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ObjectiveStudies have shown that the exercise-induced cytokine Irisin functions were as a dimer, so tandem Irisin-Irisin mock dimers were designed to explore the similarities and differences between recombinant Irisin-Irisin expressed by Escherichia coli and commercial Irisin in activity and function on tumor cells.MethodsEscherichia coli strain BL21 (DE3) and pET-30a expression vectors were selected to obtain recombinant Irisin-Irisin by isopropyl β-D-1-thiogalactopyranoside (IPTG) induction. High purity recombinant Irisin-Irisin was obtained by Ni Sepharose excel. C2C12 skeletal muscle cells were treated with recombinant Irisin-Irisin and monomeric Irisin respectively, and the expressions of mitochondrial related gene UCP-1 were observed to test the activity. The functions were verified in gastric cancer, colorectal cancer and other gastrointestinal tumors, and the activity and function of recombinant Irisin-Irisin and monomeric Irisin on tumor cells were compared.Results(1) Expression and purification of recombinant Irisin-Irisin: compared with the non-induced samples, the recombinant Irisin-Irisin was significantly expressed after IPTG induction; high purity recombinant Irisin-Irisin with a molecular weight of about 27 kDa was obtained by Ni Sepharose excel. (2) Detection of recombinant Irisin-Irisin activity: compared with the blank control group, both the recombinant Irisin-Irisin group and the Irisin group could up-regulate the expression of UCP-1 in C2C12 cells (PPPPEscherichia coli has activity, and the activity is higher than that of the monomeric Irisin; recombinant Irisin-Irisin has an effect on the migration of gastric cancer cells and colorectal cancer cells, and the effect was better than that of the monomeric Irisin.

Inflammatory bowel disease (IBD) is a chronic and recurring lifelong condition, the exact etiology of which remains obscure. However, an increasing corpus of research underscores the pivotal role of cellular signaling pathways in both the instigation and management of intestinal inflammation. Drosophila, owing to its prodigious offspring, abbreviated life cycle, and the conservation of signaling pathways with mammals, among other advantages, has become a model organism for IBD research. This review will expound on the feasibility of utilizing Drosophila as an IBD model, comparing its intestinal architecture with that of mammals, its inflammatory responses, and signaling pathways. Furthermore, it will deliberate on the role of natural products across various biological models of IBD pathways, elucidating the viability of fruit flies as IBD models and the modus operandi of cellular signaling pathways in the context of IBD. [ABSTRACT FROM AUTHOR]

The conversion of cropland to orchards is one of the main measures of the Grain for Green Program for soil and water conservation and ecosystem function maintenance in the eastern Loess Plateau, China. However, the patterns and influencing forces of soil multifunctionality during the conversion from cropland to orchard remain unclear. This study evaluated the responses and regulating factors of soil multifunctionality following the conversion of cropland to pomegranate (Punica granatum L.) orchard along a 10-year chronosequence. Results showed that the conversion of cropland to pomegranate trees significantly increased the L-leucine aminopeptidase enzyme activity from 4.77 to 17.69 nmol g−1 h−1. The 10-year pomegranate stand exhibited the highest nitrogen (N) cycle multifunctionality. The N cycle multifunctionality was positively correlated with soil dissolved organic carbon (C) content, soil available phosphorus content, microbial biomass C content, phospholipid fatty acid, and soil feature index (All p < 0.05). Structural equation modeling suggested that the increased N cycle multifunctionality was attributed to soil feature index rather than soil microbial C content and phospholipid fatty acid. Land-use change did not affect soil C cycle, phosphorus cycle, or soil multifunctionality. Overall, our findings reveal that cropland conversion to orchards significantly enhances soil N cycle multifunctionality, highlighting the soil feature index's role in maintaining soil function. The conversion from cropland to orchards, which has economic benefits and increases soil N cycle multifunctionality, is an effective approach of the Grain for Green Program in the Loess Plateau. Pomegranate forest stand age increased soil nitrogen cycle multifunctionality through soil physicochemical properties rather than microbial community. [ABSTRACT FROM AUTHOR]

