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Abstract Metastasis is the major cause of treatment failure in patients with prostate adenocarcinoma (PRAD). Diverse programmed cell death (PCD) patterns play an important role in tumor metastasis and hold promise as predictive indicators for PRAD metastasis. Using the LASSO Cox regression method, we developed PCD score (PCDS) based on differentially expressed genes (DEGs) associated with PCD. Clinical correlation, external validation, functional enrichment analysis, mutation landscape analysis, tumor immune environment analysis, and immunotherapy analysis were conducted. The role of Prostaglandin D2 Synthase (PTGDS) in PRAD was examined through in vitro experiments, single-cell, and Mendelian randomization (MR) analysis. PCDS is elevated in patients with higher Gleason scores, higher T stage, biochemical recurrence (BCR), and higher prostate-specific antigen (PSA) levels. Individuals with higher PCDS are prone to metastasis, metastasis after BCR, BCR, and castration resistance. Moreover, PRAD patients with low PCDS responded positively to immunotherapy. Random forest analysis and Mendelian randomization analysis identified PTGDS as the top gene associated with PRAD metastasis and in vitro experiments revealed that PTGDS was considerably downregulated in PRAD cells against normal prostate cells. Furthermore, the overexpression of PTGDS was found to suppress the migration, invasion, proliferationof DU145 and LNCaP cells. To sum up, PCDS may be a useful biomarker for forecasting the possibility of metastasis, recurrence, castration resistance, and the efficacy of immunotherapy in PRAD patients. Additionally, PTGDS was identified as a viable therapeutic target for the management of PRAD.

Objective To establish the internal quality control standard of leukocyte-depleted suspended red blood cell volume in our center, so as to guide the preparation of components, strengthen the internal quality control and improve the quality of blood preparations. Methods A total of 1 523 bags of whole blood collected using two manufacturers′ leukocyte-depleted blood bags from March to August 2023 at our center were extracted. The blood before and after filtration were weighed, and the volume of whole blood collected, the volume of filtration loss and the product volume based on the formula and measured specific gravity were calculated. According to the data distribution characteristics, the reference range of leukocyte-depleted suspended red blood cell volume was determined, and the differences of whole blood collection volume, filtration loss capacity and product capacity between the two manufacturers were analyzed. The quality control data of leukocyte-depleted red blood cells over the past year with the difference between another 100 bags of these cells and the reference interval were compared, and the effectiveness of reference interval was validated. Results The median whole blood collection volume in the sample size was 402.0 mL, with a median filtration loss of 42.4 mL, and an average volume of leukocyte-depleted suspended red blood cells at 322.5 mL. The whole blood collection volume (A: median 404.4 mL; B: median 397.7 mL, P0.05). Conclusion According to the actual situation of our center, the volume standard of leukocyte-depleted suspended red blood cells in our center is determined to be 284.1-360.9 mL.

Abstract Background Sweet sorghum is used mainly as an energy crop and feed crop in arid and semiarid regions, and ensiling is a satisfactory method for preserving high-quality sweet sorghum. The aim of this study was to reveal the dynamics of the fermentation quality, bacterial communities, and fermentation weight loss (FWL) of sweet sorghum silage during fermentation. Methods Sweet sorghum was harvested at the first inflorescence spikelet stage and ensiled without (CK) or with lactic acid bacterial (LAB) additives (L). After ensiling, samples were collected on days 0, 1, 3, 5, 15, 40, and 100 to assess the fermentation quality, bacterial communities, and FWL. Results For CK and L, on day 1, the pH was 5.77 and 5.57, respectively, and the lactic acid (LA) was 1.30 and 2.81 g/kg dry matter (DM), respectively. Compared with CK, L had a lower pH and higher LA from days 1 to 5 (P

Abstract Background Pre-frailty is a window of opportunity for frailty reversal and can be enhanced by multicomponent exercise. The Lifestyle-integrated Functional Exercise (LiFE) program may be a promising alternative to overcome traditional exercise barriers. The latest advancements in mobile health (mHealth) technology have enabled individuals to retain the advantages of supervised exercise training within group settings while providing exercise programs that can be accessed and completed at home. This study aims to assess the feasibility, acceptability, and primary efficacy of the PF-Life program, which is the Lifestyle-Integrated Functional Exercise program for Pre-Frail supported by an mHealth platform. Methods Sixteen pre-frail adults aged ≥ 65 years were recruited from five community health centers in Fuzhou, China. All participants were prescribed the PF-Life program by geriatricians using the mhealth platform (web-based portal). Participants engaged in the customized exercises program following in-app video instructions and feedback on the mhealth platform (smartphone application). Physical activity (PA) and sedentary behavior (SB) were registered daily through wearable devices. Study endpoints were feasibility (retention rate, compliance rate, adverse events), usability (system usability scale), acceptability (qualitative interviews), changes in physical function (timed up and go (TUG), handgrip strength (HGS), and 30-second chair rise tests), PA and SB. Results The intervention was feasible, 88% of participants adhered completely to the study protocol, and 95% had completed at least 75% of the prescribed experimental duration. System usability was high (85 out of 100 best imaginable). Changes were observed from baseline to follow-up for total HGS (21.41 ± 6.38 vs. 24.12 ± 6.62 kg, P

Abstract The incidence of multiple primary lung cancer (MPLC) is increasing, with some of our surgical patients exhibiting numerous lesions. We defined lung cancer with five or more primary lesions as super MPLCs. Elucidating the genomic characteristics of this special MPLC subtype can help reduce disease burden and understand tumor evolution. In our cohort of synchronous super early-stage MPLCs (PUMCH-ssesMPLC), whole-exome sequencing on 130 resected malignant specimens from 18 patients provided comprehensive super-MPLC genomic landscapes. Mutations are enriched in PI3k-Akt and MAPK pathways. Their BRAF mutation frequency (31.5%) is significantly higher than MPLC with fewer lesions and early-stage single-lesion cancer, while EGFR mutations are significantly fewer (13.8%). As lesion counts increase, BRAF mutations gradually become dominant. Also, invasive lesions more tend to have classic super-MPLC mutation patterns. High-frequency BRAF mutations, especially Class II, and low-frequency EGFR mutations could be a reason for the limited effectiveness of targeted therapy in super-MPLC patients.

