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Abstract Intermittent hypoxia (IH) precipitates pulmonary vasoconstriction, culminating in the onset of pulmonary hypertension (PH) among individuals afflicted with sleep apnea. While Nuclear receptor subfamily 1 group D member 1 (Nr1d1) is progressively recognized as pivotal regulator of cellular physiology, the role in the pathogenesis of IH-induced PH remains largely uncharted. The expression of Nr1d1 was examined in IH-induced rodent PH and in IH-treated PASMCs. To elucidate the contribution of Nr1d1 to the development of IH-induced PH, we employed siRNA to modulate Nr1d1 expression in vitro and employed serotype 1 adeno-associated virus (AAV1) in vivo. Nr1d1 levels were elevated in IH-induced rodents PH lung tissues and IH-treated PASMCs. Knocking down Nr1d1 by AAV1 effectively inhibited PH progression in chronic IH-induced PH models. Mechanistic investigations identified dual specificity phosphatase 1 (Dusp1), as a direct target that Nr1d1 trans-repressed, mediating Nr1d1’s regulatory influence on Erk1/2/Drp1 signaling. Nr1d1 deficiency ameliorates mitochondrial dysfunction and fission by restoring Dusp1 dysregulation and Drp1 phosphorylation. Activation of Erk1/2 with PMA reversed the Dusp1-mediated regulation of Drp1 phosphorylation, indicating the involvement of the Erk1/2 pathway in Drp1 phosphorylation controlled by Dusp1. Meanwhile, intermittent hypoxia induced more severe PH in Dusp1 knockout mice compared with wild-type mice. Our data unveil a novel role for Nr1d1 in IH-induced PH pathogenesis and an undisclosed Nr1d1-Dusp1 axis in PASMCs mitochondrial fission regulation.

Peiling Zhou,1 Shiyu Peng,2 Sizhe Wen,1 Qinghui Lan,1 Yingyin Zhuang,1 Xuyan Li,1 Mengliang Shi,1,3 Changzheng Zhang1 1Guangdong Provincial Key Laboratory of Development and Education for Special Needs Children & School of Educational Sciences, Lingnan Normal University, Zhanjiang, 524048, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Education, South China Normal University, Guangzhou, 510631, People’s Republic of ChinaCorrespondence: Changzheng Zhang, School of Educational Sciences, Lingnan Normal University, 29 Cunjin Road, Zhanjiang, Guangdong Province, 524048, People’s Republic of China, Email neurozhang@163.com Mengliang Shi, School of Education, South China Normal University, 55 West Zhongshan Avenue, Shipai Street, Guangzhou, Guangdong Province, 510631, People’s Republic of China, Email 20240169@m.scnu.edu.cnAbstract: The cerebellum has long been implicated in the etiopathogenesis of autism spectrum disorder (ASD), and emerging evidence suggests a significant contribution by reciprocal neural circuits between the cerebellum and ventral tegmental area (VTA) in symptom expression. This review provides a concise overview of morphological and functional alterations in the cerebellum and VTA associated with ASD symptoms, primarily focusing on human studies while also integrating mechanistic insights from animal models. We propose that cerebello–VTA circuit dysfunctional is a major contributor to ASD symptoms and that these circuits are promising targets for drugs and therapeutic brain stimulation methods.Keywords: autism spectrum disorder, cerebellum, ventral tegmental area, neural circuit

Huaqiong Wu,1,&ast; Guifen Yang,2,&ast; Shaohua Zhang,2 Jinxiang Luo,1 Pei Zhou,1 Yuhua Chen1 1Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 2Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Zhang, Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8618062579072, Email zhangshaohua1258@163.com Jinxiang Luo, Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8602750773333, Email luojinxiang2020@21cn.comObjective: To investigate the correlation between risk factors for coronary stenosis and the degree of coronary artery stenosis based on coronary computed tomography angiography (CCTA).Methods: Two hundred seventy-eight patients with coronary artery disease who received treatment in our hospital between January 2020 and January 2021 were selected as the experimental group, and 100 healthy people who received physical examination in our hospital during the same period were selected as the control group (age and gender matched with the study group). The clinical data and CCTA data of the two groups of patients were collected and compared. Computed tomography fractional flow reserve (FFRCT) values were calculated based on the CCTA data of the patients in the study group, risk factors for coronary artery stenosis were analysed and the correlation between the risk factors and CT flow reserve fraction was explored.Results: The serum total bilirubin (BIL), apolipoprotein A (apoA), low-density lipoprotein cholesterol (LDL-C), uric acid, total cholesterol (TC) and mean platelet volume levels were higher in the experimental group than in the control group (P < 0.05). Unconditional logistic regression analysis showed that LDL-C, uric acid, TC, triglyceride, serum total BIL and apoA were independent risk factors for coronary heart disease (P < 0.05). Serum total BIL (r = 0.27), apoA (r = − 0.30), uric acid (r = − 0.48), TC (r = − 0.35), triglyceride (r = − 0.73) and LDL-C (r = − 0.65) showed a negative correlation with FFRCT values (P < 0.05). A positive correlation was detected between high-density lipoprotein cholesterol and FFRCT values (r = 0.37, P < 0.05).Conclusion: Triglycerides, LDL-C, uric acid, TC, serum total BIL and apoA are risk factors for coronary artery stenosis that should be closely monitored and receive active intervention in clinical practice.Keywords: coronary heart disease, coronary artery stenosis, computed tomography angiography, risk factors, computed tomography fractional flow reserve

Emerging miniaturized atomic sensors such as optically pumped magnetometers (OPMs) have attracted widespread interest due to their application in high-spatial-resolution biomagnetism imaging. While optical probing systems in conventional OPMs require bulk optical devices including linear polarizers and lenses for polarization conversion and wavefront shaping, which are challenging for chip-scale integration. In this study, an integrated optical probing scheme based on localized-interference metasurface for chip-scale OPM is developed. Our monolithic metasurface allows tailorable linear polarization conversion and wavefront manipulation. Two silicon-based metasurfaces namely meta-polarizer and meta-polarizer-lens are fabricated and characterized, with maximum transmission efficiency and extinction ratio (ER) of 86.29 % and 14.2 dB for the meta-polarizer as well as focusing efficiency and ER of 72.79 % and 6.4 dB for the meta-polarizer-lens, respectively. A miniaturized vapor cell with 4 × 4 × 4 mm3 dimension containing 87Rb and N2 is combined with the meta-polarizer to construct a compact zero-field resonance OPM for proof of concept. The sensitivity of this sensor reaches approximately 9 fT/Hz1/2 with a dynamic range near zero magnetic field of about ±2.3 nT. This study provides a promising solution for chip-scale optical probing, which holds potential for the development of chip-integrated OPMs as well as other advanced atomic devices where the integration of optical probing system is expected.

Orthogonal time frequency space (OTFS) modulation is a multiplexing technique designed in the two-dimensional (2D) delay-Doppler domain suited for high Doppler fading channels. OTFS converts a doubly-selective channel into an almost non-fading channel in the delay-Doppler domain through a series of 2D transformations. OTFS has the potential of capturing time-frequency full diversity. In order to obtain the time-frequency full diversity gain, a receiver with advanced channel estimation and signal detection algorithm is needed. The basic principle and system model of OTFS was firstly introduced, then the existing channel estimation and signal detection algorithms were reviewed, finally the future challenges and solutions for channel estimation and signal detection were discussed.

