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Abstract Background Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy. Methods We utilized a juvenile rat model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics. Results Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints. Conclusions Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state in our animal model. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome.

Abstract The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m2/day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9–28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML.

Adding heterogeneous fillers with high thermal conductivity (TC) to polymer has been recognized as an effective way to increase the effective thermal conductivity (ETC) of polymer composites. Extensive researches have been conducted on the ETC of composites with heterogeneous fillers. However, the heat transfer enhancement mechanism of heterogeneous fillers remains unknown, and the combined effects of filler size, filler contact, interface thermal resistance (Rc) and other parameters on the ETC have not been explored. In this study, above combined effects are investigated. The results show that the filler contact and Rc are the key factors determining the ETC. The ETC of composite with filler contacts reaches 2.35 at filler content of 25%, which is 11.9% higher than that without filler contacts. The ETC also strongly depends on the R*c (dimensionless form of Rc) ratio (R*c1/R*c2) between two fillers, with it becoming asymmetrical when the amount of R*c(R*c1 + R*c2) is larger. The ETCs decrease with the increase of R*c1/R*c2 when the R*c1/R*c21. When R*c1 + R*c2 is a constant, the ETC increases with the competing effects of R*c. The models with filler contacts exhibit higher accuracy than other classical models in calculating the ETC across the entire range of filler content.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract The Cape hare (Lepus capensis) is among the most widely distributed hare species globally, inhabiting extensive regions across Africa, the Middle East, and Central Asia. However, evolutionary and genetic research on L. capensis was seriously impeded by the absence of a reference genome. Here, we assembled and constructed a chromosome-level genome of L. capensis (with scaffolds anchored to 25 chromosomes and a total assembled length of 2.9 Gb, achieving a contig N50 length of 124.44 Mb) using PacBio HiFi sequencing and Hi-C assembly technology. Evaluation using BUSCO indicated the genome assembly to be 98.2% complete. The de novo prediction revealed that repetitive sequences constitute 46.13% of the entire genome, and long interspersed nuclear elements (LINEs) constituted the largest portion. We annotated a total of 13, 868 protein-coding genes using transcriptomes from two tissues (muscle and skin). This high-quality reference genome serves as a valuable genomic resource for advancing genetic studies in this species.

Abstract Clostridioides difficile toxin B (TcdB) is the key virulence factor accounting for C. difficile infection-associated symptoms. Effectively neutralizing different TcdB variants with a universal solution poses a significant challenge. Here we present the de novo design and characterization of pan-specific mini-protein binders against major TcdB subtypes. Our design successfully binds to the first receptor binding interface (RBI-1) of the varied TcdB subtypes, exhibiting affinities ranging from 20 pM to 10 nM. The cryo-electron microscopy (cryo-EM) structures of the mini protein binder in complex with TcdB1 and TcdB4 are consistent with the computational design models. The engineered and evolved variants of the mini-protein binder and chondroitin sulfate proteoglycan 4 (CSPG4), another natural receptor that binds to the second RBI (RBI-2) of TcdB, better neutralize major TcdB variants both in cells and in vivo, as demonstrated by the colon-loop assay using female mice. Our findings provide valuable starting points for the development of therapeutics targeting C. difficile infections (CDI).

Abstract Phytosterols are a group of nonpharmacological alternatives to prevent or control dyslipidemias and cardiovascular disease. Increasing the phytosterol content in rapeseed oil is important to enhance daily phytosterol intake. However, the mechanisms of biosynthesis and regulation of phytosterol in rapeseed remain unclear. In this study, two representative rapeseed cultivars with extremely high (H286) and low (H174) phytosterol content were selected and treated with various concentrations (0.5−5.0 mM) of methyl jasmonate (MeJA). The results showed that treatment with 1 mM MeJA increased the phytosterol content of H174 and H286 by 17% and 27%, respectively. Based on the multiomics data, a gene‐phytosterol regulatory network was constructed. We deduced that MeJA down‐regulated the expression level of BnaA07.SCL15, BnaC05.MYB61, and BnaC03.AGL2, thereby promoting the phytosterol biosynthesis , and which were validated through the transient expression in tobacco. Notably, overexpression of Arabidopsis BnaA07.SCL15 exhibited a significant decrease in their phytosterol content. Additionally, an integrative analysis of the high‐resolution metabolome and transcriptome revealed that the accumulation patterns of 997 metabolites were highly correlated with their corresponding gene expression patterns. MeJA also significantly affected flavonoid biosynthesis, α‐linolenic acid metabolism, and amino acid metabolism. Furthermore, BnaA09.TT8 and BnaC09.TT8 were found to regulate of flavonoids. Overall, this study provides valuable insights into the phytosterol biosynthesis in rapeseed and offers a simple and effective approach for improving rapeseed quality.

Abstract Background Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome. Methods and materials The depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively. Results We found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N’-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment. Conclusion Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid).

Abstract Background The liver effects of concentrated vs. more evenly distributed moderate-to-vigorous physical activity (MVPA) patterns remain unclear. We aimed to examine the association of accelerometer-measured MVPA and different MVPA patterns with liver outcomes. Methods Eighty-eight thousand six hundred fifty-six participants without prior liver diseases from UK Biobank were included. MVPA was measured by a wrist-worn accelerometer. Based on the guideline-based threshold (≥ 150 min/week), MVPA patterns were defined as inactive (

Abstract Background CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. Method We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P

Complete wound healing without scar formation has attracted increasing attention, prompting the development of various strategies to address this challenge. In clinical settings, there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury, as they provide high efficacy, cost-effectiveness, and minimal side effects compared to invasive and costly surgical techniques. This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management. We first introduce the wound healing process and key mechanisms involved in scar formation. Subsequently, we explore common strategies for wound treatment, including their fabrication methods, superior performance and the latest research developments in this field. We then shift our focus to emerging biomedical technologies for scarless wound healing, detailing the mechanism of action, unique properties, and advanced practical applications of various biomedical technology-based therapies, such as cell therapy, drug therapy, biomaterial therapy, and synergistic therapy. Finally, we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.

