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Yinghua Xia,1,2 Gui Yu,2,3 Feixiang Min,1,2 Hui Xiang,2 Jinqing Huang,4,5 Jingxing Leng2 1Medical College of Nanchang University, Nanchang, People’s Republic of China; 2Department of Neurosurgery, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of China; 3The First Clinical Medical College of Gannan Medical University, Ganzhou, People’s Republic of China; 4Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, People’s Republic of China; 5Department of Neurosurgery, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, People’s Republic of ChinaCorrespondence: Hui Xiang, Jiangxi Provincial People’s Hospital, No. 266, Fenghe North Avenue, Honggutan District, Nanchang City, People’s Republic of China, Tel +86-13803514563, Email xianghui1991@163.com Jinqing Huang, Ganzhou People’s Hospital, No. 16, Meiguan Avenue, Zhanggong District, Ganzhou City, People’s Republic of China, Tel +86-18160779765, Email hjq1002@163.comAbstract: Trigeminal neuralgia is a condition confined to the trigeminal nerve, causing one or more branches of facial nerve pain. Surgical treatment options for trigeminal neuralgia include microvascular decompression(MVD), percutaneous balloon compression (PBC), radiofrequency thermocoagulation(RF), percutaneous retrogasserian glycerol rhizotomy(PRGR), gamma knife, etc. Of these treatments, PBC is increasingly being used by clinicians for trigeminal neuralgia. PBC is a simple surgical operation performed to treat trigeminal neuralgia. Owing to its advantages, PBC is favored by many clinicians. In this study, we aimed to emphasize the need to analyze the shape of the balloon, position, compression time, and pressure, as these factors can affect the efficacy of PBC. The relief of pain by balloon compression is related to the shape of the balloon on X-ray, which is the key to the operation. Owing to continued progress and advances in current imaging technologies, clinicians revealed that the precise positioning of the foramen ovale is no longer an intraoperative problem. Instead, the anatomy of Meckel’s cave and the shape of the balloon must be the focus to achieve the best treatment effect. For clinicians, PBC is simple and is associated with a short operation time. PBC also has other advantages, such as low cost and immediate postoperative pain relief. The recurrence rate of pain post-PBC is low, despite the occurrence of facial numbness post-op. However, this side effect is reversible and does not affect daily life of the patient. In fact, the patient can be discharged 1– 2 days after surgery. Overall, PBC can be considered as one of the preferred surgical methods for the treatment of primary trigeminal neuralgia. In this paper, we explain the main points of PBC operation in detail in terms of Meckel’s cave, surgical procedure, complications, discussion of the focus and new progress, etc.Keywords: trigeminal neuralgia, balloon compression, Meckel’s cave, trigeminocardiac reflex

Thermodynamic assessment of the Al-Mo-V ternary system was performed by means of the CALPHAD (CALculation of PHAse Diagram) approach based on the thermodynamic descriptions of three constitutive binary systems (Al-Mo, Al-V and Mo-V) as well as the experimental phase equilibria data available in the literature. The solution phases, i.e. liquid, bcc (Mo, V) and fcc (Al), were described using the substitutional solution models with the Redlich-Kister equation. The binary phases in the Al-Mo and Al-V systems with the solubilities of the third element were modeled using the sublattice models. An optimal set of thermodynamic parameters for the Al-Mo-V system was obtained. Six isothermal sections at 1200, 1000, 750, 715, 675 and 630°C and liquidus projection with isotherm were calculated. The reaction scheme for the entire Al-Mo-V system was also constructed. Comparisons between the calculated and measured phase diagrams indicated that almost all the reliable experimental information was satisfactorily accounted for by the present modeling.

