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Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study investigates the role and mechanisms of ADAM9 as a biomarker and potential therapeutic target in HCC. Utilizing RNA-sequencing data and clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted survival and meta-analyses, functional enrichment, and immune infiltration studies. Additionally, we evaluated the effects of ADAM9 silencing on HCC cell proliferation, migration, and invasion through in vitro experiments. Our results demonstrate that high ADAM9 expression is associated with poor prognosis and increased immune infiltration in HCC patients. Furthermore, ADAM9 knockdown significantly inhibited tumor cell proliferation and migration. These findings indicate that ADAM9 is a promising prognostic biomarker and potential therapeutic target in HCC. In conclusion, ADAM9 could offer avenues for developing strategies to inhibit tumor progression and improve patient outcomes.

The single-phase face-centered cubic medium-entropy alloys (MEAs) normally have coarse grains in as-cast state, which exhibit insufficient strength for engineering applications. Here, a superior tensile strength-ductility synergy in a fine grained (CoCrNi)94Al3Ti3 MEA hardened by nanoscale L12 precipitates was fabricated by spark plasma sintering (SPS) and post-sintering in-situ precipitation treatment. The SPSed MEAs have a fine grain size of ⁓ 5 μm, and a high number density of L12 precipitates form after in-situ annealing within the SPS machine. A high tensile yield strength of 1141 MPa with an adequate elongation to fracture of 25.8% was achieved in (CoCrNi)94Al3Ti3 MEA after annealing at 700 °C for 4 h. Electron backscattered diffraction and transmission electron microscopy characterizations indicate that the superior mechanical properties mainly originate from fine grains and the coherent spherical L12 precipitates. The dislocation slips and stacking faults prevail in all SPSed MEAs during tensile deformation, while extra Lomer-Cottrell locks are observed in annealed MEAs. The deformation twinning is absent in these precipitation-hardened MEAs with a low stacking fault energy, which may be attributed to the fine grains and numerous nanoscale L12 precipitates. This study not only confirms the effectiveness of powder metallurgy when sintering and precipitation are combined in-situ during the SPS cycle, but also provide guidance for the microstructure regulation process and practical applications of SPSed HEAs/MEAs.

In this paper, we introduced a new class of weak Hardy spaces, denoted by $ H^{p, \infty}_b $, and provided an analysis of their atomic decomposition. As an application, we established the boundedness of Calderón-Zygmund operators (CZOs) from $ H^p $ to $ H^{p, \infty}_b $ including cases at the critical exponent $ p = \frac{n}{n+\delta}, $ where $ \delta $ represents the regularity index of the distributional kernel. Moreover, the boundedness of CZOs from $ H^{p, \infty} $ to $ H^{p, \infty}_b $ was demonstrated for$ \frac{n}{n+\delta}

Abstract Background Neuroendocrine tumors (NETs) are rare neoplasms that originate from peptidergic neurons and neuroendocrine cells. Due to their increasing incidence, effective treatment strategies are required. Surufatinib, a novel small-molecule inhibitor with antiangiogenic and immunomodulatory effects, has shown promise in clinical trials for advanced NETs. However, the efficacy and safety of surufatinib are influenced by multiple factors, and there is currently a lack of sufficient real-world studies to explore these potential influencing factors. Methods We conducted a retrospective study on 133 patients with NETs who were treated with surufatinib at Sun Yat-sen University Cancer Center. Patients were histologically confirmed to have primary NETs. Statistical analyses, including Cox regression models and Kaplan-Meier curves, were conducted to assess the impact of the primary tumor site on progression-free survival (PFS) and overall survival (OS). Results Patients with gastroenteropancreatic NETs (GEP-NETs) exhibited significantly longer PFS and OS compared to extraGEP-NETs patients. Subgroup analyses also revealed variations in survival outcomes among patients with liver metastases depending on the primary tumor site. Adverse events (AEs), including proteinuria and increased bilirubin, were more common in GEP-NETs patients. These findings emphasize the importance of considering primary tumor site in treatment decisions for NETs. Conclusions Primary tumor site is a critical factor influencing the efficacy of surufatinib in NETs. Clinicians should consider this factor when determining treatment strategies.

The near real-time nuclear material accounting system for a spent fuel reprocessing facility was designed and preliminarily evaluated. Based on routine cycle accounting and the method of shortening the traditional accounting cycle，combined with the inventory data of nuclear materials in process equipment or containers，a preliminary real-time accounting analysis model for nuclear materials has been established. This study employed the reference 200 MTHM/a facility and its operating data from the International Atomic Energy Agency’s STR-193，the real-time balance calculation analysis across different time intervals was conducted by using a batch-wise error calculation and synthesized model. Comparative analysis was performed against semi-annual analysis data from routine closed balance calculations. The results indicate that near real-time accounting is feasible and a monthly calculation period is deemed sufficient under this specified balance model. A preliminary investigation of dynamic analysis and Page’s test was conducted using time-correlated dynamic data simulation upon this balance calculation model. The results indicate that both cumulative and Page’s test are effective in detecting significant sudden losses of nuclear materials. Page’s test，particularly in detecting cumulative losses of nuclear materials，especially under conditions with longer accounting periods and approaching detection limits，demonstrates superior anomaly detection capabilities compared to cumulative evaluation，with the ability to control false alarm rate. The near real-time accounting system makes the entire system more effective in anomaly detection and can be used for dynamic trend analysis of nuclear material management in the future，thereby improving the application value of nuclear material accounting management.

Abstract To understand the mechanical properties and deformation failure patterns of coal pillar dams in gently inclined coal seam mine underground reservoirs, compression-shear coupling tests with variable angles were conducted on coal pillar dam samples under different saturation states. The digital image correlation (DIC) technique was utilized to obtain the deformation patterns of the displacement field throughout the compression-shear failure process of the samples. Numerical simulations were used to perform a comparative analysis and validation of the experimental results. The results indicated that the load-bearing capacity of the coal pillar dam samples decreased by 12.8–17.4% under water-saturated conditions. For every 5° increase in the inclination angle, the load-bearing capacity of the coal pillar dam samples decreased by an average of 3.53%. The normal stress and shear stress on the shear surface of the saturated samples were both lower than those of the natural samples, and both exhibited a linear variation with increasing inclination angle. The deformation evolution of the coal pillar dam samples under different test conditions exhibited similarity. The initial positive and negative displacement extremities in the horizontal direction were located at the lower right and upper left corners of the samples, respectively. Ultimately, the displacement field of the samples showed a pattern of smaller displacements at the top and larger displacements at the bottom, with negative values at the top and positive values at the bottom, distributed along the direction of the sample’s bedding. The saturated state and the increase in inclination both had a weakening effect on the load-bearing performance of the samples but had a relatively small impact on the differences in the displacement field deformation patterns. The research results can provide a reference for the study of the stability of coal pillar dams under similar conditions.

