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Objective The accurate measurement of Cobb angles is crucial for the effective clinical management of patients with adolescent idiopathic scoliosis (AIS). The Lenke classification system plays a pivotal role in determining the appropriate fusion levels for treatment planning. However, the presence of interobserver variability and time‐intensive procedures presents challenges for clinicians. The purpose of this study is to compare the measurement accuracy of our developed artificial intelligence measurement system for Cobb angles and Lenke classification in AIS patients with manual measurements to validate its feasibility. Methods An artificial intelligence (AI) system measured the Cobb angle of AIS patients using convolutional neural networks, which identified the vertebral boundaries and sequences, recognized the upper and lower end vertebras, and estimated the Cobb angles of the proximal thoracic, main thoracic, and thoracolumbar/lumbar curves sequentially. Accordingly, the Lenke classifications of scoliosis were divided by oscillogram and defined by the AI system. Furthermore, a man–machine comparison (n = 300) was conducted for senior spine surgeons (n = 2), junior spine surgeons (n = 2), and the AI system for the image measurements of proximal thoracic (PT), main thoracic (MT), thoracolumbar/lumbar (TL/L), thoracic sagittal profile T5–T12, bending views PT, bending views MT, bending views TL/L, the Lenke classification system, the lumbar modifier, and sagittal thoracic alignment. Results In the AI system, the calculation time for each patient's data was 0.2 s, while the measurement time for each surgeon was 23.6 min. The AI system showed high accuracy in the recognition of the Lenke classification and had high reliability compared to senior doctors (ICC 0.962). Conclusion The AI system has high reliability for the Lenke classification and is a potential auxiliary tool for spinal surgeons.

Abstract Due to the limitations imposed by urban power grid outages for maintenance, on‐line harmonic current detection technology for distribution network cables is expected to become an effective supplement to traditional offline diagnostic methods, enhancing the real‐time diagnosis of distribution network cable insulation conditions. This study established a 10 kV distribution network cable test platform and prepared typical defective cables subjected to moisture and long‐term thermal aging. Using COMSOL finite element electromagnetic simulation, the magnetic flux evolution laws of the cable insulation under typical defects were obtained. Experimental tests provided the harmonic current characteristics and statistical features of cables with typical defects. Based on these data, a method for analysing the degradation degree of distribution network cables was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis. Furthermore, a defect‐type identification method based on cluster analysis was proposed. Results indicate that the odd harmonics and the 4th harmonic of the distribution network cable's harmonic current are closely related to the cable's degradation state. A model integrating principal component analysis (PCA) data dimensionality reduction and expectation‐maximization clustering analysis achieved a recognition accuracy of up to 75.64% in distinguishing between moisture‐affected and normal cable states. The proposed on‐line detection and evaluation methods can effectively identify high‐risk cables with latent defects.

Abstract Cross‐dataset object detection methods can adapt to the needs of rapid category expansion in object detection tasks. However, these methods are prone to generate dataset‐aware errors with false alarm objects. This study is aimed to address these issues. A box‐separated multiple‐head module and box‐separated loss function based on the YOLOv8 network are devised to achieve cross‐dataset object detection. Additionally, a sameclass‐aware fusion module to avoid gradient conflicts due to cross‐category conflicts is developed. A multiple‐head fusion module is devised to reduce the number of false alarm objects caused by dataset‐aware errors. A global class‐aware sampler is also designed to adapt to the impact of the imbalanced number of categories and training samples across datasets. The effectiveness of the box‐separated multiple‐head module is verified using cross‐datasets built using the COCO, WiderFace, WiderPerson, and OpenImages V4 datasets. Extensive experiments demonstrate the efficiency and precision of the proposed method.

Abstract Aims/Introduction We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease’s degree. Materials and Methods We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)‐194 and thrombospondin‐1 (TSP‐1) messenger ribonucleic acid (mRNA) in the participants’ circulation were measured using a quantitative real‐time polymerase chain reaction. Results Circulating TSP‐1 mRNA (P = 0.024) and miR‐194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP‐1 mRNA (P = 0.040) and miR‐194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP‐1 mRNA expression increased with urinary microalbumin. However, miR‐194 declined in group B and increased in group C. Circulating TSP‐1 mRNA was positively correlated with cystatin‐c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR‐194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin‐c (β = 0.578; P = 0.021) and UmALB/Cr (β = 0.001; P = 0.009) as independent factors for TSP‐1 mRNA; UmALB/Cr (β = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP‐1 mRNA and miR194 were 0.756 (95% confidence interval 0.620–0.893; sensitivity 0.69 and specificity 0.71, P

Abstract Background Despite the adverse effects of ambient fine particulate matter (PM2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long‐term PM2.5 exposure was calculated using 1‐km resolution satellite‐based PM2.5 estimates. PM2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort‐stratified Cox proportional hazards models, individually and in combination. Results In 488,166 person‐years of follow‐up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM2.5 stratification (≤65.02 µg/m3) other than in high PM2.5 stratification (>65.02 µg/m3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66–0.85) and 1.10 (95% CI: 0.99–1.22), respectively. Similar results were observed for PA intensity. High PM2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR = 1.79, 95% CI: 1.59–2.01 for PA volume; HR = 1.82, 95% CI: 1.64–2.02 for PA intensity). Conclusion PA could reduce type 2 diabetes risk in low‐pollution areas, but high PM2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long‐term polluted residents.