Therapeutic antibodies are an important class of biopharmaceuticals. With the rapid development of deep learning methods and the increasing amount of antibody data, antibody generative models have made great progress recently. They aim to solve the antibody space searching problems and are widely incorporated into the antibody development process. Therefore, a comprehensive introduction to the development methods in this field is imperative. Here, we collected 34 representative antibody generative models published recently and all generative models can be divided into three categories: sequence-generating models, structure-generating models, and hybrid models, based on their principles and algorithms. We further studied their performance and contributions to antibody sequence prediction, structure optimization, and affinity enhancement. Our manuscript will provide a comprehensive overview of the status of antibody generative models and also offer guidance for selecting different approaches.

Abstract Mental fatigue during long-term motor imagery (MI) may affect intention recognition in MI applications. However, the current research lacks the monitoring of mental fatigue during MI and the definition of robust biomarkers. The present study aims to reveal the effects of mental fatigue on motor imagery recognition at the brain region level and explore biomarkers of mental fatigue. To achieve this, we recruited 10 healthy participants and asked them to complete a long-term motor imagery task involving both right- and left-handed movements. During the experiment, we recorded 32-channel EEG data and carried out a fatigue questionnaire for each participant. As a result, we found that mental fatigue significantly decreased the subjects’ motor imagery recognition rate during MI. Additionally the theta power of frontal, central, parietal, and occipital clusters significantly increased after the presence of mental fatigue. Furthermore, the phase synchronization between the central cluster and the frontal and occipital lobes was significantly weakened. To summarize, the theta bands of frontal, central, and parieto–occipital clusters may serve as powerful biomarkers for monitoring mental fatigue during motor imagery. Additionally, changes in functional connectivity between the central cluster and the prefrontal and occipital lobes during motor imagery could be investigated as potential biomarkers.

Abstract Background Endometriosis (EMs) is an enigmatic disease of yet-unknown pathogenesis. Disulfidptosis, a novel identified form of programmed cell death resulting from disulfide stress, stands a chance of treating diverse ailments. However, the potential roles of disulfidptosis-related genes (DRGs) in EMs remain elusive. This study aims to thoroughly explore the key disulfidptosis genes involved in EMs, and probe novel diagnostic markers and candidate therapeutic compounds from the aspect of disulfidptosis based on bioinformatics analysis, machine learning, and animal experiments. Results Enrichment analysis on key module genes and differentially expressed genes (DEGs) of eutopic and ectopic endometrial tissues in EMs suggested that EMs was closely related to disulfidptosis. And then, we obtained 20 and 16 disulfidptosis-related DEGs in eutopic and ectopic endometrial tissue, respectively. The protein-protein interaction (PPI) network revealed complex interactions between genes, and screened nine and ten hub genes in eutopic and ectopic endometrial tissue, respectively. Furthermore, immune infiltration analysis uncovered distinct differences in the immunocyte, human leukocyte antigen (HLA) gene set, and immune checkpoints in the eutopic and ectopic endometrial tissues when compared with health control. Besides, the hub genes mentioned above showed a close correlation with the immune microenvironment of EMs. Furthermore, four machine learning algorithms were applied to screen signature genes in eutopic and ectopic endometrial tissue, including the binary logistic regression (BLR), the least absolute shrinkage and selection operator (LASSO), the support vector machine-recursive feature elimination (SVM-RFE), and the extreme gradient boosting (XGBoost). Model training and hyperparameter tuning were implemented on 80% of the data using a ten-fold cross-validation method, and tested in the testing sets which determined the excellent diagnostic performance of these models by six indicators (Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Accuracy, and Area Under Curve). And seven eutopic signature genes (ACTB, GYS1, IQGAP1, MYH10, NUBPL, SLC7A11, TLN1) and five ectopic signature genes (CAPZB, CD2AP, MYH10, OXSM, PDLIM1) were finally identified based on machine learning. The independent validation dataset also showed high accuracy of the signature genes (IQGAP1, SLC7A11, CD2AP, MYH10, PDLIM1) in predicting EMs. Moreover, we screened 12 specific compounds for EMs based on ectopic signature genes and the pharmacological impact of tretinoin on signature genes was further verified in the ectopic lesion in the EMs murine model. Conclusion This study verified a close association between disulfidptosis and EMs based on bioinformatics analysis, machine learning, and animal experiments. Further investigation on the biological mechanism of disulfidptosis in EMs is anticipated to yield novel advancements for searching for potential diagnostic biomarkers and revolutionary therapeutic approaches in EMs.

Abstract Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB2) and thromboxane B3 (TxB3) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza.

Abstract Objective Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. Methods A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40–60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. Results Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P 0.05). Conclusions These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.