Abstract Background Nintedanib is a primary antifibrosing medication available for idiopathic pulmonary fibrosis, systemic sclerosis-interstitial lung disease, and progressive pulmonary fibrosis, with scattered report of drug-induced thrombocytopenia. Case report A 60-year-old Asian male with no history of thrombocytopenia was administered with nintedanib to treat progressive pulmonary fibrosis. The platelet count dropped rapidly after introduction of nintedanib and resolved gradually by withdrawal of the medication along with thrombopoietin receptor agonist. Conclusion Based on experience from the limited reports, nintedanib-induced thrombocytopenia is typically reversible and manageable. Close monitoring of platelet counts in patients receiving this medication should be warranted.

Abstract Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment.

Background: Kidney disease has become a growing public health problem worldwide, and there is an urgent need to develop reliable models for investigating novel and effective treatment strategies. In recent years, kidney organoids, as novel models different from traditional two-dimensional cells and model animals, have attracted more and more attention. Current advances have allowed the generation of kidney organoids from the directed differentiation of induced pluripotent stem cells (iPSCs), which possess similar characteristics to embryonic stem cells (ESCs), but bypass ethical constraints and have a wide range of sources. Summary: Herein, the methods of generating renal organoids from iPSCs, the applications of iPSC-derived renal organoids in disease modeling, drug effectiveness detection, and regenerative medicine as well as the challenges were reviewed. Key messages: iPSC-derived renal organoids can be used to model kidney diseases, and are great models for studying kidney injury and toxicity. Many efforts are needed to finally apply organoids into clinical application.

Background: The escalating global burden of cardiovascular diseases, largely driven by unhealthy lifestyle choices and dietary patterns, has intensified the search for effective and safe interventions. With current treatments often marred by significant side effects, the exploration of natural compounds such as flavonoids presents a compelling alternative. Objective: This study investigated the effects of fermented citrus bioconversion product (FCBP), a fermented citrus bioflavonoid, on various markers of cardiovascular health in the context of a high-fat diet. Design: In vivo, a high-fat diet-induced mouse model was used to assess the effects of FCBP on body weight, serum nitric oxide (NO) levels, activated partial thromboplastin time (aPTT), phosphatidylserine (PS) exposure on red blood cells, and the expression of inflammatory markers Intercellular Adhesion Molecule (ICAM)-1 and Vascular Cell Adhesion Molecule (VCAM)-1 in the thoracic aorta. In vitro, EA.hy926 endothelial cells were used to evaluate the compound’s effects on cell viability, NO production, endothelial nitric oxide synthase (eNOS) expression, and cell adhesion molecule (CAM) levels to further understand the mechanisms behind the in vivo findings. Results: In vivo, FCBP supplementation led to a dose-dependent reduction in weight gain, a significant decrease in serum NO levels at 10 mg/kg, and reduced ICAM-1 and VCAM-1 expressions in the thoracic aorta, indicating anti-inflammatory properties. PS exposure on red blood cells was also reduced, suggesting decreased procoagulant activity, while aPTT remained unchanged. In vitro, FCBP was non-cytotoxic to endothelial cells, showed a trend toward increased NO production and eNOS expression, and reduced the expression of ICAM-1 and VCAM-1, supporting its potential anti-inflammatory effects. Conclusions: FCBP demonstrates potential as a bioactive compound for managing cardiovascular health by reducing inflammation, mitigating weight gain, and influencing blood circulation-related parameters under high-fat diet conditions. Further studies, including diverse models and human trials, are warranted to elucidate its mechanisms and compare its efficacy with established cardiovascular therapeutics.

Abstract Background The prognostic nutritional index (PNI), reflecting the body’s immune-nutritional status, has been established as a correlate of prognosis across various diseases. However, its significance in community-acquired pneumonia (CAP) remains unclear. This study investigated the relationship between PNI and clinical outcomes in CAP patients. Methods In this retrospective cohort study, we aimed to evaluate the prognostic value of the PNI in adults with CAP admitted to the ICU. Participants were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and categorized into quartiles (Q1–Q4) according to their PNI values. We employed Kaplan-Meier survival analysis, multivariate Cox regression, and restricted cubic spline (RCS) models to explore the association between PNI and the clinical outcomes of these CAP patients. Results In this study, we included 1,608 patients with CAP. The observed 30-day and 90-day mortality rates stood at 30.85% and 39.99%, respectively. Patients with higher PNI levels exhibited a reduced risk of both 30-day and 90-day mortality. Following adjustment for confounders, PNI showed a significant negative association with 30-day mortality [HR, 0.93 (0.91–0.94), P

Abstract Within the geo-simulation research domain, micro-simulation and agent-based modeling often require the creation of synthetic populations. Creating such data is a time-consuming task and often lacks social networks, which are crucial for studying human interactions (e.g., disease spread, disaster response) while at the same time impacting decision-making. We address these challenges by introducing a Python based method that uses the open data including that from 2020 U.S. Census data to generate a large-scale realistic geographically explicit synthetic population for America’s 50 states and Washington D.C. along with the stylized social networks (e.g., home, work and schools). The resulting synthetic population can be utilized within various geo-simulation approaches (e.g., agent-based modeling), exploring the emergence of complex phenomena through human interactions and further fostering the study of urban digital twins.

Abstract Background Ticks are vectors of numerous pathogens, with their bacterial composition, abundance, diversity, and interaction influencing both their growth and disease transmission efficiency. Despite the abundance of ticks in Inner Mongolia, China, comprehensive data on their microbial communities are lacking. This study aims to analyze the microbial communities within ticks from Inner Mongolia to inform innovative control strategies for interrupting pathogen transmission. Methods Tick samples were collected from animals and vegetation in multiple locations across Inner Mongolia and stored at − 80 °C. Ticks were identified using morphological keys and molecular biology methods. Full-length 16S rRNA gene sequencing was performed on collected samples. Bacterial community composition and diversity were mainly analyzed using bioinformatic tools such as QIIME, phyloseq, and DESeq2. Alpha diversity was assessed using Chao1, ACE, and Shannon indices, while beta diversity was evaluated using Bray-Curtis dissimilarity matrices. LEfSe analysis was applied to identify taxa associated with ecological and biological variables. Results A total of 5,048,137 high-quality read counts were obtained, forming an average of 789.3 OTUs per sample. Proteobacteria, Firmicutes, and Bacteroidetes were the most dominant phyla. Bacterial community composition varied significantly with geography, with Dermacentor nuttalli showing a higher abundance of Rickettsia in Xilingol League, while other regions had different dominant genera. The microbial community also differed based on the feeding status of ticks. Additionally, the microbiota of engorged ticks showed organ specificity. Pathogen detection efforts revealed the presence of nine pathogens across all three tick species. D. nuttalli was found to carry a significantly higher burden of pathogenic bacteria, making it the most potentially threatening tick species in Inner Mongolia. Conclusions The study highlights significant variations in tick microbiomes influenced by geographic location, feeding status, and tick species. It underscores the importance of enhancing tick and tick-borne disease surveillance in Inner Mongolia for early detection and control of emerging pathogens. Graphical Abstract

