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BackgroundWe performed a network meta-analysis of phase III trials to compare the efficacy and safety of first-line regimens for patients with advanced esophageal squamous cell carcinoma (ESCC).MethodsA systematic review and Bayesian network meta-analysis were conducted by retrieving relevant literature from PubMed, Embase, the Cochrane Library, and the Web of Science. We included published sources of randomized clinical trials comparing immunotherapy combinations for treating advanced ESCC.ResultsWe analyzed seven studies involving eight immunotherapy combinations and 4688 patients. For patients without programmed death-ligand 1 (PD-L1) selection, it was found that the combination of toripalimab and chemotherapy provided better overall survival than chemotherapy alone (hazard ratio = 0.58, 95% confidence interval (CI) 0.43-0.78). Compared with chemotherapy alone, Sintilimab or camrelizumab plus chemotherapy seemed to achieve the best progression-free survival (hazard ratio = 0.56, 95% CI 0.46-0.68). Nivolumab plus chemotherapy appeared to provide the best objective response rate, with significant differences versus chemotherapy alone (odds ratio = 0.49, 95% CI 0.38-0.64). Nivolumab plus ipilimumab resulted in a relatively lower incidence of adverse events of grade ≥3 than other regimens.ConclusionsThe combination of immune checkpoint inhibitors (ICIs) with chemotherapy provided a high probability of more effective treatment in comparison with chemotherapy alone for patients with advanced ESCC. Toripalimab and sintilimab plus chemotherapy were ranked as providing the highest OS and PFS benefit in the first-line setting, respectively.

The detection of apple leaf diseases plays a crucial role in ensuring crop health and yield. However, due to variations in lighting and shadow, as well as the complex relationships between perceptual fields and target scales, current detection methods face significant challenges. To address these issues, we propose a new model called YOLO-Leaf. Specifically, YOLO-Leaf utilizes Dynamic Snake Convolution (DSConv) for robust feature extraction, employs BiFormer to enhance the attention mechanism, and introduces IF-CIoU to improve bounding box regression for increased detection accuracy and generalization ability. Experimental results on the FGVC7 and FGVC8 datasets show that YOLO-Leaf significantly outperforms existing models in terms of detection accuracy, achieving mAP50 scores of 93.88% and 95.69%, respectively. This advancement not only validates the effectiveness of our approach but also highlights its practical application potential in agricultural disease detection.

ObjectivesDepressive symptoms are the most prevalent comorbidity in individuals with obsessive-compulsive disorder (OCD). The objective of this study was to investigate the dynamic characteristics of resting-state neural activities in OCD patients with depressive symptoms.MethodsWe recruited 29 OCD patients with depressive symptoms, 21 OCD patients without depressive symptoms, and 27 healthy controls, and collected data via structural and functional magnetic resonance imaging (fMRI). We analyzed the fMRI results using the dynamic amplitude of low-frequency fluctuation (dALFF) and support vector machine (SVM) techniques.ResultsCompared with OCD patients without depressive symptoms, OCD patients with depressive symptoms exhibited an increased dALFF in the left precuneus and decreased dALFF in the right medial frontal gyrus. The SVM indicated that the integration of aberrant dALFF values in the left precuneus and right medial frontal gyrus led to an overall accuracy of 80%, a sensitivity of 79%, and a specificity of 100% in detecting depressive symptoms among OCD patients.ConclusionTherefore, our study reveals that OCD patients with depressive symptoms display neural activities with unique dynamic characteristics in the resting state. Accordingly, abnormal dALFF values in the left precuneus and right medial frontal gyrus could be used to identify depressive symptoms in OCD patients.

The fragmentation size distribution is an important index to evaluate blasting effect. Based on stress wave theory, a blasting fragmentation distribution model is established, and the key influencing factors were clarified. Then, the distribution characteristics of rock fragmentation in water-coupled blasting and air-coupled blasting were compared and verified by numerical simulation and field test. The results show that the rock blasting fragmentation size is negatively correlated with borehole pressure and unit explosive consumption when blasting rock is determined. The existence of water slows down the attenuation of blasting load, prolongs the duration, and makes the blasting pressure transmitted to hole wall significantly greater than air-coupled one, which is equivalent to increasing the unit explosive consumption. Moreover, the rock fracture development speed and fragmentation degree of water-coupled blasting is significantly higher than air-coupled blasting. Comprehensively determined in same charging parameters, water-coupled blasting compared with air-coupled blasting can improve the degree of rock fragmentation, the average size of rock after blasting is smaller, more uniform particle size distribution. The research results for the control of blasting and optimization of explosive energy utilization have important reference significance.

The E3 enzyme in the UPS pathway is a crucial factor for inhibiting substrate specificity. In Solanaceae, the U-box E3 ubiquitin ligase has a complex relationship with plant growth and development, and plays a pivotal role in responding to various biotic and abiotic stresses. The analysis of the U-box gene family in Solanaceae and its expression profile under different stresses holds significant implications. A total of 116 tobacco NtU-boxs and 56 eggplant SmU-boxs were identified based on their respective genome sequences. Phylogenetic analysis of U-box genes in tobacco, eggplant, tomato, Arabidopsis, pepper, and potato revealed five distinct subgroups (I-V). Gene structure and protein motifs analysis found a high degree of conservation in both exon/intron organization and protein motifs among tobacco and eggplant U-box genes especially the members within the same subfamily. A total of 15 pairs of segmental duplication and 1 gene pair of tandem duplication were identified in tobacco based on the analysis of gene duplication events, while 10 pairs of segmental duplication in eggplant. It is speculated that segmental duplication events are the primary driver for the expansion of the U-box gene family in both tobacco and eggplant. The promoters of NtU-box and SmU-box genes contained cis-regulatory elements associated with cellular development, phytohormones, environment stress, and photoresponsive elements. Transcriptomic data analysis shows that the expression levels of the tobacco and eggplant U-box genes in different tissues and various abiotic stress conditions. Using cultivar Hongda of tobacco and cultivar Yanzhi of eggplant as materials, qRT-PCR analysis has revealed that 15 selected NtU-box genes and 8 SmU-box may play important roles in response to pathogen Ras invasion both in tobacco and eggplant.

In today’s digital age, multi-energy systems (MES) have become an indispensable part of the social infrastructure, providing people with diversified energy support such as electricity, gas, water and so on. However, with the increasing popularity and networking of MES, the network security threats they face are becoming more and more serious, especially the threat of network attacks. This makes it essential to detect attacks on MES and precisely classify attack types in order to establish effective defense strategies. In this paper, a Dual-Head output network attack detection and classification method based on parallel CNN-BiLSTM network is proposed. The method adopts a parallel structure and can process different aspects of information at the same time, speeding up the training and inference process of the whole network, making the system respond more quickly to potential network attacks, and improving real-time and efficiency. The multi-model fusion structure can give full play to the advantages of CNN and BiLSTM in processing different types of data, so that the system can capture attack characteristics more comprehensively in many aspects, and improve the overall detection and classification performance. The dual-head output not only improves the system’s ability to accurately detect attacks, but also can effectively classify different types of attacks in detail, which helps to formulate more targeted defense strategies. In addition, in order to effectively evaluate our proposed method, the network traffic data required for the experiment were collected in an environment very similar to the actual operating environment of a multi-energy system. Finally, the experiment verifies that our method can not only realize effective detection of network attacks, but also accurately classify different types of attacks.

BackgroundDifferences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone.MethodsThe LVA, MI, and SHAM mouse models were used. Echocardiography, Masson’s trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN.ResultsA novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment.ConclusionThe IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.