Weihua Han,1,&ast; Peiyao Zhou,2,&ast; Chun Chen,3,&ast; Chunyang Wu,2 Li Shen,1 Cailing Wan,4 Yanghua Xiao,4 Jiao Zhang,2 Bingjie Wang,1 Junhong Shi,1 Xinru Yuan,1 Haojin Gao,1 Hongxiu Wang,1 Ying Zhou,1 Fangyou Yu1 1Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China; 4School of Public Health, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou; Fangyou Yu, Email 18702195157@163.com; wzjxyfy@163.comBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective β-lactam/β-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by Klebsiella pneumoniae carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant K. pneumoniae.Methods: The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.Results: Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of blaKPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.Discussion: Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying blaKPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.Keywords: carbapenem-resistant Enterobacterales, Klebsiella pneumoniae, ceftazidime-avibactam, KPC-12, carbapenemase

Postmenopausal osteoporotic fractures are a public health problem that troubles women worldwide. As a treasure of Traditional Chinese culture, Tai Chi has unique advantages of simplicity, convenience, simplicity, and effectiveness. This article summarizes the relevant research on the prevention and treatment of postmenopausal osteoporosis fractures using Tai Chi, analyzes existing problems, and provides theoretical basis for promoting traditional exercise therapy. (绝经后骨质疏松性骨折是困扰全球的女性公共健康问题。太极拳作为中国传统的中医养生功法, 具有“简、便、廉、效”的独特优势。本研究就太极拳防治绝经后骨质疏松性骨折的相关研究进行归纳总结, 分析现存问题, 为推广传统运动疗法提供理论依据。)

A fault prediction method driven by log information was proposed to address the impact of node failures on normal business operations in computer networks. By constructing an efficient deep learning model and introducing a correction mechanism, node failures in computer networks were predicted and diagnosed to meet the needs of network operation and maintenance. Firstly, the log information generated by each node in the computer network was collected, the state vectors of each node and the state matrices of all nodes were obtained, then the dataset through the state filling principle was supplemented, and finally the fault prediction problem into a time series prediction problem was transformed. The performance evaluation is conducted on the publicly available small-scale operation and maintenance dataset GAIA, and the experimental results show that compared with other algorithms, the proposed model has good predictive performance in local network scenarios, and its predictive effectiveness is verified, providing a certain reference value for computer network fault prediction research.

Peijie Zhou,&ast; Shangshang Yu,&ast; Xuan Wang,&ast; Xiaofei Zhang, Dongyan Guo, Chongbo Zhao, Jiangxue Cheng, Jing Wang, Jing Sun Department of Pharmaceutics, College of Pharmacy, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi Provincial Engineering Technology Research Center for Traditional Chinese Medicine Decoction Pieces, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Sun, Email ph.175@163.comBackground: Cerebral ischaemia-reperfusion injury (CIRI) could worsen the inflammatory response and oxidative stress in brain tissue. According to previous studies, ferulic acid methyl ester (FAME), as the extract with the strongest comprehensive activity in the traditional Chinese medicine Huang Hua oil dot herb, has significant anti-oxidative stress and neuroprotective functions, and can effectively alleviate CIRI, but its mechanism of action is still unclear.Methods: Firstly, the pharmacological effects of FAME were investigated by in vitro oxidative stress and inflammatory experiments. Secondly, evaluate the therapeutic effects of FAME in the treatment of CIRI by brain histopathological staining and cerebral infarct area by replicating the in vivo MACO model. Thirdly, RNA-Seq and network pharmacology were utilized to predict the possible targets and mechanisms of FAME for CIRI at the molecular level. Finally, the expression of key target proteins, as well as the key regulatory relationships were verified by molecular docking visualization, Western Blotting and immunohistochemistry.Results: The results of in vitro experiments concluded that FAME could significantly reduce the content of TNF-α, IL-1β and ROS, inhibiting COX-2 and iNOS protein expression in cells(p< 0.01). FAME was demonstrated to have anti-oxidative stress and anti-inflammatory effects. The results of in vivo experiments showed that after the administration of FAME, the area of cerebral infarction in rats with CIRI was reduced, the content of Bcl-2 and VEGF was increased(p< 0.05). Network pharmacology and RNA-Seq showed that the alleviation of CIRI by FAME may be through PI3K-AKT and HIF-1 signaling pathway. Enhanced expression of HIF-1α, VEGF, p-PI3K, p-AKT proteins in the brain tissues of rats in the FAME group was verified by molecular docking and Western Blotting.Conclusion: FAME possesses significant anti-inflammatory and anti-oxidative stress activities and alleviates CIRI through the PI3K/HIF-1α/VEGF signaling pathway. Keywords: ferulic acid methyl ester, cerebral ischemia-reperfusion injury, WGCNA, RNA-Seq, network pharmacology, molecular docking techniques

BackgroundObsessive-compulsive personality disorder and obsessive-compulsive disorder （OCD） are common psychological disorders with similar clinical symptoms， but the differences between the two need further clarification.ObjectiveTo explore the clinical features of and influencing factors of obsessive-compulsive personality disorder in patients with OCD， so as to provide references for further relevant clinical diagnosis and treatment.MethodsA total of 195 patients with OCD were selected as the research subjects， who received treatment at the outpatient and inpatient departments of the Affiliated Brain Hospital of Nanjing Medical University from July 2022 to December 2023 and met the diagnostic criteria for OCD in the International Classification of Diseases， tenth edition （ICD-10）. Evaluation was conducted by using the Yale-Brown Obsessive Compulsive Scale （Y-BOCS）， Personality Diagnostic Questionnaire-4+ （PDQ-4+）， Obsessive-Compulsive Inventory-Revised （OCI-R）， Beck Depression Inventory （BDI）， Beck Anxiety Inventory （BAI） and Sheehan Disability Scale （SDS）. In accordance with the score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4+， patients were divided into the OCD group with obsessive-compulsive personality disorder （n=58） and the OCD group without obsessive-compulsive personality disorder （n=137）. Pearson correlation analysis and Spearman correlation analysis were adopted to examine the correlation between clinical features and the score of the Obsessive-Compulsive Personality Disorder Scale. Multiple linear regression analysis was used to explore the influencing factors of OCD patients with obsessive-compulsive personality disorder.ResultsStatistically significant differences were observed between OCD patients with and without obsessive-compulsive personality disorder in the age， family history of mental illness， time without treatment， hoarding and ranking dimension scores in OCI-R， OCI-R total score， score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4， and BDI score （P≤0.05）. OCD patients with obsessive-compulsive personality disorder in the time without treatment， OCI-R total score， hoarding and ranking dimension scores in OCI-R and BDI score are all positively correlated with the score of the Obsessive-Compulsive Personality Disorder Scale （r=0.120， 0.526， 0.364， 0.492， 0.414， P

Obstructive sleep apnea (OSA) incurs a huge individual, societal, and economic burden. Specific and selective targeting of hypoglossal motor neurons could be an effective means to treat OSA. Bioluminescent-optogenetics (BL-OG) is a novel genetic regulatory approach in which luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels, increase neuronal excitability when exposed to a suitable substrate. Here we develop and validate the feasibility of BL-OG for sleep-disordered breathing (SDB). Upon confirming that diet-induced obese mice represent an excellent SDB model, we employed a method of targeting the hypoglossal nucleus (12 N) by peripherally injecting retrogradely transported rAAV2/Retro. With AAV transduction, the eLMO3 protein is expressed in hypoglossal motor neurons (HMN); administration of CTZ results in production of bioluminescence that in turn activates the tethered channelrhodopsin, leading to an increase in the firing of HMN and a 2.7 ± 0.8-fold increase in phasic activity of the genioglossus muscle, a 7.6 ± 1.8-fold increase in tonic activity, and improvements in hypoventilation and apnea index without impacting sleep structure. This is therefore the first study to leverage the rAAV2/Retro vector to execute the BL-OG approach in SDB, which amplified genioglossus muscle discharge activity and increased airflow in mice after activation. This study marks the pioneering utilization of BL-OG in SDB research.

