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ObjectiveTo investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females.MethodsA total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL.ResultsSimple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (β = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (β = −0.200, 95% CI −0.348 to −0.051 for vertebral BMD; β = −0.383, 95% CI −0.589 to −0.177 for total hip BMD; and β =−0.393, 95% CI −0.598 to −0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (β = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above.ConclusionsVertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Capsaicinoids are produced uniquely in pepper fruits, and its level determines the commercial quality and health-promoting properties of pepper. So, it is particularly important to increase capsaicinoids content in pepper. Rhizosphere microbiota is critical to plant growth and performance, and affected by plant varieties. However, the impact of pepper varieties with different capsaicinoids yields on the rhizosphere microbiota is poorly understood. Using high-throughput sequencing of the 16S rRNA and internal transcribed spacer (ITS) region, we investigated the rhizosphere microbial community among five pepper varieties containing different capsaicinoids. Our results demonstrated that pepper variety significantly influenced the diversity and structure of rhizosphere microbial community. Bacterial diversity in varieties with high capsaicinoids content was significantly higher than in varieties with low capsaicinoids content, while fungal diversity was opposite to bacterial diversity. The correlation analysis revealed that 19 dominant bacterial genera (e.g., Chujaibacter, Rhodanobacter, and Gemmatimonas) were significantly correlated with capsaicinoids content, and nine of them were also significantly associated with soil nutrients, whereas only one fungal genus (Podospora) was significantly correlated with capsaicinoids content. Additionally, almost all genera which significantly correlated to capsaicinoids content were biomarkers of the five pepper varieties and the correlation was well corresponding to the capsaicinoids content. Overall, our results confirmed that the variety of pepper significantly affected the rhizosphere microbial community in the fields, and bacteria and fungi responded differently to capsaicinoids, which may affect the biosynthesis of capsaicinoids and contribute to further improvement of capsaicinoids production in pepper fruits.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

The accountability audit of natural resources (AANR) is a major institutional arrangement for advancing the construction of an ecological civilization in China. Based on the panel data of 271 cities in China from 2005 to 2017, this paper investigates the relationship between the AANR and carbon dioxide (CO2) emissions using a multi-period difference-in-differences (DID) model. The results show that AANR significantly increases the CO2 emission reduction rate by 0.009 units at the 5% significance level. The results still hold after a series of robustness tests. Given all else being equal, this significant effect is 0.001. Further analyses show that AANR improves pilot cities’ CO2 emission reduction rates mainly by enhancing their green innovation capability. The mediating effect of cities’ green technology innovation capability accounts for 96.00%, while the AANR’s direct effect only accounts for 4.00%. The AANR has significantly positive effects of 0.017% and 0.029% for western cities and cities with high fiscal pressure at the 5% and 1% significance levels, respectively. Therefore, strengthening AANR implementation by enhancing the mediating efficiency of cities’ green technology innovations and implementing dynamically differentiated AANR policies in Chinese meso-cities will contribute to the achievement of China’s carbon peaking and carbon neutrality targets.

BackgroundEngaging in regular physical activity has been consistently linked to improved physical health and academic performance. Despite its known benefits, there is a concerning trend of decreased physical activity among children globally. The study primarily aims to investigate the level of physical activity among junior high school students in Taiyuan and analyse the main affecting factors from a socio-ecological perspective.MethodsA cross-sectional study was conducted, involving 650 junior high school students from 7 schools in Taiyuan, and 648 valid questionnaires were ultimately collected. The data on students’ physical activity levels were collected through the Children’s Leisure Activities Study Survey Questionnaire, and the data on factors affecting students’ physical activity were collected through the Student Perceived Factors Affecting Physical Activity Questionnaire.ResultsIn this study, students from the 7th, 8th, and 9th grades participated in physical activities, averaging 214.500 min per week in moderate-intensity and 25.000 min in high-intensity activities, cumulatively averaging 280.000 min weekly. Notably, a significant disparity (p = 0.012) was observed in the combined duration of moderate and high-intensity activities, with male students engaging more time compared to their female counterparts (307.500 vs. 255.000 min). This variance extended across different grades, particularly evident in 8th graders who recorded the highest weekly high-intensity activity duration (31.000 min) and overall physical activity time (320.500 min), surpassing the 7th graders(p = 0.007 for high-intensity activities). Furthermore, an exploratory factor analysis of a 32-item questionnaire, designed to identify determinants of physical activity, revealed six principal components. These components were found to positively correlate with both moderate and high-intensity physical activities.ConclusionResults emphasize that educational institutions and community programs should collaborate to offer engaging weekend physical activity programs. Schools should develop and implement tailored physical education curricula addressing gender and grade differences. Furthermore, schools and local governments should invest in high-quality sports equipment and facilities.

BackgroundEvaluating the correlation between serum potassium and Parkinson’s disease (PD) in US adults.MethodsA cross-sectional study was conducted on 20,495 adults aged 40 years or older using NHANES data from 2005 to 2020. The study utilized one-way logistic regression and multifactorial logistic regression to examine the correlation between serum potassium levels and PD. Additionally, a smoothed curve fitting approach was employed to assess the concentration-response relationship between serum potassium and PD. Stratified analyses were carried out to investigate potential interactions between serum potassium levels and PD with variables such as age, sex, race, marital status, education, BMI, smoking and medical conditions like coronary, stroke, diabetes, hypertension, and hypercholesterolemia.ResultsIn this study, a total of 20,495 participants, comprising 403 PD and 20,092 non-PD individuals, were included. After adjusted for covariates, multivariable logistic regression revealed that high serum potassium level was an independent risk factor for PD (OR:1.86, 95% CI:1.45 ~ 2.39, p 0.05).ConclusionSerum potassium levels are elevated in patients with Parkinson's disease compared to non-PD patients. Additional prospective studies are required to explore the significance of serum potassium levels in individuals with Parkinson's disease.

