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Abstract Transthoracic echocardiography (TTE) is widely recognized as one of the principal modalities for diagnosing tricuspid regurgitation (TR). The diagnostic procedures associated with conventional methods are intricate and labor-intensive, with human errors leading to measurement variability, with outcomes critically dependent on the operators’ diagnostic expertise. In this study, we present an innovative assessment methodology for evaluating TR severity utilizing an end-to-end deep learning system. This deep learning system comprises a segmentation model of single cardiac cycle TR continuous wave (CW) Doppler spectra and a classification model of the spectra, trained on the TR CW Doppler spectra from a cohort of 11,654 patients. The efficacy of this intelligent assessment methodology was validated on 1500 internal cases and 573 external cases. The receiver operating characteristic (ROC) curves of the internal validation results indicate that the deep learning system achieved the areas under curve (AUCs) of 0.88, 0.84, and 0.89 for mild, moderate, and severe TR, respectively. The ROC curves of the external validation results demonstrate that the system attained the AUCs of 0.86, 0.79, and 0.87 for mild, moderate, and severe TR, respectively. Our study results confirm the feasibility and efficacy of this novel intelligent assessment method for TR severity.

Abstract Long non-coding RNAs (lncRNAs) are typically described as RNA transcripts exceeding 200 nucleotides in length, which do not code for proteins. Recent advancements in technology, including ribosome RNA sequencing and ribosome nascent-chain complex sequencing, have demonstrated that many lncRNAs retain small open reading frames and can potentially encode micropeptides. Emerging studies have revealed that these micropeptides, rather than lncRNAs themselves, are responsible for vital functions, including but not limited to regulating homeostasis, managing inflammation and the immune system, moderating metabolism, and influencing tumor progression. In this review, we initially outline the rapidly advancing computational analytical methods and public tools to predict and validate the potential encoding of lncRNAs. We then focus on the diverse functions of micropeptides and their underlying mechanisms in the pathogenesis of disease. This review aims to elucidate the functions of lncRNA-encoded micropeptides and explore their potential applications as therapeutic targets in cancer.

Abstract The absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors. Activation of this neuronal ensemble elicits marked spontaneous pain-like behaviors and enhances nociceptive responses, whereas prolonged silencing of its activities alleviates spontaneous pain and promotes overall recovery from inflammatory pain. Notably, afferents from the primary somatosensory cortex and infralimbic cortex bidirectionally modulate the activities of the spontaneous pain-responsive prelimbic cortex neuronal ensemble and pain behaviors. These findings reveal the cortical basis of spontaneous pain at the neuronal level, highlighting a distinct neuronal ensemble within the prelimbic cortex and its associated pain-regulatory brain networks.

AIM: To describe the practice patterns of intravitreal injections (IVIs) among ophthalmologists in China. METHODS: This was a cross-sectional online survey. Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center, a hospital-based national network, to complete an anonymous, 24-question, internet-based survey. They were surveyed on practices in injection techniques, pre-, and post-injections procedures. RESULTS: A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey (50.68% response rate). The 91.29% of the respondents evaluated systemic risk factors by medical history, electrocardiogram (ECG) and blood test. All the respondents used pre-injection prophylactic antibiotics. Most checked intraocular pressure (IOP, 99.1%) and blood pressure (96.1%) before injections. A majority of the respondents performed injections in the operating room (98.8%), wore masks (99.7%), gloves (99.4%) and sterile surgical clothing (96.1%), performed topical anesthetics (97.9%), and applied povidone-iodine (95.8%) pre-injection. The 61.26% of the respondents dilated pupil. About half of the respondents (51.05%) performed bilateral injections in the same setting. Superior temporal quadrant (40.54%) was the most frequent site of injection. Around three quarters used 30-gauge needles. Most respondents (97.9%) measured the site of injection from limbus. More than half (53.45%) performed conjunctiva displacement prior to injection. The 32.43% of the respondents checked IOP post-injection and 87.99% physicians checked hand motion (HM) or counting fingers (CF) after injection, while 36.94% observed optic nerve perfusion. All participants used topical antibiotics post-injections. Most physicians (91.89%) reviewed patients on the following day. CONCLUSION: This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Abstract To assess the impact of Enhanced Recovery After Surgery (ERAS) protocol in children undergoing corrective surgery for congenital scoliosis. A retrospective analysis was conducted on children undergoing surgical correction for congenital scoliosis, with participants categorized into either the ERAS group or the control group. Comparative evaluations were made across clinical, surgical, laboratory, and quality of life parameters. Following propensity score matching, 156 patients were analyzed. Within the initial 3 days following surgery, the ERAS cohort demonstrated lower pain intensity and exhibited higher daily oral intake compared to their counterparts in the control group. A mere 14.1% of patients in the ERAS group experienced a peak body temperature exceeding 38.5°, illustrating a significantly lower incidence compared to the 33.3% recorded in the control group. The ERAS cohort displayed expedited timeframes for the onset of initial bowel function and postoperative discharge when contrasted with the control group. Levels of IL-6 assessed on the third day post-surgery were markedly reduced in the ERAS group in comparison to the control group. Noteworthy is the similarity observed in postoperative hemoglobin and albumin levels measured on the first and third postoperative days between the two groups. Assessments of quality of life using SF-36 and SRS-22r questionnaires revealed comparable scores across all domains in the ERAS group when juxtaposed with the control cohort. ERAS protocol has demonstrated a capacity to bolster early perioperative recovery, alleviate postoperative stress responses, and uphold favorable quality of life outcomes in children undergoing corrective surgery for congenital scoliosis.

Abstract While protein aggregation’s association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for anti-aging drug discovery.

Abstract The high cost of medical care and its association with poverty have given rise to a growing concern for developing countries, but how insurance plans affect household income and alleviate poverty has been rarely discussed. This study aims to bridge this research gap by examining a medical insurance reform in China, a major program of the targeted poverty alleviation (TPA) strategy, which offers higher reimbursement rates and lower medical deductibles for low‐income households. We use an administrative data set on impoverished people in a Chinese county to examine how exogenous changes in the medical insurance system affect the income structure of low‐income households. We apply a two‐part model to a Difference‐in‐Differences framework, with households that received reimbursement of the insurance reform as the treatment group and others as the control group. Our results imply that the medical insurance reform could increase the overall household income diversity. The mechanism analysis suggests that the medical insurance reform improves the health conditions of patients and encourages caregivers to engage more in off‐farm work.

IntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by gradual loss of cognitive function. Understanding the molecular mechanisms is crucial for developing effective therapies.MethodsData from single-cell RNA sequencing (scRNA-seq) in the GSE181279 dataset and gene chips in the GSE63060 and GSE63061 datasets were collected and analyzed to identify immune cell types and differentially expressed genes. Cell communication, pseudotime trajectory, enrichment analysis, co- expression network, and short time-series expression miner were analyzed to identify disease-specific molecular and cellular mechanisms.ResultsWe identified eight cell types (B cells, monocytes, natural killer cells, gamma-delta T cells, CD8+ T cells, Tem/Temra cytotoxic T cells, Tem/Trm cytotoxic T cells, and mucosal-associated invariant T cells) using scRNA-seq. AD samples were enriched in monocytes, CD8+ T cells, Tem/Temra cytotoxic T cells, and Tem/Trm cytotoxic T cells, whereas samples from healthy controls were enriched in natural killer and mucosal-associated invariant T cells. Five co-expression modules that were identified through weighted gene correlation network analysis were enriched in immune- inflammatory pathways. Candidate genes with higher area under the receiver operating characteristic curve values were screened, and the expression trend of Ubiquitin-Fold Modifier Conjugating Enzyme 1 (UFC1) gradually decreased from healthy controls to mild cognitive impairment and then to AD.ConclusionOur study suggests that peripheral immune cells may be a potential therapeutic target for AD. Candidate genes, particularly UFC1, may serve as potential biomarkers for progression of AD.

Tooth development is an intricate process that encompasses cellular activities, molecular signaling pathways, and gene expression patterns. Disruptions in any of the processes can lead to structural anomalies, impairments in function, and increased vulnerability to oral disorders. Alveolar resorption, which refers to the pathological loss of alveolar bone around teeth, poses a substantial clinical problem in periodontal disorders such as periodontitis. Long non-coding RNAs (LncRNAs) have been implicated in the regulation of these physiological and pathological processes, and they exert their impact on gene expression through both transcriptional and post-transcriptional mechanisms. However, they also interact with certain microRNAs (mi-RNAs), thereby modulating the expression of downstream genes that are involved in tooth development. An exemplar is lncRNA ZFAS1, which has been demonstrated to regulate gene expression and impact these physiological and pathological processes. As a result, lncRNAs contribute to these processes by interacting with chromatin regulators, RNA enhancers, mi-RNAs, and their modulating signaling pathways involved in tooth development and alveolar resorption. Taken together, this review explores and gives a systematic account of the recent research findings that enhance our understanding of the molecular mechanisms that drive these processes and their potential consequences for the remodeling of teeth and bones in the oral cavity.

Purpose: To describe and evaluate the multimodal imaging findings in retinal microvascular ischemia associated with COVID-19 infection. Methods: Patients with COVID-19 associated retinal microvascular ischemia and visiting the outpatient Department of Ophthalmology, Shanghai General Hospital from December 2022, to February 2023, were documented and their multimodal images were retrospectively reviewed. Retinal microvascular ischemia was defined as the presence of isolated or multiple focal retinal whitening(s) on color fundus images. Patients with retinal vessel occlusion or retinopathies secondary to systematic disorders diagnosed before infection were excluded. Results: A total of 32 eyes from 21 patients were included, 24 (75.00 %) eyes with multiple retinal whitenings, while 8 (25.00 %) eyes with isolated lesions. When divided by the types of ischemia, 9 (28.13 %) eyes had only inner retinal involvement (known as cotton wool spot, CWS), 4 (12.50 %) eyes had only middle retinal involvement (known as paracentral acute middle maculopathy, PAMM), and 19 (59.38 %) eyes had both. In addition, 4 (12.50 %) eyes had coincident angular sign of Henle fiber layer hyperreflectivity (ASHH). Patients with hypertension tended to have multiple lesions rather than isolated lesion of retinal microvascular ischemia (P = 0.008). Transient uncontrolled high blood pressure or acute kidney injury was simultaneously detected in some cases. Conclusions: Ocular manifestation of COVID-19 associated microvascular ischemia can be variable, including CWS, PAMM and ASHH. Multimodal fundus imaging technologies are useful tools to reveal involved retinal layers, extent, and severity. Moreover, ocular manifestations may serve as a window of COVID-19 related microcirculation in other systems throughout the body.

Purpose This study investigated the topological structural characteristics of systemic lupus erythematosus (SLE) with and without neuropsychiatric symptoms (NPSLE and non-NPSLE), and explore their clinical implications.Methods We prospectively recruited 50 patients with SLE (21 non-NPSLE and 29 NPSLE) and 32 age-matched healthy controls (HCs), using MRI diffusion tensor imaging. Individual structural networks were constructed using fibre numbers between brain areas as edge weights. Global metrics (eg, small-worldness, global efficiency) and local network properties (eg, degree centrality, nodal efficiency) were computed. Group comparisons of network characteristics were conducted. Clinical correlations were assessed using partial correlation, and differentiation between non-NPSLE and NPSLE was performed using support vector classification.Results Patients with oth non-NPSLE and NPSLE exhibited significant global and local topological alterations compared with HCs. These changes were more pronounced in NPSLE, particularly affecting the default mode and sensorimotor networks. Topological changes in patients with SLE correlated with lesion burdens and clinical parameters such as disease duration and the systemic lupus international collaborating clinics damage index. The identified topological features enabled accurate differentiation between non-NPSLE and NPSLE with 87% accuracy.Conclusion Structural networks in patients SLE may be altered at both global and local levels, with more pronounced changes observed in NPSLE, notably affecting the default mode and sensorimotor networks. These alterations show promise as biomarkers for clinical diagnosis.

