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Abstract A low‐profile circularly polarised (CP) metasurface antenna is proposed, utilising characteristic mode analysis (CMA). The antenna design features a two‐layer laminated substrate, a 4×4 Butterfly‐shaped metasurface, a rectangular slot, an irregular transmission line, and a ground plane. The metasurface is analysed using mode significance (MS), characteristic angle (CA), and characteristic current to determine the resonance bandwidth and CA resonance points, which exhibit a near 90° difference. At the intersection of the two MS modes, their CAs differ by nearly 90°, and their far‐field radiation directions align, indicating the potential for achieving circular polarisation at the desired frequency. The integration of the metasurface with the slot antenna is simulated to validate the CMA findings. Additionally, the CP bandwidth is enhanced by modifying the transmission line branches. Measurement of the fabricated antenna reveals an impedance bandwidth (IBW) of 27.4%, a 3‐dB axial ratio bandwidth (ARBW) of 10.1%, and a peak gain of 6.9 dBic at 4.4 GHz. Compared to the design without branches, IBW and ARBW have increased by 10% and 7.3%, respectively.

Abstract The rapid development of electric vehicles (EVs) has made the construction and service capability evaluation of EV charging and battery swapping stations (CBSSs) more important. A comprehensive evaluation indicator system for the service capability evaluation of EV‐CBSSs is established, meticulously outlining the critical aspects of operational efficiency, economy, convenience, and reliability, each with multiple indicators for thorough assessment. To address the shortcomings of individual evaluation methods in evaluating the service capability of EV‐CBSSs, the game theory‐based combination weighting (GTCW) method is adopted, which integrates the advantages of the analytic hierarchy process method, entropy weight method, and grey relation analysis method. Specifically, the weights for each indicator are obtained separately using these three evaluation methods, and then combined using the GTCW method to calculate the final weights. In case studies, the service capability for each EV‐CBSS is calculated and compared between these three individual methods and the proposed GTCW method. Simulation results validate that the proposed evaluation indicator system and GTCW method can offer a more comprehensive evaluation of the service capability for EV‐CBSSs, providing guiding suggestions for future construction plans.

ABSTRACT Aims/Introduction To investigated the association between serum asprosin and metabolic characteristics in type 2 diabetes mellitus patients with different durations. Materials and Methods A total of 436 patients with type 2 diabetes mellitus were enrolled in this study from the community health service center in southeastern Shanxi Province. All the patients were divided into two groups according to their diabetes duration: diabetes duration ≤5 years group (n = 132) and diabetes duration ≥10 years group (n = 304). Fasting blood samples were gathered and serum asprosin was tested. Pearson/Spearman correlation analysis was carried out. Results Asprosin was comparable between the two groups. Asprosin was positively correlated with systolic blood pressure (SBP), triglycerides, creatinine, serum uric acid and low‐density lipoprotein cholesterol in the diabetes duration ≤5 years group (P

Abstract Aims/Introduction The association between serum angiopoietin‐like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear. Methods A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross‐sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable‐adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression. Results Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P

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 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 Distal tibial deformities can significantly impact patients if left uncorrected, often leading to pain, alterations in gait, and the eventual development of post‐traumatic arthritis. The criteria for surgical correction in these patients continues to be a subject of debate, while supramalleolar osteotomy (SMO) is an effective method for correcting distal tibial deformities. The purpose of this study was to evaluate and compare the clinical results of SMO using internal fixation or using computer‐assisted hexapod external fixator in the treatment of distal tibial deformity. Methods A retrospective study was conducted on 290 patients who underwent SMO between June 2015 and January 2023. Forty‐four patients met the inclusion and exclusion criteria. Among the participants, 19 underwent SMO combined with a computer‐assisted hexapod external fixator, while 25 received SMO with plate and screw internal fixation. The tibial anterior surface (TAS) angle, tibial lateral surface (TLS) angle, the tibiotalar (TT) angle and the talocrural (TC) angle were assessed on weight‐bearing X‐ray films. Functional assessments were performed according to the American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot score. Results The study followed patients for an average duration of 31.7 ± 15.3 months, with a range from 12 to 67 months. Successful bone union was achieved in all cases. For patients treated with the computer‐assisted hexapod external fixator, significant improvements were observed: the mean deviation in sagittal plane deformity parameters decreased from 14.3 ± 10.4 degrees preoperatively to 2.8 ± 3.8 degrees postoperatively (p

Objective Surgical technique in distraction osteogenesis for the treatment of brachymetatarsia can influence the final prognosis. However, there are currently no standardized guidelines for surgical procedures and complication management. The aim of this study is to investigate the effect of bone lengthening with external fixation by minimally invasive osteotomy based on Ilizarov technique in the treatment of congenital brachymetatarsia. Methods A retrospective study was conducted on patients with congenital brachymetatarsia treated by metatarsal lengthening, from June 2017 to December 2020. There were 11 patients with 17 shorted fourth metatarsals, including 10 females and 1 male, with age of 24.6 ± 4.5 years (16–31 years). Six patients were bilaterally involved. Orthofix external fixator mini track was installed through dorsal approach and the fourth MTP joints were temporarily fixed by Kirschner wire. Bone lengthening was performed after a minimally invasive osteotomy at the proximal metatarsals. American Orthopedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal‐interphalangeal (MTP‐IP) scores, metatarsal length, complications were recorded. Statistical comparison was performed using the paired t‐student test for pre‐ and postoperative AOFAS MTP‐IP scores. Results Patients were followed up for 55 ± 10.8 months. The mean length of the fourth metatarsal bone was 49.9 ± 2.9 mm preoperatively. The mean metatarsal shortage was 18.8 ± 3.1 mm. The mean lengthening achieved was 19.8 ± 3.3 mm, with a lengthening ratio of 39.7% ± 6.6%. The lengthened callus ossified completely at 3–4 months after operation. All patients were satisfied with the results of lengthening. The AOFAS scores were improved significantly from 83.7 ± 4.2 preoperatively to 93.2 ± 2.7 postoperatively (t = −10.27, p