Abstract Background The growing body of evidence suggests that RNA-binding proteins (RBPs) have an important function in cancer biology. This research characterizes the expression status of fragile X-related protein 1 (FXR1) in esophageal cancer (ESCA) cell lines and understands its mechanistic importance in ESCA tumor biology. Methods The role of FXR1, PDZK1IP1, and ATOH8 in the malignant biological behaviors of ESCA cells was investigated using in-vitro and in-vivo experiments. Results FXR1 was aberrantly overexpressed at both the transcript and protein levels in ESCA cells. Deficiency of FXR1 in ESCA cells was associated with decreased cell proliferation, viability and compromised cell migration compared to the control group. In addition, the inhibition of FXR1 leads to the promotion of apoptosis and cell cycle arrest in ESCA cells. Furthermore, FXR1 knockdown stabilizes senescence markers, promoting cellular senescence and decreasing cancer growth. Mechanistically, FXR1 negatively regulated PDZK1IP1 or ATOH8 transcripts by promoting mRNA degradation via direct interaction with its 3′UTR. PDZK1IP1 or ATOH8 overexpression predominantly inhibited the tumor-promotive phenotype in FXR1-overexpressed cells. Furthermore, FXR1 inhibition and PDZK1IP1 or ATOH8 overexpression in combination with FXR1-overexpressed cells significantly decreased xenograft tumor formation and enhanced nude mouse survival without causing apparent toxicity (P

Abstract Background Physical exercise is an important method for both the physical and mental health of the senior population. However, excessive exertion can lead to increased risks of falls, severe injuries, and diminished quality of life. Therefore, simple and effective methods for fatigue monitoring during exercise are highly desirable, particularly in community settings. The purpose of this study was to explore the possibility of real-time detection of exercise-induced fatigue using surface Electromyogram (sEMG) features, including the kurtosis and skewness of the Probability Density Function (PDF) in the community settings to solve the issues of low sensitivity and high computational complexity of commonly used sEMG features. Methods sEMG signals from six forearm muscles were recorded during hand grip tasks at 20% maximal voluntary contraction (MVC) task-to-failure contractions from 30 healthy community-dwelling elders at their respective community centers. PDF shape features of the sEMG, namely kurtosis and skewness, were computed from 25 s of non-fatigue stable phase and 25 s of fatigue data for comparison. Statistical tests were conducted to compare and test for the significance of these features. We further proposed a novel fatigue indicator, Temporal-Mean-Kurtosis (TMK) of channel-averaged kurtosis, to detect fatigue with relatively low computational complexity and adequate sensitivity in community settings. ANOVA and post-hoc analyses were performed to examine the performance of TMK. Results Statistically significant differences were found between the non-fatigue period and the fatigue period for both kurtosis and skewness, with increasing values when approaching fatigue. TMK was shown to be sensitive in detecting fatigue with respect to time with lower computational complexity than the Sample Entropy. Conclusion This study investigated PDF shape features of sEMG signals during a handgrip exercise to identify muscle fatigue in older adults in community experiments. Results revealed significant changes in kurtosis upon fatigue, indicating that PDF shape features were suitable convenient detectors of muscle fatigue in community experiments. The proposed indicator, TMK, showed potential sensitivity in tracking muscle fatigue over time in community-based settings with limited computational complexity, highlighting the promise of sEMG’s PDF features in detecting muscle fatigue among the elderly.

Abstract The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Abstract Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data from esophageal squamous cell carcinoma (ESCC) samples. Radioresistant ESCC cell lines were generated to explore the functional role of CCNG1. Various techniques, including gene knockdown, flow cytometry, and apoptosis assays, were utilized to evaluate alterations in radiosensitivity, cell cycle progression, and cell survival in response to CCNG1 modulation. Elevated CCNG1 expression was associated with poor clinical outcomes in ESCC patients and contributed to various malignant phenotypes in ESCC cells. In radioresistant ESCC cell lines, CCNG1 knockdown markedly increased radiosensitivity, as demonstrated by enhanced G2/M phase arrest and apoptosis following radiation exposure. CellChat analysis indicated a correlation between CCNG1 and the Wnt/β-catenin signaling pathway, while western blot (WB) analysis confirmed that CCNG1 functions as a downstream effector of Wnt/β-catenin. Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes.

Abstract In this paper, we show the interaction phenomena about the first-order lump wave and multiple solitons by four theorems. The interaction phenomena are divided into two types, one type is absorbing collision phenomenon and the other type is elastic collision phenomenon. Six sets of dynamic plots over time are showed the phenomenon of absorbing interactions with energy transfer process, the phenomenon of elastic interactions with restoration of the initial state after collision. We apply the four theorems to an equation which can characterize the Rossby waves’ amplitude, this equation can be used to describe the resonance phenomenon of Rossby waves. Different test functions with the same parameter values can present different wave-wave interaction properties. This study contributes to in-depth investigation of the mechanism of lump wave generation, evolution and interaction.

Abstract With the emergence of the new generation vision architecture Vmamba and the further demand for agricultural yield and efficiency, we propose an efficient and high-accuracy target detection network for automated pear picking tasks based on Vmamba, aiming to address the issue of low efficiency in current Transformer architectures. The proposed network, named SRSMamba, employs a Reward and Punishment Mechanism (RPM) to focus on important information while minimizing redundancy interference. It utilizes 3D Selective Scan (SS3D) to extend scanning dimensions and integrates global information across channel dimensions, thereby enhancing the model's robustness in complex agricultural environments and effectively adapting to the extraction of complex features in pear orchards and farmlands. Additionally, a Stacked Feature Pyramid Network (SFPN) is introduced to enhance semantic information during the feature fusion stage, particularly improving the detection capability for small targets. Experimental results show that SRSMamba has a low parameter count of 21.1 M, GFLOPs of 50.4, mAP of 72.0%, mAP50 reaching 94.8%, mAP75 at 68.1%, and FPS at 26.9. Compared with other state-of-the-art (SOTA) object detection methods, it achieves a good trade-off between model efficiency and detection accuracy.