Abstract Background The rapid growth of artificial intelligence (AI) technologies has been driven by the latest advances in computing power. Although, there exists a dearth of research on the application of AI in medical education. Methods this study is based on the TAM-ISSM-UTAUT model and introduces STARA awareness and chilling effect as moderating variables. A total of 657 valid questionnaires were collected from students of a medical university in Dalian, China, and data were statistically described using SPSS version 26, Amos 3.0 software was used to validate the research model, as well as moderated effects analysis using Process (3.3.1) software, and Origin (2021) software. Results The findings reveal that both information quality and perceived usefulness are pivotal factors that positively influence the willingness to use AI products. It also uncovers the moderating influence of the chilling effect and STARA awareness. Conclusions This suggests that enhancing information quality can be a key strategy to encourage the widespread use of AI products. Furthermore, this investigation offers valuable insights into the intersection of medical education and AI use from the standpoint of medical students. This research may prove to be pertinent in shaping the promotion of Medical Education Intelligence in the future.

Abstract Background Primary osteoporosis (POP) is recognized as a “silent disease” and often ignored. This meta-analysis aimed to determine the prevalence of POP in the Chinese population over the past 20 years to raise awareness of the disease’s epidemiology, which is hoped to help prevent and treat the condition better. Methods Eight English and three Chinese language databases were searched systematically from January 2002 to December 2023. Relevant data were analysed using Stata 16.0. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. A funnel plot was further drawn in combination with Egger and Begg tests to determine publication bias. Results A total of 45 studies (241,813 participants) were included. The meta-analysis revealed that the overall prevalence of POP in the Chinese population was 18.2% (95% CI: 14.7–21.7%), showing a positive correlation with age. Specifically, prevalence rates were 23.4% (18.3–28.5%) in women and 11.5% (9.1–13.9%) in men. A notable increase was observed within the span of 20 years (16.9% before 2010 and 20.3% in 2011–2020). Notably, regional variations were observed, with southern China reporting a lower prevalence of 16.4% compared to 20.2% in northern China. Meta-regression suggested that sample size significantly influenced the estimation of point prevalence (P = 0.037). Conclusions Over the past two decades, there has been an increase in the prevalence of POP within the Chinese population. The growing prevalence of older individuals and women further highlights the urgency for tailored disease prevention and control measures.

Abstract Background Nonpharmaceutical interventions (NPIs) implemented to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suppressed the spread of other respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the epidemiological trends and clinical characteristics of Mycoplasma pneumoniae (MP) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the COVID-19 pandemic, and investigate the long-term effects of China’s NPIs against COVID-19 on the epidemiology of MP among inpatient children with LRTI. Methods Children hospitalised for LRTI at the Department of Pulmonology, The Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2019 and December 2022 were tested for common respiratory pathogens, including Mycoplasma pneumoniae (MP), Chlamydia trachomatis (CT) and other bacteria. Clinical data on age, sex, season of onset, disease spectrum, and combined infection in children with MP-induced LRTI in the past 4 years were collected and analysed. Results Overall, 15909 patients were enrolled, and MP-positive cases were 1971 (34.0%), 73 (2.4%), 176 (5.8%), and 952 (20.6%) in 2019, 2020, 2021, and 2022, respectively, with a significant statistical difference in the MP-positive rate over the 4 years (p

Pain highly impacts the quality of life of patients. Morphine is used for pain treatment; however, its side effects, especially morphine tolerance, limit its use in the clinic. The problem of morphine tolerance has plagued health workers and patients for years. Unfortunately, the exact mechanism of morphine tolerance has not been fully clarified. The mechanisms of morphine tolerance that are currently being studied may include μ-opioid receptor (MOR) desensitization and internalization, mitogen-activated protein kinase (MAPK) pathway activation and crosstalk, the effects of microglia and the increase in inflammatory factors. Morphine tolerance can be alleviated by improving the pathophysiological changes that lead to morphine tolerance. Previous studies have shown that a cannabinoid type 2 (CB2) receptor agonist could attenuate morphine tolerance in a variety of animal models. Many studies have shown an interaction between the cannabinoid system and the opioid system. The CB2 receptor may modulate the effect of morphine through a pathway that is common to the MOR, since both receptors are G protein-coupled receptors (GPCRs). This study introduces the potential mechanism of morphine tolerance and the effect of CB2 receptor agonists on reducing morphine tolerance, which can provide new ideas for researchers studying morphine and provide beneficial effects for patients suffering from morphine tolerance.

Objectives The aim of this study was to evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) for heavily pretreated metastatic gastric cancer from the perspective of the Chinese healthcare system.Designs Based on the overall survival and progression-free survival (PFS) data from the Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS) trial (NCT02500043), a three-state Markov model (PFS, progressed disease and death) was constructed to analyse the cost-effectiveness of FTD/TPI compared with the placebo in heavily pretreated metastatic gastric cancer. Cost and utility were from pricing records and the literature. The model was simulated for 5 years with monthly cycles. Costs and health outcomes were discounted by 5%. We then conducted sensitivity analyses to evaluate the robustness of the parameters. The model results were from the Chinese healthcare system.Outcome measures The output results were the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER).Results According to the model results, FTD/TPI generated an additional cost of US$26 855.66 and 0.88 QALYs compared with the placebo. ICER of FTD/TPI compared with the placebo was US$30 494.89 per QALY. Sensitivity analyses revealed that the utility value of the PFS stage and FTD/TPI adverse event costs were the main influencing parameters, and the results were stable. At a threshold of three times per capita gross domestic product of China (US$35 559.34 in 2022), the probability of FTD/TPI being cost-effective compared with placebo was 99.2%.Conclusion From the perspective of the Chinese healthcare system, FTD/TPI is a more cost-effective option compared with the placebo for the treatment of heavily pretreated metastatic gastric cancer in patients who have received at least two prior advanced treatment regimens.Trial registration number The Chinese population registered in the Chinese Clinical Trial Registry (ChiCTR2400080940) and clinical trial (NCT05029102).