Abstract Presenilin-associated protein (PSAP) is a mitochondrial proapoptotic protein as established in cell biology studies. It remains unknown whether it involves in neurodegenerative diseases. Here, we explored PASP expression in adult and aged human brains and its alteration relative to Alzheimer-disease (AD)-type neuropathology. In pathology-free brains, light PASP immunoreactivity (IR) occurred among largely principal neurons in the cerebrum and subcortical structures. In the brains with AD pathology, enhanced PSAP IR occurred in neuronal and neuritic profiles with a tangle-like appearance, with PSAP and pTau protein levels elevated in neocortical lysates relative to control. Neuronal/neuritic profiles with enhanced PSAP IR partially colocalized with pTau, but invariably with Amylo-Glo labelled tangles. The neuronal somata with enhanced PASP IR also showed diminished IR for casein kinase 1 delta (Ck1δ), a marker of granulovacuolar degeneration; and diminished IR for sortilin, which is normally expressed in membrane and intracellular protein sorting/trafficking organelles. In old 3xTg-AD mice with β-amyloid and pTau pathologies developed in the brain, PSAP IR in the cerebral sections exhibited no difference relative to wildtype mice. These findings indicate that PSAP upregulation is involved in the course of tangle formation especially in the human brain during aging and in AD pathogenesis.

Abstract A novel technique that couples microbially induced calcite precipitation (MICP) and calcium carbide residue (CCR) is proposed for immobilizing Cd2+ in contaminated soil. The properties and mechanism of CCR-enhanced MICP were investigated through a series of experimental analyses considering factors such as heavy metal concentration, curing time, and the effect of Ca2+. The unconfined compressive strength (UCS) increased with increasing curing time and reached a maximum value at 28 d, and the leaching concentration of Cd2+ decreased and tended to level off with increasing curing time. The addition of CCR enhanced the immobilization performance of Cd2+ through the MICP method, resulting in UCSs that were 3.8–4.2 times those of samples without CCR and leaching concentrations of Cd2+ that were 38.9–69.2% lower at a curing time of 28 d. The addition of Ca2+ to cementation solutions further improved the immobilization effectiveness, resulting in the UCSs of the samples increasing by 18.7–49.8% and the leaching concentrations of Cd2+ decreasing by 11–40% CaCO3 and its hydration products can immobilize Cd2+ through coprecipitation, reducing its toxicity by converting weak acid-extractable cadmium into residual cadmium. Consequently, Sporosarcina pasteurii combined with CCR improved the UCS of the treated contaminated soil and greatly decreased cadmium migration.

Abstract Background Posterior reversible encephalopathy syndrome is a rare neurological syndrome that refers to reversible subcortical vasogenic brain edema disorder in patients with acute neurological symptoms. Case presentation Whether there is a direct causal relationship between pancreatitis and posterior reversible encephalopathy syndrome needs further study. We here report a 39-year-old Chinese woman who was diagnosed with pancreatitis followed by vision disturbance. The patient was finally diagnosed with posterior reversible encephalopathy syndrome. On the basis of this rare case, we analyzed the causes of visual disturbance and proposed diagnostic ideas. Conclusions For posterior reversible encephalopathy syndrome, early identification and treatment of the primary disease are particularly important. Imaging and clinical characteristics in posterior reversible encephalopathy syndrome are usually reversible.

Abstract Background Currently, several randomized controlled trials (RCTs) have been conducted to investigate the efficacy of combining immune checkpoint inhibitors (ICIs) with chemotherapy as a first-line treatment for advanced or recurrent endometrial cancer; however, the optimal treatment strategy remains undetermined. Methods A comprehensive search of online databases was conducted to identify RCTs published until December 31, 2023. Network meta-analysis was performed to evaluate PFS, OS, TRAEs, irAEs, and the ranking of different treatment regimens. Results A total of 2702 patients from five RCTs (six reports) were included in the analysis. The combination therapy of ICIs significantly prolonged PFS (HR = 0.69, 95%CI 0.63–0.76, p

Abstract The therapeutic approach to thymic cysts remains a subject of controversy. Predicted biomarkers for identifying thymic cysts and thymoma (THYM) are crucial. In this research, patients diagnosed with thymic cysts (MTC, n = 6) and thymoma (B1, n = 6; B3, n = 6) were enrolled. Proteins of superior quality were subjected to TMT labeling and UPLC-MS, and differentially expressed proteins (DEPs) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactive network analyses were applied to the DEPs. Some key differentially expressed genes(DEGs) were corroborated through GEPIA 32. The pan-cancer expression levels of key DEGs remarkably linked with prognosis were determined utilizing The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). Eventually, 49 DEPs were identified in the B1 vs. MTC comparison (17 upregulated and 32 downregulated), 27 in the B3 vs. MTC comparison (8 upregulated and 19 downregulated), and 38 in the B3 vs. B1 comparison (9 upregulated and 29 downregulated). IL13RA1 (down), galectin-3 binding protein (LGALS3BP)(up), PRCSH (down), C3 (down), MXRA5 (down), TNN (down), CFHR1 (down), SUN3 (down) were jointly altered in both B1 vs. NZ and B3 vs. NZ. GEPIA validated that LGALS3BP was significantly upregulated in thymoma patients. In conclusion, LGALS3BP might be an essential biomarker to identify thymoma from the thymic cyst.

Abstract Accurate estimation of sideslip angle and vehicle velocity is crucial for effective control of distributed drive electric vehicles. However, as these states are not directly measured, Kalman-based approaches utilizing in-vehicle sensors have been developed to estimate them. Unfortunately, existing methods tend to ignore the impact of data loss on estimation performance. Furthermore, the process noise, which changes dynamically due to varying driving conditions, is not adequately considered. In response to these constraints, we propose a novel method called the fuzzy adaptive fault-tolerant extended Kalman filter (FAFTEKF). Initially, a fault-tolerant EKF is devised to handle missing measurements. Additionally, a fuzzy logic system that dynamically updates the process noise matrix, is built to improve estimation accuracy under different driving conditions. Extensive experimental results validate the superiority of the FAFTEKF over the traditional EKF across various scenarios with different degrees of data loss.

Abstract Myeloid cells are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by myeloid cells on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal myeloid cells, primarily the M2 macrophages during bone regeneration. Knockout of periostin in myeloid cells reduces cortical bone thickness, disrupts trabecular bone connectivity, impairs repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation is a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β), it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in myeloid cells by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our findings suggest that mechanical stimulation regulates periostin expression and promotes M2 macrophage polarization, highlighting the potential of mechanically conditioned macrophages as a therapeutic strategy for enhancing bone repair.

Abstract Liver transplantation is the definitive treatment for end-stage liver disease, yet T-cell mediated rejection (TCMR) remains a major challenge. This study aims to identify key genes associated with TCMR and their potential biological processes and mechanisms. The GSE145780 dataset was subjected to differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms to pinpoint key genes associated with TCMR. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and regulatory networks were constructed to ascertain the biological relevance of these genes. Expression validation was performed using single-cell RNA-seq (scRNA-seq) data and liver biopsy tissues from patients. We identified 5 key genes (ITGB2, FCER1G, IL-18, GBP1, and CD53) that are associated with immunological functions, such as chemotactic activity, antigen processing, and T cell differentiation. GSEA highlighted enrichment in chemokine signaling and antigen presentation pathways. A lncRNA-miRNA-mRNA network was delineated, and drug target prediction yielded 26 potential drugs. Evaluation of expression levels in non-rejection (NR) and TCMR groups exhibited significant disparities in T cells and myeloid cells. Tissue analyses from patients corroborated the upregulation of GBP1, IL-18, CD53, and FCER1G in TCMR cases. Through comprehensive analysis, this research has identified 4 genes intimately connected with TCMR following liver transplantation, shedding light on the underlying immune activation pathways and suggesting putative targets for therapeutic intervention.