Soil enzymes play a central role in carbon and nutrient cycling, and their activities can be affected by drought-induced oxygen exposure. However, a systematic global estimate of enzyme sensitivity to drought in wetlands is still lacking. Through a meta-analysis of 55 studies comprising 761 paired observations, this study found that phosphorus-related enzyme activity increased by 38% as result of drought in wetlands, while the majority of other soil enzyme activities remained stable. The expansion of vascular plants under long-term drought significantly promoted the accumulation of phenolic compounds. Using a 2-week incubation experiment with phenol supplementation, we found that phosphorus-related enzyme could tolerate higher biotoxicity of phenolic compounds than other enzymes. Moreover, a long-term (35 years) drainage experiment in a northern peatland in China confirmed that the increased phenolic concentration in surface layer resulting from a shift in vegetation composition inhibited the increase in enzyme activities caused by rising oxygen availability, except for phosphorus-related enzyme. Overall, these results demonstrate the complex and resilient nature of wetland ecosystems, with soil enzymes showing a high degree of adaptation to drought conditions. These new insights could help evaluate the impact of drought on future wetland ecosystem services and provide a theoretical foundation for the remediation of degraded wetlands.

ObjectThe aim of our study was to examine the alterations in microstructure in patients with coronary artery disease (CAD) and cognitive impairment (CI) using diffusion kurtosis imaging (DKI). Additionally, we aimed to investigate the potential correlation between DKI parameters and cognitive function.Materials and methodsA total of 28 CAD patients and 30 healthy controls (HC) were prospectively enrolled in our study. All participants underwent routine and diffusion sequences of head imaging. DKE software was utilized to generate various diffusion kurtosis imaging parameters (DKI), including kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD). Nonparametric tests were conducted using tract-based spatial statistics (TBSS) to compare the parameter values between the two groups. The parameter values of the significantly different fiber tracts were extracted and correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores.ResultsCompared to the HC group, patients with coronary artery disease exhibited significant reductions in FA values in the bilateral Superior corona radiata, bilateral Anterior corona radiata, bilateral Posterior corona radiata, corpus callosum, left Posterior thalamic radiation, right Posterior limb of internal capsule, Anterior limb of internal capsule, and Cerebral peduncle, as well as in the left Superior longitudinal fasciculus. Additionally, KFA values decreased in the bilateral Anterior corona radiata, bilateral Anterior limb of internal capsule, and Genu of the corpus callosum. The MK values decreased in the right Posterior corona radiata, Retrolenticular part of the internal capsule, Posterior thalamic radiation (including optic radiation), Superior longitudinal fasciculus, and left Posterior thalamic radiation (including optic radiation). Moreover, the RK values decreased in the bilateral Retrolenticular part of the internal capsule, right Posterior thalamic radiation (including optic radiation), and Superior longitudinal fasciculus, as well as in the left Superior longitudinal fasciculus and Posterior thalamic radiation (including optic radiation) (p 0.01, TFCE corrected). The FA values of the right posterior limb of the internal capsule (r = 0.610, p = 0.001) and the right cerebral peduncle (r = 0.622, p

Aiming at the rapid development of anti-hypersonic collaborative interception technology, this paper designs an intelligent maneuver strategy of hypersonic vehicles (HV) based on deep reinforcement learning (DRL) to evade the collaborative interception by two interceptors. Under the meticulously designed collaborative interception strategy, the uncertainty and difficulty of evasion are significantly increased and the opportunity for maneuvers is further compressed. This paper, accordingly, selects the twin delayed deep deterministic gradient (TD3) strategy acting on the continuous action space and makes targeted improvements combining deep neural networks to grasp the maneuver strategy and achieve successful evasion. Focusing on the time-coordinated interception strategy of two interceptors, the three-player pursuit and evasion (PE) problem is modeled as the Markov decision process, and the double training strategy is proposed to juggle both interceptors. In reward functions of the training process, the energy saving factor is set to achieve the trade-off between miss distance and energy consumption. In addition, the regression neural network is introduced into the deep neural network of TD3 to enhance intelligent maneuver strategies’ generalization. Finally, numerical simulations are conducted to verify that the improved TD3 algorithm can effectively evade the collaborative interception of two interceptors under tough situations, and the improvements of the algorithm in terms of convergence speed, generalization, and energy-saving effect are verified.

Cultural ecosystem services (CES) based on nature experiences substantially contribute to public health and human well-being. However, CES’s supply-demand methodology remains scarcely explored on the coastal beach, and the demand relating to public preferences has not been sufficiently unveiled in spatial assessment. Here, we selected recreation services as a lens of CES and applied the knowledge of multi-source big data to better reflect public preferences. Point of Interests (POIs) refer to particularly valuable or interesting places. We proposed to integrate POIs and social media data (Weibo check-in) to quantify the demand for beach recreation services (BRS). We also used socio-ecological indicators to quantify the BRS’s supply. The supply-demand balance of BRS was further identified by quadrant analysis and coupling coordination degree. Our methodology was applied to a typical coastal zone, Shenzhen Dapeng New District, in the Greater Bay Area of China. Over 80% of the beaches in the study area exhibited an imbalanced or barely balanced supply-demand of recreation services. We found that POIs density had a significant influence on a balanced supply-demand of BRS. Multi-source big data (POIs and Weibo check-in) provided an efficient, low-cost, and across-scale approach for public preference mapping than traditional questionnaire surveys. The proposed CES’s supply-demand framework can identify coastal beaches with imbalanced recreation and support sustainable coastal management. Coastal beach management prioritizes not only waste prevention and sufficient safety signs but also proper infrastructure development that contribute sustainably to the human well-being of nature experiences.

The increasing integration of various energy sources and the adoption of smart grid technologies have revolutionized the way we generate, distribute, and consume energy. While these advancements offer numerous benefits, they also introduce vulnerabilities to cyber–physical attacks. To this aim, this paper investigates a resilient energy management strategy for integrated energy systems. By adopting a switched control approach and incorporating a local estimation mechanism, we have developed a resilient distributed energy management strategy to tackle the energy management problem (EMP) in integrated energy systems (IESs). This methodology demonstrates strong robustness and resilience, successfully detecting data integrity attacks and denial-of-service (DoS) attacks. Finally, we provide a case study to demonstrate the effectiveness of our proposed strategy in a real-world scenario.

IntroductionIn recent years, the world has faced increasingly severe climate change and ecological environmental problems. As an important part of the ecological system, rural areas also face many challenges. Rural ecological construction and carbon neutrality, as a solution, have attracted widespread attention. However, achieving the coordinated development of rural ecological construction and carbon neutrality requires more in-depth research and effective methods.MethodsThis study aims to explore how to promote the coordinated development of rural ecological construction and carbon neutrality through the combination of a Transformer-RNN model and cross-attention mechanism. We propose a deep learning framework that combines the parallelism and global dependency capturing capabilities of the Transformer model with the temporal information handling capabilities of the RNN model. By integrating these two models, we leverage their respective strengths to improve the performance of the model. Furthermore, we introduce a cross-attention mechanism that enables the model to simultaneously focus on the relationship between rural ecological construction and carbon neutrality. Through cross-attention, the model accurately captures the impact of rural ecological construction measures on carbon neutrality and the feedback effect of carbon neutrality on the rural ecological environment. In our experiments, we collected relevant data on rural ecological construction and carbon neutrality, including environmental indicators, socio-economic factors, land use patterns, energy consumption, and carbon emissions.Results and discussionWe preprocess the data and train the combined Transformer-RNN model with the cross-attention mechanism. The trained model demonstrates promising results in capturing the complex dependencies and relationships between rural ecological construction and carbon neutrality. The significance of this study lies in deepening the understanding of the coordinated development relationship between rural ecological construction and carbon neutrality and providing a novel deep learning-based method to solve related problems. By introducing the Transformer-RNN model with a cross-attention mechanism, we provide decision-makers with more scientific and accurate decision support, promoting the improvement of the rural ecological environment and the achievement of carbon neutrality goals.

