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Abstract Objective Evidence regarding the relationship between the hepatic steatosis index (HSI) and glycemic conversion outcomes in individuals with impaired fasting glucose (IFG) is still limited. Our study aims to explore the role of HSI in the reversion to normoglycemia or the progression to diabetes among Chinese IFG individuals. Methods We conducted a retrospective analysis using data from 11,327 IFG individuals who had undergone wellness examinations at Rich Healthcare Group. To analyze the association between the baseline HSI and glucose status conversion, a Cox regression model was used, and the hazard ratio (HR) and 95% confidence interval (CI) were computed. A generalized additive model was used to examine non-linear relationships. A two-piecewise binary logistic regression model was employed to further elucidate the non-linearity. Sensitivity and subgroup analyses were also conducted. Results Over an observation period spanning 33,892 person-years, the rate of normoglycemia reversion was found to be 41.75%, whereas the rate of progression to diabetes was 11.63%. After accounting for potential confounding variables, our analysis demonstrated that among IFG individuals, there was an inverse relationship between HSI and the likelihood of returning to normoglycemia (HR = 0.93, 95% CI: 0.90–0.96, P

Abstract Background Treacher Collins syndrome (TCS, MIM #154500), a severe congenital disorder, predominantly involves dysplasia of craniofacial bones and is characterized by features such as downslanting palpebral fissures, lower eyelid colobomas, microtia, and other craniofacial anomalies. Despite its clinical importance, the underlying pathogenic mutations in TCS remain largely uncharacterized, representing a critical knowledge gap for researchers in the field. Results To address this, we performed mutation screening on a familial TCS case (trio) and 11 sporadic cases from a Chinese population. We identified 11 mutations predominantly localized to the central repeat domain (CRD) and the C-terminal domain (CTD, including the nuclear localization sequence) of TCOF1. The de novo frameshift mutation identified in the trio led to TCOF1 truncation, disrupting the central repeat domain crucial for binding transcriptional factors. Immunoprecipitation assays revealed that this pathogenic mutation attenuates the interaction between TCOF1 and transcription-related proteins, such as Pol II. Furthermore, cellular luciferase assays demonstrated that the mutation compromises the nuclear localization capability of TCOF1. Conclusions Our findings establish TCOF1 as the primary pathogenic gene in this Chinese TCS cohort, with mutations predominantly in the CRD and CTD, thereby expanding the known mutation spectrum of TCS and informing its prevention strategies.

Abstract Lane detection is one of the key functions to ensure the safe driving of autonomous vehicles, and it is a challenging task. In real driving scenarios, external factors inevitably interfere with the lane detection system, such as missing lane markings, harsh weather conditions, and vehicle occlusion. To enhance the accuracy and detection speed of lane detection in complex road environments, this paper proposes an end-to-end lane detection model with a pure Transformer architecture, which exhibits excellent detection performance in complex road scenes. Firstly, a separable lane multi-head attention mechanism based on window self-attention is proposed. This mechanism can establish the attention relationship between each window faster and more effectively, reducing the computational cost and improving the detection speed. Then, an extended and overlapping strategy is designed, which solves the problem of insufficient information interaction between two adjacent windows of the standard multi-head attention mechanism, thereby obtaining more global information and effectively improving the detection accuracy in complex road environments. Finally, experiments are carried out on four data sets. The experimental results indicate that the proposed method is superior to the existing state of the arts method in terms of both effectiveness and efficiency.

Abstract CD8+T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8+T cells suppression in hepatocellular carcinoma (HCC). Our findings reveal that VCP suppresses the activation, expansion, and cytotoxic capacity of CD8+T cells both in vitro and in vivo, significantly contributing to the immunosuppressive nature of the TME. Mechanistically, VCP stabilizes the expression of glycerol-3-phosphate dehydrogenase 1-like protein (GPD1L), leading to the accumulation of glycerol-3-phosphate (G3P), a downstream metabolite of GPD1L. The accumulated G3P diffuses into the TME and directly interacts with SRC-family tyrosine kinase LCK, a critical component of the T-cell receptor (TCR) signaling pathway in CD8+T cells. This interaction heightens the phosphorylation of Tyr505, a key inhibitory residue, ultimately reducing LCK activity and impairing downstream TCR signaling. Consequently, CD8+T cells lose their functional capacity, diminishing their ability to fight against HCC. Importantly, we demonstrated that targeting VCP in combination with anti-PD1 therapy significantly suppresses HCC tumor growth and restores the anti-tumor function of CD8+T cells, suggesting synergistic therapeutic potential. These findings highlight a previously unrecognized mechanism involving VCP and G3P in suppressing T-cell-mediated immunity in the TME, positioning VCP as a promising upstream target for enhancing immunotherapy in HCC.

Abstract Spinal cord injury (SCI) is a profound ailment lacking a well-defined molecular mechanism and effective treatments. Cuproptosis, identified as a recently discovered cell death pathway, exhibits diverse roles in various cancers. Nevertheless, its involvement in SCI is yet to be elucidated. Firstly, the RNA sequencing data of 1, 3, 7 dpi SCI samples were collected from GEO database. We performed differential expression analysis on these samples with varying cuproptosis-related scores calculating by ssGSEA. Subsequently, we conducted enrichment analyses with KEGG, GO, and GSEA. Simultaneously, we executed WGCNA analysis using cuproptosis-related scores, selecting the most relevant module for enrichment analysis. Hub genes were identified at the intersection of PPI analysis results from two modules and cuproptosis-related DEGs. Additionally, relying on the immune infiltration landscape associated with cuproptosis, we carried out immune cell correlation analysis on hub genes. Finally, to corroborate our earlier findings, we utilized single-cell RNA-seq analysis and in vitro experimental validation. Based on ssGSEA, differential expression analysis and WGCNA analysis, we identified two modules that were highly relevant to cell division and immune processes, respectively. From these modules, we identified two hub genes, Cd48 and Mpeg1, which exhibited a strong positive correlation (R = 0.92) and shared similar pathways. Furthermore, we observed a positive correlation between M2 macrophages and Cd48/Mpeg1. To validate our findings, we performed external cohort validation using a single-cell RNA sequencing dataset. The results confirmed that Mpeg1 was highly expressed in microglia (macrophages in center nervous system) following spinal cord injury. Additionally, we conducted in vitro experiments to further validate the molecular functions of Mpeg1 in SCI. In summary, targeting Mpeg1, as well as cuproptosis and immune cell infiltration, holds promise as a potential strategy for reducing spinal cord tissue damage and promoting recovery after SCI. These findings provide valuable insights for future therapeutic interventions.

Abstract Studies have confirmed that elevated glucose levels could lead to renal fibrosis through the process of ferroptosis. Liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, is a potential treatment option for diabetes. This study aimed to examine the potential of liraglutide (LIRA) in inhibiting ferroptosis and reducing high glucose-induced renal fibrotic injury in mice, and whether the Fsp1-CoQ10-NAD(P)H signal pathway is a mechanism for this effect. In our study, we used db/db mice to simulate Type 2 diabetes mellitus (T2DM). The mice were intraperitoneally injected with LIRA (200 µg/kg/d) daily for 6 weeks. Renal function, pathologic changes, lipid peroxidation levels, iron levels, and ferroptosis were assessed. First, LIRA ameliorated renal dysfunction and fibrosis in db/db mice. Second, LIRA inhibited lipid peroxidation by up-regulating T-SOD, GSH-Px, and GSH activities as well as down-regulating the levels of 8-OHDG, MDA, LPO, 4-HNE, 12-Lox, and NOX4 in db/db mice. In addition, LIRA attenuated iron deposition by decreasing the expression of TfR1 and increasing the expression of FPN1. Meanwhile, LIRA reduced high levels of high glucose-induced cell viability decline and intracellular lipid peroxidation. Furthermore, LIRA inhibited ferroptosis by adjusting the Fsp1-CoQ10-NAD(P)H pathway in vivo and in vitro. These findings suggested that LIRA attenuated kidney fibrosis injury in db/db mice by inhibiting ferroptosis through the Fsp1-CoQ10-NAD(P)H pathway.

