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ABSTRACT Introduction The early detection of high‐risk individuals is crucial to delay and reduce the incidence of type 2 diabetes. In this study, we aimed to explore the performance of a novel subgroup‐specific biomarker strategy in the prediction of incident diabetes. Materials and Methods In the Taiwan Lifestyle Cohort Study, adult subjects without diabetes were included and followed for the incidence of diabetes in 2006–2019. The biomarkers measured included blood secretogranin III (SCG3), vascular adhesion protein‐1 (VAP‐1), fibrinogen‐like protein 1 (FGL1), angiopoietin‐like protein 6 (ANGPTL6), and angiopoietin‐like protein 4 (ANGPTL4). Results Among the 1,287 subjects, 12.2% developed diabetes during a 6 year follow‐up. Blood VAP‐1 was significantly associated with incident diabetes in the overall population (HR = 0.724, P

Abstract Objective We established a prospective cohort study to investigate the differences in motor and non‐motor symptoms between idiopathic Parkinson's disease (IPD) and Parkinson's disease in carriers of leucine‐rich repeat kinase 2 (LRRK2) gene risk variants (LRRK2‐PD). Methods The study included 1407 individuals with IPD and 649 individuals with LRRK2‐PD (comprising 304 with LRRK2‐G2385R, 220 with LRRK2‐R1628P, and 105 with LRRK2‐A419V). Differences in symptoms between LRRK2‐PD and IPD were analyzed using LCMM modeling and Cox regression analysis. Results The LRRK2‐G2385R variant showed slower progression in tremor symptoms and excessive daytime sleepiness compared with IPD. In contrast, symptoms associated with LRRK2‐R1628P and LRRK2‐A419V were more similar to those of IPD. Survival analysis revealed that LRRK2‐PD does not affect life expectancy compared with IPD. Interpretation Our extended longitudinal follow‐up of LRRK2‐PD in the Chinese population provided valuable insights, further confirming the clinical characteristics of the three LRRK2 variants.

Abstract Medulla Tetrapanacis (MT) is a commonly used herbal ingredient in soup to promote lactation and management of mastitis among lactating mothers worldwide, particularly in Asian countries. However, scientific evidence to support its usage in the management of mastitis is limited. This study aimed to investigate the effects of MT water extract and its underlying mechanisms in Staphylococcus aureus (SA)–induced mastitis in human mammary epithelial cells (HuMEC) and lipopolysaccharide (LPS)–induced mastitis in lactating Sprague–Dawley (SD) rats. The anti‐inflammatory and antibacterial effects of MT water extract were examined in SA‐infected HuMEC by ELISA and plate counting, respectively. The effects of MT water extract on blood‐milk barrier and the underlying mechanism of action of the MT water extract were also investigated by transendothelial electrical resistance assay and western blot. The effects and mechanisms of MT water extract on alleviating mastitis on SD rats were evaluated using LPS‐induced mastitis rat model. Our results showed that MT water extract could suppress SA‐induced mastitis by reducing SA internalization and growth, protecting blood‐milk barrier integrity, and attenuating release of cytokines (interleukin 6 [IL‐6] and tumor necrosis factor‐alpha [TNF‐α]) in HuEMC. Furthermore, the antibacterial effect might be related to the increase of antimicrobial peptides transcription, and the anti‐inflammatory effect is at least partly mediated by inactivation of p38 and JNK signaling pathways. Finally, our in vivo results showed that MT water extract ameliorated LPS‐induced mastitis in SD rats via suppressing inflammatory cytokine release (TNF‐α, IL‐6, and interleukin‐1 beta), myeloperoxidase, and alleviating pathohistological damage by downregulation of JNK signaling pathway.

Abstract Vital signs such as heart rate (HR) and respiration rate (RR) are essential physiological parameters that are routinely used to monitor human health and bodily functions. They can be continuously monitored through contact or contactless measurements performed in the home or a hospital. In this study, a contactless Doppler radar W‐band sensing system was used for short‐range, contactless vital sign estimation. Frequency‐modulated continuous wave (FMCW) measurements were performed to reduce the influence of a patient's micromotion. Sensing software was developed that can process the received chirps to filter and extract heartbeat and breathing rhythm signals. The proposed contactless sensing system eliminates the need for the contact electrodes, electric patches, photoelectric sensors, and conductive wires used in typical physiological sensing methods. The system operates at 76–81 GHz in FMCW mode and can detect objects on the basis of changes in frequency and phase. The obtained signals are used to precisely monitor a patient's HR and RR with minimal noise interference. In a laboratory setting, the heartbeats and breathing rhythm signals of healthy young participants were measured, and their HR and RR were estimated through frequency‐ and time‐domain analyses. The experimental results confirmed the feasibility of the proposed W‐band mm‐wave radar for contactless and short‐range continuous detection of human vital signs.

Abstract A novel broadband dual‐polarised transmitarray antenna (TA) utilising tightly coupled cross dipole cells is proposed in this work. The transmitarray cell using the tightly coupling wideband principle comprises two radiation patches designed as two orthogonal planar dipoles with four interdigital capacitors, two meandered parallel plate transmission lines, and a ground. Each cell has a square shape and a dimension of approximately 0.28 λc where λc is the wavelength at central frequency 5.5 GHz. The transmitarray cell can achieve 475° phase shift at central frequency and transmission magnitude better than −2.5 dB within the working band. To verify the feasibility of this design, a tightly coupled dual‐polarised transmitarray antenna (TCDPTA) is modelled and manufactured. The transmitarray aperture size is approximately 4.1 λc × 4.1 λc. The simulation and measurement illustrate that the TCDPTA has stable and distortion‐free main beams whose side lobe levels are generally below −10 dB in the band of 3.0–8.0 GHz. The measured gain at central frequency is 16.2 dBi and peak gain is 19 dBi at 7.5 GHz. The working bandwidth is 90.9% and 3 dB gain bandwidth is 66.7%. The measured cross‐polarisation levels are below −15 dB at axial direction. This TA has potential applications for high‐date‐rate communication and high‐revolution radar imaging systems at C‐band.

Abstract Smart grids represent a paradigm shift in the electricity industry, moving from traditional one‐way systems to more dynamic, interconnected networks. These grids are characterised by their intelligent automation, robust structure, and enhanced interaction with customers, backed by comprehensive monitoring and data analytics. The key of this transformation is the integration of data‐driven methods into smart grids. Compared to previous big data solutions, large language models (LLMs), with their advanced generalisation abilities and multi‐modal competencies, are crucial in effectively managing and integrating diverse data sources. They address challenges such as data inconsistency, inadequate quality, and heterogeneity, thereby enhancing the operational efficiency and reliability of smart grids. Furthermore, at the system level, LLMs improve human–system interactions, making smart grids more user‐friendly and intuitive. Last but not the least, the structure of LLMs performs inherent advantages in bolstering system security and privacy, alongside in resolving issues related to system compatibility and integration. The paper reviews the data‐empowered smart grids and for the first time finds and proposes opportunities and future directions for adopting LLMs to accelerate the mass‐scale application of Smart Grids.