Abstract Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Abstract Background The aim of this study was to analyze the influence of the positioning of the components of total hip arthroplasty (THA) evaluated by the acetabular anteversion (AA) and femoral anteversion (FA) angle on postoperative gait in patients with symptomatic hip osteoarthritis secondary to hip dysplasia undergoing THA. Methods Between May 2023 and May 2024, patients with symptomatic hip osteoarthritis secondary to hip dysplasia (Crowe Type I and IV) who underwent THA were enrolled in the study. The AA angle and FA angle were measured by computer tomography (CT). Gait data were determined by using the Dynamic Right Gait & Posture analysis system. The relationship between FA, AA and gait data was analyzed by Pearson correlation test, subgroup Pearson correlation test, multiple linear regression. Results A total of 40 patients (45hips) were included in the study. Compared with preoperative, the patient’s postoperative foot progression angle, foot contact angle, plantarflexion velocity, swing foot speed, gait velocity, cadence, stride length were significantly improved. Preoperative FA is significantly different from postoperative FA (P

Abstract Background The purpose of the study was to evaluate renal quality and predict posttransplant graft function using ex vivo sound touch elastography (STE). Methods In this prospective study, 106 donor kidneys underwent ex vivo STE examination and biopsy from March 2022 to August 2023. The mean stiffness of the superficial cortex (STEsc), deep cortex (STEdc), and medulla (STEme) was obtained and synthesized into one index (STE) through the factor analysis method. Additionally, 100 recipients were followed up for 6 months. A random forest algorithm was employed to explore significant predictive factors associated with the Remuzzi score and allograft function. The performance of parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). Results STE had AUC values of 0.803 for diagnosing low Remuzzi and 0.943 for diagnosing high Remuzzi. Meanwhile, STE had an AUC of 0.723 for diagnosing moderate to severe ATI. Random forest algorithm identified STE and Remuzzi score as significant predictors for 6-month renal function. The AUC for STE in predicting postoperative allograft function was 0.717, which was comparable with that of the Remuzzi score (AUC = 0.756). Nevertheless, the specificity of STE was significantly higher than that of Remuzzi (0.913 vs 0.652, p

Abstract Background Breast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM. Methods This study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models. Results 284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and

Abstract Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-COV-2, Influenza A, B, and respiratory syncytial virus with a sensitivity of 10 copies/mL. When integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single-copy spatial resolution of 0.83 copies/m3 for airborne virus surveillance with an air flow rate of 400 L/min and a sampling time of 30 minutes. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.

Abstract Background Pseudouridine (Ψ), a C5-glycoside isomer of uridine, stands as one of the most prevalent RNA modifications in all RNA types. Distinguishing from the C-N bond linking uridine to ribose, the link between Ψ and ribose is a C-C bond, endowing Ψ modified RNA distinct properties and functions in various biological processes. The conversion of uridine to Ψ is governed by pseudouridine synthases (PUSs). RNA pseudouridylation is implicated in cancer biology and therapeutics. Objectives In this review, we will summarize the methods for detecting Ψ, the process of Ψ generation, the impact of Ψ modification on RNA metabolism and gene expression, the roles of dysregulated Ψ and pseudouridine synthases in cancers, and the underlying mechanism. Methods We conducted a comprehensive search of PubMed from its inception through February 2024. The search terms included “pseudouridine”; “pseudouridine synthase”; “PUS”; “dyskerin”; “cancer”; “tumor”; “carcinoma”; “malignancy”; “tumorigenesis”; “biomarker”; “prognosis” and “therapy”. We included studies published in peer-reviewed journals that focused on Ψ detection, specific mechanisms involving Ψ and PUSs, and prognosis in cancer patients with high Ψ expression. We excluded studies lacking sufficient methodological details or appropriate controls. Results Ψ has been recognized as a significant biomarker in cancer diagnosis and prognosis. Abnormal Ψ modifications mediated by various PUSs result in dysregulated RNA metabolism and impaired RNA function, promoting the development of various cancers. Overexpression of PUSs is common in cancer cells and predicts poor prognosis. PUSs inhibition arrests cell proliferation and enhances apoptosis in cancer cells, suggesting PUS-targeting cancer therapy may be a potential strategy in cancer treatment. Discussion High Ψ levels in serum, urine, and saliva may suggest cancer, but do not specify the type, requiring additional lab markers and imaging for accurate diagnosis. Standardized detection methods are also crucial for reliable results. PUSs are linked to cancer, but more researches are needed to understand their mechanisms in different cancers. Anticancer treatments targeting PUSs are still under developed.

Abstract Background In recent years, radiomics has been shown to be an effective tool for the diagnosis and prediction of diseases. Existing evidence suggests that imaging features play a key role in predicting the recurrence of lumbar disk herniation (rLDH). Thus, this study aimed to evaluate the risk of rLDH in patients undergoing percutaneous endoscopic lumbar discectomy (PELD) using radiomics to facilitate the development of more rational surgical and perioperative management strategies. Method This was a retrospective case-control study involving 487 patients who underwent PELD at the L4/5 level. The rLDH and negative groups were matched using propensity score matching (PSM). A total of 1409 radiomic features were extracted from preoperative lumbar MRI images using intraclass correlation coefficient (ICC) analysis, t-test, and LASSO analysis. Afterward, 6 predictive models were constructed and evaluated using ROC curve analysis, AUC, specificity, sensitivity, confusion matrix, and 2 repeated 3-fold cross-validations. Lastly, the Shapley Additive Explanation (SHAP) analysis provided visual explanations for the models. Results Following screening and matching, 128 patients were included in both the recurrence and control groups. Moreover, 18 of the extracted radiomic features were selected for generating six models, which achieved an AUC of 0.551–0.859 for predicting rLDH. Among these models, SVM, RF, and XG Boost exhibited superior performances. Finally, cross-validation revealed that their accuracy was 0.674–0.791, 0.647–0.729, and 0.674–0.718. Conclusion Radiomics based on MRI can be used to predict the risk of rLDH, offering more comprehensive guidance for perioperative treatment by extracting imaging information that cannot be visualized with the naked eye. Meanwhile, the accuracy and generalizability of the model can be improved in the future by incorporating more data and conducting multicenter studies.

