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BackgroundM2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the “immune landscape”, and screen drugs in HCC.MethodsM2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene–drug correlation and sensitivity to anti-cancer drugs were conducted.ResultsA total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested.ConclusionsOur findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

Background To explore the potential profiling of social alienation in elderly stroke patients and to analyze their influencing factors. Methods A cross-sectional study was conducted. From June 2024 to March 2025, elderly patients with stroke who were hospitalized in the Department of Neurology and the Rehabilitation Department of the First Affiliated Hospital of Jinzhou Medical University were selected as the research subjects. A general information questionnaire, social support rating scale, psychological elasticity scale, self-perceived burden scale, and general alienation scale were used to investigate. Latent profile analysis was employed to explore potential subtypes of patients’ social alienation, and multivariate logistic regression was used to analyze the influencing factors of different categories. Results Elderly stroke patients’ social alienation was categorized into 3 subtypes: the \" Low-level social alienation \" (25.4%), the “moderate social alienation” (60.1%), and the \" High-level social alienation” (14.5%). Patient age, education level, monthly family income, degree of self-care, number of episodes, number of comorbid chronic diseases, social support, psychological resilience, and self-perceived burden were predictors of potential social alienation typology in elderly stroke patients ( p  < 0.05). Conclusion Heterogeneity exists in the social alienation of elderly stroke patients, and healthcare professionals should take targeted measures according to different categories of patients to improve their social alienation and promote their physical and mental health.

With the advancement of computer technology, machine learning-based artificial intelligence technology has been increasingly integrated and applied in the fields of medicine, biology, and pharmacy, thereby facilitating their development. Transporters have important roles in influencing drug resistance, drug–drug interactions, and tissue-specific drug targeting. The investigation of drug transporter substrates and inhibitors is a crucial aspect of pharmaceutical development. However, long duration and high expenses pose significant challenges in the investigation of drug transporters. In this review, we discuss the present situation and challenges encountered in applying machine learning techniques to investigate drug transporters. The transporters involved include ABC transporters (P-gp, BCRP, MRPs, and BSEP) and SLC transporters (OAT, OATP, OCT, MATE1,2-K, and NET). The aim is to offer a point of reference for and assistance with the progression of drug transporter research, as well as the advancement of more efficient computer technology. Machine learning methods are valuable and attractive for helping with the study of drug transporter substrates and inhibitors, but continuous efforts are still needed to develop more accurate and reliable predictive models and to apply them in the screening process of drug development to improve efficiency and success rates.

Background Anxiety and depression are closely related to digestive system diseases. However, anxiety and depression in gastroenterology outpatients are not consistently recognized or managed. This study aimed to investigate the prevalence of anxiety, depression and associated risk factors in gastroenterology outpatients. Methods We conducted a cross-sectional study from June 2021 to June 2022 in the gastroenterology outpatients of three central hospitals. Professional researchers at each center collected data from patients through face-to-face interviews using a questionnaire. The Hamilton Anxiety Scale, Hamilton Depression Scale and Pittsburgh Sleep Quality Index were respectively used to assess anxiety, depression and sleep quality. Univariate and multivariate logistic regression were performed to identify associated risk factors. Results A total of 931 patients were finally included for analysis. The overall detection rates of anxiety and depression were 26.5% and 12.2%, respectively. Gastroesophageal reflux (AOR:1.559, 95%CI:1.084–2.244), dyspepsia (AOR:2.194, 95%CI:1.302–3.696), bile reflux (AOR:3.509, 95%CI:2.413–5.103), atrophic gastritis with intestinal metaplasia or intraepithelial neoplasia (AOR:3.814, 95%CI:1.399–10.402), biliary tract disease (AOR:1.584, 95%CI:1.042–2.410), liver disease (AOR:2.401, 95%CI:1.073–5.374), and poor sleep (AOR:5.578, 95%CI:3.859–8.063) were significantly associated with anxiety. Bile reflux (AOR:5.409, 95%CI:3.190–9.173), liver disease (AOR:3.177, 95%CI:1.183–8.531), and poor sleep (AOR:8.572, 95%CI:4.952–14.840) were significantly associated with depression. Physical exercise time ≥ 150 min/week (AOR:0.550, 95%CI:0.324–0.934) was inversely associated with depression. Conclusion Anxiety and depression were prevalent among gastroenterology outpatients. Gastroenterologists should pay close attention to the psychological status of patients, especially those with gastroesophageal reflux, dyspepsia, bile reflux, atrophic gastritis with intestinal metaplasia or intraepithelial neoplasia, biliary tract disease, liver disease, and poor sleep.

