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In recent years, the prevalence of Many-Objective Optimization Problems (MaOPs) in practical applications has been increasing. However, traditional multi-objective optimization algorithms, such as Multiple Objective Particle Swarm Optimization (MOPSO), often face challenges of dimensionality and selection pressure when handling MaOPs. To overcome these challenges, this study proposes a Convergence-Driven Adaptive Many-Objective Particle Swarm Optimization (CDA-MOPSO) algorithm. This algorithm introduces a convergence metric to assess the convergence status and solution distribution quality of the particle swarm during iterations. Based on this metric, Convergence-Aware Learning Factor Adjustment (CALFA), Convergence-Oriented Dimension Variation Strategy (CODVS), and Convergence-Driven Archive Maintenance (CDAM) operations are proposed. Additionally, evolutionary search is further conducted on the external archive to enhance algorithm performance. To validate the performance of the CDA-MOPSO algorithm, extensive experiments are conducted using standard test problems such as DTLZ and WFG. Experimental results demonstrate that the CDA-MOPSO algorithm exhibits superior convergence and solution distribution characteristics across multiple standard test functions, particularly in handling many-objective optimization problems, outperforming traditional multi-objective algorithms significantly. In conclusion, the CDA-MOPSO algorithm provides a novel solution for many-objective optimization problems, offering strong convergence capability and solution diversity, with broad prospects for practical applications.

Abstract Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.

Abstract Liposarcoma (LPS) is the second most common kind of soft tissue sarcoma, and a heterogeneous malignant tumor derived from adipose tissue. Up to now, the prognostic value of BAG1 or BAG2 in LPS has not been defined yet. Expression profiling data of LPS patients were collected from TCGA and GEO database. Survival curves were plotted to verify the outcome differences of patients based on BAG1 or BAG2 expression. Univariate and multivariate Cox regression models were used to analyze the prognostic ability of BAG1 or BAG2. Chaperone’s regulators BAG1 and BAG2 were identified as prognostic biomarkers for LPS patients, which exhibited distinct expression patterns and survival outcome prediction performances. Patients with high BAG2 expression and/or low BAG1 expression had worse prognosis. Enrichment analysis showed that BAG1 was involved in negative regulation of TGF-β signaling. Low expression of BAG1 was associated with high abundance of regulatory T cells (Tregs). The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.

Abstract Background Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years. Methods In this study, models of CA10 infection were established in 7‐day‐old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10. Results After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA‐sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up‐regulated DEGs in muscle were enriched in immune‐related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll‐like receptor pathway and the nucleotide‐binding and oligomerization domain (NOD)‐like pathway. Conclusions Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.

Abstract Ultrahigh-voltage electricity systems are a vital part of energy networks, often across wide regions passing through mountainous terrains. The instability of slopes forming tower foundations along transmission lines poses a large risk to the entire energy network. Moreover, the tower foundations along extra-high-voltage electricity transmission lines are a very special type of element that are also highly vulnerable to landslides. In this study, an integrative risk assessment framework, including a hazard assessment, vulnerability analysis for the specified element at risk, and consequence estimation, is proposed to quantify the direct and indirect risks of landslides to power transmission lines. The Yanzi landslide, where a tower of the major ultrahigh-voltage transmission line from Sichuan (western China) to Shanghai (eastern China) has just been constructed, is taken as a case study. The correlation between landslide displacement and tower structure tilting is studied. In terms of the precipitation return period, factors of safety, failure probability, and deformation are simulated. A physical vulnerability curve is fitted by assuming a Weibull relationship between the horizontal deformation (hazard intensity) of the landslide and the tower inclination ratio. The total risk is calculated as the sum of the direct and indirect losses, among which the potential indirect risk due to tower damage is much greater than the direct risk. This work demonstrates the importance of landslide treatment strategies along electricity transmission lines by considering the potential indirect risks. The risk assessment model of landslides affecting ultrahigh-voltage electricity transmission lines proposed in this study could be useful for other types of indirect landslide risk evaluations.

Abstract To explore a method to identify the sensory and motor fascicles of the peripheral nerve to achieve accurate peripheral nerve functional fascicle suture. The peripheral nerve Sunderland V injury model, muscle branch of the femoral nerve and saphenous nerve were established in the bilateral femoral nerves of Sprague-Dawley (SD) rats. The specific samples were grouped as follows: the main trunk of the femoral nerve was exposed bilaterally and cut with microscopic scissors in the main trunk of the femoral nerve to prepare a model of Sunderland V injury in the mixed fascicle of peripheral nerves; the muscle branch of the femoral nerve was exposed bilaterally and cut in the middle section of the muscle branch of the femoral nerve to prepare a model of Sunderland V injury in the motor fascicle of peripheral nerves; the saphenous nerve was exposed bilaterally and cut at 1 cm below the patella to prepare a model of Sunderland V injury to the sensory fascicle of the peripheral nerves. A carbon quantum dot (CD)-annexin V antibody complex was prepared and applied to the distal and proximal nerve stumps of the peripheral nerve Sunderland V injury model groups of SD rats. Under the excitation light source of a 380 nm uv lamp, fluorescence color development was observed under a fluorescence microscope after 5, 10, 15, and 20 min. At 5 min, sections of the bilateral femoral nerve trunk, muscular branches of the femoral nerve, and Sunderland V lesion of the saphenous nerve in SD rats were only dark in color under the microscope, and there was no difference in fluorescence. The intensity of the staining increased significantly for 10–20 min. The sensory fascicles and saphenous nerves of the femoral nerve trunk showed blue fluorescence under the CD-Annexin V antibody complex staining, while the motor fascicles and muscle branches of the femoral nerve trunk showed no fluorescence. Fluorescence intensity gradually decreased after 20 min of staining. There was no significant difference in the staining intensity at 5, 10, 15, and 20 min in each group. Our results suggest that the CD-Annexin antibody complex can be used to identify functional fascicles of peripheral nerves in SD rats.