Abstract Light field (LF) depth estimation is a key task with numerous practical applications. However, achieving high‐precision depth estimation in challenging scenarios, such as occlusions and detailed regions (e.g. fine structures and edges), remains a significant challenge. To address this problem, the authors propose a LF depth estimation network based on multi‐region selection and guided optimisation. Firstly, we construct a multi‐region disparity selection module based on angular patch, which selects specific regions for generating angular patch, achieving representative sub‐angular patch by balancing different regions. Secondly, different from traditional guided deformable convolution, the guided optimisation leverages colour prior information to learn the aggregation of sampling points, which enhances the deformable convolution ability by learning deformation parameters and fitting irregular windows. Finally, to achieve high‐precision LF depth estimation, the authors have developed a network architecture based on the proposed multi‐region disparity selection and guided optimisation module. Experiments demonstrate the effectiveness of network on the HCInew dataset, especially in handling occlusions and detailed regions.

Abstract Objective Dystonic posturing (DP) is a common semiology in temporal lobe epilepsy (TLE). We aimed to explore cerebellar gradient alterations in functional connectivity in TLE patients with and without DP. Methods Resting‐state functional MRI data were obtained in 60 TLE patients and 32 matched healthy controls. Patients were further divided into two groups: TLE with DP (TLE + DP, 31 patients) and TLE without DP (TLP‐DP, 29 patients). We explored functional gradient alterations in the cerebellum based on cerebellar–cerebral functional connectivity and combined with independent component analysis to evaluate cerebellar–cerebral functional integration and reveal the contribution of the motor components to the gradient. Results There were no obvious differences in clinical features and postoperative seizure outcomes between TLE + DP and TLE‐DP patients. Patients and controls all showed a clear unimodal‐to‐transmodal gradient transition in the cerebellum, while TLE patients demonstrated an extended principal gradient in functional connectivity compared to healthy controls, which was more limited in TLE + DP patients. Gradient alterations were more widespread in TLE‐DP patients, involving bilateral cerebellum, while gradient alterations in TLE + DP patients were limited in the cerebellum ipsilateral to the seizure focus. In addition, more cerebellar motor components contributed to the gradient alterations in TLE + DP patients, mainly in ipsilateral cerebellum. Significance Extended cerebellar principal gradients in functional connectivity revealed excessive functional segregation between unimodal and transmodal systems in TLE. The functional connectivity gradients were more limited in TLE + DP patients. Functional connectivity in TLE patients with dystonic posturing involved more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Plain Language Summary Dystonic posturing contralateral to epileptic focus is a common symptom in temporal lobe epilepsy, and the cerebellum may be involved in its generation. In this study, we found cerebellar gradients alterations in functional connectivity in temporal lobe epilepsy patients with and without contralateral dystonic posturing. In particular, we found that TLE patients with dystonic posturing may have more limited cerebellar gradient in functional connectivity, involving more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Our study suggests a close relationship between ipsilateral cerebellum and contralateral dystonic posturing.

Abstract Background Oroantral fistula (OAF) is a pathological channel formed between the oral cavity and the maxillary sinus. A large size of OAF (≥5 mm) increases the risk of surgical failure, and an optimal surgical approach should be cautiously selected. Objective This study aims to characterize the application of nasal endoscopy and buccal fat pad (BFP) flaps to repair large OAFs in patients with odontogenic maxillary sinusitis (OMS). Methods A total of 32 patients with large OAF combined with OMS after dental extraction who were treated in the Department of Otorhinolaryngology, Nanjing Renpin ENT Hospital from 2018 to 2022, were retrospectively recruited. A thorough preoperative evaluation was performed and all patients were first treated with nasal endoscopy, followed by the repair of OAFs using BFP flaps under general anesthesia. The cure rate and postoperative pain score were used as outcome indicators to evaluate the effectiveness of the procedure. Results All patients completed a 12‐month follow‐up. The results showed that OFAs were cured in 25 (32 in total, 78.1%) patients by the second postoperative week. OFAs were healed in all patients at week 8 postoperatively. OMS was healed in 25 (32 in total, 78.1%) patients at the first postoperative week and all patients were healed by the disappearance of symptoms associated with OMS at week 8 postoperatively. At the second postoperative week, complete relief of pain symptoms was obtained in 18 (32 in total, 56.3%) patients (visual analog scale = 0 score), in 25 (32 in total, 78.1%) patients at the fourth postoperative week, and by the eighth postoperative week, all patients had complete resolution of pain symptoms. Conclusions Secondary maxillary sinusitis is not a contraindication to the treatment of large OAFs. Large OAFs can be effectively closed using BFP flaps combined with endoscopic maxillary sinus drainage.

Abstract Based on empirical data of an orthogonal frequency division multiplexing system in realistic environments of next‐generation cellular networks, a new analytical model of phase noise and numerical characteristics of the common phase error and intercarrier interference are derived. Applying an asymptotic theory of probability, analytical expressions are present to approximate the mean vector and the covariance matrix of the intercarrier interference. The approximation expression of the covariance matrix is accurate enough and only has three parameters. When applied to estimate original symbols based on additive white Gaussian noise channel, a Gibbs sampler performs better than the current estimation algorithm following Weiner process phase noise.

Abstract Objective The single‐center retrospective cohort study investigated underlying pathogenic mechanisms and clinical significance of patients with temporal lobe epilepsy and hippocampal sclerosis (TLE‐HS), in the presence/absence of gray–white matter abnormalities (usually called “blurring”; GMB) in ipsilateral temporopolar region (TPR) on MRI. Methods The study involved 105 patients with unilateral TLE‐HS (60 GMB+ and 45 GMB−) who underwent standard anterior temporal lobectomy, along with 61 healthy controls. Resected specimens were examined under light microscope. With combined T1‐weighted and DTI data, we quantitatively compared large‐scale morphometric features and exacted diffusion parameters of ipsilateral TPR‐related superficial and deep white matter (WM) by atlas‐based segmentation. Along‐tract analysis was added to detect heterogeneous microstructural alterations at various points along deep WM tracts, which were categorized into inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and temporal cingulum. Results Comparable seizure semiology and postoperative seizure outcome were found, while the GMB+ group had significantly higher rate of HS Type 1 and history of febrile seizures, contrasting with significantly lower proportion of interictal contralateral epileptiform discharges, HS Type 2, and increased wasteosomes in hippocampal specimens. Similar morphometric features but greater WM atrophy with more diffusion abnormalities of superficial WM was observed adjacent to ipsilateral TPR in the GMB+ group. Moreover, microstructural alterations resulting from temporopolar GMB were more localized in temporal cingulum while evenly and widely distributed along ILF and UF. Interpretation Temporopolar GMB could signify more severe and widespread microstructural damage of white matter rather than a focal cortical lesion in TLE‐HS, affecting selection of surgical procedures.