Abstract Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/β-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

Abstract Background Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. Methods Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. Results Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00–10.00) and the mean tumor thickness was 3.50 mm (range: 2.00–5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. Conclusions Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Abstract With the development of cloud computing, users are more inclined to outsource complex computing tasks to cloud servers with strong computing capacity, and the cloud returns the final calculation results. However, the cloud is not completely trustworthy, which may leak the data of user and even return incorrect calculations on purpose. Therefore, it is important to verify the results of computing tasks without revealing the privacy of the users. Among all the computing tasks, the polynomial calculation is widely used in information security, linear algebra, signal processing and other fields. Most existing polynomial-based verifiable computation schemes require that the input of the polynomial function must come from a single data source, which means that the data must be signed by a single user. However, the input of the polynomial may come from multiple users in the practical application. In order to solve this problem, the researchers have proposed some schemes for multi-source outsourced data, but these schemes have the common problem of low efficiency. To improve the efficiency, this paper proposes an efficient polynomial-based verifiable computation scheme on multi-source outsourced data. We optimize the polynomials using Horner’s method to increase the speed of verification, in which the addition gate and the multiplication gate can be interleaved to represent the polynomial function. In order to adapt to this structure, we design the corresponding homomorphic verification tag, so that the input of the polynomial can come from multiple data sources. We prove the correctness and rationality of the scheme, and carry out numerical analysis and evaluation research to verify the efficiency of the scheme. The experimental indicate that data contributors can sign 1000 new data in merely 2 s, while the verification of a delegated polynomial function with a power of 100 requires only 18 ms. These results confirm that the proposed scheme is better than the existing scheme.

Abstract Wilms tumor (WT) is the most common malignancy of the genitourinary system in children. Currently, the Integration of single-cell RNA sequencing (scRNA-Seq) and Bulk RNA sequencing (RNA-Seq) analysis of heterogeneity between different cell types in pediatric WT tissues could more accurately find prognostic markers, but this is lacking. RNA-Seq and clinical data related to WT were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Small nucleolar RNA host gene 15 (SNHG15) was identified as a risk signature from the TARGET dataset by using weighted gene co-expression network analysis, differentially expressed analysis and univariate Cox analysis. After that, the functional mechanisms, immunological and molecular characterization of SNHG15 were investigated at the scRNA-seq, pan-cancer, and RNA-seq levels using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), ESTIMATE, and CIBERSORT. Based on scRNA-seq data, we identified 20 clusters in WT and annotated 10 cell types. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing M2 macrophages as hubs for intercellular communication. In addition, in vitro cellular experiments showed that siRNAs interfering with SNHG15 significantly inhibited the proliferation and migration of G401 cells and promoted the apoptosis of G401 cells compared with the control group. The effect of siRNAs interfering with SNHG15 on EMT-related protein expression was verified by Western blotting assay. Thus, our findings will improve our current understanding of the pathogenesis of WT, and they are potentially valuable in providing novel prognosis markers for the treatment of WT.

Abstract Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL‐S) is a rare autosomal dominant systemic microvascular disorder attributed to TREX1 (three‐prime repair exonuclease‐1) gene mutations, often proned to misdiagnosed. Methods We reported a case of RVCL‐S coexisting with systemic lupus erythematosus due to a mutation in the TREX1 gene. This study provided a summary and discussion of previously documented cases related to TREX1 mutations or RVCL‐S. Results A 39‐year‐old female patient visited the clinic due to progressive memory loss and speech difficulties. Magnetic resonance imaging results showed corpus callosum atrophy and multiple subcortical calcifications in both brain hemispheres. Genetic testing revealed a TREX1 gene mutation (c.294dupA). Treatment with immunosuppressive therapy for 2 months led to improvements in communication and mobility. We also summarized previously reported cases providing an overview of TREX1 gene mutation or RCVL‐S. Conclusion Our case establishes a compelling foundation for future RVCL‐S diagnosis and treatment paradigms. Notably, conducting systemic immunity screening in patients with RVCL‐S emerges as a strategic approach to prevent potential diagnostic oversights.

ObjectiveThis study aims to determine whether tele-rehabilitation has similar effects to conventional face-to-face physical rehabilitation for diabetic patients with heart failure with preserved ejection fraction (HFpEF).Materials and methodsDemographic, laboratory, diagnostic and rehabilitation information for patients with type 2 diabetes with HFpEF were extracted from disease-specific databases. Outcome measures, including the Short Physical Performance Battery (SPPB), 6-minute walk distance, frailty status, European Quality of Life 5-Dimension 5-Level questionnaire (EQ-5D-5L) and reduction in HbA1c from admission, patients who received tele-rehabilitation therapy were compared to those received face-to-face rehabilitation.ResultsIn this study, 90 patients with type 2 diabetes and HFpEF using tele-rehabilitation were matched with 90 patients with type 2 diabetes and HFpEF using face-to-face physical rehabilitation. Improvements in the results of the SPPB scores, 6-min walk distance and gait speed and EQ-5D-5L were noted from the follow-up time point 3 months to 6 months in both two groups. There were no significant differences in functional tests and quality of life between the two groups.ConclusionOur study proved that mobile-based tele-rehabilitation programs are non-inferior to face-to-face physical rehabilitation for diabetes patients after HFpEF. In addition, adherence to the telerehabilitation program showed that the novel technology was accepted well and could be an alternative to the conventional face-to-face rehabilitation program.

Abstract Background During arthroscopic rotator cuff repair (ARCR), clear surgical field visibility (SFV) is the basis of successful surgery, but the choice of anesthesia maintenance drugs may have different effects on SFV. In this study, we aimed to compare the effects of propofol- and sevoflurane-based general anesthesia on SFV in patients undergoing ARCR. Methods Patients (n = 130) undergoing elective ARCR in the lateral decubitus position were randomized into either the propofol group or sevoflurane group (65 per group). The duration of surgery and increased pressure irrigation (IPI), Boezaart score, rocuronium consumption and usage of remifentanil were recorded. The time of both spontaneous respiration recovery and extubation and the incidences of postoperative nausea and vomiting and agitation were also recorded. Results The Boezaart score, duration of IPI and ratio of the duration of IPI to the duration of surgery (IPI/S ratio) were similar between the groups (P > 0.05). Rocuronium consumption, number of patients requiring remifentanil infusion and total remifentanil consumption were significantly lower in the sevoflurane group (P 0.05). Conclusions Compared with propofol, sevoflurane provides equally clear SFV while improving the convenience of anesthesia maintenance in ARCR patients with interscalene plexus (ISB) combined with general anesthesia. Trial registration This single-center, prospective, RCT was retrospective registered at Chinese Clinical Trial Registry with the registration number ChiCTR2300072110 (02/06/2023).