Abstract Copper is a vital trace element crucial for mediating interactions between Mycobacterium and macrophages. Within these immune cells, copper modulates oxidative stress responses and signaling pathways, enhancing macrophage immune functions and facilitating Mycobacterium clearance. Conversely, copper may promote Mycobacterium escape from macrophages through various mechanisms: inhibiting macrophage activity, diminishing phagocytic and bactericidal capacities, and supporting Mycobacterium survival and proliferation. This paradox has intensified research focus on the regulatory role of copper in immune cell–pathogen interactions. Interactions among metal ions can affect Mycobacterium concentration, distribution, and activity within an organism. In this review, we have elucidated the role of copper in these interactions, focusing on the mechanisms by which this metal influences both the immune defense mechanisms of macrophages and the survival strategies of Mycobacterium. The findings suggest that manipulating copper levels could enhance macrophage bactericidal functions and potentially limit Mycobacterium resistance. Therefore, elucidating the regulatory role of copper is pivotal for advancing our understanding of metal homeostasis in immune cell–pathogen dynamics and TB pathogenesis. Furthermore, we recommend further investigation into the role of copper in TB pathogenesis to advance tuberculosis diagnosis and treatment and gain comprehensive insights into metal homeostasis in infectious disease contexts.

ABSTRACT Background TNF‐related apoptosis‐inducing ligand (TRAIL) belongs to the tumor necrosis factor superfamily. TRAIL selectively induces apoptosis in tumor cells while sparing normal cells, which makes it an attractive candidate for cancer therapy. Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors have demonstrated safety and tolerability in clinical trials. However, they have failed to exhibit expected clinical efficacy. Consequently, extensive research has focused on optimizing TRAIL‐based therapies, with one of the most common approaches being the construction of TRAIL fusion proteins. Methods An extensive literature search was conducted to identify studies published over the past three decades related to TRAIL fusion proteins. These various TRAIL fusion strategies were categorized based on their effects achieved. Results The main fusion strategies for TRAIL include: 1. Construction of stable TRAIL trimers; 2. Enhancing the polymerization capacity of soluble TRAIL; 3. Increasing the accumulation of TRAIL at tumor sites by fusing with antibody fragments or peptides; 4. Decorating immune cells with TRAIL; 5. Prolonging the half‐life of TRAIL in vivo; 6. Sensitizing cancer cells to overcome resistance to TRAIL treatment. Conclusion This work focuses on the progress in recombinant TRAIL fusion proteins and aims to provide more rational and effective fusion strategies to enhance the efficacy of recombinant soluble TRAIL, facilitating its translation from bench to bedside as an effective anti‐cancer therapeutic.

Abstract Proteomic communications in neighboring microenvironments during early organ development is a dynamic process that continuously reshapes human embryonic stem cells (hESCs) developmental fate. Such dynamic proteomic alteration in the microenvironment consists of both freely secreted proteome and exosome‐encapsulated proteome. Simultaneous monitoring of the time‐lapse shift of both proteomes with live organoids remains technically challenging. Here, a continuous organoid secretion/encapsulation proteome tandem LC‐MS/MS (COSEP‐LCM) is introduced, which permits time‐lapse monitoring of proteomic alterations both in free secretion form and in exosome encapsulated form at live organoids’ microenvironment. Continuous growth of human cerebral organoids (COs) and free‐secretion/exosome‐encapsulation proteomics acquisition with COSEP‐LCM for 60 days is demonstrated. SERPINF1, F5, and EFNB1 are initially enriched inside exosomes as encapsulated excretion and then gradually enriched outside exosomes as freely secreted excretion, while C3 is initially enriched outside exosomes as freely secreted excretion and gradually enriched inside exosomes as encapsulated excretion. Such dynamic excretion pattern paradigm shift may imply critical developmental strategy evolution during early human cerebral development. COSEP‐LCM offers a platform technique for continuous inside/outside exosome proteomics co‐analysis in live organoids’ microenvironment.

Abstract Background Alcoholic liver disease (ALD) patients with bacterial infections usually exhibit high mortality rates. Infections frequently involve bacteria such as Vibrio vulnificus and Enterococcus faecalis. Nevertheless, the mechanisms predisposing ALD patients to bacterial infections and the role of the NLRP3 inflammasome in the intestinal epithelial barrier in ALD remain unclear. Methods We established ALD mice models of WT, Nlrp3−/− and Gsdmd−/− through chronic alcohol consumption feeding and acute alcohol induction. We compared alterations in gut microbiota, ileitis, and adhesion protein expression, to analyze the role and potential mechanism of NLRP3 in the early onset of ALD. Concurrently, we examined the changes in inflammation and liver damage in the ileum of ALD and healthy mice following foodborne infection with V. vulnificus. Results Compared with the control group, the expression levels of ZO‐1, Claudin‐1 and E‐cadherin were reduced in the ileum of ALD mice, while those of NLRP3, caspase‐1(p20), GSDMD‐N and IL‐1β were elevated. Nlrp3−/− and Gsdmd−/− ALD mice showed an increased gut bacterial load, decreased ileal expression of E‐cadherin, more severe ileitis, pronounced liver damage, steatosis and higher plasma levels of FITC‐dextran, D‐LA and ZO‐1 compared with WT mice. Notably, Nlrp3−/− ALD mice exhibited a higher presence of Deferribacterota and Enterobacteriaceae. Furthermore, ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections. Conclusions This study indicated that NLRP3 activation in the ileum of ALD mice stabilizes the inflammation‐related gut microbiota, preserves the intestinal epithelial barrier, and diminishes inflammation and liver injury. Furthermore, the compromised immune defence in ALD mice may contribute to their heightened susceptibility to bacterial pathogens. Key points Activation of the NLRP3‐GSDMD pathway in the ileum of Alcoholic liver disease (ALD) mice. NLRP3 activation maintains homeostasis of gut microbiota and intestinal epithelial barrier in ALD mice. ALD mice infected with V. vulnificus infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections.