Abstract Objective Expand genetic screening for atypical Type I sialidosis (ST‐1) could address its underdiagnosed in both progressive myoclonic ataxia (PMA) and ataxia patients. To evaluate the potential founder effect of mutation in the population. Methods We enrolled 231 patients with PMA or ataxia from the First Affiliated Hospital of Fujian Medical University. Through Whole Exome Sequencing and Sanger sequencing, we identified the causative gene in patients. Haplotype analysis was employed to explore a potential founder effect of the NEU1 c.544A>G mutation. Results A total of 31 patients from 23 unrelated families were genetically diagnosed with ST‐1. A significant 80.6% of these patients were homozygous for the c.544A>G mutation. We discovered six different NEU1 variants, including two novel mutations: c.951_968del and c.517T>G. The mean age of onset was 18.0 ± 7.1 years. The clinical spectrum of ST‐1 featured ataxia and myoclonus as the most common initial symptoms. Over 40% suffered from controlled generalized tonic–clonic seizures. Mobility and independence varied greatly across the cohort. Cherry‐red spots were rare, occurring in just 9.5% (2/21) of patients. Brain MRIs were typically unremarkable, except for two patients with unusual findings. EEGs showed diffuse paroxysmal activity in 17 patients. The c.544A>G mutation in NEU1 is a founder variant in Fujian, with a unique haplotype prevalent in East Asians. Interpretation ST‐1 should be suspected in patients with PMA or ataxia in Southeast China, even without macular cherry‐red spots and seizures, and the premier test could be a variant screening of the founder variant NEU1 c.544A>G.

Abstract Obesity has reached epidemic proportions in most parts of the world, and it is estimated that 1 billion people globally are trapped in an obesity pandemic, which has seriously compromised human health. Recently, there has been a flood of research into obesity as well as redox and lipid metabolism; however, our understanding of the pathways and specific molecular mechanisms by which obesity‐induced oxidative stress affects female reproductive function remains limited. In this review, we discuss how the obesity pandemic has led to lower female fertility. We focus on multiple facets of obesity‐mediated reproductive dysfunction, including follicular atresia, oocyte maturation, embryo implantation, reproductive aging, and discuss therapeutic interventions that have the potential to normalize reproductive function in obese females, such as targeting mitochondrial lipid metabolism and antioxidant pathways.

Background Tourniquet is applied in Total Knee Arthroplasty (TKA) to reduce intraoperative blood loss and improve view of surgical field. However, tourniquet use in TKA is still in dispute. Some researchers find that tourniquet may lead to extra side effects such as aggravated pain and limb swelling, while others consider that tourniquet has no significant adverse impact on clinical outcomes of TKA patients. This trial is conducted to evaluate tourniquet effect on TKA patients. Methods A prospective, single‐blind, randomized controlled trail is adopted with a sample size of 130 knees from August 2020 to February 2023. Patients undergoing TKA are randomly allocated to tourniquet group and non‐tourniquet group. Outcomes including quadriceps thickness and stiffness, operation time, total blood loss, intraoperative blood loss, postoperative blood loss, transfusion rate, thigh circumference, knee and thigh VAS, D‐Dimer and CRP level, knee function score, patient satisfaction, and complications are evaluated in this trial. Student's t‐test, Mann–Whitney U test, Pearson's chi‐square test, and Fisher's exact test are used in this study. Results No significant difference in demographic information and baseline outcomes were found (p > 0.05). Participants in the tourniquet group had significantly less total blood loss and intraoperative blood loss, more postoperative blood loss, and higher D‐Dimer level on postoperative day 3 when compared with non‐tourniquet group (p 0.05). Conclusion Tourniquet application can effectively reduce intraoperative blood loss and total blood loss, without significant side effects. Hence, we advocate the regular use of tourniquet in primary TKA.

Abstract Background Sarcopenia, the age‐related loss of muscle mass and function, brings multiple adverse outcomes including disability and death. Several sarcopenia consensuses have newly introduced the premorbid concept of possible sarcopenia and recommended early lifestyle interventions. Bidirectional transitions of premorbid states have been revealed in several chronic diseases yet not clarified in sarcopenia. This study aims to investigate the underlying transition patterns of sarcopenia states. Methods The study utilized three waves of data from a nationally representative survey, the China Health and Retirement Longitudinal Study (CHARLS), and included community‐dwelling individuals aged 60 years and older with at least two sarcopenia states assessments based on the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019) between 2011 and 2015. The estimated transition intensity and probability between non‐sarcopenia, possible sarcopenia, sarcopenia, and death were investigated using multi‐stage Markov (MSM) models. Results The study comprised 4395 individuals (49.2% female, median age 67 years) with a total of 10 778 records of sarcopenia state assessment, and the mean follow‐up period was 3.29 years. A total of 24.5% of individuals with a current state of possible sarcopenia returned to non‐sarcopenia, 60.3% remained possible sarcopenia, 6.7% progressed to sarcopenia, and 8.5% died by the next follow‐up. The transition intensity of recovery to non‐sarcopenia (0.252, 95% CI 0.231–0.275) was 2.8 times greater than the deterioration to sarcopenia (0.090, 95% CI 0.080–0.100) for individuals with possible sarcopenia. For individuals with possible sarcopenia, the estimated probabilities of recovering to non‐sarcopenia, progressing to sarcopenia, and transitioning to death within a 1‐year observation were 0.181, 0.066, and 0.035, respectively. For individuals with sarcopenia, the estimated probabilities of recovering to non‐sarcopenia, recovering to possible sarcopenia, and transitioning to death within 1‐year observation were 0.016, 0.125, and 0.075, respectively. In covariables analysis, age, sex, body mass index, physical function impairment, smoking, hypertension, and diabetes are important factors influencing bidirectional transitions. Conclusions The findings highlight the bidirectional transitions of sarcopenia states among older adults and reveal a notable proportion of possible sarcopenia show potential for recovery in the natural course. Screening and intensifying interventions based on risk factors may facilitate a recovery transition.

Abstract This paper proposes a novel approach for absolute velocity estimation of unmanned aerial vehicles in unknown and unmapped GNSS‐denied environments. The proposed method leverages the advantages of Fourier‐based image phase correlation and utilizes off‐the‐shelf onboard sensors, including a downward‐facing monocular camera, an inertial sensor, and a sonar. The non‐matching tracking approach is particularly appealing, offering accurate estimation while remaining robust against frequency‐dependent noise, significant intensity variations, and time‐varying illumination disturbances. In the proposed method, the first step involves computing global pixel motion from consecutive images using phase correlation, which utilizes the shift property of the Fourier transform. This pixel motion estimation serves as the basis for creating a closed‐loop solution for absolute velocity estimation. To further enhance accuracy, a Kalman filter is implemented to fuse all available data and provide a reliable velocity estimate. Validation of the proposed visual‐inertial technique is conducted through simulation experiments using AirSim and real‐world flight tests. The results demonstrate the practicality and effectiveness of the approach across a range of challenging scenarios.

Abstract MRI (magnetic resonance imaging) images can effectively show the placental haemorrhage area. In view of the special properties and real‐time detection requirements of placental haemorrhage MRI images, this paper has systematically improved the single‐shot multi‐box detector (SSD) target detection algorithm (M‐SSD). First, taking advantage of the particularity of the MRI image, the maximum stable extremum region (MSER) algorithm was used as the anchor proposal network which integrated the proposal information into the feature layer of SSD to avoid the hungry traversal of the original algorithm. Second, after the scale statistics of the placental haemorrhage area in MRI images, the bounding box matching the size of the placental haemorrhage area was redefined, in this way, the scale of the bounding box will have application pertinence, which can effectively improve the detection accuracy of the algorithm. Third, due to the small target property of the placental haemorrhage area in the MRI image, the VGG16 basic network in the original SSD was replaced by ResNet101, this made the algorithm have higher performance in small target detection. Finally, the Placental Haemorrhage MRI Detection Database (PHMD) has been built which is not only a base for this paper, but also for further research in this area.