Abstract The cladding of fast reactor fuel rods, made of stainless steel, presents significant challenges in cutting due to its ductility, which leads to increased tool wear and poor cut quality with traditional mechanical methods. Laser cutting has emerged as a superior alternative, offering non-contact precision, high efficiency, and suitability for radioactive environments. This study systematically investigates the effects of laser cutting parameters—cutting speed, focal position, power, and gas pressure—on the cutting quality of simulated fast reactor fuel rods. The results show that optimal cutting is achieved with a cutting speed of 1 m/min, a focal position between − 20 and − 25 mm, a laser power between 7200 and 9600 W, and a gas pressure of 10 MPa. These parameters provide the best balance between cutting efficiency, surface roughness, and minimal slag formation. This study contributes valuable insights into optimizing laser cutting technology for nuclear fuel rod processing, with potential applications in fuel reprocessing and decommissioning.

Abstract In the life cycle of the oriental fruit fly where larvae reside within fruits and adults exhibit high activity, the pupal stage occurs in the soil, closely tied to agricultural soil management. This study investigates the impact of four variables (body orientation, burial depth, soil particle size, and pH) on Bactrocera dorsalis’ physiological preferences, eclosion rates, and pupal stage duration. Notably, body orientation, burial depth, soil texture (particle size), and pH affect eclosion rates. The fruit fly demonstrates a preference for a supine position during eclosion, with average eclosion rates of 97.33%, contrasting with decreases to 78.00% in a head-down position. Soil with mixed particle sizes is detrimental to pupal eclosion, reducing the eclosion rate to 56.67%. And at a pH of 9.98, eclosion rates decrease to 16.67%. These factors significantly influence eclosion rates However, these factors do not significantly alter the duration of the pupal stage, with mean changes not exceeding one day when experimental conditions are modified. These findings suggests that soil manipulations affecting these variables could reduce eclosion rates without compromising the uniformity of adult emergence. This study provides a foundation for environmentally friendly pest control practices and addresses gaps in the pupal stage research of the oriental fruit fly.

Abstract The injection molding procedure and the compression molding procedure of foamed polypropylene composite are studied. The pore diameter, pore density, and microscopic topography for polypropylene composites was studied by experiments of slicing samples. The foamed temperature is very important for foamed property of the foamed polypropylene composite materials. To analyze the effect of temperature distribution, the virtual boundary meshfree Galerkin method (VBMGM) was employed the radial basis function interpolation method to obtain a detailed discretization formula. The temperature of experiment and numerical calculation from zone a to zone d in different zones of the injection molding procedure is reduced from 406.35 K to 311.63 K; the temperature from Ma zone to Md zone in the compression molding procedure is reduced from 326.35 K to 309.14 K. The experimental observation of the injection molding procedure shows that the foamed property in zone c is ideal, and the average pore diameter and pore density are 26.5 µm and 2.43×109 cells·cm−3 respectively. According to the experimental observation of compression molding process, the foamed property in Md zone is ideal, and the average pore diameter and pore density are 131.2 µm and 6.3×104 cells·cm−3. These results are of great significance to the foam molding of polypropylene composites.

Abstract In addressing the finite element model and actual structural error of the sprayer boom truss, this study aims to achieve high-precision dynamic characteristics, enhance simulation credibility, make informed optimization decisions, and reduce testing costs. The research investigates the dynamic behavior of the sprayer boom truss through modal experiments and finite element simulations. Initially, modal parameters of the sprayer boom are obtained through experimental testing, validating their reasonableness and reliability. Subsequently, Ansys Workbench18.0 simulation software was employed to analyze the finite element model of the sprayer boom, revealing a maximum relative error of 11.93% compared to experimental results. To improve accuracy, a kriging-based response surface model was constructed, and multi-objective parameter adjustments using the MOGA algorithm reduce the maximum relative error to 4.6%. Sensitivity analysis further refines the model by optimizing target parameters, resulting in a maximum relative error of 4.96%. These findings demonstrate the effective enhancement of the corrected finite element model’s precision, with the response surface method outperforming sensitivity analysis the maximum relative error between the updated finite element model and experimental results was within the engineering allowable range, confirming the effectiveness of the updated model.

Abstract Research exploring the link between immune cell profiles and the development of endometritis remains scant. This gap necessitates further study to decode the complex interrelations influencing this condition. In this analysis, we leveraged two-sample Mendelian randomization to examine the causal ties between the phenotypes of immune cells and the incidence of endometritis. Our evaluation hinged on data from 3757 participants hailing from Sardinia, focusing on a diverse array of 731 immune phenotypes, and cross-referenced with endometritis data sourced from the UK Biobank. To ensure rigor, we performed sensitivity analyses, utilized MR-Egger and MR-Presso to check for pleiotropy, and applied Cochran’s Q test for assessing the heterogeneity of our findings. Our investigation identified numerous immune characteristics associated with endometritis. For certain immune traits, a lower risk of endometritis was observed, including: Absolute Counts of CD39 + CD4 + T cells, CD25 + CD39 + CD4 regulatory T cells, and CD25 + + CD8 + T cells; Absolute Counts of Switched Memory B cells; CD19 expression on IgD + CD38dim and Switched Memory B cells; CD20 expression on IgD + CD38− Unswitched Memory B cells; percentage of Switched Memory B cells among lymphocytes; CD16-CD56 expression on HLA DR + Natural Killer cells; percentage of CD11c + CD62L− monocytes; CD86 expression on monocytes; CCR2 expression on CD14 + CD16 + monocytes; and CD14 expression on Monocytic Myeloid-Derived Suppressor Cells, with Odds Ratios (ORs) between 0.413 and 0.703. On the contrary, increased risks of endometritis were linked with: the percentage of Effector Memory CD4 + T cells within the CD4 + T cell population; percentages of HLA DR + T cells and HLA DR + CD8 + T cells among T cells; CD4 expression on CD28 + CD4 + T cells; CD20 expression on CD20- CD38- B cells; percentage of IgD + CD24 + B cells within the B cell population; CD62L expression on CD62L + myeloid Dendritic Cells; and Absolute Counts of Plasmacytoid Dendritic Cells, with ORs from 1.473 to 2.677, indicating these traits potentially elevate the risk of developing endometritis. Our research delineates distinct causal links between specific immune cell phenotypes and endometritis, offering new perspectives that could contribute to the pinpointing of new therapeutic avenues for this condition.