Abstract Background Prenatal ultrasound is the preferred modality for diagnosing fetal congenital heart disease. Given issues of physician proficiency and hospital distribution, we propose a dynamic sequential cross-sectional scanning (SCS) to explore the feasibility of cardiac screening by sonographers with less than 5 years of experience in ultrasound. Materials and methods Twenty residents were randomly divided into two groups, receiving training in the American Institute of Ultrasound in Medicine (AIUM) fetal echocardiography and the SCS method. According to the needs of training, the professional staff developed the theoretical knowledge question bank, the CHD ultrasonic video disease bank, and the assessment scale. Trainees completed the pre-training examination, theory and skill operation training, and post-training assessment. For the two groups, the theoretical knowledge, skill operation and disease diagnosis were analyzed statistically before and after training. Results After training, the trainees in both groups had significantly improved knowledge and diagnostic abilities, their diagnostic thinking about CHD was clear, and they could identify major or even all structural abnormalities and make a definite diagnosis. In terms of skill operation, both groups could complete all required scanning within the specified time. The scanning time of the SCS group was significantly lower than that of the AIUM group, and the effect of the receptor site in the AIUM group was significantly higher than that in the SCS group. Conclusion SCS can be used as a new rapid fetal cardiac scanning method and try to popularize among echocardiographer.

Abstract Objective The purpose of this study is to observe whether there is a difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery, so as to provide reference for clinical application. Methods Fifty patients, aged 18–65 years, ASA I-II, scheduled for hysteroscopy under total intravenous anesthesia were selected. The patients were randomly divided into two groups (n = 25): remimazolam tosilate group (group T) and remimazolam besylate group ( group R). The main observation index was the induction dose of remimazolam; secondary observation indicators were sleep time, anesthesia maintenance time, recovery time, induction maintenance dose of alfentanil, maintenance dose of remimazolam, and incidence of adverse events during anesthesia ( hypertension, hypotension, bradycardia, tachycardia). Results There was no significant difference in anesthesia induction dose, recovery time, sleep time, anesthesia maintenance time, and incidence of adverse events during anesthesia ( body movement, cough, hypertension, hypotension, bradycardia, tachycardia) between the two groups (P > 0.05). Conclusion There was no significant difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery. Clinical trial Registration Chinese Clinical Trial Registry, ChiCTR2400081688.

The synthesis of zeolites from natural aluminosilicate minerals has drawn extensive attention due to its significant utility in greening the zeolite manufacturing process. In this study, pure-phase NaX zeolite was synthesized via a low-temperature hydrothermal method, utilizing natural, low-quality attapulgite clay as the raw material. Acidified clay was fully activated through alkali fusion at 200 °C, and the impact of alkali fusion temperature, H2O/Na2O ratio, aging temperature, and crystallization time on the resulting crystalline NaX zeolite was investigated. The optimal conditions for obtaining pure NaX zeolite were determined to be alkali melting at 200 °C for 4 h, an H2O/Na2O ratio of 50, aging at 40 °C, and a crystallization period of 11 h at 90 °C. With a large BET surface area of 328.43 m2/g, the obtained NaX zeolite was used to adsorb Pb2+ from wastewater with a removal rate of 95%. This research provides a valuable method for the extensive and efficient utilization of low-grade natural attapulgite clay. Moreover, this is the first report on the synthesis of pure-phase NaX zeolite using only low-quality natural attapulgite clay as raw material through an atmospheric pressure water bath method.

Abstract Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use. Graphical Abstract

Fuchsia standishii J. Harrison, 1840, a perennial shrub, is renowned for its vividly colored and uniquely shaped blooms, which have an extended flowering season. Commonly cultivated as an ornamental potted plant, it is utilized in traditional Chinese medicine. In this study, we successfully sequenced and assembled the complete chloroplast genome of F. standishii using high-throughput Illumina sequencing technology. The assembled chloroplast genome displays a typical quadripartite structure, with a total length of 156,391 bp. It consists of a pair of inverted repeat regions (IRs), each measuring 25,069 bp, separated by a large single-copy region (LSC) of 87,754 bp and a small single-copy region (SSC) of 18,499 bp. The overall GC content of the genome is 37.60%. The genome includes a total of 129 genes, comprising 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis of 17 complete chloroplast genomes revealed that F. standishii forms a monophyletic group with the entire Circaea. This study provides a molecular foundation for future phylogenetic research on Fuchsia.