IntroductionAs the development process of medical industry informatization has entered the stage of smart healthcare, health management applications (apps) have played an important role in improving people’s health and preventing diseases, especially among female college students.MethodsThis study combines the UTAUT model and the Fogg behavioral model (FBM) as a theoretical framework to investigate the factors affecting female college students’ willingness to use health management apps. A survey was conducted with 624 female college students regarding their usage of AI health management mobile applications.ResultsThe analysis reveals that social influence (β = 0.497, p

Traditional denitrification methods for coal-fired power boilers face challenges like reduced flue gas temperature at low loads, decreased efficiency of existing denitrification devices, and increased ammonia consumption. Biomass, a renewable energy source, has proven effective for denitrification in medium to high-temperature ranges. To improve denitrification efficiency at low loads, this study focuses on optimizing re-burning denitrification of biomass by nitrogen-impregnated of corncob at room temperature. Investigating the effects of nitrogen impregnation and washing on biomass re-burning denitrification reactivity within 550–950 °C, the study finds that denitrification efficiency improvement is not caused only by surface-covered urea or washing. Nitrogen impregnation enhances biomass pyrolysis, releasing more CO, HCN, and NH3 products, thereby enhancing NO reduction during denitrification. Additionally, nitrogen impregnation boosts nitrogen-containing functional groups such N-6 on biomass char surfaces during the re-burning process, improving denitrification efficiency. The maximum denitrification efficiency of the nitrogen impregnated sample reached 97.52 % at 950 °C, while it reached 76.51 % at 650 °C when the coated urea was washed. Furthermore, chlorine and alkali metal contents in biomass notably decrease after nitrogen-impregnation and washing, optimizing biomass combustion conditions for furnace protection. This study offers theoretical insights for promoting and applying biomass denitrification techniques.

Renal fibrosis is a complex and multifactorial process that involves inflammation, cell proliferation, collagen, and fibronectin deposition in the kidney, ultimately leading to chronic kidney disease and even end-stage renal disease. The main goal of treatment is to slow down or halt the progression of fibrosis and to improve or preserve kidney function. Despite significant progress made in understanding the underlying mechanisms of renal fibrosis, current therapies have limited renal protection as the disease progresses. Exosomes derived from stem cells are a newer area of research for the treatment of renal fibrosis. Exosomes as nano-sized extracellular vesicles carry proteins, lipids, and nucleic acids, which can be taken up by local or distant cells, serving as mediators of intercellular communication and as drug delivery vehicles. Exosomes deliver molecules that reduce inflammation, renal fibrosis and extracellular matrix protein production, and promote tissue regeneration in animal models of kidney disease. Additionally, they have several advantages over stem cells, such as being non-immunogenic, having low risk of tumor formation, and being easier to produce and store. This review describes the use of natural and engineered exosomes containing therapeutic agents capable of mediating anti-inflammatory and anti-fibrotic processes during both acute kidney injury and chronic kidney disease. Exosome-based therapies will be compared with stem cell-based treatments for tissue regeneration, with a focus on renal protection. Finally, future directions and strategies for improving the therapeutic efficacy of exosomes are discussed.

We reviewed research on SARS-CoV-2 and influenza virus detection on surfaces, their persistence under various conditions, and response to disinfectants. Viral contamination in community and healthcare settings was analyzed, emphasizing survival on surfaces influenced by temperature, pH, and material. Findings showed higher concentrations enhance survivability at room temperature, whereas stability increases at 4°C. Both viruses decline in low pH and high heat, with influenza affected by salinity. On various material surfaces, SARS-CoV-2 and influenza viruses demonstrate considerable variations in survival durations, and SARS-CoV-2 is more stable than influenza virus. On the skin, both virus types can persist for ≥2 h. Next, we delineated the virucidal efficacy of disinfectants against SARS-CoV-2 and influenza viruses. In daily life, exposure to ethanol (70%), isopropanol (70%), bleach (10%), or hydrogen peroxide (1–3%) for 15–30 min can effectively inactive various SARS-CoV-2 variants. Povidone-iodine (1 mg/mL, 1 min) or cetylpyridinium chloride (0.1 mg/mL, 2 min) may be used to inactive different SARS-CoV-2 variants in the mouth. Chlorine disinfectants (500 mg/L) or ultraviolet light (222 nm) can effectively inhibit different SARS-CoV-2 variants in public spaces. In conclusion, our study provides a scientific basis and practical guidance for reduction of viral persistence (retention of infectivity) on surfaces and environmental cleanliness.

BackgroundPancreatic cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors.MethodsPC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection.ResultsThe number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73–1.52) and 1.00% (95% CI, 0.63–1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032.ConclusionsIt was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country’s future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important.

Thiacloprid is one of the first generation of neonicotinoid insecticide with a chloropyridine structure like imidacloprid and acetamiprid. Recent studies have revealed its environmental and non-target organism toxicity, leading to restrictions on its use in many countries and regions. Despite limitations, thiacloprid has been detected in various environmental samples, food sources, and biological specimens, posing a significant threat to human health, necessitating advanced detection methods for monitoring. In this study, a highly specific monoclonal antibody against thiacloprid via a multi-immunogen strategy was prepared and a rapid and sensitive enzyme-linked immunosorbent assay for the detection of thiacloprid residues in honey and medicinal herbs was established. The half maximal inhibitory concentration (IC50) of this method was 0.38 ng/mL, improving the sensitivity by 1.2−480.6 times compared to existing reports, and the limit of detection (IC20) was 0.097 ng/mL. The method was successfully applied to the determination of thiacloprid residues in honey and medicinal herbs (Crataegi fructus, Citri reticulatae pericarpium), achieving recovery rates ranging from 87.50 % to 116.11 %. The obtained results were verified using the LC-MS/MS method. The multi-immunogen strategy proposed in this study provides an approach for the preparation of highly sensitive and specific monoclonal antibodies, and immunoassay established based on it has good application prospects in complex matrices.

