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Abstract The rapid development of large language models (LLMs) has opened new avenues across various fields, including cybersecurity, which faces an evolving threat landscape and demand for innovative technologies. Despite initial explorations into the application of LLMs in cybersecurity, there is a lack of a comprehensive overview of this research area. This paper addresses this gap by providing a systematic literature review, covering the analysis of over 300 works, encompassing 25 LLMs and more than 10 downstream scenarios. Our comprehensive overview addresses three key research questions: the construction of cybersecurity-oriented LLMs, the application of LLMs to various cybersecurity tasks, the challenges and further research in this area. This study aims to shed light on the extensive potential of LLMs in enhancing cybersecurity practices and serve as a valuable resource for applying LLMs in this field. We also maintain and regularly update a list of practical guides on LLMs for cybersecurity at https://github.com/tmylla/Awesome-LLM4Cybersecurity .

Abstract The generation of radicals through photo-Fenton-like reactions demonstrates significant potential for remediating emerging organic contaminants (EOCs) in complex aqueous environments. However, the excitonic effect, induced by Coulomb interactions between photoexcited electrons and holes, reduces carrier utilization efficiency in these systems. In this study, we develop Cu single-atom-loaded covalent organic frameworks (CuSA/COFs) as models to modulate excitonic effects. Temperature-dependent photoluminescence and ultrafast transient absorption spectra reveal that incorporating acenaphthene units into the linker (CuSA/Ace-COF) significantly reduces exciton binding energy (E b). This modification not only enhances peroxymonosulfate adsorption at Cu active sites but also facilitates rapid electron transfer and promotes selective hydroxyl radical generation. Compared to CuSA/Obq-COF (E b = 25.6 meV), CuSA/Ace-COF (E b = 12.2 meV) shows a 39.5-fold increase in the pseudo-first-order rate constant for sulfamethoxazole degradation (0.434 min−1). This work provides insights into modulating excitonic behavior in single-atom catalysts via linker engineering for EOCs degradation.

Abstract The tertiary lymphoid structure (TLS) is recognized as a potential prognosis factor for breast cancer and is strongly associated with response to immunotherapy. Inducing TLS neogenesis can enhance the immunogenicity of tumors and improve the efficacy of immunotherapy. However, our understanding of TLS associated region at the single-cell level remains limited. Therefore, we employed high-resolution techniques, including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), and a TLS-specific signature to investigate TLS associated regions in breast cancer. We identified eighteen cell types within the TLS associated regions and calculated differential expression genes by comparing TLS associated regions with other areas. Notably, macrophages in the TLS associated regions exhibit lineage transformation, shifting from facilitators of immune activation to supporters of tumor cell growth. In terms of cell–cell communication within the TLS associated regions, KRT86+ CD8+ T cells, HISTIH4C+ cycling CD8+ T cells, IFNG+ CD8+ T cells, and IGKV3-20+ B cells demonstrate strong interactions with other cells. Additionally, we found that APOD+ fibroblast and CCL21+ fibroblast primarily recruit T and B cells through the CXCL12-CXCR4 ligand-receptor signaling pathway. We also validate these findings in four independent breast cancer datasets, which include one cell-level resolution dataset from the 10 × Xenium platform and three spot-level datasets from the 10 × Visium platform.

Abstract Neuroepithelial cell transforming gene 1 (NET1) is a member of the Ras homologue family member A (RhoA) subfamily of guanine nucleotide exchange factors and a key protein involved in the activation of Rho guanosine triphosphatases, which act as regulators of cell proliferation, cytoskeletal organization, and cell movement and are crucial for cancer spread. Research has shown that NET1 can regulate the malignant biological functions of tumour cells, such as growth, invasion, and metastasis, and it is closely related to the progression of pancreatic cancer, gastric cancer, and liver cancer. However, the comprehensive role and mechanistic function of NET1 in other types of cancer remain largely unexplored. A deeper understanding of the role of NET1 may provide new insights into the molecular mechanisms of cancer progression and metastasis. This study aims to fill this knowledge gap and provide a more comprehensive understanding of the role of NET1 in cancer biology. The Cancer Genome Atlas and Genotype-Tissue Expression databases were utilized to analyse the differential expression of NET1 in normal and cancer tissues. The prognostic value of NET1 in cancer was evaluated through log-rank tests and Cox regression models. Further analysis was conducted to assess the relationships between NET1 expression and clinical features, as well as its diagnostic value. We investigated potential factors contributing to genetic alterations in NET1 to elucidate the role of NET1 in cancer progression. We also explored the relationships between NET1 and genes associated with epigenetic modifications, oncogenes, and tumour characteristics, such as RNA stemness scores (RNAss), DNA stemness scores (DNAss), the tumour mutation burden (TMB), and microsatellite instability (MSI). Additionally, we analysed the associations between NET1 expression and immune cell infiltration, immunoregulatory genes, and sensitivity to therapeutic drugs. We conducted gene set enrichment analysis to further investigate the signalling pathways that might be affected by changes in NET1. The prognostic value of NET1 in triple-negative breast cancer (TNBC) was further validated using real-world and Gene Expression Omnibus (GEO) data. Finally, through both in vivo and in vitro experiments, we confirmed that the overexpression of NET1 contributed to the malignant progression of TNBC cells, and we explored the potential mechanism by which NET1 regulates malignant biological behaviour through cellular experiments. Our study revealed a higher expression level of NET1 in 18 types of tumour tissues than in their corresponding normal tissues. Specifically, we observed high expression of NET1 in LIHC, LUSC, PAAD, and BRCA tumour tissues, which was associated with a poor prognosis. In terms of gene alterations, “amplification”, “mutation”, and “deep deletion” were identified as the main types of changes occurring in NET1. Among these, “amplification” was predominantly observed in LIHC, LUSC, PAAD, and BRCA. Furthermore, a significant positive correlation was found between copy number variations and the NET1 expression level in various tumours, including LIHC, LUSC, PAAD, and BRCA. We also discovered that NET1 expression was positively correlated with the expression of genes related to epigenetic modification in almost all types of cancer and was related to the expression levels of numerous oncogenes. In certain tumours, a significant positive correlation was noted between the expression of NET1 and TMB, MSI, DNAss, and RNAss. Intriguingly, in most tumours, NET1 expression was strongly negatively correlated with the levels of infiltrating natural killer cells and M1 macrophages. Moreover, NET1 expression was significantly positively correlated with the expression of immune genes in nearly all types of cancer. An analysis of single-cell data revealed that NET1 was expressed primarily in malignant tumour cells in most tumours, with little to no expression in immune cells. Additionally, the expression level of NET1 was associated with sensitivity to various therapeutic drugs. Data from GEO and real-world studies indicated high expression of NET1 in TNBC tissues, which was correlated with a poor prognosis. Cellular experiments indicated that NET1 could regulate the proliferation, invasion, cell cycle, and apoptosis of TNBC cells. Furthermore, NET1 may mediate the malignant proliferation of tumour cells through the AKT signalling pathway. NET1 can serve as a potential prognostic marker for LIHC, LUSC, PAAD, and BRCA tumours. Real-world data further suggest that NET1 can also serve as a prognostic indicator for TNBC. High expression of NET1 may contribute to the malignant proliferation of TNBC cells, potentially through the AKT signalling pathway. Moreover, NET1 may contribute to the formation of an immunosuppressive microenvironment that can promote tumour progression. Therefore, targeting NET1 may represents a promising approach for inhibiting tumour progression.