ABSTRACT Background There is a lack of research examining the association between obesity and depressive symptoms in relation to mental health. This study aimed to examine the correlation between Body Roundness Index (BRI) and depressive symptoms in elderly Chinese individuals. Methods The study sample consisted of 11,842 individuals aged 65 years or older from the 2018 Chinese Longitudinal Health Longevity Survey (CLHLS) database. A multivariate logistic regression analysis was used to investigate how BRI affects the likelihood of experiencing depressive symptoms, with restricted cubic spline (RCS) curves illustrating this impact. BRI values were calculated using a predefined formula for each participant, and depressive status was assessed using the Center for Epidemiologic Studies Depression Scale (CES‐D‐10). Results The mean age of the participants was 83.1 ± 10.9 years. A non‐linear relationship was identified between the BRI score and the risk of depressive symptoms. The analysis showed that for BRI scores below 5.17, there was a significant 9% increase in the risk of depressive symptoms for every 1‐point decrease in BRI score. Conversely, when the BRI was 5.17 or higher, a decrease in the BRI score did not lead to a significant increase in the risk of depressive symptoms. Conclusion The study demonstrated a significant association between BRI and depressive symptoms in elderly Chinese individuals. Furthermore, it was noted that older adults classified as overweight and mildly obese had a lower likelihood of experiencing depressive symptoms and demonstrated improved mental health.

Abstract Antimicrobial peptides (AMPs) have become a viable source of novel antibiotics that are effective against human pathogenic bacteria. In this study, we construct a bank of culturable marine biofilm bacteria constituting 713 strains and their nearly complete genomes and predict AMPs using ribosome profiling and deep learning. Compared with previous approaches, ribosome profiling has improved the identification and validation of small open reading frames (sORFs) for AMP prediction. Among the 80,430 expressed sORFs, 341 are identified as candidate AMPs with high probability. Most potential AMPs have less than 40% similarity in their amino acid sequence compared to those listed in public databases. Furthermore, these AMPs are associated with bacterial groups that are not previously known to produce AMPs. Therefore, our deep learning model has acquired characteristics of unfamiliar AMPs. Chemical synthesis of 60 potential AMP sequences yields 54 compounds with antimicrobial activity, including potent inhibitory effects on various drug‐resistant human pathogens. This study extends the range of AMP compounds by investigating marine biofilm microbiomes using a novel approach, accelerating AMP discovery.

Abstract Linear kinetic instability analysis based on in situ observations for one typical oxygen ion cyclotron harmonic (OCH) wave event is performed to investigate the wave excitation mechanism. The observed partial‐shell velocity distribution of energetic O+s is fitted by the superposition of multiple ring‐beam distributions. The calculated linear growth rate shows that the observed OCH waves can be excited by energetic O+s with the partial‐shell velocity distribution, and the maximum growth rate occurs at the third harmonic, coinciding with the frequency associated with the maximum peak of the wave electric field power spectral density measured. In addition, it is found that cool heavy ions have a damping effect on the OCH waves near the corresponding heavy ion cyclotron frequency.

Abstract Background This study aimed to investigate the potential variance in the prevalence of early‐onset scoliosis among children aged 4–7 years and analyze the influencing factors. The goal was to establish a crucial reference point for monitoring and evaluating spinal curvature development in preschoolers, ultimately to reduce the occurrence of adverse health outcomes. Methods Children aged 4–7 years within the main urban area of Nanjing were selected using a stratified random sampling method. A team of four senior therapists conducted screenings for spinal curvature among children using visual inspection, the Adams forward bending test, and an electronic scoliometer to measure the angle of trunk rotation (ATR) and identify children displaying signs of scoliosis. Children with suspected scoliosis in the initial screening underwent X‐ray Cobb angle assessment for confirmation. The prevalence of early‐onset scoliosis was then determined from the screening results. R version 4.2.0 software was used to analyze the factors associated with scoliosis among children using partial least squares structural equation modeling. Results A total of 2281 children were included in this study, consisting of 1211 boys and 1070 girls, with a mean age of 5.44 ± 0.81 years (ranging from 4 to 7 years). Among them, 7.58% exhibited positive signs of scoliosis, 5.87% had early‐onset scoliosis, and the positive predictive value was 77.5%. Significant differences in ATR were observed among children in different age groups (Kruskal–Wallis = 15, p = 0.0104) and by sex (t = 3.17, p = 0.00153). Significant variations in ATR were noted in children with scoliosis (t = −22.7, p

Abstract The treatment of infected bone defects (IBDs) needs simultaneous elimination of infection and acceleration of bone regeneration. One mechanism that hinders the regeneration of IBDs is the iron competition between pathogens and host cells, leading to an iron deficient microenvironment that impairs the innate immune responses. In this work, an in situ modification strategy is proposed for printing iron‐active multifunctional scaffolds with iron homeostasis regulation ability for treating IBDs. As a proof‐of‐concept, ultralong hydroxyapatite (HA) nanowires are modified through in situ growth of a layer of iron gallate (FeGA) followed by incorporation in the poly(lactic‐co‐glycolic acid) (PLGA) matrix to print biomimetic PLGA based composite scaffolds containing FeGA modified HA nanowires (FeGA‐HA@PLGA). The photothermal effect of FeGA endows the scaffolds with excellent antibacterial activity. The released iron ions from the FeGA‐HA@PLGA help restore the iron homeostasis microenvironment, thereby promoting anti‐inflammatory, angiogenesis and osteogenic differentiation. The transcriptomic analysis shows that FeGA‐HA@PLGA scaffolds exert anti‐inflammatory and pro‐osteogenic differentiation by activating NF‐κB, MAPK and PI3K‐AKT signaling pathways. Animal experiments confirm the excellent bone repair performance of FeGA‐HA@PLGA scaffolds for IBDs, suggesting the promising prospect of iron homeostasis regulation therapy in future clinical applications.