The high carbon emissions of vehicles traveling on horizontal curve road sections cannot be ignored. Facing the difficulty of accurately quantifying the carbon emission of driving on horizontal curves and the unknown causes of high carbon emission, this study proposes to construct a carbon emission prediction model applicable to road sections with different planar geometries. The direct and indirect effects of horizontal curve alignment on vehicle carbon emissions are represented in the model in terms of travel stabilization and speed changes, respectively. A lateral force coefficient parameter was introduced into the model to integrate the carbon emission quantification problem for different planar geometry sections. Meanwhile, field tests were conducted to assess the reliability of the model and the research findings. The model reveals that the geometric parameters of horizontal curves that affect carbon emissions are the radius of the circular curve, the superelevation, and the length of the gentle curve. The root causes of high carbon emissions on horizontal curve road sections are curve driving resistance and speed fluctuations. Under the free-flow driving condition of the highway, the maximum curve radius affecting the carbon emissions of passenger cars and trucks is 400 m and 550 m, respectively. The research results can realize the carbon emission quantification of vehicles on the road sections with different plane geometries. Also, it is helpful to control the high carbon emission of vehicles traveling on horizontal curve road sections.

Introduction: With the aggravation of aging and the growing number of stroke patients suffering from hemiplegia in China, rehabilitation robots have become an integral part of rehabilitation training. However, traditional rehabilitation robots cannot modify the training parameters adaptively to match the upper limbs’ rehabilitation status automatically and apply them in rehabilitation training effectively, which will improve the efficacy of rehabilitation training.Methods: In this study, a two-degree-of-freedom flexible drive joint rehabilitation robot platform was built. The forgetting factor recursive least squares method (FFRLS) was utilized to estimate the impedance parameters of human upper limb end. A reward function was established to select the optimal stiffness parameters of the rehabilitation robot.Results: The results confirmed the effectiveness of the adaptive impedance control strategy. The findings of the adaptive impedance control studies showed that the adaptive impedance control had a significantly greater reward than the constant impedance control, which was in line with the simulation results of the variable impedance control. Moreover, it was observed that the levels of robot assistance could be suitably modified based on the subject’s different participation.Discussion: The results facilitated stroke patients’ upper limb rehabilitation by enabling the rehabilitation robot to adaptively change the impedance parameters according to the functional status of the affected limb. In clinic therapy, the proposed control strategy may help to adjust the reward function for different patients to improve the rehabilitation efficacy eventually.

IntroductionThromboembolic events associated with extracorporeal membrane oxygenation (ECMO) in clinical treatment are typical. Heparin coating has been widely employed as a surface modification strategy for ECMO tubes. However, its clinical application is often accompanied by unavoidable complications due to its mechanism of action. As a direct thrombin inhibitor with a single target, Bivalirudin (BV) has exhibited a lower incidence of adverse events and superior pharmacokinetic performance compared to heparin.MethodsA gelatin methacrylate hydrogel (GelMA) coating layer with BV was successfully synthesized on polyvinyl chloride, and the drug release ratio was close to complete release within 7 days.Results and discussionSimulated extracorporeal circulation experiments using roller pumps in vitro and jugular arteriovenous bypass experiments in rabbits demonstrated its outstanding anticoagulant efficacy. The systemic anticoagulant assay proved that BV hydrogel coating does not affect the coagulation level, and reduces the risk of complications such as systemic bleeding compared to intravenous injection. BV-Coating GelMA hydrogel tube has exhibited good biocompatibility and significantly improved anticoagulant performance, making it an optimal choice for surface materials used in blood-contacting medical devices.

Background/aimsTo investigate the specific effects of s odium-glucose transporter 2 inhibitor (SGLT2i) on cardiac energy metabolism.MethodsA systematic literature search was conducted in eight databases. The retrieved studies were screened according to the inclusion and exclusion criteria, and relevant information was extracted according to the purpose of the study. Two researchers independently screened the studies, extracted information, and assessed article quality.ResultsThe results of the 34 included studies (including 10 clinical and 24 animal studies) showed that SGLT2i inhibited cardiac glucose uptake and glycolysis, but promoted fatty acid (FA) metabolism in most disease states. SGLT2i upregulated ketone metabolism, improved the structure and functions of myocardial mitochondria, alleviated oxidative stress of cardiomyocytes in all literatures. SGLT2i increased cardiac glucose oxidation in diabetes mellitus (DM) and cardiac FA metabolism in heart failure (HF). However, the regulatory effects of SGLT2i on cardiac FA metabolism in DM and cardiac glucose oxidation in HF varied with disease types, stages, and intervention duration of SGLT2i.ConclusionSGLT2i improved the efficiency of cardiac energy production by regulating FA, glucose and ketone metabolism, improving mitochondria structure and functions, and decreasing oxidative stress of cardiomyocytes under pathological conditions. Thus, SGLT2i is deemed to exert a benign regulatory effect on cardiac metabolic disorders in various diseases.Systematic review registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023484295).

The New Delhi Metallo-β-lactamase (NDM) producing Enterobacterales has been detected from diverse sources but has rarely been reported in retail eggs. In this study, 144 eggshell and 96 egg content samples were collected in 2022 from Guangdong province and were screened for NDM-producing strains. Four Escherichia coli strains (ST3014, ST10, ST1485, and ST14747) recovered from two (1.39%, 2 of 144) eggshells and two (2.08%, 2 of 96) egg content samples were identified as blaNDM−5-positive strains. Oxford Nanopore MinION sequencing and conjugation assays revealed that the blaNDM−5 gene was carried by IncX3 (n = 1), IncI1 (n = 1), and IncHI2 (n = 2). The IncI1-plasmid-carrying blaNDM−5 displayed high homology with one plasmid pEC6563-NDM5 from the human clinic, while the IncHI2 plasmid harboring blaNDM−5 shared highly similar structures with plasmids of animal origin. To the best of our knowledge, this is the first report on the identification of blaNDM−5-positive bacteria in retail eggs. NDM-producing E. coli could be transmitted to humans by the consumption of eggs or direct contact, which could pose a potential threat to human health.

Genotype-to-phenotype (G2P) prediction has become a mainstream paradigm to facilitate genomic selection (GS)-assisted breeding in the seed industry. Many methods have been introduced for building GS models, but their prediction precision may vary depending on species and specific traits. Therefore, evaluation of multiple models and selection of the appropriate one is crucial to effective GS analysis. Here, we present the G2P container developed for the Singularity platform, which not only contains a library of 16 state-of-the-art GS models and 13 evaluation metrics. G2P works as an integrative environment offering comprehensive, unbiased evaluation analyses of the 16 GS models, which may be run in parallel on high-performance computing clusters. Based on the evaluation outcome, G2P performs auto-ensemble algorithms that not only can automatically select the most precise models but also can integrate prediction results from multiple models. This functionality should further improve the precision of G2P prediction. Another noteworthy function is the refinement design of the training set, in which G2P optimizes the training set based on the genetic diversity analysis of a studied population. Although the training samples in the optimized set are fewer than in the original set, the prediction precision is almost equivalent to that obtained when using the whole set. This functionality is quite useful in practice, as it reduces the cost of phenotyping when constructing training population. The G2P container and source codes are freely accessible at https://g2p-env.github.io/.

16S rRNA is the universal gene of microbes, and it is often used as a target gene to obtain profiles of microbial communities via next-generation sequencing (NGS) technology. Traditionally, sequences are clustered into operational taxonomic units (OTUs) at a 97% threshold based on the taxonomic standard using 16S rRNA, and methods for the reduction of sequencing errors are bypassed, which may lead to false classification units. Several denoising algorithms have been published to solve this problem, such as DADA2 and Deblur, which can correct sequencing errors at single-nucleotide resolution by generating amplicon sequence variants (ASVs). As high-resolution ASVs are becoming more popular than OTUs and only one analysis method is usually selected in a particular study, there is a need for a thorough comparison of OTU clustering and denoising pipelines. In this study, three of the most widely used 16S rRNA methods (two denoising algorithms, DADA2 and Deblur, along with de novo OTU clustering) were thoroughly compared using 16S rRNA amplification sequencing data generated from 358 clinical stool samples from the Colorectal Cancer (CRC) Screening Cohort. Our findings indicated that all approaches led to similar taxonomic profiles (with P > 0.05 in PERMNAOVA and P 0.05). In conclusion, this study demonstrates that DADA2, Deblur, and de novo OTU clustering display similar power levels in taxa assignment and can produce similar conclusions in the case of the CRC cohort.