Abstract Background The high comorbidity and symptom overlap of generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD), has led to the study of their shared and disorder-specific neural substrates. However, the morphometric similarity network (MSN) differences among these disorders remain unknown. Methods MSN derived from T1-weighted images in patients of GAD, PTSD, and SAD, and health controls (HC) using a Siemens 3T magnetic resonance imaging system. Covariance analysis and post hoc tests were used to investigate group differences. In addition, the relationship between MSN and clinical characteristics was analyzed. Results Increased morphometric similarity (MS) between left bankssts (BA22, superior temporal cortex, STC) and right precentral gyrus, and decreased MS between left precentral gyrus and right cuneus_part1/part2, and between right rostral middle frontal cortex (rMFC) and right STC were common in GAD and PTSD relative to HC and SAD. Compared to the other three groups, SAD exhibited disorder-specific alterations of increased MS between right rMFC and right STC, and between left cuneus and right inferior parietal cortex. Additionally, increased regional MSN in left precentral gyrus was found in PTSD compared to HC and SAD. A mild positive correlation of the MS value between left bankssts and right precentral gyrus and the Hamilton Anxiety Rating Scale scores (uncorrected p = 0.041) was found in PTSD. Conclusions Our study provides the first evidence for common and distinct brain MSN abnormalities underlying the pathophysiology of GAD, PTSD, and SAD, which may aid in differential diagnosis and determining potential disorder-specific intervention targets.

Abstract Uncontrolled TLR signaling can cause inflammatory immunopathology and trigger autoimmune diseases. For example, TLR7 promotes pathogenesis of systemic lupus erythematosus. However, whether RNA structural changes affect nucleic acids-sensing TLRs signaling and impact disease progression is unclear. Here by iCLIP-seq we identify a TLR7-binding long non-coding RNA, Lnc-Atg16l1, and find that it promotes TLR7 and other MyD88-dependent TLRs signaling in various types of immune cells. Depletion of Lnc-Atg16l1 attenuates development of TLR7-linked autoimmune phenotypes in the mouse SLE model. Mechanistically, we find that Lnc-Atg16l1 binds to TLR7 at bases near U84 and MyD88 at bases around A129. The analysis of Lnc-Atg16l1 in situ structures show that it strengthens the interaction between TIR domain of TLR7 and MyD88 through specific stem-loop structure changes as a molecular scaffold after TLR7 activation to promote TLR7 downstream signaling. Therefore, we discover a mechanism for host RNA regulation of innate signaling and autoimmune disease through its structural changes. These findings provide insights into the pro-inflammatory function of self RNA in a structure-dependent manner and suggest a potential target for TLR-related autoimmune disorders.

Abstract Background Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Methods Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. Results We uncovered that LC-BrMs exhibited a significantly greater intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic, and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry, and multiplexed immunofluorescence staining of patients’ paired tumor specimens. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids of LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Conclusions In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.

Abstract Background Informal caregivers of older adults play a vital role in improving the degree to which older adults access community and healthcare services in a seamless and timely manner. They are fulfilling important navigation and support roles for their older care recipients. However, there is still little knowledge of the most significant facilitators and barriers to effective and efficient system navigation among caregivers. This paper aims to fill these knowledge gaps through investigation of the key factors (i.e., social capital/cohesion, caregiving supports, and utilization factors) affecting navigation difficulties faced by informal caregivers of older adults. Methods The Behavioural-Ecological Framework of Healthcare Access and Navigation (BEAN) model is used to frame the study. Using the General Social Survey on Caregiving and Care Receiving 2018, we analyzed 2,733 informal caregivers whose primary care recipients were aged 65 or older. Hierarchical logistic regression was conducted to identify the relationship between system navigation difficulties among informal caregivers and four sequentially ordered blocks of predictors: (1) sociodemographic (2), social capital/cohesion (3), caregiving supports, and (4) healthcare demand. Results The fully adjusted model showed that the probability of reporting navigation difficulties was lower for caregivers with social capital/cohesion compared to those without social capital/cohesion. In comparison, the probability of reporting navigation difficulties was higher among caregivers with caregiving support and among caregivers whose care receivers use a higher amount of health service use. Several sociodemographic covariates were also identified. Conclusion Our findings support certain aspects of the BEAN model. This study extends our understanding of potential facilitators and barriers that informal caregivers of older adults face while navigating complex community and health systems. There is a need to implement coordinated schemes and health policies especially for older adults with mental/neurological issues to address the challenges of their caregivers given the specific vulnerability identified in this study. The need for further research using different approaches to examine the disproportionate impact of COVID-19 on caregivers’ system navigation experience is crucial.

Abstract Background Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. Methods We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. Results At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. Conclusions The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD.

In the context of global warming， the Qinghai-Xizang Plateau is altering atmospheric circulation through sensible heat absorption and latent heat release.This not only impacts the water and energy balance of the plateau's ecosystem but also plays a crucial role in regulating Asian and global climates.In order to explore the change characteristics and influencing factors of evapotranspiration in different regions of alpine grassland ecosystem on the Qinghai-Xizang Plateau， and deepen understanding of plateau climate change and hydrological-ecological processes， based on the observed eddy and meteorological data in 2022， the variation characteristics and environmental influencing factors of actual evapotranspiration of alpine grassland ecosystems at the same altitude in Sijinlacuo （seasonal permafrost） and Tuotuo River （permafrost） on the Qinghai-Xizang Plateau were compared and analyzed.The results show that： （1） Significant differences existed between environmental factors at these two sites， particularly in wind speed， air temperature， and precipitation.The wind speed at Tuotuo River station greatly exceeded that at Shijinlasuo station； annual average air temperature and precipitation were lower at Tuotuo River station.（2） The average hourly evapotranspiration of Sijinlacuo Station at night was higher than those recorded at Tuotuo River Station， however， this trend reverses during daytime hours.The variation characteristics of daily evapotranspiration at the two stations had a similar trend.The date of sharp increase and maximum of evapotranspiration at Sijinlacuo Station were earlier than those at Tuotuo River Station.The monthly evapotranspiration of the two stations were unimodal， with the maximum value appeared in July in summer and the smaller value appeared in December， January and February in winter.（3） Wind speed and ground radiation showed differing correlations with evaporation across both stations.Wind speed had a stronger correlation with evaporation at Tuotuo River Station due to higher wind speeds compared to weaker correlations observed for Sijinlasuo Station where winds were less intense.Conversely， ground radiation showed opposite correlations with evaporation between both locations.Air temperature， water vapor pressure， and atmospheric longwave radiation demonstrated strong correlations with evaporation across both locations while air humidity， saturated water vapor pressure difference， and precipitation displayed weaker associations.Precipitation exhibited the weakest correlation.（4） Although precipitation served as the primary source of evaporated water content， sources such as glacier melt water and thawing permafrost played significant roles as well on the Qinghai-Xizang Plateau， resulting in subdued influence of precipitation on the evaporative process at both locations.These results contribute valuable insights into understanding regional variations in high-altitude grassland ecosystems' response to changing climatic conditions on the Qinghai-Xizang Plateau.

