylated (H3K27ac), i.e., active enhancers, from bovine satellite cells before and during differentiation into myotubes. A total of 19,027 and 47,669 H3K27ac-marked enhancers were consistently identified from two biological replicates of before- and during-differentiation bovine satellite cells, respectively. Of these enhancers, 5882 were specific to before-differentiation, 35,723 to during-differentiation, and 13,199 common to before- and during-differentiation bovine satellite cells. Whereas most of the before- or during-differentiation-specific H3K27ac-marked enhancers were located distally to the transcription start site, the enhancers common to before- and during-differentiation were located both distally and proximally to the transcription start site. The three sets of H3K27ac-marked enhancers were associated with functionally different genes and enriched with different transcription factor binding sites. Specifically, many of the H3K27ac-marked enhancers specific to during-differentiation bovine satellite cells were associated with genes involved in muscle structure and development, and were enriched with binding sites for the MyoD, AP-1, KLF, TEAD, and MEF2 families of transcription factors. A positive role was validated for Fos and FosB, two AP-1 family transcription factors, in the differentiation of bovine satellite cells into myotubes by siRNA-mediated knockdown., Conclusions: Tens of thousands of H3K27ac-marked active enhancers have been identified from bovine satellite cells before or during differentiation. These enhancers contain binding sites not only for transcription factors whose role in satellite cell differentiation is well known but also for transcription factors whose role in satellite cell differentiation is unknown. These enhancers and transcription factors are valuable resources for understanding the complex mechanism that mediates gene expression during satellite cell differentiation. Because satellite cell differentiation is a key step in skeletal muscle growth, the enhancers, the transcription factors, and their target genes identified in this study are also valuable resources for identifying and interpreting skeletal muscle trait-associated DNA variants in cattle., (© 2021. The Author(s).)

This study aimed to determine the spatial effects of traffic- and industrial-related pollution on the mortality for lung cancer (LC). We conducted a retrospective cohort study by using the data from LC registry in Jiading District for the period from 2002 to 2012. Standard parametric model with Weibull distribution was used for spatial survival analysis. Shorter distance to highway (adjusted odds ratio (aOR) = 1.15, 95% confidence interval (CI): 1.03-1.30) and higher factory density (aOR = 1.20, 95% CI: 1.05-1.37) were significantly associated with an increased risk of LC death, and there was a spatial difference in the associations between northern and southern areas of Jiading District. The risk was high in suburbs as compared with urban areas. Traffic- and industrial-related pollution were significantly associated with an increased risk of LC death, which showed a spatial variation. Further studies are needed to better understand the current LC status in the suburbs and to reduce health disparities., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Skeletal muscle from meat-producing livestock such as cattle is a major source of food for humans. To improve skeletal muscle growth efficiency or quality in cattle, it is necessary to understand the genetic and physiological mechanisms that govern skeletal muscle composition, development, and growth. Satellite cells are the myogenic progenitor cells in postnatal skeletal muscle. In this study we analyzed the composition of bovine satellite cells with single-cell RNA sequencing (scRNA-seq). We isolated satellite cells from a 2-week-old male calf, cultured them in growth medium for a week, and performed scRNA-seq using the 10x Genomics platform. Deep sequencing of two scRNA-seq libraries constructed from cultured bovine satellite cells yielded 860 million reads. Cell calling analyses revealed that these reads were sequenced from 19,096 individual cells. Clustering analyses indicated that these reads represented 15 cell clusters that differed in gene expression profile. Based on the enriched expression of markers of satellite cells (PAX7 and PAX3), markers of myoblasts (MYOD1, MYF5), and markers of differentiated myoblasts or myocytes (MYOG), three clusters were determined to be satellite cells, two clusters myoblasts, and two clusters myocytes. Gene ontology and trajectory inference analyses indicated that cells in these myogenic clusters differed in proliferation rate and differentiation stage. Two of the remaining clusters were enriched with PDGFRA, a marker of fibro-adipogenic (FAP) cells, the progenitor cells for intramuscular fat, and are therefore considered to be FAP cells. Gene ontology analyses indicated active lipogenesis in one of these two clusters. The identity of the remaining six clusters could not be defined. Overall, the results of this study support the hypothesis that bovine satellite cells are composed of subpopulations that differ in transcriptional and myogenic state. The results of this study also support the hypothesis that intramuscular fat in cattle originates from fibro-adipogenic cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lyu, Qi, Tu and Jiang.)