ObjectivesThis case-control study aims to clarify the impact of single nucleotide polymorphisms (SNPs) within the P2X7 gene on susceptibility to type 2 diabetes mellitus (T2DM) and to evaluate their association with diabetic complications.MethodsThis study is comprised with 200 T2DM cases and 200 healthy controls. Seven candidate SNP loci were screened, and TaqMan-MGB real-time PCR technology was used to determine the polymorphic variants of P2X7. Different genotype and allele frequencies were compared by Pearson's χ2 tests and logistic regression analysis.ResultsThree P2X7 SNPs were found to be associated with T2DM risk. Specifically, rs7958311 GA (OR = 1.323, p = 0.002), rs7958311 AA (OR = 1.508, p = 0.038), rs208294 CC (OR = 1.854, p = 0.042) showed a higher susceptibility to T2DM, whilst rs11065464 CA (OR = 0.614, p = 0.022) was associated with a reduced risk. Logistic regression analysis indicated that rs7958311 was linked to an increased risk for nephropathy (OR = 1.833, p = 0.022), but with a decreased risk for peripheral artery disease (OR = 0.550, p = 0.042). Additionally, rs208294 was identified as a risk factor for peripheral neuropathy (OR = 2.101, p = 0.016).ConclusionsWe found that P2X7 polymorphisms are significantly associated with the risk of T2DM and its complications, suggesting that targeting P2X7 may offer a novel therapeutic strategy for the prevention and personal treatment of T2DM.

Surgical stress is one of the key factors that promote tumor metastasis and recurrence. Adopting corresponding treatment strategies based on the mechanism of surgical stress promoting tumor metastasis and recurrence is of great significance for improving the postoperative prognosis of tumor patients. This article summarized the mechanisms that may affect surgical stress-induced tumor metastasis and recurrences, such as shedding and colonization of circulating tumor cells, changes in postoperative immune microenvironment and postoperative endocrine hormone levels. It also outlined the treatment strategies related to postoperative hormone levels and cytokine regulation, immunotherapy, and tumor vaccines to provide references for the treatment of tumor metastasis and recurrence after surgery.

Abstract The current research looked at how to use the Internet of Things (IoT) to create a vital sign health monitoring system. Eight indications are employed to get critical patient information. Therefore, the number of nodes of the IoT embedded in the human body is 8, which have been worked on in different places of the body. Among the 8 nodes, node number 1 is located in the center of the grid (the center of the human body). The number of rounds is 9000 and the nodes are adopted with the initial energy of the nodes of 0.5 J and the radio range of 10 m. MATLAB software was used to simulate the WBAN network, which consists of IoT sensors embedded in the human body. The eight-item health assessment tool takes the following into account: pulse rate, blood pressure (mm Hg), serum cholesterol (mg/dl), temperature (°C), exercise-induced angina, and exercise-induced ST-wave depression, major blood vessels are counted using a medical procedure called endoscopy that involves examining the alveoli, which are small air sacs in the lungs where gas exchange occurs. We compared the number of major vessels at rest with the maximal heart rate during activity. The sensors were responsible for sending this data to the health center (base station). The data collected from the installation of these 8 sensors on 303 patients were collected and evaluated by machine learning method using MLP neural network method. Finally, it can be claimed that the present study has provided an automated method of determining the health of people using the IoT in a way that provides a state of health with an accuracy of over 99% and can be used in medical centers.

Objective This qualitative study aimed to analyse rectal cancer survivors’ lived experiences to identify facilitators and barriers to support access.Design We conducted one-on-one semi-structured interviews and employed thematic analysis to identify key themes and insights.Setting/participants Participants included eight rectal cancer survivors and three caregivers recruited at Texas Colorectal Collaborative sites.Results Results showed that adequate hospital resources, high health literacy and close connections with clinicians and peers who share similar experiences facilitate survivors’ access to social support. Conversely, ineffective healthcare team communication, financial challenges and low self-motivation hindered access.Conclusion Survivorship experiences were shaped by varying degrees of social support access, influenced by internal and external factors. We aim to establish a cross-institutional survivorship support network to address these factors, ensuring equitable access to support services and enhancing survivorship experiences.

Abstract Background Neuroinflammation is a characteristic pathological change of Alzheimer’s Diseases (AD). Microglia have been reported to participate in inflammatory responses within the central nervous system. However, the mechanism of microglia released exosome (EXO) contribute to communication within AD microenvironment remains obscure. Methods The interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay. Results Here, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading. Conclusion These results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.

Abstract Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1β (IL-1β), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.

Digital healthcare has rapidly evolved during and in the post-COVID pandemic era, expanding the roles and responsibilities of community pharmacists. Services like telepharmacy, e-prescriptions, remote medication therapy management, and digital monitoring of chronic conditions, have evolved into everyday routine pharmacy practices. Pharmacists are at the forefront and the most accessible healthcare professionals for patients and are increasingly pivotal in providing comprehensive patient care, including digital patient care services. To ensure that future generations of pharmacists are digitally competent, it is crucial that digital health education is provided to pharmacy students. Furthermore, fostering high-quality multidisciplinary research, particularly in collaboration with medicine and other health disciplines, is essential for advancing the digital health skills of the future pharmacy workforce. Despite the growing use of digital health technologies, there are significant between-country differences in digital health education, the clinical settings in which digital health technologies are used, and their implementation in day-to-day practice. This commentary summarizes key insights from the International Digital Health Workshop held at the University of Sydney in November 2023. To help ensure pharmacists are included as participants in future digital health research, recent advances in digital health education and interprofessional research projects across three universities from far-off world regions were presented. Participants discussed a possible collaborative, interprofessional, and international research project on chronic disease prevention using digital health technologies. The need for interdisciplinary digital health curricula was highlighted in the workshop discussions, specifically tailored to address the knowledge requirements of pharmacists and other healthcare professionals.

Soil organic carbon (SOC) is a crucial component of the global carbon cycle, playing a significant role in ecosystem health and carbon balance. In this study, we focused on assessing the surface SOC content in Shandong Province based on land use types, and explored its spatial distribution pattern and influencing factors. Machine learning methods including random forest (RF), extreme gradient boosting (XGBoost), and support vector machine (SVM) were employed to estimate the surface SOC content in Shandong Province using diverse data sources like sample data, remote sensing data, socio-economic data, soil texture data, topographic data, and meteorological data. The results revealed that the SOC content in Shandong Province was 8.78 g/kg, exhibiting significant variation across different regions. Comparing the model error and correlation coefficient, the XGBoost model showed the highest prediction accuracy, with a coefficient of determination (R²) of 0.7548, root mean square error (RMSE) of 7.6792, and relative percentage difference (RPD) of 1.1311. Elevation and Clay exhibited the highest explanatory power in clarifying the surface SOC content in Shandong Province, contributing 21.74% and 13.47%, respectively. The spatial distribution analysis revealed that SOC content was higher in forest-covered mountainous regions compared to cropland-covered plains and coastal areas. In conclusion, these findings offer valuable scientific insights for land use planning and SOC conservation.

Abstract Background The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. Methods Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. Results THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (

Abstract Background Aeromonas veronii is a very rare and highly pathogenic microorganism. We investigate the clinical characteristics and significance of endogenous endophthalmitis caused by Aeromonas veronii in our patient. Case presentation A 30-year-old Asian women with systemic lupus erythematosus, uremia, and hypertension developed acute infectious endophthalmitis caused by Aeromonas veronii. After emergency vitrectomy and antibiotic therapy, the clinical condition worsened requiring enucleation. Conclusions Aeromonas veronii can cause infection in the human eye, which can manifest as acute endophthalmitis. Early diagnosis and targeted therapy are important for successful treatment.

