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Phellinus pomaceus var. prunastri (Pers.) Pat. 1926 is a famous medicinal fungus that has attracted considerable interest in biotechnology because of its diverse biologically active ingredients. Here, we provide the full mitochondrial genome sequence of P. pomaceus, which spans 122,850 bp and has a GC content of 26.04%. The genome comprises 15 essential protein-coding genes, 26 distinct ORFs, 24 intronic ORFs, 25 tRNAs, and 2 rRNA genes. Bayesian inference (BI) was employed for phylogenetic analysis, revealing the evolutionary relationships among 17 Basidiomycota fungi. The results strongly supported distinct clades and indicated that P. pomaceus is closely related to Fomitiporia mediterranea.

To meet the demand for reliably evaluating the measurement accuracy of the gravity gradiometer under dynamic conditions, a method for dynamically assessing the accuracy of the gravity gradiometer in a laboratory setting was proposed. Firstly, a method for creating an environment of approximately uniform gravity gradient was introduced. It involved the symmetric distribution of rectangular mass bodies within a localized spatial range to generate an approximately uniform gravity gradient excitation, with an excitation magnitude reaching 62.4 E and non-uniformity better than 1.3 E. Secondly, an evaluation criterion was proposed based on the gravity gradiometer’s sensitivity to gravity gradient excitation produced by the movement of mass bodies under dynamic laboratory conditions, leading to the proposal of a method for evaluating the dynamic accuracy of the gravity gradiometer in the laboratory. Finally, a laboratory dynamic accuracy evaluation system for the gravity gradiometer was established using a gravity gradient excitation device and a six-degree-of-freedom motion simulation platform. Validation experiments were conducted in the laboratory using a self-developed gravity gradiometer. The experimental results indicate that this evaluation system is capable of assessing the dynamic measurement accuracy of the gravity gradiometer in the laboratory, meeting the evaluation requirements for domestically developed dynamic gravity gradiometers.

Taking a certain type of domestically produced aviation gravity meter as an example, this paper introduces the working principle, equipment composition, and field performance testing methods of the three-axis inertial stabilizer platform aviation gravimeter. Through error model analysis, it is pointed out that high-precision horizontal attitude holding is one of the key factors to further improve the accuracy of aviation gravity measurement. A rotation combination calibration method under inertial stabilization conditions combined with Kalman filter error estimation is established to improve the efficiency of field implementation while maintaining the calibration accuracy of inertial components. In addition, based on the characteristics of aviation gravity measurement, a set of instrument performance evaluation methods including static accuracy measurement and dynamic accuracy testing before formal field operation is summarized. The test results show that the static accuracy of this type of aviation gravimeter reaches 0.14×10−5 m/s2, the dynamic internal consistency is better than 0.63×10−5 m/s2, and the system difference is better than 0.23×10−5 m/s2, reaching the level of high-end foreign aviation gravimeters. In the future, with further improvement of instrument and differential GNSS accuracy, its application in the field of seismic science will be expanded.

Abstract The brain’s white matter connections are thought to provide the structural basis for its functional connections between distant brain regions but how our brain selects the best structural routes for functional communications remains poorly understood. In this study, we propose a Unified Structural and Functional Connectivity (USFC) model and use an “economical assumption” to create the brain’s first “traffic map” reflecting how frequently each segment of the brain structural connection is used to achieve the global functional communication system. The resulting USFC map highlights regions in the subcortical, default-mode, and salience networks as the most heavily traversed nodes and a midline frontal-caudate-thalamus-posterior cingulate-visual cortex corridor as the backbone of the whole brain connectivity system. Our results further revealed a striking negative association between structural and functional connectivity strengths in routes supporting negative functional connections, as well as significantly higher efficiency metrics and better predictive performance for cognition in the USFC connectome when compared to structural and functional ones alone. Overall, the proposed USFC model opens up a new window for integrated brain connectome modeling and provides a major leap forward in brain mapping efforts for a better understanding of the brain’s fundamental communication mechanisms.

Abstract This study investigated the role of mitochondrial dynamics in postoperative cognitive dysfunction (POCD) and assessed the therapeutic potential of mitochondrial modulation, particularly through the inhibition of dynamin-related protein 1 (DRP1) with Mdivi-1. Our findings indicated that DRP1 inhibition substantially mitigated neuroinflammation mediated by microglial cells, contributing to improved cognitive function in POCD models. The administration of Mdivi-1 led to a notable decrease in mitochondrial fission, reduced reactive oxygen species (ROS) production, and stabilization of mitochondrial membrane potential, all of which correlate with diminished neuroinflammation, as evidenced by lower NOD-like receptor family pyrin domain containing 3 (NLRP3)/ interleukin-1β (IL-1β) expression in microglial cells. Importantly, Mdivi-1 treatment was also found to enhance synaptic plasticity, increasing synaptic spine density in the hippocampal region of POCD mice. This improvement in mitochondrial health and synaptic integrity was paralleled by enhanced cognitive performance, as demonstrated in Y-maze tests. These results underscored the critical role of mitochondrial dynamics in the pathophysiology of POCD and suggested that targeting mitochondrial dysfunction, specifically through DRP1 inhibition, could be an effective approach for POCD treatment.

Abstract Timely and effective interventions after tracheal mucosal injury are lack in clinical practices, which elevate the risks of airway infection, tracheal cartilage deterioration, and even asphyxiated death. Herein, we proposed a biomaterial-based strategy for the repair of injured tracheal mucosal based on a copper hydrogen phosphate nanosheets (CuHP NSs) functionalized commercial hydrogel (polyethylene glycol disuccinimidyl succinate-human serum albumin, PH). Such CuHP/PH hydrogel achieved favorable injectability, stable gelation, and excellent adhesiveness within the tracheal lumen. Moreover, CuHP NSs within the CuHP/PH hydrogel effectively stimulate the proliferation and migration of endothelial/epithelial cells, enhancing angiogenesis and demonstrating excellent tissue regenerative potential. Additionally, it exhibited significant inhibitory effects on both bacteria and bacterial biofilms. More importantly, when injected injured site of tracheal mucosa under fiberoptic bronchoscopy guidance, our results demonstrated CuHP/PH hydrogel adhered tightly to the tracheal mucosa. The therapeutic effects of the CuHP/PH hydrogel were further confirmed, which significantly improved survival rates, vascular and mucosal regeneration, reduced occurrences of intraluminal infections, tracheal stenosis, and cartilage damage complications. This research presents an initial proposition outlining a strategy employing biomaterials to mitigate tracheal mucosal injury, offering novel perspectives on the treatment of mucosal injuries and other tracheal diseases.

The genus Micryletta is widely distributed in South China and Southeast Asia. Although significant progress has been made in the diversity and taxonomy of this genus over the past few years, the distribution range and taxonomy of some species still remain controversial, especially in M. inornata sensu lato. Consequently, limitations at national borders have resulted in a lack of comparative research on species from different countries. To resolve the classification dispute, assess species diversity, and determine the distribution range of Micryletta, a series of specimens were collected from the Yunnan Province of China and Thailand during herpetological surveys from 2009 to 2020. Subsequent analyses based on morphological and molecular data revealed a distinct and previously unknown lineage from western Thailand, which we formally describe as a new species. Furthermore, our study confirms that M. ‘inornata’, previously known from Mengla, Yunnan, was actually M. menglienica, and further extends its distribution range to Thailand and Laos. In addition, our findings extend the latitudinal distribution of M. inornata and M. subaraji northward into southern Thailand. Notably, this study brings the total number of known species in the genus Micryletta from 13 to 14, with the count rising from three to six species in Thailand and from one to three in Laos. Our study further confirms that species diversity within the genus Micryletta is underestimated and emphasizes the important role that international collaborations play in taxonomy. Intensifying field surveys in other regions (e.g., Myanmar, Vietnam, and Guangxi of China) will be extremely necessary in the future to clarify any taxonomic questions and reevaluate the distribution range of these species.