Background Currently, there is a lack of evidence for the long‐term bioprosthetic valve durability of patients with bicuspid aortic valve (BAV) following transcatheter aortic valve replacement (TAVR). Methods and Results This study aimed to evaluate hemodynamic outcome, structural valve deterioration, and bioprosthetic valve failure during long‐term follow‐up after TAVR in patients with BAV versus patients with tricuspid aortic valve (TAV). Patients with BAV and TAV who underwent TAVR between 2012 and 2020, with echocardiography followed for at least 3 years, were included. Baseline characteristics, long‐term valve hemodynamic performance, structural valve deterioration, and bioprosthetic valve failure were compared between patients with BAV and TAV. A total of 170 patients with BAV and 145 patients with TAV were included. The mean duration of follow‐up for patients with BAV and TAV was 5.2±1.8 and 5.0±1.7 years. No significant differences were observed in the rates of structural valve deterioration and bioprosthetic valve failure between patients with BAV and TAV: structural valve deterioration, BAV 20 (11.8%) versus TAV 16 (11.0%) at last follow‐up (P=0.861); bioprosthetic valve failure, BAV 3 (1.8%) versus TAV 7 (4.8%) at last follow‐up (P=0.196). More than moderate intravalvular aortic regurgitation (1.8% versus 4.8%, P=0.196) and paravalvular leak (6.5% versus 3.4%, P=0.305) were rare in both patients with BAV and patients with TAV. Conclusions This study indicated satisfactory long‐term valve durability of TAVR in patients with BAV. Comparable hemodynamic outcome, structural valve deterioration, and bioprosthetic valve failure could be achieved in patients with BAV and TAV during long‐term follow‐up after TAVR.

Abstract Proton cyclotron waves (PCWs) upstream of Mars are thought to be associated with the instabilities of pickup ions. The instabilities of pickup ions of ring distributions have larger maximum growth rates compared with beam distributions. However, observations revealed a notably‐reduced occurrence rate of PCWs for pickup ions of ring distributions. Linear instability analysis and a corresponding two‐dimensional particle‐in‐cell (PIC) simulation are performed to investigate the instabilities of pickup ion ring distributions upstream of Mars. Linear instability analysis indicates that a pickup ion ring distribution is unstable to the ion cyclotron, ion Bernstein, and mirror instabilities. The corresponding PIC simulation confirms the linear analysis results and further demonstrates that the pickup ions are scattered toward an isotropic shell distribution by the waves excited. Interestingly, the saturation energy of the waves is much lower than that driven by a corresponding pickup ion beam distribution, and mirror waves eventually dominate the system.

Abstract Coronavirus stands for a large family of viruses characterized by protruding spikes surrounding a lipidic membrane adorned with proteins. The present study explores the adhesion of transmissible gastroenteritis coronavirus (TGEV) particles on a variety of reference solid surfaces that emulate typical virus‐surface interactions. Atomic force microscopy informs about trapping effectivity and the shape of the virus envelope on each surface, revealing that the deformation of TGEV particles spans from 20% to 50% in diameter. Given this large deformation range, experimental Langmuir isotherms convey an unexpectedly moderate variation in the adsorption‐free energy, indicating a viral adhesion adaptability which goes beyond the membrane. The combination of an extended Helfrich theory and coarse‐grained simulations reveals that, in fact, the envelope and the spikes present complementary adsorption affinities. While strong membrane‐surface interaction lead to highly deformed TGEV particles, surfaces with strong spike attraction yield smaller deformations with similar or even larger adsorption‐free energies.

Abstract Background Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

Abstract The human retina perceives and preprocesses the spectral information of incident light, enabling fast image recognition and efficient chromatic adaptation. In comparison, it is reluctant to implement parallel spectral preprocessing and temporal information fusion in current complementary metal‐oxide‐semiconductor (CMOS) image sensors, requiring intricate circuitry, frequent data transmission, and color filters. Herein, an active‐matrix synaptic phototransistor array (AMSPA) is developed based on organic/inorganic semiconductor heterostructures. The AMSPA provides wavelength‐dependent, bidirectional photoresponses, enabling dynamic imaging and in‐sensor spectral preprocessing functions. Specifically, near‐infrared light induces inhibitory photoresponse while UV light results in exhibitory photoresponse. With rational structural design of the organic/inorganic hybrid heterostructures, the current dynamic range of phototransistor is improved to over 90 dB. Finally, a 32 × 64 AMSPA (128 pixels per inch) is demonstrated with one‐switch‐transistor and one‐synaptic phototransistor (1‐T‐1‐PT) structure, achieving spatial chromatic enhancement and temporal trajectory imaging. These results reveal the feasibility of AMSPA for constructing artificial vision systems.

Abstract Background Patients with non‐alcoholic fatty liver disease (NAFLD) often exhibit hepatic steatosis and dyslipidemia. Studies have shown that intestinal microorganisms are closely related to the occurrence of NAFLD and atherosclerosis. Our previous study has underscored the protective role of microRNA‐30a‐5p (miR‐30a‐5p) against atherosclerosis. Methods and Results In the present study, we aimed to elucidate the effect and underlying mechanism of the intestinal microorganisms of miR‐30a‐5p knockout (KO) mice on NAFLD. Our findings demonstrated that KO exacerbated high‐fat diet (HFD)‐induced hepatic steatosis and disrupted liver function, as evidenced by elevated levels of total cholesterol, low‐density lipoprotein, alanine aminotransferase, aspartate transaminase, and total bile acids in serum. Fecal microbiota from HFD‐fed KO mice induced hepatic steatosis, dyslipidemia, and higher levels of enzymes indicative of liver damage in wild‐type mice. Remarkably, KO mice significantly intensified the above effects. 16s rDNA sequencing and metabolomics of the intestinal microbiota in the HFD‐treated KO and WT mice showed that the loss of miR‐30a‐5p resulted in intestinal microbiota imbalance and was highly related to the arachidonic acid metabolic pathway. Targeted metabolomic in the liver tissues unveiled upregulation of COX‐related (PGF2a, 8‐iso‐PGF2a and PGF2) and LOX‐related (LTB4, LTD4, 12S‐HETE and 15S‐HETE) factors in HFD‐treated KO mice. Immunohistochemistry and transcriptional analyses showed that miR‐30a‐5p affected arachidonic acid metabolism through the LOX/COX pathways. Besides, COX/LOX pathways and hepatic steatosis were reversed after reintroducing miR‐30a‐5p in HFD‐treated KO mice. Conclusions This study reveals the pivotal mechanism by which miR‐30a‐5p and intestinal microbes regulate hepatic steatosis and abnormal lipid metabolism, offering promising avenues for NAFLD and atherosclerosis therapeutics. Highlights MiR‐30a‐5p deletion aggravated hepatic steatosis and lipid disorder induced by an HFD in mice. Gut microbiota participated in the regulation of hepatic steatosis in the context of miR‐30a‐5p. Gut microbiota metabolism‐related arachidonic acid metabolic pathway contributed to miR‐30a‐5p‐regulated hepatic steatosis and lipid disorder. Reintroducing miR‐30a‐5p reversed hepatic steatosis and arachidonic acid metabolism disorder caused by HFD and miR‐30a‐5p deletion.