PurposeThe cause of spontaneous subarachnoid hemorrhage (SAH) is unknown in 10% of cases. The aim of this study was to demonstrate the characteristics of patients with angiography-negative subarachnoid hemorrhage (anSAH) and to analyze factors influencing the clinical outcome in patients suffering from anSAH.MethodsA retrospective cohort of 75 patients with anSAH [26 perimesencephalic (pmSAH) and 49 non-perimesencephalic SAH (npmSAH)] admitted between January 2016 and June 2022 was included. We analyzed demographic, clinical data and 6-month functional outcomes. Enter regression analysis was performed to identify factors associated with outcomes.ResultsUnfavorable outcome was achieved in 10 of 75 patients (13.3%). Unfavorable outcome was associated with senior adults (p = 0.008), Hijdra cistern score (HCS) elevation (p = 0.015), long-time lumbar cistern continuous drainage (LCFD; p = 0.029) and hydrocephalus (p = 0.046). The only significant risk factor for unfavorable outcome after npmSAH was the HCS (OR 1.213 (95%CI 1.007–1.462), p = 0.042).ConclusionOur study provides valuable information on both SAH patterns and functional outcome in patients suffering from anSAH and should be taken into consideration during management of these patients.

Background and aimsAccumulated evidence indicates that the intestinal microbiota plays crucial roles in the initiation and progression of colorectal cancer (CRC). However, the effects of the tissue-associated microbiota on CRC metastasis are poorly defined. The aim of this study was to explore the differences in bacteria between metastatic and non-metastatic CRC tissues and identify potential bacterial species that associate with CRC metastasis.Methods16S rDNA amplicon high-throughput sequencing was used to test the intestinal tissue-associated microbiota in patients with metastatic CRC (n = 48) and non-metastatic CRC (n = 44). The microbial diversity and differential species were analysed by standard microbiological methods, and then the differential bacteria were confirmed by qPCR. Receiver operating characteristic (ROC) curves were plotted to evaluate the ability of the differential bacteria in predicting the metastasis of CRC. In addition, the microbial compositions of tumor-adjacent tissues from the metastatic and non-metastatic CRC groups were analysed.ResultsThe α- or β-diversity of microbial community between the metastatic and non-metastatic CRC groups did not exhibit significant differences. However, some bacterial abundances between two groups showed significant differences. At the phylum level, Bacteroidota and Desulfobacterota were significantly higher in the metastatic group than in the non-metastatic group, while Proteobacteria was significantly decreased in the metastatic group. At the genus level, Bacteroides (mainly composed of Bacteroides fragilis and Bacteroides uniformis) was significantly higher in the metastatic group than in the non-metastatic group, while Streptococcus and Escherichia-Shigella were significantly decreased. The ROC curves of the selected bacteria showed area under the curve (AUC) values ranging from 0.598 to 0.69; when CEA and the selected bacteria were combined, the AUC values increased from 0.678 to 0.705. In addition, the bacterial composition of tumor-adjacent tissues from the metastatic and non-metastatic CRC groups were also different, and the differential bacteria were consistent with those between metastatic and non-metastatic CRC tumor tissues.ConclusionThe bacterial composition of tumor and tumor adjacent tissue from the metastatic CRC group was different from that of the non-metastatic CRC group; in particular, Bacteroides was increased, and Streptococcus was decreased. These findings are helpful to further reveal the mechanism of CRC metastasis and provide new ideas for the clinical diagnosis and treatment of CRC metastasis.

BackgroundSalidroside (Sal), the main component of a famous herb Rhodiola rosea L, enhances memory performance and reduces fatigue. Therefore, this study assessed the effect of Sal on memory impairment induced by a long-term intake of ethanol (EtOH) in rats and investigated its relevant mechanisms using gut microbiota metagenomic analysis and hippocampal transcriptomic analysis.MethodsEighteen male SD rats were divided into the normal control group (CON group), EtOH model group (Model group), and Sal treatment group (Sal group). The rats in the Model and Sal groups intragastrically (i.g.) received 2 g/kg EtOH for 30 consecutive days, whereas the CON group was given an equal volume of distilled water. Meanwhile, the rats in the Sal group were administered i.g. 30 mg/kg Sal 60 min after EtOH intake. All rats were tested in the eight-arm maze for their memory function every 3 days. On the 30th day, metagenomic analyses of gut microbiota and transcriptomic analyses of the hippocampus were performed.ResultsCompared with the Model group, Sal treatment reduced the total time to complete the eight-arm maze task, decreased the number of arm entries, and abated the working memory error that was significant from the 9th day. Additionally, Sal intervention improved the gut microbiota composition, such as the increased abundance of Actinobacteria and Bifidobacterium, which was related to the metabolism of amino acids and terpenoid carbohydrate, endocrine function, and signal transduction by neurotransmitters. In the hippocampus, the EtOH intake differentially expressed 68 genes (54 genes increased, whereas 14 genes decreased), compared with the CON group, whereas Sal intervention affected these changes: 15 genes increased whereas 11 genes decreased. And, enrichment analyses revealed these genes were related to the structural components of the ribosome, mRNA splicing process, protein translation, mitochondria function, and immunological reaction. Finally, a correlation analysis found the memory impairment was positively correlated with the abnormal upregulation of Tomm7 but negatively correlated with decreased abundance of gut Alistipes_indistinctus, Lactobacillus_taiwanensis, Lactobacillus_paragasseri, and Lactobacillus johnsonii.ConclusionSal improved memory impairment caused by long-term EtOH intake in rats, which may be related to its regulation of gut dysbiosis and hippocampal dysfunction.

ObjectiveThe environment influences the sow's health and physiology during gestation. This study was conducted to evaluate indoor environmental parameters and physiological responses of early-gestation sows and investigate the possible methods for assessing the thermal environment in commercial houses.MethodsA total of 20 early-gestation sows (commercial purebred Yorkshire) with an average body weight of 193.20 ± 3.62 kg were used for this study in winter, spring, summer, and autumn. The indoor environment parameters comprising dry-bulb temperature (Tdb), relative humidity (RH), and carbon dioxide (CO2) were recorded in 30-min intervals. Physiological parameters including heart rate (HR) and respiration rate (RR) of sows were also measured every 30 min. Wet-bulb temperature (Twb) was calculated using Tdb, RH and atmospheric pressure was recorded at a nearby weather station.ResultsThe average indoor Tdb and RH were 12.98 ± 2.03°C and 80.4 ± 6.4% in winter, 18.98 ± 2.68°C and 74.4 ± 9.0% in spring, 27.49 ± 2.05°C and 90.6 ± 6.4% in summer, and 17.10 ± 2.72°C and 64.5 ± 10.9% in autumn. A higher average concentration of CO2 was observed in winter (1,493 ± 578 mg/m3) than in spring (1,299 ± 489 mg/m3), autumn (1,269 ± 229 mg/m3), and summer (702 ± 128 mg/m3). Compared with the HR and RR in the optimum environment, high RH in the house led to a significant decrease in both HR and RR (P < 0.05). In addition, a significant decline in HR was also obtained at high temperatures (P < 0.05). A temperature humidity index (THI), THI = 0.82 × Tdb + 0.18 × Twb, was determined for early-gestation sows, and the THI thresholds were 25.6 for HR. The variation in THI in summer showed that heat stress still occurred under the pad-fan cooling system.ConclusionThis study demonstrated the critical significance of considering physiological responses of early-gestation sows in commercial houses and THI thresholds. We recommend that much more cooling measures should be taken for early-gestation sows in summer.