Non-motor symptoms are prevalent among individuals with Parkinson’s disease (PD) and seriously affect patient quality of life, even more so than motor symptoms. In the past decade, an increasing number of studies have investigated non-motor symptoms in PD. The present study aimed to comprehensively analyze the global literature, trends, and hotspots of research investigating non-motor symptoms in PD through bibliometric methods. Studies addressing non-motor symptoms in the Web of Science Core Collection (WoSCC), published between January 2013 and December 2022, were retrieved. Bibliometric methods, including the R package “Bibliometrix,” VOS viewer, and CiteSpace software, were used to investigate and visualize parameters, including yearly publications, country/region, institution, and authors, to collate and quantify information. Analysis of keywords and co-cited references explored trends and hotspots. There was a significant increase in the number of publications addressing the non-motor symptoms of PD, with a total of 3,521 articles retrieved. The United States was ranked first in terms of publications (n = 763) and citations (n = 11,269), maintaining its leadership position among all countries. King’s College London (United Kingdom) was the most active institution among all publications (n = 133) and K Ray Chaudhuri was the author with the most publications (n = 131). Parkinsonism & Related Disorders published the most articles, while Movement Disorders was the most cited journal. Reference explosions have shown that early diagnosis, biomarkers, novel magnetic resonance imaging techniques, and deep brain stimulation have become research “hotspots” in recent years. Keyword clustering revealed that alpha-synuclein is the largest cluster for PD. The keyword heatmap revealed that non-motor symptoms appeared most frequently (n = 1,104), followed by quality of life (n = 502), dementia (n = 403), and depression (n = 397). Results of the present study provide an objective, comprehensive, and systematic analysis of these publications, and identifies trends and “hot” developments in this field of research. This work will inform investigators worldwide to help them conduct further research and develop new therapies.

Introduction: Prothioconazole is a triazolinthione fungicide widely used to control diseases on various crops caused by Ascomycetes, Basidiomycetes, and Imperfecti fungi. However, in view of the rapid transformation of parent prothioconazole to its major metabolite prothioconazole-desthio during application and the fact that the latter is of higher toxicity, prothioconazole poses a potential threat to the health of operators in direct contact with it. Currently, very few studies have been carried out regarding prothioconazole and prothioconazole-desthio exposure.Methods: Therefore, a typical exposure scenario from wheat-planting provinces in China was chosen, and a motorized backpack-type sprayer was used as the application equipment. The actual exposure doses of prothioconazole and prothioconazole-desthio for mixers/loaders and applicators under different exposure routes were determined, and a tiered risk assessment was conducted considering different conditions.Results: The results of this study indicated that the exposure risk to operators after spraying with 30% prothioconazole oil dispersion was unacceptable in the primary risk assessment, while the risk was acceptable with integrated risk quotients less than 1 at a better level of protection. Moreover, the upper legs and hands were regarded as the most contaminated sections during the mixing/loading process, and legs were the most contaminated sections during spraying. Good protection equipment, such as hats, long-sleeve shirts, long pants, socks, shoes, and rubber or nitrile gloves, was effective at alleviating prothioconazole and prothioconazole-desthio exposure. This study aims to provide important references for the safe use and risk management of prothioconazole.

BackgroundFinerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), while the relative efficacy has not been determined.MethodsThe databases of PubMed, Embase and Cochrane were searched for relevant cardiovascular or renal outcome trials of SGLT2i or finerenone. The end points were major adverse cardiovascular events (MACE), nonfatal stroke (NS), myocardial infarction (MI), hospitalization for heart failure (HHF), cardiovascular death (CVD), and renal composite outcome (RCO). Network meta-analysis was performed using Bayesian networks to obtain pooled hazard ratios (HR) and 95% confidence intervals (CI). The probability values for ranking active and placebo interventions were calculated using cumulative ranking curves.Results1024 articles were searched, and only 9 studies were screened and included in this meta-analysis with 71793 randomized participants. Sotagliflozin (HR 0.72 95%CI 0.59-0.88, SUCAR=0.93) and canagliflozin (HR 0.80 95%CI 0.67-0.97, SUCAR=0.73) can significantly reduce the risk of MACE compared with placebo. Canagliflozin (HR 0.64 95%CI 0.48-0.86, SUCAR=0.73), sotagliflozin (HR 0.66 95%CI 0.50-0.87, SUCAR=0.69) and empagliflozin (HR 0.65 95%CI 0.43-0.98, SUCAR=0.68) can significantly reduce the risk of HHF compared with placebo. Empagliflozin (HR 0.62 95%CI 0.43-0.89, SUCAR=0.96) can significantly reduce the risk of CVD compared with placebo. Empagliflozin (HR 0.61 95%CI 0.39-0.96, SUCAR=0.74), canagliflozin (HR 0.66 95%CI 0.46-0.92, SUCAR=0.63), and dapagliflozin (HR 0.53 95%CI 0.32-0.85, SUCAR=0.88) can significantly reduce the risk of RCO compared with placebo. Finerenone has reduced the risk of MACE, MI, HHF, CVD and RCO to varying degrees, but they do not show significant difference from placebo and each SGLT2i.ConclusionBoth SGLT2i and finerenone could reduce the risk of MACE, HHF, MI, CVD, RCO. Finerenone has no obvious advantage than SGLT2i on the effects of cardiovascular and renal protective.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022375092.

Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in both innate and acquired immune responses against pathogens. However, the role of DCs in coronavirus disease 2019 (COVID-19) is unclear. Virus-like particles (VLPs) that structurally mimic the original virus are one of the candidates COVID-19 vaccines. In the present study, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VLPs were used as an alternative to live virus to evaluate the interaction of the virus with DCs. The results revealed that SARS-CoV-2 VLPs induced DC maturation by augmenting cell surface molecule expression (CD80, CD86, and major histocompatibility complex class II (MHC-II)) and inflammatory cytokine production (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-12p70) in DCs via the mitogen-activated protein kinase and nuclear factor-κB signaling pathways. In addition, mature DCs induced by SARS-CoV-2 VLPs promoted T cell proliferation, which was dependent on VLPs concentration. Our results suggest that SARS-CoV-2 VLPs regulate the immune response by interacting with DCs. These findings will improve the understanding of SARS-CoV-2 pathogenesis and SARS-CoV-2 vaccine development.