The Traditional Chinese Medicine compound preparation known as Diwu Yanggan capsule (DWYG) can effectively hinder the onset and progression of hepatocellular carcinoma (HCC), which is recognized worldwide as a significant contributor to fatalities associated with cancer. Nevertheless, the precise mechanisms implicated have remained ambiguous. In present study, the model of HCC was set up by the 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH) in rats. To confirm the differentially expressed genes (DEGs) identified in the microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted. In the meantime, the liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was employed to characterize the component profile of DWYG. Consequently, the DWYG treatment exhibited the ability to reverse 51 variation genes induced by 2-AAF/PH. Additionally, there was an overlap of 54 variation genes between the normal and model groups. Upon conducting RT-qPCR analysis, it was observed that the expression levels of all genes were increased by 2-AAF/PH and subsequently reversed after DWYG treatment. Notably, the fold change of expression levels for all genes was below 0.5, with 3 genes falling below 0.25. Moreover, an investigation was conducted to determine the signaling pathway that was activated/inhibited in the HCC group and subsequently reversed in the DWYG group. Moreover, the component profile of DWYG encompassed a comprehensive compilation of 206 compounds that were identified or characterized. The findings of this study elucidated the potential alleviative mechanisms of DWYG in the context of HCC, thereby holding significant implications for its future clinical utilization and widespread adoption.

When the fault in a focal area enters the critical state, nonlinear accelerated deformation and disturbance changes may occur during tide-induced loading and unloading. In this study, the anomalies in the Korla volumetric strain caused by earth tide were investigated using a theoretical model of tidal force. Results show that the step changes in the Korla volumetric strain may be triggered by tidal force within a short time frame, ranging from a few to tens of days, prior to a moderate earthquake. The azimuthal angles at the time of step changes are mainly distributed in the ranges of 124–158° and 185–228°, and the azimuth angle at the time of many nearby medium-to-strong earthquakes occurring in this step concentration area, suggesting that the step anomalies in the Korla volumetric strain are closely related to the horizontal tide-induced force in a specific direction. Using the Schuster method, it was found that the tide-induced azimuth angle of the step changes occurred mostly at the minimum value of the solid tide, providing evidences of the modulation of the solid tide. These results may present new ideas for using crustal deformation observations for short-term earthquake predictions.

The sub-instability refers to a stress state that exists between the maximum stress the rock can withstand and its final failure. This stress state should be an indicator of impending large earthquakes, as it occurs in the final stage of earthquake nucleation. We apply the Load/Unload Response Ratio (LURR) method to explore sub-instability in the source media before large earthquakes. The earthquake-related observation data such as the groundwater, crustal deformation, electromagnetism and so on were adopted as data input. The load and unload phases at each observation station are discriminated by the change of Coulomb failure stress caused by earth tides along the tectonically optimal sliding direction. Retrospective studies of this approach on the 2020 Mw6.0 Jiashi, Xinjiang, 2022 Mw6.6 Menyuan, Qinghai, and Mw6.6 Luding, Sichuan earthquakes show that the LURR time series derived from the observation stations near the epicenter exceed 2 standard deviations of the mean within several days to years before the mainshocks. Additionally, as the time of mainshock approaches, the distance between the stations detecting LURR anomaly and epicenter decreases. The LURR anomalies indicate the presence of sub-instability prior to a large earthquake, and their spatio-temporal evolution may suggest the weakening processes in the source media.

Previous studies on landslide susceptibility (LS) and hazard (LH) assessments have overlooked a crucial measure for evaluating validation effectiveness, which involves the use of post-temporal landslide inventories instead of solely relying on historical data. Therefore, this study constructed a regional LH prediction and validation framework at different timescales using the landslide data from 2002 to 2021. Firstly, based on updated landslide data and conditioning factors, the datasets for susceptibility modelling were built for various periods. Then, the performances of traditional ma chine learning, ensemble and deep learning models were compared. Finally, the multi-period rainfall data and susceptibility results were used in innovative LH forecasting. Our study results show that the ensemble learning model (random forest) has stronger generalisation ability in different time periods, with all Area Under Curve (AUC) values exceeding 0.9. The hazard modelling framework based on rainfall erosion intensity and susceptibility can effectively forecast LH, and the shortened timescale for rainfall erosion intensity can improve the accuracy of LH forecasting. At the very high hazard level, the percentage of landslides forecast increased from 25.23% to 42.86%. This study comprehensively explores spatio-temporal dynamic changes in LH, accurately identifying areas posing threats to the National Transmission Line Protection Regions (NTLPR).

Abstract Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single‐cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular‐stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.