Abstract Background As a dual-function metabolite, succinate has emerged in cell function and plays a key signaling role in linking mitochondrial function to other cellular functions. Succinate accumulation in the cytoplasm is commonly associated with hypoxia in the microenvironment and immune cell activation. Extracellular succinate released into the microenvironment is considered an inflammatory alarm that can be sensed by its membrane receptor SUCNR1, which boosts proinflammatory responses and acts akin to classical hormones and cytokines. Succinate plays an important role in the development of inflammatory diseases. Whether succinate facilitates the progression of endometriosis (EMs), characterized by chronic inflammation and peritoneal adhesion, is worth exploring. Objective We mimicked the ectopic milieu in vitro and in vivo to evaluate the main source and potential role of succinate in endometriosis. We assessed the molecular and functional effects of succinate on macrophages and peritoneal mesothelial cells in peritoneal cavity. The effect of succinate/SUCNR1 signaling on ectopic endometrial stromal cells (ESCs) was further explored in this study. Methods In this study, we used targeted organic acid metabolomics analysis and in vitro assays to assess the potential accumulation of succinate in the peritoneal fluid of EMs patients. We examined its correlation with disease severity, Visual Analogue Scale, and the Endometriosis Fertility Index. Flow cytometry, enzyme linked immunosorbent assay, western blot assay, quantitative real-time PCR, and other molecular biology techniques were used to explore the potential mechanisms. Results By mimicking the ectopic milieu, we constructed an in vitro co-culture system and found that M1 polarized macrophages and that the peritoneal mesothelial cell line (HMrSV5) mainly released succinate into their microenvironment and activated the succinate receptor (SUCNR1) signal, which further polarized the macrophages and significantly enhanced the invasive survival of ESCs, and the adhesion to the peritoneum. We further investigated the pathological effects of extracellular succinate in vivo using a xenograft mouse models of endometriosis. Conclusions Succinate-SUCNR1 signaling facilitates the creation of inflammatory cells and plays a vital role in EMs progression and peritoneal adhesion. Our work on the molecular mechanisms underlying succinate accumulation and function will help elucidate the phenotypic mysteries of pain and infertility in EMs. Video Abstract

Abstract In this paper, we proposed a sliding mode control method for the bearingless permanent magnet slice motor for the blood pump based on the genetic particle swarm algorithm, which aims to solve the problems of strong coupling, strong interference, nonlinearity and uncertainty. Firstly, the mathematical model of rotor torque and suspension force of the bearingless permanent magnet slice motor is established. Secondly, the structure of sliding mode observer is deduced by designing sliding mode surface and control law. And, the performance parameters of sliding mode observer are optimized by the genetic particle swarm optimization algorithm. Thirdly, electromagnetic torque and suspension force control under this control method is studied by Simulink. Finally, the control method is applied to the control of the blood flow of the blood pump, and the rotation speed can effectively control the blood flow. The results indicate that compared with PID control and traditional sliding mode control methods, the sliding mode control method optimized by the genetic particle swarm optimization algorithm greatly improves the control performance of bearingless permanent magnet slice motor. The results show that the blood flow can meet expectations with a small error, which fully meets the blood perfusion requirements of the blood pump.

Abstract Background UV-induced cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The constant alterations of the lymphatic-centered immune microenvironment are essential in transforming from photoaging to cSCC. Studying the mechanism will be beneficial for new targets exploration to the early prediction of cSCC. Aims To investigate the dynamic changes and mechanism of the lymphatic-centered immune microenvironment in transforming from photoaging to cSCC induced by ultraviolet irradiation (UVR). Methods TIMER2.0 was used to analyze whether YAP1/VEGFC signaling pathway is involved in lymphangiogenesis in head and neck squamous cell carcinoma (HNSCC). Meanwhile, lymphatic-centered immune microenvironments alterations and the related cumulative survival time were also analyzed. With the accumulated UVR, skin photoaging developed and gradually progressed into actinic keratosis and cSCC on SKH-1 hairless mice. The skin lymphatic-centered immune microenvironment was evaluated at the 0th, 8th, 12th, 16-18th, and 20-24th week of UVR. Skin phenotype was assessed using optical coherence tomography (OCT) and skin image. H&E and Masson’s trichrome staining evaluated epidermis and dermis. The structure of lymphatic vessels (LVs), blood vessels, and different types of T cells were evaluated by immunohistochemistry staining. The expression of Piezo1 whose deletion in adult lymphatics led to substantial valve degeneration, VE-cadherin that maintained the permeability of LVs, and YAP1 were evaluated by immunohistochemistry staining as well. Besides, the drainage function of LVs was assessed by Evans Blue assay in vivo. Results The lymphatic function and immune cell infiltration underwent adaptive changes under continuous UVR. TIMER2.0 analysis indicated that VEGFC genes high expressed in HNSCC. YAP1 gene expression was positive correlated with VEGFC in HNSCC. LV density increased in human cSCC. More LVs in HNSCC were beneficial to prolong the survival time. VEGFC gene overexpression was positive correlated to CD8+T cell infiltration. More CD8A+T cells and CD8B+T cell infiltration in HNSCC extended survival time. When YAP1 gene overexpression and high infiltration of endothelial cells took place simultaneously might prolong the survival time of HNSCC patients. And high infiltration of CD8+T cells prolonged the survival time as well. In animal studies, UVR-induced eight weeks (photoaging) and 16–18 weeks (precancerous) were two turning points. The density of LVs in UV-8w was the least. When photoaged skin developed into AK lesions (UV-16-18w), LV slightly exceeded healthy skin and proliferated sharply in cSCC (UV-20-24w). YAP1 expression was almost consistent with LV but rose after the photoaging stage. The drainage of cSCC mice induced by UVR was better than that of photoaged skin and worse than that of health skin. The dynamic alterations of LVs number, Piezo1 expression, and collagen might be reasons for it. The expression of Piezo1 was in the highest point after 8 weeks of UVR, then gradually descended to the platform. The total T cells increased slowly, but the infiltration of CD4+T cells increased, and CD8+T cells decreased after eight weeks of UVR. The CD8+T cells and CD4+T cells increased sharply in UV-16-18w and UV-20-24w groups. Conclusion The lymphatic-centered immune microenvironment underwent adaptive changes under continuous UVR via regulating YAP1/VEGFC and Piezo1. During the formation of cSCC, there are two turning points, eight weeks (photoaging) and 16–18 weeks (precancerous). YAP1, Piezo1, LVs, and immune cells constantly changed with the skin state induced by UVR. According to these changes the process of cSCC can be identified in advance and intervene timely.

Abstract Background Pulmonary hypertension (PH), an infrequent disease, is characterized by excessive pulmonary vascular remodeling and proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its underlying molecular mechanisms remain unclear. Uncovering its molecular mechanisms will be beneficial to the treatment of PH. Methods Differently expressed genes (DEGs) in the lung tissues of PH patients were analyzed with a GEO dataset GSE113439. From these DEGs, we focused on TRIM59 which was highly expressed in PH patients. Subsequently, the expression of TRIM59 in the pulmonary arteries of PH patients, lung tissues of PH rat model and PASMCs cultured in a hypoxic condition was verified by quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Furthermore, the role of TRIM59 in PAMSC proliferation and pathological changes in PH rats was assessed via gain-of-function and loss-of-function experiments. In addition, the transcriptional regulation of YAP1/TEAD4 on TRIM59 was confirmed by qPCR, western blot, luciferase reporter assay, ChIP and DNA pull-down. In order to uncover the underlying mechanisms of TRIM59, a protein ubiquitomics and a CoIP- HPLC–MS/MS were companied to identify the direct targets of TRIM59. Results TRIM59 was highly expressed in the pulmonary arteries of PH patients and lung tissues of PH rats. Over-expression of TRIM59 accelerated the proliferation of PASMCs, while TRIM59 silencing resulted in the opposite results. Moreover, TRIM59 silencing mitigated the injuries in heart and lung and attenuated pulmonary vascular remodeling during PH. In addition, its transcription was positively regulated by YAP1/TEAD4. Then we further explored the underlying mechanisms of TRIM59 and found that TRIM59 overexpression resulted in an altered ubiquitylation of proteins. Accompanied with the results of CoIP- HPLC–MS/MS, 34 proteins were identified as the direct targets of TRIM59. Conclusion TRIM59 was highly expressed in PH patients and promoted the proliferation of PASMCs and pulmonary vascular remodeling, thus contributing to the pathogenesis of PH. It is indicated that TRIM59 may become a potential target for PH treatment.