The accuracy of digital elevation models (DEMs) in forested areas plays a crucial role in canopy height monitoring and ecological sensitivity analysis. Despite extensive research on DEMs in recent years, significant errors still exist in forested areas due to factors such as canopy occlusion, terrain complexity, and limited penetration, posing challenges for subsequent analyses based on DEMs. Therefore, a CNN-LightGBM hybrid model is proposed in this paper, with four different types of forests (tropical rainforest, coniferous forest, mixed coniferous and broad-leaved forest, and broad-leaved forest) selected as study sites to validate the performance of the hybrid model in correcting COP30DEM in different forest area DEMs. In the hybrid model of this paper, the choice was made to use the Densenet architecture of CNN models with LightGBM as the primary model. This choice is based on LightGBM's leaf-growth strategy and histogram linking methods, which are effective in reducing the data's memory footprint and utilising more of the data without sacrificing speed. The study uses elevation values from ICESat-2 as ground truth, covering several parameters including COP30DEM, canopy height, forest coverage, slope, terrain roughness and relief amplitude. To validate the superiority of the CNN-LightGBM hybrid model in DEMs correction compared to other models, a test of LightGBM model, CNN-SVR model, and SVR model is conducted within the same sample space. To prevent issues such as overfitting or underfitting during model training, although common meta-heuristic optimisation algorithms can alleviate these problems to a certain extent, they still have some shortcomings. To overcome these shortcomings, this paper cites an improved SSA search algorithm that incorporates the ingestion strategy of the FA algorithm to increase the diversity of solutions and global search capability, the Firefly Algorithm-based Sparrow Search Optimization Algorithm (FA-SSA algorithm) is introduced. By comparing multiple models and validating the data with an airborne LiDAR reference dataset, the results show that the R2 (R-Square) of the CNN-LightGBM model improves by more than 0.05 compared to the other models, and performs better in the experiments. The FA-SSA-CNN-LightGBM model has the highest accuracy, with an RMSE of 1.09 meters, and a reduction of more than 30% of the RMSE when compared to the LightGBM and other hybrid models. Compared to other forested area DEMs (such as FABDEM and GEDI), its accuracy is improved by more than 50%, and the performance is significantly better than other commonly used DEMs in forested areas, indicating the feasibility of this method in correcting elevation errors in forested area DEMs and its significant importance in advancing global topographic mapping. [ABSTRACT FROM AUTHOR]

Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m6A) modifications. A better understanding of the association of these genetic variants with susceptibility to cervical cancer (CC) can promote advances in disease screening and treatment. Genome-wide identification of m6A-associated functional SNPs for CC was performed using the TCGA and JENGER databases, incorporating the data from RNA-seq and MeRIP-seq. The screened risk-associated SNP rs1059288 (A>G), which is located in the 3′ UTR of TAPBP, was further validated in a case–control study involving 921 cases and 1077 controls. The results revealed a significant association between rs1059288 and the risk of CC (OR 1.48, 95% CI 1.13–1.92). Mechanistically, the presence of the risk G allele of rs1059288 was associated with increased m6A modification of TAPBP compared with the A allele. This modification was facilitated by the m6A methyltransferase METTL14 and the reading protein YTHDF2. Immunohistochemical staining of tissue microarrays containing 61 CC and 45 normal tissues showed an overexpression of TAPBP in CC. Furthermore, the upregulation of TAPBP promoted the growth and migration of CC cells as well as tumor-forming ability, inhibited apoptosis, and conferred increased resistance to commonly used chemotherapeutic drugs such as bleomycin, cisplatin, and doxorubicin. Knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway in CC cells and upregulated certain immune genes including ISG15, IRF3, PTPN6, and HLA-A. These findings offer insights into the involvement of genetic variations in TAPBP in the development and progression of CC. [ABSTRACT FROM AUTHOR]

BackgroundCrowdsourcing, the process of shifting individual tasks to a large group, may enhance human immunodeficiency virus (HIV) testing interventions. We conducted a noninferiority, randomized controlled trial to compare first-time HIV testing rates among men who have sex with men (MSM) and transgender individuals who received a crowdsourced or a health marketing HIV test promotion video.MethodsSeven hundred twenty-one MSM and transgender participants (≥16 years old, never before tested for HIV) were recruited through 3 Chinese MSM Web portals and randomly assigned to 1 of 2 videos. The crowdsourced video was developed using an open contest and formal transparent judging while the evidence-based health marketing video was designed by experts. Study objectives were to measure HIV test uptake within 3 weeks of watching either HIV test promotion video and cost per new HIV test and diagnosis.ResultsOverall, 624 of 721 (87%) participants from 31 provinces in 217 Chinese cities completed the study. HIV test uptake was similar between the crowdsourced arm (37% [114/307]) and the health marketing arm (35% [111/317]). The estimated difference between the interventions was 2.1% (95% confidence interval, -5.4% to 9.7%). Among those tested, 31% (69/225) reported a new HIV diagnosis. The crowdsourced intervention cost substantially less than the health marketing intervention per first-time HIV test (US$131 vs US$238 per person) and per new HIV diagnosis (US$415 vs US$799 per person).ConclusionsOur nationwide study demonstrates that crowdsourcing may be an effective tool for improving HIV testing messaging campaigns and could increase community engagement in health campaigns.Clinical trials registrationNCT02248558.