Objectives The purpose of this review is to summarise the evidence from a systematic review and meta-analysis of observational studies that objectively measure daily steps and health outcomes.Design This is an umbrella review.Data sources PubMed, Embase, Scopus, the Cochrane Library and Web of Science databases were searched through 31 January 2024.Eligibility We included systematic reviews of observational studies (with or without meta-analysis) that assessed the association of objectively measured daily steps with human health-related outcomes. Methodological quality was assessed using ‘A MeaSurement Tool to Assess systematic Reviews 2’.Results A total of 10 systematic reviews and 6 health outcomes were included after excluding irrelevant and duplicate studies. Higher daily steps were associated with more benefits than harms for a range of health-related outcomes, including all-cause mortality, cardiovascular event, skeletal muscle lesions, metabolic diseases and respiratory disease. A dose-response analysis showed that an increase of 500–1000 steps per day was associated with lower all-cause mortality and cardiovascular events. Beneficial associations were also found in patients with asthma and acutely hospitalised older adults. Conversely, one study within a systematic review suggested that higher daily steps (≥10 000) might be associated with an increased 52% risk of meniscal pathologies in individuals without knee osteoarthritis. However, one study within a systematic review suggested a potential increased risk of meniscal pathologies in individuals without knee osteoarthritis. Specifically, those exceeding 10 000 steps per day showed a 52% increase in risk.Conclusion The results of this study suggest that daily steps are associated with a lower risk of all-cause mortality and cardiovascular events. Future research could focus on identifying specific populations that may benefit most from increased daily steps and exploring potential mechanisms to enhance our understanding of how daily steps contribute to improved health outcomes.PROSPERO registration number CRD42022347055.

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway allergic disease may not be a high-risk factor, but may be a protective factor for COVID-19 infection, which is closely related to its low-level expression of the ACE2 receptor and the complex cytokines network as underlying molecular regulatory mechanisms. In addition, steroid hormones and age factors could not be ignored. In this review, we have summarized some current evidence on the relationship between COVID-19 and allergic rhinitis to highlight the underlying mechanisms of COVID-19 infection and provide novel insights for its prevention and treatment. The key findings show that allergic rhinitis and its related molecular mechanisms may have a protective effect against COVID-19 infection.

The use of satellite imagery for surface deformation monitoring has been steadily increasing. However, the study of extracting deformation slopes from deformation data requires further advancement. This limitation not only poses challenges for subsequent studies but also restricts the potential for deeper exploration and utilization of deformation data. The LT-1 satellite, China’s largest L-band synthetic aperture radar satellite, offers a new perspective for monitoring. In this study, we extracted deformation slopes in Chongqing and its surrounding areas of China based on deformation data generated by LT-1. Twelve factors were selected to analyze their influence on slope deformation, including elevation, topographic position, slope, landcover, soil, lithology, relief, average rainfall intensity, and distances to rivers, roads, railways, and active faults. A total of 5863 deformation slopes were identified, covering an area of 140 km2, mainly concentrated in the central part of the study area, with the highest area density reaching 0.22%. Among these factors, average rainfall intensity was found to have the greatest impact on deformation slope. These findings provide valuable information for geological disaster early warning and management in Chongqing and surrounding areas, while also demonstrating the practical value of the LT-1 satellite in deformation monitoring.

Abstract Background Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. Methods The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein–protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. Results 60 lipid metabolic genes differentially expressed in early AD patients’ cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. Conclusions AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Abstract Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

Waves generated by a horizontally moving disturbance on the seabed have been studied by developing two numerical models, namely, the Navier–Stokes and the Green–Naghdi equations. Various geometries of the bottom disturbances are considered, and waves generated due to a single motion and multiple oscillatory motions of the bottom disturbances are investigated by the two models. Discussion is provided on how the motion of the disturbance on the seafloor results in the generation of surface waves. The wave-field parameters investigated include the surface elevation, velocity, pressure fields and wave celerity. A parametric study is conducted to assess the effect of the geometry of the disturbance and the kinematic characteristics on the wave generation. It is shown that both linear and nonlinear waves can be generated by a horizontally moving disturbance on the seabed. Long waves, followed by a series of dispersive waves, are produced by the single motion of the bottom disturbance. It is also found that, under appropriate conditions, there would be a balance between nonlinearity and dispersion, such that the generated waves propagate over a flat seafloor with little to no change in their form and shape.

The development of immunoprophylactic products against respiratory syncytial virus (RSV) has resulted in notable advancements, leading to an increased demand for preclinical experiments and placing greater demands on animal models. Nevertheless, the field of RSV research continues to face the challenge of a lack of ideal animal models. Despite the demonstration of efficacy in animal studies, numerous RSV vaccine candidates have been unsuccessful in clinical trials, primarily due to the lack of suitable animal models. The most commonly utilized animal models for RSV research are cotton rats, mice, lambs, and non-human primates. These animals have been extensively employed in mechanistic studies and in the development and evaluation of vaccines and therapeutics. However, each model only exemplifies some, but not all, aspects of human RSV disease. The aim of this study was to provide a comprehensive summary of the disease symptoms, viral replication, pathological damage, and enhanced RSV disease (ERD) conditions across different RSV animal models. Furthermore, the advantages and disadvantages of each model are discussed, with the intention of providing a valuable reference for related RSV research.