Abstract Background Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia. Methods We employed a triangulation approach combining three methodologies. We analyzed 90,893 UK Biobank (UKB) adults to explore single and joint effects of hearing and vision impairments on all-cause and Alzheimer’s disease (AD), vascular dementia (VD) and non-AD non-VD (NAVD). A meta-analysis of prospective studies involving 937,908 participants provided stronger evidence. Finally, we conducted Mendelian randomization (MR) analysis using genome-wide association studies from UKB (361,194 participants) and FinnGen (412,181 participants) to validate relationships between sensory impairments and dementia occurrence. Results In the UKB cohort study, compared to participants with normal hearing, those in the mild and severe hearing impairment groups had progressively and significantly higher risk of all-cause dementia (mild: HR1.52, 95%CI 1.31–1.77; severe: HR1.80, 95%CI 1.36–2.38), AD (mild: HR1.63, 95%CI 1.30–2.04; severe: HR2.18, 95%CI 1.45–3.27), VD (mild: HR1.68, 95%CI 1.19–2.37; severe: HR1.47, 95%CI 1.22–1.78), and NAVD (mild: HR1.47, 95%CI 1.22–1.78; severe: HR1.98, 95%CI 1.43–2.75). Besides, vision impairment was associated with an increased risk of all-cause dementia (HR1.55, 95%CI 1.18–2.04) and NAVD (HR1.51, 95%CI 1.07–2.13). Furthermore, dual sensory impairment was associated with stepwise increased risks of all-cause and cause-specific dementia than single hearing or vision impairment. In the meta-analysis of 31 prospective cohort studies, risks of all-cause dementia and AD were elevated in participants with single hearing impairment (all-cause dementia: HR1.30, 95%CI 1.21–1.40; AD: HR1.30, 95%CI 1.21–1.40) and dual sensory impairment (all-cause dementia: HR1.63, 95%CI1.14–2.12; AD: HR 2.55, 95%CI 1.19–3.91), while single vision impairment only associated with higher risk of all-cause dementia (HR1.43, 95%CI 1.16–1.71) but not AD. Finally, the MR analysis revealed a significant association between hearing impairment and all-cause dementia (OR1.74, 95%CI 1.01–2.99), AD (OR1.56, 95%CI 1.09–2.23), and NAVD (OR1.14, 1.02–1.26), as well as vision impairment and NAVD (OR1.62, 95%CI 1.13–2.33). Conclusions Our findings showed significant associations between hearing and vision impairments and increased risks of all-cause and cause-specific dementia. Standardized hearing and vision assessment and intervention should be emphasized in dementia prevention strategies.

Abstract Ceria (CeO2) is a widely used oxide catalyst, yet the nature of its active sites remains elusive. This study combines model and powder catalyst studies to elucidate the structure-activity relationships in ceria-catalyzed CO activation and hydrogenation. Well-defined ceria clusters are synthesized on planar CeO2(111) and exhibit dynamic and tunable ranges of Ce coordination numbers, which enhance their interaction with CO. Reduced ceria clusters (e.g., Ce3O3) bind CO strongly and facilitate its dissociation, while near-stoichiometric clusters (e.g., Ce3O7) adsorb CO weakly and promote oxidation via carbonate formation. Unlike planar ceria surfaces, supported ceria clusters exhibit dynamic properties and enhanced catalytic activity, that mimic those of powder ceria catalysts. Insight from model studies provide a method to quantify active sites on powder ceria and guide further optimization of ceria catalysts for syngas conversion. This work marks a leap toward model-guided catalyst design and highlights the importance of site-specific catalysis.

Abstract Asparagales, the largest monocot order, is renowned for its ecological, economic, and medicinal significance. Here, we leverage transcriptome data from 455 Asparagales species to explore the phylogeny of Asparagales. Moreover, we investigate the evolutionary patterns of the genes involved in allium flavor formation. We not only establish a robust bifurcating phylogeny of Asparagales but also explore their reticulate relationships. Notably, we find that eight genes involved in the biosynthesis of allium flavor compounds underwent expansion in Allium species. Furthermore, we observe Allium-specific mutations in one amino acid within alliinase and three within lachrymatory factor synthase. Overall, our findings highlight the role of gene expansion, increased expression, and amino acid mutations in driving the evolution of Allium-specific compounds. These insights not only deepen our understanding of the phylogeny of Asparagales but also illuminate the genetic mechanisms underpinning specialized compounds.

Abstract Retinal neovascularization (RNV) disease is one of the leading causes of blindness, yet the molecular underpinnings of this condition are not well understood. To delve into the critical aspects of cell-mediated angiogenesis, we analyzed our previously published single-cell data. Our analysis revealed that retinal pigment epithelium (RPE) cells serve a crucial promotional function in angiogenesis. RPE cells were regulated by N6-methyladenosine (m6A). Next, we detected several critical m6A methylase in hypoxic ARPE-19 cells and in oxygen-induced retinopathy (OIR) mice, our results revealed a significant decrease in the level of methyltransferase like 3 (METTL3). METTL3 specific inhibitor STM2457 intravitreal injection or METTL3 conditional knockout mice both showed a significantly reduced neovascularization area of retina. Additionally, the angiogenesis-related abilities of human retinal endothelial cells (HRECs) were diminished after co-cultured with ARPE-19 treated with STM2457 or sh-METTL3 in vitro. Furthermore, through the integration of Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing, we discovered that the metabolic enzyme quinolinate phosphoribosyltransferase (QPRT) was directly modified by METTL3 and recognized by the YTH N6-methyladenosine RNA binding protein C1 (YTHDC1). Moreover, after over-expressing QPRT, the angiogenic abilities of HRECs were improved through the phosphorylated phosphatidylinositol-3-kinase (p-PI3K)/ phosphorylated threonine kinase (p-AKT) pathway. Collectively, our study provided a novel therapeutic target for retinal angiogenesis.

Abstract Objective This study aimed to investigate the relationship between serum lactate levels at admission to the intensive care unit (ICU) and the clinical outcomes of children with sepsis. Methods We used the Pediatric Intensive Care (PIC) database to identify 288 pediatric patients with sepsis. We analyzed the relationship between lactate levels and hospital and ICU mortality in sepsis by establishing a segmented multivariable Cox regression model. We also conducted subgroup analysis as well as analyzed the restricted cubic spline curves. Results After adjusting for all potential confounding factors, an increase of 1 mmol/L in lactate levels was found to be associated with an 17% rise in the 28-day hospital mortality risk among sepsis patients (HR: 1.17, 95% CI: 1.08–1.27, P = 0.0002). When considering lactate as a categorical variable, the mortality risk of patients with lactate levels ≥ 2.2 mmol/L was significantly increased (HR: 3.61, 95% CI: 1.24–10.54, P = 0.0189). The restricted cubic spline curve analysis revealed a nonlinear correlation between lactate and 28-day mortality, with an inflection point at 2.2 mmol/L. Similar findings were also observed in the assessment of secondary outcomes. Conclusions Our study demonstrates a non-linear correlation between lactate levels and 28-day mortality in pediatric sepsis, with a critical threshold of 2.2mmol/l for lactate levels in septic patients. Early assessment of lactate levels is recommended for children with sepsis to facilitate prompt intervention and mitigate the risk of fatality.