Abstract Background Cannabis use has been increasing among older adults in Canada, particularly during the COVID-19 pandemic. This study aims to examine the association between loneliness and cannabis use among older Canadians during the pandemic. Methods Quantitative data analyses were performed based on 2,020 participants aged 55 years and older from the Canadian Perspectives Survey Series 6, 2021: Substance Use and Stigma During the Pandemic. Results This study found that participants who used cannabis in the 30 days before the survey reported significantly higher loneliness scores than those who never used cannabis after adjusting social-demographic, social interaction, and pandemic-related factors. Participants who kept using cannabis during the pandemic also reported significantly higher loneliness scores than those who never used cannabis. Conclusion The findings about the correlation between cannabis use and greater loneliness contribute to the discourse on potential health and wellbeing harms of cannabis use among older adults.

The Jingyang–Weinan Fault that Xi’an Metro Line 10 crosses is a Holocene active fault, and its future stick-slip earthquakes and coseismic dislocations pose a potential threat to the metro line. To reveal the deformation and stratum stress characteristics of the site caused by the stick-slip seismic and coseismic dislocations of the Jingyang–Weinan Fault zone, based on the Jingyang–Weinan fault zone crossed by Xi’an Metro Line 10, the geomechanical model of the fault zone site coseismic dislocations and stick-slip seismic was established, and the numerical simulation analysis of the stratum deformation and stress field characteristics of fault zone site was carried out considering different dislocation amounts and seismic intensity. The results show that under the coseismic dislocation, the stress reduction and strengthening zones appear in the hanging wall and footwall near the fault zone, and the site presents an inverse “S” shaped differential settlement failure. The differential displacement peaks at the fault zone, and the plastic zone is concentrated here. The deformation range and plastic zone of the hanging wall are 1.67 times and 2.50 times more than that of the footwall, respectively. The displacement and differential deformation of the site near the fault zone reach the peak value under the stick-slip earthquake. The influence range of the site displacement during the large earthquake is approximately 6.50 times more than that during the medium earthquake. It has a typical magnification effect on the hanging wall, and the displacement decreases linearly far away from the fault zone. The amplification factor of peak surface acceleration (PGA) in the large earthquake is 1.14 times more than that in the medium earthquake. The site shows “V” shear failure; the plastic zones of hanging wall and footwall in the large earthquake is about 1.40 times and 1.00 times larger than that in the medium earthquake, respectively. This study can provide a scientific basis for the seismic fortification of Xi’an Metro Line lines crossing the Jingyang–Weinan fault zone.

Abstract Objective Multimorbidity is recognized as a serious health condition faced by a majority of older adults. Research investigating adaptive responses to multimorbidity, termed multimorbidity resilience, has been growing. This paper examines protective and risk factors, with a focus on health behaviours, socio-economic resources, and social support using an established measure of resilience (Connor-Davidson Resilience Scale) among older adults, focusing on older persons with two or more concurrent chronic conditions. Methods Using Baseline (2011–2015), Follow-up One (2015–2018), and Follow-up Two (2018–2021) data from the Comprehensive Cohort of the Canadian Longitudinal Study on Aging, we tested hypotheses using 13,064 participants aged 65 years and older, who completed all waves and reported two or more of 27 chronic conditions, for the full sample of multimorbid individuals and three multimorbidity clusters: Cardiovascular/Metabolic, Musculoskeletal, and Mental Health. Associations between protective and risk factors and resilience were examined using linear regression to model the Connor-Davidson resilience scale, adjusting for illness context and social determinants of health. Results Among all multimorbid individuals, the strongest associations with resilience were found for higher self-rated health, greater sleep satisfaction, better appetite, higher household income, more relatives and friends, being overweight (compared to normal weight), fewer housing problems, and fewer skipped meals. Weaker associations were found for non-smokers, less alcohol consumption, less pain, sedentary behaviour, being non-married (compared to married), and among Canadian born (compared to foreign). The analyses for the three multimorbidity clusters were largely replicated for the three multimorbidity clusters, but with some nuances depending on the cluster. Discussion This research provides confirmatory evidence for several protective and risk factors affecting the ability to cope and recover from multimorbidity adversity among older adults. There are consistent patterns for the multimorbidity disease clusters, but some distinct relationships arise that are worthy of attention. The implications of the findings for modifiable health behaviours and socio-economic factors are discussed for their public health and clinical relevance.

Abstract Observational studies have suggested a bidirectional relationship between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD). However, the causal association between these two neurodegenerative disorders remains unclear. This study aimed to explore the causal relationship between iNPH and AD using a two-sample bidirectional Mendelian randomization (MR) method. Large-scale genome-wide association studies of iNPH (Ncase = 767, Ncontrol = 375,610) and AD (Ncase/proxy = 111,326, Ncontrol = 677,663) in European individuals were used to screen genetic instruments for MR analysis. Inverse variance-weighted (IVW) method was used as the main analysis, other MR methods and a series of sensitivity analyses were performed to ensure the reliability. In the forward MR analysis, genetic predisposition to iNPH had no effects on the risk of AD development. Likewise, in the reverse MR analysis, AD did not demonstrate a significant causal effect on iNPH. Sensitivity analyses bolstered the reliability of the MR results. Our MR study indicated no genetic evidence supporting a suggestive association between AD and iNPH in either direction, and provided evidence on the dichotomy between true iNPH and neurodegenerative NPH.