Abstract Support vector machine (SVM) is a binary classifier widely used in machine learning. However, neglecting the latent data structure in previous SVM can limit the performance of SVM and its extensions. To address this issue, the authors propose a novel SVM with discriminative low‐rank embedding (LRSVM) that finds a discriminative latent low‐rank subspace more suitable for SVM classification. The extension models of LRSVM are introduced by imposing different orthogonality constraints to prevent computational inaccuracies. A detailed derivation of the authors’ iterative algorithms are given that is essentially for solving the SVM on the low‐rank subspace. Additionally, some theorems and properties of the proposed models are presented by the authors. It is worth mentioning that the subproblems of the proposed algorithms are equivalent to the standard or the weighted linear discriminant analysis (LDA) problems. This indicates that the projection subspaces obtained by the authors’ algorithms are more suitable for SVM classification compared to those from the LDA method. The convergence analysis for the authors proposed algorithms are also provided. Furthermore, the authors conduct experiments on various machine learning data sets to evaluate the algorithms. The experiment results show that the authors’ algorithms perform significantly better than other algorithms, which indicates their superior abilities on classification tasks.

Abstract Vector‐borne diseases caused by arthropod‐borne viruses (arboviruses) are a considerable challenge to public health globally. Mosquito‐borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of human illnesses and may be fatal. Currently, efforts to control these diseases still face challenges due to growing vector resistance towards insecticides, urbanization, and limited effective antiviral treatments and vaccines. Animal models are crucial in antiviral research on mosquito‐borne arboviruses, playing a role in understanding disease mechanisms, vaccine development, and toxicity testing, but the application of animal models still faces the challenges of ethical considerations and animal‐to‐human translational success. Genetically engineered mouse models, hamster models and non‐human primate (NHP) are currently used in arbovirus research, but new models such as tree shrews and novel humanized mice are emerging. In the context of Malaysian research, the use of long‐tailed macaques as potential NHP models for arbovirus research is possible; however, it faces the ethical dilemma of using an endangered species for scientific purposes. Overall, animal models play a crucial role in advancing infectious disease research, but a balance between medical research and species conservation must be upheld.

Abstract In order to enhance the dynamic performance of aircraft high‐voltage direct current wound rotor synchronous generator (WRSG) system under load variations, a dual internal model control (DIMC) method utilising improved load current feedback (ILCF) is proposed. It employs internal model controllers in both voltage and current loops, thereby significantly augmenting the system's disturbance rejection capabilities. Improved load current feedback is incorporated between the DC voltage loop and the field current loop. Additionally, a method for designing a feedback fitting function is established, enhancing the system's adaptability to changes in operational speed and load. The authors outline parameter design methods for voltage and current loops in DIMC, based on the internal model control principle. Adjustments to these parameters can further enhance the system's disturbance rejection capabilities. Finally, comparative experiments between the PI method with ILCF and the DIMC method with ILCF are conducted on a 15 kW WRSG experimental platform. These experiments demonstrate that the proposed DIMC method with ILCF optimises dynamic performance across the entire speed range, enhancing the competitiveness of WRSG systems in aircraft applications.

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 The management of femoral multiplanar deformity remains a great challenge for orthopaedic surgeons. The focal dome osteotomy (FDO) combined with Ilizarov technique is a theoretically ideal method for treating femoral multiplanar deformity, but the clinical evidence is limited. The aim of this study is to assess the clinical and radiological outcomes of this combined strategy for correcting femoral multiplanar deformities. Methods A retrospective analysis was conducted to analyze 20 patients (29 limbs) with femoral multiplanar deformities treated by FDO combined with Ilizarov external fixation in our limb deformity center between 2017 and 2022. Preoperative and postoperative radiographical parameters were measured, including lateral proximal femoral angle (LPFA), mechanical lateral distal femoral angle (mLDFA), middle diaphysis angle (MDA), anatomic posterior distal femoral angle (aPDFA), mechanical axis deviation (MAD), and limb length discrepancy (LLD). Clinical assessments included a self‐made questionnaire for exercise capacity score (ECS), visual analog scale (VAS), and the 36‐Item Short‐Form Health Survey (SF‐36) score. Results There were eight males and 12 females, with a mean age of 32.8 years (14–61 years). All patients completed follow‐up with a mean follow‐up duration of 41.5 (27–81) months. The mean EFT was 8.9 (1.4–20.2) months. At final follow‐up, significantly improvement was noted regarding mean LLD (from 1.8 to 0.4 cm, p 0.5 cm) was noted in four patients but without significant symptoms. No serious complications occurred. Conclusions The strategy of FDO combined with Ilizarov fixation could provide powerful ability and good flexibility for correcting femoral multiplanar deformities without significant complications.

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

Objective Although several reconstructive methods have been developed to manage large segmental tibial bone defects including bone transport (distraction osteogenesis), contralateral fibular graft, allograft, tibiofibular synostosis, Masquelet technique, and 3D printed scaffold, neglected large tibial defects in adults remain challenging problems. This study describes gradual transverse transport of naturally tibialized fibula using hexapod frames in management of adult patients with neglected large tibial defects. Methods We retrospectively reviewed four cases of transverse transport of naturally tibialized fibula from November 2018 to February 2022. We measured the length of the tibial defect and the transported fibular segment, the mid‐diaphyseal diameter and cortical thickness of the affected fibula, contralateral fibula, and tibia. The parameters measured both preoperatively and postoperatively were leg length discrepancy, hip‐knee‐ankle angle, medial proximal tibial angle, posterior proximal tibial angle, lateral distal tibial angle, range of motion of the knee and ankle joints, and Lower Extremity Functional Scores (LEFS). Patients' satisfaction rates using Likert scale were also recorded. Results Among four female patients, three suffered from tibial osteomyelitis, and one was due to congenital pseudarthrosis of the tibia. The average follow‐up time was 2.7 ± 1.4 years. The average length of tibial defect was 14.0 ± 0.8 cm. The average preoperative shortening of the affected leg was 9.0 ± 2.5 cm, which changed to 0.6 ± 0.8 cm postoperatively. The median length of the transported fibular segment was 15.2 cm. Two patients had varus deformity, two had recurvatum, and one had procurvatum preoperatively. Postoperative radiological measurement showed all deformities corrected and no ankle valgus deformity developed during follow‐up. All patients achieved union and can fully weight bear on the affected extremity. The average fixator time was 12.9 ± 2.9 months. The average preoperative and postoperative LEFS, respectively, were 53.5 ± 5.0, 70.5 ± 1.3, with a significant difference (p = 0.003). Three patients reported very satisfied with the outcome, and one patient reported satisfied. Three patients had pin tract infections, and one patient had skin necrosis which healed after additional surgery. One patient had surgical release of the hamstring tendons due to flexion contracture of the knee. Two patients had 15° of reduction in ankle range of motion. One patient had transient common peroneal nerve palsy which spontaneously recovered within 6 weeks. Conclusion The transverse transport of naturally tibialized fibula was both a safe and effective method to treat the long‐standing type V tibial segmental defect.