Abstract Prostate cancer (PC) is one of the most common cancers in men and becoming the second leading cause of cancer fatalities. At present, the lack of effective strategies for prognosis of PC patients is still a problem to be solved. Therefore, it is significant to identify potential gene signatures for PC patients’ prognosis. Here, we summarized 71 different prognostic gene signatures for PC and concluded 3 strategies for signature construction after extensive investigation. In addition, 14 genes frequently appeared in 71 different gene signatures, which enriched in mitotic and cell cycle. This review provides extensive understanding and integrated analysis of current prognostic signatures of PC, which may help researchers to construct gene signatures of PC and guide future clinical treatment.

In this paper, we analyze the transient behavior of nonlinear magneto-optical rotation in a 87Rb vapor cell. Our focus is on optimizing the optical rotation signal by identifying influential factors. We investigate the impact of cell temperature on alkali atom density and consider characteristics of the light field, such as polarization direction, frequency, intensity, and beam diameter. Low scanning magnetic field rates produce the usual absorption signal, whereas high rates show an asymmetric transient response with oscillatory decay. To further investigate this phenomenon, we evaluate signal amplitude and resonant peaks along the x-, y-, and z-axis directions. Notably, we establish a one-dimensional quadratic equation that describes the relationship between magnetic field scan rate and signal amplitude/peak value. Our findings facilitate the quick evaluation of cell performance, provide insights into the dynamics of ground-state coherence generation, and have potential applications in detecting transient spin coupling or monitoring magnetic fields.

Purpose. Specific retinal abnormalities of neurofibromatosis type 2 (NF2) commonly include retinal astrocytoma and combined hamartoma of the retina and retinal pigment epithelium. Vasculopathy is an uncommon manifestation of NF2. We reported an NF2 patient presenting with retinal ischemia. Observations. An 18-year-old healthy Chinese female with acute decreased vision. The fundus examination and optical coherence tomography revealed optic disc hamartoma in the right eye and paracentral acute middle maculopathy (PAMM) and cotton wool spot indicating retinal ischemia in the left eye. Brain MRI showed bilateral acoustic neuroma, parasellar meningioma, and cervical extramedullary tumor. The genetic test confirmed the diagnosis of NF2. Conclusions and Importance. Our case suggests that retinal ischemia could be the presenting sign of NF2. NF2 could be associated with retinal vasculopathy in addition to retina tumors.

Abstract Despite extensive research on astrocytic Ca2+ in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains largely unknown. Here, by using two-photon microscopy and whole-cell recordings, we show two distinct astrocytic Ca2+ signals in the murine barrel cortex: a small, long-lasting Ca2+ increase during sleep and a large, widespread but short-lasting Ca2+ spike when aroused. The large Ca2+ wave in aroused mice was inositol trisphosphate (IP3)-dependent, evoked by the locus coeruleus-norepinephrine system, and enhanced sensory input, contributing to reliable sensory transmission. However, the small Ca2+ transient was IP3-independent and contributed to decreased extracellular K+, hyperpolarization of the neurons, and suppression of sensory transmission. These events respond to different pharmacological inputs and contribute to distinct sleep and arousal functions by modulating the efficacy of sensory transmission. Together, our data demonstrate an important function for astrocytes in sleep and arousal states via astrocytic Ca2+ waves.

Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A10 (CA10), and Coxsackievirus A6 (CA6). The high pathogenicity of HFMD has garnered significant attention. Currently, there is no specific treatment or broad-spectrum preventive measure available for HFMD, and existing monovalent vaccines have limited impact on the overall incidence or prevalence of the disease. Consequently, with the emergence of new viral strains driven by vaccine pressure, there is an urgent need to develop strategies for the rapid response and control of new outbreaks. In this study, we demonstrated the broad protective effect of maternal antibodies against three types of HFMD by immunizing mother mice with a trivalent inactivated vaccine targeting EV71, CA16, and CA10, using a neonatal mouse challenge model. Based on the feasibility of maternal antibodies as a form of passive immunization to prevent HFMD, we prepared a multivalent antiviral milk by immunizing dairy cows with the trivalent inactivated vaccine to target multiple HFMD viruses. In the neonatal mouse challenge model, this immunized milk exhibited extensive passive protection against oral infections caused by the three HFMD viruses. Compared to vaccines, this strategy may offer a rapid and broadly applicable approach to providing passive immunity for the prevention of HFMD, particularly in response to the swift emergence and spread of new variants.

Abstract Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

In this paper, we propose a three-axis atomic magnetometer (AM), in which one light beam is divided into two orthogonal spatially separated pump beams by a lateral displacement polarized beam splitter and reflector mirrors; this scheme suppresses the three-axis crosstalk caused by the interaction between the two beams and atoms in the cell. When the AM operates in the direct-current (DC) mode, the three-axis crosstalk is significant. To solve this problem, three modulation fields with the same amplitudes, frequencies, and different phases are applied, which allow the AM operated in modulation mode to perform a highly sensitive synchronous and independent measurement of the three-axis magnetic field with low crosstalk. The experimental results showed that the three-axis crosstalk was less than 2%. In the modulation mode, the sensitivities were 22, 23, and 26 fT/Hz1/2 on the x-, y-, and z-axes, respectively. The 3-dB bandwidths of the three axes were 126, 124, and 112 Hz. In addition, we demonstrated a three-axis in-situ magnetic compensation method with a magnetic compensation accuracy of the pT level in the DC mode. The proposed triaxial AM can be easily miniaturized and used in biomedical applications, such as in magnetocardiography and magnetoencephalography.