ABSTRACT Background and Purpose Basilar artery (BA) tortuosity is closely associated with posterior circulation infarction (PCI) and dizziness/unsteadiness. This study aims to determine the relationship between BA tortuosity and the outcome of dizziness and unsteadiness in PCI patients. Method This study prospectively recruited PCI patients presenting with dizziness and unsteadiness. BA tortuosity was diagnosed based on Smoker's criteria. The BA tortuosity index (BATI) was measured from magnetic resonance angiography (MRA) images. Posterior circulation was divided into proximal (medulla oblongata and posterior inferior cerebellar), middle, and distal territories. Symptoms, risk of falls, and quality of life were followed up in 3 months after stroke. Logistic regression was used to identify possible factors associated with the persistence of dizziness and unsteadiness. Results Among 182 PCI patients presenting with dizziness and unsteadiness, 97 (53.3%) had BA tortuosity, including 19 (10.4%) with moderate‐to‐severe BA tortuosity. At the 3‐month follow‐up, 58 (31.9%) patients continued to experience dizziness and unsteadiness, with significantly decreased quality of life and a high risk of falls. Binary logistic regression analysis identified moderate‐to‐severe BA tortuosity (OR, 4.474; 95% CI, 1.591–12.579; p = 0.004) and lesions involving the proximal posterior circulation territory (OR, 2.146; 95% CI, 1.097–4.199; p = 0.026) as risk factors for persistent dizziness and unsteadiness after PCI, while thrombolysis (OR, 0.280; 95% CI, 0.079–0.992; p = 0.049) as a protective factor. BATI (OR, 1.072; 95% CI, 1.028–1.119; p = 0.001) was also independently associated with dizziness and unsteadiness after PCI. Conclusion Prominent BA tortuosity increases the risk of persistent dizziness and unsteadiness after PCI, leading to a high risk of falls and decreased quality of life. This warrants more attention in clinical practice.

Abstract In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S‐catalyzing enzymes, such as cystathionine‐β‐synthase, cystathionine‐γ‐lyase, and 3‐mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia–reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

Abstract Endocrine‐resistant ER+HER2– breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine‐resistant BC remain elusive. Here, analysis of the RNA‐sequencing data from ER+HER2– BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine‐resistant BC cells, not immune cells. Indeed, compared with endocrine‐sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS‐STING pathway is attenuated in endocrine‐resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS–STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2– BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine‐resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine‐resistant BC.

Abstract O6‐methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6‐MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression‐free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on β‐Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating β‐Catenin‐MGMT axis activation and chemosensitivity to TMZ. Interference with β‐Catenin re‐sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high‐dose TMZ treatment, and MGMT overexpression counteracts the effects of β‐Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ‐resistant PanNETs.

Abstract Statins, the first‐line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short‐term statin therapy on hyperlipidemia mice show that hepatic insulin resistance is a cause of statin‐induced diabetes. Statin medication raises the expression of progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits insulin signaling through degradation of protein phosphatase, Mg2+/Mn2+ dependent 1 (PPM1α) to activate ERK pathway. STIP1 homology and U‐box containing protein 1 (STUB1) is found to mediate ubiquitination of PPM1α promoted by PAQR9. On the other hand, decreased activity of hepatocyte nuclear factor 4 alpha (HNF4α) seems to be the cause of PAQR9 expression under statin therapy. The interventions on PAQR9, including deletion of PAQR9, caloric restriction and HNF4α activation, are all effective treatments for statin‐induced diabetes, while liver specific over‐expression of PPM1α is another possible tactic. The results reveal the importance of HNF4α‐PAQR9‐STUB1‐PPM1α axis in controlling the statin‐induced hepatic insulin resistance, offering a fresh insight into the molecular mechanisms underlying statin therapy.

Abstract Objective This study aims to clarify the uncertain association between vasopressor administration and the development of intensive care unit‐acquired weakness (ICUAW) in critically ill adult patients. Methods We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials up to October 10, 2023. Titles and abstracts were independently screened by two authors, who then reviewed full texts and extracted relevant data from the studies that met the inclusion criteria. This review included prospective and retrospective cohort studies that explored the relationship between vasopressor use and ICUAW utilizing univariate or multivariate analysis in adult ICU patients. Results A total of 15 studies were included in our review, collectively indicating a statistically significant association between the use of vasopressors and the occurrence of ICUAW (odds ratio [OR], 3.43; 95% confidence intervals [CI], 1.95–6.04), including studies utilizing multivariate analysis (OR, 3.43; 95% CI, 1.76–6.70). Specifically, the use of noradrenaline was significantly associated with ICUAW (OR, 4.42; 95% CI, 1.69–11.56). Subgroup and sensitivity analyses further underscored the significant relationship between vasopressor use and ICUAW, particularly in studies focusing on patients with clinical weakness, varying study designs, different sample sizes, and relatively low risk of bias. However, this association was not observed in studies limited to patients with abnormal electrophysiology. Conclusions Our review underscores a significant link between the use of vasopressors and the development of ICUAW in critically ill adult patients. This finding helps better identify patients at higher risk of ICUAW and suggests considering targeted therapies to mitigate this risk.