Abstract This was a retrospective study. This study investigated the occurrence of a composite endpoints (cardiovascular and cerebrovascular events, end‐stage renal disease, and death) in 153 patients (aged ≥ 18 years) with a diagnosis of in chronic kidney disease (CKD). Based on morning blood pressure surge (MBPS) defined as ≥35 mm Hg, patients were divided into two groups: with MBPS (n = 50) and without MBPS (n = 103). All patients were followed up for at least 1 year. Baseline demographic, laboratory and follow‐up data were collected. The clinical characteristics of the two groups were compared. The relationships between MBPS and endpoint events were analyzed using the Kaplan–Meier method and Cox regression model. In total, 153 patients (mean age 41.8 years; 56.86% males) were included in this study. During the follow‐up period (mean 4.3 years), 34 endpoint events occurred. After adjustment for the covariates, the risk of cardiovascular and cerebrovascular events, end‐stage renal disease and death remained significantly higher in patients with MBPS (hazard ratio [HR] and 95% confidence interval [CI] 3.124 [1.096–9.130]]) Among the other variables, systolic blood pressure, and night‐time and daytime pulse pressures remained significantly associated with outcome in patients of CKD (1.789 [1.205–2.654], 1.710 [1.200–2.437], and 1.318 [1.096–1.586], respectively]. In conclusions, MBPS was identified as an independent prognostic factor for composite endpoint events (cardiovascular and cerebrovascular events, end‐stage renal disease and death) patients with chronic kidney disease patients.

Objective The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi‐rod constructs in the revision of thoracolumbar fractures. Methods Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi‐rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow‐up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow‐up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). Results The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow‐up period. The paired t‐test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre‐revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post‐revision and last follow‐up (p = 0.551). VAS and ODI were greatly improved at the last follow‐up. Conclusion The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi‐rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Purpose Oblique lumbar interbody fusion (OLIF) has become a popular technique for treating adult degenerative scoliosis (ADS), but traditional OLIF technology often requires repositioning for one‐stage or staged posterior fixation. The objective of this pilot study was to describe the surgical technique of simultaneous single‐position OLIF and percutaneous pedicle screw fixation (OLIF 360) under O‐Arm navigation for modified MISDEF type II ADS. Methods Between June 2022 and December 2023, six patients classified as having modified MISDEF type II ADS underwent OLIF 360 assisted by O‐Arm navigation at our institution. Intraoperative blood loss, duration of operation, and complications related to the OLIF 360 procedure were recorded. The preoperative and postoperative spinal pelvic parameters were measured using X‐rays. The accuracy of pedicel screws was recorded in accordance with the modified Gertzbein–Robbins classification on CT. Postoperative MRI was performed to evaluate the indirect decompressive effect. The Japanese Orthopedic Association score for low back pain was used to evaluate surgical outcomes. Results Navigated OLIF 360 were performed in six ADS patients with 44 percutaneous pedicel screws and 16 cages placement, including four women and two men. The mean operation time was 160.83 ± 33.23 min, and the mean blood loss was 111.67 ± 39.71 mL. Postoperative spinal pelvic parameters and spinal stenosis degree improved significantly on X‐ray and MRI. All screws were clinically acceptable according to the Gertzbein–Robbins classification, with 92.7% grade A and 7.3% grade B. No serious intraoperative and postoperative adverse events were recorded in all patients. The JOA scores for low back pain of all patients were significantly improved at postoperative 1 month and the final follow‐up. Conclusion We report on a case series and describe navigated OLIF 360 in treating modified MISDEF type II ADS patients. Navigation‐assisted OLIF 360 has shown encouraging surgical outcomes with good spinal imbalance correction and indirect decompression.

Abstract This study aims to investigate the effects of the Galectin‐3 (Gal‐3) inhibitor TD139 on inflammation and the extracellular signal‐regulated kinase (ERK)/c‐Jun N‐terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF‐α, assessing Gal‐3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post‐delivery placental tissues were analyzed. Data were analyzed using one‐way or two‐way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF‐α‐induced increases in Gal‐3, IL‐1β, IL‐6, MCP‐1, and ERK/JNK/p38 activation in placental tissues. In STZ‐induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF‐α, IL‐1β, IL‐6, and MCP‐1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF‐α stimulated placental tissues and STZ‐induced GDM mice, suggesting its therapeutic potential for managing GDM‐related placental inflammation and improving pregnancy outcomes. The study used TNF‐α to mimic GDM in placental tissues and an STZ‐induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.

Abstract Background To investigate the efficiency of a new method for the prevention of argentinian flag sign during the process of continuous, circular, and centered anterior capsulotomy (CCC) on the anterior capsule in cortically liquefied intumescent cataracts. This study was registered in an appropriate registry and the registration number of registration was xyy11[2022]-XJSFX-087; The date of of registration was 2022-04-29. Methods Preoperative examinations including slit-lamp examination, ocular A-scan ultrasonography, and Ultrasound Biomicroscopy (UBM) UBM were conducted on 61 patients with intumescent cataracts. Cases with cortically liquefied intumescent cataracts were selected and after staining with indocyanine green, the anterior chamber air bubble technique was used to compress the anterior capsule, and liquefied cortex was aspirated using a puncture needle. Corrected Distance Visual Acuity (CDVA) and intraocular pressure were recorded on postoperative days 1, 1 week, 1 month, and 6 months. Intraoperative and postoperative complications were documented and analyzed. Results Fifty eyes were identified as having cortically liquefied intumescent cataracts. No cases of the Argentinian flag sign occurred, and standard capsulorrhexis was achieved, facilitating smooth phacoemulsification. All patients achieved satisfactory outcomes at follow-ups of 1 day, 1 week, 1 month, and 6 months postoperatively. Mild corneal edema was observed in three cases on the first postoperative day, with no other complications noted. Conclusions The anterior chamber air bubble technique combined with cortical fluid release technique can prevent the occurrence of the Argentinian flag sign in cortically liquefied intumescent cataracts, this method is simple, convenient and economic for the clinical promotion.

Abstract This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

Abstract Keratoconus (KC) is an irreversible blinding eye disease; therefore, early screening of KC suspects (KCS) is crucial for protecting patients’ quality of life. Scheimpflug imaging is a commonly used screening device in clinical practice. We aimed to evaluate the diagnostic ability of a Scheimpflug imaging device (Scansys) for KC and KCS and compared it with other Scheimpflug-based devices (Pentacam and Corvis ST). This prospective case-control study included 107 normal eyes, 72 KCS, and 57 KC. Scansys screening index Keratoconus probability (KCP) showed excellent performance in diagnosing KC at a cutoff value of 16.4 (area under the receiver operating characteristic [AUROC] = 1.000), with 100% sensitivity and 98.11% specificity. KCP had a better KCS diagnostic ability at a cutoff value of 8.9 (AUROC = 0.813) than Corvis biomechanical index (CBI, AUROC = 0.764), reaching 67.61% sensitivity and 85.85% specificity. Pentacam screening index Belin/Ambrósio enhanced ectasia display deviation (BAD-D) showed the best performance with 92.96% sensitivity and 89.62% specificity at a cutoff value of 1.525 (AUROC = 0.970) in diagnosing KCS. Scansys provides accurate KCP parameters in diagnosing KC; however, the efficiency of diagnosing KCS should be further optimized.