Garcinia esculenta Y. H. Li. 1981 (Clusiaceae) is an endemic tree species in China, primarily found in western and northwestern Yunnan Province. In this research, the complete chloroplast genome of G. esculenta was sequenced using the Illumina NovaSeq6000 platform. The result showed that the length of the complete chloroplast genome was 155,853 bp, which was composed of a large single-copy region (LSC) of 84,534 bp, a small single-copy region (SSC) of 17,175 bp, and a pair of inverted repeat (IR) regions of 27,072 bp. The overall GC content was 36.1%. The complete chloroplast genome encompassed 128 genes, comprising 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis of the complete chloroplast genome sequences of 22 species revealed that G. esculenta is most closely related to G. oblongifolia.

ObjectiveTo analyze the effects of aryl organophosphate esters (aryl-OPEs) on female reproductive health. MethodsUrine samples from 571 women with infertility who sought in vitro fertilization-embryo transfer treatment at the Reproductive Center of Peking University People's Hospital from January 2018 to January 2021 were tested for concentrations of four aryl-OPE metabolites: diphenyl phosphate (DPHP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP), 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), and 4-(hydroxymethyl)phenyl di-p-tolyl phosphate (4-OH-MDTP). Continuous independent variable data were converted into categorical variables, divided into four levels (Q1, Q2, Q3, Q4) using the 25th, 50th, and 75th percentiles as cut-off points. After reassigning values to the independent variables in each group, they were incorporated into the regression model as continuous variables for trend testing. Using multivariable linear mixed models, the correlations between aryl-OPE metabolite concentrations and reproductive hormones [estradiol (E2), progesterone (P), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL)] and infertility causes were assessed by adjusting for relevant covariates (age, BMI, smoking status, education level, infertility reason, and primary infertility diagnosis). ResultsThe detection rates of the four aryl-OPE metabolites were all > 80%. The results of the multivariable linear regression model showed that the concentrations of 4-OH-MDTP and 5-OH-EHDPP in urine were associated with decreased E2 levels (P < 0.05). The E2 level in the 4-OH-MDTP Q3 group was significantly lower by 20.59% compared to the Q1 group, and in the 5-OH-EHDPP Q4 group, it decreased by 34.52% compared to the Q1 group. The exposure concentrations of 4-OH-TPHP and DPHP showed a significant positive correlation with progesterone levels (P < 0.05). The progesterone level in the 4-OH-TPHP Q3 group was significantly increased by 42.42% compared to the Q1 group, and in the DPHP Q4 group, it was significantly increased by 32.85% compared to the Q1 group. In the analysis of infertility causes, the concentrations of 4-OH-TPHP and 4-OH-MDTP in patients with polycystic ovary syndrome (PCOS) and endometriosis were significantly higher than those in women undergoing in vitro fertilization due to male factors. Moreover, the risk of PCOS and endometriosis increased in the 4-OH-TPHP and 4-OH-MDTP Q2-Q4 groups compared to the Q1 group. ConclusionAryl-OPEs can interfere with estrogen and progesterone levels in women. The parent compounds and metabolites may be associated with the occurrence of PCOS and endometriosis and could be one of the causes of infertility.

Abstract The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient’s images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p

Abstract Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

Abstract Background Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Methods We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. Results We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21–27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. Conclusions Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Objective During pipe jacking construction, aging sewage pipes within the construction area are prone to rupture, leading to sewage infiltration into the thixotropic slurry along the soil body, thus impacting the performance of the thixotropic slurry to some extent. In order to ensure the construction safety, it is necessary to study the change law of performance indicator after sewage infiltration of the thixotropic slurry. Method Using the No. 1 entrance and exit project of Baohua Street Station on Jinan Rail Transit Line 2 as a case study, combined with the construction conditions of the sewage pipe rupture due to the jacking pipe underpass at the entrance and exit of the station, the change law of the thixotropic slurry performance indicators after sewage infiltration is studied, and the sewage infiltration impact on the drag reduction effect of thixotropic slurry is analyzed by drag reduction test. Result & Conclusion After sewage infiltration, the performance of the thixotropic slurry deteriorates, with a reduction in slurry funnel viscosity and a significant increase in water separation rate and water loss. The positive charges of inorganic salts in the sewage and the negative charges of the slurry soil particles attract each other, causing the slurry Zeta potential dropping from a stable 31.0 mV to below 20.0 mV. Sewage infiltration results in a noticeable increase in the mass fraction of large-size soil particles, and aggregation and precipitation of the slurry, this is the reason for the significant increase in slurry water separation rate. Sewage infiltration also leads to the decrease in the slurry drag reduction effect, with an increase in the friction factor and pipe jacking thrust.