Abstract It has been reported that schizophrenia (SCZ) and inflammatory bowel disease (IBD) are related. However, whether there is a bidirectional interaction between them remains unclear. The aim of this study was to conduct a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationship between SCZ and IBD and its subtypes, including Crohn’s disease (CD) and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) extracted from the summary data of genome-wide association studies were used as genetic instruments. MR was performed using the inverse-variance-weighted method. The MR-Egger and weighted median methods were used for sensitivity analyses. Analysis using 70 SNPs as genetic instruments showed that SCZ was associated with an increased risk of IBD (OR = 1.14, 95% CI: 1.09–1.20, P = 9.21 × 10−8), CD (OR = 1.16, 95% CI: 1.07–1.25, P = 1.42 × 10−4), and UC (OR = 1.14, 95% CI: 1.07–1.21, P = 2.72 × 10−5). The results of the sensitivity analyses were robust and no evidence of pleiotropy was observed. Bidirectional MR analyses showed no causal effects of IBD, CD, or UC on SCZ. This study suggests that SCZ has causal effects on IBD and its subtypes, whereas IBD has no effect on SCZ. Brain-gut axis interactions may help clarify the causal relationship between SCZ and IBD. However, further studies are needed to elucidate the biological mechanisms behind the brain-gut interactions.

Background Previous studies found an association between self‐reported sleep duration and mortality. This study aimed to compare the effects of objective and self‐reported sleep duration on all‐cause and cardiovascular disease (CVD) mortality. Methods and Results A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in‐home polysomnography records, and self‐reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self‐reported sleep duration with all‐cause and CVD mortality. During a mean follow‐up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All‐cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all‐cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J‐shaped association of self‐reported sleep duration on both weekdays and weekends with all‐cause and CVD mortality. Self‐reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all‐cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self‐reported sleep duration. Conclusions This study showed that both objective and self‐reported sleep duration were associated with all‐cause and CVD mortality, but with different characteristics. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00005275; Unique identifier: NCT00005275.

The bolted joints exhibit typical nonlinear hysteresis under tangential loading, and the deviations of the preload in the bolt group add to the complexity of the model describing this behavior. In this paper, based on the mechanical analysis of the bolt group, a new methodology for predicting hysteresis behavior under non-uniform preload was proposed. Firstly, based on the moment equilibrium within the framework of material mechanics and the tangential stiffness model of the joint interface, a new coordination equation of displacement and force between the bolted joints was deduced, which could realize the calculation of the bolt group loading curve. Then, the PCOM (Preload Co-Occurrence Matrix) was constructed considering the arrangement of the joints, and the indices related to the spatial distribution of the preload were extracted from PCOM. The results of GCA (Grey Correlation Analysis) showed that the indices of PCOM were closely related to the hysteresis behavior of the bolt group. Finally, the prediction of energy dissipation could be realized by using the indices extracted from PCOM and the SVM(Support Vector Machine) regression model. The prediction results were in good agreement with the simulation and experiment, which verified the validity of the methodology proposed in this paper.

Displacement prediction of transmission towers is essential for the early warning of transmission network deformation. However, there is still a lack of prediction on the ground subsidence of the tower foundation. In this study, we first used the multi-temporal interferometric synthetic aperture radar (MT-InSAR) approach to acquire time series deformation for the transmission lines in the Salt Lake area. Based on the K-shape clustering method and field investigation results, towers #95 and #151 with representative foundation deformation characteristics were selected for displacement prediction. Combined with field investigations and the characteristics of saline soil in the Salt Lake area, the trigger factors of transmission tower deformation were analyzed. Then, the displacement and trigger factors of the transmission tower were decomposed by variational mode decomposition (VMD), which could closely connect the characteristics of the foundation saline soil with the influence of the trigger factors. To analyze the contribution of each trigger factor, the maximum information coefficient (MIC) was quantified, and the best choice was made. Finally, the hyperparameters of the long short-term memory (LSTM) neural networks were optimized using a convolutional neural network (CNN) and the grey wolf optimizer (GWO). The findings reveal that the refined deep learning models outperform the initial model in generalization potential and prediction precision, with the CNN–LSTM model demonstrating the highest accuracy in predicting the total displacement of tower #151 (RMSE and R2 for the validation set are 0.485 and 0.972, respectively). Given the scant research on the multifactorial influence on the ground subsidence displacement of transmission towers, this study’s methodology offers a novel perspective for monitoring and early warning of ground subsidence disasters in transmission networks.

The purpose of this work is to investigate the responses of multiple parameters to the Madoi earthquake preparation. A new method is employed to extract anomalies in a geomagnetic field. The results show that there were abnormal changes in the lithosphere, atmosphere, and ionosphere near the epicenter before the earthquake. Despite the differences in spatial and temporal resolutions, the increase in geomagnetic residuals in the lithosphere exhibits similar temporal characteristics to the enhancement of thermal infrared radiation in the atmosphere. Two high–value regions are present in the ground–based geomagnetic high residuals and the ionospheric disturbances. The northern one is around the epicenter of the Madoi earthquake. Near the southern one, an M6.4 Yangbi earthquake occurred four hours before the Madoi earthquake. In this study, we have observed almost all of the physical phenomena that can occur during the preparation of an earthquake, as predicted using the electrostatic channel model. It can be inferred that the electrostatic channel is a possible mechanism for coupling between the lithosphere, atmosphere, and ionosphere during the Madoi earthquake.