P53, a well-known tumor suppressor, has been confirmed to regulate the infection of various viruses, including chicken viruses. Our previous study observed antiviral effect of p53 inhibitor Pifithrin-α (PFT-α) on the infection of avian infectious laryngotracheitis virus (ILTV), one of the major avian viruses economically significant to the poultry industry globally. However, the potential link between this antiviral effect of PFT-α and p53 remains unclear. Using chicken LMH cell line which is permissive for ILTV infection as model, we explore the effects of p53 on ILTV replication and its underlying molecular mechanism based on genome-wide transcriptome analysis of genes with p53 binding sites. The putative p53 target genes were validated by ChIP-qPCR and RT-qPCR. Results demonstrated that, consistent with the effects of PFT-α on ILTV replication we previously reported, knockdown of p53 repressed viral gene transcription and the genome replication of ILTV effectively. The production of infectious virions was also suppressed significantly by p53 knockdown. Further bioinformatic analysis of genes with p53 binding sites revealed extensive repression of these putative p53 target genes enriched in the metabolic processes, especially nucleotide metabolism and ATP synthesis, upon p53 repression by PFT-α in ILTV infected LMH cells. Among these genes, eighteen were involved in nucleotide metabolism and ATP synthesis. Then eight of the 18 genes were selected randomly for validations, all of which were successfully identified as p53 target genes. Our findings shed light on the mechanisms through which p53 controls ILTV infection, meanwhile expand our knowledge of chicken p53 target genes.

The dissolution of invaded gas in the drilling fluid during drilling results in an increase in the gas invasion concealment. This is of great significance for the development of acid gas reservoirs to determine the solubility change and multiphase flow law in an annulus after invasion by natural gas with high CO2 content. In this study, control equations of gas–liquid flow during drilling gas invasion are established considering the influence of gas solubility. For the prediction of gas solubility, the interaction parameters of CH4 and water in the Peng–Robinson equation of state are optimised to establish a gas solubility prediction model. The solubility of natural gas with high CO2 content in water and brine solution is measured through phase-equilibrium experiments. The results indicate that the newly optimised solubility model can accurately predict the solubility of CH4 and CO2 in water, and the prediction error is within 5%. Moreover, the prediction error for the solubility of CH4 and CO2 mixed gas is within 15%. The analysis of gas invasion in example engineering drilling applications reveals that an increase in the CO2 content in the invaded gas leads to a slow change in the mud-pit increment, and the concealment strengthens as the distance between the gas-migration front and the wellhead increases. Gas solubility has a significant impact on the monitoring of gas invasion in low permeability reservoirs.

Recombinant adeno-associated virus (AAV) is a promising delivery vehicle for in vivo gene therapy and has been widely used in >200 clinical trials globally. There are already several approved gene therapy products, e.g., Luxturna and Zolgensma, highlighting the remarkable potential of AAV delivery. In the past, AAV has been seen as a relatively non-immunogenic vector associated with low risk of toxicity. However, an increasing number of recent studies indicate that immune responses against AAV and transgene products could be the bottleneck of AAV gene therapy. In clinical studies, pre-existing antibodies against AAV capsids exclude many patients from receiving the treatment as there is high prevalence of antibodies among humans. Moreover, immune response could lead to loss of efficacy over time and severe toxicity, manifested as liver enzyme elevations, kidney injury, and thrombocytopenia, resulting in deaths of non-human primates and patients. Therefore, extensive efforts have been attempted to address these issues, including capsid engineering, plasmapheresis, IgG proteases, CpG depletion, empty capsid decoy, exosome encapsulation, capsid variant switch, induction of regulatory T cells, and immunosuppressants. This review will discuss these methods in detail and highlight important milestones along the way.

BackgroundFor patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), azacitidine with donor lymphocyte infusion (DLI) is a feasible option to perform a preemptive or salvage treatment. However, its efficacy lacked comprehensive analysis, and this study aimed to fill this gap.MethodsWe searched potential studies in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials. Thirteen studies involving 811 patients were analyzed. The inverse variance method was used to calculate the pooled proportion and 95% confidence interval (CI). Subgroup analysis was performed to explore the source of heterogeneity.ResultsThe rate of pooled complete remission + partial remission (CR + PR), CR, and 2-year overall survival (OS) were 30% (95% CI: 22%–39%), 21% (95% CI: 16%–28%), and 31% (95% CI: 27%–35%), respectively. The pooled acute graft-versus-host disease (GvHD) and chronic GvHD rates were 15% (95% CI: 9%–23%) and 14% (95% CI: 8%–23%), respectively. Adverse cytogenetics and a higher percentage of bone marrow (BM) blasts at relapse were correlated with worse CR + PR and CR (interaction p < 0.05). Higher 2-year OS was found in patients with lower BM blasts at relapse or a longer time from allo-HSCT to relapse (interaction p < 0.05). Furthermore, the preemptive treatment for molecular relapse/minimal residual disease positivity resulted in much better outcomes than that for hematological relapse, both in terms of CR and 2-year OS (interaction p < 0.001).ConclusionThe regimen of azacitidine and DLI could safely improve the outcomes of relapsed AML/MDS after allo-HSCT, especially in those with signs of early relapse. The administration of targeted medicines in azacitidine-based therapies may further improve the outcomes of relapsed AML/MDS.

In aquatic ecosystems, pesticide residues meanly present as mixtures of varying complexity, which may lead to compound pollution of organisms. Therefore, it is of great practical importance to evaluate the combined toxic effects of pesticides. In this study, the mixture acute toxicities of fenvalerate with tebuconazole on zebrafish larvae and adults were investigated. The effects of mixture toxicity on swimming behavior of larvae were also analyzed. The mixture acute toxicity of the systems showed antagonistic effects on adult zebrafish when the mixing ratios of fenvalerate and tebuconazole were equal, but the other two ratios of the mixes both showed synergistic effects. The strongest synergistic effect was observed when fenvalerate was mixed with tebuconazole in the ratio of 8:2. The swimming behavior of zebrafish larvae was significantly inhibited after exposure to single or mixed systems for 2 days. However, significant up-regulation of behavioral indicators in zebrafish larvae was observed at the beginning of exposure in the mixture exposure groups. The results showed that fenvalerate and tebuconazole had the risk of synergistic toxic effect on zebrafish. It is recommended that the simultaneous use of both pesticides in agricultural activities near water bodies should be scientifically controlled to avoid adverse effects on aquatic organisms.