Abstract Background Respiratory infectious diseases have the highest incidence among infectious diseases worldwide. Currently, global monitoring of respiratory pathogens primarily focuses on influenza and coronaviruses. This study included influenza and other common respiratory pathogens to establish a local respiratory pathogen spectrum. We investigated and analyzed the co-infection patterns of these pathogens and explored the impact of lifting non-pharmaceutical interventions (NPIs) on the transmission of influenza and other respiratory pathogens. Additionally, we used a predictive model for infectious diseases, utilizing the commonly used An autoregressive comprehensive moving average model (ARIMA), which can effectively forecast disease incidence. Methods From June 2023 to February 2024, we collected influenza-like illness (ILI) cases weekly from the community in Xuanwu District, Nanjing, and obtained 2046 samples. We established a spectrum of respiratory pathogens in Nanjing and analysed the age distribution and clinical symptom distribution of various pathogens. We compared age, gender, symptom counts, and viral loads between individuals with co-infections and those with single infections. An autoregressive comprehensive moving average model (ARIMA) was constructed to predict the incidence of respiratory infectious diseases. Results Among 2046 samples, the total detection rate of respiratory pathogen nucleic acids was 53.37% (1092/2046), with influenza A virus 479 cases (23.41%), influenza B virus 224 cases (10.95%), and HCoV 95 cases (4.64%) being predominant. Some pathogens were statistically significant in age and number of symptoms. The positive rate of mixed infections was 6.11% (125/2046). There was no significant difference in age or number of symptoms between co-infection and simple infection. After multiple iterative analyses, an ARIMA model (0,1,4), (0,0,0) was established as the optimal model, with an R2 value of 0.930, indicating good predictive performance. Conclusions The spectrum of respiratory pathogens in Nanjing, Jiangsu Province, was complex in the past. The primary age groups of different viruses were different, causing various symptoms, and the co-infection of viruses did not correlate with the age and gender of patients. The ARIMA model estimated future incidence, which plateaued in subsequent months.

Abstract Background With the fast-paced advancements of robot technology, human–robot interaction (HRI) has become increasingly popular and complex, and self-efficacy in HRI has received extensive attention. Despite its popularity, this topic remains understudied in China. Objective In order to provide a psychometrically sound instrument in China, this study aimed to translate and validate the Self-Efficacy in Human–Robot Interaction Scale (SE-HRI) in two Chinese adult samples (N1 = 300, N2 = 500). Methods The data was analyzed by SPSS 26.0 and Amos 24.0. Item analysis and exploratory factor analysis were conducted using Sample 1 data. Confirmatory factor analysis, criterion-related validity analysis, and reliability analysis were then performed using Sample 2 data. Results The results revealed that the Chinese SE-HRI scale consisted of 13 items in a two-factor model, suggesting a good model fit. Moreover, general self-efficacy and willingness to accept the use of artificial intelligence (AI) were both positively correlated with self-efficacy in HRI, while negative attitudes toward robots showed an inverse correlation, proving the Chinese SE-HRI scale exhibited excellent criterion-related validity. Conclusion The Chinese SE-HRI scale is a reliable assessment tool for evaluating self-efficacy in HRI in China. The study discussed implications and limitations, and suggested future directions.

Abstract Background Recent studies have highlighted type 2 diabetes (T2DM) as a significant risk factor for the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This investigation aimed to assess electroacupuncture’s (EA) impact on liver morphology and function in T2DM rats, furnishing experimental substantiation for its potential to stall MAFLD progression in T2DM. Methods T2DM rats were induced by a high-fat diet and a single intraperitoneal injection of streptozotocin, and then randomly assigned to five groups: the T2DM group, the electroacupuncture group, the metformin group, combination group of electroacupuncture and metformin, combination group of electroacupuncture and Compound C. The control group received a standard diet alongside intraperitoneal citric acid - sodium citrate solution injections. After a 6-week intervention, the effects of each group on fasting blood glucose, lipids, liver function, morphology, lipid droplet infiltration, and fibrosis were evaluated. Techniques including Western blotting, qPCR, immunohistochemistry, and immunofluorescence were employed to gauge the expression of key molecules in AMPK-associated glycolipid metabolism, insulin signaling, autophagy, and fibrosis pathways. Additionally, transmission electron microscopy facilitated the observation of liver autophagy, lipid droplets, and fibrosis. Results Our studies indicated that hyperglycemia, hyperlipidemia and IR promoted lipid accumulation, pathological and functional damage, and resulting in hepatic steatosis and fibrosis. Meanwhile, EA enhanced the activation of AMPK, which in turn improved glycolipid metabolism and autophagy through promoting the expression of PPARα/CPT1A and AMPK/mTOR pathway, inhibiting the expression of SREBP1c, PGC-1α/PCK2 and TGFβ1/Smad2/3 signaling pathway, ultimately exerting its effect on ameliorating hepatic steatosis and fibrosis in T2DM rats. The above effects of EA were consistent with metformin. The combination of EA and metformin had significant advantages in increasing hepatic AMPK expression, improving liver morphology, lipid droplet infiltration, fibrosis, and reducing serum ALT levels. In addition, the ameliorating effects of EA on the progression of MAFLD in T2DM rats were partly disrupted by Compound C, an inhibitor of AMPK. Conclusions EA upregulated hepatic AMPK expression, curtailing gluconeogenesis and lipogenesis while boosting fatty acid oxidation and autophagy levels. Consequently, it mitigated blood glucose, lipids, and insulin resistance in T2DM rats, thus impeding liver steatosis and fibrosis progression and retarding MAFLD advancement.

This paper presents a novel approach that simultaneously enables photovoltaic (PV) inversion and flexible arc suppression during single-phase grounding faults. Inverters compensate for ground currents through an arc-elimination function, while outputting a PV direct current (DC) power supply. This method effectively reduces the residual grounding current. To reduce the dependence of the arc-suppression performance on accurate compensation current-injection models, an adaptive fuzzy neural network imitating a sliding mode controller was designed. An online adaptive adjustment law for network parameters was developed, based on the Lyapunov stability theorem, to improve the robustness of the inverter to fault and connection locations. Furthermore, a new arc-suppression control exit strategy is proposed to allow a zero- sequence voltage amplitude to quickly and smoothly track a target value by controlling the nonlinear decrease in current and reducing the regulation time. Simulation results showed that the proposed method can effectively achieve fast arc suppression and reduce the fault impact current in single-phase grounding faults. Compared to other methods, the proposed method can generate a lower residual grounding current and maintain good arc-suppression performance under different transition resistances and fault locations.