Abstract Studies have shown that the microbiome of saline‐tolerant plants plays a significant role in promoting salt stress in non‐saline‐tolerant plants, but the microorganisms are still unclear. In the present study, the microbial diversity changes in Suaeda salsa (L.) Pall. in the Yellow River Delta region were investigated. In the bacterial community, the dominant bacteria in the rhizosphere soil of the low‐saline soil (YDL), moderate‐saline soil (YDM), and high‐saline soil (YDH) groups were Proteobacteria, Chloroflexi, Bacteroidota, and Actinobacteriota (at the phylum level), while Ascomycota and Basidiomycota were the dominant fungi in the fungal community. At the family level, with the increase of salinity, the relative abundance of Rhodobacteraceae (bacterial community), Thermoascaceae, and Phaffomycetaceae (fungal community) gradually increased; and to the best of our knowledge, there are no reports on the relationship between Thermoascaceae and Phaffomycetaceae families with salt stress. At the genus level, Salinimicrobium (bacterial community) was the dominant bacterium in the rhizosphere soil of the YDL, YDM, and YDH groups, while with the increase of salinity, the relative abundance of Byssochlamys and Wickerhamomyces (fungal community) gradually increased, and to the best of our knowledge there are no reports on the relationship between Byssochlamys and salt stress. Salinity mainly affected the bacterial community abundance, but it had little effect on the fungi community abundance. The bacterial community of the YDH group was dominated by bacteria of unknown origin (52.76%), while bacteria of unknown origin accounted for 26.46% and 20.78% of the bacterial communities in the YDM and YDL groups, respectively. The fungi community of the YDH group was dominated by YDL group fungi (relative abundance of 44.44%), followed by YDM group fungi (29.42%) and fungi of unknown origin (26.14%). These results provide a better understanding of the rhizosphere microbial diversity of saline–alkali‐tolerant plants, laying a foundation for developing a saline–alkali‐tolerant plant microbiome.

Abstract Although in vitro experiments have demonstrated the potential of flavonoid compounds in regulating blood pressure, there is still a lack of evidence from large population studies. We conducted a cross‐sectional study using the National Health and Nutrition Examination Survey to investigate the relationship between flavonoid intake levels (natural log transformation) and hypertension events. A total of 15 752 participants aged over 20 years were included, and a weighted multivariable logistic regression analysis was performed to explore the relationship between total flavonoids, five sub types intake, and hypertension events. Smooth curve fitting was used to explore potential nonlinear relationships. Higher total flavonoids intake was associated with a lower risk of hypertension than the lowest group. The adjusted odds ratios (95% CIs) were 0.79 (0.70–0.88) for total flavonoids intake. Elevated total flavonoids intake levels were significantly and linearly associated with a lower risk of hypertension. For each unit increase in the total flavonoids intake level, the adjusted ORs for risk of hypertension decrease by 5% (OR 0.95; 95% CI, 0.92–0.98). In addition, in restricted cubic spline regression, we found that flavan‐3‐ols, anthocyanidins, and flavonols intake were linearly and negatively related to prevalence of hypertension. Flavones intake showed nonlinear associations with prevalence of hypertension with inflection points of ‐1.90. Within a certain range, a negative correlation exists between flavonoids intake and hypertension events. This finding provides insights into dietary modifications in the prevention of hypertension.

Abstract Aims To assess the different imaging characteristics between corticosteroid‐sensitive (CS) and corticosteroid‐refractory (CR) immune checkpoint inhibitor‐associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. Methods and results Thirty‐five patients diagnosed with ICIaM and 30 age and gender‐matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub‐endocardial (GLSendo) and sub‐epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non‐fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (−14.61 ± 2.67 vs. −18.50 ± 2.53, P

Objective The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence‐based foundation for assessing postoperative efficacy. Methods From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2‐weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS‐back/VAS‐leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow‐up appointments 3, 6, and 12 months after the surgery. The follow‐up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. Results Parameters such as area and circumference of intervertebral discs in the cross‐section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. Conclusion For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross‐sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short‐term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.

Abstract Accurately predicting traffic flow is crucial for intelligent transportation systems (ITS). In recent years, many deep learning‐based prediction models have been widely applied in traffic flow prediction, and various spatio‐temporal networks have been proposed. However, most of the existing models follow a general technical route to extract the spatio‐temporal features, which lack the capacity of extracting the important historical information with the high spatial and temporal correlations dynamically and deeply. How to develop a well‐performance traffic flow prediction model for a complex transportation network is still facing some challenges. In this paper, a hybrid dynamic spatio‐temporal network (HD‐Net) for traffic flow prediction is proposed. In HD‐Net, the authors first extract the dynamic spatio‐temporal features using dynamic graph convolution and bidirectional gate recurrent uni (BiGRU). Subsequently, the authors extract the important features with high spatial and temporal correlations from the obtained dynamic spatio‐temporal features using an auto‐correlation mechanism from a local perspective, and self‐attention mechanism from a global perspective, respectively. Extensive experiments have been conducted on two real‐world traffic datasets. The experimental results demonstrate that the proposed HD‐Net outperforms the baselines in the field of capturing the dynamic and important spatio‐temporal features with high correlations.

Abstract Background To identify independent factors of cognitive frailty (CF) and construct a nomogram to predict cognitive frailty risk in patients with lung cancer receiving drug therapy. Methods In this cross‐sectional study, patients with lung cancer undergoing drug therapy from October 2022 to July 2023 were enrolled. The data collected includes general demographic characteristics, clinical data characteristics and assessment of tools for cognitive frailty and other factors. Logistic regression was harnessed to determine the influencing factors, R software was used to establish a nomogram model to predict the risk of cognitive frailty. The enhanced bootstrap method was employed for internal verification of the model. The performance of the nomogram was evaluated by using calibration curves, the area under the receiver operating characteristic curve, and decision curve analysis. Results A total of 372 patients were recruited, with a cognitive frailty prevalence of 56.2%. Age, education background, diabetes mellitus, insomnia, sarcopenia, and nutrition status were identified as independent factors. Then, a nomogram model was constructed and patients were classified into high‐ and low‐risk groups with a cutoff value of 0.552. The internal validation results revealed good concordance, calibration and discrimination. The decision curve analysis presented prominent clinical utility. Conclusions The prevalence of cognitive frailty was higher in lung cancer patients receiving drug therapy. The nomogram could identify the risk of cognitive frailty intuitively and simply in patients with lung cancer, so as to provide references for early screening and intervention for cognitive frailty at the early phases of drug treatment.