The microbiota and its metabolites play an important role in regulating the host metabolism and immunity. However, the underlying mechanism is still not well studied. Thus, we conducted the LC-MS/MS analysis and RNA-seq analysis on Equus przewalskii with and without horse botfly infestation to determine the metabolites produced by intestinal microbiota in feces and differentially expressed genes (DEGs) related to the immune response in blood and attempted to link them together. The results showed that parasite infection could change the composition of microbial metabolites. These identified metabolites could be divided into six categories, including compounds with biological roles, bioactive peptides, endocrine-disrupting compounds, pesticides, phytochemical compounds, and lipids. The three pathways involving most metabolites were lipid metabolism, amino acid metabolism, and biosynthesis of other secondary metabolites. The significant differences between the host with and without parasites were shown in 31 metabolites with known functions, which were related to physiological activities of the host. For the gene analysis, we found that parasite infection could alarm the host immune response. The gene of “cathepsin W” involved in innate and adaptive immune responses was upregulated. The two genes of the following functions were downregulated: “protein S100-A8” and “protein S100-A9-like isoform X2” involved in chemokine and cytokine production, the toll-like receptor signaling pathway, and immune and inflammatory responses. GO and KEGG analyses showed that immune-related functions of defense response and Th17 cell differentiation had significant differences between the host with and without parasites, respectively. Last, the relationship between metabolites and genes was determined in this study. The purine metabolism and pyrimidine metabolism contained the most altered metabolites and DEGs, which mainly influenced the conversion of ATP, ADP, AMP, GTP, GMP, GDP, UTP, UDP, UMP, dTTP, dTDP, dTMP, and RNA. Thus, it could be concluded that parasitic infection can change the intestinal microbial metabolic activity and enhance immune response of the host through the pathway of purine and pyrimidine metabolism. This results will be a valuable contribution to understanding the bidirectional association of the parasite, intestinal microbiota, and host.

Even frequently used in wheat breeding, we still have an insufficient understanding of the biology of the products via distant hybridization. In this study, a transcriptomic analysis was performed for six Triticum aestivum-Thinopyrum elongatum substitution lines in comparison with the host plants. All the six disomic substitution lines showed much stronger “transcriptomic-shock” occurred on alien genomes with 57.43–69.22% genes changed expression level but less on the recipient genome (2.19–8.97%). Genome-wide suppression of alien genes along chromosomes was observed with a high proportion of downregulated genes (39.69–48.21%). Oppositely, the wheat recipient showed genome-wide compensation with more upregulated genes, occurring on all chromosomes but not limited to the homeologous groups. Moreover, strong co-upregulation of the orthologs between wheat and Thinopyrum sub-genomes was enriched in photosynthesis with predicted chloroplastic localization, which indicates that the compensation happened not only on wheat host genomes but also on alien genomes.

The objective of this study was to assess the effect of harvesting time on the fermentation characteristics, chemical composition, and microbial community of king grass silage. King grass was harvested at three growth periods of 90 days (KN90S), 110 days (KN110S), and 130 days (KN130S); chopped into 2–3-cm particle size; and ensiled in polyethylene bags (20 × 30 cm). The fermentation quality and chemical composition of silages were analyzed after 1, 3, 7, 14, 30, and 60 days of ensiling. Bacterial community of silage ensiled for 60 days was profiled using next generation sequencing (NGS) technology. The KN110S showed the most extensive lactic acid (LA) fermentation during 7 days of fermentation compared to KN90S and KN130S. After 60 days of fermentation, the KN110S showed the lowest pH and the highest lactic acid content among the three treatments. The butyric acid and ammonia nitrogen contents of KN90S and KN130S were significantly greater than those of KN110S (p < 0.05). After a timespan of 60 days of ensiling, the bacterial community of king grass silage was predominantly populated by Proteobacteria in phylum level, whereas unclassified Enterobacteriaceae genus remained dominant in all silages. A higher relative abundance of Clostridium was observed in KN90S and KN130S, but not in KN110S, and greater abundance of Lactococcus appeared in KN110S and KN130S silages than KN90S. It is concluded that harvesting time had an important effect on the fermentation quality and microbial community of king grass silage.

The outbreak of COVID-19 and the uncertainty it brings have created enormous pressure on governments to control the global pandemic and restore economic growth. It is an inevitable choice for governments of various countries to seek to control the pandemic and to provide support such as subsidies to people who lose their jobs or cannot work. However, governments should evaluate their pandemic policies to determine their effectiveness. To maintain social stability and help vulnerable groups, governments also must determine when subsidies are needed and when these support policies should be withdrawn. This research demonstrates that the administration of vaccines and the wearing of masks have a relatively limited impact on preventing the spread of the COVID-19 virus. By contrast, strict school closure policies combined with personal movement restrictions are more helpful in mitigating the spread of the virus. Compared with vaccine policies and wearing masks, controlling internal movement is the most effective way to manage the pandemic in schools. Additionally, economic support such as subsidies for the unemployed and underemployed is not only conducive to prevention of the virus' spread but also to economic recovery and social stability. When the pandemic is brought under control, economic support for vulnerable groups can be gradually reduced or even withdrawn.

Rice–crab co-culture is a high-benefit eco-breeding pattern that has been extensively developed in many regions of China. However, little attention has been paid to the safety of pesticides used to control rice pests in the crab–rice co-culture system. This study monitored the actual residue levels of propiconazole in water and soil of rice–crab co-culture fields and evaluated the acute toxicity, subchronic toxicity, and bioaccumulation of propiconazole to Eriocheir sinensis. We observed that the residue level of propiconazole in paddy soil was higher than that in paddy water within 42-day field monitoring. Propiconazole demonstrated a low acute toxicity (96 h-LC50 > 100 mg/L) to E. sinensis and exhibited no obvious adverse impact on the growth of E. sinensis after exposure to 500 μg/L, which was 10 times the actual residual concentration of propiconazole in the crab–rice co-culture field. The highest bioaccumulation of propiconazole was obtained from gills, followed by the hepatopancreas and meat. These results will contribute to the guidance of scientific utilization of pesticides in the crab–rice co-culture field.

Little is known about whether the application of biogas residues in rice fields will affect the degradation of pesticides. This study investigated the dissipation behavior of the fungicide difenoconazole in paddy water and sediment after the application of a chemical fertilizer or biogas residues. The results showed that the application of biogas residues changes the dissipation of difenoconazole in both paddy water and sediment. The half-lives of difenoconazole in paddy water and sediment with biogas residues were 0.50 and 10.09 days, respectively, while the half-lives of difenoconazole in paddy water and sediment with chemical fertilizer were only 0.22 and 4.64 days, respectively. After biogas residues were applied in a paddy field, no significant changes in pH value of paddy water and sediment and soil microorganisms were observed, but soil organic matter decreased by 30%. The above studies suggest that biogas residues may affect the dissipation of pesticides in paddy field water and sediments, which provides a new focus on the scientific and rational use of biogas residues as organic fertilizer in rice fields.