Abstract The freezing and thawing cycle is one of the primary causes of damage and instability to buildings in seasonal frost regions. During this process, the mechanical properties of soil are affected, leading to settlement, cracking, or deformation of infrastructure. Mitigating or reducing the occurrence of building frost damage in seasonal frost regions has become an important subject of study. Freeze–thaw (F–T) action will influence the distribution of moisture inside the reinforced soil and change the strength of thawing soil, which is closely related to the main influencing factors, such as initial moisture content, compaction degree, reinforced spacing, number of freeze–thaw cycles (FTC), freezing temperature, and effective vertical stress. Cohesion is an important index to determine the shear strength of clay, which is important to analyze the change in cohesion after F–T. Meanwhile, cohesion is closely related to soil moisture content. This study conducted orthogonal experiments on these primary influencing factors (6 factors at 5 levels) through FTC tests, triaxial tests, and moisture content tests to determine the undrained cohesion and moisture content of the clay after FTC, thereby establishing the influence of reinforcement on soil strength under freeze–thaw conditions. Based on the experimental results, SPSS software was used to fit the regression equations of undrained cohesion and moisture content expressed by the main influencing factors at different heights of the clay. Optimization options for the main influencing factors were obtained with Matlab software when the highest undrained cohesion values 6.8, 10.6, 8.9 kPa and lowest moisture content values 24.0%, 24.3%, 26.2% appeared in upper, middle and lower parts of the testing clay structure respectively, in conditions of − 15 °C freezing temperature and 5 times FTC. And determined the optimal combinations of moisture content, reinforcement spacing, compaction density, and vertical load at different heights. Decreasing reinforced spacing in silty clay was beneficial for liquid underwater seepage after F–T. The redistribution of internal moisture in the soil sample strengthened its undrained cohesion, thereby increasing the soil's shear strength. Comparing reinforcement conditions at different locations, it was found that when there were 3 layers of reinforcement with a spacing of 150 mm between them, this spacing was optimal. It played a significant role in improving the soil's shear strength and enhancing its bearing capacity. For reinforced clay itself, the order of the main factors influencing the undrained cohesion of soil after F–T, from high to low, was initial moisture content, reinforced spacing, and compaction degree.

Abstract Fungal diseases are the main factors affecting the quality and production of vegetables. Rapid and accurate detection of pathogenic spores is of great practical significance for early prediction and prevention of diseases. However, there are some problems with microscopic images collected in the natural environment, such as complex backgrounds, more disturbing materials, small size of spores, and various forms. Therefore, this study proposed an improved detection method of GCS-YOLOv8 (Global context and CARFAE and Small detector-optimized YOLOv8), effectively improving the detection accuracy of small-target pathogen spores in natural scenes. Firstly, by adding a small target detection layer in the network, the network’s sensitivity to small targets is enhanced, and the problem of low detection accuracy of the small target is effectively improved. Secondly, Global Context attention is introduced in Backbone to optimize the CSPDarknet53 to 2-Stage FPN (C2F) module and model global context information. At the same time, the feature up-sampling module Content-Aware Reassembly of Features (CARAFE) was introduced into Neck to enhance the ability of the network to extract spore features in natural scenes further. Finally, we used an Explainable Artificial Intelligence (XAI) approach to interpret the model’s predictions. The experimental results showed that the improved GCS-YOLOv8 model could detect the spores of the three fungi with an accuracy of 0.926 and a model size of 22.8 MB, which was significantly superior to the existing model and showed good robustness under different brightness conditions. The test on the microscopic images of the infection structure of cucumber down mildew also proved that the model had good generalization. Therefore, this study realized the accurate detection of pathogen spores in natural scenes and provided feasible technical support for early predicting and preventing fungal diseases.

Abstract Slot structure is the equilibrium result of market demand side and slot resource supply side, while slot parameters reflect the operational support capacity of the aviation system. Time parameters reflect the operational support capability of the aviation system. Time structure should not only reflect changes in market demand, but also meet the constraints of operational efficiency. Constructing a reasonable 18–24 h timetable profile for busy airports that meets normal expectations for declared capacity and seasonal scheduling is a challenge in civil aviation slot management. This study utilizes historical data on airport flights and weather conditions to establish a regression prediction model for the time structure using K-means clustering and partial least squares regression. Additionally, ensemble learning is employed to forecast flight delay levels. The findings demonstrate that random forest yields favorable results in regression and prediction tasks, allowing for the integration of upper (good weather) and lower (severse weather) limits of the time profile with delay predictions as time parameter intervals. Consequently, the flights falling within these intervals achieve an average delay level of less than 15 min which meets the expectations of normal flight.

Seed coat color affects the appearance and commodity quality of mung beans (Vigna radiata L.). The substances that affect mung bean seed coat color are mainly flavonoids, which have important medicinal value. Mapping the seed coat color gene in mung beans would facilitate the development of new varieties and improve their value. In this study, an F2 mapping population consisting of 546 plants was constructed using Jilv9 (black seed coat) and BIS9805 (green seed coat). Using bulk segregated analysis (BSA) sequencing and kompetitive allele-specific PCR (KASP) markers, the candidate region related to seed coat color was finally narrowed to 0.66 Mb on chromosome (Chr.) 4 and included eight candidate genes. Combined transcriptome and metabolome analyses showed that three of the eight candidate genes (LOC106758748, LOC106758747, and LOC106759075) were differentially expressed, which may have caused the differences in flavonoid metabolite content between Jilv9 and BIS9805. These findings can provide a research basis for cloning the genes related to seed coat color and accelerate molecular marker-assisted selection breeding in mung beans.

Abstract Backgrounds Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. Methods Denervation‐induced muscle atrophy model was constructed in wild‐type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol‐free RBP4 (apo‐RBP4), retinol‐bound RBP4 (holo‐RBP4) or oral gavage of RBP4 inhibitor A1120. Holo‐RBP4‐stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross‐sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. Results The expression levels of RBP4 in skeletal muscles were significantly up‐regulated more than 2‐fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation‐induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin‐1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol‐bound holo‐RBP4 aggregated denervation‐induced ectopic fat accumulation and muscle atrophy. Consistently, holo‐RBP4 stimulation also had a dose‐dependent effect on the reduction of C2C12 myotube diameter and myofibre cross‐sectional area, as well as on the increase of Atrogin‐1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo‐RBP4 treatment increased the expression of its membrane receptor STRA6 (>3‐fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin‐1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3‐fold) in holo‐RBP4‐treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation‐induced muscle atrophy (30% increased myofibre cross‐sectional area) in mice. Conclusions In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6‐dependent and JAK2/STAT3 pathway‐mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

Abstract Background The Health and Medical Assistance Program for Poverty Alleviation is part of China’s targeted poverty elimination strategy, which aims to protect poor people’s right to health and prevent them from becoming trapped in or returning to poverty because of illness. Many tasks have been defined in this program, including raising the medical insurance level, providing a triage system, improving medical and health services, and enhancing people’s health. One pivotal aspect of this initiative involves equitable health resource allocation, a key measure aimed at bolstering medical and health services. This study aimed to analyze and compare health resource allocations in different counties in Northwest China after the implementation of the program. Methods The Gini coefficient quantifies the level of distributional equality, the Theil index assesses the sources of inequality, and the Health Resource Agglomeration Degree gauges the accessibility of health resources. Results 1) The health resource allocation distributed based on population(Gini Coefficient 0.35) among counties in Northwest China. 2) The contribution rate within non-impoverished counties is higher than that of impoverished counties, which means the inequality within non-impoverished counties. 3) The allocation of beds in medical institutions by area in non-impoverished counties was better than that in impoverished counties, and accessibility to health services for residents in non-impoverished counties was better than that in impoverished counties. Conclusion The analysis of health resource allocation among the five provinces in Northwest China revealed significant differences in equality among the five provinces in Northwest China, and the differences were mainly derived from the non-impoverished counties. Although the equality is gradually improving, the number of health resources in impoverished counties remain lower than that in non-impoverished counties.Subsequently, it is essential to ensure equitable distribution of healthcare resources while also taking into account their utilization and quality.