ObjectiveWe aimed to evaluate the effects of integrated Chinese and Western medical therapeutic modalities on clinical prognosis in a population with stable angina pectoris (SAP) of coronary heart disease (CHD).MethodsIn a prospective cohort study, 732 patients with SAP of CHD hospitalized in the Integrated Cardiology Unit of the China-Japan Friendship Hospital From October 2020 to October 2021 were included. The patients were divided into integrated treatment and conventional treatment groups according to whether they had been taking Chinese medicine for more than 6 months per year. The occurrence of composite cardiovascular events (CVEs), including cardiac death, non-fatal myocardial infarction, revascularization, stroke, all-cause death, and readmission due to angina attack, heart failure, or malignant arrhythmia, was recorded during follow-up. The effects of different treatment modalities on prognosis were evaluated using univariate and multifactorial logistic regression. Logistic regression models were evaluated using receiver operating characteristic (ROC) curves. In sensitivity analysis, the correlation between treatment modality and outcome events was corrected by rematching the two groups of patients using the propensity score matching (PSM) method.ResultsThe data from 690 patients were included in the analysis, with 327 patients in the integrated treatment group and 363 patients in the conventional treatment group. CVEs occurred in 19 patients (5.8%) in the integrated treatment group and 37 patients (10.2%) in the conventional treatment group. The proportion of outcome events was significantly lower in the combination treatment group than in the conventional treatment group (P = 0.037). Covariate correction by multimodal multifactorial logistic regression revealed a lower risk of CVEs in patients receiving integrated therapy compared with conventional therapy (OR = 0.246, 95% CI = 0.097–0.622, P = 0.003). Moreover, a history of renal insufficiency (OR = 3.991, 95% CI = 1.164–13.684, P = 0.028) and a higher Gensini score (OR = 1.039, 95% CI = 1.028–1.050, P

Light is an important abiotic factor affecting insect behavior. In nature, linearly polarized light is common, but circularly polarized light is rare. Left circularly polarized (LCP) light is selectively reflected by the exocuticle of most scarab beetles, including Anomala corpulenta. Despite our previous research showing that this visual signal probably mediates their mating behavior, the way in which it does so is not well elucidated. In this study, we investigated how LCP light affects not only mating behavior but also gene expression in this species using RNA-seq. The results indicated that disruption of LCP light reflection by females of A. corpulenta probably affects the process by which males of A. corpulenta search for mates. Furthermore, the RNA-seq results showed that genes of the environmental signaling pathways and also of several insect reproduction-related amino acid metabolic pathways were differentially expressed in groups exposed and not exposed to LCP light. This implies that A. corpulenta reproduction is probably regulated by LCP light-induced stress. Herein, the results show that LCP light is probably perceived by males of the species, further mediating their mating behavior. However, this hypothesis needs future verification with additional samples.

Both heart failure (HF) and cognitive impairment (CI) have a significant negative impact on the health of the elderly individuals. Magnetic resonance imaging (MRI) can non-invasively detect functional and structural variations in the heart and brain, making it easier to explore the connection between the heart and brain. According to neuroimaging studies, HF patients have a higher chance of developing CI because they have a variety of different types of brain injuries. To examine how HF and CI are influenced by one another, English-language literature was searched in the Web of Science, PubMed EMBASE (OVID), PsycInfo, and Scopus databases. The search terms included “high-frequency,” “brain function,” “brain injury,” “cognition,” “cognitive impairment,” and “magnetic resonance imaging.” Normal brain function is typically impaired by HF in the form of decreased cerebral perfusion pressure, inflammation, oxidative stress, and damage to the BBB, resulting in CI and subsequent HF. Early pathophysiological alterations in patients’ brains have been widely detected using a range of novel MRI techniques, opening up new avenues for investigating the connection between HF and CI. This review aims to describe the pathogenesis of HF with CI and the early diagnostic role of MRI in the heart-brain domain.

BackgroundTraumatic spinal cord injury (TSCI) is a highly fatal and disabling event, and its incidence rate is increasing in China. Therefore, we collated the epidemiological factors of TSCI in different regions of China to update the earlier systematic review published in 2018.MethodWe searched four English and three Chinese electronic databases from 1978 to October 1, 2022. From the included reports, information on sample characteristics, incidence, injury characteristics, prognostic factors, and economic burden was extracted. The selection of data was based on the PRISMA statement. The quality of the included studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) tool. The results of the meta-analysis were presented in the form of pooled frequency and forest plots.ResultsA total of 59 reports (60 studies) from 23 provinces were included, of which 41 were in the Chinese language. The random pooled incidence of TSCI in China was estimated to be 65.15 per million (95% CI: 47.20–83.10 per million), with a range of 6.7 to 569.7 per million. The pooled male-to-female ratio was 1.95:1. The pooled mean age of the cases at the time of injury was 45.4 years. Motor vehicle accidents (MVAs) and high falls were found to be the leading causes of TSCI. Incomplete quadriplegia and AISA/Frankel grade D were the most common types of TSCI. Cervical level injury was the most prevalent. The pooled in-hospital mortality and complication rates for TSCI in China were 3% (95% CI: 2–4%) and 35% (95% CI: 23–47%). Respiratory problems were the most common complication and the leading cause of death.ConclusionCompared with previous studies, the epidemiological data on TSCI in China has changed significantly. A need to update the data over time is essential to implement appropriate preventive measures and formulate interventions according to the characteristics of the Chinese population.

Genomic selection (GS), a strategy to use genotypes to predict phenotypes via statistical or machine learning models, has become a routine practice in plant breeding programs. GS can speed up the genetic gain by reducing phenotyping costs and/or shortening the breeding cycles. GS analysis is complicated involving data clean up and formatting, training and test population analysis, model selection and evaluation, and parameter optimization. In addition, GS analysis also requires some programming skills and knowledge of statistical modeling. Thus, we need a more practical GS tools for breeders. To alleviate this difficulty, we developed the web-based platform IP4GS (https://ngdc.cncb.ac.cn/ip4gs/), which offers a user-friendly interface to perform GS analysis simply through point-and-click actions. IP4GS currently includes seven commonly used models, eleven evaluation metrics, and visualization modules, offering great convenience for plant breeders with limited bioinformatics knowledge to apply GS analysis.

Introduction: Holt–Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS.Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3′-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells.Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.

Sitobion miscanthi, Rhopalosiphum padi, and Schizaphis graminum are the three main pests in Chinese wheat-producing regions. In 2020, they are classified into the Chinese Class I list of agricultural diseases and pests, due to their severe harm to wheat plantings. S. miscanthi, R. padi, and S. graminum are migrant pests, and understanding their migration patterns and simulating their migration trajectories would improve forecasting and controlling them. Furthermore, the bacterial community of the migrant wheat aphid is also less known. In this study, we employed a suction trap to uncover the migration patterns of the three wheat aphid species in Yuanyang county, Henan province, during 2018 to 2020. And then the migration trajectories of S. miscanthi and R. padi were simulated using the NOAA HYSPLIT model. The interactions between wheat aphids and bacteria were further revealed by specific PCR and 16S rRNA amplicon sequencing. The results showed that the population dynamics of migrant wheat aphids was varied. Most of the trapped samples were identified to be R. padi, and S. graminum was the least collected sample. Typically, R. padi had two migration peaks in the 3 years, whereas S. miscanthi and S. graminum only exhibited one migration peak in 2018 and 2019. Moreover, the aphid migration trajectories varied over the years. Generally, the aphids originated from the south and migrated to the north. Herein, the infections of three main aphid facultative bacterial symbionts, Serratia symbiotica, Hamiltonella defensa, and Regiella insercticola, were detected in S. miscanthi and R. padi with specific PCR. Rickettsiella, Arsenophonus, Rickettsia, and Wolbachia were further identified with 16S rRNA amplicon sequencing. Biomarker searching indicated that Arsenophonus was significantly enriched in R. padi. Furthermore, diversity analyses showed that the bacterial community of R. padi had a higher richness and evenness than that of S. miscanthi. In conclusion, this study expands our knowledge about the migration patterns of aphids in the main wheat plant region of China and reveals the interactions between bacterial symbionts and migrant aphids.