Sulfur-doped biochar (S4BC) was prepared with cherry kernel powder as carbon source, Na2S2O3 as sulfur source and chemical activator. Na2S2O3 can activate biochar through the reaction with carbon, intercalation of alkali metals and the generated gas rushing out of pores, and at the same time, active sulfur atoms are doped into biochar during pyrolysis. The physical and chemical properties of S4BC adsorbent were evaluated by various characterization techniques. The results show that S4BC calcined at 800 °C has huge specific surface area of 959.6 m2/g, developed pore structure, and high content of S (18.84 wt%). Moreover, due to the existence of sulfur and oxygen functional groups, S4BC-800 provides sufficient active sites for the adsorption of Hg2+. According to Langmuir model, the maximum adsorption capacity of S4BC-800 for Hg2+ is 724 mg/g at 313 K, and the adsorption speed is fast with excellent stability and reusability. The microfiltration membrane device based on S4BC-800 can effectively remove the low concentration of Hg2+ in the solution. In this study, a simple method for preparing SBC materials is developed, which is not only of great significance as an adsorbent for Hg2+, but also provides a new choice for the preparation of heteroatom-doped materials.

IntroductionSepsis poses a serious threat to individual life and health. Early and accessible diagnosis and targeted treatment are crucial. This study aims to explore the relationship between microbes, metabolic pathways, and blood test indicators in sepsis patients and develop a machine learning model for clinical diagnosis.MethodsBlood samples from sepsis patients were sequenced. α-diversity and β-diversity analyses were performed to compare the microbial diversity between the sepsis group and the normal group. Correlation analysis was conducted on microbes, metabolic pathways, and blood test indicators. In addition, a model was developed based on medical records and radiomic features using machine learning algorithms.ResultsThe results of α-diversity and β-diversity analyses showed that the microbial diversity of sepsis group was significantly higher than that of normal group (p < 0.05). The top 10 microbial abundances in the sepsis and normal groups were Vitis vinifera, Mycobacterium canettii, Solanum pennellii, Ralstonia insidiosa, Ananas comosus, Moraxella osloensis, Escherichia coli, Staphylococcus hominis, Camelina sativa, and Cutibacterium acnes. The enriched metabolic pathways mainly included Protein families: genetic information processing, Translation, Protein families: signaling and cellular processes, and Unclassified: genetic information processing. The correlation analysis revealed a significant positive correlation (p < 0.05) between IL-6 and Membrane transport. Metabolism of other amino acids showed a significant positive correlation (p < 0.05) with Cutibacterium acnes, Ralstonia insidiosa, Moraxella osloensis, and Staphylococcus hominis. Ananas comosus showed a significant positive correlation (p < 0.05) with Poorly characterized and Unclassified: metabolism. Blood test-related indicators showed a significant negative correlation (p < 0.05) with microorganisms. Logistic regression (LR) was used as the optimal model in six machine learning models based on medical records and radiomic features. The nomogram, calibration curves, and AUC values demonstrated that LR performed best for prediction.DiscussionThis study provides insights into the relationship between microbes, metabolic pathways, and blood test indicators in sepsis. The developed machine learning model shows potential for aiding in clinical diagnosis. However, further research is needed to validate and improve the model.

The widespread occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) in aquatic environments and its hazards to aquatic species underscore the necessity of comprehending its environmental fate. Here, we investigated the transformation from 6PPD to 6PPD-Q and the attenuation of 6PPD-Q in surface water under natural conditions. Contrary to prior findings, this work revealed that 6PPD-Q and its precursor 6PPD-OH/6PPD-(OH)2, were not detected through target analysis and suspect screening during 6PPD transformation in the surface water under the natural conditions. 6PPD-Q predominantly accumulated in TWPs in ambient atmosphere with 1.28 % mass yield from the 6PPD dissipation. Subsequently, 6PPD-Q was eluted from TWPs and released to the water environment. The investigation on the natural attenuation of 6PPD-Q in the surface water demonstrated that direct and indirect photolysis facilitated the rapid dissipation of 6PPD-Q with a half-life of 2.57 h. Utilizing the liquid chromatography high resolution mass spectrometry (LC-HRMS), including both time of flight (TOF) MS and Orbitrap MS, twelve novel transformation products (TPs) of 6PPD-Q were identified by using a comprehensive non-targeted screening strategy. The results from two dimensions gas chromatography (GC×GC) TOF-MS revealed additional two TPs. Based on the molecular structure of TPs, four major pathways of 6PPD-Q attenuation were proposed, including bond cleavage, hydroxylation, quinone cleavage and rearrangement. All TPs were predicted to exhibit lower toxicity, indicating the natural attenuation of 6PPD-Q reduced its toxicity and potential environmental risks. This study provides crucial insights into the environmental fate of 6PPD-Q, highlighting the significance of understanding both its formation from 6PPD and its subsequent attenuation processes under natural conditions.