Abstract Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus, leading to more serious respiratory diseases during this winter. However, the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear. Using a mammalian model, sequential infection was performed in ferrets and in K18-hACE2 mice, with SARS-CoV-2 infection following H1N1. We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19, and enhanced pulmonary damage, but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets. Moreover, mortality was increased in sequentially infected mice compared with single-infection mice. Compared with single-vaccine inoculation, co-inoculation of PiCoVacc (a SARS-CoV-2 vaccine) and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses. Combined immunization effectively protected K18-hACE2 mice against both H1N1 and SARS-CoV-2 infection. Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2, which together notably enhanced pneumonia in ferrets and mice, as well as demonstrated that simultaneous vaccination against H1N1 and SARS-CoV-2 may be an effective prevention strategy for the coming winter.

Abstract Computer vision recognition refers to the use of cameras and computers to replace the human eyes with computer vision, such as target recognition, tracking, measurement, and in-depth graphics processing, to process images to make them more suitable for human vision. Aiming at the problem of combining basketball shooting technology with visual recognition motion capture technology, this article mainly introduces the research of basketball shooting technology based on computer vision recognition fusion motion capture technology. This paper proposes that this technology first performs preprocessing operations such as background removal and filtering denoising on the acquired shooting video images to obtain the action characteristics of the characters in the video sequence and then uses the support vector machine (SVM) and the Gaussian mixture model to obtain the characteristics of the objects. Part of the data samples are extracted from the sample set for the learning and training of the model. After the training is completed, the other parts are classified and recognized. The simulation test results of the action database and the real shot video show that the support vector machine (SVM) can more quickly and effectively identify the actions that appear in the shot video, and the average recognition accuracy rate reaches 95.9%, which verifies the application and feasibility of this technology in the recognition of shooting actions is conducive to follow up and improve shooting techniques.

By using the normal and tangential forces measured in experiments of granular flow impact against a retaining wall, the effective interface friction angle of the wall was calculated in the dynamic phase and the static phase respectively, designated as δec and δes, and both of them are smaller than the interface friction angle measured by laboratory test (δ2). It is found δec shows an increasing trend against inclination angle (β), which is opposite to that of δes; and δec has an underestimation of effective interface friction angle. By comparing the calculated normal forces of static phase and of dynamic phase with the measured values, it is found the lower bound relation between δes/δ2 and β obtained from regression analysis could well calibrate the effective interface friction angle for both the wall and flume base. It is also noted that the increasing trend of δec against β may be explained by the higher proportion of gravity-friction force at lower inclination angle, i.e., the higher proportion of drag force at higher inclination angle.

From a variety of yield stress fluid models, an elastoviscoplastic Herschel-Bulkley (EVPHB) model written in 3D is selected and coupled with a Finite Element Method with Lagrangian Integration Points (FEMLIP) to solve boundary value problems with large deformation process. By tracing the historical variables of a material point, it is verified that in a time-independent flow the elastic strain and viscous strain rate could be accurately reproduced by EVPHB model. For a time-dependent flow, because of the addition of elasticity, the EVPHB model makes the material experience a deformation process which is significantly distinctive from that produced by a pure regularized Herschel-Bulkley model. Benchmarks also show that in FEMLIP the yielded and unyielded zones could be easily defined by EVPHB model according to the stress of a material point. Lastly, it is shown that EVPHB model also induces a stress relaxation process for materials under constant strain. The suitability of FEMLIP to model elastoviscoplastic fluid is verified.

The detection of the potential of a larger event immediately after a moderate earthquake is a quite difficult problem. In this work, we devised an approach to determine whether an earthquake is a foreshock to a larger mainshock by evaluating loading/unloading states. This is done by calculating the Coulomb failure stress (CFS) change induced by Earth tides along the tectonically preferred slip direction on the seismogenic fault surface of each of the candidates. The technique is based on the load/unload response ratio (LURR) method, but the determination of the sliding direction of CFS is different, which is derived from the moderate earthquake that has just occurred rather than the assumption from the regional stress setting. Using the approach, we tested since the year 2000 the Ms ≥ 4.0 foreshocks of the Ms ≥ 6.0 earthquakes on the Chinese mainland, and also the earthquake swarms where no subsequent larger mainshocks were expected in the previous 10 years. The former mostly occurred in the loading process, while the latter arose more frequently in a random process. The marked difference indicates that the occurrence of earthquakes during loading may imply the critical state of the seismogenic faults, and the derived stress is more likely to trigger a larger event than that of the earthquakes that occurred during unloading.

Abstract Intelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (PIVW = 9.25 × 10–5). The causal relationship was robust when sensitivity analyses were applied (PMR-Egger = 0.0001, PWeighted median = 6.29 × 10–6, PMR-PRESSO = 0.0007), and repeated analysis yielded consistent result (PIVW = 0.0087). Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

Abstract Background Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. Methods To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. Results The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. Conclusions The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.

In plants, branching is regulated by both hormones and external cues such as light. Here the authors show that in Arabidopsis, the phytochrome A-signaling components FHY3 and FAR1, and SMXL proteins that repress strigolactone signaling, both interact with SPL proteins to control expression of the branching regulator BRC1.