ObjectiveManual disinfection in large-scale sheep farm is laborious, time-consuming, and often results in incomplete coverage and inadequate disinfection. With the rapid development of the application of artificial intelligence and automation technology, the automatic navigation and spraying robot for livestock and poultry breeding, has become a research hotspot. To maintain shed hygiene and ensure sheep health, an automatic navigation and spraying robot was proposed for sheep sheds.MethodsThe automatic navigation and spraying robot was designed with a focus on three aspects: hardware, semantic segmentation model, and control algorithm. In terms of hardware, it consisted of a tracked chassis, cameras, and a collapsible spraying device. For the semantic segmentation model, enhancements were made to the lightweight semantic segmentation model ENet, including the addition of residual structures to prevent network degradation and the incorporation of a squeeze-and-excitation network (SENet) attention mechanism in the initialization module. This helped to capture global features when feature map resolution was high, addressing precision issues. The original 6-layer ENet network was reduced to 5 layers to balance the encoder and decoder. Drawing inspiration from dilated spatial pyramid pooling, a context convolution module (CCM) was introduced to improve scene understanding. A criss-cross attention (CCA) mechanism was adapted to acquire context global features of different scales without cascading, reducing information loss. This led to the development of a double attention enet (DAENet) semantic segmentation model was proposed to achieve real-time and accurate segmentation of sheep shed surfaces. Regarding control algorithms, a method was devised to address the robot's difficulty in controlling its direction at junctions. Lane recognition and lane center point identification algorithms were proposed to identify and mark navigation points during the robot's movement outside the sheep shed by simulating real roads. Two cameras were employed, and a camera switching algorithm was developed to enable seamless switching between them while also controlling the spraying device. Additionally, a novel offset and velocity calculation algorithm was proposed to control the speeds of the robot's left and right tracks, enabling control over the robot's movement, stopping, and turning.Results and DiscussionsThe DAENet model achieved a mean intersection over union (mIoU) of 0.945 3 in image segmentation tasks, meeting the required segmentation accuracy. During testing of the camera switching algorithm, it was observed that the time taken for the complete transition from camera to spraying device action does not exceed 15 seconds when road conditions changed. Testing of the center point and offset calculation algorithm revealed that, when processing multiple frames of video streams, the algorithm averages 0.04 to 0.055 per frame, achieving frame rates of 20 to 24 frames per second, meeting real-time operational requirements. In field experiments conducted in sheep farm, the robot successfully completed automatic navigation and spraying tasks in two sheds without colliding with roadside troughs. The deviation from the road and lane centerlines did not exceed 0.3 meters. Operating at a travel speed of 0.2 m/s, the liquid in the medicine tank was adequate to complete the spraying tasks for two sheds. Additionally, the time taken for the complete transition from camera to spraying device action did not exceed 15 when road conditions changed. The robot maintained an average frame rate of 22.4 frames per second during operation, meeting the experimental requirements for accurate and real-time information processing. Observation indicated that the spraying coverage rate of the robot exceeds 90%, meeting the experimental coverage requirements.ConclusionsThe proposed automatic navigation and spraying robot, based on the DAENet semantic segmentation model and center point recognition algorithm, combined with hardware design and control algorithms, achieves comprehensive disinfection within sheep sheds while ensuring safety and real-time operation.

Peng Zhou,1 Lingling Ye,2 Shixiao Li3 1Department of Pharmacy, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Science and Education, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 3Department of Clinical Microbiology Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Shixiao Li, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, No. 150, Ximen Street, Taizhou, Zhejiang Province, 317000, People’s Republic of China, Email lsx0992@126.comObjective: Klebsiella pneumoniae liver abscess (KPLA) is an invasive infectious disease with a considerable prevalence and complications. This study aimed to determine the predicted value of aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) for positive blood cultures and sepsis in patients with KPLA.Methods: We evaluated 248 consecutive participants diagnosed with KPLA. Demographic characteristics, clinical features, and laboratory test results of the participants were recorded. Multivariate logistic regression analysis was performed to identify the risk factors. Receiver operating characteristic (ROC) analyses were conducted to evaluate the discriminatory ability of APRI and FIB-4.Results: 30.2% (75 of 248) KPLA patients presented with positive blood cultures, and 70 (28.2%) developed sepsis. Among the positive blood culture and sepsis groups, the APRI and FIB-4 showed statistically significant increases. Multivariate analysis showed that APRI (odds ratio [OR] = 1.190, 95% confidence interval [CI] 1.051– 1.347, p = 0.006) and FIB-4 (OR = 1.110, 95% CI 1.046– 1.179, p = 0.001) were independent prognostic factors for positive blood cultures. Both APRI (OR = 1.505, 95% CI 1.149-1.988, p = 0.004) and FIB-4 (OR = 1.187, 95% CI 1.054-1.336, p = 0.005) were independent risk factors for sepsis. The area under the ROC curve (AUC) of APRI and FIB-4 for predicting positive blood cultures of KPLA was 0.783 and 0.766, respectively. APRI had an AUC of 0.801, with a sensitivity and specificity of 71.4% and 81.5%, respectively, for predicting sepsis in patients with KPLA, and the prediction performance of APRI was better than that of FIB-4 (AUC = 0.798).Conclusion: In our study, APRI and FIB-4 are effective methods for predicting KPLA patients with positive blood cultures and sepsis.Keywords: klebsiella pneumoniae liver abscess, positive blood culture, sepsis, aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index

Sequential recommendation predicts next items for users based on their historical interactions. Existing methods capture long-term dependencies but struggle to recommend precisely for users with short interaction sequences, especially for long-tail users. Therefore, a sequential recommendation algorithm for long-tail users based on knowledge-enhanced contrastive learning was proposed. Firstly, semantic item similarity was introduced by leveraging relationships between entities in the knowledge graph to extract correlated items from original sequences. Secondly, two sequence augmentation operators were proposed based on different contrastive learning views, addressing the problem of insufficient training for long-tail user sequences by augmenting self-supervised signals. Finally, precise sequence recommendations were provided for long-tail users by utilizing the joint training of shared network parameters between contrastive self-supervised tasks and the recommendation task. Experimental results on real-world datasets demonstrate the effectiveness of the proposed algorithm in improving performance for long-tail users.

Aiming at the problem of poor generalization ability in hand-crafted architectures that overly rely on expert experience, a neural network architecture search method with an adaptive smoothness strategy was proposed. Firstly, an improved candidate operation selection strategy and a continuous relaxation method were used to convert discrete search space into continuous space, and a weight-sharing mechanism was employed to enhance search efficiency. Secondly, a regularization operation with an adaptive smoothness strategy was added to the loss function, whose smoothness degree was controlled by a temperature parameter. Finally, the loss function was calculated using an exponential normalization method to avoid loss value overflow. Experimental results on 3D point cloud datasets and protein-protein interaction datasets showed that the proposed method achieved higher classification accuracy and more stable performance under the same training samples and iterations.

[Objective] This study was aimed to estimate the amount of water conservation in Shaanxi Province. [Methods] The InVEST model and PLUS model were coupled to calculate the water conservation amount in Shaanxi Province from 2000 to 2020 and predict the water conservation amount under land use changes in the future in 2030. [Results] The average water conservation amount in Shaanxi Province from 2000 to 2020 was 132.25 mm, with a spatial distribution characteristic of gradually increasing water conservation from north to south. From the perspective of vegetation types, forest land was the main body of water conservation in Shaanxi Province. The average annual water conservation amount was 199.55×108 m3. From the administrative region, Ankang City had the largest water conservation amount(308.96 mm). The total amount of water source conservation in 2030 will be 285.16×108 m3 and 8.68×108 m3 less than that in 2020. [Conclusion] The water conservation amount of Shaanxi Province will show a slight downward trend from 2020 to 2030 in the future.