Abstract Background A minority of people who need alcohol treatment receive it. Unhealthy alcohol use is common among people with HIV (PWH) and can lead to negative health outcomes. The aims of this multi-methods study are to (1) quantitatively describe the prevalence, psychosocial characteristics, and demographic traits of a sample of PWH currently receiving HIV care in Florida who had a self-reported need for alcohol treatment but did not seek care and (2) qualitatively explore reasons why PWH did not seek treatment. Methods PWH enrolled in the Florida Cohort Study between October 2020 and February 2023 who had drinking history (N = 487) completed a cross-sectional survey that asked if there was a time when they recognized they needed help for their drinking but did not seek it. If yes, they were asked an open-ended follow-up question about reasons why they did not seek care. Demographic and behavioral differences between those who did and did not endorse a time when they needed alcohol treatment were determined using multivariable logistic regression, while qualitative data were analyzed with thematic analysis based in the Social-Ecological Model to assess reasons for not seeking care at the individual, social, and systems levels. Results A quarter of PWH (n = 129) with lifetime drinking indicated a time they needed care but did not seek it. Patients who endorsed a time where they perceived the need for treatment but did not seek it were more likely to endorse current at-risk drinking and a history of ever trying to reduce their drinking or formally seek professional alcohol treatment. The most common reasons participants did not seek care were individual level factors and included shame, denial, fear, wanting to do it on their own, not feeling ready, and not wanting to seek care. Conclusions PWH experienced barriers largely at the individual level that prevented them from seeking alcohol treatment despite a recognized need, though many eventually sought care. Providers and public health professionals should consider helping to address various barriers, particularly internal barriers, when designing interventions to help PWH seek care.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology. Despite the increasing global incidence and poor prognosis, the exact pathogenic mechanisms remain elusive. Currently, effective therapeutic targets and treatment methods for this disease are still lacking. This study tried to explore the pathogenic mechanisms of IPF. We found elevated expression of SULF1 in lung tissues of IPF patients compared to normal control lung tissues. SULF1 is an enzyme that modifies heparan sulfate chains of heparan sulfate proteoglycans, playing a critical role in biological regulation. However, the effect of SULF1 in pulmonary fibrosis remains incompletely understood. Our study aimed to investigate the impact and mechanisms of SULF1 in fibrosis. Methods We collected lung specimens from IPF patients for transcriptome sequencing. Validation of SULF1 expression in IPF patients was performed using Western blotting and RT-qPCR on lung tissues. ELISA experiments were employed to detect SULF1 concentrations in IPF patient plasma and TGF-β1 levels in cell culture supernatants. We used lentiviral delivery of SULF1 shRNA to knock down SULF1 in HFL1 cells, evaluating its effects on fibroblast secretion, activation, proliferation, migration, and invasion capabilities. Furthermore, we employed Co-Immunoprecipitation (Co-IP) to investigate the regulatory mechanisms involved. Results Through bioinformatic analysis of IPF transcriptomic sequencing data (HTIPF) and datasets GSE24206, and GSE53845, we identified SULF1 may potentially play a crucial role in IPF. Subsequently, we verified that SULF1 was upregulated in IPF and predominantly increased in fibroblasts. Furthermore, SULF1 expression was induced in HFL1 cells following exposure to TGF-β1. Knockdown of SULF1 suppressed fibroblast secretion, activation, proliferation, migration, and invasion under both TGF-β1-driven and non-TGF-β1-driven conditions. We found that SULF1 catalyzes the release of TGF-β1 bound to TGFβRIII, thereby activating the TGF-β1/SMAD pathway to promote fibrosis. Additionally, TGF-β1 induces SULF1 expression through the TGF-β1/SMAD pathway, suggesting a potential positive feedback loop between SULF1 and the TGF-β1/SMAD pathway. Conclusions Our findings reveal that SULF1 promotes fibrosis through the TGF-β1/SMAD pathway in pulmonary fibrosis. Targeting SULF1 may offer a promising therapeutic strategy against IPF.

Abstract Small-cell lung cancer (SCLC) transformation accounts for 3–14% of resistance in EGFR-TKI relapsed lung adenocarcinomas (LUADs), with unknown molecular mechanisms and optimal treatment strategies. We performed transcriptomic analyses (including bulk and spatial transcriptomics) and multiplex immunofluorescence on pre-treated samples from LUADs without transformation after EGFR-TKI treatment (LUAD-NT), primary SCLCs (SCLC-P) and LUADs with transformation after EGFR-TKI treatment (before transformation: LUAD-BT; after transformation: SCLC-AT). Our study found that LUAD-BT exhibited potential transcriptomic characteristics for transformation compared with LUAD-NT. We identified several pathways that shifted during transformation, and the transformation might be promoted by epigenetic alterations (such as HDAC10, HDAC1, DNMT3A) within the tumor cells instead of within the tumor microenvironment. For druggable pathways, transformed-SCLC were proved to be less dependent on EGF signaling but more relied on FGF signaling, while VEGF-VEGFR pathway remained active, indicating potential treatments after transformation. We also found transformed-SCLC showed an immuno-exhausted status which was associated with the duration of EGFR-TKI before transformation. Besides, SCLC-AT exhibited distinct molecular subtypes from SCLC-P. Moreover, we constructed an ideal 4-marker model based on transcriptomic and IHC data to predict SCLC transformation, which obtained a sensitivity of 100% and 87.5%, a specificity of 95.7% and 100% in the training and test cohorts, respectively. We provided insights into the molecular mechanisms of SCLC transformation and the differences between SCLC-AT and SCLC-P, which might shed light on prevention strategies and subsequent therapeutic strategies for SCLC transformation in the future.

Improving plant resistance to Verticillium wilt (VW), which causes massive losses in Gossypium hirsutum, is a global challenge. Crop plants need to efficiently allocate their limited energy resources to maintain a balance between growth and defense. However, few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in cotton. In this study, we found that the that expression of most R2R3-MYB members in cotton is significantly changed by V. dahliae infection relative to the other MYB types. One novel R2R3-MYB transcription factor (TF) that specifically responds to V. dahliae, GhMYB3D5, was identified. GhMYB3D5 was not expressed in 15 cotton tissues under normal conditions, but it was dramatically induced by V. dahliae stress. We functionally characterized its positive role and underlying mechanism in VW resistance. Upon V. dahliae infection, the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated GhADH1 expression. In addition, GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of GhADH1. Consequently, the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis (GhPAL, GhC4H, Gh4CL, and GhPOD/GhLAC) in cotton, thereby enhancing cotton VW resistance. Our results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation, which can be regarded as an effective way to orchestrate plant immunity and growth.