Abstract Disruption of the bone metabolic balance with advancing age leads to an escalating prevalence of bone‐related diseases, significantly compromising individuals’ quality of life. The gut microbiota actively participates in the regulation of bone metabolism, and perturbations in the gut microbiota can exacerbate bone diseases by compromising gut barrier integrity. Determining the microbial taxa involved in bone loss could offer valuable insights into the development of alternative therapies and nutritional interventions for disease management. Therefore, based on metagenomic and 16S ribosomal RNA data, this study analyzed the gut microbiota structure of 488 individuals with different bone masses (NC, normal; ON, osteopenia; OP, osteoporosis) to identify significant associations between the gut microbiota and bone loss. The results showed that at the genus and species levels, the microbiota diversity of the ON population increased, whereas that of the OP population decreased. Bacteroides were significantly enriched in the OP population, whereas the beneficial bacteria Bifidobacterium, Akkermansia, and lactobacilli decreased. Subsequent analyses revealed no significant variation in different bone populations in terms of Bifidobacterium levels, whereas lactobacilli exhibited diverse responses across distinct bone populations. The administration of lactobacilli effectively enhanced lumbar spine bone mineral density and modulated the gut microbiota structure in a population with unhealthy bone mass. This study contributes to the validation of the association between the gut microbiota and bone mass, enhances our understanding of the potential impact of probiotics (lactobacilli) on bone mass, and establishes a robust scientific basis for the application of probiotics in the regulation of bone mass.

Abstract Nutritional intervention can greatly benefit people who suffer from side effects of medical treatments by improving intestinal post‐damage recovery. The recovery process is dependent on the regeneration of intestinal epithelial cells, which is driven by Lgr5+ intestinal stem cells (ISCs). Lactoferrin (LF) is a natural milk‐abundant protein with several gut health‐related functions such as antibacterial and immunoregulation activities, thus protecting intestine from damage. However, it is unclear whether LF also plays a role in the repair of the injured intestine, despite limited clues on its ability to modulate intestinal epithelial cell growth in vitro. Here, we show that LF accelerates intestinal epithelial recovery after both dextran sulfate sodium challenge on mice and TNF‐α treatment on intestinal organoids. Furthermore, we find LF gives rise to ISC‐mediated epithelial regeneration by directly activating the Lgr5+ stem cells. Finally, we identify Lrp5/Wnt signaling as the key pathway for LF‐enhancing ISC stemness and function. Overall, our study reveals the potential of LF as a nutrient that can be applied to promote intestinal healing.

Abstract Left ventricular (LV) hypertrophy (LVH) is frequently observed in patients with hypertension (HTN). LV myocardial work (MW) has recently emerged as a non‐invasive method to assess systolic myocardial deformation relative to afterload conditions. The authors investigated the characteristics of myocardial work with different degrees of LVH in HTN patients. From December 2020 to February 2024, 255 HTN patients and 26 healthy controls undergoing transthoracic echocardiography were included in the current study. Hypertension patients were divided into quintile groups based on left ventricular mass index (LVMI), for the first to fourth LVMI quantiles, global work index (GWI) and global constructive work (GCW) were higher compared to the control group, but the difference was not statistically significant. In the sixth LVMI quantile, GWI and GCW showed a significant decrease. The restricted cubic splines showed that both GWI and GCW exhibited an inverted U‐shaped relationship with LVMI. A LVMI of >151.39 g/m2 could accurately predict reduction both in GWI and GCW (Sensitivity: 0.78, Specificity: 0.89, AUC: 0.90, P

Abstract Solar hydrogen peroxide (H2O2) production has garnered increased research interest owing to its safety, cost‐effectiveness, environmental friendliness, and sustainability. The synthesis of H2O2 relies mainly on renewable resources such as water, oxygen, and solar energy, resulting in minimal waste. Bismuth vanadate (BiVO4) stands out among various oxide semiconductors for selective H2O2 production under visible light via direct two‐electron oxygen reduction reaction (ORR) and two‐electron water oxidation reaction (WOR) pathways. Significant advancements have been achieved using BiVO4‐based materials in solar H2O2 production over the last decade. This review explores advancements in BiVO4‐based photocatalysts for H2O2 production, focusing on photocatalytic powder suspension (PS) and photoelectrochemical (PEC) systems, representing the main approaches for heterogenous artificial photosynthesis. An overview of fundamental principles, performance assessment methodologies, photocatalyst and photoelectrode development, and optimization of reaction conditions is provided. While diverse strategies, such as heterojunction, doping, crystal facet engineering, cocatalyst loading, and surface passivation, have proven effective in enhancing H2O2 generation, this review offers insights into their similar and distinct implementations within the PS and PEC systems. The challenges and future prospects in this field are also discussed to facilitate the rational design of high‐performing BiVO4‐based photocatalysts and photoelectrodes for H2O2 generation under visible light.

Abstract On 7–8 September 2023, Hong Kong was hit by a historical and record‐breaking rainstorm associated with the remnant of Tropical Cyclone Haikui (2311). The hourly rainfall recorded at the Hong Kong Observatory Headquarters once reached 158.1 mm, the highest since record began in 1884. The 24‐h rainfall even exceeded 600 mm in some parts of the territory. The historical rainstorm resulted in heavy flooding and landslides, bringing significant societal impact to Hong Kong. This paper aims to review this unprecedented heavy rain event from the aspects of diagnosis, forecasting and nowcasting. Early indicators of such events over Hong Kong with substantial lead time are limited from the dynamics and thermodynamics consideration, the numerical weather prediction models, given the present technology. The only indication may come from the climatologically extreme total precipitable water. While recent research of developing a regional risk‐based alerting system on the higher impact event of flooding associated with heavy rain might have potential to enhance the weather service, and emerging AI model showed some promising post‐simulations, predicting historical and record‐breaking rainstorms remains a challenge for operational weather forecasting and warning services.

Abstract Electrocatalytic reduction of nitrate pollutants to produce ammonia offers an effective approach to realizing the artificial nitrogen cycle and replacing the energy‐intensive Haber‐Bosch process. Nitrite is an important intermediate product in the reduction of nitrate to ammonia. Therefore, the mechanism of converting nitrite into ammonia warrants further investigation. Molecular cobalt catalysts are regarded as promising for nitrite reduction reactions (NO2−RR). However, designing and controlling the coordination environment of molecular catalysts is crucial for studying the mechanism of NO2−RR and catalyst design. Herein, we develop a molecular platform of cobalt porphyrin with three coordination microenvironments (Co‐N3X1, X = N, O, S). Electrochemical experiments demonstrate that cobalt porphyrin with O coordination (CoOTPP) exhibits the lowest onset potential and the highest activity for NO2−RR in ammonia production. Under neutral, non‐buffered conditions over a wide potential range (−1.0 to −1.5 V versus AgCl/Ag), the Faradaic efficiency of nearly 90% for ammonia was achieved and reached 94.5% at −1.4 V versus AgCl/Ag, with an ammonia yield of 6,498 μg h−1 and a turnover number of 22,869 at −1.5 V versus AgCl/Ag. In situ characterization and density functional theory calculations reveal that modulating the coordination environment alters the electron transfer mode of the cobalt active center and the charge redistribution caused by the break of the ligand field. Therefore, this results in enhanced electrochemical activity for NO2−RR in ammonia production. This study provides valuable guidance for designing adjustments to the coordination environment of molecular catalysts to enhance catalytic activity.