Abstract Objectives Parkinson disease (PD) is the third leading cause of mortality among middle‐aged and older individuals in China. This study aimed to explore the trends and distribution features of PD mortality in China from 2013 to 2021 and make predictions for the next few decades. Methods Relevant data were obtained from the Chinese Center for Disease Control and Prevention Disease Surveillance Point system. The joinpoint regression model was used to evaluate trends. The R software was used to predict future trends. Results Age‐standardized mortality rate (ASMR) of PD increased from 0.59 per 100,000 individuals to 1.22 per 100,000 individuals from 2013 to 2021, with an average annual percent change (AAPC) of 9.50 (95% CI: 8.24–10.78). The all‐age ASMR of PD were higher in male individuals than in female individuals, and ASMR increased with age. The number of deaths and ASMR increased gradually from west to east and from rural to urban areas. Furthermore, ASMR is expected to increase to 2.66 per 100,000 individuals by 2040. Conclusions The heightened focus on the ASMR of PD among male individuals, urban areas, eastern China, and individuals aged ≥85 years has become a key determinant in further decreasing mortality, thereby exhibiting novel challenges to effective strategies for disease prevention and control.

Abstract EMT dysfunction is a dominant mechanisms of hypospadias. Thus, identification of EMT‐related lncRNAs based on transcriptome sequencing data of hypospadias might provide novel molecular markers and therapeutic targets for hypospadias. First, the microarray data related to hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the differentially expressed lncRNAs and messenger RNAs (mRNAs) related to EMT were screened to construct lncRNA‐mRNA co‐expression interaction pairs. In addition, the microRNA (miRNA) prediction analysis was performed through bioinformatics methods to construct a ceRNA network. Moreover, function prediction and function enrichment and pathway analyses were also performed. Finally, the core EMT‐related lncRNAs were verified based on mRNA expression changes and cell functions. A total of 6 EMT‐related lncRNAs were identified and 123 mRNA‐lncRNA co‐expression interaction pairs were screened in this study. Additionally, a ceRNA regulatory network comprising 17 mRNAs, 4 lncRNAs, and 28 miRNAs was constructed based on the prediction of hypospadias‐related miRNAs. The validation results of the dataset GSE121712 revealed that only BEX1 was positively correlated with the expression of the lncRNA GNAS‐AS1 (r = 0.874, P < 0.01), both of which had high expression. The cell experiment results demonstrated that interfering with the expression of GNAS‐AS1 significantly promoted the proliferation, migration, and EMT of cells. Importantly, it was confirmed that GNAS‐AS1 can serve as a ceRNA and play an important role in the EMT of hypospadias. Hence, it may be considered as a potential target in the treatment of this disease.

Abstract Background Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. Methods The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. Results The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2‐butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2‐butoxyethyl) phosphate (r = 0.88, p

Abstract Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo‐HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS‐IB‐1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow‐up was 507 days for survivors. The 2‐year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT‐CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05‐60.03, p = 0.045; HR = 3.64, 95%CI 1.40‐9.44, p = 0.008; respectively), while post‐transplantation cyclophosphamide based graft‐versus‐host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11‐0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

Abstract A dual‐band shared‐aperture antenna array is presented, involving a combined scheme to suppress mutual coupling interference. The proposed array is comprised of a low‐band (LB) antenna, a frequency selective surface (FSS), sixteen high‐band (HB) antennas, and a reflector. The LB antenna utilises electromagnetic transparent (ET) characteristics to minimise scattering interference, while the FSS isolates resonance interference and port signal interference. The combined scheme integrates the benefits of both the ET antenna and FSS to suppress mutual coupling interference effectively. A prototype of the proposed antenna was fabricated and measured, operating at 1.7–2.7 GHz and 3.3–3.9 GHz. The simulated and measured results demonstrate stable patterns for both the LB antenna and the HB antennas. The cross‐band isolation is higher than 28 dB in the low‐band. With these advantages, the antenna array is suitable for base station applications.

Abstract Background Airway pressure release ventilation (APRV) has become increasingly popular for the management of acute respiratory distress syndrome (ARDS); however, its clinical impact remains a topic of debate. Furthermore, there is a gap between the guidelines and the actual clinical practices in mechanical ventilation management for ARDS. This survey aimed to explore the utilization of APRV and mechanical ventilation strategies for ARDS in Chinese intensive care unit (ICU) clinicians. Methods A comprehensive 34‐item survey was distributed online platforms amongst ICU clinicians across mainland China from June to August 2019. Results A total of 420 valid responses were collected, with 57.4% (241) originating from academic hospitals and 42.6% (179) from non‐academic hospitals. Of the respondents, 98.6% (414) recognized the significance of low tidal volume ventilation for ARDS prognosis, 85.2% adhered to a tidal volume below 8 mL/kg predicted body weight, and most (46.4%) selected the initial positive end‐expiratory pressure within the range of 5–10 cmH2O based on experience. Among the respondents, 62.1% (261) reported familiarity with APRV and 41.9% (176) had implemented APRV. Of those who had utilized APRV, 93.2% (164) believed in its effectiveness for ARDS patients and 69.3% (122) advocated for early application of APRV. Substantial variations were noted regarding APRV initiation settings and the preservation of spontaneous breathing during APRV. Academic hospitals exhibited higher usage rates of lung recruitment, neuromuscular blockade, prone ventilation, and acquaintance with and utilization of APRV compared to non‐academic hospitals (all p values ≤ 0.001). Conclusions Our findings highlight opportunities for improvement in mechanical ventilation management for ARDS, particularly in non‐academic hospitals. Additionally, a significant proportion of clinicians demonstrated limited knowledge of APRV, and there was a lack of consensus on its application. Further training and larger‐scale clinical trials are required to validate the efficacy and utilization of APRV in managing ARDS.