Peng Zhou,1,2,&ast; Ling Li,3,&ast; Zehua Lin,1,2,&ast; Xiaoping Ming,1,2 Yiwei Feng,1,2 Yifan Hu,1,2 Xiong Chen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Sleep Medicine Centre, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Chen, Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, Hubei, 430071, People’s Republic of China, Email zn_chenxiong@whu.edu.cnPurpose: The reciprocal comorbidity of obstructive sleep apnea (OSA) and body mass index (BMI) has been observed, yet the shared genetic architecture between them remains unclear. This study aimed to explore the genetic overlaps between them.Methods: Summary statistics were acquired from the genome-wide association studies (GWASs) on OSA (Ncase = 41,704; Ncontrol = 335,573) and BMI (Noverall = 461,460). A comprehensive genome-wide cross-trait analysis was performed to quantify global and local genetic correlation, infer the bidirectional causal relationships, detect independent pleiotropic loci, and investigate potential comorbid genes.Results: A positive significant global genetic correlation between OSA and BMI was observed (rg = 0.52, P = 2.85e-122), which was supported by three local signal. The Mendelian randomization analysis confirmed bidirectional causal associations. In the meta-analysis of cross-traits GWAS, a total of 151 single-nucleotide polymorphisms were found to be pleiotropic between OSA and BMI. Additionally, we discovered that the genetic association between OSA and BMI is concentrated in 12 brain regions. Finally, a total 134 expression-tissue pairs were observed to have a significant impact on both OSA and BMI within the specified brain regions.Conclusion: Our comprehensive genome-wide cross-trait analysis indicates a shared genetic architecture between OSA and BMI, offering new perspectives on the possible mechanisms involved.Keywords: genome-wide cross-trait analysis, Mendelian randomization, genetic architecture

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

With the development of digital technology， an increasing number of artificial intelligence （AI） technologies are being applied in the field of public health， significantly improving the efficiency of healthcare systems. However， such technological advancement also introduces a series of ethical risks. In this article， we conducted a systematic review by searching nine domestic and international databases and analyzing the ethical issues related to AI in public health， ultimately including 158 articles. Based on the analysis of the included literature， ethical risks were categorized into four aspects： data， algorithms， rights and responsibilities， and social impact. A total of 15 key issues were identified， among which privacy and confidentiality， informed consent， data security， and fairness， justice and inclusion emerged as the most prominent issues. The ethical challenges posed by AI in the field of public health cannot be ignored， and it is necessary to formulate ethical guidelines and practical recommendations for AI in this field， establish sound regulatory and review mechanisms， thereby ensuring the healthy development of AI research in public health.

[Objective] With the ongoing urbanization in China, the frequency of heavy-duty vehicles traversing buried pipelines is steadily increasing. Therefore, it is of paramount importance to investigate the mechanical response patterns of buried pipelines subjected to heavyduty vehicle rolling in order to ensure the safety of oil and gas pipelines. [Methods] Field tests were conducted to investigate the rolling of heavy-duty vehicles on a buried X70 pipeline. Strain gauge technology was employed to gather pipeline response data and summarize the response patterns of soil pressure and axial stress. Additionally, an ABAQUS software-based finite element simulation model was established to simulate the soil-pipeline interaction using a nonlinear contact model. The vehicle load was simplified as the dead load of a moving plane source, and a DLOAD subprogram was developed to implement the loading. Subsequently, simulations were conducted based on the test conditions. [Results] The results demonstrated a negligible deviation between the simulated and tested values of the additional axial stress in the pipeline. Furthermore, the simulated distribution patterns of soil pressure and axial stress aligned with those observed in the tests, thus the response patterns of soil pressure and axial stress were verified. Based on the verified finite element model, the impact of six parameters, i.e.,vehicle load, vehicle speed, pipe diameter, pipe wall thickness, fill height, and pipeline internal pressure, on the axial stress of the pipeline was explored through simulation by employing a single-variable approach. [Conclusion] The topsoil pressure and axial stress at the section beneath the crawler belts on both sides are higher than those at the central section. Conversely, the bottom axial stress is lower than that at the central section. Augmenting the pipe diameter, pipe wall thickness, or fill height can diminish the additional axial stress induced by vehicle rolling on the pipeline. However, altering the vehicle speed and pipeline internal pressure does not yield significant effects on the axial stress.The obtained mechanical response patterns of the buried pipeline can be used as a reference for evaluating the safety margin of pipelines under heavy-duty vehicle rolling.

Postharvest preservation of edible fungi is crucial for promoting the healthy development of the edible fungi industry. To systematically review the development history of research on postharvest preservation of edible fungi and to predict future trends, this paper used bibliometric methods to analyzes 421 pieces of relevant literature published in the Web of Science database between 2000 and the first three quarter of 2022 in terms of literature publishing, research collaboration, key authors, important literature, literature citations, and keywords. CiteSpace software was used for visual analysis. The results indicated that the amount and citations of literature on the preservation of edible fungi had steadily increased since 2000, with a trend of rapid growth since 2015 until the third quarter of 2022. Chinese research institutions and authors had significant impact in this field, who had participated in international collaboration most extensively and produced the most research achievements. The analysis of literature citations and keywords revealed that the frontier hotspots in this field were cell wall metabolism, energy metabolism, and active packaging research. The direction of energy metabolism was particularly noteworthy. Maintaining normal cell energy metabolism and antioxidant activity is essential for edible fungi to resist postharvest deterioration. Therefore, exploring new preservation technologies and elucidating their molecular mechanisms will be an important research direction in the future.

Runzhen Chen,1,2,&ast; Jiannan Li,1,3,&ast; Zhaoxue Sheng,4 Jinying Zhou,1,3 Ying Wang,1 Xiaoxiao Zhao,1,3 Nan Li,1 Weida Liu,5 Chen Liu,1,3 Peng Zhou,1,3 Yi Chen,1,3 Shaodi Yan,2 Li Song,1– 3 Hongbing Yan,2,3 Hanjun Zhao1,3 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 3Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Medical Research Center, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Nanshan District, Shenzhen, 510000, People’s Republic of China, Email hbyanfuwai2018@163.com; hbyanfuwai@aliyun.com Hanjun Zhao, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email 15210020808@163.comBackground: As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features.Results: The median RvD1 level was 129.7 (56.6– 297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥ 111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20– 3.66, P = 0.010), healed plaques (≥ 246.4 pg/mL, OR: 2.17, 95% CI: 1.11– 4.24, P = 0.023), and calcification (≥ 293.38 pg/mL, OR: 2.10, 95% CI: 1.21– 3.66, P = 0.008) at culprit lesions.Conclusion: Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.Keywords: resolvin D1, specialized pro-resolving lipid mediator, myocardial infarction, optical coherence tomography, atherosclerosis, inflammation

Osteosarcoma is a highly aggressive bone tumor primarily affecting children and adolescents. Despite advancements in treatment modalities, the prognosis for osteosarcoma patients remains poor, emphasizing the need for a deeper understanding of its underlying mechanisms. In recent years, the concept of cancer stem cells (CSCs) has emerged as a crucial factor in tumor initiation, progression, and therapy resistance. These specialized subpopulations of cells possess self-renewal capacity, tumorigenic potential, and contribute to tumor heterogeneity. Sox9, a transcription factor known for its critical role in embryonic development and tissue homeostasis, has been implicated in various malignancies, including osteosarcoma. This review aims to summarize the current knowledge regarding the role of Sox9 in CSCs in osteosarcoma and its potential implications as a prognosis and therapeutic target.

With the development of detection methods, the intelligent and high-precision military stealth detection technology has put forward higher requirements for the performance of stealth materials, the traditional materials are limited by their own performance, and it is difficult to achieve stealth requirements such as lightweight, broadband, and strong absorption. However, the metamaterials have great potential for development in the field of stealth due to their ability to design, adjust structures, and achieve related performance according to human will. Therefore, the research on metamaterials in the field of military stealth has received great attention.The development, special properties and applications of metamaterials were reviewed in this paper, focusing on the research and development of radar stealth metamaterials, infrared stealth metamaterials, radar/infrared compatible stealth metamaterials, and laser/infrared compatible stealth metamaterials. Finally, it was pointed out that the research of metamaterials in the field of military stealth mostly stays in the experimental stage, and it is difficult to adapt to the complex and changeable practical environment for practical application, the research of metamaterials should be focused on low-cost preparation and application, broadband multi-band compatibility, as well as high temperature resistance, high corrosion resistance and high outdoor stability.