The kidney is critical in the human body’s excretion of drugs and their metabolites. Renal transporters participate in actively secreting substances from the proximal tubular cells and reabsorbing them in the distal renal tubules. They can affect the clearance rates (CLr) of drugs and their metabolites, eventually influence the clinical efficiency and side effects of drugs, and may produce drug–drug interactions (DDIs) of clinical significance. Renal transporters and renal transporter-mediated DDIs have also been studied by many researchers. In this article, the main types of in vitro research models used for the study of renal transporter-mediated DDIs are membrane-based assays, cell-based assays, and the renal slice uptake model. In vivo research models include animal experiments, gene knockout animal models, positron emission tomography (PET) technology, and studies on human beings. In addition, in vitro–in vivo extrapolation (IVIVE), ex vivo kidney perfusion (EVKP) models, and, more recently, biomarker methods and in silico models are included. This article reviews the traditional research methods of renal transporter-mediated DDIs, updates the recent progress in the development of the methods, and then classifies and summarizes the advantages and disadvantages of each method. Through the sorting work conducted in this paper, it will be convenient for researchers at different learning stages to choose the best method for their own research based on their own subject’s situation when they are going to study DDIs mediated by renal transporters.

Plants possess intricate defense mechanisms to resist cadmium (Cd) stress, including strategies like metal exclusion, chelation, osmoprotection, and the regulation of photosynthesis, with antioxidants playing a pivotal role. The application of nitrogen (N) and phosphorus (P) fertilizers are reported to bolster these defenses against Cd stress. Several studies investigated the effects of N or P on Cd stress in non-woody plants and crops. However, the relationship between N, P application, and Cd stress resistance in valuable timber trees remains largely unexplored. This study delves into the Cd tolerance mechanisms of Phoebe zhennan , a forest tree species, under various treatments: Cd exposure alone, combined Cd stress with either N or P and Cd stress with both N and P application. Our results revealed that the P application enhanced root biomass and facilitated the translocation of essential nutrients like K, Mn, and Zn. Conversely, N application, especially under Cd stress, significantly inhibited plant growth, with marked reductions in leaf and stem biomass. Additionally, while the application of P resulted in reduced antioxidant enzyme levels, the combined application of N and P markedly amplified the activities of peroxidase by 266.36%, superoxide dismutase by 168.44%, and ascorbate peroxidase by 26.58% under Cd stress. This indicates an amplified capacity of the plant to neutralize reactive oxygen species. The combined treatment also led to effective regulation of nutrient and Cd distribution in roots, shoots, and leaves, illustrating a synergistic effect in mitigating toxic impact of N. The study also highlights a significant alteration in photosynthetic activities under different treatments. The N addition generally reduced chlorophyll content by over 50%, while P and NP treatments enhanced transpiration rates by up to 58.02%. Our findings suggest P and NP fertilization can manage Cd toxicity by facilitating antioxidant production, osmoprotectant, and root development, thus enhancing Cd tolerance processes, and providing novel strategies for managing Cd contamination in the environment.

Pitaya is a high-value perennial tropical fruit known for its nutritional and health benefits. It is now widely cultivated in many tropical and subtropical countries, offering strong economic returns. China ranks first globally in pitaya cultivation, which includes both open-field production in tropical and subtropical regions and facility-based cultivation in temperate zones. As a long-day, light-loving plant, pitaya can be produced year-round. However, during off-season cultivation in winter and spring, weak light conditions and limited daylight hours lead to low flowering and fruit-setting rates, resulting in reduced yield and quality, factors that significantly constrain the industry’s development. The core technological challenge in achieving high-quality, high-yield, multi-cropping pitaya production lies in inducing abundant, high-quality blooms in a staged manner using LED artificial lighting. Based on current domestic and international research on the physiological mechanisms and technical strategies of light-induced flowering in pitaya, the effects of LED light supplementation on flowering and yield, along with relevant technical parameters, have been clarified. Practical applications have demonstrated the feasibility of using three-dimensional, precise LED supplemental lighting to regulate flowering and photosynthesis in both facility and open-field cultivation. This technology synergistically promotes both vegetative and reproductive growth, significantly improving flowering and fruit-setting rates, increasing single fruit weight, enhancing yield and quality, and boosting annual production efficiency. This article comprehensively summarizes the enhancement effects and physiological mechanisms of LED supplemental lighting on pitaya flowering regulation, focusing on light intensity, light quality, and photoperiod, within the context of international research. It also analyzes existing challenges and proposes strategies such as optimizing LED light source design, accurately planning supplemental light periods and durations, and establishing three-dimensional lighting methods. These strategies aim to improve the efficiency of LED lighting systems and provide a theoretical foundation for developing a precise and efficient pitaya LED supplemental lighting technology system. In conclusion, LED supplemental lighting promotes both the quantity and timing of pitaya flowering, as well as fruit yield and quality. Red, blue, and far-red light, combined with a photoperiod of 4–6 h, are recommended for effective application.