ObjectiveAccording to the characteristics of the complex waterways of inland rivers, a DC grid solution based on a multi-energy parallel hybrid green intelligent bulk carrier is proposed. MethodsThe advantages of a DC grid for hybrid power are analyzed and the DC grid propulsion efficiencies of each typical working condition for hybrid power are obtained through power chain calculation. The design characteristics of the DC grid are researched according to the specific requirements for the additional signs of green intelligent ships. The DC power system design schemes focused on protection and safety for real ships are then analyzed.ResultsThe results show that the comprehensive performance of the DC grid propulsion system for multi-energy parallel diesel-electric/gas-electric hybrid ships is superior to that of main engine propulsion systems and full electric propulsion systems. The multi-equipment protection mode and blackout recovery solution can ensure the safe application of the DC grid.ConclusionsThe DC grid can build a flexible energy platform for the highest level of green inland river ships, and provide comprehensive support for the intelligent engine room, intelligent energy efficiency and intelligent integrated platform technology and its applications. The results of this study can provide valuable references for other green intelligent hybrid ships.

Abstract Inspired by biological vision mechanism, event‐based cameras have been developed to capture continuous object motion and detect brightness changes independently and asynchronously, which overcome the limitations of traditional frame‐based cameras. Complementarily, spiking neural networks (SNNs) offer asynchronous computations and exploit the inherent sparseness of spatio‐temporal events. Notably, event‐based pixel‐wise optical flow estimations calculate the positions and relationships of objects in adjacent frames; however, as event camera outputs are sparse and uneven, dense scene information is difficult to generate and the local receptive fields of the neural network also lead to poor moving objects tracking. To address these issues, an improved event‐based self‐attention optical flow estimation network (SA‐FlowNet) that independently uses criss‐cross and temporal self‐attention mechanisms, directly capturing long‐range dependencies and efficiently extracting the temporal and spatial features from the event streams is proposed. In the former mechanism, a cross‐domain attention scheme dynamically fusing the temporal‐spatial features is introduced. The proposed network adopts a spiking‐analogue neural network architecture using an end‐to‐end learning method and gains significant computational energy benefits especially for SNNs. The state‐of‐the‐art results of the error rate for optical flow prediction on the Multi‐Vehicle Stereo Event Camera (MVSEC) dataset compared with the current SNN‐based approaches is demonstrated.

Thanks to their event-driven asynchronous computing capabilities and low power consumption advantages, spiking neural networks (SNNs) show significant potential for computer vision tasks, especially in object detection. However, effective training methods and optimization mechanisms for SNNs remain underexplored. This study proposes two high accuracy SNNs for object detection, AMS_YOLO and AMSpiking_VGG, integrating neuronal variants and attention mechanisms. To enhance these proposed networks, we explore the impact of incorporating different neuronal variants.The results show that the optimization in the SNN’s structure with neuronal variants outperforms that in the attention mechanism for object detection. Compared to the state-of-the-art in the current SNNs, AMS_YOLO improved by 6.7% in accuracy on the static dataset COCO2017, and AMS_Spiking has improved by 11.4% on the dynamic dataset GEN1.

ObjectiveThe purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsThis study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.ResultsA total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.ConclusionIn summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

Abstract Background Patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy experience significant fatigue, which is frequently underestimated due to the lack of objective indicators for its evaluation. This study aimed to explore the longitudinal association between fatigue and nutrition status 1 week in advance. Methods From January 2021 to June 2022, a total of 105 NPC patients who received intensity‐modulated radiation therapy were enrolled in the observational longitudinal study. The significant outcomes, including the Piper Fatigue Scale‐12 (PFS‐12), the Scored Patient‐Generated Subjective Global Assessment (PG‐SGA), four body composition indices, and the Hospital Anxiety and Depression Scale (HADS), were assessed weekly from pre‐treatment until the completion of radiotherapy (T0–T7) to explore their relationship. Results The trajectories of PFS‐12 and all dimensions for 105 participants reached a peak during the fifth week. Sensory fatigue consistently received the highest scores (T0 = 1.60 ± 2.20, T5 = 6.15 ± 1.57), whereas behavior fatigue exhibited the fastest increase over time (T0 = 1.11 ± 1.86, T5 = 5.47 ± 1.70). Higher PG‐SGA scores were found to be weakly explainable for aggravating fatigue (β = 0.02 ~ 0.04). Unlike generalized additive mixed models, marginal structural models (MSM) produced larger effect values (β = 0.12 ~ 0.21). Additionally, body composition indices showed weakly negative relationships with fatigue in MSMs one week in advance. Conclusions The PG‐SGA may be a more accurate predictor of future‐week fatigue than individual body composition indicators, particularly when HADS is controlled for as a time‐dependent confounder.

Background: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. Methods: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer’s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. Results: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00–2.02), ADHD (1.51, 1.15–1.98), schizophrenia (1.47, 1.15–1.87), and AD (1.57, 1.16–2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. Conclusions: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Summary: Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR. We further showed that OX2R agonism could partially rescue acute myocardial infarction by reducing sympathetic overactivation. Our data indicate that epicardial application of OX2R agonist exerts a cardioprotective effect by attenuating CSAR. This OX2R-mediated heart-brain axis may provide therapeutic targets for acute cardiovascular diseases.