Haopeng Wang,1,&ast; Hua Zhao,1,&ast; Zheng Chen,1,&ast; Xiaomin Cai,1 Xuhui Wang,1 Ping Zhou,1 Yinda Tang,1 Tingting Ying,1 Xin Zhang,1 Yiman Shen,1 Baimiao Wang,1 Wanchun Zhu,1 Jin Zhu,1 Xinjun Wang,2 Shiting Li1 1Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiting Li, Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China, Email lishiting@xinhuamed.com.cn Xinjun Wang, Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Email wangxj@zzu.edu.cnBackground: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism.Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments.Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p.Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI. Keywords: hypoxic, BMSCs, exosomes, Schwann cells, facial nerve injury

Abstract Purpose The adverse health consequences of premarital sex and childhood sexual abuse (CSA) are both global public health problems. Based on a random sample of college students from a Chinese city, this study investigated the relationship between CSA severity and premarital sex among students, focusing on sex differences. Methods A total of 2722 college students from 4 schools in Luzhou were recruited by multistage random sampling. Self-administered questionnaires were used to measure CSA experiences and premarital sex. Binary logistic regression analyses were conducted to analyse the relationship between CSA and premarital sex. Results The prevalence of CSA was 9.39%, and that of mild, moderate and severe CSA was 4.04%, 2.90% and 2.46%, respectively. The premarital sex reporting rate was 22.42%. After adjusting for confounding variables, CSA was positively associated with premarital sex. Notably, a cumulative effect of CSA on premarital sex was observed among students. Further stratification analyses showed that males who experienced CSA had a higher premarital sex rate than females, and this sex difference was also observed among students with different CSA severities. Conclusion CSA and its severity were associated with premarital sex among college students. Furthermore, this association was stronger for males than females. Therefore, it is important to emphasize CSA prevention, especially for boys. These findings can promote understanding of the effects of CSA on premarital sex, and CSA prevention and intervention strategies should consider CSA severity and sex differences.

As a forward position to realize urban-rural integration development, the rural multi-functionality of metropolitan suburbs, which faces higher requirements in terms of governance, taking over the core functions of the metropolis and meeting its consumption needs, has recently gained much attention among scholars and policymakers. However, there is a shortage of comprehensive summaries of the rural multi-functional development rules(about patterns, differentiation characteristics, etc.) in metropolitan suburbs, as well as relatively little research specifically on the multi-functional development of such areas. This has led to the emergence of a range of issues such as unclear connotations, lack of guidance, and disability of revitalization. In the future, establishing how to meet the diversified needs of cities and residents through function expansion, and how to revitalize such rural areas through the optimal combination and coordinated development of functions will be key issues that need to be solved in the practice of urban-rural integration development. Consequently, based on scientific identification regarding different needs of the urban-rural subject in the metropolis, this paper first defines the connotation of the rural multi-functionality of metropolitan suburbs—the sum of all kinds of services and functions that can be provided to meet the various needs of urban and rural residents, maintain the suburban villages themselves, and rely on the integration and symbiosis of the metropolis and the coordinated development of urban and rural areas—and then presents a multi-functional classification system from the perspective of "production-living-ecology" functions. Second, this thesis summarizes the mechanisms and trends that motivate the evolution of multi-functionality in the suburban villages of the metropolis: 1) Overall, the multi-functional development of rural areas is generally considered to be the result of the joint action of natural geographical systems, socio-economic systems, policies and systems, and human activities, similar to that of the evolution of traditional village functions. However, the contribution of such factors that influence the choice of direction of functional expansion, the speed of functional evolution, and changes in functional intensity in the suburban villages of the metropolis varies enormously. 2) Compared with general rural areas, the rural multifunction of metropolitan suburbs is the first to present the evolution trend of "modernization and characterization of production functions, convenience and humanization of living functions, and greenization and sustainability of ecological functions." Finally, the innovative directions of the future collaborative evolution of rural multi-function in the suburbs of the metropolis are drawn from four aspects: 1) construction of a basic theory and classification system, 2) identification method of rural multi-functional zoning under the constraints of innovative development planning policies, 3) active exploration of typical paths and modes of multi-function collaboration, and 4) improvement of the policy support system for the transformation and development of rural multi-function. This study will be of great significance in optimizing urban-rural relations in the metropolis, promoting urban-rural integration, and guiding the optimization and development of local rural functions and rural revitalization.

With increasing aging population, osteoporosis has emerged as a public health problem worldwide. Epidemiological data reveal that the prevalence of osteoporosis in cold regions is high, and low temperatures may crucially affect bone mass. Recent studies have found that the transient receptor potential melastatin-8 (TRPM8) channel, a cold-sensitive ion channel, can sense cold environment, and can be activated in cold environment. It may play an antagonistic role in low temperature-induced bone mass reduction. Mechanistically, this function may be ascribed to the activation of TRPM8 channel proteins in human bone marrow mesenchymal stem cells (hBM-MSCs), which causes osteoblast differentiation and mineralization in the bone. TRPM8 channel on the surface of brown adipocytes participates in the thermogenesis in brown adipose tissue (BAT) and the regulation of whole-body energy balance to maintain bone homeostasis. TRPM8 may be involved in bone remodeling throughout life. This paper reviews recent research on the possible antagonistic mechanism of TRPM8 in signaling pathways related to low temperature-induced bone mass loss and assesses the possibility of TRPM8 as a molecular target for the prevention and treatment of low temperature-induced osteoporosis in cold regions.

Lan Chen,1,&ast; Ying Zhou,2,&ast; Shanshan Wang,1 Chunyang Wu,3 Peiyao Zhou,4 Bingjie Wang,2 Zhu Chen,5 Fangyou Yu2 1Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People’s Republic of China; 3Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Clinical Laboratory Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang, 315010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhu Chen; Fangyou Yu, Email mars853234@163.com; wzjxyfy@163.comBackground: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has become a clinical crisis and is associated with significant morbidity and mortality. The prevalence of CR-hvKP has trended upward since 2010. This study aims to describe the clinical and genomic characteristics of CR-hvKP collected from a tertiary hospital in eastern China, from August 2020 to October 2021.Methods: We tested the susceptibility to common antibiotics in these isolates to feature the antibiotic-resistant phenotypes. We also applied whole-genome sequencing and core-genome phylogenetic to analysis the genetic features of these isolates. Plasmid replicons were identified by using the PlasmidFinder database, and core-genome phylogenetic analysis by Parsnp database.Results: All these strains isolated from the patients with serious underlying diseases and poor prognosis. We found all CR-hvKp isolates exhibited a multidrug-resistant (MDR) phenotype. These results revealed that blaKPC-2 was the predominant carbapenemases gene (n = 53, 84.1%), and ST11-KL64 CR-hvKP strains dominated, forming a single cluster, and differed by an average of 26 core SNPs. We only found eight ST15 isolates containing KL24 and KL112 type capsules, with the main carbapenem resistance genes being blaOXA-232 and blaKPC-2. All ST11-KL64 strains had a series of resistance and virulence genes, along with IncHIB-FIB virulence plasmids and IncFII resistance plasmids, while the prevalence of resistance plasmids like the IncFII plasmid was absence in ST15 isolates.Conclusion: This suggests that ST11-KL64 CR-hvKP has emerged as the most prevalent hypervirulence and carbapenem-resistant K. pneumoniae and may contribute to hospital outbreaks of infection, which required most clinical attention.Keywords: carbapenem-resistant, hypervirulence, Klebsiella pneumoniae, whole-genome sequencing, antimicrobial resistance, virulence genes

BackgroundTalaromycosis is a serious opportunistic infectious disease caused by Talaromyces marneffei, which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death.Case presentationBoth patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for T. marneffei. T. marneffei was detected in the blood culture of case 2, with infection of Candida parapsilosis and Pneumocystis jirovecii. Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy.ConclusionTalaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.