The capillary component and adsorptive component of matric suction differently impact the soil strength. Due to the cavitation effects of pore water, the adsorption effect dominates the behavior of soil when matric suction exceeds the cavitation tension. Based on the binary medium theory, a compression-shear strength model for unsaturated soils considering both capillary effect and adsorption effect is established. Compared with test data, the proposed compression-shear strength model has better prediction performance on the compression-shear strength of soil over a range of wide suction. The soil failure depends both on tension-shear stress and compression-shear stress. The tension-shear coupling mechanism in the soil is first investigated. A concept of closed stress point is introduced to divide the two zones of tension-shear coupling stress and compression-shear stress. According to the compression-shear strength model and tension-shear failure mechanism, the tension-shear and compression-shear joint strength model applicable to plane stress conditions is then established. Compared with test data, the proposed model in this article can better predict the nonlinear strength characteristics of clays and has better applicability. Finally, using the user material subroutine (UMAT), the secondary development of the joint strength model is conducted in ABAQUS and then applied to the slope stability analysis. The calculation results show that the established strength model presents a reasonable description of the development of the tension-shear coupling plastic zone in slope and gives an accurate safety factor.

Summary: Background: Childhood neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS), comprise a major cause of health-related disabilities in children. However, biomarkers towards pathogenesis or novel drug targets are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on ASD, ADHD, and TS using the two-sample Mendelian Randomization (MR) approach. Methods: Genetic associations with 2994 plasma proteins were selected as exposures and genome-wide association data of ASD, ADHD, TS were utilized as outcomes. MR analyses were carried out using the inverse-variance weighted method, and the MR-Egger and weighted median methods were used for sensitivity analysis. Findings: Using single-nucleotide polymorphisms as instruments, the study suggested increased levels of MAPKAPK3 (OR: 1.09; 95% CI: 1.05–1.13; P = 1.43 × 10−6) and MRPL33 (OR: 1.07; 95% CI: 1.04–1.11; P = 5.37 × 10−6) were causally associated with a higher risk of ASD, and increased MANBA level was associated with a lower risk of ADHD (OR: 0.91; 95% CI: 0.88–0.95; P = 8.97 × 10−6). The causal associations were robust in sensitivity analysis, leave-one-out analysis and Multivariable MR, and no pleiotropy was observed. No significant risk protein was identified for TS. Interpretation: The study findings support the idea that the MAPK/ERK signaling pathway and mitochondrial dysfunction are involved in the pathogenesis of ASD, while a deficiency in beta-mannosidase might play a role in the development of ADHD.

Objectives:The purpose of our study was to investigate the effect of objective sleep characteristics on the incidence of depression.MethodsThe participants of our study (1,595 men and 1,780 women with 63.1 ± 10.7 years) were selected from the Sleep Heart Health Study (SHHS) datasets. Depression was defined as the first occurrence between SHHS visit 1 and visit 2. Objective sleep characteristics, including sleep efficiency (SE), wake after sleep onset (WASO), sleep fragmentation index (SFI) and arousal index (ArI), were monitored by polysomnography. Multivariable logistic regression was used to explore the relationship between sleep characteristics and depression.ResultsA total of 248 patients with depression (7.3%) were observed between SHHS visits 1 and 2. After adjusting for covariates, SE (odds ratio [OR], 0.891; 95% confidence interval [CI] 0.811–0.978; P = 0.016) and WASO (OR, 1.021; 95% CI 1.002–1.039; P = 0.026) were associated with the incidence of depression. Moreover, the relationship between SE and depression was more pronounced in men (OR, 0.820; 95% CI 0.711–0.946; P = 0.007) than in women (OR, 0.950; 95% CI 0.838–1.078; P = 0.429) in subgroup analysis (Pinteraction < 0.05).ConclusionsSE and WASO may be markers for the incidence of depression. The association between SE and depression was intensified in men.

Schizophrenia (SCZ) is associated with several immune dysfunctions, including elevated levels of pro-inflammatory cytokines. Microorganisms and their metabolites have been found to regulate the immune system, and that intestinal microbiota is significantly disturbed in schizophrenic patients. To systematically investigate aberrant gut-metabolome-immune network in schizophrenia, we performed an integrative analysis of intestinal microbiota, serum metabolome, and serum inflammatory cytokines in 63 SCZ patients and 57 healthy controls using a multi-omics strategy. Eighteen differentially abundant metabolite clusters were altered in patients displayed higher cytokine levels, with a significant increase in pro-inflammatory metabolites and a significant decrease in anti-inflammatory metabolites (such as oleic acid and linolenic acid). The bacterial co-abundance groups in the gut displayed more numerous and stronger correlations with circulating metabolites than with cytokines. By integrating these data, we identified that certain bacteria might affect inflammatory cytokines by modulating host metabolites, such as amino acids and fatty acids. A random forest model was constructed based on omics data, and seven serum metabolites significantly associated with cytokines and α-diversity of intestinal microbiota were able to accurately distinguish the cases from the controls with an area under the receiver operating characteristic curve of 0.99. Our results indicated aberrant gut-metabolome-immune network in SCZ and gut microbiota may influence immune responses by regulating host metabolic processes. These findings suggest a mechanism by which microbial-derived metabolites regulated inflammatory cytokines and insights into the diagnosis and treatment of mental disorders from the microbial-immune system in the future.