Probiotics are one of the management tools to improve the host’s healthy microbiota. The positive effects of probiotics on host health are species-specific, so probiotics isolated from host’s own gut may be most beneficial. Many of the metabolites (e.g., short-chain fatty acids, bacteriocins, and hydrogen peroxide) produced by Lactobacillus johnsonii have specific inhibitory profiles against invading pathogens. In this study, we isolated L. johnsonii GJ231 from the intestinal tract of healthy female beagles. The genome size of 1.763 M encoded a total of 1,691 predicted genes. Many carbohydrate-active enzymes responsible for carbohydrate degradation and the production of short-chain fatty acids were also predicted. The metabolic profile of short-chain fatty acids in L. johnsonii GJ231 was determined using LC–MS/MS. The bacteriocin-producing gene bacteriocin (lactacin F) in L. johnsonii GJ231 was also predicted. In vitro, experiments demonstrated that GJ231 can thrive in weak acids, 0.3% bile salts, and artificial gastrointestinal fluid models. It was tolerant of to high temperatures up to 70°C, was non- hemolytic, inhibited pathogenic bacteria, and had a high antioxidant capacity. In vivo safety experiments conducted in mice revealed that oral administration of GJ231 not only had no toxic side effect but also increased their antioxidant capacity. In conclusion, combining the above test results, which collectively demonstrate that canine-derived L. johnsonii GJ231 was a non-pathogenic, acid-tolerant and bile-salt-tolerant probiotic strain that inhibits pathogenic bacteria and improves host antioxidant function. This may make it a promising candidate for the development of innovative functional foods for pets.

Abstract The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs’ potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Abstract. Background:. Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association. Methods:. About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health. Results:. At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD. Conclusion:. Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

316L stainless steel (SS) is widely applied as microimplant anchorage (MIA) due to its excellent mechanical properties. However, the risk that the oral microorganisms can corrode 316L SS is fully neglected. Microbiologically influenced corrosion (MIC) of 316L SS is essential to the health and safety of all patients because the accelerated corrosion caused by the oral microbiota can trigger the release of Cr and Ni ions. This study investigated the corrosion behavior and mechanism of subgingival microbiota on 316L SS by 16S rRNA and metagenome sequencing, electrochemical measurements, and surface characterization techniques. Multispecies biofilms were formed by the oral subgingival microbiota in the simulated oral anaerobic environment on 316L SS surfaces, significantly accelerating the corrosion in the form of pitting. The microbiota samples collected from the subjects differed in biofilm compositions, corrosion behaviors, and mechanisms. The oral subgingival microbiota contributed to the accelerated corrosion of 316L SS via acidic metabolites and extracellular electron transfer. Our findings provide a new insight into the underlying mechanisms of oral microbial corrosion and guide the design of oral microbial corrosion-resistant materials.

Abstract Background This study reported height prediction and longitudinal growth changes in Chinese pediatric patients with acute myeloid leukemia (AML) during and after treatment and their associations with outcomes. Methods Changes in 88 children with AML in percentages according to the growth percentile curve for Chinese boys/girls aged 2–18/0–2 years for body mass index (BMI), height, and weight from the time of diagnosis to 2 years off therapy were evaluated. The outcomes of AML were compared among patients with different BMI levels. Results The proportion of underweight children (weight 75th percentile) after 2 years of drug withdrawal. Unhealthy BMI at the initial diagnosis and during intensive chemotherapy leads to poorer outcomes. For height, all patients were in the range of genetic height predicted based on their parents’ height at final follow-up. Conclusions Physicians should pay more attention to the changes in height and weight of children with AML at these crucial treatment stages and intervene in time.

Abstract PbZrO3 has been broadly considered as a prototypical antiferroelectric material for high-power energy storage. A recent theoretical study suggests that the ground state of PbZrO3 is threefold-modulated ferrielectric, which challenges the generally accepted antiferroelectric configuration. However, such a novel ferrielectric phase was predicted only to be accessible at low temperatures. Here, we successfully achieve the room-temperature construction of the strongly competing ferrielectric and antiferroelectric state by strain-mediated phase separation in PbZrO3/SrTiO3 thin film. We demonstrate that the phase separation occurs spontaneously in quasi-periodic stripe-like patterns under a compressive misfit strain and can be tailored by varying the film thickness. The ferrielectric phase strikingly exhibitsa threefold modulation period with a nearly up-up-down configuration, which could be stabilized and manipulated by the formation and evolution of interfacial defects under applied strain. The present results construct a fertile ground for further exploring the physical properties and applications based on the novel ferrielectric phase.

Abstract Background Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking. Results Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc. In addition to revealing the regulatory landscape of eRNAs at the tissue level, we developed an innovative network construction and refinement method by integrating RNA-seq, ChIP-seq, genome-wide association study (GWAS) signals and enhancer-modulating effects of single nucleotide polymorphisms (SNPs) measured by self-transcribing active regulatory region sequencing (STARR-seq) experiments. Using this approach, we unraveled eGRN that significantly influence the growth and development of muscle and fat tissues, and identified several novel genes that affect adipocyte differentiation in a cell line model. Conclusions Our work not only provides novel insights into the genetic basis of economic pig traits, but also offers a generalizable approach to elucidate the eRNA-mediated transcriptional regulation underlying a wide spectrum of complex traits for diverse organisms.