Abstract The mechanism underlying acute kidney injury (AKI) and AKI-to-Chronic kidney disease (CKD) transition remains unclear, but mitochondrial dysfunction may be a key driving factor. Literature reports suggest that dual-specificity phosphatase 1 (DUSP1) plays a critical role in maintaining mitochondrial function and structural integrity. In this study, ischemic Acute Kidney Injury (AKI) and post-ischemic fibrosis models were established by clamping the renal pedicle with different reperfusion times. To investigate the role of DUSP1, constitutional Dusp1 knockout mice and tubular-specific Sting knockout mice were used. Mitochondrial damage was assessed through electron microscopy observation, measurements of mitochondrial membrane potential, mtDNA release, and BAX translocation. We found that Dusp1 expression was significantly upregulated in human transplant kidney tissue and mouse AKI tissue. Dusp1 gene deletion exacerbated acute ischemic injury, post-ischemic renal fibrosis, and tubular mitochondrial dysfunction in mice. Mechanistically, DUSP1 could directly bind to JNK, and DUSP1 deficiency could lead to aberrant phosphorylation of JNK and BAX mitochondria translocation. BAX translocation promoted mitochondrial DNA (mtDNA) leakage and activated the cGAS-STING pathway. Inhibition of JNK or BAX could inhibit mtDNA leakage. Furthermore, STING knockout or JNK inhibition could significantly mitigate the adverse effects of DUSP1 deficiency in ischemic AKI model. Collectively, our findings suggest that DUSP1 is a regulator for the protective response during AKI. DUSP1 protects against AKI by preventing BAX-induced mtDNA leakage and blocking excessive activation of the cGAS-STING signaling axis through JNK dephosphorylation.

Due to the large-scale development of rooftop photovoltaics and the continuous improvement of the national carbon trading market, the carbon credits generated by rooftop photovoltaics power generation can obtain additional income through carbon allocation offset or participation in carbon trading market. Firstly, the path and methods of participating in the carbon trading market for rooftop photovoltaic projects are studied, focusing on how large-scale rooftop photovoltaic projects participate in the carbon trading market and the degree of impact on the project's economy. Secondly, the life-cycle economic model of rooftop photovoltaic with carbon trading income is established based on the power generation model. Thirdly, in order to quantitatively analyze the income of carbon trading, an improved grey prediction GM(1, 1) model based on the differential threshold filtering method is proposed to predict the future carbon price. Finally, an example of large-scale rooftop photovoltaic is analyzed. The results show that large-scale rooftop photovoltaic considering participation in the carbon trading market has a relatively significant economic improvement.

Zequn Zhuang,1,&ast; Peng Zhou,1,&ast; Jing Wang,2 Xiaojing Lu,1 Yigang Chen1– 3 1Department of General Surgery, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 2Jiangnan University Medical Center, Wuxi, People’s Republic of China; 3Wuxi Clinical College, Nantong University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yigang Chen, Department of General Surgery, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China, Email 9862023226@jiangnan.edu.cnAbstract: Presently, obesity has emerged as a significant global public health concern due to its escalating prevalence and incidence rates. The gut microbiota, being a crucial environmental factor, has emerged as a key player in the etiology of obesity. Nevertheless, the intricate and specific interactions between obesity and gut microbiota, along with the underlying mechanisms, remain incompletely understood. This review comprehensively summarizes the gut microbiota characteristics in obesity, the mechanisms by which it induces obesity, and explores targeted therapies centered on gut microbiota restoration.Keywords: gut microbiota, obesity, dysbiosis, metabolism

[Objective] The response of soil labile organic carbon components and enzyme activities to natural forest conversion was analyzed in order to provide a scientific basis for predicting regional soil health evolution and environmental change. [Methods] A native evergreen broad-leaved forest and a converted conifer plantation, an orchard, a sloping tillage area, and a paddy with similar geographical background and clear land use history were studied. The responses of labile organic carbon fractions and enzyme activities in topsoil to native forest conversion were investigated using various physical, chemical, and biochemical techniques. [Results] The native forest conversion to an orchard, a sloping tillage area, and a paddy significantly reduced the soil organic carbon content, labile carbon fraction contents, and enzyme activities by 42%—67%, 47%—88%, and 36%—89%, respectively. Notably, the readily oxidizable organic carbon, microbial biomass carbon, and invertase activity experienced the greatest reduction compared with the native forest conversion, sensitively indicating the reduction in soil organic carbon content and its lability. Readily oxidizable organic carbon was, therefore, considered to be a practical index. Reductions in soil labile organic carbon fractions and enzyme activities were lower for the conversion of native forest conversion to plantation than for the native forest conversion to orchard and sloping tillage area, showing the preservation capacity of soil labile carbon in the plantation. The ratio of labile organic carbon to total organic carbon in soil was significantly reduced after the native forest conversion to plantation, sensitively reflecting the reduction in soil carbon quality. [Conclusion] Native forest conversion led to substantial reductions in labile organic carbon quantity, carbon quality, and related enzyme activities in soil, suggesting a degradation of soil biological health and a decline in soil quality.

BackgroundThe obsessive-compulsive disorder （OCD） features complexity in etiological factors and high heterogeneity in clinical manifestations. OCD patients with different ages of onset vary in clinical symptoms and etiology. However， current studies on inpatients with early- and late-onset OCD are limited.ObjectiveTo explore the differences in clinical characteristics between early- and late-onset OCD inpatients as well as the factors affecting the onset age of OCD， so as to provide references for early screening and treatment of OCD patients.MethodsThis study was based on collected medical records of 540 patients with OCD who received inpatient treatments at the Affiliated Brain Hospital of Nanjing Medical University between March 2012 and March 2023. Patients with onset age above 18 were placed into early-onset group （n=310） and the others into late-onset group （n=230）. Then differences in demographic data and clinical symptoms between two groups of patients were compared. Binary logistic regression was used to analyze the factors that affect the onset age of OCD.ResultsObserving the demographic data， there were significant differences between the two groups in the results in gender， marital status， family history of mental illness， ratio of comorbidities with other mental illnesses， occupational composition， education level and types of obsessive-compulsive symptoms （χ2=22.302、170.556， 9.224， 13.624， 242.277， 59.791， 7.231， P

This study evaluated the protective effects of naringin (NRG) against 5-fluorouracil (5-FU)-elicited neurotoxicity. The animals were orally administered with NRG and subsequently injected with 5-FU. Injection of 5-FU caused depression in cerebral antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, catalase, reduced glutathione and total protein levels, whereas malondialdehyde and acetylcholinesterase levels/activities were considerably upregulated. In addition, 5-FU-triggered cerebral pro-inflammation was shown via significantly increased levels of pro-inflammatory cytokines, inducible nitric oxide synthase, nuclear factor-ĸB, and caspase-3. Furthermore, necrotic and inflammatory histopathological lesions were observed in the cerebral tissues. Interestingly, the NRG administration considerably inhibited 5-FU-instigated cerebral oxido-inflammatory and apoptotic parameters in the treated animals. Thus, NRG could mitigate the neurotoxicity of 5-FU via the inhibition of oxido-inflammation and apoptosis in rats. These results suggested that NRG may have a relevant therapeutic importance in the management of 5-FU-elicited neurotoxicity.

Abstract Background Sepsis-induced acute lung injury (ALI) is associated with poor survival rates. The identification of potential therapeutic targets for preventing sepsis-induced ALI has clinical importance. This study aims to investigate the role of estrogen-related receptor alpha (ERRα) in sepsis-induced ALI. Methods Lipopolysaccharide (LPS) was used to simulate sepsis-induced ALI model in rat pulmonary microvascular endothelial cells (PMVECs). The effects of ERRα overexpression and knockdown on LPS-induced endothelial permeability, apoptosis and autophagy were determined by horseradish peroxidase permeability assay, TdT-mediated dUTP Nick End Labeling (TUNEL) assay, flow cytometry, immunofluorescence staining, RT-PCR and Western Blotting. The rat model with sepsis-induced ALI was established by cecal ligation and puncture in anesthetized rats to verify the results of in vitro experiments. Animals were randomly assigned to receive intraperitoneal injection of vehicle or ERRα agonist. Lung vascular permeability, pathological injury, apoptosis and autophagy were examined. Results Overexpression of ERRα ameliorated LPS-induced endothelial hyperpermeability, degradation of adherens junctional molecules, upregulation of bax, cleaved caspase 3 and cleaved caspase 9 levels, downregulation of anti-apoptotic protein Bcl-2 level, and promoted the formation of autophagic flux, while the knockdown of ERRα exacerbated LPS-induced apoptosis and inhibited the activation of autophagy. Administration of ERRα agonist alleviated the pathological damage of lung tissue, increased the levels of tight junction proteins and adherens junction proteins, and decreased the expression of apoptosis-related proteins. Promoting the expression of ERRα significantly enhanced the process of autophagy and reduced CLP-induced ALI. Mechanistically, ERRα is essential to regulate the balance between autophagy and apoptosis to maintain the adherens junctional integrity. Conclusion ERRα protects against sepsis-induced ALI through ERRα-mediated apoptosis and autophagy. Activation of ERRα provides a new therapeutic opportunity to prevent sepsis-induced ALI.