Abstract Objective Radiofrequency thermocoagulation (RFTC) has emerged as an effective and safe treatment method for patients with refractory focal epilepsy, when stereo‐electroencephalography (SEEG) is implanted. Although real‐world research results are still limited, a considerable number of patients have shown favorable outcomes with this less invasive method. This study aims to describe the outcomes and predictive factors of SEEG‐RFTC in real‐world research. Methods A retrospective observational study was conducted on patients in the authors' epilepsy center. In total, 121 patients who underwent RFTC were included in the study. Post‐RFTC outcomes were evaluated using the seizure‐free rate and response rate (seizure frequency reduction more than 50%). Predictive factors influencing post‐RFTC outcome were considered by comparing different variables. Results The mean follow‐up period was 18.3 months. Eighty‐two patients (67.8%) were responders and 54 (44.6%) were seizure free. In 36 patients with malformation of cortical development, the seizure‐free rate and the response rate were 69.44% and 83.33%, respectively. In 20 patients with hippocampal sclerosis, 19 patients were responders and 14 (70%) patients were seizure free at the last follow‐up. The MRI feature and etiology of epilepsy are correlated with the outcome. MR‐positive is a predictive factor for seizure freedom (p

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Abstract Monascus red pigments (MRP) may have benefits against NAFLD with an unclear mechanism. This study aimed to explore the protective effect of MRP supplementation against NAFLD through regulation of gut microbiota and metabolites. The C57BL/6 mice animals were randomly allocated into the normal diet (NC), HFHS diet‐induced NAFLD model, and MRP intervention group fed with HFHS diet. Serum lipid profiles and liver function parameters were measured. Liver and colon histopathology analysis was conducted to determine the injury in the liver and colon. 16S rRNA gene sequencing was employed to analyze gut microbial composition from fecal samples. Untargeted metabonomics was performed to analyze changes in metabolites in serum and fecal samples. MRP supplementation significantly improved the HFHS‐induced alterations in body weight, lipid profiles, and liver function (p

Abstract Adriamycin (ADR) is a frequently employed chemotherapeutic agent for the management of breast cancer. Nevertheless, multidrug resistance (MDR) can impair its therapeutic efficacy in breast cancer. MDR is characterized by increased expression of the P‐glycoprotein (P‐gp) efflux pump, up‐regulation of anti‐apoptotic proteins, and downregulation of pro‐apoptotic proteins. Consequently, inhibition of ATP‐binding cassette (ABC) transporter proteins has been deemed the most efficacious approach to overcome MDR. In this study, we used MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide), Western blots, flow cytometry, immunofluorescence, and constructed xenograft tumors to investigate whether ginsenoside Rg3‐near‐infrared photothermal (Rg3‐NIR) combination reversed multidrug resistance in MCF‐7/ADR breast cancer. In vivo and in vitro experiments, the results showed that Rg3‐NIR co‐treatment was effective in inducing the apoptosis of MCF‐7/ADR breast cancer cells. This was achieved by reversing the expression of drug resistance‐associated proteins, while also inhibiting cell proliferation, migration, and epithelial–mesenchymal transition (EMT) processes via attenuation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway transduction. Ginsenoside Rg3 combined with near‐infrared photothermal therapy (NIR) effectively reverses multidrug resistance in breast cancer MCF‐7/ADR cells, providing a new therapeutic strategy for breast cancer drug resistance.

Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient‐derived xenograft (PDX) and cell line‐derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia‐activated prodrugs (HAPs). PDX models showed greater fidelity in gene expression to clinical HNSCC than cell lines, as did CDX models relative to their paired cell lines. PDX models were significantly more hypoxic than CDX models, as assessed by hypoxia gene signatures and pimonidazole immunohistochemistry, and showed similar hypoxia gene expression to clinical HNSCC tumours. Hypoxia or proliferation status alone could not determine HAP sensitivity across our 20 HNSCC and two non‐HNSCC tumour models by either tumour growth inhibition or killing of hypoxia cells in an ex vivo clonogenic assay. In summary, our tumour models provide clinically relevant HNSCC models that are suitable for evaluating hypoxia‐targeting therapies; however, additional biomarkers to hypoxia are required to accurately predict drug sensitivity.

Abstract Synthetic images facilitate stereo matching. However, synthetic images may suffer from image distortion, domain bias, and stereo mismatch, which would significantly restrict the widespread use of stereo matching models in the real world. The first goal in this paper is to synthesize real‐looking images for minimizing the domain bias between the synthesized and real images. For this purpose, sharpened disparity maps are produced from a mono real image. Then, stereo image pairs are synthesized using these imperfect disparity maps and the single real image in the proposed pipeline. Although the synthesized images are as realistic as possible, the domain styles of the synthesized images are always very different from the real images. Thus, the second goal is to enhance the domain generalization ability of the stereo matching network. For that, the feature extraction layer is replaced with a teacher–student model. Then, a constraint of binocular contrast features is imposed on the output of the model. When tested on the KITTI, ETH3D, and Middlebury datasets, the accuracy of the method outperforms traditional methods by at least 30%. Experiments demonstrate that the approaches are general and can be conveniently embedded into existing stereo networks.