Salinity is a major abiotic stress that seriously affects crop growth worldwide. In this work, we aimed to isolate potential halotolerant plant growth-promoting rhizobacteria (PGPR) to mitigate the adverse impacts of salt stress in rice. An isolate, D2, with multiple plant growth-promoting (PGP) characteristics was identified as Enterobacter asburiae D2. Strain D2 could produce indole-3-acetic acid and siderophore. It also exhibited phosphate solubilization and 1-aminocyclopropane-1-carboxylic deaminase activity. Genome analysis further provided insights into the molecular mechanism of its PGP abilities. Strain D2 inoculation efficiently stimulated rice growth under both normal and saline conditions. Compared with the non-inoculated plants, a significant increase in plant height (18.1–34.7%), root length (25.9–57.1%), root dry weight (57.1–150%), and shoot dry weight (17.3–50.4%) was recorded in inoculated rice seedlings. Meanwhile, rice seedlings inoculated with strain D2 showed improvement in chlorophyll and proline content, while the oxidant damage was reduced in these plants in comparison with the control group. Moreover, the K+/Na+ ratio of the inoculated rice seedlings exposed to NaCl and Na2CO3 was higher than that of the uninoculated groups. These results imply that Enterobacter asburiae D2 is a potential PGPR that can be used for alleviation of salt stress in rice.

Objective The aim of this study was to analyze the clinical significance and prognostic value of CD8+ T cell-related regulatory genes in hepatocellular carcinoma (HCC). Methods This was a retrospective study. We combined TCGA-LIHC and single-cell RNA sequencing data for Lasso-Cox regression analysis to screen for CD8+ T cell-associated genes to construct a novel signature. The expression of the signature genes was detected at cellular and tissue levels using qRT-PCR, immunohistochemistry, and tissue microarrays. The CIBERSORT algorithm was then used to assess the immune microenvironmental differences between the different risk groups and a drug sensitivity analysis was performed to screen for potential HCC therapeutic agents. Results An 8-gene CD8 + T cell-associated signature (FABP5, GZMH, ANXA2, KLRB1, CD7, IL7R, BATF, and RGS2) was constructed. Survival analysis showed that high-risk patients had a poorer prognosis in all cohorts. Tumor immune microenvironment analysis revealed 22 immune cell types that differed significantly between patients in different risk groups, with patients in the low-risk group having an immune system that was more active in terms of immune function. Patients in the high-risk group were more prone to immune escape and had a poorer response to immunotherapy, and AZD7762 was screened as the most sensitive drug in the high-risk group. Finally, preliminary experiments have shown that BATF has a promoting effect on the proliferation, migration and invasion of HuH-7 cells. Conclusions The CD8+ T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.

Vancomycin (VCM) is a first-line antibiotic for severe infections, but its clinical utility is limited by nephrotoxicity. Atorvastatin (ATO), a widely used lipid-lowering agent, has shown renoprotective potential. However, whether ATO mitigates vancomycin-induced nephrotoxicity (VIN) remains unclear. We investigated the effects of ATO on VIN using male C57BL/6 mice and HK-2 cells. Renal function, histopathology, inflammation, oxidative stress, and apoptosis were assessed. Transcriptome sequencing of renal tissue was performed to explore underlying mechanisms. In vivo, ATO significantly improved VCM-induced renal dysfunction and renal pathological damage in mice. It significantly suppressed the release of inflammatory cytokines, enhanced renal antioxidant capacity, and reduced renal cell apoptosis. In vitro, ATO significantly increased HK-2 cell viability while reducing inflammation, reactive oxygen species (ROS) production, and renal cell apoptosis. Transcriptomic analysis revealed that ATO modulated peroxisome proliferator-activated receptor α (PPARα) signaling activity, which was accompanied by upregulated expression of solute carrier (SLC) transporters. This preclinical study demonstrates for the first time that ATO attenuates VIN by a PPARα-associated signaling pathway that orchestrates the upregulation of SLC transporters (including OAT1, OAT3, OCT2, and MATE1) to promote the excretion of endogenous toxins, with concomitant integrated protective effects against inflammation, oxidative stress, and apoptosis. These findings identify a novel mechanism and potential therapeutic strategy for VIN.