Rumen epithelium plays an essential role in absorption, transport, and metabolism of short-chain fatty acids, the main products of rumen fermentation, and in preventing microbes and other potentially harmful rumen contents from entering the systemic circulation. The objective of this study was to generate an immortal rumen epithelial cell line that can be used as a convenient model of rumen epithelial cells in vitro. We isolated primary rumen epithelial cells from a steer through trypsin digestion and transduced them with lentiviruses expressing the Simian Virus (SV) 40 T antigen. We cloned the transduced cells by limiting dilution. Western blotting analysis confirmed the expression of the SV40 T antigen in two single-cell clones. Cells from one clone, named bovine rumen epithelial clone 1 (BREC1), displayed a flat and squamous morphology in culture. RNA sequencing revealed that BREC1 cells expressed many markers of epithelial cells, including keratins, the epidermal growth factor receptor, and the short-chain fatty acid transporters monocarboxylic acid transporter (MCT) 1 (MCT-1) and MCT-4. RNA sequencing revealed that BREC1 cells expressed key enzymes such as 3-hydroxymethyl-3-methylglutaryl-CoA lyase and 3-hydroxy-3-methylglutaryl-CoA synthase 1 involved in ketogenesis, a unique function of rumen epithelial cells. RNA sequencing also revealed the expression of genes encoding tight junctions, desmosomes, anchoring junctions, and polarized plasma membranes, structures typical of epithelial cells, in BREC1 cells. Cell proliferation assays indicated that BREC1 cells were similar to primary rumen epithelial cells in response to insulin-like growth factor 1, insulin, and butyrate. In conclusion, BREC1 is not only a convenient but an appropriate model for studying the factors and mechanisms that control proliferation, apoptosis, differentiation, nutrient transport, metabolism, and barrier function in rumen epithelium., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Short-term prognosis of advanced schistosomiasis has not been well studied. We aimed to construct prognostic models using machine learning algorithms and to identify the most important predictors by utilising routinely available data under the government medical assistance programme. An established database of advanced schistosomiasis in Hunan, China was utilised for analysis. A total of 9541 patients for the period from January 2008 to December 2018 were enrolled in this study. Candidate predictors were selected from demographics, clinical features, medical examinations and test results. We applied five machine learning algorithms to construct 1 year prognostic models: logistic regression (LR), decision tree (DT), random forest (RF), artificial neural network (ANN) and extreme gradient boosting (XGBoost). An area under the receiver operating characteristic curve (AUC) was used to evaluate the model performance. The important predictors of the optimal model for unfavourable prognosis within 1 year were identified and ranked. There were 1249 (13.1%) cases having unfavourable prognoses within 1 year of discharge. The mean age of all participants was 61.94 years, of whom 70.9% were male. In general, XGBoost showed the best predictive performance with the highest AUC (0.846; 95% confidence interval (CI): 0.821, 0.871), compared with LR (0.798; 95% CI: 0.770, 0.827), DT (0.766; 95% CI: 0.733, 0.800), RF (0.823; 95% CI: 0.796, 0.851), and ANN (0.806; 95% CI: 0.778, 0.835). Five most important predictors identified by XGBoost were ascitic fluid volume, haemoglobin (HB), total bilirubin (TB), albumin (ALB), and platelets (PT). We proposed XGBoost as the best algorithm for the evaluation of a 1 year prognosis of advanced schistosomiasis. It is considered to be a simple and useful tool for the short-term prediction of an unfavourable prognosis for advanced schistosomiasis in clinical settings., (Copyright © 2021 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Deoxynivalenol (DON) is a prevalent Fusarium mycotoxin, occurs predominantly in the global environment, especially in cereals, animal feed and food commodities. The widespread contamination causes a serious risk to human and animal health. DON usually impairs weight gain, which is presumably from its capacity to reduce feed intake by interfering with intestinal motility. To clarify the role of smooth muscle cells (SMCs) contractility in intestinal motility and growth inhibition caused by DON, twelve weaned piglets were firstly divided into two groups to feed control or Fusarium mycotoxin-contaminated (MC) diet. Results showed that the final body weight, average daily gain and average daily feed intake were significantly reduced in piglets fed the MC diet. Exposure to the MC diet also significantly decreased the thickness of smooth muscle layer and SMCs contractile markers expression (myosin heavy chain 11, smooth muscle actin gamma 2, transgelin, calponin 1) in jejunum and ileum of piglets. Furthermore, oral DON supplementation (3 mg/kg body weight) to mice in six consecutive days could significantly inhibit the upper intestinal transit, impede normal defecation and downregulate SMCs contractile markers expression in small intestine. Finally, we generated a porcine enteric smooth muscle cell line (PISMC), and found that DON could depress its contractility by decreasing PISMC proliferation, migration and contractile markers expression. In conclusion, these findings in vivo and in vitro suggest that DON, as a common environmental toxin, can not only reduce proliferative and motile phenotype, but also decrease contractile apparatus components (contractile markers expression) in SMCs, which in turn influences SMCs contractility and then interferes with intestinal motility and growth performance., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