Abstract Colorectal cancer (CRC) is a common malignant tumor of the digestive tract in China; its incidence rates and mortality rates have been on the rise in recent years, ranking third in terms of incidence and second in mortality. Rational dietary intervention plays an important role in human health, and prevention and adjuvant treatment of CRC through dietary supplementation is the most ideal and safest way to treat the disease at present. More importantly, dietary protein is the basis of our diet and the key nutrient to maintain the normal function of the human body. Therefore, this narrative review delivered an overview of the common causes and therapeutic treatments for CRC. It emphasized the importance of dietary interventions, with a particular focus on elucidating the distinct regulatory impacts of plant proteins, animal proteins, and their mixed proteins.

Abstract To discuss the application value of Case-based Learning (CBL) combined with Bridge-In, Objective, Pre-assessment, Participatory Learning, Post-assessment, and Summary (BOPPPS) model into master students’ program of oral and maxillofacial surgery. 38 master’s students in oral and maxillofacial surgery at Y2 and Y3 from January 2022 to December 2022 are selected as the research objects. They are randomly assigned into two learning groups, namely the traditional LBL (Learn-based Learning) (19 participants) and CBL combined with BOPPPS mode (19 participants). Their theoretical knowledge was assessed after training and the modified Mini-Clinical Evaluation Exercise (Mini-CEX) scale was used to score their clinical thinking. At the same time, the Personal Teaching Efficiency and the Teachers’ Sense of Teaching Efficiency (TSTE) were evaluated, and students’ satisfaction with teaching outcomes was investigated. The basic theoretical knowledge, clinical case analysis and total scores of the experimental group were better than those of the control group, with statistically significant difference (P 0.05), the other four items and total scores in the experimental group were better than those in the control group, with statistically significant difference (P 0.05). CBL combined with BOPPPS teaching method can improve students’ clinical critical thinking ability and help them adapt to the clinical rhythm. It is an effective measure to ensure teaching quality and is worthy of promotion. It is worthwhile to promote the application of CBL combined with BOPPPS mode into master’s course of oral and maxillofacial surgery, which not only improve the basic theoretical knowledge and speculative thinking ability of master’s students, but also improve the teaching efficiency.

Hesperidin is a dihydroflavonoids, accounting for more than 50% of the total flavonoids in Citri Reticulatae Pericarpium (CRP) of traditional Chinese medicine. It is an effective antioxidant and free radical scavenger that has anti-inflammatory, antiviral and hypoglycemic properties. The latest studies reported that hesperidin has a potential for novel coronavirus resistance. However, little is known about the synthesis regulation and accumulation site of hesperidin in plants. In this study, hesperidin synthase gene Crc1,6RhaT was cloned, and the protein can be completely transformed flavanone-7-O-glucoside into hesperidin in vitro and in vivo. Studies on biological characteristics of ovary walls and exocarps showed that the relative expression levels of the Crc1,6RhaT gene and protein decreased gradually with the development of citrus fruits, and the relative content of hesperidin firstly increased, then sequentially decreased. In situ hybridization results further revealed that Crc1,6RhaT transcription was mainly concentrated in the secretory cavity cells, which are revealed to be the site of flavonoid synthesis. Immunocytochemistry localization results showed that the Crc1,6RhaT was mainly located in the endoplasmic reticulum, nucleus and vacuole of secretory cells. We inferred that the Crc1,6RhaT was synthesized in the endoplasmic reticulum, then was transported into the vacuoles through enlarged vesicles at the end of the endoplasmic reticulum. Our results not only revealed that Crc1,6RhaT may be involved in the synthesis of hesperidin of the main bioactive substance in the medicinal plant Citrus reticulata ‘Chachi’ fruit, but also provided novel insights into the main subcellular sites of hesperidin biosynthesis in vacuoles.

AIM: To investigate the proliferation regulatory effect of cone-rod homeobox (CRX) in retinal pigment epithelium (RPE) and retinoblastoma (RB) cells to explore the potential application and side effect (oncogenic potential) of CRX-based gene therapy in RPE-based retinopathies. METHODS: Adult human retinal pigment epithelial (ARPE)-19 and human retinal pigment epithelial (RPE)-1 cells and Y79 RB cell were used in the study. Genetic manipulation was performed by lentivirus-based technology. The cell proliferation was determined by a CellTiter-Glo Reagent. The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot assay. The transcriptional activity of the promoter was determined by luciferase reporter gene assay. The bindings between CRX and transcription factor 7 (TCF7) promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation (ChIP) assay. The transcription of the TCF7 was determined by a modified nuclear run-on assay. RESULTS: CRX overexpression and knockdown significantly increased (n=3, P

Introduction: The proportion of animal based foods in daily diet of consumers is constantly increasing, with chicken being highly favored due to its high protein and low fat characteristics. The consumption of chicken around the world is steadily increasing. Intramuscular fat (IMF) is a key indicator affecting meat quality. Object: High IMF content can contribute to improve the quality of chicken meat. The regulatory mechanism of IMF deposition in chicken is poorly understood, so its complete elucidation is essential to improve chicken meat quality. Method: Here, we performed whole genome resequencing on 516 yellow feather chickens and single-cell RNA sequencing on 3 63-day-old female JXY chickens. In addition, transcriptome sequencing techniques were also performed on breast muscle tissue of JXY chickens at different developmental stages. And 13C isotope tracing technique was applied. Results: In this study, a large-scale genetic analysis of an IMF-selected population and a control population identified fatty acid synthase (FASN) as a key gene for improving IMF content. Also, contrary to conventional view, de novo lipogenesis (DNL) was deemed to be an important contributor to IMF deposition. As expected, further analyses by isotope tracing and other techniques, confirmed that DNL mainly occurs in myocytes, contributing about 40% of the total fatty acids through the regulation of FASN, using the available FAs as substrates. Additionally, we also identified a relevant causal mutation in the FASN gene with effects on FA composition. Conclusion: These findings contribute to the understanding of fat metabolism in muscle tissue of poultry, and provide the feasible strategy for the production of high-quality chicken meat.