Abstract Cuproptosis is a recently discovered novel programmed cell death pathway that differs from traditional programmed cell death and has an important role in cancer and immune regulation. Long noncoding RNA (lncRNA) is considered new potential prognostic biomarkers in pancreatic adenocarcinoma (PAAD). However, the prognostic role and immune landscape of cuproptosis-related lncRNA in PAAD remain unclear. The transcriptome and clinical data of PAAD were obtained from The Cancer Genome Atlas (TCGA) database. Cuproptosis-related lncRNA was identified using Pearson correlation analysis. The optimal lncRNA was screened by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression mode, and for the construction of risk scoring system. PAAD patients were divided into high- and low-risk groups according to the risk score. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore differences in biological function between different risk groups. Single-sample gene set enrichment analysis (ssGSEA) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm were used to analyze the differences in tumor immune microenvironment (TIME) in different risk groups of PAAD. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapy response and identify potential immune beneficiaries. Immune checkpoints and tumor mutation burden (TMB) were also systematically analyzed. Finally, drug sensitivity analysis was used to explore the reactivity of different drugs in high- and low-risk groups to provide a reference for the selection of precise therapeutic drugs. Six cuproptosis-related lncRNAs (AL117335.1, AC044849.1, AL358944.1, ZNF236-DT, Z97832.2, and CASC8) were used to construct risk model. Survival analysis showed that overall survival and progression-free survival in the low-risk group were better than those in the high-risk group, and it is suitable for PAAD patients with different clinical characteristics. Univariate and multifactorial Cox regression analysis showed that risk score was an independent prognostic factor in PAAD patients. ROC analysis showed that the AUC values of the risk score in 1 year, 3 years and 5 years were 0.707,0.762 and 0.880, respectively. Nomogram showed that the total points of PAAD patients at 1 year, 3 years, and 5 years were 0.914,0.648, and 0.543. GO and KEGG analyses indicated that the differential genes in the high- and low-risk groups were associated with tumor proliferation and metastasis and immune regulatory pathway. Immune correlation analysis showed that the amount of pro-inflammatory cells, including CD8+ T cells, was significantly higher in the low-risk group than in the high-risk group, and the expression of immune checkpoint genes, including PD-1 and CTLA-4, was increased in the low-risk group. TIDE analysis suggests that patients in the low-risk group may benefit from immunotherapy. Finally, there was significant variability in multiple chemotherapeutic and targeted drugs across the risk groups, which informs our clinical drug selection. Our cuproptosis-related lncRNA scoring system (CRLss) could predict the clinical outcome and immune landscape of PAAD patients, identify the potential beneficiaries of immunotherapy, and provide a reference for precise therapeutic drug selection.

Abstract Identifying spatially variable genes (SVGs) is critical in linking molecular cell functions with tissue phenotypes. Spatially resolved transcriptomics captures cellular-level gene expression with corresponding spatial coordinates in two or three dimensions and can be used to infer SVGs effectively. However, current computational methods may not achieve reliable results and often cannot handle three-dimensional spatial transcriptomic data. Here we introduce BSP (big-small patch), a non-parametric model by comparing gene expression pattens at two spatial granularities to identify SVGs from two or three-dimensional spatial transcriptomics data in a fast and robust manner. This method has been extensively tested in simulations, demonstrating superior accuracy, robustness, and high efficiency. BSP is further validated by substantiated biological discoveries in cancer, neural science, rheumatoid arthritis, and kidney studies with various types of spatial transcriptomics technologies.

Agricultural products usually contain a large number of spoilage bacteria and endogenous enzymes, which can adversely affect the quality of agricultural products. Radio frequency is a kind of dielectric heating technology, which has fast heating speed and high efficiency, can effectively inactivate microorganisms and endogenous enzymes in agricultural products and has little influence on the quality of agricultural products， such as color, texture and nutritional composition, etc. This review summarized the mechanism of action of radiofrequency sterilization blunt enzyme technology and its application in agricultural products processing in recent years, and the shortcomings and solutions of radiofrequency sterilization blunt enzyme technology was pointed out. Moreover, the future application of radiofrequency sterilization blunt enzyme technology in agricultural products and food was also prospected.

Abstract Background After decades of rapid economic development, anemia remains a significant public health challenge globally. This study aimed to estimate the associations of sociodemographic, dietary, and body composition factors with anemia among the Zhuang in Guangxi Zhuang Autonomous Region, China. Methods Our study population from the baseline survey of the Guangxi ethnic minority Cohort Study of Chronic Diseases consisted of 13,465 adults (6,779 women and 6,686 men) aged 24–82 years. A validated interviewer-administered laptop-based questionnaire system was used to collect information on participants’ sociodemographic, lifestyle, and dietary factors. Each participant underwent a physical examination, and hematological indices were measured. Least absolute shrinkage and selection operator (LASSO) regression was used to select the variables, and logistic regression was applied to estimate the associations of independent risk factors with anemia. Results The overall prevalences of anemia in men and women were 9.63% (95% CI: 8.94–10.36%) and 18.33% (95% CI: 17.42─19.28%), respectively. LASSO and logistic regression analyses showed that age was positively associated with anemia for both women and men. For diet in women, red meat consumption for 5–7 days/week (OR = 0.79, 95% CI: 0.65–0.98, p = 0.0290) and corn/sweet potato consumption for 5–7 days/week (OR = 0.73, 95% CI: 0.55–0.96, p = 0.0281) were negatively associated with anemia. For men, fruit consumption for 5–7 days/week (OR = 0.75, 95% CI: 0.60–0.94, p = 0.0130) and corn/sweet potato consumption for 5–7 days/week (OR = 0.66, 95% CI: 0.46–0.91, p = 0.0136) were negatively correlated with anemia. Compared with a normal body water percentage (55–65%), a body water percentage below normal ( 65%) was positively correlated with anemia in men (OR = 1.73, 95% CI: 1.38–2.17, p

The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-α and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-α and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-α and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-α and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-α and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-α and IL-8 levels are positively correlated with PVR severity.

ObjectiveVagus nerve stimulation (VNS) has been widely used in the treatment of drug-resistant epilepsy (DRE) in children. We aimed to explore the efficacy and safety of VNS, focusing on factors that can influence the efficacy of VNS, and construct a prediction model for the efficacy of VNS in the treatment of DRE children.MethodsRetrospectively analyzed 45 DRE children who underwent VNS at Qilu Hospital of Shandong University from June 2016 to November 2022. A ≥50% reduction in seizure frequency was defined as responder, logistic regression analyses were performed to analyze factors affecting the efficacy of VNS, and a predictive model was constructed. The predictive model was evaluated by receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA).ResultsA total of 45 DRE children were included in this study, and the frequency of seizures was significantly reduced after VNS treatment, with 25 responders (55.6%), of whom 6 (13.3%) achieved seizure freedom. There was a significant improvement in the Quality of Life in Childhood Epilepsy Questionnaire (15.5%) and Seizure Severity Score (46.2%). 16 potential factors affecting the efficacy of VNS were included, and three statistically significant positive predictors were ultimately screened: shorter seizure duration, focal seizure, and absence of intellectual disability. We developed a nomogram for predicting the efficacy of VNS in the treatment of DRE children. The ROC curve confirmed that the predictive model has good diagnostic performance (AUC = 0.864, P < 0.05), and the nomogram can be further validated by bootstrapping for 1,000 repetitions, with a C-index of 0.837. Besides, this model showed good fitting and calibration and positive net benefits in decision curve analysis.ConclusionVNS is a safe and effective treatment for DRE children. We developed a predictive nomogram for the efficacy of VNS, which provides a basis for more accurate selection of VNS patients.