Gynostemma pentaphyllum (GP), recognized as both an edible vegetable and health tea, has been consumed for thousands of years. Chemical research indicates GP primarily contains active ingredients including saponins, polysaccharides, and flavonoids. Notably, saponins and polysaccharides are among the main active components of GP, which have been extensively utilized in medicine, food, healthcare, and cosmetics due to their bioactivities including anti-tumor, anti-oxidation, hypoglycemic, cardioprotective, neuroprotective and anti-inflammatory activities. We conducted searches in various online databases, including Elsevier, Springer, PubMed, Web of Science, and China Knowledge Network (CNKI), to gather literature on the traditional uses, structural characteristics, and biological activities of the active ingredients of GP published prior to October 2024. In this review, GP saponins were categorized and GP polysaccharides discovered in the last ten years were highlighted. Then, the bioactivities of GP are summarized and lays a solid foundation for its development as a functional health food.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved many high‐risk variants, resulting in repeated COVID‐19 waves over the past years. Therefore, accurate early warning of high‐risk variants is vital for epidemic prevention and control. However, detecting high‐risk variants through experimental and epidemiological research is time‐consuming and often lags behind the emergence and spread of these variants. In this study, HiRisk‐Detector a machine learning algorithm based on haplotype network, is developed for computationally early detecting high‐risk SARS‐CoV‐2 variants. Leveraging over 7.6 million high‐quality and complete SARS‐CoV‐2 genomes and metadata, the effectiveness, robustness, and generalizability of HiRisk‐Detector are validated. First, HiRisk‐Detector is evaluated on actual empirical data, successfully detecting all 13 high‐risk variants, preceding World Health Organization announcements by 27 days on average. Second, its robustness is tested by reducing sequencing intensity to one‐fourth, noting only a minimal delay of 3.8 days, demonstrating its effectiveness. Third, HiRisk‐Detector is applied to detect risks among SARS‐CoV‐2 Omicron variant sub‐lineages, confirming its broad applicability and high ROC‐AUC and PR‐AUC performance. Overall, HiRisk‐Detector features powerful capacity for early detection of high‐risk variants, bearing great utility for any public emergency caused by infectious diseases or viruses.

Brain arteriovenous malformations (AVMs) are vascular lesions characterized by abnormal connections between parenchymal arteries and veins, bypassing a capillary bed, and forming a nidus. Brain AVMs are consequential as they are prone to rupture and associated with significant morbidity. They can broadly be subdivided into hereditary vs. sporadic lesions with sporadic brain AVMs representing the majority of all brain AVMs. However, little had been known about the pathogenesis of sporadic brain AVMs until the landmark discovery in 2018 that the majority of sporadic brain AVMs carry somatic activating mutations of the oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS), in their endothelial cells. Here, we review the history of brain AVMs, their treatments, and recent advances in uncovering the pathogenesis of sporadic brain AVMs. We specifically focus on the latest studies suggesting that pharmacologically targeting the KRAS/MEK pathway may be a potentially efficacious treatment for sporadic brain AVMs.

The Chinese proverb “One mountain, one flavor” reflects that raw pu-erh tea (RPT) from different tea-producing mountains (TPMs) possesses distinct flavor profiles. However, limited research has been conducted on the chemical composition underlying distinct flavor profiles. In this study, sensory evaluation and main phytochemical compositions revealed diverse aromas of RPTs from 26 TPMs. A total of 225 volatile compounds were analyzed qualitatively and quantitatively by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry, including hydrocarbon compounds, ketones, alcohols, and aldehydes. Furthermore, twenty-one common key odor-active compounds, potentially influencing the regional flavor, were identified by gas chromatography-olfactometry and odor activity value. Multivariate statistical analysis showed that geographical factors—longitudes, latitudes, counties, and elevations—account for 37.02 % of the aroma profile variance, implying the possible influence of other potential factors. The study results serve as a reference for a better understanding of the correlation between the RPT flavor characteristics and geographical attributes in TPMs.

Abstract Streamflow in source region of Yellow River (SRYR) matters with regard to the adjacent and downstream water resources. Intraseasonal oscillation (ISO) in the streamflow in SRYR is of great significance to the sub-seasonal prediction of streamflow in SRYR, but is unknown. Here, we first report a 30–60-day ISO in the streamflow in SRYR, which is regulated by the atmospheric 30–60-day ISO at mid-high latitude over North Eurasia. The 30–60-day ISO in atmosphere is featured by a Rossby wavetrain, and the wave energy propagates southward onto the TP, which causes anomalous wind response over TP. The leading anomalous high (low) with anti-cyclonic (cyclonic) wind anomalies over the TP favors dry (wet) air in lower troposphere in SRYR, via enhancing the water vapor divergence (convergence). Dry (wet) air always results in strong (weak) evaporation from the Yellow River, which causes the later streamflow valley (peak) and thereby the 30–60-day ISO in the streamflow in SRYR.

Abstract In recent years, the widespread adoption of wireless sensor networks (WSN) has resulted in the growing integration of the internet of things (IoT). However, WSN encounters limitations related to energy and sensor node lifespan, making the development of an efficient routing protocol a critical concern. Cluster technology offers a promising solution to this challenge. This study introduces a novel cluster routing protocol for WSN. The system selects cluster heads and relay nodes utilizing the multi-strategy fusion snake optimizer (MSSO) and employs the minimum spanning tree algorithm for inter-cluster routing planning, thereby extending the system’s lifecycle and conserving network energy. In pursuit of an optimal clustering scheme, the paper also introduces tactics involving dynamic parameter updating, adaptive alpha mutation, and bi-directional search optimization within MSSO. These techniques significantly increase the algorithm convergence speed and expand the available search space. Furthermore, a novel efficient clustering routing model for WSN is presented. The model generates different objective functions for selecting cluster heads and relay nodes, considering factors such as location, energy, base station distance, intra-cluster compactness, inter-cluster separation, and other relevant criteria. When selecting cluster heads, the fuzzy c-means (FCM) algorithm is integrated into MSSO to improve the optimization performance of the algorithm. When planning inter-cluster routing, the next hop node is selected for the relay node based on distance, residual energy, and direction.The experimental results demonstrate that the proposed protocol reduces energy consumption by at least 26.64% compared to other cluster routing protocols including LEACH, ESO, EEWC, GWO, and EECHS-ISSADE. Additionally, it increases the network lifetime of WSN by at least 25.84%, extends the stable period by at least 52.43%, and boosts the network throughput by at least 40.99%.

Abstract Background Anthracnose, mainly caused by Colletotrichum fructicola, leads to severe losses in pear production. However, there is limited information available regarding the molecular response to anthracnose in pears. Results In this study, the anthracnose-resistant variety ‘Seli’ and susceptible pear cultivar ‘Cuiguan’ were subjected to transcriptome analysis following C. fructicola inoculation at 6 and 24 h using RNA sequencing. A total of 3186 differentially expressed genes were detected in ‘Seli’ and ‘Cuiguan’ using Illumina sequencing technology. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the transcriptional response of pears to C. fructicola infection included responses to reactive oxygen species, phytohormone signaling, phenylpropanoid biosynthesis, and secondary metabolite biosynthetic processes. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway and phenylpropanoid biosynthesis were involved in the defense of ‘Seli’. Furthermore, the gene coexpression network data showed that genes related to plant–pathogen interactions were associated with C. fructicola resistance in ‘Seli’ at the early stage. Conclusion Our results showed that the activation of specific genes in MAPK, calcium signaling pathways and phenylpropanoid biosynthesis was highly related to C. fructicola resistance in ‘Seli’ and providing several potential candidate genes for breeding anthracnose-resistant pear varieties.