Abstract Canavan disease is a leukodystrophy caused by ASPA mutations that diminish oligodendroglial aspartoacylase activity, and is characterized by markedly elevated brain concentrations of the aspartoacylase substrate N‐acetyl‐l‐aspartate (NAA) and by astroglial and intramyelinic vacuolation. Astroglia express NaDC3 (encoded by SLC13A3), a sodium‐coupled transporter for NAA and other dicarboxylates. Astroglial conditional Slc13a3 deletion in aspartoacylase‐deficient Canavan disease model mice (“CD mice”) reversed brain NAA elevation and improved motor function. These results demonstrate that astroglial NaDC3 contributes to brain NAA elevation in CD mice, and suggest that suppressing astroglial NaDC3 activity would ameliorate human Canavan disease.

Abstract Background CDK4/6 inhibitors in combination with traditional endocrine therapy (ET) have become the recommended first‐line therapy for HR‐positive/HER2‐negative metastatic breast cancer (MBC). The aim of this prospective study was to evaluate the relationship between HER2‐low expression and clinical outcomes in HR‐positive/HER2‐negative MBC patients receiving ET with or without CDK4/6 inhibitors. Methods Between April 2016 and November 2019, 233 women with HR‐positive/HER2‐negative MBC who received ET with or without CDK4/6 inhibitors were enrolled into the study. The primary endpoint was progression‐free survival (PFS). Statistical analysis included descriptive statistics, Kaplan–Meier curves, and Cox proportional hazards models. Results HER2‐low and HER2‐zero subgroups in the CDK4/6 inhibitor plus ET cohort showed no significant difference in the median PFS (10.9 vs. 8.0 months; hazard ratio: 0.92; 95% confidence interval [CI]: 0.64–1. 30; p = 0.65), while HER2‐low subgroup showed a significantly shorter median PFS compared to the HER2‐zero subgroup in the ET alone cohort (5.6 vs. 17.0 months; hazard ratio: 2.82; 95% CI: 1.34–5.93; p = 0.0044). Moreover, the objective response rate was significantly lower in the HER2‐low subgroup than the HER2‐zero subgroup in the ET alone cohort (10.5% vs. 40.0%, p = 0.047). Lastly, no significant difference was observed in the overall survival between the HER2‐low and HER2‐zero subgroups in both cohorts. Conclusion This study suggested that HER2‐low expression may predict the efficacy of ET but not that of CDK4/6 inhibitor plus ET in HR‐positive/HER2‐negative MBC patients. The results of this study highlight the importance of integrating HER2 status in tailoring personalized treatment strategies for HR‐positive MBC.

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with a multifaceted pathogenesis involving genetic, epigenetic, and environmental factors. It mainly targets the synovium, leading to synovitis and subsequently bone erosion. Novel effective treatments for RA are imperative. Matrine, the main active constituent of Sophora flavescens Ait (known as Kushen in Chinese medicine), has been used to treat fever, dysentery, hematochezia, jaundice, oliguria, vulvar swelling, asthma, eczema, and inflammatory disorders. Matrine exhibits diverse pharmacological effects, including antitumor, anti‐inflammatory, antifibrotic, and antiviral properties. Animal studies have suggested that matrine mitigates inflammation and reduces RA severity by modulating inflammation‐related expression. Its therapeutic mechanism in RA may involve several signaling pathways, including the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of the rapamycin, nuclear factor‐κB, Janus kinase/signal transducers and activators of transcription, and mitogen‐activated protein kinase pathways, all of which are associated with various biological processes, such as cell proliferation and differentiation, apoptosis, and immune regulation. Moreover, mitochondrial homeostasis disruption and epigenetic modifications, mediated by long noncoding RNAs, play crucial roles in RA pathogenesis. Experimental evidence suggests that matrine exerts therapeutic effects by modulating mitochondrial homeostasis and long noncoding RNAs. We summarize the molecular mechanisms of matrine in RA treatment to provide theoretical support for expanding its clinical applications to the treatment of RA.

Abstract The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre‐mRNA alternative splicing (AS) at the post‐transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA‐seq and LACE‐seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre‐mRNA splicing during the early steps of spermatogenesis.

Abstract In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles‐based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate‐specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (p = 0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (p

Abstract Background Despite advances in treatments for gastric cancer (GC), new targets are needed to enhance treatment, especially when mesenchymal‐epithelial transition (MET) amplification is involved. Therefore, we investigated the genomic features of MET‐amplified GC and efficacy of anti‐MET therapy. Methods Genomic features were investigated in 2284 patients (cohort 1) and 438 patients in the Cancer Genome Atlas (TCGA cohort). RNA data were obtained from TCGA for expression analysis. Clinical responses of 71 patients (cohort 2) were investigated. Survival rates were compared by Kaplan–Meier and log‐rank tests. Results In cohort 1, 95 (4.2%) exhibited MET amplifications. In TCGA cohort, 15 (3.4%) exhibited MET amplifications. The five top mutated genes were TP53, CDH1, ARID1A, KMT2D and PIK3CA in cohort 1 and TTN, TP53, MUC16, LRP1B and SYNE1 in TCGA cohort. TP53, PIK3CA, KRAS and GNAS showed significant single nucleotide variants (SNVs) in cohort 1, and TP53 SNVs were significant in TCGA cohort. Fifteen and 18 genes showed significant copy number variations (CNVs) between the MET‐ and non‐MET‐amplified groups in cohort 1 and TCGA cohort, respectively. The PI3K pathway was significantly activated in Chinese patients with MET‐amplified GC (p = 0.002). TP53 expression is negatively associated with MET amplification. Real‐world data obtained with cohort 2 revealed that anti‐MET treatment significantly affected overall survival (OS) (p = 0.002), whereas CNVs did not affect progression‐free or OS even when treatment lines were considered. Conclusions MET‐amplified GC has a distinctive mutation landscape. Our findings provide valuable information for clinicians who treat patients with MET‐amplified GC.