Introduction: The mechanistic associations between small vessel disease (SVD) and dementia are still poorly understood. The APOE ε4 allele, recognised as the strongest genetic risk factor for Alzheimer's disease, has been previously implicated in SVD, although it remains unclear whether this association is gene-dose dependent. An emerging neuroimaging biomarker of SVD is Peak Width of Skeletonised Mean Diffusivity (PSMD), obtained from histogram analyses of diffusion weighted imaging (DWI) datasets. Here, we investigated the relationship between APOE ε4 gene dose and PSMD, as a surrogate marker of SVD, in a group of cognitively normal middle-aged adults. Methods: The study included data from 1954 asymptomatic middle-aged adults from the ALFA (ALzheimer and FAmilies) and PREVENT-Dementia cohorts (See Table 1 for sample characteristics). PSMD was calculated from the DWI datasets using a publicly available script, and harmonised using COMBAT to account for site-related differences. Using non-parametric permutation models, our primary analyses focused on the (a) comparison of group differences (APOE ε4 heterozygotes vs homozygotes vs non-carriers) in PSMD, adjusting for age, sex, years of formal education, and sites; and (b) potential interactions between APOE ε4 gene dose and age on PSMD values. Marginal predictions were used to estimate the earliest age at which differences might emerge between the APOE ε4 groups and non-carriers. Results: There were no significant differences in PSMD values across the non-carriers (n=1,197), heterozygous carriers (n=659), and homozygous APOE ε4 carriers (n=98) (p = 0.6; Figure 1). However, there was a statistically significant interaction between APOE ε4 gene dose and age on PSMD. Specifically, homozygous APOE ε4 carriers exhibited a steeper increase in PSMD with age compared to non-carriers and heterozygous carriers (T = 4.7, p

In this paper, we focus on a dynamic Cournot game in the market with a nonlinear (isoelastic) demand function. In our model, there are N competing firms featured by nonlinear cost functions, which enhances our model's resemblance to real-world scenarios. Firstly, we focus on the homogeneous case where firms' marginal costs change at equal rates. We establish analytical expressions of the market supply at equilibrium and perform comparative static analysis. In addition, we investigate the local stability under different economies of scale and show that there could be multiple stable equilibria if firms face economies of scale. The heterogeneous case where firms' marginal costs change at distinct rates is much more complex, thus we investigate the duopoly game with only two firms involved. Methods of symbolic computations such as triangular decomposition and partial cylindrical algebraic decomposition are employed in the analytical investigations of the equilibrium, which is nearly impossible by using the pencil-and-paper approach since the closed-form equilibrium is quite complicated. According to the computational results, we derive that two stable positive equilibria may coexist if both firms face economies of scale. Additionally, we conduct preliminary numerical simulations and find two different types of complex dynamics of the model considered in this paper: complex trajectories such as periodic and chaotic orbits may appear; the topological structure of the basins of attraction may be complex.

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib–cyclophosphamide–dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide–dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri’s diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CR V ) rate was 67.9%, and the cumulative complete hematological response (CR H ) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CR V rate (median time from diagnosis to CR V = 130 days) and 66.7% CR H rate (median time from diagnosis to CR H = 218 days). In addition, the VEGF response was less than the partial remission (PR V ) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.

Self-regulated language learning (SRLL) plays a crucial role in the language development of Chinese college English as a Foreign Language (EFL) learners. This study presents a systematic literature review aimed at identifying the key variables associated with SRLL among Chinese college EFL learners. By conducting an extensive search of the Web of Science and Scopus databases, 88 relevant research articles were analyzed to gain insights into the effectiveness of SRLL in this context. Through a meticulous analysis of the target articles, this review uncovers the essential variables that shape the landscape of SRLL in the context of China’s tertiary education. To examine the interrelationship among these variables, this study utilized Partial Least Squares Structural Equation Modeling (PLS-SEM) for a comprehensive quantitative analysis. PLS-SEM enables a robust examination of multiple variables simultaneously, making it an ideal statistical technique for analyzing the complex dynamics of SRLL. By identifying the crucial factors that drive the SRLL process, researchers and educators can develop targeted interventions to enhance language learning outcomes among Chinese college EFL learners. Moreover, this research will shed light on the existing gaps in the literature and pave the way for future investigations in areas such as technology-assisted learning, individual differences, and the relationship between self-regulation and language proficiency. By unraveling the complexities of SRLL among Chinese college EFL learners, this study strives to empower educators and researchers with valuable insights to foster successful language acquisition and proficiency.

Abstract Effective treatment for metastasis, a leading cause of cancer‐associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro‐metastatic niche signals. Here, systemic motif‐enrichment identified myocyte enhancer factor 2D (MEF2D) as a critical sensor of niche signals to regulate DCCs adhesion and colonization, leading to intrahepatic metastasis and recurrence of liver cancer. In this context, MEF2D transactivates Itgb1 (coding β1‐integrin) and Itgb4 (coding β4‐integrin) to execute temporally unique functions, where ITGB1 recognizes extracellular matrix for early seeding, and ITGB4 acts as a novel sensor of neutrophil extracellular traps‐DNA (NETs‐DNA) for subsequent chemotaxis and colonization. In turn, an integrin‐FAK circuit promotes a phosphorylation‐dependent USP14‐orchastrated deubiquitination switch to stabilize MEF2D via circumventing degradation by the E3‐ubiquitin‐ligase MDM2. Clinically, the USP14(pS432)‐MEF2D‐ITGB1/4 feedback loop is often hyper‐active and indicative of inferior outcomes in human malignancies, while its blockade abrogated intrahepatic metastasis of DCCs. Together, DCCs exploit a deubiquitination‐dependent switch on MEF2D to integrate niche signals in the liver mesenchyme, thereby amplifying the pro‐metastatic integrin‐FAK signaling. Disruption of this feedback loop is clinically applicable with fast‐track potential to block microenvironmental cues driving metastasis.