Abstract Personalized, ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) is designed to administer tumoricidal doses in a pulsed mode with extended intervals, spanning weeks or months. This approach leverages longer intervals to adapt the treatment plan based on tumor changes and enhance immune-modulated effects. In this investigation, we seek to elucidate the potential synergy between combined PULSAR and PD-L1 blockade immunotherapy using experimental data from a Lewis Lung Carcinoma (LLC) syngeneic murine cancer model. Employing a long short-term memory (LSTM) recurrent neural network (RNN) model, we simulated the treatment response by treating irradiation and anti-PD-L1 as external stimuli occurring in a temporal sequence. Our findings demonstrate that: (1) The model can simulate tumor growth by integrating various parameters such as timing and dose, and (2) The model provides mechanistic interpretations of a “causal relationship” in combined treatment, offering a completely novel perspective. The model can be utilized for in-silico modeling, facilitating exploration of innovative treatment combinations to optimize therapeutic outcomes. Advanced modeling techniques, coupled with additional efforts in biomarker identification, may deepen our understanding of the biological mechanisms underlying the combined treatment.

Abstract Background Scientific research activities are crucial for the development of clinician-scientists. However, few people pay attention to the current situation of medical research in pediatric medical students in China. This study aims to assess the perceptions, practices and barriers toward medical research of pediatric undergraduates. Methods This cross-sectional study was conducted among third-year, fourth-year and fifth-year pediatric students from Zhejiang University School of Medicine in China via an anonymous online questionnaire. The questionnaires were also received from fifth-year students majoring in other medicine programs [clinical medicine (“5 + 3”) and clinical medicine (5-year)]. Results The response rate of pediatric undergraduates was 88.3% (68/77). The total sample of students enrolled in the study was 124, including 36 students majoring in clinical medicine (“5 + 3”) and 20 students majoring in clinical medicine (5-year). Most students from pediatrics (“5 + 3”) recognized that research was important. Practices in scientific research activities are not satisfactory. A total of 51.5%, 35.3% and 36.8% of the pediatric students participated in research training, research projects and scientific article writing, respectively. Only 4.4% of the pediatric students contributed to publishing a scientific article, and 14.7% had attended medical congresses. None of them had given a presentation at a congress. When compared with fifth-year students in the other medicine program, the frequency of practices toward research projects and training was lower in the pediatric fifth-year students. Lack of time, lack of guidance and lack of training were perceived as the main barriers to scientific work. Limited English was another obvious barrier for pediatric undergraduates. Pediatric undergraduates preferred to participate in clinical research (80.9%) rather than basic research. Conclusions Although pediatric undergraduates recognized the importance of medical research, interest and practices in research still require improvement. Lack of time, lack of guidance, lack of training and limited English were the common barriers to scientific work. Therefore, research training and English improvement were recommended for pediatric undergraduates.

Nonunions and delayed unions pose significant challenges in orthopedic treatment, with current therapies often proving inadequate. Bone tissue engineering (BTE), particularly through endochondral ossification (ECO), emerges as a promising strategy for addressing critical bone defects. This study introduces mesenchymal stem cells overexpressing Exendin-4 (MSC-E4), designed to modulate bone remodeling via their autocrine and paracrine functions. We established a type I collagen (Col-I) sponge-based in vitro model that effectively recapitulates the ECO pathway. MSC-E4 demonstrated superior chondrogenic and hypertrophic differentiation and enhanced the ECO cell fate in single-cell sequencing analysis. Furthermore, MSC-E4 encapsulated in microscaffold, effectively facilitated bone regeneration in a rat calvarial defect model, underscoring its potential as a therapeutic agent for bone regeneration. Our findings advocate for MSC-E4 within a BTE framework as a novel and potent approach for treating significant bone defects, leveraging the intrinsic ECO process.

In order to study the influence of low temperature liquid nitrogen immersion treatment on the pore structure and fractal characteristics of middle grade coal in Huainan Mining Area, coal samples were treated with different liquid nitrogen immersion time, and the pore structure of coal was measured by mercury injection and liquid nitrogen adsorption method. The fractal theory was combined to analyze the development law and scale characteristics of coal pores under different immersion time from multiple angles. The results show that with the increase of liquid nitrogen immersion time, the total pore volume of coal increases from 198.089×10−3 cm3/g to 371.553×10−3 cm3/g, while the total specific surface area decreases from 4.984 m2/g to 4.496 m2/g, and the effect is significant. The adsorption pore decreases, the seepage pore increases, and the pore connectivity of the adsorption pore increases to form a larger level of pore, which gradually changes to the seepage pore. There was a negative linear correlation between D1 (fractal dimension of seepage pore) and D2 (fractal dimension of adsorption pore) and the immersion time of liquid nitrogen, and the influence of liquid nitrogen immersion on D1 was more significant than that of D2. D1 and D2 decreased gradually with the increase of liquid nitrogen immersion time, indicating that the structural complexity of internal pores decreased with the increase of liquid nitrogen immersion time, and the porosity and permeability of coal increased. Dc (comprehensive fractal dimension) decreases with the increase of average pore diameter and total pore volume of coal body, and increases with the increase of total specific surface area. With the increase of liquid nitrogen immersion time, the comprehensive fractal dimension of coal body decreases, the adsorption capacity of coal body is weakened, and the seepage capacity is enhanced, which is helpful to improve the coal-bed methane extraction effect of low permeability coal seam in Huainan Mining Area.