Circular RNAs (circRNAs) are a type of long non-coding RNA with covalently closed loops that are naturally resistant to exoribonuclease. With the rapid development of high-throughput sequencing technologies and bioinformatics, increasing data suggest that circRNAs are abnormally expressed in renal cell carcinoma (RCC) and act as important regulators of RCC carcinogenesis and progression. CircRNAs play important biological roles in modulating cell proliferation, migration, invasion, apoptosis, and gemcitabine chemoresistance in RCC. Most of the circRNAs studied in RCC have been reported to be significantly associated with many clinicopathologic characteristics and survival parameters of RCC. The stability and specificity of circRNAs enable them potential molecular markers for RCC diagnosis and prognosis. Moreover, circRNAs have emerged as targets for developing new therapies, because they can regulate various signaling pathways associated with RCC initiation and progression. In this review, we briefly summarize the biogenesis, degradation, and biological functions of circRNAs as well as the potential clinical applications of these molecules for RCC diagnosis, prognosis, and targeted therapy.

Soil organic carbon (SOC) is significant for soil quality and global carbon cycles. SOC was observed to be related to soil geochemistry, and soils originating from different bedrocks have different geochemical properties, but the effect of bedrock on SOC is still undefined. Soils overlying different bedrocks in Zhenxiong County and Weixin County were sampled. Specifically, soils in the mineral horizon, which are less affected by the external environment than surface soils, are focused on to reveal the effect of bedrock on SOC. Al/Ti, Fe/Ti, and Al/Fe indicate a soil–rock successive relationship. SOC contents in the mineral horizon are 0.19–2.74% (1.24% on average), and those in the surface horizon are 1.26–4.01% (2.63% on average). SOC contents in the surface and mineral horizons of the same bedrock are significantly positively correlated, implying that the bedrock is an important factor affecting SOC. SOC in the mineral horizon is related to the first transition metal ions. Significantly, positive correlations of SOC (p < 0.01) with Co, Cu, Ti, V, and Zn, and a positive correlation (p < 0.05) with Ni were observed in the mineral horizon. Organic transition metal complexation seems to play an important role in governing SOC in the mineral horizon. That is, the complexation maintains organic carbon stability, slows down its decomposition rate, and accumulates organic carbon. The Ca–SOC positive correlation in the mineral horizon exits because Ca also can complex with organic carbon. Co, Cu, and V–SOC positive correlations (p < 0.05) were also observed, but there were no significant positive correlations (p < 0.01) in the surface horizon because surface SOC had diversified sources. An SOC evolution model influenced by the bedrock was forwarded. Thus, the different soil geochemistry originating from different bedrocks should be noticed when SOC and global carbon cycles are discussed.

Sepsis, an infection-induced systemic inflammatory disorder, is often accompanied by multiple organ dysfunction syndromes with high incidence and mortality rates, and those who survive are often left with long-term sequelae, bringing great burden to social economy. Therefore, novel approaches to solve this puzzle are urgently needed. Previous studies revealed that long non-coding RNAs (lncRNAs) have exerted significant influences on the process of sepsis. The aim of this review is to summarize our understanding of lncRNAs as potential sepsis-related diagnostic markers and therapeutic targets, and provide new insights into the diagnosis and treatment for sepsis. In this study, we also introduced the current diagnostic markers of sepsis and discussed their limitations, while review the research advances in lncRNAs as promising biomarkers for diagnosis and prognosis of sepsis. Furthermore, the roles of lncRNAs in sepsis-induced organ dysfunction were illustrated in terms of different organ systems. Nevertheless, further studies should be carried out to elucidate underlying molecular mechanisms and pathological process of sepsis.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that causes high rates of disability and mortality worldwide because of severe progressive and irreversible symptoms. During the period of COPD initiation and progression, the immune system triggers the activation of various immune cells, including Regulatory T cells (Tregs), dendritic cells (DCs) and Th17 cells, and also the release of many different cytokines and chemokines, such as IL-17A and TGF-β. In recent years, studies have focused on the role of IL-17A in chronic inflammation process, which was found to play a highly critical role in facilitating COPD. Specially, IL-17A and its downstream regulators are potential therapeutic targets for COPD. We mainly focused on the possibility of IL-17A signaling pathways that involved in the progression of COPD; for instance, how IL-17A promotes airway remodeling in COPD? How IL-17A facilitates neutrophil inflammation in COPD? How IL-17A induces the expression of TSLP to promote the progression of COPD? Whether the mature DCs and Tregs participate in this process and how they cooperate with IL-17A to accelerate the development of COPD? And above associated studies could benefit clinical application of therapeutic targets of the disease. Moreover, four novel efficient therapies targeting IL-17A and other molecules for COPD are also concluded, such as Bufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), and curcumin, a natural polyphenol extracted from the root of Curcuma longa.

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs’ therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.

Soft-oxometalates (SOMs) are colloid suspensions of superstructured assemblies of polyoxometalates (POMs) and are found to be very effective photo-catalysts in a number of chemical reactions. The stabilization of SOMs generally requires legends or stabilizers, e.g., polymers and surfactants. In this paper, a light responsive azobenzene surfactant, C10AZOC2N3, was developed and used to stable {Mo132} SOMs. Various techniques such as Dynamic light scattering, TEM, UV-Vis spectra and cyclic voltammetry were employed to characterize the experimental results. The outstanding structure-directing effect of surfactant self-assembly micelles in solution on inorganic counter-anions was demonstrated. Different amount of cyclohexane was solubilized into C10AZOC2N3 micelles to successfully control the size of {Mo132} SOMs cluster. Furthermore, the clusters exposed to UV light for a certain time can be served as a second trigger to control the size of SOMs due to the trans-cis conformation transition of surfactant molecules. The redox potentials of C10AZOC2N3-{Mo132} SOMs were investigated as the cluster size varied. Interestingly, the redox potential of {Mo132} was not affected by the cluster size, indicating that the presence of surfactant did not change the main function of {Mo132} as an electrochemical catalyst, but merely assisted in the size control of SOM aggregation.