BackgroundHypertrophic cardiomyopathy (HCM) is recognized as the most prevalent form of genetic cardiomyopathy, and recent investigations have shed light on the existence of sex disparities in terms of clinical presentation, disease progression, and outcomes.ObjectivesThis study aimed to systematically review the literature and perform a meta-analysis to comprehensively compare the clinical outcomes between female and male patients with HCM.MethodsA thorough search was conducted in databases including PubMed, Embase, Cochrane Library, and Web of Science, encompassing literature from inception until June 2023. The primary endpoints examined were: (1) all-cause mortality; (2) an arrhythmic endpoint comprising sudden cardiac death (SCD), sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and (3) a composite endpoint incorporating either (1) or (2), in addition to hospitalization for heart failure or cardiac transplantation. Pooled estimates were derived using a random-effects meta-analysis model.ResultsThe analysis encompassed a total of 29 observational studies, involving 44,677 patients diagnosed with HCM, of which 16,807 were female. Baseline characteristics revealed that the female group exhibited an advanced age [55.66 ± 0.04 years vs. 50.38 ± 0.03 years, pooled mean difference (MD) = 0.31, 95% CI: 0.22–0.40, p = 0.000, I2 = 88.89%], a higher proportion of New York Heart Association class III/IV patients [pooled odds ratio (OR) = 1.94, 95% CI: 1.55–2.43, p = 0.000, I2 = 85.92%], and a greater prevalence of left ventricular outflow tract gradient greater than or equal to 30 mmHg (pooled OR = 1.48, 95% CI: 1.27–1.73, p = 0.000, I2 = 68.88%) compared to the male group. The female group were more likely to have a positive genetic test (pooled OR = 1.27, 95% CI: 1.08–1.48, p = 0.000, I2 = 42.74%) and to carry the myosin heavy chain beta 7 mutation (pooled OR = 1.26, 95% CI: 1.04–1.54, p = 0.020, I2 = 0.00%) compared to the male group. Female sex exhibited a significant association with increased risks of all-cause mortality (pooled OR = 1.62, 95% CI: 1.38–1.89, p = 0.000, I2 = 72.78%) and the composite endpoint (pooled OR = 1.47, 95% CI: 1.20–1.79, p = 0.000, I2 = 84.96%), while no substantial difference was observed in the arrhythmic endpoint (pooled OR = 1.08, 95% CI: 0.87–1.34, p = 0.490, I2 = 55.48%).ConclusionsThe present findings suggest that female patients with HCM tend to experience poorer clinical outcomes. It is imperative to critically reevaluate disease definitions and enhance awareness to mitigate delays in the diagnosis and treatment of HCM in women, thereby fostering equitable healthcare practices.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023431881).

Channa argus is a bottom-dwelling freshwater fish with high nutritional and economic value and, in China, is known as the "treasure of fish". C. argus meat is mainly used to produce fish fillets; however, head and bone are occasionally utilized in food production. The head of C. argus is rich in mineral elements, amino acids, and unsaturated fatty acids and is commonly used in China for fish head soup. The preparation of fish head soup is particularly time-consuming and can take several hours. Therefore, a high demand exists for the research and development of instant fish head soup products. With the development of modern food colloid research technology, the formation of micro/nanoparticles (MNPs) in soups and the biological effects of the tissue units as active ingredients have attracted increasing attention. In terms of the cooking process of fish soup, in addition to the heating method and cooking time, the seasoning added during cooking is also an important factor. In particular, salt is a key determinant of soup flavor. Although the content is the same, the addition of salt affects the dissolution and migration of nutrients from the fish head during the cooking process. However, the effect of the addition time of salt on the nutritious flavor during the preparation of fish soup has not been studied clearly. Furthermore, the stability of fish soup has not been adequately evaluated.In this work, the C. argus head was chosen as the base material for the soup and the nutrient migration and particles in the C. argus head soup were studied. Water-soluble protein, total sugar, total minerals, solids, nucleotides, free amino acid content, and colloidal particle stability were chosen as indicators to evaluate the transfer of nutrients and flavor. In addition, the morphological structure and distribution of MNPs in the soup were observed using laser scanning confocal microscopy (LSCM). The results showed that the content of water-soluble proteins first increased and then decreased with the delay in salt addition time. The migration trend of total sugars was similar to that of the proteins. Meanwhile, the ash content in the soup generally increased and then decreased. The change in the content of soluble solids could represent changes in various nutrients. The migration of solids and the content of ash peaked when the salting time was at 90 min. The boiled samples with salt added at different times showed significant differences in the migration of nucleotides. It could be concluded that salting was ideal at 60 min or 90 min, based on the changes in the total amount of nucleotides. Furthermore, the contents of total free amino acids and umami-flavored amino acids were also the highest in the samples with salt added at 60 min or 90 min. When the addition time was 60 min, the stability of the MNP system in the fish head soup could effectively be improved by inhibiting the aggregation of macromolecules, which would promote the retention of various nutrients. The particle size and polydispersity (PDI) were lowest in the samples with salt added at 60 min. In addition, the zeta potential value of the sample with salt added at 60 min was higher than that at 90 min. Therefore, the system was relatively stable at 60 min, which was conducive to nutrient retention. This is consistent with the results of the microstructure analysis.The maximum dissolution of nutrients and flavor substances occurred when salt was added after boiling for 60 min. Meanwhile, MNPs in the soup were stable, uniform, double-layer, spherical particles. The results of LSCM showed that nonpolar triglycerides self-assembled into spherical particles, which were located in the center of the particles, and protein molecules dispersed around or were bound to the surface of the particles. The fish head soup system was the most stable under the conditions of particle size, potential, and polydispersion index. Therefore, adding salt after boiling for 60 min was the optimal procedure for making fish soup with high nutritional value, delicious taste, and stable content. This study provides a baseline procedure for C. argus head soup with high and stable nutritional content.The results provide technical support for preparing a convenient and delicious fish head soup. People can enjoy delicious food shortly after a hard day´s work. In addition, the results showed that the timing of adding salt had a significant impact on the nutrition of fish head soup, which suggests that attention should be paid to the timing of adding salt when preparing fish head soup at home. C. argus head, a by-product of processing, can increase in value and provide a solution for producers to decrease waste and increase profits.

Abstract This article explores the impact of language proficiency on international trade by using panel data analysis. To do so, we construct a time‐variant test‐score‐based measure of common language. Controlling for the standard gravity model variables, we find strong empirical evidence that English proficiency promotes bilateral trade flows through facilitating direct communication. We confirm that this finding is robust even when we estimate its effects separately on goods and services trade flows at a disaggregated level. Furthermore, we show that institutional similarities between trading partners play a role that is similar to communication easiness in trade. Our study provides a policy implication for government support for attaining second language fluency.