Abstract Objective Subcortical nuclei such as the thalamus and striatum have been shown to be related to seizure modulation and termination, especially in drug‐resistant epilepsy. Enhance diffusion‐weighted imaging (eDWI) technique and tri‐component model have been used in previous studies to calculate apparent diffusion coefficient from ultra high b‐values (ADCuh). This study aimed to explore the alterations of ADCuh in the bilateral thalamus and striatum in MRI‐negative drug‐resistant epilepsy. Methods Twenty‐nine patients with MRI‐negative drug‐resistant epilepsy and 18 healthy controls underwent eDWI scan with 15 b‐values (0–5000 s/mm2). The eDWI parameters including standard ADC (ADCst), pure water diffusion (D), and ADCuh were calculated from the 15 b‐values. Regions‐of‐interest (ROIs) analyses were conducted in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus. ADCst, D, and ADCuh values were compared between the MRI‐negative drug‐resistant epilepsy patients and controls using multivariate generalized linear models. Inter‐rater reliability was assessed using the intra‐class correlation coefficient (ICC) and Bland–Altman (BA) analysis. False discovery rate (FDR) method was applied for multiple comparisons correction. Results ADCuh values in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus in MRI‐negative drug‐resistant epilepsy were significantly higher than those in the healthy control subjects (all p

Abstract Background There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets. Methods We integrated druggable genome data, cis‐eQTL/cis‐pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia‐related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome‐wide MR (Phe‐MR) approach and investigated actionable drugs for target genes using available databases. Results MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA‐DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up‐regulation of HP [higher ALM (beta: 0.012, 95% CI: 0.007–0.018, P = 1.2*10−5) and higher grip strength (OR: 0.96, 95% CI: 0.94–0.98, P = 4.2*10−5)], MAP 3K3 [higher ALM (beta: 0.24, 95% CI: 0.21–0.26, P = 1.8*10−94), higher grip strength (OR: 0.82, 95% CI: 0.75–0.90, P = 2.1*10−5), and faster walking pace (beta: 0.03, 95% CI: 0.02–0.05, P = 8.5*10−6)], and MFGE8 [higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06–0.11, P = 6.1*10−13; blood pQTL, beta: 0.05, 95% CI: 0.03–0.07, P = 3.8*10−09)], as well as the down‐regulation of HLA‐DRA [lower ALM (beta: ‐0.09, 95% CI: −0.11 to −0.08, P = 5.4*10−36) and lower grip strength (OR: 1.13, 95% CI: 1.07–1.20, P = 1.8*10−5)] and COL15A1 [higher ALM (muscle eQTL, beta: ‐0.07, 95% CI: −0.10 to −0.04, P = 3.4*10−07; blood pQTL, beta: ‐0.05, 95% CI: −0.06 to −0.03, P = 1.6*10−07)], decreased the risk of sarcopenia. AURKA in blood (beta: ‐0.16, 95% CI: −0.22 to −0.09, P = 2.1*10−06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P = 5.3*10−05) tissues showed an inverse relationship with sarcopenia risk. The Phe‐MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticum might be potential therapeutics for sarcopenia by activating HP and inhibiting COL15A1, respectively. Conclusions Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA‐DRA may serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticum for sarcopenia requires further validation.

Abstract Background Muscle satellite cells (MuSCs) exert essential roles in skeletal muscle adaptation to growth, injury and ageing, and their functions are extensively modulated by microenvironmental factors. However, the current knowledge about the interaction of MuSCs with niche cells is quite limited. Methods A 10× single‐cell RNA sequencing (scRNA‐seq) was performed on porcine longissimus dorsi and soleus (SOL) muscles to generate a single‐cell transcriptomic dataset of myogenic cells and other cell types. Sophisticated bioinformatic analyses, including unsupervised clustering analysis, marker gene, gene set variation analysis (GSVA), AUCell, pseudotime analysis and RNA velocity analysis, were performed to explore the heterogeneity of myogenic cells. CellChat analysis was used to demonstrate cell–cell communications across myogenic cell subpopulations and niche cells, especially fibro‐adipogenic progenitors (FAPs). Integrated analysis with human and mice datasets was performed to verify the expression of FGF7 across diverse species. The role of FGF7 on MuSC proliferation was evaluated through administering recombinant FGF7 to porcine MuSCs, C2C12, cardiotoxin (CTX)‐injured muscle and d‐galactose (d‐gal)‐induced ageing model. Results ScRNA‐seq totally figured out five cell types including myo‐lineage cells and FAPs, and myo‐lineage cells were further classified into six subpopulations, termed as RCN3+, S100A4+, ID3+, cycling (MKI67+), MYF6+ and MYMK+ satellite cells, respectively. There was a higher proportion of cycling and MYF6+ cells in the SOL population. CellChat analysis uncovered a particular impact of FAPs on myogenic cells mediated by FGF7, which was relatively highly expressed in SOL samples. Administration of FGF7 (10 ng/mL) significantly increased the proportion of EdU+ porcine MuSCs and C2C12 by 4.03 ± 0.81% (P

Abstract Backgrounds Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. Methods Denervation‐induced muscle atrophy model was constructed in wild‐type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol‐free RBP4 (apo‐RBP4), retinol‐bound RBP4 (holo‐RBP4) or oral gavage of RBP4 inhibitor A1120. Holo‐RBP4‐stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross‐sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. Results The expression levels of RBP4 in skeletal muscles were significantly up‐regulated more than 2‐fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation‐induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin‐1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol‐bound holo‐RBP4 aggregated denervation‐induced ectopic fat accumulation and muscle atrophy. Consistently, holo‐RBP4 stimulation also had a dose‐dependent effect on the reduction of C2C12 myotube diameter and myofibre cross‐sectional area, as well as on the increase of Atrogin‐1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo‐RBP4 treatment increased the expression of its membrane receptor STRA6 (>3‐fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin‐1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3‐fold) in holo‐RBP4‐treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation‐induced muscle atrophy (30% increased myofibre cross‐sectional area) in mice. Conclusions In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6‐dependent and JAK2/STAT3 pathway‐mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