To study disease development, an inventory of an organ's cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA-sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We describe an epithelial-mesenchymal transitory axis in our three pancreatic duct subpopulations and identify osteopontin as a regulator of this fate decision as well as human duct cell dedifferentiation. Our results further identify functional heterogeneity within pancreatic duct subpopulations by elucidating a role for geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in maintenance of duct cell identity and disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis., Competing Interests: AH, AR, LL, SA, JS, SG, XP, HJ, DB, MP, LL, JL, EC, MA, GF, JY, CY, GK, VW, MH No competing interests declared, (© 2021, Hendley et al.)

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in China. Although numerous studies have been conducted to determine the risk factors for COPD mortality such as ambient air pollution, the results are not fully consistent. Methods: This study included mortality analysis and a case-control design by using the data extracted from the Mortality Registration System in Jiading District, Shanghai. Traditional logistic regression, geographically weighted logistic regression (GWLR), and spatial scan statistical analysis were performed to explore the geographic variation of COPD mortality and the possible influencing factors. Results: Traditional logistic regression showed that extreme lower temperature in the month prior to death, shorter distance to highway, lower GDP level were associated with increased COPD mortality. GWRL model further demonstrated obvious geographical discrepancies for the above associations. We additionally identified a significant cluster of low COPD mortality (OR = 0.36, P = 0.002) in the southwest region of Jiading District with a radius of 3.55 km by using the Bernoulli model. The geographical variation in age-standardized mortality rate for COPD in Jiading District was explained to a certain degree by these factors. Conclusion: The risk of COPD mortality in Jiading District showed obvious geographical variation, which were partially explained by the geographical variations in effects of the extreme low temperature in the month prior to death, residential proximity to highway, and GDP level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Peng, Zhang, Yu, Shao, Ji, Jin, Zhong, Zhang, Jiang, Li, Shi, Zheng, Xiong, Wang, Jiang, Chen, Jiang and Zhou.)

COVID-19 positive (194) and negative (212) pneumonia patients were selected to analyze bacterial pathogens coinfection. Results showed that 50% of COVID-19 patients were coinfected or carried bacterial pathogens. Bordetella pertussis infection rate was significantly higher in positive patients. Consequently, preventions should be taken to control bacterial pathogens coinfection in COVID-19 patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Precise and rapid sensing of Fe(III) under concerned facile conditions is important in environmental monitoring. Herein, a facile and label-free ratiometric sensor is constructed for selective determination of Fe(III) ions by coupling second-order scattering (SOS) and fluorescence. We were synthesized fluorescent N, S-doped carbon dots (N/S-CDs) via facile one-step hydrothermal treatment with an intensive fluorescence and a weak SOS signal and high quantum yield (32%). The fluorescence of N/S-CDs was quenched whereas the intensity of SOS was relatively increased by Fe(III) ions due to aggregation-induced fluorescence quenching or enhancement. Based on this effect, a novel fluorescent ratiometric probe with the combined fluorescence and SOS is proposed for the sensing of Fe(III) ions, and with the detection limit of 83 nM and linear range of 0.1-10 μM and 10-40 μM, respectively.

Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors. Experimentally manipulating stromal matrix with an anti-lysyl oxidase like-2 (anti-LOXL2) antibody in syngeneic orthotopic PDA mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival. These studies suggest an important protective role of stroma in PDA and urge caution in clinically deploying stromal depletion strategies.

The pre-mounted dry transcatheter aortic valve implantation (TAVI) valve is a new technology in the development of biological heart valves. Dry valves do not need to be placed in special preservation solution and can be opened and used immediately, meeting the needs of clinical emergency valve implantation. However, current biological valves obtained by simple air drying cannot be unfolded quickly. In addition, the crimping process leads to structural damage to the valve fiber microstructure, reducing the service life of biological valves. Furthermore, current biological valves still have problems such as calcification, endothelialization difficulty, and immune rejection. In this study, a poly(ethylene glycol)methacrylate (PEGMA) hydrogel hybrid pericardium loaded with REDV was developed. The PEGMA monomer solution can penetrate the space of the pericardium. REDV was loaded into the PEGMA hydrogel, which was hybridized with pericardium via in situ polymerization. The results showed improved unfolding properties, less mechanical damage after crimping, and improved endothelialization potential of the biological valve. Thus, REDV-loaded PEGMA hydrogel hybrid pericardium is a promising approach for obtaining pre-mounted dry TAVI valves with enhanced endothelialization properties.

Smooth muscle cells (SMCs) play an important role in physiology and production in farm animals such as pigs. Here, we report the generation of a pig SMC line. Our original objective was to establish an enteroendocrine cell line from the pig ileum epithelium through lentiviral transduction of the Simian Virus (SV) 40 large T antigen. However, an initial expression analysis of marker genes in nine cell clones revealed that none of them were enteroendocrine cells or absorptive enterocytes, goblet cells, or Paneth cells, some of the major cell types existing in the ileum epithelium. A more detailed characterization of one clone named PIC7 by RNA-seq showed that these cells expressed many of the known smooth muscle-specific or -enriched genes, including smooth muscle actin alpha 2, calponin 1, calponin 3, myosin heavy chain 11, myosin light chain kinase, smoothelin, tenascin C, transgelin, tropomyosin 1, and tropomyosin 2. Both quantitative PCR and RNA-seq analyses showed that the PIC7 cells had a high expression of mRNA for smooth muscle actin gamma 2, also known as enteric smooth muscle actin. A Western blot analysis confirmed the expression of SV40 T antigen in the PIC7 cells. An immunohistochemical analysis demonstrated the expression of smooth muscle actin alpha 2 filaments in the PIC7 cells. A collagen gel contraction assay showed that the PIC7 cells were capable of both spontaneous contraction and contraction in response to serotonin stimulation. We conclude that the PIC7 cells are derived from an enteric SMC from the pig ileum. These cells may be a useful model for studying the cellular and molecular physiology of pig enteric SMCs. Because pigs are similar to humans in anatomy and physiology, the PIC7 cells may be also used as a model for human intestinal SMCs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study was conducted to further understand the mechanism that controls myoblast differentiation, a key step in skeletal muscle formation. RNA sequencing of primary bovine myoblasts revealed many genes encoding the ubiquitin-proteasome system were up-regulated during myoblast differentiation. This up-regulation was accompanied by increased proteasomal activity. Treating myoblasts with the proteasome-specific inhibitor lactacystin impeded myoblast differentiation. Adenovirus-mediated overexpression of inhibitor of DNA binding 1 (ID1) protein inhibited myoblast differentiation too. Further experiments were conducted to determine whether the proteasome promotes myoblast differentiation by degrading ID1 protein. Both ID1 protein and mRNA expression decreased during myoblast differentiation. However, treating myoblasts with lactacystin reversed the decrease in ID1 protein but not in ID1 mRNA expression. Surprisingly, this reversal was not observed when myoblasts were also treated with the mRNA translation inhibitor cycloheximide. Direct incubation of ID1 protein with proteasomes from myoblasts did not show differentiation stage-associated degradation of ID1 protein. Furthermore, ubiquitinated ID1 protein was not detected in lactacystin-treated myoblasts. Overall, the results of this study suggest that, during myoblast differentiation, the proteasomal activity is up-regulated to further myoblast differentiation and that the increased proteasomal activity improves myoblast differentiation partly by inhibiting the synthesis, not the degradation, of ID1 protein.-Leng, X., Ji, X., Hou, Y., Settlage, R., Jiang, H. Roles of the proteasome and inhibitor of DNA binding 1 protein in myoblast differentiation.