Objectives: This study aimed to characterize a tigecycline-resistant hypervirulent Klebsiella pneumoniae (HvKP) strain, identified as KLZT, which carries the tigecycline resistance gene cluster tmexC2-tmexD2-toprJ2 belonging to ST29 and serotype K212. Methods: Antimicrobial susceptibility and virulence phenotypes were assessed, followed by whole-genome sequencing (WGS) using PacBio II and MiSeq sequencers. Genome annotation was carried out using the RAST server and bioinformatics analysis revealed the genetic characteristics of this strain. Results: Antimicrobial and virulence phenotype testing indicated that K. pneumoniae strain KLZT could be considered as a multidrug-resistant HvKP. WGS analysis showed that KLZT has a single 5,536,506-bp chromosome containing three plasmids 290,963 bp (pKLZT-1), 199,302 bp (pKLZT-2), and 4820 bp (pKLZT-3) in size, and also includes the ST29 and K212 serotypes. Four (blaSHV-187, oqxA, oqxB, and fosA6) and six resistance genes (tmexC2-tmxeD2-toprJ2, blaOXA-1, aac(6′)-Ib-cr, catB3, arr-3, and blaLEN27) were identified from chromosomal and plasmid pKLZT-1, respectively. Gene-based analysis of the resistance genes of plasmid pKLZT-1 showed that the tigecycline resistance gene cluster-carrying region was flanked by umuC and umuD (umuD-hps-IS5-tmexC2-tmexD2-toprJ2-umuC), as well as other resistance genes and virulence factors (ureB, ureC, and ureG), which were carried by IS5075-Tn3-intI1 -aac(6′)-Ib-cr-blaOXA-1-catB3-arr-3-blaLEN27-Tn3-ISkpn26-ureBCG-IS5075. Conclusions: WGS has revealed that a multidrug-resistant strain, HvKP KLZT, belonging to ST29 with capsular serotype K212, contains a multidrug-resistance plasmid.

Abstract The mineralization mechanism responsible for the fossilization of archaeological textiles in close proximity to metal artifacts presents a sophisticated preservation process at both macro and micro levels. This study examines archaeological textiles dating from 2200 BC to AD 1900, sourced from three distinct archaeological sites. The focus is on understanding the microstructural degradation of fibers within a specific burial environment and the preservation achieved through mineralization. These archaeological fibers of archaeological textiles exhibit morphological preservation in the immediate vicinity of copper-based objects. Utilizing tools such as a digital camera, scanning electron microscopy with energy dispersive spectroscopy (SEM–EDS), high-resolution synchrotron-based microtomography (μCT), and enzyme-linked immunosorbent assay (ELISA), we examined fiber morphology, conducted elemental analysis, identified fiber types, and analyzed fiber characteristics. Our findings reveal the presence of smooth-surfaced wools and silks, fibers covered with calculi, and fiber impressions—all subjected to mineralization. These mineralized fibers can be categorized into three distinct stages of mineralization, each exhibiting varying carbon content. We inferred a correlation between mineralization rate and carbon content while also identifying mineralization density distribution on these textiles. Lastly, this study provides insights into the preservation states of textiles across three different mineralization stages, enriching our understanding of the deterioration of organic archaeological material.