Cutaneous vesiculobullous eruptions associated with multiple myeloma (MM) are rare. Although the development of blisters is mostly driven by amyloid deposits of paraproteins in the skin, autoimmunity may play a role. In this study, we report an unusual case of an MM patient with blisters who presented with both flaccid and tense vesicles and bullae. Direct immunofluorescence revealed IgA autoantibody deposits in the basement membrane zone (BMZ) and intercellular space of the epidermis, which displayed an atypical autoantibody deposition pattern. The patient showed rapid disease progression and died during follow-up. We performed a literature review of autoimmune bullous diseases (AIBDs) associated with MM or its precursors and found 17 previously reported cases. Together with the present case, cutaneous involvement of the skin folds was frequently reported, and mucous membranes were barely affected. IgA pemphigus, with consistent IgA monoclonality, was observed in half of the cases. Five patients displayed atypical autoantibody deposition patterns in the skin; the prognosis of these patients appeared to be poorer than that of other patients. We aim to increase our understanding of AIBDs associated with MM or its precursors.

The objective of this study was to evaluate symptoms of depression and anxiety as well as changes in spontaneous neuronal activity in college students studying abroad during the coronavirus 2019 (COVID-19) pandemic. We examined functional brain changes using resting-state functional magnetic resonance imaging (fMRI), the amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo) in overseas students with enforced isolation due to the COVID-19 pandemic. Additionally, emotional assessments were administered to determine the severity of depression and anxiety. The questionnaire results showed that anxiety and depressive symptoms differed between overseas students (i.e., those attending an overseas college virtually) and local students (i.e., those attending a local college in person). The fMRI data revealed higher ALFF values in the bilateral superior medial frontal gyrus, bilateral pre-central gyrus, left insula, and left superior temporal gyrus as well as lower ALFF values in the bilateral paracentral lobule (supplementary motor area) in overseas students. Moreover, ReHo analysis also revealed significant differences between overseas students and local students. Compared with local students, overseas students showed significantly increased ReHo in the right inferior frontal and superior temporal gyri and decreased ReHo in the bilateral paracentral lobule, bilateral superior medial frontal gyrus (supplementary motor area), and bilateral pre-central gyrus. In addition, in overseas students, altered ReHo in the cluster including the left superior and medial frontal gyri, pre-central gyrus, and paracentral lobule was significantly positively correlated with Self-Rating Depression Scale scores. Thus, spontaneous brain activity in overseas students changed during the COVID-19 pandemic. This change in brain function might be related to depression and anxiety symptoms. These results suggest that mental health services are needed to decrease the risk of anxiety and depression among college students studying abroad during the COVID-19 pandemic.

With the proposal of the two-carbon goal, energy conservation and emission reduction will become the focus of China’s energy system in the future for a long time to come. The establishment of a complete and efficient carbon traceability system will play an important role in promoting carbon emission reduction in the power system. Based on blockchain, this paper uses the consensus mechanism, time stamp, decentralization features, smart contract and other functions of blockchain, combined with the power flow calculation and the characteristics related to carbon emission and active power of the generator set, to obtain the corresponding carbon emission intensity of the generator set and carbon flow rate. It realizes the calculation and tracing of carbon emission flow in power distribution network and ensures the reliability of carbon traceability results, high efficiency of information transmission and transparency of traceability process. Firstly, based on the characteristics of the master-slave multi-chain structure in the consortium chain, In this paper, high-voltage substation nodes are the main chain nodes, and carbon flow tracing and calculation are carried out for the associated low-voltage substations, and the information of high-voltage or low-voltage substation nodes is guaranteed to be tamper-free through the hash anchoring method. The master-slave multi-chain model adopted in this paper is that the main chain adopts EA-DPoS (Evaluation and Agent-DPoS) algorithm, the slave chain adopts improved PBFT algorithm, and the comprehensive evaluation and reward and punishment mechanism are introduced to complete the consensus. Secondly, considering the security requirements of the power system data and the fact that some nodes of the distribution network do not have powerful computing resources comparable to those of the power grid company or major nodes, this paper encrypts and decrypts relevant data in the main chain node by combining the smart contract of blockchain. Meanwhile, cloud service providers with computing resources are responsible for generator power distribution combined with power flow calculation and carbon emission intensity calculation of the generator set. The power grid company adopts the cloud computing framework based on the double check mechanism to calculate the carbon flow rate while verifying the correct calculation results of the cloud service provider, and finally realizes the safe and accurate tracing of the carbon flow of the distribution network.

Breast, ovarian, prostate, lung, and head/neck cancers are five solid cancers with complex interrelationships. However, the shared genetic factors of the five cancers were often revealed either by the combination of individual genome-wide association study (GWAS) approach or by the fixed-effect model-based meta-analysis approach with practically impossible assumptions. Here, we presented a random-effect model-based cross-cancer meta-analysis framework for identifying the genetic variants jointly influencing the five solid cancers. A comprehensive genetic correlation analysis (genome-wide, partitioned, and local) approach was performed by using GWAS summary statistics of the five cancers, and we observed three cancer pairs with significant genetic correlation: breast–ovarian cancer (rg = 0.221, p = 0.0003), breast–lung cancer (rg = 0.234, p = 7.6 × 10−6), and lung–head/neck cancer (rg = 0.652, p = 0.010). Furthermore, a random-effect model-based cross-trait meta-analysis was conducted for each significant cancer pair, and we found 27 shared genetic loci between breast and ovarian cancers, 18 loci between breast and lung cancers, and three loci between lung and head/neck cancers. Functional analysis indicates that the shared genes are enriched in human T-cell leukemia virus 1 infection (HTLV-1) and antigen processing and presentation (APP) pathways. Our study investigates the shared genetic links across five solid cancers and will help to reveal their potential molecular mechanisms.

Abnormal gray matter (GM) asymmetry has been verified in autism spectrum disorder (ASD), which is characterized by high heterogeneity. ASD is distinguished by three core symptom domains. Previous neuroimaging studies have offered support for divergent neural substrates of different core symptom domains in ASD. However, no previous study has explored GM asymmetry alterations underlying different core symptom domains. This study sought to clarify atypical GM asymmetry patterns underlying three core symptom domains in ASD with a large sample of 230 minors with ASD (ages 7–18 years) and 274 matched TD controls from the Autism Brain Imaging Data Exchange I (ABIDE I) repository. To this end, the scores of the revised autism diagnostic interview (ADI-R) subscales were normalized for grouping ASD into three core-symptom-defined subgroups: social interaction (SI), verbal communication (VA), and restricted repetitive behaviors (RRB). We investigated core-symptom-related GM asymmetry alterations in ASD resulting from advanced voxel-based morphometry (VBM) by general linear models. We also examined the relationship between GM asymmetry and age and between GM asymmetry and symptom severity assessed by the Autism Diagnostic Observation Schedule (ADOS). We found unique GM asymmetry alterations underlying three core-symptom-defined subgroups in ASD: more rightward asymmetry in the thalamus for SI, less rightward asymmetry in the superior temporal gyrus, anterior cingulate and caudate for VA, and less rightward asymmetry in the middle and inferior frontal gyrus for RRB. Furthermore, the asymmetry indexes in the thalamus were negatively associated with ADOS_SOCIAL scores in the general ASD group. We also showed significant correlations between GM asymmetry and age in ASD and TD individuals. Our results support the theory that each core symptom domain of ASD may have independent etiological and neurobiological underpinnings, which is essential for the interpretation of heterogeneity and the future diagnosis and treatment of ASD.

BackgroudThe high or low inferior mesenteric artery (IMA) ligation in rectal cancer remains a great debate. This study retrospectively discussed the outcomes of the perioperative period, defecation and urinary function and long-term prognosis in rectal cancer patients with high or low IMA ligation.MethodsThis study enrolled 220 consecutive rectal cancer cases, including 134 with high IMA ligation and 86 with low ligation. A comparison between the two groups was made for anastomotic leakage, low anterior resection syndrome (LARS), international prostate symptom score (IPSS), 5-year disease-free survival (DFS) and 5-year overall survival (OS).ResultsLow-ligation group had a longer operative time, and larger intraoperative blood loss. No significant difference was noted in anastomotic leakage incidence. In multivariable analysis, the male gender and tumor located at the lower rectum were identified as risk factors for anastomotic leakage. No significant differences were observed between groups in their LARS and IPSS questionnaire responses. The high-ligation vs. the low-ligation 5-year OS and DFS were 78.3% vs. 82.4% and 72.4% vs. 76.6%, respectively, which were not statistically different.ConclusionThe ligation level of the IMA had no significant effect on the anastomotic leakage incidence, defecation, urinary function, and long-term prognosis.