Abstract Aquilaria sinensis is a significant resin-producing plant worldwide that is crucial for agarwood production. Agarwood has different qualities depending on the method with which it is formed, and the microbial community structures that are present during these methods are also diverse. Furthermore, the microbial communities of plants play crucial roles in determining their health and productivity. While previous studies have investigated the impact of microorganisms on agarwood formation, they lack comprehensiveness, particularly regarding the properties of the microbial community throughout the entire process from seedling to adult to incense formation. We collected roots, stems, leaves, flowers, fruits and other tissues from seedlings, healthy plants and agarwood-producing plants to address this gap and assess the dominant bacterial species in the microbial community structures of A. sinensis at different growth stages and their impacts on growth and agarwood formation. The bacteria and fungi in these tissues were classified and counted from different perspectives. The samples were sequenced using the Illumina sequencing platform, and sequence analyses and species annotations were performed using a range of bioinformatics tools to assess the plant community compositions. An additional comparison of the samples was conducted using diversity analyses to assess their differences. This research revealed that Listeria, Kurtzmanomyces, Ascotaiwania, Acinetobacter, Sphingobium, Fonsecaea, Acrocalymma, Allorhizobium, Bacillus, Pseudomonas, Peethambara, and Debaryomyces are potentially associated with the formation of agarwood. Overall, the data provided in this article help us understand the important roles played by bacteria and fungi in the growth and agarwood formation process of A. sinensis, will support the theoretical basis for the large-scale cultivation of A. sinensis, and provide a basis for further research on microbial community applications in agarwood production and beyond.

Abstract Background Physical symptoms and aversion induced by opioid withdrawal strongly affect the management of opioid addiction. YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1), an m6A-binding protein, from the periaqueductal gray (PAG) reportedly contributes to morphine tolerance and hyperalgesia. However, the role of YTHDF1 in morphine withdrawal remains unclear. Methods A naloxone-precipitated morphine withdrawal model was established in C57/BL6 mice or transgenic mice. YTHDF1 was knocked down via adeno-associated virus transfection. Combined with the results of the single-cell RNA sequencing analysis, the changes in morphine withdrawal somatic signs and conditioned place aversion (CPA) scores were compared when YTHDF1 originating from different neurons in the ventrolateral periaqueductal gray (vlPAG) was knocked down. We further explored the role of inflammatory factors and transcription factors related to inflammatory response in morphine withdrawal. Results Our results revealed that YTHDF1 expression was upregulated in the vlPAG of mice with morphine withdrawal and that the knockdown of vlPAG YTHDF1 attenuated morphine withdrawal-related somatic signs and aversion. The levels of NF-κB and p-NF-κB were reduced after the inhibition of YTHDF1 in the vlPAG. YTHDF1 from vlPAG inhibitory neurons, rather than excitatory neurons, facilitated morphine withdrawal responses. The inhibition of YTHDF1 in vlPAG somatostatin (Sst)-expressing neurons relieved somatic signs of morphine withdrawal and aversion, whereas the knockdown of YTHDF1 in cholecystokinin (Cck)-expressing or parvalbumin (PV)-expressing neurons did not change morphine withdrawal-induced responses. The activity of c-fos + neurons, the intensity of the calcium signal, the density of dendritic spines, and the frequency of mIPSCs in the vlPAG, which were increased in mice with morphine withdrawal, were decreased with the inhibition of YTHDF1 from vlPAG inhibitory neurons or Sst-expressing neurons. Knockdown of NF-κB in Sst-expressing neurons also alleviated morphine withdrawal-induced responses. Conclusions YTHDF1 originating from Sst-expressing neurons in the vlPAG is crucial for the modulation of morphine withdrawal responses, and the underlying mechanism might be related to the regulation of the expression and phosphorylation of NF-κB.

Abstract Background Cardiac maladaptive remodeling is one of the leading causes of heart failure with highly complicated pathogeneses. The E3 ligase tripartite motif containing 35 (TRIM35) has been identified as a crucial regulator governing cellular growth, immune responses, and metabolism. Nonetheless, the role of TRIM35 in fibroblasts in cardiac remodeling remains elusive. Methods Heart tissues from human donors were used to verify tissue-specific expression of TRIM35. Fibroblast-specific Trim35 gene knockout mice (Trim35cKO) were used to investigate the function of TRIM35 in fibroblasts. Cardiac function, morphology, and molecular changes in the heart tissues were analyzed after transverse aortic constriction (TAC) surgery. The mechanisms by which TRIM35 regulates fibroblast phenotypes were elucidated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA sequencing (RNA-Seq). These findings were further validated through the use of adenoviral and adeno-associated viral transfection systems, as well as the mTORC1 inhibitor Rapamycin. Results TRIM35 expression is primarily up-regulated in cardiac fibroblasts in both murine and human fibrotic hearts, and responds to TGF-β1 stimulation. Specific deletion of TRIM35 in cardiac fibroblasts significantly improves cardiac fibrosis and hypertrophy. Consistently, the overexpression of TRIM35 promotes fibroblast proliferation, migration, and differentiation. Through paracrine signaling, it induces hypertrophic growth of cardiomyocytes. Mechanistically, we found that TRIM35 interacts with, ubiquitinates, and up-regulates the amino acid transporter SLC7A5, which enhances amino acid transport and activates the mTORC1 signaling pathway. Furthermore, overexpression of SLC7A5 significantly reverses the reduced cardiac fibrosis and hypertrophy caused by conditional knockout of TRIM35. Conclusion Our findings demonstrate a novel role of fibroblast-TRIM35 in cardiac remodeling and uncover the mechanism underlying SLC7A5-mediated amino acid transport and mTORC1 activation. These results provide a potential novel therapeutic target for treating cardiac remodeling.

Abstract Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints. Graphical Abstract

Abstract Objective To evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI Ktrans map, and metabolomics. Materials and methods 24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI Ktrans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research. Results The FF ratio and Ktrans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P

In this paper，the typical site environmental events covered by 48 stations in 7 center stations of Hebei geophysical station network are reviewed, involving deformation, geoelectricity, geomagnetic and fluid disciplines. According to the number of recorded events and the number of affecting instrument sets, typical influential factors such as HVDC transmission, equipment leakage, water (oil) well spring pumping, and reservoir water level fluctuation are selected for analysis. The process of occurrence of the event is described in detail, its rules and reasons are found, and effective solutions are proposed to provide reference for anomaly verification, analysis and prediction.

Abstract Background Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias, strongly associated with neutrophils. However, the underlying mechanism remain unclear. This study aims to explore the interaction between neutrophils and atrial myocytes in the pathogenesis of AF. Methods Patch-clamp was employed to record the action potential duration (APD) and ion channels in HL-1 cells. Flow cytometry was used to assess the differentiation of neutrophils. The mRNA and protein levels of CACNA1C, CACNA2D, and CACNB2 in HL-1 cells were detected. Results High-frequency electrical stimulation resulted in a shortening of the APD in HL-1 cells. Flow cytometry demonstrated that neutrophils were polarized into N1 phenotype when cultured with stimulated HL-1 cells medium. Compared to control neutrophils conditioned medium (CM), cocultured with TNF-α knockout neutrophils CM prolonged APD and the L-type Ca (2+) channel (LTCC) of HL-1 cells. Additionally, the expression of CACNA2D, CACNB2 and CACNA1C in HL-1 cells were upregulated. Compared with CACNA1C siRNA-transfected HL-1 cells treated with TNF-α siRNA-transfected neutrophils CM, the APD and LTCC of CACNA1C siRNA-transfected HL-1 cells were shortened in control N1 neutrophil CM. The APD and LTCC of control HL-1 cells were also shortened in control N1 neutrophil CM, but prolonged in TNF-α siRNA-transfected neutrophils CM. Conclusion These findings suggest that neutrophils were polarized into N1 phenotype in AF, TNF-α released from N1 neutrophils contributes to the pathogenesis of AF, via decreasing the APD and LTCC in atrial myocytes through down-regulation of CACNA1C expression.