Abstract Visual adaptive devices have potential to simplify circuits and algorithms in machine vision systems to adapt and perceive images with varying brightness levels, which is however limited by sluggish adaptation process. Here, the avalanche tuning as feedforward inhibition in bionic two-dimensional (2D) transistor is proposed for fast and high-frequency visual adaptation behavior with microsecond-level accurate perception, the adaptation speed is over 104 times faster than that of human retina and reported bionic sensors. As light intensity changes, the bionic transistor spontaneously switches between avalanche and photoconductive effect, varying responsivity in both magnitude and sign (from 7.6 × 104 to −1 × 103 A/W), thereby achieving ultra-fast scotopic and photopic adaptation process of 108 and 268 μs, respectively. By further combining convolutional neural networks with avalanche-tuned bionic transistor, an adaptative machine vision is achieved with remarkable microsecond-level rapid adaptation capabilities and robust image recognition with over 98% precision in both dim and bright conditions.

Abstract The blood–brain barrier is often altered in glioblastoma (GBM) creating a blood–brain–tumor barrier (BBTB) composed of pericytes. The BBTB affects chemotherapy efficacy. However, the expression signatures of BBTB‐associated pericytes remain unclear. We aimed to identify BBTB‐associated pericytes in single‐cell RNA sequencing data of GBM using pericyte markers, a normal brain pericyte expression signature, and functional enrichment. We identified parathyroid hormone receptor‐1 (PTH1R) as a potential marker of pericytes associated with BBTB function. These pericytes interact with other cells in GBM mainly through extracellular matrix–integrin signaling pathways. Compared with normal pericytes, pericytes in GBM exhibited upregulation of several ECM genes (including collagen IV and FN1), and high expression levels of these genes were associated with a poor prognosis. Cell line experiments showed that PTH1R knockdown in pericytes increased collagen IV and FN1 expression levels. In mice models, the expression levels of PTH1R, collagen IV, and FN1 were consistent with these trends. Evans Blue leakage and IgG detection in the brain tissue suggested a negative correlation between PTH1R expression levels and blood–brain barrier function. Further, a risk model based on differentially expressed genes in PTH1R+ pericytes had predictive value for GBM, as validated using independent and in‐house cohorts.

ABSTRACT Corynebacterium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum, C. pseudodiphtheriticum, C. accolens, and C. tuberculostearicum. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the metabolic capabilities of 87 distinct human nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the United States. C. pseudodiphtheriticum had geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution spanning Africa and North America. All species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent versus accessory genome of each species indicating limited strain-level variability in metabolic capacity. Based on prevalence data, at least two Corynebacterium species likely coexist in the nasal microbiota of 82% of adults. So, it was surprising that core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the U.S. clade of C. pseudodiphtheriticum lacked genes for assimilatory sulfate reduction present in most of the strains in the Botswana clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches.IMPORTANCEPangenomic analysis with estimation of functional capabilities facilitates our understanding of the full biologic diversity of bacterial species. We performed systematic genomic, phylogenomic, and pangenomic analyses with qualitative estimation of the metabolic capabilities of four common human nasal Corynebacterium species, along with focused experimental validations, generating a foundational resource. The prevalence of each species in human nasal microbiota is consistent with the common coexistence of at least two species. We identified a notably high level of metabolic conservation within and among species indicating limited options for species to occupy distinct metabolic niches, highlighting the importance of investigating interactions among nasal Corynebacterium species. Comparing strains from two continents, C. pseudodiphtheriticum had restricted geographic strain distribution characterized by an evolutionarily recent loss of assimilatory sulfate reduction in U.S. strains. Our findings contribute to understanding the functions of Corynebacterium within human nasal microbiota and to evaluating their potential for future use as biotherapeutics.

Abstract N‐butylphthalide (NBP) has been reported to have potential protective effects in ischemic stroke via its antioxidative properties. The present study was aimed to investigate the protective effects of NBP on ischemia/reperfusion (I/R)‐induced skeletal muscle injury. Mouse model of I/R‐induced skeletal muscle injury and hypoxia/reoxygenation (H/R)‐induced C2C12 myotube injury model were constructed to test the protective effects of NBP both in vivo and in vitro. Our results showed that I/R resulted in skeletal muscle injury, as evidenced by elevated levels of LDH, CK, ROS, 3‐NT, MDA, and 4‐HNE as well as decreased activities of SOD, GSH‐Px, and decreased expression of Myog and MyoD in gastrocnemius muscle, which was ameliorated by NBP treatment. Mechanistically, NBP treatment increased the expression of Sirt1 and Nrf2 in the injured skeletal muscle. Notably, the protective effects of NBP on I/R‐induced skeletal muscle injury was diminished by the treatment of Sirt1 inhibitor. Further studies in H/R‐induced C2C12 myotubes injury model also showed that NBP activated the Sirt1/Nrf2 pathway. NBP treatment upregulated the expression of myog and MyoD in H/R‐stimulated C2C12 myotubes, which was eliminated by silencing of Sirt1. Taken together, our results suggest that NBP may alleviated I/R‐induced skeletal muscle injury by activating Sirt1/Nrf2 signaling pathway.

PurposeThis study explored the clinical characteristics of patients with tinnitus who responded to sound therapy and established a predictive model to evaluate the effectiveness of this therapy according to the clinical characteristics.MethodsA retrospective analysis was performed on 991 subjective tinnitus patients who received compound sound therapy in the Department of Otolaryngology of the local hospital from November 2019 to January 2022.ResultsWe found that tinnitus patients with different therapeutic effects had significant differences in the tinnitus side (p = 0.007), tone loudness distortion feedback test (FBT) (p = 0.000), residual inhibition test (RIT) (p = 0.000), tinnitus frequency (p = 0.012) and sensation level (p = 0.023). The corresponding variables were screened by univariate logistic regression, and the selected variables were analyzed using multivariate logistic regression. The results showed that FBT (p = 0.003), RIT (p = 0.000) and tinnitus frequency (p = 0.029) were independent risk factors affecting the efficacy of compound sound therapy. A predictive model and nomogram for the efficacy of compound sound therapy for tinnitus were constructed based on independent risk factors. The area under the curve (AUC) of the model constructed in this study was 0.766 (95% CI = 0.725–0.807), indicating a certain prediction ability. The calibration curve revealed that the predicted results were in good agreement with the actual results.ConclusionThe model can predict the prognosis of tinnitus in patients receiving compound sound therapy and help otolaryngologists make the best clinical decisions regarding tinnitus treatment.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study’s core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain.

PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions that lead to overgrowth of various body parts resulting from activating variants in PIK3CA. The absence of ideal cell models significantly impedes progress in PROS research. In this study, we focused on facial infiltrating lipomatosis (FIL) (A disorder within PROS) and aimed to establish and characterize an immortalized PROS cell line. Primary adipose-derived stem cells of FIL were immortal-ized through the transfection of simian virus 40 large T antigen (SV40LT). No significant mor-phological differences were observed in immortalized FIL-ADSCs (Im FIL-ADSCs). Im FIL-ADSCs expressed original mesenchymal surface markers, confirmed by flow cytometry. It harbored PIK3CA mutation and an increased level of PI3K/AKT activation, revealed by sanger sequencing and Western blot respectively. Karyotype analysis revealed a stable chromosome in Im FIL-ADSCs. Higher adipogenic potential and lower osteogenic differentiation properties were de-tected in Im FIL-ADSCs. The proliferative potential of Im FIL-ADSCs increased, whereas malig-nant transformation was not observed in the tumorigenesis assay. Moreover, RNA sequencing further elucidated the role of the transcription factor E2F1 in Im FIL-ADSCs. Drug screening unveiled that STAT3, HSP, EGFR, and NF-kB might be potential therapeutic targets for FIL. This study provided a valuable cellular resource for exploring the underlying pathogenic mechanisms and developing new targeted therapeutic options for PROS.

Appropriate nitrogen (N) fertilization and planting density management are critical for efficient production of grain maize (Zea mays L.) and for environmental protection. However, the optimal N fertilization and planting density is still not established for forage maize that is cultivated to promote its vegetative growth and utilized for the above-ground vegetative mass. A two-year field experiment was conducted in the rainfed semiarid region of the Chinese Loess Plateau during the 2021 and 2022 growing seasons. The effects of N application rates and planting densities on the dry matter yields and the water- and N-use efficiencies of forage maize were studied. The experiment includes four N application rates (0, 90, 180, and 270 kg ha−1) and three plant densities (70000, 90000, and 110000 plants ha−1), covering the conventional practices of local farmers. The treatments were organized in a randomized complete block design with four replications. Averaged over the three plant densities, N application rate of 180 kg ha−1 resulted in the maximum average aboveground dry matter yield (18.6 t ha−1), crop N accumulation (228.5 kg ha−1), dry matter water productivity (51.9 kg ha−1 mm−1), and dry matter precipitation productivity (62.9 kg ha−1 mm−1) over the two years. Moreover, increasing N application rates significantly increased the soil nitrate-N accumulation (0–200 cm) but reduced the partial factor productivity of applied N fertilizer. Across the three plant densities, the two-year average soil nitrate-N accumulation was 12.6, 32.1, and 75.7 % higher with 90, 180, and 270 kg N ha−1 compared to no N treatment, respectively. The highest soil nitrate accumulation under 270 kg ha−1 N application rate in 2021 (229.5 kg ha−1) and in 2022 (329.7 kg ha−1) may cause severe nitrate leaching loss and potential soil water contamination, driven by intensive rainfalls. Averaged over the four N rates, planting density of 110000 plants ha−1 increased the crop N accumulation and PFP by 21.2 % and 15.8 % in 2021, compared to 70000 plants ha−1, respectively. The interaction of N application and planting density significantly affected the aboveground dry matter yield, crop water consumption, dry matter precipitation productivity, and crop N accumulation in 2021, but the effect was non-significant in 2022. Based on these findings, application of 180 kg N ha−1 and planting density of 110000 plants ha−1 are suggested as an efficient management strategy for improving productivity of forage maize and soil water and N resources utilization in the arid region of the Loess Plateau and similar areas.

Accurate paddy rice mapping is crucial for ensuring food security and guiding agricultural production. Vegetation indices are extensively employed to map paddy rice. However, most traditional normalized indices tend to be oversaturated during periods of lush vegetation due to normalization errors, resulting in uncertainties in paddy rice mapping. To address this issue, we introduce a novel red-edge rice index (RERI) in this study; this index comprises information from red, near-infrared, and red-edge bands without normalization. To extract single- and double-cropping rice features from potential rice areas, we employ GF-6 and Sentinel-2 images based on the proposed RERI and the random forest algorithm. The proposed method is validated in the Dingcheng District of Changde city, China, and the results are compared with those based on three normalized vegetation indices. The results show that the RERI yielded the highest levels of the accuracy for all the metrics, achieving an overall accuracy (OA) of 92.50% and a kappa coefficient of 0.8875. The RERI exhibited F1 scores of 92.26% for single-cropping rice, 93.00% for double-cropping rice, and 92.28% for non-rice areas. Our results highlight the potential of using the RERI for rice identification, and the effectiveness of our method for rice extraction is demonstrated.

ABSTRACTBackground: Maternal experiences of childhood maltreatment (CM) constitute a risk factor for impairments in the mother–child relationship. One mechanism underlying this intergenerational transmission may be maternal hypothalamic–pituitary–adrenal axis dysregulation. Yet, few studies have examined different maltreatment subtypes, including emotional neglect, considered concurrent depressive symptoms, and used long-term integrated glucocorticoid measures.Objective: This study aimed to investigate associations between maternal CM history, postpartum glucocorticoids in hair, and mother–child bonding. In exploratory analyses, we tested whether specific subtypes of CM had differential implications for glucocorticoid secretion and bonding.Methods: During pregnancy, N = 269 mothers from the prospective cohort study DREAMHAIR provided retrospective information on CM and current information regarding psychological and hair-related variables. Hair samples were collected 8 weeks after delivery for quantification of maternal long-term hair cortisol and cortisone concentrations in 2-cm scalp-near hair samples. Mother–child bonding was measured 8 weeks and 14 months after birth using the Postpartum Bonding Questionnaire.Results: While bivariate correlations revealed significant associations of CM with bonding and hair cortisol, regression findings showed CM was associated with impaired bonding 8 weeks (overall CM trend-level; emotional neglect p = .038) and 14 months (emotional neglect trend level p = .041) after birth, however not after controlling for depressive symptoms at the time point of the outcome. In regression analyses, CM was not associated with maternal hair glucocorticoids 8 weeks postpartum. Maternal hair glucocorticoid concentrations were not related to mother–child bonding and did not mediate associations between CM and mother–child bonding.Conclusion: Data tentatively suggest that mothers with CM experiences, in particular emotional neglect, may be at risk for suboptimal bonding to their child, however current depressive symptoms seem to be more important. Our data provide no evidence for a crucial role of glucocorticoid secretion, yet aetiological processes of long-term glucocorticoid secretion and bonding are complex and more severely affected samples should be examined.

Herein, a sandwich electrochemical sensing strategy for aflatoxin b1 (AFB1) detection based on hybrid-nanoengineering was presented. First, Au nanoparticle was doped into zeolitic imidazolate framework-8 (ZIF-8) to form Au@ZIF-8 by in-situ growth method, followed by multi-walled carbon nanotubes (MWCNTs) addition to synthesize MWCNTs/Au@ZIF-8 via self-assembly. The structural “confinement effect” of ZIF-8 afforded a microenvironment for Au nanoparticles and SMCNTs in a certain spatial region, giving MWCNTs/Au@ZIF-8 excellent electrochemical property as the substrate material. In addition, Au-Pt bimetallic nanoparticle, which exhibited excellent stability and catalytic activity was loaded on the hollow cerium oxide (CeO2) to form AuPt@CeO2 nanoparticle through one-step aqueous phase reduction. Owning to its high surface-to-volume ratio, satisfied electron transfer efficiency and biocompatibility, massive toluidine blue (TB) and AFB1 antibody (Ab) could be modified on the AuPt@CeO2 to form AuPt@CeO2-Ab-TB, which acted as signal tag for the ultrasensitive assay of AFB1. The proposed electrochemical sensing system exhibited wide detection range (2 × 10-5 − 20 ng/mL) and low detection limit (2.13 fg/mL), which has been successfully applied to AFB1 determination in four real samples. The hybrid nanoengineering presented in this work is an active attempt to prepare high-performance substrate material and signal tag, which provides a new insight for the development of highly sensitive and specific electrochemical sensing systems.