Abstract We present an in‐depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low‐density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence‐based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the “bibliometrix” R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co‐cited journal. These publications come from 14,801 authors, with Liu Zong‐Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong‐Yan having published the most papers. Ronald S. Weinstein was co‐cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

Abstract In 2015, the Indian Ocean exhibits an exceptionally weakened CO2 uptake, highlighting strong interannual variability of ocean carbon sink. By utilizing multiple ocean CO2 partial pressure (pCO2) data and a state‐of‐the‐art ocean biogeochemical model, we show that the 2015 ocean CO2 anomaly is characterized by a basin‐wide amplification of ocean pCO2, differing from ocean pCO2 responses to other Indian Ocean Dipole events (e.g., 1997 and 2019). The distinct ocean pCO2 anomaly is attributed to an amplified warming and an unprecedented weakening Indonesian Throughflow under the influence of co‐occurrence of positive IOD and extreme El Niño in 2015. The amplified warming drives higher ocean pCO2 in the western and central Indian Ocean, while the ITF transports anomalously high ocean pCO2 water from the Pacific Ocean to the southeastern Indian Ocean. This newly identified ocean carbon response provides deeper insights into the Indian Ocean carbon interannual variability.

Abstract Two‐dimensional (2D) semiconductors, such as monolayer MoS2, has emerged as a profound material platform in the post‐Moore era due to their versatile applications for high‐performance transistors, memories, photodetectors, neuristors, and so on. Nevertheless, the inherent defects in these atomically thin materials have given rise to significant hysteresis in their field‐effect transistors (FETs), resulting in shifted threshold voltages and elevated power consumptions not only on single‐device levels but also at circuitry scales. We herein report that, by vertically integrating an in‐plane ferroelectric, NbOCl2, with monolayer MoS2 FETs, the hysteresis in both the output and transfer curves of the latter can be greatly suppressed, which we attribute to compensated electromigration currents by the polarization currents of the 2D ferroelectric. This work opens a new avenue to hysteresis‐free 2D transistors without necessitating defect‐free channels, thus allowing for their use in high driving‐voltage scenarios such as power electronics.

Abstract Mixed‐flow pump is a typical pump using in low‐head cases of water lifting. The flow field pulsation is usually an important issue in the operation of mixed‐flow pumps and their pumping statins. Due to its large size, it is difficult to monitor the internal flow characteristics well, based on computational fluid dynamics, we use 5678 monitoring points which arranged in the impeller and fixed vane with using the high pulsation tracking network, and the pressure pulsation signals are analyzed by fast Fourier transform and variable mode decomposition to decompose the main frequency and intensity of the pressure pulsation signals, then analyze the energy dissipation with the entropy production rate (EPR). It is found that there are strong low‐frequency (0.416, 0.625, and 1.67 Hz) pressure pulsation near hub, and the pressure pulsation on the shroud is stronger than that on the hub (at least three times or more); there are strong and stable pressure pulsation (25 Hz) on the shroud generated by the rotor–stator interference (RSI); and the EPR in the flow field can be well combined with the signal. Reasonably allocating material strength and controlling the number of vanes and impellers to avoid producing a common multiple can avoid pressure pulsation caused by RSI and reduce energy dissipation. Therefore, it is very effective in improving the efficiency of this part. Under low flow conditions, the siphon outflow passage can predict the high‐frequency (45.833 Hz) attenuation area well through the phase signal decomposition of the signal, which has certain significance for improving its stability and efficiency.

Abstract Our previous clinical metabolomics study illustrated that energy metabolism disorder is an underlying pathogenesis mechanism for the development of alcoholic liver disease (ALD). Supplementation of nicotinamide (NAM), the precursor of nicotinamide adenine dinucleotide (NAD+), may restore the energy metabolism homeostasis of ALD and thus serves as potential therapeutics to treat ALD. In this bedside‐to‐bench study, the protective effect of NAM against ALD was investigated by using the NIAAA mice model (chronic‐plus‐binge ethanol), and the liver regeneration boosting capability of NAM was evaluated by the partial hepatectomy mice model. Our results showed that NAM supplements not only protected the liver from alcohol‐induced injury and improved alcohol‐induced mitochondrial structure and function change, but also boosted liver regeneration in postpartial hepatectomy mice by increasing liver NAD+ content. These findings suggested that NAM, a water‐soluble form of vitamin B3, can promote liver regeneration and improves liver function by alleviating alcohol‐induced energy metabolism disorder.

Abstract Changes in physiological factors may result in large pharmacokinetic variability of vancomycin in pediatric patients, thereby leading to either supratherapeutic or subtherapeutic exposure and potentially affecting clinical outcomes. This study set out to characterize the disposition of vancomycin, quantify the exposure target and establish an optimal dosage regimen among the Southern Chinese pediatric population. Routine therapeutic drug monitoring data of 453 patients were available. We performed a retrospective population pharmacokinetic analysis of hospitalized children prescribed intravenous vancomycin using NONMEM® software. A one‐compartment PPK model of vancomycin with body weight and renal functions as covariates based on a cutoff of 2 years old children was proposed in this study. Both internal and external validation showing acceptable and robust predictive performance of the model to estimate PK parameters. The value of area under the curve over 24 h to minimum inhibitory concentration ratio (AUC0‐24/MIC) ≥ 260 was a significant predictor for therapeutic efficacy. Monte Carlo simulations served as a model‐informed precision dosing approach and suggested that different optimal dose regimens in various scenarios should be considered rather than flat dosing. The evaluation of vancomycin exposure‐efficacy relationship indicated that lower target level of AUC0‐24/MIC may be needed to achieve clinical effectiveness in children, which was used to derive the recommended dosing regimen. Further prospective studies will be needed to corroborate and elucidate these results.