Abstract Circulating genetically abnormal cells (CACs) have emerged as a promising biomarker for the early diagnosis of lung cancer, particularly in patients with pulmonary nodules. However, their performance may be suboptimal in certain patient populations. This study aimed to refine patient selection to improve the detection of CACs in pulmonary nodules. A retrospective analysis was conducted on 241 patients with pulmonary nodules who had undergone pathological diagnosis through surgical tissue specimens. Utilizing consensus clustering analysis, the patients were categorized into three distinct clusters. Cluster 1 was characterized by older age, larger nodule size, and a higher prevalence of hypertension and diabetes. Notably, the diagnostic efficacy of CACs in Cluster 1 surpassed that of the overall patient population (AUC: 0.855 vs. 0.689, P = 0.044). Moreover, for Cluster 1, an integrated diagnostic model was developed, incorporating CACs, sex, maximum nodule type, and maximum nodule size, resulting in a further improved AUC of 0.925 (95% CI 0.846–1.000). In conclusion, our study demonstrates that CACs detection shows better diagnostic performance in aiding the differentiation between benign and malignant nodules in older patients with larger pulmonary nodules and comorbidities such as diabetes and hypertension. Further research and validation are needed to explore how to better integrate CACs detection into clinical practice.

Abstract Silk fabrics hold immense historical value as precious legacies left by our ancestors, yet they face significant damage during archaeological excavations, necessitating urgent protective measures. However, The current protective materials can’t effectively prevent the degradation of silk fabrics. Nanotechnology has emerged as a promising avenue for the consolidation and preservation of silk fabrics, offering novel concepts and materials. In this study, we propose an innovative and cost-effective method that uses the MOF-818 with a radical scavenging ability to enhance the protection of silk fabrics. The resulting demonstrates that the MOF-818 was the large surface area and porous properties, which exhibited excellent superoxide dismutase (SOD)-like activity at 10 ug/mL. The silk fabrics treated by MOF-818 displays small color difference, reduced the oxidation of functional group and prevents the degradation of silk fabrics. The successful development of this nanocomposite marks a significant advancement in silk protection, opening new horizons for the preservation of silk cultural relics.

Abstract Objective This retrospective cohort identified the association of human serum albumin (HSA) with adverse outcomes (septic shock, in-hospital and out-of-hospital mortality) in elderly hospitalized patients who have community-acquired pneumonia (CAP) and specific body mass index (BMI). Materials and methods This research included hospitalized CAP individuals (≥ 60 years) and was conducted at a teaching hospital in western China. All the patients were categorized into three populations based on two BMI cutoff values (18.5 kg/m2 and 24 kg/m2). The data was acquired from medical records, local government mortality databases, and telephone interviews. Binomial logistic regression analysis was used to explore the associations between low HSA and septic shock and in-hospital mortality, and Cox regression analysis was used to explore the association between low HSA and out-of-hospital mortality. Results A total of 627 patients were included in the analysis of in-hospital death and septic shock, and 431 patients were included in the analysis of out-of-hospital death. The study showed that 120 elderly patients with CAP (19.14%) died in the hospital, while 141 patients (32.71%) died out of the hospital, and 93 patients (14.83%) developed septic shock. No differences in in-hospital and out-of-hospital mortality were observed for BMI values

Abstract Cachexia, which affects 50–80% of cancer patients, is a debilitating syndrome that leads to 20% of cancer-related deaths. A key feature of cachexia is adipose tissue atrophy, but how it contributes to the development of cachexia is poorly understood. Here, we demonstrate in mouse models of cancer cachexia that white adipose tissue browning, which can be a characteristic early-onset manifestation, occurs prior to the loss of body weight and skeletal muscle wasting. By analysing the proteins differentially expressed in extracellular vesicles derived from cachexia-inducing tumours, we identified a molecular chaperone, Glucose-regulated protein 75 (GRP75), as a critical mediator of adipocyte browning. Mechanistically, GRP75 binds adenine nucleotide translocase 2 (ANT2) to form a GRP75–ANT2 complex. Strikingly, stabilized ANT2 enhances its interaction with uncoupling protein 1, leading to elevated expression of the latter, which, in turn, promotes adipocyte browning. Treatment with withanone, a GRP75 inhibitor, can reverse this browning and alleviate cachectic phenotypes in vivo. Overall, our findings reveal a novel mechanism by which tumour-derived GRP75 regulates white adipose tissue browning during cachexia development and suggest a potential white adipose tissue-centred targeting approach for early cachexia intervention.

Objective To explore the influencing factors of incision infection in elderly patients with traumatic limb fracture after surgery, and to construct a nomographic model. Methods A total of 360 elderly patients with traumatic limb fracture who received surgical treatment in the First Affiliated Hospital of Chengdu Medical College from May 2021 to September 2023 were selected as the study subjects and divided into the modeling group (n = 252) and the verification group (n = 108) by the computer random number table. LASSO regression and logistic regression were used to analyze the influencing factors of postoperative incision infection, and column line diagrams were constructed according to the influencing factors, and the predictive performance and effect of the risk prediction model were evaluated by ROC curve and calibration curve. Results Twenty-seven research variables were included in the LASSO regression model for screening, and two models were constructed based on minimum values and standardization. Model 1 included 12 variables, including body mass index (BMI), use of steel plate, diabetes, drainage tube placement time, incision type, operation time, incision length, the ratio of peripheral blood C-reactive protein to albumin (CAR), serum procalcitonin (PCT)/albumin (ALB), interleukin-6 (IL-6), neutrophil to lymphocyte ratio (NLR), and serum erythrocyte sedimentation rate (ESR) three days after operation. Seven variables were included in model 2, including diabetes, drainage tube placement time, and peripheral blood CAR, PCT/ ALB, IL-6, NLR, ESR 3 days after surgery. The logistic regression analysis models were constructed with the dependent variable of whether the incision infection occurred after surgery, and the variables screened by LASSO regression in model 1 and model 2 as independent variables. The results of model 1 showed that BMI ≥28 kg/ m2, combined with diabetes, incision type Ⅲ, operation time, incision length, use of steel plate, placement time of drainage tube ≥ 6 days, and peripheral blood CAR, PCT/ ALB, IL-6, NLR, ESR 3 days after surgery were independent risk factors for postoperative incision infection in elderly patients with traumatic limb fracture (P < 0.05) . The results of model 2 showed that the combination of diabetes, the placement time of drainage tube ≥6 days and the peripheral blood CAR, PCT/ ALB, IL-6, NLR, ESR 3 days after operation were independent risk factors for postoperative incision infection in elderly patients with traumatic limb fracture (P < 0.05) . The area under the ROC curve of Model 1 in the modeling and validation groups was respectively 0.949 (95% CI: 0.898 - 1.000) and 0.981 (95% CI: 0.956 - 1.000), respectively. The results of the Hosmer Lemeshow test for Model 1 in the modeling and validation groups showed that the model did not deviate from a perfect fit, and the consistency of the calibration curve was good. The area under the ROC curve of Model 2 in the modeling and validation groups was respectively 0.882 (95% CI: 0.787 - 0.977) and 0.921 (95% CI: 0.843 - 1.000), respectively. Furthermore, the Hosmer Lemeshow test of Model 2 in the modeling and validation groups showed that the model deviated from a perfect fit and the consistency of the calibration curve was poor. Conclusion BMI, combined diabetes, incision type, operation time, incision length, use of steel plate, placement time of drainage tube, CAR, PCT/ ALB, IL-6, NLR and ESR of peripheral blood 3 days after operation are the influencing factors of postoperative incision infection in elderly patients with traumatic limb fracture.