Abstract Antibody technology is widely used in the fields of biomedical and clinical therapies. Nonetheless, the complex in vitro expression of recombinant proteins, long production cycles, and harsh storage conditions have limited their applications in medicine, especially in clinical therapies. Recently, this dilemma has been overcome to a certain extent by the development of mRNA delivery systems, in which antibody-encoding mRNAs are enclosed in nanomaterials and delivered to the body. On entering the cytoplasm, the mRNAs immediately bind to ribosomes and undergo translation and post-translational modifications. This process produces monoclonal or bispecific antibodies that act directly on the patient. Additionally, it eliminates the cumbersome process of in vitro protein expression and extends the half-life of short-lived proteins, which significantly reduces the cost and duration of antibody production. This review focuses on the benefits and drawbacks of mRNA antibodies compared with the traditional in vitro expressed antibodies. In addition, it elucidates the progress of mRNA antibodies in the prevention of infectious diseases and oncology therapy.

Abstract Allergic rhinitis (AR) is a prevalent chronic inflammatory disease of the nasal mucosa primarily characterized by symptoms, such as nasal itching, sneezing, runny nose, and nasal congestion. It has a high recurrence rate and low cure rate, with a lack of effective drugs for treatment. The current approach to management focuses on symptom control. High mobility group box-1 (HMGB1) is a highly conserved non-histone protein widely present in the nucleus of eukaryotes. It is recognized as a proinflammatory agent, and recent studies have demonstrated its close association with AR. Here, we will elaborate the role and mechanism of HMGB1 in AR, so as to reveal the potential value of HMGB1 in the occurrence and development of AR, and provide a new target for clinical research on the treatment of AR.

BackgroundTo investigate the impacts of the COVID-19 pandemic on the health workforce, we aimed to develop a framework that synergizes natural language processing (NLP) techniques and human-generated analysis to reduce, organize, classify, and analyze a vast volume of publicly available news articles to complement scientific literature and support strategic policy dialogue, advocacy, and decision-making. ObjectiveThis study aimed to explore the possibility of systematically scanning intelligence from media that are usually not captured or best gathered through structured academic channels and inform on the impacts of the COVID-19 pandemic on the health workforce, contributing factors to the pervasiveness of the impacts, and policy responses, as depicted in publicly available news articles. Our focus was to investigate the impacts of the COVID-19 pandemic and, concurrently, assess the feasibility of gathering health workforce insights from open sources rapidly. MethodsWe conducted an NLP-assisted media content analysis of open-source news coverage on the COVID-19 pandemic published between January 2020 and June 2022. A data set of 3,299,158 English news articles on the COVID-19 pandemic was extracted from the World Health Organization Epidemic Intelligence through Open Sources (EIOS) system. The data preparation phase included developing rules-based classification, fine-tuning an NLP summarization model, and further data processing. Following relevancy evaluation, a deductive-inductive approach was used for the analysis of the summarizations. This included data extraction, inductive coding, and theme grouping. ResultsAfter processing and classifying the initial data set comprising 3,299,158 news articles and reports, a data set of 5131 articles with 3,007,693 words was devised. The NLP summarization model allowed for a reduction in the length of each article resulting in 496,209 words that facilitated agile analysis performed by humans. Media content analysis yielded results in 3 sections: areas of COVID-19 impacts and their pervasiveness, contributing factors to COVID-19–related impacts, and responses to the impacts. The results suggest that insufficient remuneration and compensation packages have been key disruptors for the health workforce during the COVID-19 pandemic, leading to industrial actions and mental health burdens. Shortages of personal protective equipment and occupational risks have increased infection and death risks, particularly at the pandemic’s onset. Workload and staff shortages became a growing disruption as the pandemic progressed. ConclusionsThis study demonstrates the capacity of artificial intelligence–assisted media content analysis applied to open-source news articles and reports concerning the health workforce. Adequate remuneration packages and personal protective equipment supplies should be prioritized as preventive measures to reduce the initial impact of future pandemics on the health workforce. Interventions aimed at lessening the emotional toll and workload need to be formulated as a part of reactive measures, enhancing the efficiency and maintainability of health delivery during a pandemic.

Phosphorus is one of the lowest elements absorbed and utilized by plants in the soil. SPX domain-containing genes family play an important role in plant response to phosphate deficiency signaling pathway, and related to seed development, disease resistance, absorption and transport of other nutrients. However, there are no reports on the mechanism of SPX domain-containing genes in response to phosphorus deficiency in eggplant. In this study, the whole genome identification and functional analysis of SPX domain-containing genes family in eggplant were carried out. Sixteen eggplant SPX domain-containing genes were identified and divided into four categories. Subcellular localization showed that these proteins were located in different cell compartments, including nucleus and membrane system. The expression patterns of these genes in different tissues as well as under phosphate deficiency with auxin were explored. The results showed that SmSPX1, SmSPX5 and SmSPX12 were highest expressed in roots. SmSPX1, SmSPX4, SmSPX5 and SmSPX14 were significantly induced by phosphate deficiency and may be the key candidate genes in response to phosphate starvation in eggplant. Among them, SmSPX1 and SmSPX5 can be induced by auxin under phosphate deficiency. In conclusion, our study preliminary identified the SPX domain genes in eggplant, and the relationship between SPX domain-containing genes and auxin was first analyzed in response to phosphate deficiency, which will provide theoretical basis for improving the absorption of phosphorus in eggplants through molecular breeding technology.

Objective To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) for early perforation of the appendix in patients with acute appendicitis (AA). Methods Two hundred and 80eighty patients with the first episode of AA within 48 hours and not yet treated with antibiotics were included in this study retrospectively; divided into two groups by the presence or absence of perforation. The clinical data, traditional inflammatory indexes, and NLR were compared between the two groups. The predictive value of inflammatory indexes on the early appendiceal perforation was explored. Results Patients in the perforated group were older, with higher blood WBC, NEU% and NLR, lower LYM% and PLT, higher serum CRP and PCT, and longer hospitalization time. Multivariate regression analysis revealed that high WBC, NEU%, NLR, CRP, PCT, and low LYM% were independent risk factors for early appendiceal perforation. The ROC curves revealed that the predictive value of WBC, CRP, and PCT for early appendiceal perforation was low. NLR, LYM%, and NEU% had a higher predictive value, with AUC values of 0.947, 0.928, and 0.920, respectively. NLR had the highest predictive value. The diagnostic Cut-off value of NLR is 10.83 with a sensitivity of 0.963, and a specificity of 0.850. Conclusion NLR can be used as an effective and sensitive predictive maker of early appendiceal perforation in AA patients. It is easy to generate from existing routine clinical laboratory testing for AA and can be included in complete blood count (CBC) as a routine or add-on value.