Abstract Ulcerative colitis is intricately linked to intestinal oxidative stress and dysbiosis of the gut microbiota. Lonicera japonica Thunb. (LJ) is a traditional edible and medical flower in China, and chlorogenic acid (CGA) is one of its characteristic components. However, it remains unclear whether gut microbiota plays a role in the therapeutic effects of LJ and GCA on colitis. Here, we first observed that oral administration of LJ and CGA for 3 weeks dramatically promoted the growth of Lactobacillus and fecal short‐chain fatty acids (SCFAs) production in healthy mice. Subsequently, the alleviating effects of LJ and CGA on colitis were explored with a dextran sulfate sodium‐induced colitis mice model. The intervention of LJ and CGA notably alleviated inflammation, intestinal barrier impairment, and oxidative stress in colitis and led to a significant elevation in Lactobacillus and fecal SCFAs. Eventually, the key role of gut microbiota and their metabolites on the therapeutic effects was validated by performing fecal microbiota transplantation and sterile fecal suspensions transplantation from LJ and CGA‐treated healthy mice to colitis mice. Our findings demonstrated that consumption of LJ and CGA could benefit the host both in healthy condition and colitis. The beneficial effects were attributed to the improvement of the endogenous antioxidant system and promotion of the probiotic Lactobacillus and SCFAs production. Our study highlighted the great potential of LJ and CGA to be consumed as functional foods and provided novel mechanisms by which they alleviated colitis.

Abstract This paper is dedicated to proposing improved input‐to‐state stability (ISS) criteria for a class of continuous‐time time‐varying switched singular systems (CTSSS) under slow/fast/slow‐fast switching signals. Specifically, for a CTSSS with time‐varying singular matrices, the authors start with an improved sufficient condition for verifying its ISS under slow switching signals based on the average dwell time method and a relaxed multiple Lyapunov function. Then, considering several or all subsystems may destroy the overall ISS, relaxed sufficient conditions are presented to ensure the ISS of the CTSSS under fast switching signals and slow‐fast switching signals, respectively. Note that the improvement of the proposed ISS criteria is embodied in the derivative of the required multiple Lyapunov functions along with the state trajectories of CTSSS can be positive or negative. Finally, three numerical examples are provided to illustrate the feasibility of the obtained results.

Abstract Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM), and cell death plays an important role. Ferroptosis is a recently discovered type of iron‐dependent cell death and one that is different from other kinds of cell death including apoptosis and necrosis. However, ferroptosis has not been described in the context of DN. This study explored the role of ferroptosis in DN pathophysiology and aimed to confirm the efficacy of the ferroptosis inhibitor SRS 16‐86 on DN. Streptozotocin injection was used to establish the DM and DN animal models. To investigate the presence or occurrence of ferroptosis in DN, we assessed the concentrations of iron, reactive oxygen species and specific markers associated with ferroptosis in a rat model of DN. Additionally, we performed haematoxylin–eosin staining, blood biochemistry, urine biochemistry and kidney function analysis to evaluate the efficacy of the ferroptosis inhibitor SRS 16‐86 in ameliorating DN. We found that SRS 16‐86 could improve the recovery of renal function after DN by upregulating glutathione peroxidase 4, glutathione and system xc−light chain and by downregulating the lipid peroxidation markers and 4‐hydroxynonenal. SRS 16‐86 treatment could improve renal organization after DN. The inflammatory cytokines interleukin 1β and tumour necrosis factor α and intercellular adhesion molecule 1 were significantly decreased following SRS 16‐86 treatment after DN. The results indicate that there is a strong connection between ferroptosis and the pathological mechanism of DN. The efficacy of the ferroptosis inhibitor SRS 16‐86 in DN repair supports its use as a new therapeutic treatment for DN.

ABSTRACT Aims/Introduction To assess the effect of empagliflozin treatment on left ventricular (LV), right ventricular (RV) and left atrial (LA) functions in diabetes patients with normal ejection fraction. Materials and Methods The study included a total of 128 diabetes patients with multiple cardiovascular risk factors who were subjected to a 6‐month follow up from the initiation of empagliflozin treatment. Before and after treatment with empagliflozin, LV, RV and LA strain, and noninvasive myocardial work parameters were evaluated by speckle tracking echocardiography. Results In 128 diabetes patients (mean age 56 ± 8 years, 85 men) with multiple cardiovascular risk factors, myocardial strain and work parameters were impaired, despite the absence of significant clinical symptoms of heart failure. After 6‐month treatment with empagliflozin, the absolute value of LV strain in all directions increased, represented by LV global longitudinal strain (−18.0 ± 1.7% to −19.2 ± 1.7% [mean ± SD]). The same trend in LV global work efficiency (93 [91–94] % to 94 [93–95] % [median (IQR)]), RV free‐wall longitudinal strain (−24.0 ± 2.7% to −25.0 ± 2.8%), LA reservoir (31 ± 5% to 34 ± 5%) and conduit strain (−14 ± 4% to −16 ± 4%) was also observed. LV mass index (106.9 ± 16.8–103.6 ± 16.4 g/m2) and LV global wasted work (143 [111–185] mmHg% to 108 [88–141] mmHg%) decreased after treatment (P

Abstract Aims/Introduction Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti‐oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes‐related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model. Materials and Methods To induce insulin resistance, mice were fed a high‐fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose‐regulated protein 78, phosphodiesterase type 5, protein kinase R‐like endoplasmic reticulum (ER) kinase, and phospho‐protein kinase R‐like endoplasmic reticulum kinase in heart tissue. Results The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate‐specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high‐fat diet‐induced cardiac dysfunction and decreased ER stress. Conclusions PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.