BackgroundAs a minimally invasive approach to treating congenital heart disease (CHD), the application of the right subaxillary small incision (RSSI) has been developing fast in its indication spectrum. However, RSSI's use is still quite challenging for the surgical treatment of the low-age and low-weight infant patient group.ObjectivesTo investigate the safety and efficacy of performing RSSI surgery, treating CHD for infants with low-age and low-weight.MethodsBetween March 2010 and April 2023, Low-age (≤6 months) and low-weight (≤5 kg) infants with ventricular or atrial septal defect (ASD) as the main diagnosis were retrospectively included in this study. The infants were divided into the RSSI group and the median sternotomy (MS) group. Preoperative conditions, general surgical conditions, perioperative and postoperative outcomes, and long-term follow-up results were compared between the 2 groups.ResultsThe study included 783 cases. Of these, 434 were operated with MS, and 349 were operated with RSSI. A1:1 matched MS group (282 cases) and RSSI group (282 cases) were obtained after performing propensity score matching (PSM). Analysis of the 2 groups after PSM showed the differences in residual ASD/VSD, peak airway pressure, fraction of inspired oxygen/partial pressure of oxygen (PaO2/FiO2), and partial pressure of carbon dioxide (PaCO2) before return to the intensive care unit (ICU) and extubation were not statistically significant between groups, whereas mechanical ventilation time (P

Background: Pegylated liposomal doxorubicin (PLD), epirubicin and pirarubicin are the main anthracyclines widely used in China. PLD demonstrates therapeutic response comparable to epirubicin and pirarubicin in neoadjuvant chemotherapy (NAC) of breast cancer. Objectives: The objectives of our study were to retrospectively assess the real-world effectiveness and prognostic characteristics of PLD as NAC for HR ⩽ 10%/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Design: This was a retrospective study. Methods: Our study enrolled patients with HR ⩽ 10%/HER2-negative breast cancer who received PLD-, epirubicin- or pirarubicin-based NAC from three centres in Hunan Province, China, between 2015 and 2022. We employed inverse probability of treatment weighting to balance the differences in patients’ characteristics among the PLD, epirubicin, and pirarubicin groups. The endpoints were pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Results: A total of 267 patients were included. After NAC, the pCR rates in PLD group were superior to epirubicin group (PLD, 34.1%; epirubicin, 20.8%, p = 0.038). The differences in EFS (log-rank p = 0.99) and OS (log-rank p = 0.33) among the three groups were not statistically significant. Among the three groups, non-pCR patients had worse EFS than pCR patients (log-rank p = 0.014). For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups. Conclusion: PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.

IntroductionMultiple linked single nucleotide polymorphisms (SNPs) have shown potential in personal identification and mixture detection. However, the limited number of marker and sequencing errors have obstructed accurate DNA typing.MethodsTo develop more candidate loci, the diversity value (D-value) was introduced as a new parameter for screening the novel polymorphic multiple linked-SNP markers, referred to as multi-SNP. In this study, a “FD Multi-SNP Mixture Kit” comprising 567 multi-SNPs was developed for mixture detection. Additionally, a new computational error correction method was applied as a quality control approach for sequencing data.ResultsThe results demonstrated higher typing success rates than the conventional CE typing method. For single-source DNA, approximately 70–80 loci were detected with a DNA input of 0.009765625 ng. More than 65% of the minor alleles were distinguishable at 1 ng DNA with a frequency of 0.5% in 2- to 4-person mixtures.ConclusionThis study offers a polymorphic and high-resolution detection method for DNA genotyping and complex mixture detection, providing an alternative strategy for addressing challenging mixed DNA traces.

Objective This study aims to assess the accuracy and stability of smartwatches in predicting acute mountain sickness (AMS). Methods In locations exceeding an altitude of 2500 m, a cohort of 42 subjects had their Lake Louise AMS self-assessment score, blood oxygen saturation (SpO 2 ), heart rate, and perfusion index measured using smartwatches, with the data seamlessly conveyed to the Huawei Cloud. Results A significant decrease in SpO 2 was observed in individuals positive for AMS compared to those negative ( p

Abstract Purpose To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. Methods This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. Results From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p

Abstract Background Chlorophyll (Chl) is an agronomic trait associated with photosynthesis and yield. Gibberellin 2-oxidases (GA2oxs) have previously been shown to be involved in Chl accumulation. However, whether and how the PbrGA2ox proteins (PbrGA2oxs) mediate Chl accumulation in pear (Pyrus spp.) is scarce. Results Here, we aimed to elucidate the role of the pear GA2ox gene family in Chl accumulation and the related underlying mechanisms. We isolated 13 PbrGA2ox genes (PbrGA2oxs) from the pear database and identified PbrGA2ox1 as a potential regulator of Chl accumulation. We found that transiently overexpressing PbrGA2ox1 in chlorotic pear leaves led to Chl accumulation, and PbrGA2ox1 silencing in normal pear leaves led to Chl degradation, as evident by the regreening and chlorosis phenomenon, respectively. Meanwhile, PbrGA2ox1-overexpressing (OE) tobacco plants discernably exhibited Chl built-up, as evidenced by significantly higher Pn and Fv/Fm. In addition, RNA sequencing (RNA-seq), physiological and biochemical investigations revealed an increase in abscisic acid (ABA), methyl jasmonate (MeJA), and salicylic acid (SA) concentrations and signaling pathways; a marked elevation in reducing and soluble sugar contents; and a marginal decline in the starch and sucrose levels in OE plants. Interestingly, PbrGA2ox1 overexpression did not prominently affect Chl synthesis. However, it indeed facilitated chloroplast development by increasing chloroplast number per cell and compacting the thylakoid granum stacks. These findings might jointly contribute to Chl accumulation in OE plants. Conclusion Overall, our results suggested that GA2oxs accelerate Chl accumulation by stimulating chloroplast development and proved the potential of PbrGA2ox1 as a candidate gene for genetically breeding biofortified pear plants with a higher yield.