Crowd density is an important metric for preventing excessive crowding in a particular area, but it still faces challenges such as perspective distortion, scale variation, and pedestrian occlusion. Existing studies have attempted to model the spatio-temporal dependencies in videos using LSTM and 3D CNNs. However, these methods suffer from large computational costs, excessive parameter redundancy, and loss of temporal information, leading to difficulties in model convergence and limited recognition performance. To address these issues, we propose a lightweight multi-stage temporal inference network (LMSTIN) for video crowd counting. LMSTIN effectively models the spatio-temporal dependencies in video sequences at a fine-grained level, enabling real-time and accurate video crowd counting. Our proposed method achieves significant performance improvements on three public crowd counting datasets.

Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer’s disease and Parkinson’s disease). Therefore, NDDs have profound negative impacts on patients, their families, and society, making them a major global health concern. Rho-associated kinases (ROCKs) belong to the serine/threonine protein kinases family, which modulate diverse cellular processes (e.g., apoptosis). ROCKs may elevate the risk of various NDDs (including Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease) by disrupting synaptic plasticity and promoting inflammatory responses. Therefore, ROCK inhibitors have been regarded as ideal therapies for NDDs in recent years. Fasudil, one of the classic ROCK inhibitor, is a potential drug for treating NDDs, as it repairs nerve damage and promotes axonal regeneration. Thus, the current review summarizes the relationship between ROCKs and NDDs and the mechanism by which fasudil inhibits ROCKs to provide new ideas for the treatment of NDDs.

IntroductionScalp arteriovenous fistula (AVF) is a rare and intricate vascular anomaly characterized by a direct connection between an artery and a vein, without an intervening capillary system. This anomaly can induce significant local hemodynamic changes and is associated with various complications, such as pain, a pulsatile mass, increasing swelling, and venous hypertension skin ulcerations which may be non-healing. This study aimed to evaluate the efficacy and safety of interventional embolization treatments for scalp AVF at Shandong Provincial Hospital.MethodsThis retrospective clinical analysis assessed 21 patients who underwent interventional embolization between 2018 and 2024. Patients included were those treated in the vascular surgery department at Shandong Provincial Hospital, who had comprehensive medical records and follow-up data. Treatment methods, outcomes, and complications were thoroughly analyzed through patient medical records.ResultsAmong the patients studied, direct puncture was the most prevalent treatment method, employed in 42.86% (9/21) of cases, followed by various combinations of arterial, venous, and direct approaches. Ethanol, used in 85.71% (18/21) of the cases, demonstrated its broad efficacy and application in clinical settings. Immediate imaging post-treatment confirmed a cure rate of 85.71% (18/21). The main postoperative complications included swelling, with some patients also experiencing nodules, scabbing, or hair loss.ConclusionInterventional embolization has proven to be a safe and effective method for managing scalp AVF, significantly minimizing complications. Future research should focus on further optimizing these treatment methods to enhance efficacy and improve patient quality of life.

The receptive field (RF) plays a crucial role in convolutional neural networks (CNNs) because it determines the amount of input information that each neuron in a CNN can perceive, which directly affects the feature extraction ability. As the number of convolutional layers in CNNs increases, there is a decay of the RF according to the two-dimensional Gaussian distribution. Thus, an effective receptive field (ERF) can be used to characterize the available part of the RF. The ERF is calculated by the kernel size and layer number within the neural network architecture. Currently, ERF calculation methods are typically applied to single-channel input data that are both independent and identically distributed. However, such methods may result in a loss of effective information if they are applied to more general (i.e., multi-channel) datasets. Therefore, we proposed a multi-channel ERF calculation method. By conducting a series of numerical experiments, we determined the relationship between the ERF and the convolutional kernel size in conjunction with the layer number. To validate the new method, we used the recently published global wave surrogate model for climate simulation (GWSM4C) and its accompanying dataset. According to the newly established relationship, we refined the kernel size and layer number in each neural network of the GWSM4C to produce the same ERF but lower RF attenuation rates than those of the original version. By visualizing the gradient map at several points in West African and East Pacific areas, the high gradient value regions confirmed the known swell sources, which indicated effective feature extraction in these areas. Furthermore, the new version of the GWSM4C yielded better prediction accuracy for significant wave height in global swell pools. The root mean square errors in the West African and East Pacific regions reduced from approximately 0.3 m, in the original model to about 0.15 m, in the new model. Moreover, these improvements were attributed to the higher efficiency of the newly modified neural network structure that allows the inclusion of more historical winds while maintaining acceptable computational consumption.

Abstract With the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guidelines in effect from 2018, the design of Asia‐inclusive multiregional clinical trials (MRCTs) has been streamlined, thereby enabling efficient simultaneous global development. Furthermore, with the recent regulatory reforms in China and its drug administration joining the ICH as a full regulatory member, early participation of China in the global clinical development of novel investigational drugs is now feasible. This would also allow for inclusion of the region in the geographic footprint of pivotal MRCTs leveraging principles of the ICH E5 and E17. Herein, we describe recent case examples of model‐informed Asia‐inclusive global clinical development in the EMD Serono portfolio, as applied to the ataxia telangiectasia and Rad3‐related inhibitors, tuvusertib and berzosertib (oncology), the toll‐like receptor 7/8 antagonist, enpatoran (autoimmune diseases), the mesenchymal–epithelial transition factor inhibitor tepotinib (oncology), and the antimetabolite cladribine (neuroimmunological disease). Through these case studies, we illustrate pragmatic approaches to ethnic sensitivity assessments and the application of a model‐informed drug development toolkit including population pharmacokinetic/pharmacodynamic modeling and pharmacometric disease progression modeling and simulation to enable early conduct of Asia‐inclusive MRCTs. These examples demonstrate the value of a Totality of Evidence approach where every patient's data matter for de‐risking ethnic sensitivity to inter‐population variations in drug‐ and disease‐related intrinsic and extrinsic factors, enabling inclusive global development strategies and timely evidence generation for characterizing benefit/risk of the proposed dosage in Asian populations.

ObjectiveThe aim of this investigation is to explore the efficacy of combined exercise in elderly patients with hypertension. Moreover, we aim to delve into the underlying mechanisms governing blood pressure regulation, with the objective of promoting the adoption of this exercise regimen among elderly hypertensive individuals.MethodsIn our study, we conducted a thorough search across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and Scopus. This extensive search resulted in the preliminary screening of 2,347 articles. Among these, 9 studies were carefully selected for an in-depth analysis. For our meta-analysis, we employed Review Manager 5.3 and Stata 15.0, enabling us to perform detailed subgroup analyses and assess the possibility of publication bias.ResultsIn comparison to the control group (n = 194), individuals enrolled in the combined exercise group (n = 200) exhibited a notable decrease in both resting systolic blood pressure (SBP) [weighted mean difference (WMD) = −11.17 mm Hg, 95% confidence interval (CI) (−17.13, −5.22), Z = 3.68, P