Abstract Insulin resistance (IR) is associated with a variety of cardiovascular diseases, but there are few studies on the correlation between IR and calcified aortic stenosis (CAS). In this study, the triglyceride-glucose (TyG) index, which reflects IR, was used to investigate the correlation between IR and CAS. The study included 183 elderly patients who were diagnosed with CAS by transthoracic echocardiography. The patients were matched 1:1 according to age and sex, and elderly patients who were hospitalized during the same period and underwent transthoracic echocardiography without aortic stenosis were included as the control group. The relationship between the TyG index and CAS was analyzed by a multivariable logistic regression model, curve fitting and trend test. Multivariate logistic regression analysis showed that the TyG index as a continuous variable was negatively associated with CAS (P

This paper explores whether it is feasible to use the RGB color information in images of wheat canopies that were exposed to low temperatures during the growth season to achieve fast, non-destructive, and accurate determination of the severity of any freeze injury it may have incurred. For the study presented in this paper, we compared the accuracy of a number of algorithmic classification models using either meteorological data reported by weather services or the color gradation skewness-distribution from high-definition digital canopy images acquired in situ as inputs against a reference obtained by manually assessing the severity of the freeze injury inflicted upon wheat populations at three experimental stations in Shandong, China. The algorithms we used to construct the models included in our study were based on either K-means clustering, systematic clustering, or naïve Bayesian classification. When analyzing the reliability of our models, we found that, at more than 85%, the accuracy of the Bayesian model, which used the color information as inputs and involved the use of prior data in the form of the reference data we had obtained through manual classification, was significantly higher than that of the models based on systematic or the K-means clustering, which did not involve the use of prior data. It was interesting to note that the determination accuracy of algorithms using meteorological factors as inputs was significantly lower than that of those using color information. We also noted that the determination accuracy of the Bayesian model had some potential for optimization, which prompted us to subject the inputs of the model to a factor analysis in order to identify the key independent leaf color distribution parameters characterizing wheat freeze injury severity. This optimization allowed us to improve the determination accuracy of the model to over 90%, even in environments comprising several different ecological zones, as was the case at one of our experimental sites. In conclusion, our naïve Bayesian classification algorithm, which uses six key color gradation skewness-distribution parameters as inputs and involves the use of prior data in the form of manual assessments, qualifies as a contender for the development of commercial-grade wheat freeze injury severity monitoring systems supporting post-freeze management measures aimed at ensuring food security.

Abstract Hypothermia is a promising neuroprotective treatment. This study aims to explore and optimize the intervention scheme of intra-arterial hypothermia (IAH) in a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model. The MCAO/R model was established with a thread that could be retracted 2 h after occlusion. Cold normal saline was injected into the internal carotid artery (ICA) through a microcatheter in different infusion conditions. Grouping followed an orthogonal design (L9[34]) based on three critical factors closely associated with IAH: perfusate temperature (4, 10, 15 °C), infusion flow rate (1/3, 1/2, 2/3 blood flow rate of ICA), and duration (10, 20, 30 min), resulting in 9 subgroups (H1, H2 to H9). A myriad of indexes were monitored, such as vital signs, blood parameters, changes in local ischemic brain tissue temperature (Tb), ipsilateral jugular venous bulb temperature (Tjvb), and the core temperature of the anus (Tcore). After 24 h and 72 h of cerebral ischemia, cerebral infarction volume, cerebral water content, and neurological function were assessed to explore the optimal IAH conditions. The results revealed that the three critical factors were independent predictors for cerebral infarction volume, cerebral water content, and neurological function. The optimal perfusion conditions were 4 °C, 2/3 RICA (0.50 ml/min) for 20 min, and there was a significant correlation between Tb and Tjvb (R = 0.994, P

Abstract Urinary incontinence is one of the common clinical problems of females passing middle age. Traditional pelvic floor muscle training to alleviate urinary incontinence is too dull and unpleasant. Therefore, we were motivated to purpose a modified lumbo-pelvic exercise training incorporating simplified dancing components with pelvic floor muscle training. The objective of this study was to evaluate the 16-week modified lumbo-pelvic exercise program that incorporated dance and abdominal drawing-in maneuvers. Middle-aged females were randomly assigned into the experimental (n = 13) and control (n = 11) groups. Compared to the control group, the exercise group significantly reduced body fat, visceral fat index, waistline, waist-hip ratio, perceived incontinence score, frequency of urine leakage, and pad testing index (p

Abstract Background Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of chemotherapy with poorly understood mechanisms and few treatments. High-mobility group box 1 (HMGB1)-induced neuroinflammation is the main cause of CIPN. Here, we aimed to illustrate the role of the macrophage scavenger receptor A1 (SR-A1) in HMGB1 clearance and CIPN resolution. Methods Oxaliplatin (L-OHP) was used to establish a CIPN model. Recombinant HMGB1 (rHMGB1) (his tag) was used to evaluate the phagocytosis of HMGB1 by macrophages. Results In the clinic, HMGB1 expression and MMP-9 activity were increased in the plasma of patients with CIPN. Plasma HMGB1 expression was positively correlated with the cumulative dose of L-OHP and the visual analog scale. In vitro, engulfment and degradation of rHMGB1 increased and inflammatory factor expression decreased after AMP-activated protein kinase (AMPK) activation. Neutralizing antibodies, inhibitors, or knockout of SR-A1 abolished the effects of AMPK activation on rHMGB1 engulfment. In vivo, AMPK activation increased SR-A1 expression in the dorsal root ganglion, decreased plasma HMGB1 expression and MMP-9 activity, and attenuated CIPN, which was abolished by AMPK inhibition or SR-A1 knockout in the CIPN mice model. Conclusion Activation of the AMPK/SR-A1 axis alleviated CIPN by increasing macrophage-mediated HMGB1 engulfment and degradation. Therefore, promoting HMGB1 clearance may be a potential treatment strategy for CIPN. Video abstract

Abstract Soil microbial community composition plays a key role in the decomposition of organic matter, while the quality of exogenous organic matter (EOM: rice straw, roots and pig manure) can influence soil chemical and biological properties. However, the evidences of the effect of combination of crop residues and pig manure on the changes in soil microbial community and enzymes activities are scarce. A greenhouse pot experiment was conducted to investigate the potential effect of EOM by analyzing soil properties, enzyme activities and microbial communities. The experiment consisted of eight treatments: CK (control), S (1% (w/w) rice straw), R (1% (w/w) rice root), SR (1% (w/w) rice straw + 1% (w/w) rice root), and added 1% (w/w) pig manure to CK, S, R and SR, respectively. Results showed that the straw treatment significantly increased the microbial biomass (carbon and nitrogen) and total carbon and nitrogen contents, cellulase and β-1,4-glucosidase activities, bacteria (i.e., gram-positive bacteria and gram-negative bacteria) PLFAs contents relative to CK regardless of whether pig manure was added. Moreover, the interaction between crop residues (e.g., straw and roots) and pig manure significantly influenced the contents of microbial biomass nitrogen and microbial biomass phosphorus, and the ratio of gram-positive bacteria to gram-negative bacteria. Redundance analysis confirmed that pH, nitrate nitrogen, ammonium nitrogen and dissolve organic carbon contents were significantly associated with soil microbial community under crop residues without pig manure addition. Furthermore, the experiment results showed that pig manure application not only provided more abundant nutrients (C, N and P) but also induced higher microbial and enzymatic activity compared with no pig manure addition. Our findings suggest that the combination of above-ground straw and pig manure is a better option for improving the functions of soil ecosystem.