This study summarizes the internal relationship and mechanism of industrialization, business culture, and higher education that affect the development of modern industrial and commercial culture, and consequently, the construction of free trade ports in Hainan. The cases of Hong Kong, Singapore, and Dubai free trade ports were considered as references. Based on immigration, naturalization, and education in Hainan’s history, Hainan’s cultural base map, which influences the construction of modern industrial and commercial culture, was proposed to be formed by splicing and overlapping of the free, guarding, farming-reading, farming-marine, and immigrant cultures. The development course of Hainan in the past 30 years indicated that although Hainan has always been at the forefront and highland of reform and opening up, it is still relatively backward despite the implementation of long-term policies; moreover, its development performance is not ideal. The existing problems and factors related to the present ideology mainly include the following: 1) The pursuit of “making quick money” has led to the ups and downs of Hainan’s development. 2) Lack of innovation hinders functional improvement leading to poor sustainability. 3) The course of modern industrial civilization based on a cultural base map is short. 4) Although bottom-up industrialization plays a key role in the formation of modern industrial civilization, it is not followed by Hainan. Furthermore, the cultural development path of Hainan Free Trade Port construction should 1) strongly promote industrialization by overcoming the shortcomings of industrial development, 2) deepen the reform of the agricultural reclamation system, improve the business environment, and cultivate a healthy modern industrial and commercial culture, 3) standardize the tourism market, and build the most advanced tourism industry culture, 4) improve the basic education level and develop excellent higher education opportunities, 5) enhance the diversity of human resources structure, and 6) revitalize literature and art, and showcase and develop Hainan’s fine culture. Overall, the construction of the Hainan Free Trade Port requires long-term upgrading and development. It is necessary to continue cultural construction, adapt to the requirements of the highest level of openness and realize the healthy development of the Hainan Free Trade Port.

Background: Atherosclerosis can impact cancer progression due to the cholesterol and calcium metabolism, illustrating the links between atherosclerosis and cancer metastasis. Tetraspanin 4 (TSPAN4) may help understand migrasomes in diseases and provide novel targets for treatment.Methods: TSPAN4 expression in atherosclerosis Gene Expression Omnibus (EO) dataset and multiple omics data were explored, such as enriched pathways analysis, protein-protein interaction analysis, immune subtypes as well as diagnostic and prognostic value in pan-cancer. The relationship between Glioblastoma multiforme (GBM) and TSPAN4 was further investigated.Results: Compared to control, TSPAN4 expression was upregulated in foam cells from patients with atherosclerosis and survival analysis demonstrated high TSPAN4 expression contributes to poor prognosis. TSPAN4 expression differs significantly in immune subtypes of cancers, which can be a diagnostic and prognostic target of cancers due to the high accuracy. Overall survival analysis of subgroups demonstrated that higher TSPAN4 expression had a worse prognosis and the univariate analysis and multivariate analysis demonstrated age, TSPAN4 expression, WHO grade, IDH status and histological types were independent risk factors of Glioblastoma multiforme.Conclusion: The TSPAN4 expression was associated with atherosclerosis progression and pan-cancer, especially in Glioblastoma multiforme and GBMLGG. Therefore, TSPAN4 may serve as a potential biomarker and the crosstalk between atherosclerosis and tumor progression. The results are not fully validated and further studies are still needed to validate in vivo and in vitro.

Porcine circovirus type 2 (PCV2) has been identified as the causal agent of postweaning multisystemic wasting syndrome (PMWS), an economically important multifactorial disease of the swine industry worldwide. This research designed a dual nested polymerase chain reaction (PCR) detection method to simultaneously monitor porcine circovirus type 2 (PCV2) and PCV3. The limit of detection (LoD) of sensitivity for PCV2 and PCV3 was ten copies/mL for both viruses. There was no cross-reaction with any other porcine pathogens tested and no non-specific amplification. The coincidence and repetition rates were both 100%. Through the systematic and clinical sampling, 15,130 samples collected from 30 large-scale pig farms in eight provinces in China (including Hubei, Hunan, Henan, Jiangxi, Shanxi, Guangdong, Hainan, and Heilongjiang) were subjected to early warning surveillance and/or clinical diagnosis. These results revealed that the overall positive rates of PCV3 and PCV2 were 0 and 28.29%, respectively, with the lowest level recorded in Jiangxi province. The highest carrying rate was observed in Hainan province. Pigs at different ages displayed varying carrying rates for PCV: fattening pigs and gilts had the highest and the lowest carrying rates for PCV, respectively. In addition, the excretion rates for PCV of colostrum, semen, and nasal, anal, and vulval swabs were tested. The colostrum, anal swabs, and semen had higher excretion rates for PCV; these were followed by the vulval and nasal swabs that had excretion rates for PCV. Furthermore, a high blood virus-carrying rate was detected in moribund pigs, especially in pigs with fever and red skin. As to the virus-carrying rate in the pig organs received from clinical necropsy, the highest rate was found in placental tissue, followed by the kidneys, and the virus also was detected in lymphoid organs, liver, stomach, and intestines. The PCV2-positive samples were sequenced to reveal the molecular epidemic dynamics of PCV2. The results indicated four major branches, namely, PCV2a, PCV2b, PCV2c, and PCV2d, concerning PCV2 molecular epidemiology in China, with PCV2a, PCV2b, and PCV2d dominating. In conclusion, the results obtained in this study elucidated the molecular epidemiology, transmission, and positive blood samples of PCV and provided new ideas for developing comprehensive PCV control technologies to begin eliminating the disease caused by PCV by cleaning pig farms.

As a systemic autoimmune disease, rheumatoid arthritis (RA) usually causes damage not only to joints, but also to other tissues and organs including the heart, kidneys, lungs, digestive system, eyes, skin, and nervous system. Excessive complications are closely related to the prognosis of RA patients and even lead to increased mortality. This article summarizes the serious complications of RA, focusing on its incidence, pathogenesis, clinical features, and treatment methods, aiming to provide a reference for clinicians to better manage the complications of RA.

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis.Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome.Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49–1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups.Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.

The current study aims to examine the effect of trait awe on college students’ procrastination with a focus on confirming the mediating role of stress and the moderating role of future time perspective (FTP). Measures of procrastination, trait awe, stress, and future time perspective were completed by 512 Chinese college students. The results indicate that trait awe had a negative effect on procrastination, that stress was a significant mediator between trait awe and procrastination, and that FTP moderated the mediation effect. These findings not only demonstrate the crucial role of awe in alleviating procrastination but also elucidate the underlying mechanisms and relevant populations. Limitations and directions for future research were also discussed.

Zinc oxide is a popular semiconductor used in catalysts due to its wide bandgap and high exciton binding energy. However, the photocatalytic performance of ZnO was compromised by its insufficient electron-hole separation efficiency and electron transfer rate. Herein, ZnO-reduced graphene oxide (rGO) composite solid catalyst was synthesized by one-step electrodeposition method on FTO substrate using lithium perchlorate (LiClO4) as the supporting electrolyte. Scanning electron microscopy, Raman, Fourier Transform Infrared, and XRD characterizations confirmed the deposition of ZnO and the reduction of graphene oxide Owing to the cooperative effect between rGO and ZnO, the as-prepared ZnO-rGO composites show much enhanced photocatalytic degradation ability compared with pure ZnO nanorods. By optimizing the conditions of electrodeposition of ZnO-rGO composites, the degradation rate of methylene blue can reach 99.1% within 120 min. Thus, the simple preparation and the excellent performance could endow the ZnO-rGO composites with promising application in practical dye-polluted water treatment.