Background: Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar (in yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules or organelles for degradation, a process termed selective autophagy. Recently, accumulating studies have demonstrated that the abnormality of selective autophagy is closely associated with the occurrence and progression of many human diseases, including neurodegenerative diseases, cancers, metabolic diseases, and cardiovascular diseases. Aim of Review: This review aims at systematically and comprehensively introducing selective autophagy and its role in various diseases, while unravelling the molecular mechanisms of selective autophagy. By providing a theoretical basis for the development of related small-molecule drugs as well as treating related human diseases, this review seeks to contribute to the understanding of selective autophagy and its therapeutic potential. Key Scientific Concepts of Review: In this review, we systematically introduce and dissect the major categories of selective autophagy that have been discovered. We also focus on recent advances in understanding the molecular mechanisms underlying both classical and non-classical selective autophagy. Moreover, the current situation of small-molecule drugs targeting different types of selective autophagy is further summarized, providing valuable insights into the discovery of more candidate small-molecule drugs targeting selective autophagy in the future. On the other hand, we also reveal clinically relevant implementations that are potentially related to selective autophagy, such as predictive approaches and treatments tailored to individual patients.

The growth and yield of tea plants are seriously limited by drought stress. Fatty acid desaturases (FADs) contribute to the mediation of membrane fluidity in response to different stresses, although the role of ω-3 FAD (Omega-3 fatty acid desaturase)-mediated damage induced by drought stress in tea plants is poorly understood. In this study, drought stress significantly promoted the synthesis of C18:3 (linolenic acid) and the expression level of CsFAD3. Yeast experiments further demonstrated that CsFAD3 can convert C18:2 to C18:3, and that the 35S:GFP-CsFAD3 fusion protein was localized in the endoplasmic reticulum of Nicotiana benthamiana cells. CsFAD3-silenced tea leaves exhibited poor drought tolerance, with a lower Fv/Fm and a higher malondialdehyde (MDA) content than the control plants. However, transgenic 35S:CsFAD3 Arabidopsis plants showed the opposite phenotypes. In addition, the jasmonic acid (JA) content and the expression levels of CsLOX2, CsLOX4, CsAOS, CsAOC3 and CsOPR2 were significantly reduced in CsFAD3-silenced leaves under drought stress. However, no substantial difference in the salicylic acid (SA) content was detected under normal or drought conditions. An analysis of Atcoi1 (JA receptor) or Atnpr1 (SA receptor) mutant Arabidopsis plants in 35S:CsFAD3 backgrounds further revealed that knockout of Atcoi1 impaired the drought-tolerant phenotypes of CsFAD3 overexpression lines. Therefore, this study demonstrated that CsFAD3 plays a crucial role in drought tolerance by mediating JA pathways.

High-performance titanium alloys with good corrosion resistance are expected to be applied in marine environments. In this work, we developed a Ti20W alloy using powder metallurgy and hot extrusion, which combined remarkable mechanical properties and good corrosion resistance. The Ti20W alloys exhibited ultrahigh strength (>1400 MPa) and good ductility (>7%), and the specific yield strength was comparable to the common high-strength Ti alloys. The ultrahigh-strength Ti20W alloys had characteristics of the solid solution of W atoms and the precipitation of fine α phases. Compared with Ti6Al4V alloy, the Ti20W alloys showed lower corrosion current density values in 3.5 wt% NaCl solution, which was attributed to the solid solution of W elements and the finer α phases. The W oxides, particularly WO3, acted as the barrier to effectively block the penetration of Cl− into the inner oxide layer, thereby enhancing the corrosion resistance. The fine α phases could be bridged by the surrounding matrix oxides during the passivation process, which contributed to decreasing the galvanic corrosion between the α phases and the matrix, further improving the corrosion resistance.

Wound repair is the practice of repairing the skin and other soft tissues after an injury. An inflammatory response is activated after an injury, and cells below the dermis (deepest skin layer) begin to produce more collagen (connective tissue). A scientific assessment was made for the wound-healing potential of Ipomoea staphylina leaves extract, using ethanol. The crude extract was made into a 2.5% and 5% (w/w) ointment and tested for wound healing activity in Wistar rats using excision and incision wound models. In the excision wound model, the period of epithelialization was reduced and an increase in wound contraction rate was observed in the extract treated groups (III and IV). On the tenth day, tissue from the excision wound area was taken and processed for the assessment of pro-inflammatory cytokines (TNF-α), and it was found that there was a notable decrease in the TNF-α concentration in the extract-treated animals. In an incision wound model, the breaking strength was significantly increased in animals treated with 2.5% and 5% (w/w) ointment of I. staphylina leaves extract. The extract significantly promoted fibroblast migration in an in vitro experiment (scratch assay), which may have been caused by the presence of flavonoids.

Abstract Asthma is a complex chronic respiratory inflammatory disease affected by both genetic and environmental factors. Therefore, our study explored the influence of TRIM11 on asthma and its underlying mechanisms. Our research involved patients diagnosed with asthma and healthy volunteers recruited from our hospital. We observed a reduction in serum TRIM11 expression in asthma patients, which positively correlated with the levels of anti-IgE or IgE. Additionally, both TRIM11 mRNA and protein expression in lung tissue were diminished. The introduction of the TRIM11 gene resulted in a reduction in inflammation in an in vitro asthma model and prevented the development of asthma in a mouse model. Moreover, the TRIM11 gene exhibited a suppressive effect on Ferroptosis and mitigated ROS-induced mitochondrial damage in the asthma model. TRIM11 was found to stimulate UBE2N-TAX1BP1 signaling in the asthma model, with UBE2N being identified as the specific target for TRIM11’s effects on Ferroptosis. Furthermore, TRIM11 protein interacted with UBE2N protein and facilitated the dissociation of UBE2N-UBE2N in the asthma model. In conclusion, TRIM11 plays a vital role in preventing Ferroptosis in the asthma model through UBE2N-TAX1BP1 signaling. This indicates that targeting the TRIM11 mechanism could serve as a promising strategy for anti-Ferroptosis immunotherapy in asthma treatment.