Fruitlet calyx shedding in pear plants is apparently regulated via numerous pathways that involve both environmental triggers and phytohormones cues such as auxin. In this study, we found at 10 days after full bloom (DAFB) higher levels of indoleacetic acid (IAA) and tryptophan (Trp) in calyx persistence fruitlet (CPF) than calyx shedding fruitlet (CSF) of ‘Danshan Suli’ pear (Pyrus bretschneideri Rhed.). Consisting with this, the activity of indolealdehyde oxidase (IAAIdO), which promotes IAA synthesis, was remarkably increased, and that of peroxidase (POD), which degrades IAA, dropped markedly in CPF but not in CSF. Further, qRT-PCR results revealed that most of 31 PbrARFs (encoding auxin response factors) in Pyrus bretschneideri were highly expressed in CPF, whereas PbrARF4, PbrARF24 and PbrARF26 were significantly down-regulated in CPF vis-a-vis CSF. Phylogenetic analysis revealed that 6 PbrARFs clustered in the group Ⅲ, where PbrARF4 showed the closest affinity with AtARF1 that promotes organ abscission, indicating a putative role of PbrARF4 in mediating the process of calyx shedding in pear. In fact, the ectopic overexpression of PbrARF4 in Solanum lycopersicum resulted in an earlier-formed and deeper abscission layer (AL) in the transgenic plants, whose calyxes were more prone to wilt at the mature red stage (MR) compared with the control plants (wild-type). More importantly, expression levels of the abscission genes SlLS and SlCel2 in transgenic plants overexpressing PbrARF4 were significantly up-regulated in comparation with the WT, whereas those of SlBI and SlTAPG2 were considerably inhibited. Further, PbrJOINTLESS and PbrIDA, the two genes related to calyx shedding in pear, were up-regulated more in CSF than CPF. The findings contribute to a better understanding of PbrARFs involved in fruitlet calyx shedding of pear, which could prove beneficial to improving the quality of pear fruit.

With the rapid increase in vehicle ownership and increasingly stringent emission regulations, addressing the energy consumption of and emissions from commercial vehicles have become critical challenges. This study introduces a multi-objective cooperative adaptive cruise control (CACC) strategy, designed for intelligent connected commercial vehicle platoons, operating in event-triggered conditions. A hierarchical control framework is utilized: the upper layer handles reference speed planning based on vehicle dynamics and constraints, while the lower layer uses distributed model predictive control (DMPC) to manage vehicle following. DMPC is chosen for its ability to manage distributed platoons by enabling vehicles to make local decisions, while maintaining system-wide coordination. Additionally, adaptive particle swarm optimization (APSO) is employed during the optimization process to solve the optimal problem efficiently. APSO is employed for its computational efficiency and adaptability, ensuring quick convergence to optimal solutions with reduced overheads. An event-triggering mechanism is integrated to further reduce the computational demands. The simulation results show that the proposed approach reduces fuel consumption by 8.05% and NOx emissions by 10.15%, while ensuring stable platoon operation during dynamic driving conditions. The effectiveness of the control strategy is validated through extensive simulations, highlighting superior performance compared to conventional methods.

ObjectiveExperienced 3 years of pandemic-induced home life, in the post-epidemic period, preschoolers in China are falling short of the World Health Organization’s standards for screen time and outdoor activities. This notably impacts their physical well-being. The study aims to probe the associations between screen time, outdoor activities, and the physical health of preschoolers, offering insights to shape interventions targeting myopia and obesity prevention in children.MethodsA cross-sectional study was conducted in Guangdong Province, involving a representative sample of 23,992 preschoolers and their caregivers recruited through proportional stratified cluster sampling. Data collection utilized the Chinese Early Human Capability Index (CHeHCI, eHCi), a questionnaire on children’s media use in daily family life, and Body Mass Index (BMI). Linear regression and binary logistic regression models were employed to analyze the impact of screen time and outdoor activity duration on the physical health of preschoolers.ResultsIn the high family socioeconomic status (SES) group, children had significantly less screen time compared to those in the medium and low SES groups. Outdoor activity time varied significantly based on SES, with higher SES linked to extended outdoor engagement. Additionally, children’s eHCi health dimension score exhibited significant SES-related differences, showcasing higher scores for children in higher SES groups. In terms of gender differences, boys dedicated significantly more time to outdoor activities than girls, yet boys had a notably higher overweight rate. Furthermore, girls demonstrated better health outcomes based on eHCi health scores. A significant association emerged between overweight and screen time in children with high SES, indicating that prolonged screen time was linked to a higher likelihood of overweight based on BMI. Additionally, a substantial negative correlation was observed between children’s eHCi health dimension score and screen time. Furthermore, children’s outdoor activity time exhibited a significant positive correlation with eHCi health dimension score. Regression analysis revealed that screen time could significantly negatively predict children’s physical health score, while outdoor activity time could significantly positively predict children’s eHCi physical health score.ConclusionThe current study highlights that family SES, age, and gender play pivotal roles in influencing preschoolers’ screen time and outdoor activity duration, with family SES being particularly influential. Higher family SES correlates with reduced screen time, increased outdoor activity, and elevated health levels among children. Importantly, children’s screen time negatively predicts their health status, while outdoor time positively predicts their health status.

Objective Breast-conserving therapy (BCT) includes breast-conserving surgery (BCS) combined with radiation therapy (RT). RT plays a crucial role in improving the prognosis of patients who undergo BCS. However, obesity is a potential risk factor for resistance to radiation. The aim of this study was to evaluate any difference in the long-term prognosis of patients with early stage breast cancer and obesity treated with BCT or total mastectomy (TM).Design, setting and participants This was a retrospective cohort study involving 1125 patients diagnosed with early stage breast cancer and obesity at the Shanghai Cancer Center of Fudan University from 2013 to 2016.Outcome measures Obesity in the Chinese population was defined as a body mass index ≥28 kg/m2. Surgical options included BCT and TM. The primary survival outcomes were overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS). Inverse probability of treatment weighting (IPTW) was used to control for the impact of confounding factors on prognosis.Results The median follow-up times in the BCT group and TM group without postoperative RT were 51.1 months (IQR of 40.6–68.1 months) and 61.8 months (IQR of 46.5–76.7 months), respectively. After IPTW, the baseline data were balanced. Compared with those in the TM cohort, patients in the whole IPTW cohort in the BCT cohort had worse DFS (HR 4.280, 95% CI 2.180 to 8.400; p

Summary: Glioblastoma (GBM) is characterized by aggressive growth, invasiveness, and poor prognosis. Elucidating the molecular mechanisms underlying GBM is crucial. This study explores the role of Sm-like protein 14 homolog A (LSM14A) in GBM. Bioinformatics and clinical tissue samples analysis demonstrated that overexpression of LSM14A in GBM correlates with poorer prognosis. CCK8, EdU, colony formation, and transwell assays revealed that LSM14A promotes proliferation, migration, and invasion in GBM in vitro. In vivo mouse xenograft models confirmed the results of the in vitro experiments. The mechanism of LSM14A modulating GBM cell proliferation was investigated using mass spectrometry, co-immunoprecipitation (coIP), protein half-life, and methylated RNA immunoprecipitation (MeRIP) analyses. The findings indicate that during the G1/S phase, LSM14A stabilizes DDX5 in the cytoplasm, regulating CDK4 and P21 levels. Furthermore, METTL1 modulates LSM14A expression via mRNA m7G methylation. Altogether, our work highlights the METTL1-LSM14A-DDX5 pathway as a potential therapeutic target in GBM.