Objected: To evaluate the association between osteoarthritis (OA) and Parkinson's disease (PD) in adults in the United States. Methods: Using 2011-2020 NHANES data, a cross-sectional study of 11,117 adults over the age of 40 was conducted. Univariate logistic regression and multivariate logistic regression were used to analyze the relationship between arthritis and PD. In addition, stratified analysis was used to examine whether the relationship between arthritis and PD was interactive with age, gender, race, education, BMI. Results: In this study, a total of 11,117 participants were included, and we found that osteoarthritis was positively correlated with the development of PD compared with non-arthritis patients [1.95 (1.44 ~ 2.62)] (p < 0.001). After adjusting the covariates, the results are still stable. Conclusion: PD patients were positively correlated with OA. Among people with OA, there was a 95% increased risk of PD compared to people without arthritis. Therefore, when treating OA, attention should be paid to the increased risk of PD. In the meantime, further studies are needed to explore the link between OA and PD patients. [ABSTRACT FROM AUTHOR]

IntroductionJacaranda mimosifolia, native to South America, is a notable ornamental tree widely used in Chinese urban landscaping due to its aesthetic and environmental value. Despite its popularity, the cultivation of J. mimosifolia in China faces challenges, including intermittent failures in various regions. This study assesses the potential distribution of J. mimosifolia in China and its response to climate change, providing insights for its application and promotion.MethodsUsing MaxEnt software, we developed an ecological niche model from 218 distribution records and selected 10 environmental variables to predict the tree’s distribution under various climate scenarios (SSP126, SSP245, SSP370).ResultsOur model demonstrates high predictive accuracy (AUC > 0.90) across scenarios, identifying key factors such as the mean temperature of the coldest quarter (bio11), precipitation of the driest month (bio14), temperature annual range (bio7), and minimum temperature of the coldest month (bio6). Their relative contribution rates were 49.3%, 18.4%, 15.6%, and 2.0%, respectively. The average temperature of the coldest quarter was not lower than 5°C, with the ideal range being 7.38~14.88°C. Currently, J. mimosifolia predominantly thrives in Taiwan, Fujian, Guangdong, Hainan, Guangxi, Yunnan, and to a lesser extent in the Sichuan Basin, southern Guizhou, Tibet, Hunan, Jiangxi, and Zhejiang province, covering a total area of approximately 122.19 × 104 km2. Future predictions indicate that under the SSP126 scenario, the most significant contraction occurs between the 2050s and 2070s, with a total change of −1.08 × 104 km2. Conversely, under the SSP370 scenario, the greatest expansion is observed from the 2030s to the 2050s, amounting to a change of 2.08 × 104 km2. Suitable area expansion is anticipated in most periods and scenarios, except for SSP126 in the 2070s, SSP245 in the 2050s, and SSP370 in the 2030s and 2070s. The distribution center shifts observed include movements northwestward, southwestward, and eastward with distances ranging from 5.12 km to 18.84 km. These shifts are likely driven by global warming, resulting in movements to higher elevations and latitudes.DiscussionThese predictions will provide a solid theoretical foundation for the future application of J. mimosifolia in urban landscaping and serve as a valuable reference for its introduction and cultivation.

Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in both innate and acquired immune responses against pathogens. However, the role of DCs in coronavirus disease 2019 (COVID-19) is unclear. Virus-like particles (VLPs) that structurally mimic the original virus are one of the candidates COVID-19 vaccines. In the present study, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VLPs were used as an alternative to live virus to evaluate the interaction of the virus with DCs. The results revealed that SARS-CoV-2 VLPs induced DC maturation by augmenting cell surface molecule expression (CD80, CD86, and major histocompatibility complex class II (MHC-II)) and inflammatory cytokine production (tumor necrosis factor-a, interleukin (IL)-1b, IL-6, and IL-12p70) in DCs via the mitogen-activated protein kinase and nuclear factor-kB signaling pathways. In addition, mature DCs induced by SARS-CoV-2 VLPs promoted T cell proliferation, which was dependent on VLPs concentration. Our results suggest that SARS-CoV-2 VLPs regulate the immune response by interacting with DCs. These findings will improve the understanding of SARS-CoV-2 pathogenesis and SARS-CoV-2 vaccine development. [ABSTRACT FROM AUTHOR]

BackgroundThe tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we aim to establish a prognostic model for LUAD.MethodUtilizing the Seurat and Scanpy packages, we successfully constructed an immune microenvironment atlas for LUAD. The Monocle3 and PAGA algorithms were employed for pseudotime analysis, pySCENIC for transcription factor analysis, and CellChat for analyzing intercellular communication. Following this, a prognostic model for LUAD was developed, based on the marker genes of exhausted CD8+ T cells, enabling effective risk stratification in LUAD patients. Our study included a thorough analysis to identify differences in TME, mutation landscape, and enrichment across varying risk groups. Moreover, by integrating risk scores with clinical features, we developed a new nomogram. The expression of model genes was validated via RT-PCR, and a series of cellular experiments were conducted, elucidating the potential oncogenic mechanisms of GALNT2.ResultsOur study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD’s microenvironment. We underscored pDCs’ role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2’s function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment.ConclusionThe creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.

Analog memory presents a promising solution in the face of the growing demand for energy-efficient artificial intelligence (AI) at the edge. In this study, we demonstrate efficient deep neural network transfer learning utilizing hardware and algorithm co-optimization in an analog resistive random-access memory (ReRAM) array. For the first time, we illustrate that in open-loop deep neural network (DNN) transfer learning for image classification tasks, convergence rates can be accelerated by approximately 3.5 times through the utilization of co-optimized analog ReRAM hardware and the hardware-aware Tiki-Taka v2 (TTv2) algorithm. A simulation based on statistical 14 nm CMOS ReRAM array data provides insights into the performance of transfer learning on larger network workloads, exhibiting notable improvement over conventional training with random initialization. This study shows that analog DNN transfer learning using an optimized ReRAM array can achieve faster convergence with a smaller dataset compared to training from scratch, thus augmenting AI capability at the edge.