Abstract RNA pseudouridylation, a dynamic and reversible post‐transcriptional modification found in diverse RNA species, is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre‐mRNA splicing, enhancement of mRNA translation, and translational fidelity. Disruption of pseudouridylation impairs cellular homeostasis, contributing to pathological alterations. Recent studies have highlighted its regulatory role in human diseases, particularly in tumourigenesis. Cellular stresses trigger RNA pseudouridylation in organisms, suggesting that pseudouridylation‐mediated epigenetic reprogramming is essential for maintaining cellular viability and responding to stress. This review examines the regulatory mechanisms and pathological implications of pseudouridylation in human diseases, with a focus on its involvement in tumourigenesis. Additionally, it explores the therapeutic potential of targeting pseudouridylation, presenting novel strategies for disease treatment. Highlights Methods to detect pseudouridine were introduced from classic mass spectrometry‐based methods to newer approaches such as nanopore‐based technologies and BID sequencing, each with its advantages and limitations. RNA pseudouridylation is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre‐mRNA splicing, enhancement of mRNA translation, and translational fidelity. Increased pseudouridylation is frequently associated with tumour initiation, progression, and poor prognosis, whereas its reduction is predominantly implicated in non‐tumour diseases. A comprehensive understanding of the inducing factors for RNA pseudouridylation will be essential for elucidating its role in diseases. Such insights can provide robust evidence for how pseudouridylation influences disease progression and offer new avenues for therapeutic strategies targeting pseudouridylation dysregulation. The therapeutic potential of RNA pseudouridylation in diseases is enormous, including inhibitors targeting pseudouridine synthases, the application of RNA pseudouridylation in RNA therapeutics, and its role as a biological marker.

Abstract Backgroud Oesophageal cancer ranks among the most prevalent malignant tumours globally, primarily consisting of oesophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSCs) accelerate the progression ESCC via their strong self‐renewal and tumourigenic capabilities, presenting significant clinical challenges due to increased risks of recurrence and drug resistance. Methods Our previous study has reported WYC‐209, which is capable of inducing apoptosis of CSCs in melanoma and hepatoma, but is ineffective against ESCC. Additionally, clinical studies in ESCC still lack drug candidates that effectively target CSCs. Therefore, our team developed a series of novel retinoids that target retinoic acid receptors (RARs), with enhanced potency, broader efficacy and minimised toxic side effects against CSCs. Following iterative optimisation and pharmacological validation, ZSH‐2208 was identified as the most promising candidate for effectively targeting ESCC tumour‐repopulating cells (TRCs). Mechanistic exploration revealed that ZSH‐2208 inhibits the growth of ESCC‐TRCs through modulation of the RARγ–TNFAIP3 axis. The clinical significance of the key molecule TNFAIP3 in ESCC has also been demonstrated. Results This study introduces ZSH‐2208, a novel retinoid specifically targeting ESCC‐TRCs, which holds significant potential for clinical application in ESCC. Key points The ESCC‐TRCs replicates the characteristics of ESCC stem cells, which are inhibited by ZSH‐2208. In vivo and in vitro experiments demonstrated that ZSH‐2208, a novel RA analogue, effectively inhibits the growth of ESCC‐TRCs through the RARγ–TNFAIP3 axis. Low levels of TNFIP3 protein may be associated with improved survival probability in ESCC patients.

Abstract Background Vitamin K‐dependent γ‐glutamic acid carboxylation (Gla) proteins are calcium‐binding and membrane‐associated, participating in coagulation, bone turnover, and cancer biology. The molecular function of transmembrane proline‐rich Gla proteins (PRRGs) remains unexplored. Methods Analysis of pancreatic ductal adenocarcinoma (PDAC) datasets, including transcription profiles, clinical data, and tissue microarrays, was conducted to evaluate PRRG1 expression and its clinical relevance. PDAC cell lines with overexpressed, knockdown, and mutated PRRG1 were developed to study biological functions and pathways using RNA‐seq, co‐immunoprecipitation with mass spectrometry, Western blotting, and immunofluorescence. In vivo xenograft and orthotopic models assessed PRRG1's impact on PDAC progression, with and without warfarin treatment. Results PRRG1 was significantly upregulated in PDAC compared to normal pancreas, correlating with poorer patient survival. PRRG1 knockdown reduced PDAC cell proliferation, anchorage‐independent growth in vitro, and tumor growth in vivo. PRRG1 localized at the plasma membrane, interacted with the HECT E3 ligase NEDD4 via the C‐terminal PPXY motif, and promoted NEDD4 self‐ubiquitination, reducing its protein levels. PRRG1 knockdown elevated NEDD4, destabilizing the oncoprotein KRAS and receptor EGFR, and attenuating downstream signaling and macropinocytosis under nutrient deprivation. The vitamin K‐dependent Gla modification of PRRG1 was crucial for its membrane localization and pro‐tumorigenic effects, and was inhibited by low‐dose warfarin, a clinical vitamin K antagonist. Conclusions This study identifies PRRG1 as a key regulator of pro‐tumorigenic signaling in PDAC, suggesting the potential of repurposing the anticoagulant warfarin as a therapeutic strategy. Key points PRRG1 is identified as the transmembrane Gla protein mediating PDAC malignancy. PRRG1 recruits and induces self‐ubiquitination of membrane‐anchoring E3 ligase NEDD4. PRRG1 exerts a protective role toward KRAS and EGFR by inhibiting NEDD4. The anticoagulant warfarin can be utilized to inhibit PRRG1 and PDAC advancement.