Abstract Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates the pharmacotherapy for CNS disorders as the most chemical drugs and biopharmaceuticals have been impeded to enter the brain. Insufficient drug delivery into the brain leads to low therapeutic efficacy as well as aggravated side effects due to the accumulation in other organs and tissues. Recent breakthrough in materials science and nanotechnology provides a library of advanced materials with customized structure and property serving as a powerful toolkit for targeted drug delivery. In-depth research in the field of anatomical and pathological study on brain and BBB further facilitates the development of brain-targeted strategies for enhanced BBB crossing. In this review, the physiological structure and different cells contributing to this barrier are summarized. Various emerging strategies for permeability regulation and BBB crossing including passive transcytosis, intranasal administration, ligands conjugation, membrane coating, stimuli-triggered BBB disruption, and other strategies to overcome BBB obstacle are highlighted. Versatile drug delivery systems ranging from organic, inorganic, and biologics-derived materials with their synthesis procedures and unique physio-chemical properties are summarized and analyzed. This review aims to provide an up-to-date and comprehensive guideline for researchers in diverse fields, offering perspectives on further development of brain-targeted drug delivery system.

Abstract A new, precast concrete frame beam-column connection is designed in this research. The connection adopts the assembly mode of the precast column and seam area jointly to maintain the integrity of the joint area and increase the assembly efficiency. Based on the conventional grouting sleeve connection, a disc spring device is constructed on the beam end to improve the ductility of the joint. Ten connecting specimens were tested under low cyclic loads, including two monolithic connections, four ordinary precast connections, and four new precast connections. The test parameters included the joint type and axial pressure ratio, and the difference in the seismic performance was determined by evaluating the failure mode, hysteresis characteristics, stiffness degradation, energy dissipation, and shear deformation of the joint area. Compared to monolithic connections, conventional precast connections display similar hysteresis characteristics. Although their ductility is slightly lower, their bearing capacity is higher. Compared with the previous two connections, the new connection with the built-in disc spring device has superior seismic performance. The axial pressure ratio is a significant aspect in determining the failure mode of the precast connection, and the specimen exhibits less shear damage at a larger axial pressure ratio.

Abstract Background Cancer associated fibroblasts (CAFs) communicate metabolically with tumor genesis and development. Rocuronium bromide (RB) is reported to exert certain inhibitory effect on tumor. Here, we investigate the role of RB in esophageal cancer (EC) malignant progression. Methods Tumor xenograft models with EC cells were locally and systemically administrated with RB to detect the influence of different administrations on tumor progression. Mouse CAFs PDGFRα+/F4/80− were sorted by Flow cytometry with specific antibodies. CAFs were treated with RB and co-cultured with EC cells. The proliferation, invasion and apoptosis assays of EC cells were performed to detect the influences of RB targeting CAFs on EC cell malignant progression. Human fibroblasts were employed to perform these detections to confirm RB indirect effect on EC cells. The gene expression changes of CAFs response to RB treatment were detected using RNA sequencing and verified by Western blot, immunohistochemistry and ELISA. Results Tumors in xenograft mice were observed significantly inhibited by local RB administration, but not by systemic administration. Moreover EC cells did not show obvious change in viability when direct stimulated with RB in vitro. However, when CAFs treated with RB were co-cultured with EC cells, obvious suppressions were observed in EC cell malignancy, including proliferation, invasion and apoptosis. Human fibroblasts were employed to perform these assays and similar results were obtained. RNA sequencing data of human fibroblast treated with RB, and Western blot, immunohistochemistry and ELISA results all showed that CXCL12 expression was significantly diminished in vivo and in vitro by RB. EC cells direct treated with CXCL12 showed much higher malignancy. Moreover cell autophagy and PI3K/AKT/mTOR signaling pathway in CAFs were both suppressed by RB which can be reversed by Rapamycin pretreatment. Conclusions Our data suggest that RB could repress PI3K/AKT/mTOR signaling pathway and autophagy to block the CXCL12 expression in CAFs, thereby weakening the CXCL12-mediated EC tumor progression. Our data provide a novel insight into the underlying mechanism of RB inhibiting EC, and emphasize the importance of tumor microenvironment (cytokines from CAFs) in modulating cancer malignant progression.

Abstract Background Heart failure (HF) after myocardial infarction (MI) is a prevalent disease with a poor prognosis. Relieving pathological cardiac remodeling and preserving cardiac function is a critical link in the treatment of post-MI HF. Thus, more new therapeutic targets are urgently needed. The expression of ADAM17 is increased in patients with acute MI, but its functional role in post-MI HF remains unclear. Methods To address this question, we examined the effects of ADAM17 on the severity and prognosis of HF within 1 year of MI in 152 MI patients with or without HF. In mechanistic studies, the effects of ADAM17 on ventricular remodeling and systolic function were extensively assessed at the tissue and cellular levels by establishing animal model of post-MI HF and in vitro hypoxic cell model. Results High levels of ADAM17 predicted a higher incidence of post-MI HF, poorer cardiac function and higher mortality. Animal studies demonstrated that ADAM17 promoted the occurrence of post-MI HF, as indicated by increased infarct size, cardiomyocyte hypertrophy, myocardial interstitial collagen deposition and cardiac failure. ADAM17 knock down significantly improved pathological cardiac remodeling and cardiac function in mice with MI. Mechanistically, activated ADAM17 inhibited the cardioprotective effects of ACE2 by promoting hydrolytic shedding of the transmembrane protein ACE2 in cardiomyocytes, which subsequently mediated the occurrence of cardiac remodeling and the progression of heart failure. Moreover, the activation of ADAM17 in hypoxic cardiomyocytes was dependent on p38 MAPK phosphorylation at threonine 735. Conclusions These data highlight a novel and important mechanism for ADAM17 to cause post-MI HF, which will hopefully be a new potential target for early prediction or intervention of post-MI HF. Video abstract

Abstract PANoptosis, a programmed cell death, shares key characteristics of apoptosis, pyroptosis, and necroptosis. Accumulating evidence suggests that PANoptosis plays a crucial role in tumorigenesis. However, the respective regulation mechanisms in cancer are so far unclear. Using various bioinformatic approaches, we comprehensively analyzed the expression patterns, genetic alterations, prognostic value, and immunological role of PANoptosis genes in pan-cancer. Expression of the PANoptosis gene, PYCARD, was validated based on the Human Protein Atlas database and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). We found that PANoptosis genes were aberrantly expressed in most cancer types, which was consistent with the validation of PYCARD expression. Concurrently, PANoptosis genes and PANoptosis scores were significantly associated with patient survival in 21 and 14 cancer types, respectively. Pathway analysis showed that PANoptosis score was positively correlated with pathways linked to immune and inflammatory responses in pan-cancer, such as IL6-JAK-STAT3 signaling, the interferon-gamma response, and IL2-STAT5 signaling. In addition, the PANoptosis score was significantly correlated with the tumor microenvironment, the infiltration levels of most immune cells (i.e.NK cells, CD8+ T cells, CD4+ T cells, DC cells), and immune-related genes. Furthermore, it was a predictive indicator of immunotherapy response in patients with tumors. These insights substantially improve our understanding of PANoptosis components in cancers and may inspire the discovery of novel prognostic and immunotherapy response biomarkers.