Abstract Background Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biological function of DCHS1 in pan-cancer. Materials and methods We evaluated the expression, the prognostic value, the diagnostic value and genomic alterations of DCHS1 by using the databases, including TCGA, UALCAN, HPA, GEPIA2.0 and GSCA. We employed the databases of UCSC, TIMER2.0, TISIDB, GSCA to analyze the association between DCHS1 expression and the immune microenvironment, stemness, TMB, MSI and anticancer drug sensitivity. BioGRID, STRING and GEPIA2.0 were used to perform protein interaction and functional enrichment analysis. Real-time quantitative PCR, CCK8, Transwell assay and Western blot were performed to determine the function of DCHS1 in UCEC. Results DCHS1 is differentially expressed in many cancers and its expression is significantly associated with tumor prognosis and diagnosis. DCHS1 expression was significantly correlated with the infiltration of cancer-associated fibroblasts (CAFs), Endothelial cell (ECs), and Hematopoietic stem cell in most cancers. In addition, DCHS1 was significantly associated with sensitivity to many antitumor drugs. Functional enrichment analysis revealed that DCHS1-related proteins were involved in Focal adhesion, Endometrial cancer and Wnt signaling pathway. GSEA results showed that DCHS1 was related to epithelial-mesenchymal transition (EMT) in many cancers. In vitro experiments in UCEC showed that DCHS1 regulated cell proliferation, migration and EMT. Conclusions Our findings indicated that DCHS1 might be a novel prognostic and diagnostic biomarker and immunotherapy target, and plays an important role in the proliferation, migration and EMT in UCEC.

Abstract Background There are currently no effective prediction methods for evaluating the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD). Aims To investigate the risk factors for cognitive dysfunction in patients with CSVD and to construct a risk prediction model. Methods A retrospective study was conducted on 227 patients with CSVD. All patients were assessed by brain magnetic resonance imaging (MRI), and the Montreal Cognitive Assessment (MoCA) was used to assess cognitive status. In addition, the patient’s medical records were also recorded. The clinical data were divided into a normal cognitive function group and a cognitive impairment group. A MoCA score

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions: Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Abstract Simulating and predicting Arctic sea ice accurately remains an academic focus due to the complex and unclear mechanisms of Arctic sea ice variability and model biases. Meanwhile, the relevant forecasting and monitoring authorities are searching for models to meet practical needs. Given the previous ideal performance of cGENIE model in other fields and notable features, we evaluated the model’s skill in simulating Arctic sea ice using multiple methods and it demonstrates great potential and combined advantages. On this basis, we examined the direct drivers of sea-ice variability and predicted the future spatio-temporal changes of Arctic sea ice using the model under different Representative Concentration Pathways (RCP) scenarios. Further studies also found that Arctic sea ice concentration shows large regional differences under RCP 8.5, while the magnitude of the reduction in Arctic sea ice thickness is generally greater compared to concentration, showing a more uniform consistency of change.

Abstract With the rapid development of the digital economy, its environmental impact, particularly on carbon dioxide emissions in resource-based cities, has emerged as a vital research topic. Resource-based cities, often central to traditional industries, are confronted with the dual challenges of environmental pollution and economic transformation. This study employs empirical analysis to examine the influence of the digital economy on carbon dioxide emissions in these cities. The findings reveal that the digital economy significantly reduces carbon dioxide emissions, with this impact being more pronounced in the early stages of digital economic development and gradually diminishing thereafter. In the mechanism analysis, we found that the digital economy can reduce carbon dioxide emissions in resource-based cities by raising public concern about the environment. Moreover, the study highlights significant variations in carbon reduction effects among different types of resource-based cities, noting that stronger environmental regulations further enhance these effects. These insights not only provide a new theoretical perspective but also offer practical guidance for policymakers in promoting sustainable development within the digital economy.

The current design of member foundation only considers horizontal forces (H) and ignores the effect of torque (T), which may lead to torsional failure of the foundation. To analyze the bearing characteristics of rigid rectangular foundation subjected to horizontal force and torque (H-T), according to the stress characteristics of the foundation, the corresponding simplified calculation model is established, and the theoretical solutions of the stress and deformation analysis of the foundation under the two bearing modes of torque (T), horizontal force (H) - eccentric bending moment (M) are derived; numerical simulation analysis is carried out to obtain the failure envelope of rigid rectangular foundations under push torsion H-T load. And then the rationality of the theoretical calculation method is verified by the indoor model test. Finally, the influences of torsion ratio and foundation resistance ratio coefficient m on the stress and deformation of foundation are analyzed. The results show that the failure envelope of rigid rectangular foundation under push torsion H-T load is approximately parabolic. With the increase of torsion-thrust ratio, the horizontal bearing capacity of the foundation decreases, and its failure mode changes from horizontal deformation failure to torsional deformation failure. The increase of the proportional coefficient m can reduce the horizontal displacement and rotation angle at the foundation ground effectively. To ensure the safety and stability of the rigid rectangular foundation, the nature and compaction of the overlying backfill should satisfy the design requirements. This study can provide basic information for the design of multi-rod unified rod foundations.