One of the critical technologies to ensure cyberspace security is network traffic anomaly detection, which detects malicious attacks by analyzing and identifying network traffic behavior. The rapid development of the network has led to explosive growth in network traffic, which seriously impacts the user's information security. Researchers have delved into intrusion detection as an active defense technology to address this challenge. However, traditional machine learning methods struggle to capture complex threats and attack patterns when dealing with large-scale network data. In contrast, deep learning methods have the advantages of automatically extracting features from network traffic data and strong generalization capabilities. Aiming to enhance the ability of network anomaly traffic detection, this paper proposes a network traffic anomaly detection based on Deep Residual Shrinkage Network (DRSN), namely ''GSOOA-1DDRSN''. This method uses an improved Osprey optimization algorithm to select the most relevant and essential features in network traffic, reducing the features' dimensionality. For better detection performance of network traffic anomalies, a one-dimensional deep residual shrinkage network (1DDRSN) is designed as a classifier. Validation is performed using the NSL-KDD and UNSW-NB15 datasets and compared with other methods. The experimental results show that GSOOA-1DDRSN has improved multi-classification accuracy, precision, recall, and F1 Score by approximately 2 % and 3 %, respectively, compared to the 1DDRSN model on two datasets. Additionally, it reduces the time computation costs by 20 % and 30 % on these datasets. Furthermore, compared to other models, GSOOA-1DDRSN offers superior classification accuracy and effectively reduces the number of features.

Abstract Research on amateur mountaineers is scarce, and this study aims to delve into the emotional experiences of ten amateur mountaineers during their ascent using the "Befindlichkeitsskala" (BFS) and Lake Louise Acute Mountain Sickness scoring system (LLS). These subjects were exposed to altitudes of 3140 m, 4300 m, and 5276 m, respectively. We found that LLS scores were negatively correlated with positive emotions (β = −27.54, p

Abstract Background The primary management modalities for the patella in TKA include patellar resurfacing, patellar non-resurfacing, patellar resurfacing with denervation, and patellar non-resurfacing with denervation. Traditionally, meta-analyses have predominantly focused on examining comparisons between two management modalities. However, this study performed a network meta-analysis to compare all four patellar management interventions to identify the most optimal approach for patellar management in TKA. Methods A computer-based search of PubMed, China National Knowledge Infrastructure (CNKI), The Cochrane Library, Web of science, Embase, and MEDLINE databases was performed to identify randomized controlled trials focusing on the four management interventions for the patella in TKA. Comparisons included two-by-two comparisons as well as those involving more than two concurrent comparisons. The search timeframe spanned from inception to June 30, 2023. Two independent authors extracted the data and evaluated the quality of the literature. The Cochrane Collaboration Risk of Bias (ROB) tool was used to evaluate the overall quality of the literature. Subsequently, a network meta-analysis was conducted using the “gemtc” package of the R-4.2.3 software. Outcome measures such as anterior knee pain (AKP), reoperation rate, and patient satisfaction rate were evaluated using odd ratio (OR) and 95% confidence intervals (CI). Additionally, the knee society score (KSS), function score (FS), and range of motion (ROM) were evaluated using mean differences (MD) with associated 95% CI. The different treatment measures were ranked using the surfaces under the cumulative ranking curves (SUCRA). Results A total of 50 randomized controlled trials involving 9,283 patients were included in the analysis. The findings from this network meta-analysis revealed that patellar resurfacing exhibited significantly lower postoperative reoperation rate (OR 0.44, 95% CI 0.24–0.63) and AKP (OR 0.58, 95% CI 0.32–1) compared to non-resurfacing. Additionally, patellar resurfacing exhibited higher postoperative KSS clinical scores in comparison with non-resurfacing (MD: 1.13, 95% CI 0.18–2.11). However, for postoperative FS, ROM, and patient satisfaction, no significant differences were observed among the four management interventions. Conclusion Patellar resurfacing emerges as the optimal management modality in primary TKA. However, future studies should aim to reduce sources of heterogeneity and minimize the influence of confounding factors on outcomes. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023434418 identifier: CRD42023434418

Abstract Background The long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne infectious diseases (ZVBs) remains uncertain. This study sought to examine the changes in ZVBs in China during the COVID-19 pandemic and predict their future trends. Methods Monthly incidents of seven ZVBs (Hemorrhagic fever with renal syndrome [HFRS], Rabies, Dengue fever [DF], Human brucellosis [HB], Leptospirosis, Malaria, and Schistosomiasis) were gathered from January 2004 to July 2023. An autoregressive fractionally integrated moving average (ARFIMA) by incorporating the COVID-19-associated public health intervention variables was developed to evaluate the long-term effectiveness of interventions and forecast ZVBs epidemics from August 2023 to December 2025. Results Over the study period, there were 1,599,647 ZVBs incidents. HFRS and rabies exhibited declining trends, HB showed an upward trajectory, while the others remained relatively stable. The ARFIMA, incorporating a pulse pattern, estimated the average monthly number of changes of − 83 (95% confidence interval [CI] − 353–189) cases, − 3 (95% CI − 33–29) cases, − 468 (95% CI − 1531–597) cases, 2191 (95% CI 1056–3326) cases, 7 (95% CI − 24–38) cases, − 84 (95% CI – 222–55) cases, and − 214 (95% CI − 1036–608) cases for HFRS, rabies, DF, HB, leptospirosis, malaria, and schistosomiasis, respectively, although these changes were not statistically significant besides HB. ARFIMA predicted a decrease in HB cases between August 2023 and December 2025, while indicating a relative plateau for the others. Conclusions China's dynamic zero COVID-19 strategy may have exerted a lasting influence on HFRS, rabies, DF, malaria, and schistosomiasis, beyond immediate consequences, but not affect HB and leptospirosis. ARFIMA emerges as a potent tool for intervention analysis, providing valuable insights into the sustained effectiveness of interventions. Consequently, the application of ARFIMA contributes to informed decision-making, the design of effective interventions, and advancements across various fields.

The terahertz range, as a type of electromagnetic wave with wavelengths between microwaves and the infrared band, has the characteristics of penetration, low energy and a stable absorption spectrum of specific substances, and is widely used in non-destructive testing, human security inspections, biological tissue diagnoses and military detection. In particular, terahertz wave 3D imaging technology can detect the internal information of the target of detection, and it has become the focus of current research. This study carried out research on 3D reconstruction and object detection algorithms based on terahertz images. In view of the problem that the MVS (Multi-ViewStereo) series of 3D reconstruction algorithms ignore the context information between the cost layers and have unsatisfactory reconstruction effects when used on complex regions, an improved MVSNet 3D reconstruction algorithm FCTMVSNet(Feature and Cost Transformer Depth Inference for Unstructured Multi-view Stereo) based on Transformer is proposed here. A structured object recognition algorithm was designed to provide theoretical support for subsequent terahertz image-based object detection algorithms.