BackgroundTo investigate the value of serum Cyclophilin A(Cyp A) in evaluating the prognosis of patients with different severity of craniocerebral injury.MethodsThe clinical data of patients with craniocerebral injury treated in the Department of Emergency from July 2014 to August 2017 were collected. The patients were divided into survival group and death group, good neurological function group and poor neurological function group with 28-day prognosis and were divided into mild (13–15) group, moderate (9–12) group, and severe (3–8) group with Glasgow Coma Scale (GCS) score. Clinical parameters such as Cyp A and mortality in groups and the relationship between Cyp A and GCS score were compared and its predictive value for prognosis was analyzed with Binary Logistics regression, Cox proportional hazards model and kaplan-meier survival curve.ResultsIn a single-center retrospective study, 503 patients were enrolled, including 365 males and 138 females; serum Cyp A in the survival group was significantly smaller than the death group [18.7 (10.1, 51.5) ng/mL vs. 149.8 (79.5, 194.4) ng/mL, P < 0.005]. There were significant differences in mortality and Cyp A levels between patients with different severity of craniocerebral injury (P < 0.001). Serum Cyp A levels were negatively correlated with GCS scores in all patients with craniocerebral injury, mild, moderate, or severe craniocerebral injury (r = −0.844, r = −0.256, r = −0.540, r = −0.531, P < 0.001). Predictive value of Serum Cyp A level for all patients with craniocerebral injury, mild, moderate, and severe craniocerebral injury is 0.890, 0.789, 0.806, and 0.833, respectively. Logistics regression analysis showed that lactate (OR = 1.260, 95%CI: 1.023–1.551) and Cyp A (OR = 1.021, 95%CI: 1.011–1.031) were positively correlated with death (P < 0.05), Lactic acid (HR 1.115; 95%CI:1.001–1.243; P = 0.048), GCS score (HR 0.888; 95% CI: 0.794–0.993; P = 0.038), Cyp A levels (HR 1.009; 95% CI: 1.004–1.013; P < 0.001) had a significant effect on short-term mortality. Similar results were seen when neurologic function was used as the outcome. Kaplan-meier survival curve analysis found survival rate of patients with Cyp A level below the cut-off value was significantly higher.ConclusionSerum Cyp A has a certain predictive value for the prognosis of patients with different severity of craniocerebral injury. Among them, patients with severe craniocerebral injury have the highest predictive value and mild craniocerebral injury patients have the least.

Aphids are major crop pests, and they can be controlled through the application of the promising RNA interference (RNAi) techniques. However, chemical synthesis yield of dsRNA for RNAi is low and costly. Another sustainable aphid pest control strategy takes advantage of symbiont-mediated RNAi (SMR), which can generate dsRNA by engineered microbes. Aphid host the obligate endosymbiont Buchnera aphidicola and various facultative symbionts that not only have a wide host range but are also vertically and horizontally transmitted. Thus, we described the potential of facultative symbionts in aphid pest control by SMR. We summarized the community and host range of these facultative symbionts, and then reviewed their probable horizontal transmitted routes and ecological functions. Moreover, recent advances in the cultivation and genetic engineering of aphid facultative symbionts were discussed. In addition, current legislation of dsRNA-based pest control strategies and their safety assessments were reviewed.

When the world is recovering from the chaos that COVID-19 creates, the epidemic is still posing challenges to the public health system and communication. However, a case of information communication during the COVID-19 outbreak can provide a reference for the current information promulgate strategy in China. In January 2020, CCTV broadcasted the construction of two cabin hospitals on a 24-h Livestream (24H-LS), creating a remarkable viewing effect. We conducted a quantitative analysis based on the number of views, social media communication, and internet search index. We collected posts and comment data of the 24H-LS audience and related topics on Weibo, using sentiment classification and word frequency analysis to study the communication effect of 24H-LS from three perspectives: perception effect, psychology, and subject issue. The results show that, first, 24H-LS has attracted extensive public attention on the Internet and social media after its launch. Second, the public's perception of the risks of the COVID-19 outbreak and its uncertainty has decreased after watching the 24H-LS. At the same time, the positive emotions of the public have been enhanced to a certain extent. Third, through subject analysis, we found that the public had high participation and strong interaction in 24H-LS, which produced collective symbols and emotions. The study shows that through 24H-LS, a new information form, the media can effectively convey important information and resolve the public's fear and anxiety.

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a global public health concern. One-carbon (1C) metabolism plays a crucial role in the occurrence and development of multiple cancer types. However, there are limited studies investigating 1C metabolism in LUAD. This study aims to evaluate the prognostic value of 1C metabolism-related genes in LUAD and to explore the potential correlation of these genes with gene methylation, the tumor microenvironment, and immunotherapy.Methods: We identified 26 1C metabolism-related genes and performed a Kaplan-Meier and Cox regression analysis to evaluate the prognostic value of these genes. Consensus clustering was further performed to determine the 1C metabolism-related gene patterns in LUAD. The clinical and molecular characteristics of subgroups were investigated based on consensus clustering. CIBERSORT and ssGSEA algorithms were used to calculate the relative infiltration levels of multiple immune cell subsets. The relationship between 1C metabolism-related genes and drug sensitivity to immunotherapy was evaluated using the CellMiner database and IMvigor210 cohort, respectively.Results: The expression levels of 23 1C metabolism-related genes were significantly different between LUAD tumor tissues and normal tissues. Seventeen of these genes were related to prognosis. Two clusters (cluster 1 and cluster 2) were identified among 497 LUAD samples based on the expression of 7 prognosis-related genes. Distinct expression patterns were observed between the two clusters. Compared to cluster 2, cluster 1 was characterized by inferior overall survival (OS) (median OS = 41 vs. 60 months, p = 0.00031), increased tumor mutation burden (15.8 vs. 7.5 mut/Mb, p < 0.001), high expression of PD-1 (p < 0.001) and PD-L1 (p < 0.001), as well as enhanced immune infiltration. 1C metabolism-related genes were positively correlated with the expression of methylation enzymes, and a lower methylation level was observed in cluster 1 (p = 0.0062). Patients in cluster 1 were resistant to chemotherapy drugs including pemetrexed, gemcitabine, paclitaxel, etoposide, oxaliplatin, and carboplatin. The specific expression pattern of 1C metabolism-related genes was correlated with a better OS in patients treated with immunotherapy (median OS: 11.2 vs. 7.8 months, p = 0.0034).Conclusion: This study highlights that 1C metabolism is correlated with the prognosis of LUAD patients and immunotherapy efficacy. Our findings provide novel insights into the role of 1C metabolism in the occurrence, development, and treatment of LUAD, and can assist in guiding immunotherapy for LUAD patients.

The aim of this study was to investigate the diagnostic value of hsa_circ_0058514 in plasma extracellular vesicles (EVs) in BC patients and its predictive value for neoadjuvant chemotherapy. The expression of hsa_circ_0058514 in a large sample of BC plasma and healthy subjects’ plasma was detected by qPCR, and the ROC curve was drawn to verify its diagnostic value as a plasma tumor marker. Furthermore, the association between the expression of hsa_circ_0058514 and clinicopathological characteristics before and after treatment was detected in the plasma of 40 pairs of BC patients undergoing neoadjuvant therapy. The expression level of hsa_circ_0058514 in the plasma of BC patients was significantly higher than that of healthy subjects. The ROC curve showed that plasma hsa_circ_0058514 ROC in differentiating non-metastatic BC and healthy people had better diagnostic efficiency than conventional tumor markers CA153, CA125, and CEA. In patients with neoadjuvant therapy, the decrease in plasma hsa_circ_0058514 value before and after treatment correlated with pathological MP grade (r = 0.444, p = 0.004) and imaging tumor regression value (r = 0.43, p = 0.005) positive correlation. The detection of hsa_circ_0058514 in both extracellular vesicles of BC cell culture medium and human plasma was demonstrated. Hsa_circ_0058514 is detected in the plasma from BC cells secreted in the form of vesicles. Hsa_circ_0058514 can be used as an early plasma biological indicator for the diagnosis of BC in clinical applications, with a higher risk of recurrence and metastasis, and as a predictor of the effect of neoadjuvant therapy to guide the clinical use of neoadjuvant therapy.