With the rapid development of life science, laboratory animals play an important role in many fields, such as biomedicine. In recent years, the national reforms “to delegate power, streamline administration and optimize government services” continues deepen, the laboratory animals administrative departments have paid more attention to interim and post-event supervision, in which the safety management of laboratory animals is the key and challenging point in the supervision process. In this paper, the information regarding licenses for laboratory animals in Jiangsu, facility areas, animal production and usage, employees, and other information the past three years were introduced. Combined with legal administrative management in recent years, the potential safety risks in the production and use of laboratory animals were analyzed, such as risks in management systems, employees, facility operation, animal quality control, accidental injury and zoonosis, animal transportation, and waste disposal. Additionally, the current construction, daily management services, and the list of interim and post-event supervision of the laboratory animal safety management system were introduced. Based on this discussion, we proposed relevant safety management countermeasures and suggestions and provided support for further improvements to laboratory animal safety management.

Abstract Cancer of the central nervous system (CNS) can crosstalk systemically and locally in the tumor microenvironment and has become a topic of attention for tumor initiation and advancement. Recently studied neuronal and cancer interaction fundamentally altered the knowledge about glioma and metastases, indicating how cancers invade complex neuronal networks. This review systematically discussed the interactions between neurons and cancers and elucidates new therapeutic avenues. We have overviewed the current understanding of direct or indirect communications of neuronal cells with cancer and the mechanisms associated with cancer invasion. Besides, tumor‐associated neuronal dysfunction and the influence of cancer therapies on the CNS are highlighted. Furthermore, interactions between peripheral nervous system and various cancers have also been discussed separately. Intriguingly and importantly, it cannot be ignored that exosomes could mediate the “wireless communications” between nervous system and cancer. Finally, promising future strategies targeting neuronal–brain tumor interactions were reviewed. A great deal of work remains to be done to elucidate the neuroscience of cancer, and future more research should be directed toward clarifying the precise mechanisms of cancer neuroscience, which hold enormous promise to improve outcomes for a wide range of malignancies.

AbstractBackground Atelectasis affects approximately 90% of anaesthetized patients, with laparoscopic surgery and pneumoperitoneum reported to exacerbate this condition. High-frequency oscillation therapy applies continuous positive pressure pulses to oscillate the airway, creating a pressure difference in small airways obstructed by secretions. This process helps reduce peak airway pressure, open small airways, and decrease atelectasis incidence, while also facilitating respiratory tract clearance. This study examines the efficacy of high-frequency oscillation on reduction of atelectasis in laparoscopic cholecystectomy (LC) patients under general anaesthesia, evaluated using lung ultrasound.Methods Sixty-four patients undergoing laparoscopic cholecystectomy were randomly divided into a control group and a high-frequency oscillation (HFO) group. Both groups underwent total intravenous anaesthesia under invasive arterial monitoring. The HFO group received a 10-minute continuous high-frequency oscillation therapy during surgery, while the control group received no intervention. Lung ultrasound evaluations were performed three times: five minutes post-intubation (T1), at the end of the surgery (T2), and before leaving the Post-Anaesthesia Care Unit (PACU; T3). Blood gas analysis was performed twice: prior to induction with no oxygen supply and before PACU discharge (oxygen supply off).Results The HFO group displayed a significantly lower incidence of atelectasis at T3 (57.5% vs. 90.3%, OR 6.88, 95%CI (1.74 to 27.24)) compared to the control group. Moreover, the HFO group’s PaO2 levels remained consistent with baseline levels before PACU discharge, unlike the control group. Although there was no significant difference in LUS scores between the groups at T1 (8.56 ± 0.15 vs. 8.19 ± 0.18, p = 0.1090), the HFO group had considerably lower scores at T2 (13.41 ± 0.17 vs.7.59 ± 0.17, p

BackgroundDiabetic foot ulcers (DFUs) cause significant morbidity affecting 19% to 34% of people living with diabetes mellitus. DFUs not only impair quality of life but may also result in limb loss and mortality. Patient education has been advocated to raise awareness of proper foot self-care and the necessity of seeking assistance when a foot wound occurs. Modern technologies, including mobile health (mHealth) interventions such as health apps, bring the potential for more cost-effective and scalable interventions. ObjectiveThis study aims to examine the feasibility and usability of a newly developed mHealth app called Well Feet, which is a diabetes and foot care education app for individuals at risk of developing DFU. MethodsWell Feet was developed using an evidence-based and expert panel cocreation approach to deliver educational content available in 3 languages (ie, English, Chinese, and Malay) via animation videos and a range of additional features, including adaptive learning. A nonrandomized, single-arm feasibility study using a mixed methods approach with a series of validated questionnaires and focus group discussions will be conducted. In total, 40 patients and carers will be recruited from a tertiary hospital diabetes clinic to receive a 1-month mHealth intervention. The primary outcomes are the usability of the app and a qualitative perspective on user experience. Secondary outcomes include changes in foot care knowledge, self-management behaviors, and quality of life. ResultsPatient recruitment began in July 2023, and the intervention and data collection will be completed by the end of September 2023. This study has been approved by National Healthcare Group Domain Specific Review Board (2022/00614) on February 10, 2023. The expected results will be published in spring 2024. ConclusionsThrough this feasibility study, the Well Feet DFU education app will undergo a comprehensive quantitative and qualitative evaluation of its usability and acceptance for future improvement in its design. With local contextualization, cultural adaptation, and its multilingual functionality, the app addresses a critical aspect of DFU health education and self-management in a multiethnic population. Findings from this study will refine and enhance the features of the app based on user feedback and shape the procedural framework for a subsequent randomized controlled trial to assess the effectiveness of Well Feet. Trial RegistrationClinicalTrials.gov NCT05564728; https://clinicaltrials.gov/study/NCT05564728 International Registered Report Identifier (IRRID)DERR1-10.2196/52036

Abstract Background Understanding resident physicians’ perceptions of competency-based medical education(CBME) may help improve approaches for implementing such education in standardized resident training (SRT). We conducted surveys of residents in China to identify their perceptions of CBME and determine the degree to which such education impacts their career plans. Methods Questionnaire contained a total of 24 questions, which were answered using multiple choice or yes/no, was distributed to residents who were undergoing SRT, regardless of specialty, at 7 accredited training bases located across six provinces of China. The survey aimed to investigate residents’ reasons for participating in SRT, perceptions of CBME, interest in receiving CBME-associated courses, and attitudes towards CBME. Results Overall, 441 residents completed the questionnaire.17.7% (78/441) responded “no clear objective” before the participated in SRT. Only 3.9% (17/441) fully understood the objectives, training contents, and assessment system of the current “competency-based” standardized training program for residents in China. Residents ranked clinical skills and patient care, interpersonal communication, and professionalism, as the three most important competencies. Most were interested in the CBME residency programs. 90.7% felt that implementing CBME could help them clarify their professional direction and improve their career planning. Conclusion Residents had positive perceptions of the incorporation of CBME into SRT. Administrators, educational leaders, and clinical faculty should seek to further publicize and increase the popularity of CBME.

Abstract There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Chinese history contains an abundance of records discussing contact with the outside world. In the ever elusive search for the origin of the meridian theory, an extended investigation into the Hippocratic Corpus reveals parallels with the Huáng Dì Nèi Jīng (黃帝內經) medical text of the Chinese tradition that provide an alternative perspective into the origins of meridian channels theory. Though this topic has been discussed in the past, this paper provides new and developed insight into theories associated with the liver and gallbladder channel systems of each tradition. Condensing the scope of the analysis between the Huáng Dì Nèi Jīng and Hippocratic text traditions and focusing on the liver and gall bladder channels aids to expound on the theoretical background required to advance the comprehension and understanding regarding the origins of each tradition. This paper reveals content that further the relationship between the two traditions, including demonstrating the existence of theoretical parallels existing between the liver and gall bladder channels of these two texts.