Abstract Precision medicine in less‐defined subtype diffuse large B‐cell lymphoma (DLBCL) remains a challenge due to the heterogeneous nature of the disease. Programmed cell death (PCD) pathways are crucial in the advancement of lymphoma and serve as significant prognostic markers for individuals afflicted with lymphoid cancers. To identify robust prognostic biomarkers that can guide personalized management for less‐defined subtype DLBCL patients, we integrated multi‐omics data derived from 339 standard R‐CHOP‐treated patients diagnosed with less‐defined subtype DLBCL from three independent cohorts. By employing various machine learning algorithms, we pinpointed eight pivotal genes linked to PCD, specifically FLT3, SORL1, CD8A, BCL2L1, COL13A1, MPG, DYRK2 and CAMK2B. Following this, we established a Programmed Cell Death Index (PCDI) utilizing the aforementioned genes and amalgamated it with pertinent clinical characteristics to formulate a predictive nomogram model for prognosis. We observed a significant correlation between the PCDI, pre‐treatment circulating tumour DNA (ctDNA) burden, minimal residual disease (MRD) status and immune features. Furthermore, our research indicated that patients with elevated PCDI scores could potentially show resistance to conventional chemotherapy treatments, yet they might derive an advantage from alternative inhibitors targeting specific signalling pathways. Conclusively, leveraging these results, we have created an online analytical tool (https://xulymphoma.shinyapps.io/PCDI_pred/) designed for the prognostic prediction of patients with less‐defined subtype DLBCL. This tool facilitates the forecasting of outcomes for these patients, enhancing the precision of their clinical management. Key points Developing the Programmed Cell Death Index (PCDI) utilizing multiple machine learning algorithms for patients with less‐defined subtype diffuse large B‐cell lymphoma. The difference in clinical characteristics, circulating tumour DNA burden and immune profiling between patients with distinct PCDI groups. A potentially effective regimen was speculated for patients with high PCDI scores who tend to exhibit worse progression‐free survival.

Abstract Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.

Abstract Dynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat‐to‐human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre‐pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor‐binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre‐incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre‐pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2‐related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross‐reactive immunity to SCV2 prior to the global pandemic.

Abstract Acute lung injury (ALI) is a common and severe complication of sepsis with a high mortality rate. Ferroptosis, an iron‐dependent form of cell death, contributes to lung injury. Homeobox A5 (HOXA5) is involved in the regulation of septic acute kidney damage; however, its function on ferroptosis in septic ALI remains unclear. An in vitro model of septic lung injury was established in the pulmonary epithelial cell line (MLE‐12) via lipopolysaccharide (LPS) stimulation. Cell viability, ferrous iron (Fe2+) level, and cellular lipid reactive oxygen species (ROS) were determined with Cell Counting Kit‐8 assay, iron assay kit, and BODIPY™ 665/676 molecular probe, respectively. HOXA5, ferroptosis suppressor protein 1 (FSP1), sirtuin 5 (SIRT5), and glutathione peroxidase 4 (GPX4) expressions were measured using western blotting and Real‐Time Quantitative Polymerase Chain Reaction (RT‐qPCR. Chromatin immunoprecipitation and luciferase reporter assays were performed to validate HOXA5 binding to the FSP1/GPX4 promoter, and regulation of SIRT5 on HOXA5 desuccinylation was confirmed through co‐immunoprecipitation. LPS stimulation induced ferroptosis (reduced cell viability, elevated Fe2+ and lipid ROS levels, and decreased GPX4 levels) and downregulated FSP1 and HOXA5 protein levels. HOXA5 overexpression neutralized LPS‐induced ferroptosis. Moreover, LPS exposure inhibited HOXA5 binding to the FSP1 promoter, which was counteracted via HOXA5 overexpression. Furthermore, SIRT5 overexpression suppressed LPS‐induced ferroptosis. In LPS‐challenged MLE‐12 cells, SIRT5‐mediated HOXA5 desuccinylation was reduced. HOXA5 depletion neutralized the suppressive role of SIRT5 overexpression in LPS‐induced ferroptosis. SIRT5‐mediated HOXA5 desuccinylation inhibited LPS‐induced ferroptosis by upregulating FSP1, which may offer a prospective therapeutic strategy for septic lung injury.

Abstract The amygdaloid complex consists of multiple nuclei and is a key node in controlling temporal lobe epilepsy (TLE) in both human and animal model studies. However, the specific nucleus in the amygdaloid complex and the neural circuitry governing seizures remain unknown. Here, it is discovered that activation of glutamatergic neurons in the posterior basolateral amygdala (pBLA) induces severe seizures and even mortality. The pBLA glutamatergic neurons project collateral connections to multiple brain regions, including the insular cortex (IC), bed nucleus of the stria terminalis (BNST), and central amygdala (CeA). Stimulation of pBLA‐targeted IC neurons triggers seizures, whereas ablation of IC neurons suppresses seizures induced by activating pBLA glutamatergic neurons. GABAergic neurons in the BNST and CeA establish feedback inhibition on pBLA glutamatergic neurons. Deleting GABAergic neurons in the BNST or CeA leads to sporadic seizures, highlighting their role in balancing pBLA activity. Furthermore, pBLA neurons receive glutamatergic inputs from the ventral hippocampal CA1 (vCA1). Ablation of pBLA glutamatergic neurons mitigates both acute and chronic seizures in the intrahippocampal kainic acid‐induced mouse model of TLE. Together, these findings identify the pBLA as a pivotal nucleus in the amygdaloid complex for regulating epileptic seizures in TLE.

Abstract Structural battery integrated composites (SBICs) combining outstanding strength and heat resistance are highly desirable candidates for next generation high speed aircraft. Here, a novel high‐temperature‐resistant bi‐continuous electrolyte based on phthalonitrile resin is presented, allowing the construction of SBICs capable of stable operation across a wide temperature range. Excellent mechanical strength and high ionic conductivity can coexist in a bi‐continuous structure electrolyte (PL50) where the phthalonitrile resin serves as the matrix phase and the ionic liquid electrolyte serves as the conductive phase. Benefiting from the thermal stability of the phthalonitrile resin, SBICs assembled with a PL50 bi‐continuous electrolyte deliver excellent mechanical performance even at temperatures exceeding 200 °C, with a flexural strength of 299 MPa and a flexural modulus of 31.8 GPa. Additionally, with an increase in operating temperature, PL50@SBICs demonstrated enhanced rate performance while maintaining good cycling stability. The demonstration of resisting mechanical abuse at high temperatures and flame retardance further suggests the promise of SBICs with PL50 bi‐continuous electrolytes operating under extreme conditions.

Abstract Massive numbers of modified bases in mRNAs sculpt the epitranscriptome and play vital roles in RNA metabolism. The only known acetylated RNA modification, N‐4‐acetylcytidine (ac4C), is highly conserved across cell types and among species. Although the GCN5‐related acetyltransferase 10 (NAT10) functions as an ac4C writer, the mechanism underlying the acetylation process is largely unknown. In this study, the NAT10/PCBP/TDP43 complex mediated mRNA ac4C formation in mammalian cells is identified. RNA‐binding proteins (RBPs) are identified, affiliated with two different families, poly(rC)‐binding protein 1/2 (PCBP1/2) and TAR DNA binding protein 43 (TDP43), as NAT10 adaptors for mRNA tethering and substrate selection. Knockdown of the adaptors resulted in decreased mRNA acetylation abundance in HEK293T cells and ablated cytidine‐rich ac4C motifs. The adaptors also affect the ac4C sites by recruiting NAT10 to their binding sequences. The presence of the NAT10/PCBP/TDP43 complex in mouse testes highlights its potential physiological functions in vivo. These findings reveal the composition of the mRNA ac4C writer complex in mammalian cells and expand the knowledge of mRNA acetylation and ac4C site preferences.