Introduction: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. Objectives: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. Methods: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Results: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Conclusions: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Abstract Introduction Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies. Methods A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay. Results Pharmacokinetic analysis of the drug concentration–time data showed that the mean maximum observed serum QX002N concentration (C max) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration–time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration–time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%. Conclusions Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects. Trial Registration www.chinadrugtirals.org.cn , CTR20220430.

Introduction We conducted analyses of the association between smoking and osteoporosis and osteoporotic fractures using a secondary dataset analysis of the National Health and Nutrition Examination Survey (NHANES) database and the two-sample Mendelian randomization (MR) method. Methods The associations between smoking and osteoporosis or osteoporotic fractures were analyzed using weighted logistic regression models for both univariate and multivariable analyses using pooled 1999–2018 NHANES data. The summary-level data of genome-wide association studies (GWAS) of smoking and osteoporosis were extracted from the IEU Open GWAS project. The inverse variance weighted method was used as the main method for the two-sample MR analysis. Results We obtained the following main findings based on the NHANES data: smoking was associated with osteoporosis according to the analyses of 30856 participants (OR=1.21; 95% CI: 1.06–1.39, p=0.004); smoking was associated with hip osteoporotic fracture according to the analyses of 30928 participants (OR=1.47; 95% CI: 1.14–1.90, p=0.004); smoking was associated with wrist osteoporotic fracture according to the analyses of 30923 participants (OR=1.33; 95% CI: 1.18–1.49, p

Abstract Introduction Previous studies have explored the connections between various ocular biological parameters with myopia. Our previous study also found that pupil data can predict the myopic progression during the interventions for myopia. However, studies exploring the association between pupil diameter and myopia in preschoolers with myopia were lacking. Hence this study was aimed to investigate the association between pupil diameter and myopia in preschoolers with myopia based on a real-world, large-scale dataset. Methods Data containing 650,671 preschoolers were collected from a total of 1943 kindergartens in Shenzhen, China. Refraction and pupil parameters were collected. After data filtering, the occurrence of myopia and its association with age, gender, pupil diameter, and other variables, were analyzed. Random forest (RF) and eXtreme gradient boosting (XGBoost) were selected from seven machine learning algorithms to build the model. The mean decrease accuracy (MDA), mean decrease Gini (MDG), and gain feature importance (GFI) techniques were employed to quantify the importance of pupil diameter and other features. Results After the assessments, 51,325 valid records with complete pupil data were included, and 3468 (6.76%) were identified as myopia based on the calculated cycloplegic refraction. Preschoolers with myopia presented reduced pupil diameter and greater variation (5.00 ± 0.99 mm) compared to non-myopic preschoolers (6.22 ± 0.67 mm). A nonlinear relationship was found according to the scatterplots between pupil diameter and refraction (R 2 = 0.14). Especially preschoolers with myopia had reduced pupil diameter compared to emmetropic preschoolers, but hyperope did not experience additional pupil enlargement. After adjusting for other covariates, this relationship is still consistent (P