This study reviews the metal corrosion problem regarding the carbon capture, utilization, and storage (CCUS) technology and aims to deepen the understanding and research on this problem and thus deal with the severe material corrosion failures in the capture, transportation, utilization, and storage systems. Based on the novel corrosion environments, the uniqueness of corrosion behaviors, limited cognition, and relative lack of protective measures in CCUS technology systems, this study analyzes the possible types of metal corrosion and its major influencing factors, explores the challenges it brings, and draws the following conclusions. For the CO2 organic amine capture system, the degradation mechanism of absorbents and the impact of degradation products on the corrosion process are complex, and some degradation products have a inhibitory effect on metal corrosion. The internal corrosion issue of dense-phase CO2 transmission pipelines cannot be ignored, and controlling the moisture content is the key to controlling this corrosion problem. The risk of corrosion failures leading to CO2 leakage is high in the wellbore tubing of CO2 enhanced oil recovery utilization and storage systems under the long-term coupled effects of ultra-high CO2 partial pressure, carbon source impurities, high mineralized formation water, microorganisms, and stress. Finally, the research that needs to be conducted urgently in the future is prospected, including the corrosion impact of different carbon source impurities on each subsystem, the material degradation law in the wellbore area under long-term storage conditions, and corrosion protection technologies of CCUS systems.

ObjectiveThis study aimed to provide evidence for early warning， prevention， and monitoring strategies relating to the spatial distribution and clustering characteristics of diarrhetic shellfish poison （DSP） contamination and dietary exposure of commercially available shellfish in coastal areas in China.MethodsClassical substitution and the inverse normal imputation method were used to indicate undetected DSP values and calculate dietary exposure. Based on the provincial spatial scale， the global and local spatial autocorrelation analyses of food contamination and exposure in the DSP in coastal China were explored.ResultsFrom 2016 to 2021， a total of 6 355 shellfish samples were collected from 10 coastal provinces in China. The detection rate of DSP was 6.34%. Yessotoxins （YTX） reported the highest detection rate at 5.41%. The main contaminated areas include Fujian， Guangxi， Hebei， and Guangdong. The global Moran’s I value of contamination of pectenotoxins was 0.55 （P = 0.02） and of YTX was 0.27 （P = 0.01）， this demonstrated a spatial clustering effect on the contamination and dietary exposure of DSP. Local spatial autocorrelation analysis showed that two high-high clustering were detected in Liaoning and Shandong for DSP contamination. For dietary exposure to DSP， there was a high-low clustering phenomenon in Hebei， Guangxi， and Liaoning.ConclusionThere are regional differences in DSP contamination and dietary exposure in coastal China， demonstrating localized regionalization. To improve shellfish food safety， government agencies should formulate regionalized precision monitoring and dietary interventions based on the spatial distribution of DSP contamination and dietary exposure.

The selective broadband absorption of solar radiation plays a crucial role in applying solar energy. However, despite being a decade-old technology, the rapid and precise designs of selective absorbers spanning from the solar spectrum to the infrared region remain a significant challenge. This work develops a high-performance design paradigm that combines deep learning and multi-objective double annealing algorithms to optimize multilayer nanostructures for maximizing solar spectral absorption and minimum infrared radiation. Based on deep learning design, we experimentally fabricate the designed absorber and demonstrate its photothermal effect under sunlight. The absorber exhibits exceptional absorption in the solar spectrum (calculated/measured = 0.98/0.94) and low average emissivity in the infrared region (calculated/measured = 0.08/0.19). This absorber has the potential to result in annual energy savings of up to 1743 kW h/m2 in areas with abundant solar radiation resources. Our study opens a powerful design method to study solar-thermal energy harvesting and manipulation, which will facilitate for their broad applications in other engineering applications.

With the increase of software tools used in the airborne software development and verification process to meet DO-178C, in order to ensure its airworthiness and safety, DO-330 is taken as a guide for software tool qualification process of DO-178C. At present, the commercial off-the-shelf (COTS) tools cannot meet the requirements of specific project development and verification. The evaluation tool qualification level, life cycle process and objective of tool qualification in DO-330 are used as the guidance basis. The main concerns and difficulties in the process of DO-330 engineering practice are analyzed. Combined with the actual project, the qualification process of self-developed tool to meet the requirements of DO-330 is given. The results show that the self-developed tool qualification of tool qualification level 5 (TQL-5) proposed in this paper has engineering feasibility, and has made substantial progress, which provides reference and guidance to meet specific project requirements and perform software tool qualification according to DO-330 requirements.

Xin Zhao,1,&ast; Pingyuan Ge,1,&ast; Shaohua Lei,1 Siqi Guo,1 Peng Zhou,1 Li Zhao,1 Yiyu Qi,1 Xiaotong Wei,2 Weizhen Wu,2 Ningjing Wang,2 Rui Guo,3 Nianyun Yang,1 Qingqing Xiao,1 Qichun Zhang,1,2 Huaxu Zhu1 1Department of Traditional Chinese Medicine Processing and Preparation, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qichun Zhang; Huaxu Zhu, Email zhangqichun@njucm.edu.cn; zhuhx@njucm.edu.cnIntroduction: Neuroinflammation is one of the major pathogeneses in Alzheimer’s disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD.Methods: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1β, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of β-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of β-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo.Results: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aβ plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB.Conclusion: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.Keywords: Alzheimer’s disease, neuroinflammation, phytoconstituents, drug combination, BBB permeability, exosomes

Shixiao Li,1 Peng Zhou,2 Lihong Yang,1 Tianbin Tang,1 Jiajia Qin,1 Jiao Qian,1 Shen Bo,1 Sufei Yu1 1Department of Clinical Microbiology Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Sufei Yu, Email ysf5236791@163.comObjective: Severe pneumonia is a common infectious disease with high morbidity and mortality. Early etiological diagnosis is crucial for improving the prognosis. The aim of this study is to evaluate the clinical value of sampling time of mNGS in patients with severe pneumonia.Methods: This retrospective study enrolled 105 patients with severe pneumonia. mNGS was performed on bronchoalveolar lavage fluid (BALF). Patients were divided into the sampling time ≤ 72h vs sampling time > 72h groups and survivors vs non-survivors groups according to their sampling time and prognosis. Clinical characteristics, the adjustment of antibiotics and clinical prognostic value were evaluated.Results: Our study showed that, early sampling of mNGS can significantly shorten the mechanical ventilation time (p = 0.007) and hospitalization time (p = 0.004). In the non-survivors group, CURB-65, SOFA, and APACHE II scores were higher. Age (OR: 1.051, 95% CI: 1.004– 1.100, p = 0.034), chronic respiratory diseases (OR: 4.639, 95% CI: 1.260– 17.082, p = 0.021), immunosuppression (OR: 5.008, 95% CI: 1.617– 15.510, p = 0.005) and SOFA score on the day of mNGS sampling (OR: 1.492, 95% CI: 1.212– 1.837, p < 0.001) were independent risk factors of in-hospital mortality. The most common pathogens were Klebsiella pneumoniae and Human gammaherpesvirus 4. The proportion of appropriate and targeted antibiotics adjusted was significantly higher than that in the sampling time > 72h group, and the proportion of antifungal and antiviral agents adjusted was lower. In the early sampling group, it was significantly decreased in the CRP, PCT level and NEU% at discharge.Conclusion: This study demonstrated that early sampling of mNGS could shorten the time of mechanical ventilation and hospitalization of patients with severe pneumonia. Patients with higher SOFA score on the day of sampling had a poorer prognosis. It emphasizes that early sampling of mNGS has a positive value.Keywords: metagenomic next generation sequencing, severe pneumonia, sampling time, mortality