Background The effectiveness of statin use in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Methods and Results We enrolled 397 787 patients with AF from January 1, 2012 to December 31, 2020. Patients with AF were divided into 2 groups (statin user and statin nonuser), and the risks of composite outcomes (including ischemic stroke, hemorrhagic stroke, and transient ischemic attack), all‐cause death, and major adverse cardiovascular events (which encompassed cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization) were analyzed. We analyzed 288 958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2‐VASc score, 3.5). Compared with patients without statin use, statin users had lower risks of composite end points (adjusted hazard ratio [HR], 0.91 [95% CI, 0.87–0.94]; P

Abstract Tumor‐associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor‐derived G‐CSF and GM‐CSF through the activation of the PI3K‐AKT signaling pathway, upregulation of anti‐apoptotic Mcl‐1 expression, and downregulation of activated Caspase‐3 levels. It is found that prolonged survival of TANs leads to the accumulation of aged CXCR4+ neutrophils that exhibit potent immunosuppressive properties and are associated with poor patient prognosis. Furthermore, extended survival promotes the enhanced immunosuppressive function of CD8+ T cells by TANs, thereby facilitating the in vitro and in vivo progression and growth of human LSCC tumors. Importantly, this effect could be reversed by blocking G‐CSF and GM‐CSF stimulation of neutrophils. These findings elucidate the pivotal role of pathologically prolonged neutrophil survival in impairing CD8+ T cell immunity and suggest targeting it as a potential therapeutic strategy for tumors.

Abstract Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus‐based nanoplatforms, more stable yet less‐explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5–7 nm VPNSs are fabricated through the liquid‐phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti‐inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near‐infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection‐related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet‐phosphorus‐based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti‐infective and anti‐inflammatory applications.

ABSTRACT Purpose To identify the prevalence and predictive factors of body image dissatisfaction among Chinese adolescent and young adult (AYA) survivors of sarcoma and to evaluate its associations with behavioral outcomes. Methods In total, 116 AYA survivors (response rate: 88%; 48.3% female; mean age 28.2 years, SD = 8.2 years) of osteosarcoma (49.1%) or soft‐tissue sarcoma (50.9%) were recruited from an academic hospital. The survivors self‐reported their perceived body image using the Body Image Scale. Behavioral outcomes were assessed using DSM‐oriented scales of the ASEBA Adult Self‐Report checklist. Multivariable linear regression was conducted to identify predictors of body image perception and to investigate the association between body image dissatisfaction and behavioral outcomes (adjusted for clinically relevant variables and corrected for false discovery rate). Mediation analyses were performed to examine the mediating effects of body image perception between clinical, treatment, or socioenvironmental risk factors and behavioral outcomes. Results At 15 years post‐cancer diagnosis, one‐third of the cohort (39.7%) reported dissatisfaction with their body image. The significant risk factors associated with body image dissatisfaction were being female (standardized coefficient estimate [Est] = 0.21, SE = 0.10; p = 0.047), surgery treatment (Est = 0.19, SE = 0.09; p = 0.046), and worse family functioning (Est = 0.27, SE = 0.10, p = 0.013). Body image dissatisfaction was associated with symptoms of depression (Est = 0.30, SE = 0.10; p = 0.005) and avoidant personality problems (Est = 0.37, SE = 0.11; p

Background Inflammation and metabolic disturbances are key culprits in the pathogenesis of obesity‐associated cardiomyopathy. The NLRP3 (nucleotide‐binding oligomerization domain‐like receptor 3) inflammasome mediates the release of the proinflammatory cytokines IL‐1β (interleukin‐1β) and IL‐18 by activating caspase‐1, which is strongly implicated in metabolic disturbances. We here sought to determine whether NLRP3 inflammasome inhibition could ameliorate obesity cardiomyopathy and if so, to further explore its underlying mechanisms. Methods and Results Male mice were fed a high‐fat diet for 24 weeks to induce obesity cardiomyopathy. MCC950 was used to inhibit NLRP3 inflammasome activation. Recombinant adeno‐associated virus serotype 9 encoding TXNIP (thioredoxin‐interacting protein) under cTnT (cardiac troponin T) promoter and the mitochondrial‐targeted antioxidant MitoTEMPO were injected into obese mice to investigate the specific mechanism. To mimic obesity cardiomyopathy in vitro, neonatal rat ventricular myocytes transfected with the small interfering RNA against TXNIP were incubated with 400 μmol palmitic acid for 24 hours. NLRP3 inflammasome was significantly increased in obese hearts. NLRP3 inflammasome inhibition by NLRP3 deletion or MCC950 prevented obesity‐induced cardiac systolic and diastolic dysfunction, myocardial hypertrophy and fibrosis, and excessive lipid accumulation in male mice. Conversely, TXNIP overexpression worsened obesity‐associated cardiomyopathy. Similarly, MCC950 treatment or TXNIP knockdown reduced palmitic acid‐induced NLRP3 inflammasome activation and lipid storage. Mechanistically, abnormal NF‐κB (nuclear factor kappa B) pathway activation, increased mitochondrial reactive oxygen species, and elevated TXNIP levels led to excessive NLRP3 inflammasome activation. Conclusions Our study confirms that aberrant NLRP3 inflammasome activation in cardiomyocytes worsens obesity‐associated cardiomyopathy and implicates inhibition of NLRP3 inflammasome as a potent therapeutic approach for obesity cardiomyopathy.

Background Survival following an out‐of‐hospital cardiac arrest depends on prompt defibrillation. Despite the efforts made to install automated external defibrillators (AEDs) in crowded areas, their usage rate remains suboptimal. This study evaluated the efficiency of installing AEDs at key landmarks in Taoyuan City to enhance accessibility and usage. METHODS AND RESULTS This retrospective cohort study analyzed nontraumatic public out‐of‐hospital cardiac arrest cases in Taoyuan City from 2017 to 2021, using data from the Taoyuan Fire Department and a regional registry. AED data were collected for 1163 devices. A geographic information system mapped target locations within the city, and real‐world walking routes were examined to assess coverage. The primary outcome was actual coverage and the coverage efficiency ratio, calculated as the actual coverage divided by the number of facilities at a location. The coverage efficiency ratio compared the coverage efficiency of target locations with existing public access defibrillators (PADs). Top locations for superior coverage in both downtown and outside downtown areas were bus stops and convenience stores (7‐Eleven and FamilyMart), which outperformed existing PADs. Convenience stores had a higher coverage efficiency ratio than the public service sector. Bus stops showed high AED usage rates before ambulance arrival. Conclusions The current PAD locations in Taoyuan City offer limited coverage, which highlights the need for strategically installed AEDs, particularly in convenience stores. Policymakers should consider using the cultural relevance and accessibility of convenience stores, particularly 7‐Eleven branches, to enhance AED usage rates.

Abstract Objective High‐risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild‐type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high‐risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment. Methods We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high‐risk molecular markers were tested, and various habitat models and whole‐tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high‐risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank‐sum test was employed to explore the correlation between habitat quantitative features (intra‐tumor heterogeneity score，ITH score) and heterogeneity, as well as high‐risk molecular subtypes. Results The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model's performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high‐risk and non‐high‐risk molecular subtypes. Interpretation The habitat model based on DKI is an ideal means for preoperatively predicting high‐risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.