Abstract Acute pancreatitis (AP) continues to pose a major challenge as targeted therapeutic interventions are absent. Mitochondrial dysfunction and inflammasome-dependent pyroptosis are involved in the pathogenic mechanisms of AP. CIRP is a stress-response protein and a damage-associated molecular pattern (DAMP) molecule. In our previous studies, we discovered that excessive CIRP can directly damage pancreatic acinar cells. Nonetheless, the precise involvement of CIRP in AP is still unexplored. The primary aim of this study was to examine the potential involvement of CIRP in the development of pyroptosis and mitochondrial dysfunction in AP. To study this, an L-arginine-induced AP mouse model was used. Our results showed that Caspase-1-mediated pyroptosis and mitochondria-derived reactive oxygen species (ROS) were crucial factors in the occurrence of tissue damage and inflammation in AP. A substantial increase in the CIRP serum levels was observed in AP mice. Blocking CIRP by either CIRP gene knockout or systemic administration of C23, a competing inhibitor of CIRP, reduced ROS accumulation and pyroptosis in AP mice. These effects were associated with attenuated pancreatic injury and inflammation. In addition, CIRP-triggered mitochondrial dysfunction, autophagy impairment, and pyroptosis in pancreatic acinar cells were prevented by TAK242, an inhibitor of CIRP receptor TLR4. In conclusion, CIRP can induce mitochondrial dysfunction and pyroptosis in pancreatic acinar cells, and blocking CIRP may be a valuable approach to treating patients with AP.

Abstract Background Insulin resistance (IR) was a prominent feature commonly observed in individuals with type 2 diabetes mellitus (T2DM). T2DM Individuals often exhibited a concomitant presence of low-grade chronic inflammation. In this study conducted retrospectively, the aim was to investigate the connection between neutrophils-lymphocytes rate (NLR), monocytes-lymphocytes rate (MLR), platelets-lymphocytes rate (PLR) and IR, specifically among individuals with T2DM. Method This study encompassed a cohort of 405 individuals diagnosed with T2DM, comprising cases from January 2021 to November 2022. On the basis of whether there was IR or not, these sufferers were categorized into two cohorts, namely T2DM with IR group (292 cases) and T2DM without IR group (113 cases), as determined by a homeostasis model assessment-IR (HOMA-IR) value exceeding 2.0. Results The findings of this study demonstrated compelling evidence of distinct biomarker profiles between individuals with T2DM who had IR and those without IR. Specifically, the IR individuals displayed notably raise NLR, MLR, PLR, C reactive protein (CRP) and serum amyloid A (SAA). Additionally, there was a noticeable decrease in superoxide dismutase (SOD) levels. Furthermore, IR was negatively correlated with SOD values, while positive associations were found between IR and NLR, CRP, and SAA levels (p

Abstract Background Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. Methods Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. Results Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403–0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420–1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). Conclusions In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

Abstract Background DNA mismatch repair (MMR) is a highly conserved pathway that corrects DNA replication errors, the loss of which is attributed to the development of various types of cancers. Although well characterized, MMR factors remain to be identified. As a 3′–5′ exonuclease and endonuclease, meiotic recombination 11 homolog A (MRE11A) is implicated in multiple DNA repair pathways. However, the role of MRE11A in MMR is unclear. Methods Initially, short-term and long-term survival assays were used to measure the cells’ sensitivity to N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Meanwhile, the level of apoptosis was also determined by flow cytometry after MNNG treatment. Western blotting and immunofluorescence assays were used to evaluate the DNA damage within one cell cycle after MNNG treatment. Next, a GFP-heteroduplex repair assay and microsatellite stability test were used to measure the MMR activities in cells. To investigate the mechanisms, western blotting, the GFP-heteroduplex repair assay, and chromatin immunoprecipitation were used. Results We show that knockdown of MRE11A increased the sensitivity of HeLa cells to MNNG treatment, as well as the MNNG-induced DNA damage and apoptosis, implying a potential role of MRE11 in MMR. Moreover, we found that MRE11A was largely recruited to chromatin and negatively regulated the DNA damage signals within the first cell cycle after MNNG treatment. We also showed that knockdown of MRE11A increased, while overexpressing MRE11A decreased, MMR activity in HeLa cells, suggesting that MRE11A negatively regulates MMR activity. Furthermore, we show that recruitment of MRE11A to chromatin requires MLH1 and that MRE11A competes with PMS2 for binding to MLH1. This decreases PMS2 levels in whole cells and on chromatin, and consequently comprises MMR activity. Conclusions Our findings reveal that MRE11A is a negative regulator of human MMR. Graphical Abstract

Abstract Iron-based nanotubes are promising candidates for high performance electromagnetic wave absorbing fillers due to their high aspect ratio, light weight, high axial permeability and high saturation magnetization. Furthermore, the introduction of carbon can improve dielectric loss and block the agglomeration of iron nanotubes. Here, Fe@C composite nanotubes were prepared by introducing carbon onto the surface of precursor α-FeOOH’ fibers followed by hydrogen-thermal annealing. We find that Fe@C composite nanotubes retain the one-dimensional nanostructure of the precursor throughout the annealing. The well-developed lattice and nanostructure of Fe@C nanotubes endow high saturation magnetization, high anisotropy, suppressed eddy current effect and cross-particle exchange coupling as well, and thus contribute to an enhanced permeability. Coatings with Fe@C as fillers achieve a reflection loss of up to −69.34 dB at 3.37 GHz at the matching thickness of 3.97 mm. The Fe@C composite nanotubes developed here are a promising candidate for high performance electromagnetic wave absorbing fillers.

Abstract Background The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN). Methods A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment. Results (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3−CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3−CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers. Conclusions RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production. Trial registration The research was registered at the First Affiliated Hospital of Soochow University. Registration Number: MR-32-23-016211. Registration Date: May 31, 2023.