Abstract Recently, human motion prediction has gained significant attention and achieved notable success. However, current methods primarily rely on training and testing with ideal datasets, overlooking the impact of variations in the viewing distance and viewing angle, which are commonly encountered in practical scenarios. In this study, we address the issue of model invariance by ensuring robust performance despite variations in view distances and angles. To achieve this, we employed Riemannian geometry methods to constrain the learning process of neural networks, enabling the prediction of invariances using a simple network. Furthermore, this enhances the application of motion prediction in various scenarios. Our framework uses Riemannian geometry to encode motion into a novel motion space to achieve prediction with an invariant viewing distance and angle using a simple network. Specifically, the specified path transport square-root velocity function is proposed to aid in removing the view-angle equivalence class and encode motion sequences into a flattened space. Motion coding by the geometry method linearizes the optimization problem in a non-flattened space and effectively extracts motion information, allowing the proposed method to achieve competitive performance using a simple network. Experimental results on Human 3.6M and CMU MoCap demonstrate that the proposed framework has competitive performance and invariance to the viewing distance and viewing angle.

Abstract Citrus red mites (P. citri) are key pests affecting citrus production worldwide due to pesticide resistance. The resistance mechanisms of ten pesticides are known, but a comprehensive study using transcriptome data is missing. This study employed deeptools, cuffdiff, rmats, bcftools and other software to examine gene expression variation, alternative splicing (AS), and mutations in mite resistance. The research highlighted that pesticides can regulate gene transcription, and red mites with resistance increase cytochrome P450, glutathione S-transferases, carboxylesterase, and acetylcholinesterase expression. Pyridaben also induces new AS events. Fluazinam-induced mites show mRNA splicing peaking earlier than transcription, both peaking at one day and returning to baseline after two days. AS profiles are similar in different mite populations with overlapping pesticide resistances. Lastly, specific mitochondrial SNPs in mites might mediate resistance against select pesticides.

Abstract Few studies evaluated patient-reported outcomes (PROs) for patients with hematologic malignancies receiving with Chimeric Antigen Receptor T (CAR-T) cell therapy. We performed a systematic review and meta-analysis to evaluate the benefits of CAR-T cell therapies focused on PROs. A systematic literature searched from PubMed, Cochrane, and the Web of Science from inception to September 2023. Study selection and data extraction were conducted independently by two reviewers based on pre-specified criteria. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist was used to evaluate the methodological quality of the included studies. The random-effects model was employed to calculate the combined effect and 95% Confidence intervals. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and the protocol was registered with PROSPERO (CRD42024586706). We identified 20,110 studies. Of those, 15 studies with 16 different PRO measures (PROMs) were included in the meta-analysis. CAR-T cell therapy improved PROs in the six domains of general health status, pain, fatigue, depression, social function, and cognitive function: from the general health status (SMD: 0.57, 95% CI: 0.34 to 0.81) to cognitive function (SMD: 0.25, 95% CI: 0.14 to 0.37). The current meta-analysis shows that CAR-T cell therapy produces clinically meaningful differences in PROs. These results suggest that the professional perspective and patient values and preferences should be weighed equally when considering CAR-T cell therapy for hematologic malignancies.

Abstract The causal link between serum uric acid (SUA) levels and gastric cancer susceptibility remains inadequately elucidated. This investigation employed a two-sample Mendelian randomization (MR) framework to assess the potential causative link between SUA concentrations and the propensity for developing gastric cancer. To further explore potential racial differences, this MR analysis was conducted on cohorts of both European and East Asian descent. Data from a large-scale GWAS in 343,836 Europeans and 92,615 East Asians were screened for 206 and 45 SNPs significantly linked to SUA levels, respectively, as genetic variants. Subsequently, four distinct MR methodologies were deployed to determine how SUA levels affected gastric cancer risk. Using the fixed-effects IVW approach, our analysis revealed no significant association between SUA levels and gastric cancer risk, with P-values exceeding the threshold of significance in both populations (European P = 0.778; East Asian P = 0.245). The findings were supported by three additional MR methods. The reliability of these results was substantiated by comprehensive sensitivity analyses. In summary, our data do not support a significant causal linkage between SUA levels and gastric cancer risk.

Abstract Background Accurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers’ anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect. Methods A search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications’ details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting. Results Among the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38). Conclusions Registered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs.

Abstract Background Inflammation significantly impacts Parkinson’s disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive. Objective To identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD. Methods 79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD. Results Compared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups. Conclusion Elevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD.

Abstract Introduction Cognitive dysfunction is believed to be among the core features of Bipolar Depression(BD-D). However, its evaluation and available treatments are limited. Here, we conducted a longitudinal follow-up clinical trial using the THINC-it tool to evaluate temporal sensitivity to change over time in cognitive function among patients with bipolar depression from a Chinese cohort. It is helpful to verify whether the scale can continuously and reliably measure cognitive function in different time points and reduce the measurement error caused by time factors. Hope our findings could provide insights into the significance of the THINC-it tool as an iterative clinical cognitive evaluation tool. Methods A total of 120 patients with bipolar depression(40 males and 80 females, respectively) alongside 100 healthy controls(23 males and 77 females, respectively) were recruited in the study. All participants were interviewed for 8 weeks, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale(YMRS). The primary dependent measure was the previously validated THINC-it tool, followed by psychometric analysis. Results Repeated measures of the THINC-it tool at baseline, one-week, and eight-week periods were conducted after controlling for age, gender, and education effects. Results from the general linear model revealed no significant time differences in variances(P > 0.05). Similarly, adjusting for confounding factors (age, gender, education, and HAMD-17 scores), results from the longitudinal analysis showed that there were no significant differences in cognitive impairment over time(P > 0.05). However, we found significant differences between BD-D and Healthy Control(HC) groups with regards to Spotter, Codebreaker, Trails, Perceived Deficits Questionnaire for Depression-5-items(PDQ-5-D), and THINC-it Total composite(P

Abstract Background Childhood emotional maltreatment, non-suicidal self-injury and depression are prevalent among adolescents with mood disorders. While existing model indicated that childhood emotional maltreatment, functions of non-suicidal self-injury and depression are interrelated, not much is understood about the interplay of functions of non-suicidal self-injury in the relationship between childhood emotional maltreatment and depression. Thus, the goal of this research was to ascertain how functions of non-suicidal self-injury relate to childhood emotional maltreatment and depression. Methods The participants were adolescents with mood disorders from three hospitals in Sichuan Province, data was collected using self-administered questionnaires, including the Childhood Trauma Questionnaire, Ottawa Self-injury Inventory-Functions, and Childhood Depression Inventory. SPSS26.0 software and PROCESS v3.3 model 4 were used for analysis. Results In all, 235 adolescents (M age=14.8, SD = 1.62) participated in the research. The functions of non-suicidal self-injury (r = 0.289, P