When classifying breeds of dogs, the accuracy of classification significantly affects breed identification and dog research. Using images to classify dog breeds can improve classification efficiency; however, it is increasingly challenging due to the diversities and similarities among dog breeds. Traditional image classification methods primarily rely on extracting simple geometric features, while current convolutional neural networks (CNNs) are capable of learning high-level semantic features. However, the diversity of dog breeds continues to pose a challenge to classification accuracy. To address this, we developed a model that integrates multiple CNNs with a machine learning method, significantly improving the accuracy of dog images classification. We used the Stanford Dog Dataset, combined image features from four CNN models, filtered the features using principal component analysis (PCA) and gray wolf optimization algorithm (GWO), and then classified the features with support vector machine (SVM). The classification accuracy rate reached 95.24% for 120 breeds and 99.34% for 76 selected breeds, respectively, demonstrating a significant improvement over existing methods using the same Stanford Dog Dataset. It is expected that our proposed method will further serve as a fundamental framework for the accurate classification of a wider range of species.

‘Akizuki’ pear (Pyrus pyrifolia Nakai) corky disease is a physiological disease that strongly affects the fruit quality of ‘Akizuki’ pear and its economic value. In this study, Raman spectroscopy was employed to develop an early diagnosis model by integrating support vector machine (SVM), random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and convolutional neural network (CNN) modeling techniques. The effects of various pretreatment methods and combinations of methods on modeling results were studied. The relative optimal index formula was utilized to identify the SG and SG+WT as the most effective preprocessing methods. Following the optimal preprocessing method, the performance of the majority of the models was markedly enhanced through the process of model reconditioning, among which XGBoost achieved 80% accuracy under SG+WT pretreatment, and F1 and kappa both performed best. The results show that RF, GBDT, and XGBoost are more sensitive to the pretreatment method, whereas SVM and CNN are more dependent on internal parameter tuning. The results of this study indicate that the early detection of Raman spectroscopy represents a novel approach for the nondestructive identification of asymptomatic ‘Akizuki’ pear corky disease, which is of paramount importance for the realization of large-scale detection across orchards.

Abstract Background To predict the microvascular invasion (MVI) in patients with cHCC-ICC. Methods A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. Results The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p

The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19. The complete contents of RCoV19 are available to the public at https://ngdc.cncb.ac.cn/ncov/.

Abstract To explore the clinical role of QPRT in breast cancer. The gene expression, methylation levels and prognostic value of QPRT in breast cancer was analyzed using TCGA data. Validation was performed using the data from GEO dataset and TNMPLOT database. Meta analysis method was used to pool the survival data for QPRT. The predictive values of QPRT for different drugs were retrieved from the ROC plot. The expression differences of QPRT in acquired drug-resistant and sensitive cell lines were analyzed using GEO datasets. GO and KEGG enrichment analysis were conducted for those genes which were highly co-expressed with QPRT in tissue based on TCGA data and which changed after QPRT knockdown. Timer2.0 was utilized to explore the correlation between QPRT and immune cells infiltration, and the Human Protein Atlas was used to analyse QPRT’s single-cell sequencing data across different human tissues. The expression of QPRT in different types of macrophages, and the expression of QPRT were analysed after coculturing HER2+ breast cancer cells with macrophages. Additionally, TargetScan, Comparative Toxicogenomics and the connectivity map were used to research miRNAs and drugs that could regulate QPRT expression. Cytoscape was used to map the interaction networks between QPRT and other proteins. QPRT was highly expressed in breast cancer tissue and highly expressed in HER2+ breast cancer patients (P

Abstract Background Sentinel lymph node biopsy (SLNB) is a common choice for axillary surgery in patients with early‐stage breast cancer (BC) who have clinically negative lymph nodes. Most research indicates that obesity is a prognostic factor for BC patients, but studies assessing its association with the rate of positive sentinel lymph nodes (SLN) and the prognosis of patients with early BC undergoing SLNB are limited. Methods Between 2013 and 2016, 7062 early‐stage BC patients from the Shanghai Cancer Center of Fudan University were included. Based on the Chinese Body Mass Index (BMI) classification standards, the patients were divided into three groups as follows: normal weight, overweight, and obese. Propensity score matching analysis was used to balance the baseline characteristics of the participants. Logistic regression analysis was used to determine the association between obesity and positive SLN rate. Cox regression analysis was used to investigate whether obesity was an independent prognostic factor for early‐stage BC patients who had undergone SLNB. Results No significant association was observed between obesity and positive SLN rate in early‐stage BC patients who had undergone SLNB. However, multivariate analysis revealed that compared to patients with normal BMI, the overall survival (hazard ratio (HR) 2.240, 95% confidence interval (CI) 1.27–3.95, p = 0.005) and disease‐free survival (HR 1.750, 95% CI 1.16–2.62, p = 0.007) were poorer in patients with high BMI. Conclusion Obesity is an independent prognostic factor for early‐stage BC patients who undergo SLNB; however, it does not affect the positive SLN rate.

Summary: Cardiac dysfunction, an early complication of endotoxemia, is the major cause of death in intensive care units. No specific therapy is available at present for this cardiac dysfunction. Here, we show that the N-terminal gasdermin D (GSDMD-N) initiates mitochondrial apoptotic pore and cardiac dysfunction by directly interacting with cardiolipin oxidized by complex II-generated reactive oxygen species (ROS) during endotoxemia. Caspase-4/11 initiates GSDMD-N pores that are subsequently amplified by the upregulation and activation of NLRP3 inflammation through further generation of ROS. GSDMD-N pores form prior to BAX and VDAC1 apoptotic pores and further incorporate into BAX and VDAC1 oligomers within mitochondria membranes to exacerbate the apoptotic process. Our findings identify oxidized cardiolipin as the definitive target of GSDMD-N in mitochondria of cardiomyocytes during endotoxin-induced myocardial dysfunction (EIMD), and modulation of cardiolipin oxidation could be a therapeutic target early in the disease process to prevent EIMD.

IntroductionThe use of online follow-up services (OFUS) is becoming an increasingly important supplement to hospital care. Through OFUS, patients can find their doctors in online health communities (OHCs) and receive remote medical follow-ups after hospital treatment. However, the rate of effective use of OFUS by current patients is still low, and there is an urgent need for research to investigate the online information factors that affect patients' effective use of OFUS.MethodsBased on the elaboration likelihood model (ELM) of persuasion and an analysis of a panel dataset including 3,672 doctors in a leading OHC in China, this study explores how online information from doctors' knowledge contributions and patient feedback influences patients' effective use of OFUS.ResultsThe results show that both doctors' knowledge contributions and patient feedback positively influence patients' effective use of OFUS. Doctors' paid knowledge contributions and patients' paid feedback have stronger persuasive effects than doctors' free knowledge contributions and patients' free feedback, respectively. Moreover, there is a substitutional relationship between doctors' paid and free knowledge contributions and between patients' paid and free feedback in influencing patients' effective use of OFUS.DiscussionThe findings of this study suggest that OHC platforms and healthcare providers should account not only for the persuasive effects of doctors' knowledge contributions and patient feedback but also for influential differences and relationships between the types of doctors' knowledge contributions and patient feedback to better persuade patients to effectively use OFUS.