Objective: This study aimed to investigate the effect of whole-body vibration training (WBVT) combined with KAATSU training (KT) on lower limb joint muscle strength and to provide a reference for improving muscle strength in older women.Methods: A total of 86 healthy older people was randomly divided into WBVT group (WG, n = 21), KT group (KG, n = 22), combined intervention group (CIG, n = 20) and control group (CG, n = 23). WG and CIG subjects underwent WBVT, and KG and CIG subjects underwent 150 mmHg and lower limb joint and local compression intervention for 16 weeks (three times per week, about 15 min/time). The peak torque (PT) and endurance ratio (ER) of joint flexion or extension were tested for all subjects.Results: 1) Results at 16 weeks were compared with the baseline data. The knee extension and ankle flexion PT (60°/s) in CIG increased by 14.3% and 15.3%, respectively (p < 0.05). The knee extension PT (180°/s) increased by 16.9, 18.4% and 33.3% in WG, KG and CIG (p < 0.05), respectively, and the ankle extension PT (180°/s) in CIG increased by 31.1% (p < 0.05). The hip, knee extension and ankle flexion ER increased by 10.0, 10.9% and 5.7% in CIG (p < 0.05), respectively. 2) Results were compared among groups at 16 weeks. The relative changes were significantly lower in WG, KG and CG compared to CIG in the knee extension and ankle flexion PT (60°/s) (p < 0.05). The relative changes were significantly greater in WG, KG and CIG compared to CG in the knee extension PT (180°/s) (p < 0.05). The relative changes were significantly lower in WG, KG and CG compared to CIG in the ankle extension PT (180°/s) (p < 0.05). The relative changes were significantly lower in WG, KG and CG compared to CIG in the hip extension ER (p < 0.05). The relative changes were significantly lower in CG compared to CIG in the knee extension ER (p < 0.05).Conclusion: Sixteen-week WBVT and KT increased the knee extensor strength in older women. Compared with a single intervention, the combined intervention had better improvements in the knee extensor and ankle flexor and extensor strength and hip extension muscle endurance. Appears to be some additional benefit from combined intervention above those derived from single-interventions.

The complex and variable oceanic environment challenges channel modeling of Underwater Wireless Optical Communication (UWOC) systems. Most of the classical modeling methods focus mainly on the water environment and ignore the effect of communication equipment on signal transmission, thus making it difficult to model the UWOC channel’s complicated characteristics comprehensively. In this work, a UWOC channel emulator based on Deep Convolutional Conditional Generative Adversarial Networks is established and verified to address the challenge, which can effectively learn the characteristics of channel response and generate emulated signals with randomness like a real UWOC system in a practical application environment. Compared with the approaches based on multi-layer perceptron and convolutional neural network, the experimental results of the proposed method indicate outstanding performances in time domain, frequency domain and universality with different turbidity levels, respectively. This approach provides a new idea for applying deep learning techniques to the field of UWOC channel modeling.

ObjectivesThis study aimed to explore the value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) radiomics to diagnose breast cancer and predict its molecular subtype.MethodA total of 170 lesions (121 malignant, 49 benign) were selected from March 2019 to January 2022. Malignant lesions were further divided into six categories of molecular subtype: (non-)Luminal A, (non-)Luminal B, (non-)human epidermal growth factor receptor 2 (HER2) overexpression, (non-)triple-negative breast cancer (TNBC), hormone receptor (HR) positivity/negativity, and HER2 positivity/negativity. Participants were examined using CUS and CEUS before surgery. Regions of interest images were manually segmented. The pyradiomics toolkit and the maximum relevance minimum redundancy algorithm were utilized to extract and select features, multivariate logistic regression models of CUS, CEUS, and CUS combined with CEUS radiomics were then constructed and evaluated by fivefold cross-validation.ResultsThe accuracy of the CUS combined with CEUS model was superior to CUS model (85.4% vs. 81.3%, p

Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.

The widespread surface of the air-water interface plays a crucial role in the partitioning processes between the atmosphere and the hydrosphere. As one of the prime CWAs (Chemical Warfare Agents) abandoned by Japanese, the unfound 2-Chloroacetophenone posed a severe threat to the Chinese people. In this study, the interface partition constant of 2-Chloroacetophenone was obtained by measuring the mass uptake vapor on different environmental water films with various thicknesses. The surface tension, dissolved organic matter, and salinity of the environmental samples were analyzed. The partition constant of 2-Chloroacetophenone in pure water, river water and sea water samples at 288 K were 1182.2 ± 49.9, 1606.6 ± 101.3 and 408.9 ± 18.3, respectively. Surface adsorption is the predominant mechanism. The results also indicate that the adsorption partitioning ability of 2-Chloroacetophenone at the air/water interface was negatively correlated with surface tension. 2-Chloroacetophenone is more likely to adsorb at the gas/water interface with lower surface tension.

The high recurrence rate of non-muscle invasive bladder cancer (BC) and poor prognosis of advanced BC are therapeutic challenges that need to be solved. Bacillus Calmette-Guerin (BCG) perfusion was the pioneer immunotherapy for early BC, and the discovery of immune checkpoint inhibitors has created a new chapter in the treatment of advanced BC. The benefit of immunotherapy is highly anticipated, but its effectiveness still needs to be improved. In this review, we collated and analysed the currently available information and explored the mechaisms by which the internal immune imbalance of BC leads to tumour progression. The relationship between immunity and progression and the prognosis of BC has been explored through tests using body fluids such as blood and urine. These analytical tests have attempted to identify specific immuyne cells and cytokines to predict treatment outcomes and recurrence. The diversity and proportion of immune and matrix cells in BC determine the heterogeneity and immune status of tumours. The role and classification of immune cells have also been redefined, e.g., CD4 cells having recognised cytotoxicity in BC. Type 2 immunity, including that mediated by M2 macrophages, Th2 cells, and interleukin (IL)-13, plays an important role in the recurrence and progression of BC. Pathological fibrosis, activated by type 2 immunity and cancer cells, enhances the rate of cancer progression and irreversibility. Elucidating the immune status of BC and clarifying the mechanisms of action of different cells in the tumour microenvironment is the research direction to be explored in the future.

ObjectiveTo evaluate the association between perioperative estimated glomerular filtration rate (eGFR) and postoperative oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU),and to evaluate the effect of sex on this association.MethodsThe medical records of patients with UTUC who underwent RNU between January 2012 and December 2017 at our hospital were retrospectively reviewed. Patients were divided into three groups based on preoperative eGFRs: normal eGFR (>60 mL/min/1.73 m2; n = 179), moderately reduced eGFR (45–60 mL/min/1.73 m2; n = 45), and severely reduced eGFR (≤ 45 mL/min/1.73 m2; n = 36). Statistical analyses were performed to evaluate the prognostic impact of preoperative eGFR on prognosis.ResultsPatient mean age was 66.7 ± 9.6 years, and 47.9% were female. Multivariate regression analysis based on Cox proportional risk models and Kaplan-Meier survival rates showed that lower preoperative eGFR was associated with decreased OS, PFS, and CSS. In the adjusted Cox regression model, patients with normal and moderately reduced eGFRs had a decreased hazard for mortality, with adjusted hazard ratios of 0.13 [95% confidence interval (CI): 0.07–0.26] and 0.36 (95% CI: 0.18–0.73), respectively (P < 0.001). The smooth fitting curve suggested a linear relationship between eGFR and prognostic survival. Additionally, sensitivity subgroup analyses verified an inverse relationship between the reduced eGFR and OS. Women had a lower eGFR and worse oncological outcomes than men. A nomogram for OS was developed based on multivariate analysis with a C-index of 0.754 (95% CI: 0.728–0.779).ConclusionPreoperative renal insufficiency is strongly associated with a higher risk of cancer progression and a lower survival probability. It is important to identify preoperative renal insufficiency in patients with UTUC, particularly female patients.