Abstract The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72–57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G+) and gram-negative (G−) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry. Graphical Abstract

Abstract To improve the portability of dried pork tendons for consumption, this study investigated the effects of different puffing temperatures (190 °C - 250 °C) and times (1-7 min) on the quality and flavor of pork tendons. As the temperature and time increased, the expansion ratio of pork tendons exhibited a gradual increase. The microstructure of the puffed pork tendons exhibited a uniform porous structure at 230 °C and 250 °C for 6 min. However, further puffing treatment destroyed the spatial structure. GC-IMS identified 68 volatile organic compounds (VOCs), and a total of 16 key VOCs including 2-trans-4-trans-decadienal were screened by GC-MS. Nonanal, 1-octen-3-ol, 2-amylfuran and 2-ethylfuran proved to have a significant effect on the flavor of the puffed pork tendon. The combined puffing performance and flavor analysis revealed that puffing at 230 °C for 6 min was the preferred parameter for puffed pork tendons.

Abstract Introduction Preoperative evaluation of inferior vena cava (IVC) wall invasion is very important to improve outcomes of patients with renal cell carcinoma (RCC), and may allow surgical urologists to treat the IVC more effectively. The objective of this study was to evaluate preoperative 18F-FDG PET/CT in patients with RCC and IVC tumor thrombus (IVCTT) for the diagnosis of IVC wall invasion. Methods This retrospective case-control study evaluated 68 patients with RCC with level I-IV tumor thrombus. According to the histopathologic examination result, the patients were divided into IVC wall invasion group and non-invasion group. The 18F-FDG PET/CT features between two groups were analyzed. Furthermore, a logistic regression model was used to determine if there was an association between PET/CT features and IVC wall invasion. Results Sixty-eight patients were evaluated, and 55.9% (38/68) had IVC wall invasion. Compared with non-invasion group, invasion group had higher SUVmax of RCC, higher SURmax (tumor to tumor thrombus ratio, Tu/Th), higher IVCTT coronal diameter, and longer IVCTT craniocaudal extent (all p

Abstract Background Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years. Methods In this study, models of CA10 infection were established in 7‐day‐old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10. Results After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA‐sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up‐regulated DEGs in muscle were enriched in immune‐related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll‐like receptor pathway and the nucleotide‐binding and oligomerization domain (NOD)‐like pathway. Conclusions Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.

Aim: The cardio-ankle vascular index (CAVI) is a new evaluation indicator for arteriosclerosis. This study investigated the relationship between the CAVI and lipid levels in patients with hypertension in a real clinical environment. Methods: This descriptive study enrolled 2,656 patients (male/female: 1,016/1,640) from the Outpatient Department of Vascular Medicine of Peking University Shougang Hospital and Jinding Street Community Health Service Center. CAVI was measured using a VaseraVS-1000 vascular screening system (Fukuda Denshi, Tokyo, Japan). Results: Age, body mass index (BMI), waist circumference, hip circumference, CAVI, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatinine, fasting plasma glucose (FPG), uric acid (UA), hypersensitive C-reactive protein (hs-CRP), homocysteine, HbA1c, and triglyceride (TG) were significantly higher in the hypertension group than in the non-hypertension group. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in the hypertension group than in the non-hypertension group. The CAVI value was significantly higher in patients with hypertriglyceridemia and normal LDL-C than in those with normal TG and hyper-LDL-C. Age, waist circumference, UA, FPG, HDL-C, hs-CRP, HbA1c, BMI, SBP, and DBP were independently associated with CAVI in all patients. Beta blockers were negatively correlated with CAVI (β = –0.411, P = 0.011). Sex (male) and history of hypertension and diabetes mellitus were positively correlated with CAVI (β = 0.419, P < 0.001; β = 0.247, P = 0.011; β = 0.638, P < 0.001; respectively). Conclusions: The CAVI was significantly higher in patients with hypertension and exhibited differences based on sex. Although we did not find a significant correlation between CAVI and TG, it remains crucial to maintain blood pressure to prevent the development of arteriosclerosis.

Purpose This study aims to explore the factors influencing nursing professionalism among nursing students, focusing on the image of nurses, satisfaction with their major, and career metacognition. Methods We conducted a descriptive survey with 185 nursing students from D city and K region on June 10–30, 2024. Data were analyzed using IBM SPSS ver. 27.0 (IBM Corp.), employing descriptive statistics, t tests, one-way ANOVA, Scheffé tests, Pearson’s correlation coefficients, and regression analysis. Multiple linear regression analysis was used to identify factors affecting nursing professionalism among nursing students. Results The regression analysis revealed that the image of nurses (β=.69, p

Abstract Purpose Our institution developed the subspecialized medical team (SMT) mode in radiology reporting workflows in July 2022 to strengthen professionalism in radiology residency training. This study aimed to investigate whether adopting the SMT mode facilitated radiology resident training. Method This observational study was conducted in October 2022. An online questionnaire was distributed among first‐to third‐year radiology residents to determine their levels of perceived stress, anxiety, competency in image interpretation, and learning effectiveness in using the SMT mode and other approaches. Responses were on 4 or 5 point Likert scales, and multiple‐choice responses were used for semi‐open questions. The turnaround time for radiology reports was measured for both residents and senior radiologists. Statistical significance (p

Abstract As the third most important temperate fruit, Pear (Pyrus spp.) exhibits a remarkable genetic diversity and is classified into two mainly categories known as Asian pear and European pear. Although several pear genomes are available, most of the released versions are fragmented and not chromosome-level high-quality. In this study, we report two high-quality genomes for Pyrus bretschneideri Rhed. cv. ‘Danshansuli’ (DS) and Pyrus communis L. cv. ‘Conference’ (KFL), which represent the predominant Asian and European cultivars, respectively, with nearly telomere-to-telomere (T2T) gap-free level. The finally assembled genome sizes for DS and KFL were 510.98 Mb and 510.71 Mb, respectively, with Contig N50 of 29.47 Mb and 30.47 Mb, where each chromosome was represented by a single contig. The DS and KFL genomes yielded a total of 46,394 and 44,702 protein-coding genes, respectively. Among these genes, the functional annotation accounted for 96.47% and 96.46% in the DS and KFL genomes. The two novels nearly T2T genomic information offers an invaluable resource for comparative genomics, genetic diversity analysis, molecular breeding strategies, and functional exploration.