Copy number variation (CNV) is an important genetic mechanism that drives evolution and generates new phenotypic variations. To explore the impact of CNV on chicken domestication and breed shaping, the whole-genome CNVs were detected via multiple methods. Using the whole-genome sequencing data from 51 individuals, corresponding to six domestic breeds and wild red jungle fowl (RJF), we determined 19,329 duplications and 98,736 deletions, which covered 11,123 copy number variation regions (CNVRs) and 2,636 protein-coding genes. The principal component analysis (PCA) showed that these individuals could be divided into four populations according to their domestication and selection purpose. Seventy-two highly duplicated CNVRs were detected across all individuals, revealing pivotal roles of nervous system (NRG3, NCAM2), sensory (OR), and follicle development (VTG2) in chicken genome. When contrasting the CNVs of domestic breeds to those of RJFs, 235 CNVRs harboring 255 protein-coding genes, which were predominantly involved in pathways of nervous, immunity, and reproductive system development, were discovered. In breed-specific CNVRs, some valuable genes were identified, including HOXB7 for beard trait in Beijing You chicken; EDN3, SLMO2, TUBB1, and GFPT1 for melanin deposition in Silkie chicken; and SORCS2 for aggressiveness in Luxi Game fowl. Moreover, CSMD1 and NTRK3 with high duplications found exclusively in White Leghorn chicken, and POLR3H, MCM9, DOCK3, and AKR1B1L found in Recessive White Rock chicken may contribute to high egg production and fast-growing traits, respectively. The candidate genes of breed characteristics are valuable resources for further studies on phenotypic variation and the artificial breeding of chickens.

ObjectivesRapid eye movement (REM) sleep is closely related to all-cause mortality. The aim of this study is to explore the role of REM sleep on the incident heart failure (HF).MethodsWe selected 4490 participants (2480 women and 2010 men; mean age, 63.2 ± 11.0 years) from the Sleep Heart Health Study. HF was identified as the first occurrence during a mean follow-up period of 10.9 years. REM sleep including percentage of REM sleep and total REM sleep time were monitored using in-home polysomnography at baseline. Multivariable Cox regression analysis was utilized to explore the relationship between REM sleep and HF.ResultsIn total, 436 (9.7%) cases of HF were observed during the entire follow-up period. After adjusting for potential covariates, an increased percentage of REM sleep (per 5%) was independently associated with a reduced incidence of HF [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.82–0.94, P < 0.001]. A similar result was also found between total REM sleep time (increased per 5 min) and incident HF (HR 0.97, 95% CI 0.95–0.99, P < 0.001). Moreover, the fourth quartile of both percentage of REM sleep (HR 0.65, 95% CI 0.48–0.88, P = 0.005) and total REM sleep time (HR 0.64, 95% CI 0.45–0.90, P = 0.010) had lower risk of incident HF when compared with the first quartile.ConclusionAn increased percentage of REM sleep and total REM sleep time were associated with a reduced risk of HF. REM sleep may be a predictor of the incident HF.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT00005275].

Rock temperature reflects the adjustment in crustal stress, and the fluctuation of ionospheric electron concentration is closely related to short-term disturbances of the stress field. Their coupling may reveal short-term effects before strong earthquakes. This study explores the rock temperature changes and mechanical-electrical coupling in the lithosphere–ionosphere before the Jiashi Ms6.4 earthquake on 19 January 2020. The observed data were detrended by general polynomial piecewise fitting; three observation points within 150 km of the epicenter were found to show significant temperature fluctuations in the 15 days before the earthquake. The peak occurred synchronously five days before the earthquake, and the variation range was approximately 10−3 orders of magnitude. Five days before the earthquake, the electromagnetic satellite Zhangheng-1 synchronously observed an anomalous electron concentration in orbit near the epicenter, with a maximum value of 2.01 × 1010 m−3. The loading/unloading response ratio (LURR) was calculated using small earthquakes within 100 km of the epicenter; it showed that the large changes in rock temperature and the ionosphere occurred at high LURR, indicating high-stress accumulation in the region. Various anomalies appeared simultaneously and may indicate fault rupture, which may be caused by an acoustic-gravity wave, indicating a synchronous coupling between the lithosphere atmosphere and the ionosphere.

Gut microbiome has been linked to neurogenerative diseases. Here, the authors present a metagenome-wide association study of schizophrenia (SZ) in human cohorts and identify SZ-associated specific gut-brain functional modules and pathways including SCFAs and neurotransmitters.

Image captchas have recently become very popular and are widely deployed across the Internet to defend against abusive programs. However, the ever-advancing capabilities of computer vision have gradually diminished the security of image captchas and made them vulnerable to attack. In this paper, we first classify the currently popular image captchas into three categories: selection-based captchas, slide-based captchas, and click-based captchas. Second, we propose simple yet powerful attack frameworks against each of these categories of image captchas. Third, we systematically evaluate our attack frameworks against 10 popular real-world image captchas, including captchas from tencent.com, google.com, and 12306.cn. Fourth, we compare our attacks against nine online image recognition services and against human labors from eight underground captcha-solving services. Our evaluation results show that (1) each of the popular image captchas that we study is vulnerable to our attacks; (2) our attacks yield the highest captcha-breaking success rate compared with state-of-the-art methods in almost all scenarios; and (3) our attacks achieve almost as high a success rate as human labor while being much faster. Based on our evaluation, we identify some design flaws in these popular schemes, along with some best practices and design principles for more secure captchas. We also examine the underground market for captcha-solving services, identifying 152 such services. We then seek to measure this underground market with data from these services. Our findings shed light on understanding the scale, impact, and commercial landscape of the underground market for captcha solving.