Abstract To enhance the anesthetic efficacy and reduce toxic side effects, a strategy is proposed involving the utilization of general anesthetics of Propofol (Pro) and Etomidate (Eto) to synergistic inhibition GABA receptors simultaneously. Four‐in‐one molecular aggregates were prepared to implement this strategy, which comprised of Pro and Eto with the bridging molecule monoglyceride monooleate (GMO) and surfactant F127 through intermolecular forces. The blood‐brain barrier (BBB) targeted lactoferrin (LF) is affixed to their surface, obtaining the final molecular aggregates. By employing lactoferrin enrich aggregates to the BBB, followed by ultrasound combine microbubbles to open the BBB, a remarkable 4.5‐fold enhancement in brain drug delivery was achieved. The molecular aggregates group maintained stable parameters of heart rate, diastolic blood pressure, and systolic blood pressure. A notable increase of more than twice therapeutic index (TI) value was observed, implying their higher anesthesia efficiency and reduced toxicity. Electroencephalogram (EEG) experiments demonstrate a significant elevation in the proportion of δ waves from 28% to 80% for aggregates, accompanied by a nearly fivefold reduction in the proportion of θ waves, meaning a significant improvement in synergistic anesthesia effectiveness (interaction index 0.289) with lower drug dosage. Furthermore, mouse immunofluorescence brain slice experiments suggest Pro and Eto enter the GABA receptor simultaneously, resulting in synergistic inhibition of GABA receptors.

Abstract BackgroundVideo-based error correction (VBEC) in medical education could offer immediate feedback, promote enhanced learning retention, and foster reflective practice. However, its application in cardiopulmonary resuscitation (CPR) training has not been investigated. ObjectiveThe objective of this study is to assess whether the VBEC procedure could improve the training performance of CPR among anesthesiology residents. MethodsA quasi-experimental study was conducted among anesthesiology residents between December 2022 and April 2023. Primary outcomes included a posttraining knowledge test and practical assessment scores. Secondary outcomes included the number of residents who correctly conducted CPR at each step, the rate of common mistakes during the CPR process, and the self-assessment results. A total of 80 anesthesiology residents were divided into a VBEC group (n=40) and a control group (n=40). The VBEC group underwent a 15-minute VBEC CPR training, whereas the control group underwent a 15-minute video-prompting CPR training. ResultsThe posttraining knowledge test score of the VBEC group was significantly higher than that of the control group (73, SD 10.5 vs 65.1, SD 11.4; PPPPP ConclusionsVBEC may be a promising strategy compared to video prompting for CPR training among anesthesiology residents.

Summary: Lavender essential oil (LEO) has been shown to relieve pain in humans, but the underlying neural mechanisms remain unknown. Here, we found that inhalation exposure to 0.1% LEO confers antinociceptive effects in mice with complete Freund adjuvant (CFA)-induced inflammatory pain through activation of projections from the anterior piriform cortex (aPir) to the insular cortex (IC). Specifically, in vivo fiber photometry recordings and viral tracing data show that glutamatergic projections from the aPir (aPirGlu) innervate GABAergic neurons in the IC (ICGABA) to inhibit local glutamatergic neurons (ICGlu) that are hyperactivated in inflammatory pain. Optogenetic or chemogenetic activation of this aPirGlu→ICGABA→Glu pathway can recapitulate the antinociceptive effects of LEO inhalation in CFA mice. Conversely, artificial inhibition of IC-projecting aPirGlu neurons abolishes LEO-induced antinociception. Our study thus depicts an LEO-responsive olfactory system circuit mechanism for alleviating inflammatory pain via aPir→IC neural connections, providing evidence to support development of aroma-based treatments for alleviating pain.

Giant cell glioblastoma often exhibits genome instability and is frequently associated with mutations in genes involved in DNA repair pathways including TP53 and DNA mismatch repair genes. Several germline mutations have been identified in giant cell glioblastoma, including mutations of MSH1 and MSH2, TP53, and POLE. We have documented a case of a germline mutation in CHEK2, another gene crucial to DNA repair, in a patient with giant cell glioblastoma. The CHEK2 mutation was inherited from the patient’s father, who had a history of gastric cancer and renal cell carcinoma. In addition to the germline CHEK2 mutation, the giant cell glioblastoma exhibited a genome-wide loss of heterozygosity, a characteristic observed in a subset of giant cell glioblastomas. Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.

Background: Few studies have compared the performances of those reported miRNAs as biomarkers for heart failure with reduced EF (HFrEF) in a population at high risk. The purpose of this study is to investigate comprehensively the performance of those miRNAs as biomarkers for HFrEF. Methods: By using bioinformatics methods, we also examined these miRNAs' target genes and possible signal transduction pathways. We collected serum samples from patients with HFrEF at Zhongshan Hospital. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for HFrEF. miRWALK2.0, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. Results: The study included 48 participants, of whom 30 had HFrEF and 18 had hypertension with normal left ventricular ejection fraction (LVEF). MiR-378, miR-195-5p were significantly decreased meanwhile ten miRNAs were remarkably elevated (miR-21-3p, miR-21-5p, miR-106-5p, miR-23a-3p, miR-208a-3p, miR-1-3p, miR-126-5p, miR-133a-3p, miR-133b, miR-223-3p) in the serum of the HFrEF group. Conclusion: The combination of miR 133a-3p, miR 378, miR 1-3p, miR 106b-5p, and miR 133b has excellent diagnostic performance for HFrEF, and there is a throng of mechanisms and pathways by which regulation of these miRNAs may affect the risk of HFrEF.

Analyzing capacity degradation characteristics and accurately predicting the knee point of capacity are crucial for the safety management of lithium-ion batteries (LIBs). However, the degradation mechanism of LIBs is complex. A key but challenging problem is how to clarify the degradation mechanism and predict the knee point. According to the external characteristics such as capacity decline gradievnt and the peak value of increment capacity curve (IC curve), the capacity degradation can be divided into four stages, including initial decline stage, slow decline stage, transition stage and high-speed decline stage. The degradation mechanism of LIBs is compared from the longitudinal and horizontal aspects, respectively. Among them, the battery usage from the initial stage to the end of life (EOL) is longitudinal analysis. The battery under different conditions, such as charging and discharging, different discharge rate, different cathode material degradation mechanism is horizontal analysis. Moreover, a method based on neural network is proposed to predict the knee point. Two features are used to predict the capacity and cycle of the knee point, which are the gradient of the capacity degradation curve and the difference of the IC curve with the maximum correlation. The experimental results show that a two-dimensional surface can be obtained using only the first 100 cycles, which can provide a reference for the position of the knee point accurately prediction.

Background: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. Methods: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. Results: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. Conclusion: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

The protection dead-zone and threshold setting difficulties of the residual current devices (RCDs) in low-voltage distribution networks may lead to the misidentification of electric shock fault, resulting in severe life-threatening accidents. This paper proposes an electric shock fault identification method based on artificial intelligence for RCDs. Firstly, Mallat discrete wavelet transform (DWT) is applied to efficiently extract non-stationary electric shock feature signals from the total residual current with various noises, preventing weak non-stationary electric shock feature signals from being filtered out. Based on the average and maximum components of the signal mutation, an adaptive threshold can be determined to detect electric shock accurately, avoiding the false activation of RCDs caused by load fluctuations. Subsequently, an autoencoder (AE) is built to mine the non-linear features in which the signal of electric shock on living gradually rises and the signal of electric shock on non-living remains stable. Finally, a back propagation neural network (BPNN) is trained to classify the electric shock types from the non-linear features. The simulation and experiment have been conducted to obtain total residual current data under different conditions, and the electric shock fault real-time identification hardware platforms are developed. The accuracy of electric shock fault detection and classification can reach 100 %, which has advanced its practical applicability.