UF-SiAPP was prepared by modifying ammonium polyphosphate with the urea formaldehyde resin (UF), tetraethylorthosilicate (TEOS), and vinyltriethoxysilane (A-151). Moreover, a new intumescent flame retardant (IFR) used for low density polyethylene (LDPE) flame retardant was obtained by mixing UF-SiAPP with tris(2-hydroxyethyl) isocynurate (THEIC). The structure, morphology, and mechanical properties of flame retardants and LDPE composites were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, TG, and universal material testing machines. Furthermore, the flame-retardant properties of LDPE composites were comprehensively investigated by limiting oxygen index (LOI), UL-94, and cone calorimetry tests. The results show that UF-SiAPP exhibits excellent hydrophobic properties and good compatibility with LDPE after being modified by UF, TEOS, and A-151. And the flame-retardant properties of LDPE composites are significantly improved by adding IFR-containing UF-SiAPP. Especially, the LDPE composites attained the LOI value of 30.5% and reached the V-0 level after introducing 20.0 wt% UF-SiAPP and 10.0 wt% THEIC. And the tensile strength reached 13.55 MPa, which was 10.33% higher than that of LDPE/IFR with UF-APP and 13.21% higher than that of LDPE/IFR without THEIC in the same proportion. The smoke density tests demonstrate that the addition of UF-SiAPP not only effectively improves the residual carbon content and thermal stability of LDPE composites but also significantly reduces smoke emissions.

Cuiling Li, Peng Zhou, Yuanqin Liu, Lei Zhang Department of Neurosurgery, Shandong Medicine and Health Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of ChinaCorrespondence: Lei Zhang, Department of Neurosurgery, Shandong Medicine and Health Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Lixia District, Jinan, People’s Republic of China, Email zhanglei134@163.comAbstract: Post-neurosurgical infection is a common complication of neurosurgery, and serious infection can threaten the life of patients. In recent years, the increase in multidrug-resistant bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), has proved fatal to patients. Although there are a few cases of CRE meningitis and few clinical trials have been carried out, it has attracted increasing attention with the increasing probability of its occurrence, especially considering that there are few successful cases. An increasing number of studies are also looking for the risk factors and clinical symptoms of CRE intracranial infection. In terms of treatment, some new antibiotics are gradually being used in the clinic, but due to the complicated drug-resistant mechanism of CRE and the obstruction of the blood‒brain barrier (BBB), the therapeutic effect is still very poor. In addition, obstructive hydrocephalus and brain abscess caused by CRE meningitis are still important causes of patient death and are also difficult to treat.Keywords: CRE, ventriculitis and meningitis, polymyxin, ceftazidime-avibactam, cefiderocol

Notch pathway has played a significant role in the pathophysiology of pulmonary hypertension (PH). However, the role of Jagged 2 (Jag2), one ligand of Notch, remains to be elucidated.Therefore, determining the contribution of Jag2 to PH and its impact on pulmonary artery smooth muscle cells (PASMCs) was the aim of this investigation. Adeno-associated virus-mediated Jag2 inhibition was used to explore the role of Jag2 in peripheral pulmonary vascular remodeling assessed in a rat model of chronic hypoxia (10% O2, 4 weeks) induced pulmonary hypertension. In vitro, the effect of Jag2 silencing on hypoxia (1% O2, 24h) induced rat PASMCs was determined. Group differences were assessed using a 2-sided unpaired Student's t-test for two groups and one-way ANOVA for multiple groups. Jag2 upregulation was first confirmed in rats with sustained hypoxia-induced PH using publicly available gene expression data, experimental PH rat models and hypoxia induced rat PASMCs. Jag2 deficiency decreased oxidative stress injury, peripheral pulmonary vascular remodeling (0.276±0.020 vs. 0.451±0.033 μm, P

According to traditional Chinese medicine theory, tongue coatings reflect changes in the body. The goal of this study was to identify a metabolite or a set of metabolites capable of classifying characteristics of traditional Chinese medicine syndromes in erosive gastritis. In this study, we collected tongue coatings of patients with erosive gastritis with damp-heat syndrome (DHS), liver depression and qi stagnation syndrome (LDQSS), and healthy volunteers. Then, we analyzed the differences in metabolic characteristics between the two groups based on metabolomics. We identified 14 potential biomarkers related to the DHS group, and six metabolic pathways were enriched. The differential pathways included pyrimidine metabolism, pantothenate and CoA biosynthesis, citrate cycle (TCA cycle), pyruvate metabolism, glycolysis/gluconeogenesis, and purine metabolism. Similarly, in the LDQSS group, we identified 25 potential biomarkers and 18 metabolic pathways were enriched. The top five pathways were the TCA cycle, sphingolipid metabolism, fatty acid biosynthesis, pantothenate and CoA biosynthesis, and the pentose phosphate pathway. In conclusion, the DHS group and the LDQSS group have different characteristics.

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence in situ hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC.

Hao Zhang,1,&ast; Ping Zhou,1,&ast; Yi Jiang,1 Liu Li,1 Fei Ju,2 Quan Cheng,1 You Lang Zhou,2 Yuan Zhou1 1Department of Pain, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, People’s Republic of China; 2Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Zhou; You Lang Zhou, Tel +86 0513 85052222 ; +86 0513 85052488, Email nina_shine@126.com; zhouyoulang@ntu.edu.cnIntroduction: Esketamine, one of the few non-opioid potent analgesics, has demonstrated efficacy in the treatment of various chronic pain, particularly neuropathic pain. However, its potential clinical applications are confined due to its short half-life and severe side effects including delirium, hallucinations, and other psychiatric symptoms. Here, we reported a nanosized drug delivery system for sustained-release esketamine based on polylactic-co-glycolic acid (PLGA) nanoparticles and hyaluronic acid (HA) hydrogel.Results: In this study, esketamine in the delivery system was continuously released in vitro for at least 21 days, and spinal nerve root administration of the delivery system successfully attenuated (spinal nerve ligation) SNL-induced pain hypersensitivity for at least 14 days. Notably, the excitability of neurons in murine dorsal root ganglion (DRG) was inhibited and the activation of astrocytes in the spinal cord was additionally reduced after administration. Finally, there was no obvious pathophysiological change in the nerves at the administration site after treatment at 14 days.Conclusion: These results indicate that the sustained-release esketamine based on the nanoparticle-hydrogel delivery system can safely produce a lasting analgesic effect on SNL mice, and its mechanism might be related to modulating the activation of astrocytes in the spinal cord and inhibiting the excitability of neurons in DRG.Keywords: esketamine, nanoparticles, hyaluronic acid hydrogel, neuropathic pain

BackgroundCircadian rhythm disruption and immune infiltration are both closely associated with the development of Obstructive sleep apnea (OSA) disease and a variety of cardiovascular and neurological complications, but their interactions with OSA disease are not clear. In this study, we used bioinformatics to investigate the roles of circadian rhythm disruption and immune microenvironments in OSA.MethodsWe analyzed differential genes and their associated functional pathways in the circadian rhythm-associated OSA dataset, then regrouped OSA samples using the differential genes and explored differences in immune cell infiltration between the two different subgroups. Meanwhile, we used two machine learning algorithms to further define circadian rhythm-related signature genes and to explore the relationship between key genes and immune cell infiltration. Finally, we searched for the transcription factors of the key differential gene JUN.ResultsWe screened 15 circadian rhythm-related differential genes in the OSA-related dataset and further defined 3 signature genes by machine learning algorithms. Immunoassays showed a significant increase in resting mast cell infiltration and a decrease in monocyte infiltration in the OSA group. The results of our animal experiments also confirmed that the expression of these 3 key genes, as well as the immune cell infiltration, showed a trend consistent with the results of the bioinformatics analysis.ConclusionsIn conclusion, this study reveals the interaction between circadian rhythm disruption and immune infiltration in OSA, providing new insights into the potential pathogenesis of OSA.