Abstract Pyrolysis of animal manure at high temperature is necessary to effectively immobilize heavy metals, while the available phosphorus (P) level in biochar is relatively low, rendering it unsuitable for use as fertilizer. In this study, the pretreatment of swine manure with different potassium (K) sources (KOH, K2CO3, CH3COOK and C6H5K3O7) was conducted to produce a biochar with enhanced P availability and heavy metals immobility. The addition of all K compounds lowered the peak temperature of decomposition of cellulose in swine manure. The percentage of ammonium citrate and formic acid extractable P in biochar increased with K addition compared to undoped biochar, with CH3COOK and C6H5K3O7 showing greater effectiveness than KOH and K2CO3, however, water- extractable P did not exhibit significant changes. Additionally, the available and dissolved Si increased due to the doping of K, with KOH and K2CO3 having a stronger effect than CH3COOK and C6H5K3O7. X-Ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) analysis revealed that K addition led to the formation of soluble CaKPO4 and silicate. In addition, the incorporation of K promoted the transformation of labile copper (Cu) and znic (Zn) into the stable fraction while simultaneously reducing their environmental risk. Our study suggest that the co-pyrolysis of swine manure and organic K represents an effective and valuable method for producing biochar with optimized P availability and heavy metals immobility.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high incidence of acute exacerbation and an increasing mortality rate. Currently, treatment methods and effects are limited. Therefore, we conducted a meta-analysis of the incidence of acute exacerbation in patients with IPF, hoping to provide reference for the prevention and management of IPF. We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases. From the creation of the database to the cohort study on April 3, 2023, we collected studies on the incidence of acute exacerbation of IPF patients, and used Stata software (version 16.0) for meta analysis. We used the Newcastle Ottawa Quality Assessment Scale (NOS) to assess the risk of bias for each study. We calculated the incidence of acute exacerbation in IPF patients and analyzed the risk factors for acute exacerbation in IPF patients and prognostic factors for overall survival from the initial IPF diagnosis. A total of ten cohort studies on the incidence of AE-IPF were included, including 11,855 IPF patients. The results showed that the incidence of acute exacerbation within one year was 9%; the incidence of acute exacerbation within 2 years is 13%; the incidence of acute exacerbation within 3 years is 19%; the incidence of acute exacerbation within 4 years is 11%. In addition, one study reported an acute exacerbation rate of 1.9% within 30 days. The incidence of acute exacerbation within ten years reported in one study was 9.8%. Mura et al.'s article included a retrospective cohort study and a prospective cohort study. The prospective cohort study showed that the incidence of acute exacerbation within 3 years was 18.6%, similar to the results of the retrospective cohort study meta-analysis. Our system evaluation and meta-analysis results show that the incidence of AE-IPF is relatively high. Therefore, sufficient attention should be paid to the research results, including the management and prevention of the disease, in order to reduce the risk of AE. Trial registration: PROSPERO, identifier CRD42022341323.

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration, destruction, and excessive ossification of articular cartilage. The prevalence of OA is rising annually, concomitant with the aging global population and increasing rates of obesity. This condition imposes a substantial and escalating burden on individual health, healthcare systems, and broader social and economic frameworks. The etiology of OA is multifaceted and not fully understood. Current research suggests that the death of chondrocytes, encompassing mechanisms such as cellular apoptosis, pyroptosis, autophagy, ferroptosis and cuproptosis, contributes to both the initiation and progression of the disease. These cell death pathways not only diminish the population of chondrocytes but also exacerbate joint damage through the induction of inflammation and other deleterious processes. This paper delineates the morphological characteristics associated with various modes of cell death and summarizes current research results on the molecular mechanisms of different cell death patterns in OA. The objective is to review the advancements in understanding chondrocyte cell death in OA, thereby offering novel insights for potential clinical interventions.

This is the third paper in the series Catalogue of fungi in China that aims to systematically and promptly publish Chinese fungal species. In this paper of the series, we focus on macrofungi from the southern border area of Xizang, a previously less concerned region. A total of 15 new species in six orders, 11 families, and 12 genera from Agaricomycetes, Basidiomycota are described. Both morphological and phylogenetic analyses support the identity of these new species and their taxonomic placements. In addition, one new combination Trechispora cryptomerioides is proposed. We hope that the third paper in the series Catalogue of fungi in China will draw more attention to reporting Chinese fungal diversity in the border areas of Xizang and other special geographic regions besides the aim of this series itself.

Flame temperature and spectral emissivity were the important parameters characterizing the sufficient degree of fuel combustion and the particle radiative characteristics in the Rocket Based Combined Cycle (RBCC) combustor. To investigate the combustion characteristics of the complex supersonic flame in the RBCC combustor, a new radiation thermometry combined with Levenberg-Marquardt (LM) algorithm and the least squares method was proposed to measure the temperature, emissivity and spectral radiative properties based on the flame emission spectrum. In-situ measurements of the flame temperature, emissivity and spectral radiative properties were carried out in the RBCC direct-connected test bench with laser-induced plasma combustion enhancement (LIPCE) and without LIPCE. The flame average temperatures at fuel global equivalence ratio (α) of 1.0b and 0.6 with LIPCE were 4.51% and 2.08% higher than those without LIPCE. The flame combustion oscillation of kerosene tended to be stable in the recirculation zone of cavity with the thermal and chemical effects of laser induced plasma. The differences of flame temperature at α = 1.0b and 0.6 were 503 K and 523 K with LIPCE, which were 20.07% and 42.64% lower than those without LIPCE. The flame emissivity with methane assisted ignition was 80.46% lower than that without methane assisted ignition, due to the carbon-hydrogen ratio of kerosene was higher than that of methane. The spectral emissivities at 600 nm with LIPCE were 1.25%, 22.2%, and 4.22% lower than those without LIPCE at α = 1.0a (with methane assisted ignition), 1.0b (without methane assisted ignition) and 0.6. The effect of concentration in the emissivity was removed by normalization to analyze the flame radiative properties in the RBCC combustor chamber. The maximum differences of flame normalized emissivity were 50.91% without LIPCE and 27.53% with LIPCE. The flame radiative properties were stabilized under the thermal and chemical effects of laser induced plasma at α = 0.6.