Abstract Background Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune‐inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single‐cell level. Methods We performed single‐cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co‐culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single‐cell analyses. Results LSCC with COPD showed increased proportions of tumour‐associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐programmed cell death‐1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. Conclusions Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. Highlight Our results demonstrated higher proportions of tumour‐associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐PD‐L1 signalling pathway, facilitating immune evasion.

Abstract In the realms of 5G and the upcoming 6G communications, the millimeter‐wave bands offer substantially greater bandwidth. However, due to their propagation characteristics, aligning antennas becomes a challenging issue, particularly at the node side in industrial and vehicular network applications. Angle‐scanning antennas can significantly enhance communication reliability or provide new possibilities for spatial multiplexing. Previous studies have predominantly concentrated on frequency‐scanning antennas characterized by either low‐gain individual units or expensive digital arrays. Consequently, there has been a scarcity of solutions that are both cost‐effective and high‐gain. In this study, a method is proposed for achieving frequency scanning by extending the feed lines between elements. Based on this approach, a millimeter‐wave high‐gain serial‐feed frequency‐scanning antenna is developed. This antenna operates within the 60–64 GHz millimeter‐wave ISM (Industrial, Scientific, and Medical) band and is capable of performing a 10∘ scan in the E‐plane. Moreover, the antenna maintains a width of less than half a wavelength, allowing for the assembly of multiple antennas into a MIMO array.

Abstract Deep low‐frequency earthquakes (DLFE) are observed beneath volcanoes worldwide but are limited to island arc volcanoes, hotspot volcanoes, and rift zones. Here we show DLFEs in the Tengchong Volcano Field, southeast Tibet, located ∼300 km from the Indo‐Burma volcanic arc, by analyzing a 12‐year continuous seismic data set. The earthquakes were at a depth of ∼12 km, near the sidewall of the magma body detected by the magnetotelluric survey. The features of isotropic focal mechanism, episodic occurrence, and possible non‐power‐law scaling, with no detectable geodetic deformation, as well as the petrological signatures of the Holocene eruption product, suggest that the earthquakes were likely associated with the weak intermittent magma flows near the magma body. This finding may demonstrate the existence of unsteady magmatic processes in the margin of the Indo‐Eurasia collision zone, which could indicate unneglectable volcanic hazards, underestimated geothermal resources, and mineralization processes in similar regions.

Background Vascular smooth muscle cell (VSMC) proliferation is involved in many types of arterial diseases, including neointima hyperplasia, in which Ca2+ has been recognized as a key player. However, the physiological role of Ca2+ release via inositol 1,4,5‐trisphosphate receptors (IP3Rs) from endoplasmic reticulum in regulating VSMC proliferation has not been well determined. Methods and Results Both in vitro cell culture models and in vivo mouse models were generated to investigate the role of IP3Rs in regulating VSMC proliferation. Expression of all 3 IP3R subtypes was increased in cultured VSMCs upon platelet‐derived growth factor‐BB and FBS stimulation as well as in the left carotid artery undergoing intimal thickening after vascular occlusion. Genetic ablation of all 3 IP3R subtypes abolished endoplasmic reticulum Ca2+ release in cultured VSMCs, significantly reduced cell proliferation induced by platelet‐derived growth factor‐BB and FBS stimulation, and also decreased cell migration of VSMCs. Furthermore, smooth muscle–specific deletion of all IP3R subtypes in adult mice dramatically attenuated neointima formation induced by left carotid artery ligation, accompanied by significant decreases in cell proliferation and matrix metalloproteinase‐9 expression in injured vessels. Mechanistically, IP3R‐mediated Ca2+ release may activate cAMP response element–binding protein, a key player in controlling VSMC proliferation, via Ca2+/calmodulin‐dependent protein kinase II and Akt. Loss of IP3Rs suppressed cAMP response element–binding protein phosphorylation at Ser133 in both cultured VSMCs and injured vessels, whereas application of Ca2+ permeable ionophore, ionomycin, can reverse cAMP response element–binding protein phosphorylation in IP3R triple knockout VSMCs. Conclusions Our results demonstrated an essential role of IP3R‐mediated Ca2+ release from endoplasmic reticulum in regulating cAMP response element–binding protein activation, VSMC proliferation, and neointima formation in mouse arteries.

Abstract The application of deep learning in high‐precision ionospheric parameter prediction has become one of the focus in space weather research. In this study, an improved model called Mixed Convolutional Neural Networks (CNN)—Bi‐Long Short Term Memory is proposed for predicting future ionospheric Total Electron Content (TEC). The model is trained using the longest available (25 years) Global Ionospheric Maps‐TEC and evaluated the accuracy of ionospheric storm predictions. The results indicate that using historical TEC in the solar‐geographical reference frame as input driving data achieves higher prediction accuracy compared to that in the geocentric coordinate system. Additionally, by comparing different input parameters, it is found that incorporating the Kp, ap, and Dst indices as inputs to the model effectively improves its accuracy, especially in long‐term forecasting where R2 increased by 3.49% and Root Mean Square Error decreased by 13.48%. Compared with BiLSTM‐Deep Neural Networks (DNN) and CNN‐BiLSTM, the Mixed CNN‐BiLSTM model has the highest prediction accuracy. It suggests that the utilization of CNN modules for processing spatial information, along with the incorporation of DNN modules to incorporate geomagnetic indices for result correction. Moreover, in short‐term predictions, the model accurately forecasts the evolution process of ionospheric storms. When extending the predicted length, although there are cases of prediction errors, the model still captures the entire process of ionospheric storms. Furthermore, the predicted results are significantly influenced by longitude, magnetic latitude, and local time.