Abstract Stomatal movement is vital for plants to exchange gases and adaption to terrestrial habitats, which is regulated by environmental and phytohormonal signals. Here, we demonstrate that hydrogen peroxide (H2O2) is required for light-induced stomatal opening. H2O2 accumulates specifically in guard cells even when plants are under unstressed conditions. Reducing H2O2 content through chemical treatments or genetic manipulations results in impaired stomatal opening in response to light. This phenomenon is observed across different plant species, including lycopodium, fern, and monocotyledonous wheat. Additionally, we show that H2O2 induces the nuclear localization of KIN10 protein, the catalytic subunit of plant energy sensor SnRK1. The nuclear-localized KIN10 interacts with and phosphorylates the bZIP transcription factor bZIP30, leading to the formation of a heterodimer between bZIP30 and BRASSINAZOLE-RESISTANT1 (BZR1), the master regulator of brassinosteroid signaling. This heterodimer complex activates the expression of amylase, which enables guard cell starch degradation and promotes stomatal opening. Overall, these findings suggest that H2O2 plays a critical role in light-induced stomatal opening across different plant species.

Abstract Background The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients. Methods Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained. Results Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94—14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24—14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23—8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4–6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively. Conclusions Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4–6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes’ cytoplasm from P-ICSI varied that from R-ICSI.

Due to the complex background, small and dense targets, and large scale continuous changes in remote sensing images, universal object detectors are difficult to adapt well, resulting in poor detection performance. To address the above issues, a multi-branch feature mapping based remote sensing image object detection algorithm is proposed based on the YOLOv5s model. Firstly, a RepVGG module combined with gated channel transformation is designed using structural reparameterization technology. Its series structure is used to replace the C3 module of the original backbone network, aggregating global contextual information and enhancing feature expression and extraction capabilities. Secondly, the adaptive exponential weighted pooling method and the sampling method of inverse process reconstruction feature fusion network are used to maximize the retention of feature information and improve the detection performance of smaller targets. Finally, the combination of EIoU and Focal Loss is introduced as the loss function of the model to optimize the regression rate of the prediction box and the loss weight distribution of difficult and easy samples, further improving the positioning accuracy. The experimental results on the DIOR and NWPU VHR-10 datasets show that the average accuracy of the proposed algorithm reaches 92.2% and 92.5%, respectively, which is 3.5 percentage points and 5.6 percentage points higher than YOLOv5s, achieving better detection performance. At the same time, the real-time performance also meets the requirements of remote sensing image object detection in actual scenes.

IntroductionDermatomyositis (DM) is an idiopathic inflammatory myopathy. Because of clinical heterogeneity, the metabolite profile of DM patients with different myositis-specific autoantibodies (MSAs) remains elusive. This study aimed to explore the metabolomics characteristics of the serum in DM with different MSAs, low or high disease activity, and interstitial lung disease.MethodsUntargeted metabolomics profiling was performed in the serum of a discovery cohort (n=96) and a validation cohort (n=40), consisting of DM patients with MSAs, low or high disease activity, and/or interstitial lung disease (DM-ILD) compared to age- and gender-matched healthy controls (HCs).ResultsThe lipid profile in DM was found to be abnormal, especially dysregulated glycerophospholipid metabolism and fatty acid oxidation, which might affect the pathogenesis of DM by disrupting the balance of Th17 and Treg. We identified potential biomarkers of DM that can distinguish between low or high disease activity and reflect lung involvement. Two metabolite combinations including pro-leu, FA 14:0;O can distinguish high disease activity DM from low disease activity DM and HCs, and five including indole-3-lactic acid, dihydrosphingosine, SM 32:1;O2, NAE 17:1, and cholic acid can distinguish DM-ILD from DM without ILD (DM-nonILD). DM with different MSAs had unique metabolic characteristics, which can distinguish between MDA5+DM, Jo-1+DM, and TIF1-γ+DM, and from the antibody-negative groups. The sphingosine metabolism has been found to play an important role in MDA5+DM, which was associated with the occurrence of ILD.DiscussionAltered metabolic profiles of dermatomyositis were associated with different myositisspecific autoantibodies, disease activity, and interstitial lung disease, which can help in the early diagnosis, prognosis, or selection of new therapeutic targets for DM.