Background and AimsThe extent of surgical treatment for most patients with thyroid cancer (TC) remains controversial and varies widely. As an emerging technology, genetic testing facilitates tumor typing and disease progression monitoring and is expected to influence the choice of surgical approach for patients with TC. Recent genome-wide association studies (GWASs) have identified that rs2439302 (8p12) variants near NRG1 are associated with TC risk; however, the results remain inconclusive. Therefore, we aimed to perform a meta-analysis to clarify the association between rs2439302 variants and the risk of TC.MethodsWe search eligible studies using Pubmed, Scopus, Embase, Web of Science, and Cochrane library by July 2021. We analyzed the pooled OR and the corresponding 95% confidence interval (95% CI) of the included studies and then conducted subgroup analysis according to the ethnicity. We also performed a sensitivity analysis to validate the findings.ResultsThis meta-analysis finally included 7 studies involving 6,090 cases and 14,461 controls. Results showed that the G allele of the rs2439302 polymorphism was a significant risk factor of TC in Allele (G/C), Dominant (GG+GC/CC), Recessive (GG/GC+CC), Homozygote (GG/CC), Heterozygote (GC/CC) models, with pooled ORs of 1.38 (95%CI, 1.31–1.45), 1.51 (95%CI, 1.41–1.62), 1.52 (95%CI, 1.40–1.66), 1.90 (95%CI, 1.71–2.10), and 1.40 (95%CI, 1.30–1.51), respectively. The subgroup analysis showed that rs2439302 polymorphism was associated with higher TC risk in different ethnicities with OR > 1. The sensitivity analysis exhibited that the results were stable by omitting any included studies.ConclusionsThe study revealed that rs2439302 variants were associated with higher TC risk and may have a major influence on the choice of operative approach for patients with TC.

Rhesus macaques (Macaca mulatta) are the most widely distributed species of Old World monkey and are frequently used as animal models to study human health and disease. Their gastrointestinal microbial community likely plays a major role in their physiology, ecology and evolution. Herein, we compared the fecal microbiome and antibiotic resistance genes in 15 free-ranging and 81 zoo-captive rhesus macaques sampled from two zoos in China, using both 16S amplicon sequencing and whole genome shotgun DNA sequencing approaches. Our data revealed similar levels of microbial diversity/richness among the three groups, although the composition of each group differed significantly and were particularly marked between the two zoo-captive and one wild groups. Zoo-captive animals also demonstrated a greater abundance and diversity of antibiotic genes. Through whole genome shotgun sequencing we also identified a mammalian (simian) associated adenovirus. Overall, this study provides a comprehensive analysis of resistomes and microbiomes in zoo-captive and free-ranging monkeys, revealing that semi-captive wildlife might harbor a higher diversity of antimicrobial resistant genes.

Cardiovascular diseases, including cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, vascular injury, stroke, and arrhythmia, are correlated with cardiac and vascular cell death. Ferroptosis is a novel form of non-apoptotic regulated cell death which is characterized by an iron-driven accumulation of lethal lipid hydroperoxides. The initiation and execution of ferroptosis are under the control of several mechanisms, including iron metabolism, glutamine metabolism, and lipid peroxidation. Recently, emerging evidence has demonstrated that ferroptosis can play an essential role in the development of various cardiovascular diseases. Recent researches have shown the ferroptosis inhibitors, iron chelators, genetic manipulations, and antioxidants can alleviate myocardial injury by blocking ferroptosis pathway. In this review, we systematically described the mechanisms of ferroptosis and discussed the role of ferroptosis as a novel therapeutic strategy in the treatment of cardiovascular diseases.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.

Digestive diseases have become an important source of morbidity and mortality. The considerable financial and health burdens caused by digestive diseases confirm the importance of extensive research to better understand and treat these diseases. The development of reliable preclinical models is essential for understanding the pathogenesis of digestive diseases and developing treatment and prevention methods. However, traditional established cell lines and animal models still have many limitations in the study of the digestive system. Conditional reprogramming (CR) cell culture is a newly developed primary technology that uses irradiated Swiss-3T3-J2 mouse fibroblast cells and the Rho-associated kinase (ROCK) inhibitor Y-27632 to rapidly and efficiently generate many cells from diseased and normal tissues. CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and recapitulate the histological and genomic features of the original tissue. Moreover, after removing these conditions, the phenotype was completely reversible. Therefore, CR technology may represent an ideal model to study digestive system diseases, to test drug sensitivity, to perform gene profile analysis, and to undertake xenograft research and regenerative medicine. Indeed, together with organoid cultures, CR technology has been recognized as one of the key new technologies by NIH precision oncology and also used for NCI human cancer model initiatives (HCMI) program with ATCC. In this article, we review studies that use CR technology to conduct research on diseases of the digestive system.

ObjectiveSerum albumin-to-alkaline phosphatase ratio (AAPR) has been proven to be a prognostic indicator of many malignant tumors. However, whether it can predict the prognosis of bladder cancer (BC) patients who underwent radical cystectomy (RC) remains unclear. This study was designed to assess the relationship between AAPR and clinical outcomes in patients with BC treated with RC.MethodsThe clinicopathological data of 199 BC patients receiving RC in our institution from January 2012 to December 2017 were retrospectively collected and analyzed. They were divided into three groups based on the optimal cut-off values and the association between AAPR groups and their clinical outcomes were evaluated.ResultsThe average age of the patients was (64.0 ± 8.7) years and 79.9% were male. Based on the cut-off values of AAPR, patients were divided into three groups: low-AAPR group (AAPR < 0.37, n = 35), medium-AAPR group (AAPR = 0.37-0.59, n = 61) and high-AAPR group (AAPR > 0.59, n = 103). The median overall survival (OS) of each AAPR group was 12.5, 24, and 29 months, respectively (P value