Accelerating the exploration and development of deep ( > 1 000 m)coalbed methane (CBM) resources is an important way for the large-scale development of CBM and an important development direction in recent years. Guizhou Province is rich in CBM resources, with a large proportion of deep CBM resources. However, up to now, the geological research and exploration of deep CBM resources have not been carried out. Based on the geological background of CBM in Guizhou, this paper analyzes the geological characteristics and resource potential of deep CBM in Guizhou Province using a large number of CBM well test data. The research results show that the deep CBM resources in Guizhou are mainly distributed in many syncline units of the Liupanshui, North Guizhou and Zhina coalfields. Sedimentary differentiation and structural zoning lead to regional differences in the geological conditions of deep CBM reservoirs. The Liupanshui coalfield is characterized by “obvious overpressure, low temperature and high stress”, the Zhina coalfield is characterized by “overpressure, high temperature and low stress”, and the northern Guizhou coalfield is characterized by “overpressure, high temperature and high stress”. The permeability of deep CBM reservoir is low, and the permeability of 1 000 m deep will be generally lower than 0.1×10−15 m2. The CBM content of the coal reservoir is relatively high. The average CBM content of the middle-rank coal reservoir represented by the Liupanshui coalfield is 10.03 m3/t, and the average CBM content of the high-rank coal reservoir represented by the Zhina and Qianbei coalfields is 14.51 m3/t, and the deep supersaturation phenomenon is more obvious at 400 m. Based on the prediction model of free gas and adsorbed gas, considering the change of coal rack, it is predicted that the overall gas content in the deep part will further increase, and the supersaturation phenomenon will be more obvious, and the proportion of free gas will increase. At about 2000 m, the proportion of free gas will generally reach 10%−25%, and the proportion of free gas in medium-rank coal is higher than that in high-rank coal. On this basis, the geological resources of CBM in the key synclines of Guizhou Province with a depth of more than 2000 m are calculated. Based on the calculation results, the geological resources of CBM in Guizhou Province is 3.85 trillion m3, of which the geological resources of CBM in the depth of 1000 m reach 1.90 trillion m3, and the deep CBM resources in the Liupanshui and northern Guizhou coalfields account for a large proportion. Considering the scale and abundance of resources comprehensively, the development sequence is proposed. The Panguan-Tucheng-Zhaozihe-Jiupu'an syncline and the Gemudi syncline are the preferred development units. The above synclines are large gas fields with high abundance.

In Guizhou Province, there are many coal-bearing structural units, many layers of coal, thin thickness, and most of them are low permeability reservoirs, so it is advisable to adopt the process of “staged fracturing and combined layer drainage and production” to develop coalbed methane. Taking Banguan syncline coalbed methane well as an example, this study analyzed the fracturing effect of two vertical Wells on the basis of the scale of fracturing reconstruction, and then studied the influence of fracturing reconstruction effect on the gas and water production of coalbed methane Wells, and finally summarized the reasonable threshold of efficient fracturing construction parameters of Banguan syncline coalbed methane Wells. The results show that hydraulic fracturing is an effective way to increase permeability of low permeability reservoir, and the permeability increase multiple is closely related to the scale of fracturing reconstruction. The differences of sand addition, liquid addition and single-hole displacement per meter of coal seam between the two Wells of Banguan syncline lead to the permeability ratio of 55∶1 after fracturing reconstruction, and the permeability difference after reconstruction is large. Increasing the liquid addition, sand addition and single hole displacement per meter of coal seam is beneficial to improving the transformation effect of coal seam and gas production. It is recommended that the liquid addition per meter of coal seam should not be less than 400 m3, the sand addition per meter of coal seam should not be less than 20 m3, the fracturing construction displacement should not be less than 8 m3/min, and the single hole displacement should be controlled above 0.2 m3/min. According to the permeability of the coal seam after fracturing and reconstruction, it can be appropriate to quickly discharge and depressurize the coalbed methane Wells with good reconstruction effect. Otherwise, the intensity of discharge and production should be controlled to reduce the sensitivity damage of the reservoir caused by fast discharge and depressurization. The research results can provide technical reference for the permeability and energy improvement of low permeability coal seam in this block.

Abstract Objective The objective of the present study was to explore the correlation between the advanced lung cancer inflammation index (ALI) and in‐hospital mortality among patients diagnosed with community‐acquired pneumonia (CAP). Methods Data from the Medical Information Mart for Intensive Care‐IV database were adopted to analyze the in‐hospital mortality of ICU patients with CAP. Upon admission to the ICU, fundamental data including vital signs, critical illness scores, comorbidities, and laboratory results, were collected. The in‐hospital mortality of all CAP patients was documented. Multivariate logistic regression (MLR) models and restricted cubic spline (RCS) analysis together with subgroup analyses were conducted. Results This study includes 311 CAP individuals, involving 218 survivors as well as 93 nonsurvivors. The participants had an average age of 63.57 years, and the females accounted for approximately 45.33%. The in‐hospital mortality was documented to be 29.90%. MLR analysis found that ALI was identified as an independent predictor for in‐hospital mortality among patients with CAP solely in the Q1 group with ALI ≤ 39.38 (HR: 2.227, 95% CI: 1.026–4.831, P = 0.043). RCS analysis showed a nonlinear relationship between the ALI and in‐hospital mortality, with a turning point at 81, and on the left side of the inflection point, a negative correlation was observed between ALI and in‐hospital mortality (HR: 0.984, 95% CI: 0.975–0.994, P = 0.002). The subgroup with high blood pressure showed significant interaction with the ALI. Conclusion The present study demonstrated a nonlinear correlation of the ALI with in‐hospital mortality among individuals with CAP. Additional confirmation of these findings requires conducting larger prospective investigations.

Abstract Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic effects on cryptosporidiosis. However, the underlying mechanism of its action remains unclear. In this study, we utilized network pharmacology and experimental validation to investigate the mechanism of oxymatrine in the treatment of cryptosporidiosis. First, the potential targets of drugs and diseases were predicted by TCMSP, Gene Cards, and other databases. Following the intersection of drug-disease targets, the DAVID database was used to implement the enrichment analysis of GO functions and KEGG pathways, and then the network diagram of "intersected target-KEGG" relationship was constructed. Autodock 4.2.6 software was used to carry out the molecular docking of core targets to drug components. Based on the establishment of a mouse model of cryptosporidiosis, the validity of the targets in the TNF/NF-κB signaling pathway was confirmed using Western blot analysis and Quantitative Rea-ltime-PCR. A total of 41 intersectional targets of oxymatrine and Cryptosporidium were generated from the results, and five core targets were screened out by network analysis, including RELA, AKT1, ESR1, TNF, and CASP3. The enrichment analysis showed that oxymatrine could regulate multiple gene targets, mediate TNF, Apoptpsis, IL-17, NF-κB and other signaling pathways. Molecular docking experiments revealed that oxymatrine was tightly bound to core targets with stable conformation. Furthermore, we found through animal experiments that oxymatrine could regulate the mRNA and protein expression of IL-6, NF-κB, and TNF-α in the intestinal tissues of post-infected mice through the TNF/NF-κB signaling pathway. Therefore, it can be concluded that oxymatrine can regulate the inflammatory factors TNF-α, NF-κB, and IL-6 through the TNF/NF-κB signaling pathway for the treatment of cryptosporidiosis. This prediction has also been validated by network pharmacology and animal experiments.