Abstract Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR‐136‐5p or Smurf1 expression were transfected into BMSCs. The effects of miR‐136‐5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR‐136‐5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR‐136‐5p/BMSCs/β‐TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro‐CT and HE staining. Elevating miR‐136‐5p‐3p or suppressing Smurf1 could stimulate OD of BMSCs. miR‐136‐5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR‐136‐5p on the OD of BMSCs. miR‐136‐5p/BMSCs/β‐TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1‐targeting miR‐136‐5p‐modified BMSCs combined with 3D‐printed β‐TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

Objective Management of extensive acetabular bone defects in total hip arthroplasty (THA) remains challenging. This study aims to investigate the feasibility and preliminary outcomes of 3D‐printed personalized porous acetabular components for the reconstruction of acetabular defects in primary THA. Methods This retrospective study involved seven patients who received 3D‐printed acetabular components in primary THA between July 2018 and March 2021. Preoperatively, acetabular bone defects were evaluated by referencing the Paprosky classification. There were two "Paprosky type IIIA" defects and five "Paprosky type IIIB" defects. The acetabular components were custom‐made for each patient to reconstruct the extensive acetabular defects. The hip function was assessed according to the Harris hip score (HHS). Clinical and radiographic outcomes were assessed. Results The average follow‐up period was 40 months, ranging from 26 to 57 months. There were no patients lost to follow‐up. The HHS improved from 44 (range: 33–53) before the operation to 88 (range: 79–93) at the final follow‐up. Postoperative X‐rays showed that the 3D‐printed personalized components were properly fitted with the acetabulum. The average center of rotation (COR) discrepancy was 2.3 mm horizontally and 2.1 mm vertically, respectively. Tomosynthesis‐Shimadzu metal artifact reduction technology images showed that the implant was in close contact with the host bone. Moreover, no complications were observed during the follow‐up period, including loosening, dislocation, or component protrusion. Conclusion The implantation of 3D‐printed personalized acetabular components showed accurate reconstruction, stable mechanical support, and favorable function at short‐term follow‐up. This may be a viable alternative method for reconstructing extensive acetabular defects in THA.

Objective How to minimize postoperative pain following knee replacement surgery has been a great challenge. This study was performed to evaluate the effect of applying a topical nonsteroidal anti‐inflammatory drug (NSAID) lateral to the incision for postoperative pain following unicompartmental knee arthroplasty (UKA). Methods The randomized controlled trial enrolled 100 patients from August 2023 to January 2024. One hundred patients who underwent UKA were randomized into two groups. The intervention group received a topical NSAID lateral to the incision postoperatively, and the control group received a placebo lateral to the incision postoperatively. The primary outcome measures were the amount of opioid consumption and the visual analogue scale (VAS) score (12, 24, 36, 48, and 72 h after operation) for pain. The secondary outcome measures were the American Knee Society Score (AKSS, preoperation and 1‐month follow‐up after operation), the time of first analgesic demand, side effects of opioids, operation time, postoperative stay, surgery‐related complications, and postoperative incision healing grade. Independent sample t test and paired sample t test were used to compare continuous data. Chi‐square test and Fisher's precision probability tests were used to analyze the categorical data. Results Ninety‐eight patients (intervention group, 48 patients; control group, 50 patients) were analyzed. Opioid consumption was significantly lower in the intervention group than in the control group during the first 12 h, 12 to 24 h, and 24 to 48 h postoperatively (p

Abstract Background This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1. Methods Humanized fragments, consisting of the endothelial cell‐specific K18 promoter, human ST6GAL1‐encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed. Results Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range. Conclusion A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Abstract When some new‐type sensors are subjected electromagnetic interference (EMI), the traditional standard can no longer serve as the guidance for their EMI protection. Therefore, it is necessary to evaluate the complexity of the new sensing equipment's suffering from electromagnetic interference. A hybrid method of feature extraction and complexity evaluation of Electromagnetic Interference signals based on generalised correntropy criterion (GCC) is proposed. First, a variational mode decomposition algorithm for adaptive extraction of decomposed signals is constructed using GCC, and Generalised S‐transform is used for processing and reorganisation. Then, according to the time‐frequency space model, a new quantitative evaluation criterion interference factor is proposed, which overcomes the shortcomings of the traditional qualitative classification and the inability to solve the cross classification of indicators. Then, the Gated Recurrent Unit is introduced, and the GCC‐GRU evaluation model with GCC as the loss function is derived. The authors conduct EMI tests and measured signal evaluation with Medium Voltage and High Voltage switches, and the results show that the method proposed is correct and effective.