Abstract Although a variety of brain lesions may contribute to the pathological assessment of dementia, the relationship of these lesions to dementia, how they interact and how to quantify them remains uncertain. Systematically assessing neuropathological measures by their degree of association with dementia may lead to better diagnostic systems and treatment targets. This study aims to apply machine learning approaches to feature selection in order to identify critical features of Alzheimer-related pathologies associated with dementia. We applied machine learning techniques for feature ranking and classification to objectively compare neuropathological features and their relationship to dementia status during life using a cohort (n=186) from the Cognitive Function and Ageing Study (CFAS). We first tested Alzheimer’s Disease and tau markers and then other neuropathologies associated with dementia. Seven feature ranking methods using different information criteria consistently ranked 22 out of the 34 neuropathology features for importance to dementia classification. Although highly correlated, Braak neurofibrillary tangle stage, beta-amyloid and cerebral amyloid angiopathy features were ranked the highest. The best-performing dementia classifier using the top eight neuropathological features achieved 79% sensitivity, 69% specificity and 75% precision. However, when assessing all seven classifiers and the 22 ranked features, a substantial proportion (40.4%) of dementia cases was consistently misclassified. These results highlight the benefits of using machine learning to identify critical indices of plaque, tangle and cerebral amyloid angiopathy burdens that may be useful for classifying dementia.

Personality is widely observed in animals and has important ecological and evolutionary implications. In addition to being heritable, personality traits are also influenced by the environment. Population density commonly affects animal behavior, but the way in which it shapes animal personality remains largely unknown. In this study, we reared juvenile crayfish at different population densities and measured their personality traits (shyness, exploration, and aggression) after reaching sexual maturity. Our results showed repeatability for each behavior in all treatments, except for the shyness of females at medium density. There was a negative correlation between shyness and exploration in each treatment, and aggression and exploration were positively correlated in medium- and high-density females. These indicate the presence of a behavior syndrome. On average, the crayfish raised at higher population densities were less shy, more exploratory, and more aggressive. We found no behavioral differences between the sexes in crayfish. These results suggested that population density may affect the average values of behavioral traits rather than the occurrence of personality traits. Our study highlights the importance of considering population density as a factor influencing personality traits in animals and, therefore, might help us to understand animal personality development.

Animal personality, which describes inter-individual differences and intra-individual consistency in behaviors across time and contexts, has been widely observed and has significance for both ecology and evolution. Morphological modifications, particularly during early life stages, may highly influence animal behavior in adulthood; thus, exploring this relationship can elucidate personality development throughout ontogeny. In this study, we reared juvenile crayfish (Procambarus clarkii) with different degrees of cheliped mutilation and explored their personality patterns, including exploration and aggression, when they reached sexual maturity. Male crayfish showed repeatability in exploration, and both sexes showed repeatability in aggression. We observed no significant correlation between the two behavioral traits, indicating the absence of behavioral syndromes. Moreover, exploration did not differ according to the type of mutilation, but crayfish with more intact chelipeds were more aggressive, and males were more aggressive than females. These results indicate that cheliped mutilation may modify the average levels of personality traits associated with competition or self-defense. Our study provides insights into how morphological modifications may shape animal personalities in adulthood.

S14G-humanin (HNG), an analog of the mitochondria-derived peptide humanin, has demonstrated protective effects against various cardiovascular diseases. However, the specific pharmacological effects of HNG in heart failure (HF) have not been previously reported. Therefore, in this study, we aimed to investigate the potential protective effect of HNG in HF using a mouse model. HF was induced in mice through intraperitoneal injection of isoproterenol or transverse aortic constriction, followed by separate administration of HNG to assess its therapeutic impact. Our results revealed that HNG treatment significantly delayed the onset of cardiac dysfunction and structural remodeling in the HF mouse model. Furthermore, HNG administration was associated with reduced infiltration of inflammatory cells, improved myocardial fibrosis, and attenuation of cardiomyocyte apoptosis in the treated cardiac tissues. Additionally, we identified the involvement of the transforming growth factor-beta signaling pathway in the beneficial effects of HNG in isoproterenol-induced HF mice. Collectively, these findings underscore the therapeutic potential of HNG in preventing the progression of HF, as demonstrated in two distinct HF mouse models.

The Stimulator of Interferon Genes (STING) is predominantly expressed in immune cells, including macrophages, natural killer cells, dendritic cells, and T cells, functioning as a pattern recognition receptor. STING activation upon detecting cytosolic DNA released from damaged cells initiates downstream pathways, leading to the production of inflammatory cytokines such as IFNs, IL-6, and TNF-α. Dysregulated STING activation has been implicated in inflammatory and metabolic diseases. Ischemia/reperfusion injury (I/RI) is common in stroke, acute myocardial infarction, organ transplantation, and surgeries for certain end-stage diseases. Recent studies suggest that STING could be a novel therapeutic target for I/RI treatment. In this review, we provide a concise overview of the cGAS-STING signaling pathway's general functions and summarize STING's role in I/RI across various organs, including the heart, liver, kidney, and lung. Moreover, we explore potential therapeutic approaches for I/RI by targeting STING.

Background: The process of lactate metabolism has been proved to play a critical role in the progression of various cancers and to influence the immune microenvironment, but its potential role in osteosarcoma remains unclear. Methods: We have acquired transcriptomic and clinical data from 84 osteosarcoma samples and 70 normal bone samples from the TARGET and GTEx databases. We identified differentially expressed lactate metabolism-related LncRNAs (LRLs) in osteosarcoma and performed Cox regression and LASSO regression to establish LRLs prognostic signature (LRPS). The reliability of LRPS performance was examined by separate prognostic analysis, viability curves and receiver operating characteristic (ROC) curves. Furthermore, the effects of LRPS on the immune microenvironment of osteosarcoma were investigated, and the functions of the focal genes were experimentally validated. Result: A total of 856 differentially expressed LRLs were identified and 5 of them were selected to construct LRPS, which was a better prognostic predictor for osteosarcoma compared with other published prognostic signatures (AUC up to 0.947 and 0.839 in the training and test groups, respectively, with adj-p

Abstract This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (β), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high–high clusters), α, β, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV’s distribution in Gansu Province are needed.