BackgroundThe increasing burden of sexually transmitted infections (STIs) including HIV and syphilis among male sex workers (MSWs) is a major global concern. The aim of our study was to evaluate the difference between MSWs and non-commercial MSMs in China.MethodsDuring 2008-09, in a cross-sectional study, 2618 adult MSM were recruited through respondent-driven and snowball sampling from seven cities of China. Information regarding socio-demographics, risk behaviors, HIV-related knowledge and STI-related symptoms were collected and participants were tested for HIV and syphilis.ResultsAmong 2618 participating MSM, 9.97% sold sex to males. HIV prevalence was 7.45% (6.13% among MSWs and 7.59% among non-MSW MSM) and syphilis prevalence was 14.32% (10.73% for MSWs and 14.72% for non-MSW MSM). Compared to non-MSW MSM, MSWs were more likely to be younger (adjusted odds ratio: aOR = 0.91, 95% confidence interval: 95%CI=0.88-0.93), never married (aOR = 4.38, 95% CI = 2.38-6.80), less educated, heterosexual (aOR = 13.04, 95% CI = 6.08-27.95), less knowledgeable regarding HIV (aOR = 0.70, 95% CI=0.51-0.96), experiencing symptoms of STI (aOR = 2.16, 95% CI = 1.47-3.19), engaging in condomless vaginal intercourse (aOR = 2.16, 95% CI = 1.47-3.19) and less likely to engage in condomless anal intercourse (aOR = 0.62, 95% CI = 0.46-0.85).ConclusionsHigh HIV and syphilis prevalence warranted urgent intervention targeting MSWs as a separate sentinel group for efficient surveillance owing to their different distribution from non-MSW MSM. Although male sex workers and non-commercial homosexuals have similar rates of HIV and syphilis, MSWs have different characteristics which should be considered in designing intervention programs targeting them.

The Multi‐Threat Medical Countermeasure (MTMC) technique is crucial for developing common biochemical signaling pathways, molecular mediators, and cellular processes. This study revealed that the Nod‐like receptor 3 (NLRP3) inflammasome pathway may be a significant contributor to the cytotoxicity induced by various organophosphorus pesticides (OPPs). The study demonstrated that exposure to six different types of OPPs (paraoxon, dichlorvos, fenthion, dipterex, dibrom, and dimethoate) led to significant cytotoxicity in BV2 cells, which was accompanied by increased expression of NLRP3 inflammasome complexes (NLRP3, ASC, Caspase‐1) and downstream inflammatory cytokines (IL‐1β, IL‐18), in which the order of cytotoxicity was dichlorvos > dipterex > dibrom > paraoxon > fenthion > dimethoate, based on the IC50 values of 274, 410, 551, 585, 2,158, and 1,527,566 μM, respectively. The findings suggest that targeting the NLRP3 inflammasome pathway could be a potential approach for developing broad‐spectrum antitoxic drugs to combat multi‐OPPs‐induced toxicity. Moreover, inhibition of NLRP3 efficiently protected the cells against cytotoxicity induced by these six OPPs, and the expression of NLRP3, ASC, Caspase‐1, IL‐1β, and IL‐18 decreased accordingly. The order of NLRP3 affinity for OPPs was dimethoate > paraoxon > dichlorvos > dibrom > (fenthion and dipterex) based on KD values of 89.8, 325, 1,460, and 2,690 μM, respectively. Furthermore, the common molecular mechanism of NLRP3‐OPPs was clarified by the presence of toxicity effector groups (benzene ring, nitrogen/oxygen‐containing functional group); =O, ‐O‐, or =S (active) groups; and combination residues (Gly271, Asp272). This finding provided valuable insights into exploring the common mechanisms of multiple threats and developing effective therapeutic strategies to prevent OPPs poisoning. Plain Language Summary: This study aimed to explore the role of Nod‐like receptor 3 (NLRP3) inflammasome activation in organophosphorus pesticide (OPPs)‐induced cytotoxicity. Six different OPPs, including dimethoate, paraoxon, dichlorvos, dibrom, fenthion, and dipterex, were introduced to BV2 cells and caused significant cytotoxicity along with increased expression of NLRP3 inflammasome complexes and downstream cytokines. Inversely, inhibition of NLRP3 protected against these OPPs. We believe that our study makes a significant contribution to the literature because it suggests that the NLRP3 inflammasome pathway may be a common mechanism of multi‐OPPs‐induced cytotoxicity. By introducing a therapeutic target for OPPs poisoning prevention, broad‐spectrum antitoxic drugs may be designed to effectively protect against OPPs‐induced cytotoxicity. Key Points: The NLRP3 inflammasome potentially contributes to cytotoxicity induced by six types of OPPsInhibition of the NLRP3 pathway effectively prevented cytotoxicity caused by six OPPsThe study proposed targets for broad‐spectrum antitoxic drugs to prevent OPPs‐poisoning [ABSTRACT FROM AUTHOR]