Sex steroid hormones are used in the meat industry due to their ability to regulate muscle hypertrophy. However, the mechanisms underlying their action are not fully elucidated. Recent reports demonstrate that steroid hormones increase oxytocin (OXT) expression in skeletal muscle, indicating that OXT may play a role in satellite cell activity. This hypothesis was tested using steroid hormones (17β-estradiol [E2]; trenbolone acetate [TBA]), tamoxifen (TAM), OXT, and atosiban (A: OXT receptor inhibitor) applied to bovine satellite cells (BSCs) to investigate BSC regulation by OXT. Oxytocin alone increased fusion index (P < 0.05) but not BSC proliferation. Oxytocin reduced (P < 0.05) apoptotic nuclei and stimulated migration rate (P < 0.05). Similarly, E2 and TBA increased (P < 0.05) BSC proliferation rate, fusion index, and migration and decreased (P < 0.05) apoptotic nuclei. 17β-Estradiol or TBA supplemented with A had lower (P < 0.05) BSC proliferation rate, fusion index, and migration and more (P < 0.05) apoptotic nuclei compared with E2 or TBA alone. Furthermore, OXT expression increased (P < 0.05) in E2 or TBA-treated proliferating BSC. Oxytocin, E2, and TBA increased (P < 0.05) MyoD and MyoG expression in proliferating BSC. During BSC differentiation, OXT expression increased (P < 0.05) with E2 or TBA treatments. MyoG expression increased (P < 0.05) in OXT, E2, and TBA compared with control. However, A, OXT + A, TAM, TAM + OXT, E2 + TAM, E2 + A, and TBA + A decreased (P < 0.05) MyoG expression during BSC differentiation. These results indicate that OXT is involved in steroid hormone-stimulated BSC activity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The C3H10T1/2 cells are considered mesenchymal stem cells (MSCs) because they can be induced to become the progenitor cells for myocytes, adipocytes, osteoblasts, and chondrocytes by the DNA methyltransferase inhibitor 5'-azacytidine. In this study, we determined the effect of growth hormone (GH) on the myogenic and adipogenic lineage commitment in C3H10T1/2 cells. The C3H10T1/2 cells were treated with recombinant bovine GH in the presence or absence of 5'-azacytidine for 4 days. The myogenic commitment in C3H10T1/2 cells was assessed by immunostaining them for MyoD, the marker for myoblasts, and by determining their capacity to differentiate into the multinucleated myotubes. The adipogenic commitment in C3H10T1/2 cells was assessed by determining their ability to differentiate into adipocytes. Myotubes and adipocyteswere identified by immunocytochemistry and Oil Red O staining, respectively. C3H10T1/2 cells treated with 5'-azacytidine and GH for 4 days contained a greater percentage of MyoD-positive cells than those treated with 5'-axacytidine alone (P < 0.05). The former generated more myotubes than the latter upon induced myoblast differentiation (P < 0.05). However, C3H10T1/2 cells treated with GH alone did not form any myotubes. C3H10T1/2 cells treated with 5'-azacytidine formed adipocytes upon adipocyte differentiation induction, whereas C3H10T1/2 cells treated with GH alone did not form any adipocytes. C3H10T1/2 cells treated with both 5'-azacytidine and GH formed fewer adipocytes than those treated with 5'-azacytidine alone (P < 0.05). Both GHR and IGF-I mRNA expression in C3H10T1/2 cells were increased by 5'-azacytidine (P < 0.05), but neither was affected by GH. Overall, this study showed that GH enhanced 5'-azacytidine-induced commitment in C3H10T1/2 cells to myoblasts but inhibited 5'-azacytidine-induced commitment to preadipocytes. These results support the possibility that GH stimulates skeletal muscle growth and inhibits adipose tissue growth in part by stimulating the myogenic commitment and inhibiting the adipogenic commitment, respectively, in mesenchymal stem cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)