Abstract Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta‐analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P

Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

Abstract Noncompartmental analysis (NCA) is a model‐independent approach for assessing pharmacokinetics (PKs). Although the existing NCA algorithms are very well‐established and widely utilized, they suffer from low accuracies in the setting of sparse PK samples. In response, we developed Deep‐NCA, a deep learning (DL) model to improve the prediction of key noncompartmental PK parameters. Our methodology utilizes synthetic PK data for model training and uses an innovative patient‐specific normalization method for data preprocessing. Deep‐NCA demonstrated adequate performance across six previously unseen simulated drugs under multiple dosing, showcasing effective generalization. Compared to traditional NCA, Deep‐NCA exhibited superior performance for sparse PK data. This study advances the application of DL to PK studies and introduces an effective method for handling sparse PK data. With further validation and refinement, Deep‐NCA could significantly enhance the efficiency of drug development by providing more accurate NCA estimates while requiring fewer PK samples.

Abstract Marine resources are rich. In recent years, more and more people have paid attention to the development of blue food. Fish protein is one of the essential biomolecules in blue food. It is a natural emulsifier because of its natural, nontoxic, easily obtained, degradable, and good surface activity. The research and application of fish protein as an emulsifier were reviewed in this paper. The emulsifying mechanism of fish protein was discussed. The emulsifying property of fish protein was affected by natural factors (source and protein concentration) and processing environment (ion strength, temperature, and pH). The emulsifying property of fish protein was improved by ultrasound, high pressure, microgel, complexation, glycosylation, and enzyme cross‐linking. It was pointed out that future research of fish protein applications should focus on the problems of shortening the gap between laboratory and commercial; stable emulsion of fish protein is difficult to preserve and single loading. It provides a reference for the development of fish protein emulsifiers.

Objective The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. Methods From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side‐to‐side difference by the KT‐1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow‐up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2‐test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t‐test, and the Mann–Whitney U‐test was undertaken between the two groups without normal distribution. Results Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient‐reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient‐reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. Conclusions No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.

Abstract The newly identified XBB.1.16‐containing sublineages, including XBB.1.5, have become the prevailing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variant in circulation. Unlike previous Omicron XBB variants (e.g., XBB.1.5 and XBB.1.9) harboring the F486P substitution, XBB.1.16 also carries a T478R substitution in the receptor‐binding domain (RBD). Numerous researchers have delved into the high transmissibility and immune evasion of XBB.1.16 subvariant. Therefore, developing a new vaccine targeting XBB.1.16, including variants of concern (VOCs), is paramount. In our study, we engineered a recombinant protein by directly linking the S‐RBD sequence of the XBB.1.16 strain of SARS‐CoV‐2 to the sequences of two heptad repeat sequences (HR1 and HR2) from the SARS‐CoV‐2 S2 subunit. Named the recombinant RBDXBB.1.16‐HR/trimeric protein, this fusion protein autonomously assembles into a trimer. Combined with an MF59‐like adjuvant, the RBDXBB.1.16‐HR vaccine induces a robust humoral immune response characterized by high titers of neutralizing antibodies against variant pseudovirus and authentic VOCs and cellular immune responses. Additionally, a fourth heterologous RBDXBB.1.16‐HR vaccine enhances both humoral and cellular immune response elicited by three‐dose mRNA vaccines. These findings demonstrate that the recombinant RBDXBB.1.16‐HR protein, featuring the new T478R mutation, effectively induces solid neutralizing antibodies to combat newly emerged XBB variants.

Abstract Objectives To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. Methods Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether‐filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI‐based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. Results The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. Conclusion Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

Abstract The genetic basis of vertebrate emergence during metazoan evolution has remained largely unknown. Understanding vertebrate‐specific genes, such as the tight junction protein Occludin (Ocln), may help answer this question. Here, it is shown that mammary glands lacking Ocln exhibit retarded epithelial branching, owing to reduced cell proliferation and surface expansion. Interestingly, Ocln regulates mitotic spindle orientation and function, and its loss leads to a range of defects, including prolonged prophase and failed nuclear and/or cytoplasmic division. Mechanistically, Ocln binds to the RabGTPase‐11 adaptor FIP5 and recruits recycling endosomes to the centrosome to participate in spindle assembly and function. FIP5 loss recapitulates Ocln null, leading to prolonged prophase, reduced cell proliferation, and retarded epithelial branching. These results identify a novel role in OCLN‐mediated endosomal trafficking and potentially highlight its involvement in mediating membranous vesicle trafficking and function, which is evolutionarily conserved and essential.

Abstract Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.

Abstract Cholesterol 25‐hydroxylase (CH25H), an enzyme involved in cholesterol metabolism, regulates inflammatory responses and lipid metabolism. However, its role in kidney disease is not known. The author found that CH25H transcript is expressed mostly in glomerular and peritubular endothelial cells and that its expression increased in human and mouse diabetic kidneys. Global deletion of Ch25h in Leprdb/db mice aggravated diabetic kidney disease (DKD), which is associated with increased endothelial cell apoptosis. Treatment of 25‐hydroxycholesterol (25‐HC), the product of CH25H, alleviated kidney injury in Leprdb/db mice. Mechanistically, 25‐HC binds to GTP‐binding protein ADP‐ribosylation factor 4 (ARF4), an essential protein required for maintaining protein transport in the Golgi apparatus. Interestingly, ARF4's GTPase‐activating protein ASAP1 is also predominantly expressed in endothelial cells and its expression increased in DKD. Suppression of ARF4 activity by deleting ARF4 or overexpressing ASAP1 results in endothelial cell death. These results indicate that 25‐HC binds ARF4 to inhibit its interaction with ASAP1, and thereby resulting in enhanced ARF4 activity to confer renoprotection. Therefore, treatment of 25‐HC improves kidney injury in DKD in part by restoring ARF4 activity to maintain endothelial cell survival. This study provides a novel mechanism and a potential new therapy for DKD.