BackgroundClonorchis sinensis (C. sinensis) infection plays an important role in the progression of hepatocarcinogenesis. However, its specific role in HCC progression remains unclear. This study aimed to investigate whether C. sinensis contributes to angiogenesis in HCC.MethodsA comprehensive clinical analysis was conducted on 947 HCC patients, divided into two groups: C. sinensis (-) HCC and C. sinensis (+) HCC. Kaplan-Meier survival curves and log-rank tests were utilized to assess survival outcomes. Microvessel density (MVD) was evaluated through CD34 immunohistochemistry on hepatectomy specimens. A chemistry analyzer and blood analyzer were employed to measure the concentration of circulating angiogenesis-related biomarkers. Quantitative reverse transcription-PCR (qRT-PCR) was used to analyze the expression of angiogenesis-related genes (CD34, Ang1, Ang2, VEGF, PDGF) in HCC tissues.ResultsC. sinensis infection was associated with poorer outcomes in HCC patients, with significantly shorter overall survival (OS) (p = 0.014) and recurrence-free survival (RFS) (pConclusionC. sinensis infection is closely associated with inflammatory responses and may promote metabolic reprogramming in HCC, thereby enhancing its malignant characteristics.

ObjectiveBaduanjin, a traditional Chinese exercise for health enhancement and chronic disease prevention, has been practiced for millennia. However, studies on the exercise intensity of Baduanjin are limited. Most existing studies focus on its general health benefits rather than quantifying its specific intensity levels. This study aims to measure and compare the exercise intensity indices of long-term Baduanjin practitioners and beginners, providing insights into its mechanisms for disease prevention and treatment and supporting the scientific formulation of clinical exercise prescriptions.MethodsTwenty healthy adults aged 35–45 years old and the mean BMI was 24.45 were recruited and divided into a beginner group (A group, no prior practice, 10 participants) and a skilled group (B group, practice duration ≥3 years, 10 participants). The Italian Cosmed/K5 wireless portable cardiopulmonary testing system was used to measure indicators during the practice.ResultsWithin-group analysis revealed statistically significant differences in oxygen consumption (VO2), oxygen consumption per kilogram of body weight (VO2/kg), metabolic equivalent (METs), heart rate (HR), oxygen pulse (VO2/HR), respiratory rate (RR), and minute ventilation (VE) between exercise and resting states in both the B and A groups (P

Background Increasing evidence has emerged for traditional, complementary and integrative medicine (TCIM) to treat COVID-19 which requires systematic summaries of the net benefits of interventions against standard care and one another. The study aims to conduct a systematic review and network meta-analysis (NMA) regarding TCIM therapies for treating mild/moderate acute COVID-19, potentially informing the WHO guideline development and clinical decision-making.Methods and analysis We will search Embase, MEDLINE, Virtual Health Library on Traditional Complementary and Integrative Medicine, Cochrane Central Register of Controlled Trials, WHO’s International Clinical Trials Registry Platform with additional searches of Chinese and Korean literature sources for randomised controlled trials comparing TCIM with placebo, standard care, no treatment or with an alternate type of TCIM to treat COVID-19. We will limit the search dates from 2020 to 28 March 2024. Reviewers will, in duplicate, screen eligible articles, extract data and evaluate the risk of bias. We will conduct frequentist network meta-analyses for network comparisons and each outcome. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach and classify interventions from most to least effective or harmful.Ethics and dissemination This NMA is based on the existing trials and data which is not subject to ethical approval. We will publish the NMA in a peer-reviewed journal. This may provide methodological reference and clinical evidence for TCIM on future epidemic-prone diseases.PROSPERO registration number CRD42024517321.

Three-dimensional (3D) geological models can visually present various underground geological body forms, geological structures, geological hazards, which is of great significance for urban spatial planning and urban geological hazard prevention and control. To overcome technical difficulties such as poor accuracy, poor aesthetics and the difficulty to modify and improve the model afterward, this paper proposes a 3D modeling technology for urban geology with multiple complex geological structures based on multi-source heterogeneous data with the common constraints of geological knowledge and geological laws. This technique can utilize various modeling data, such as DEM data, geological profiles, drillhole data, geophysical interpretation data and structure outline maps. Under the common constraints of geological prior knowledge and geological laws, the block modeling technique is used to complete the construction of 3D urban geological models under complex geological conditions. Taking the construction of 3D geological model in Chengdu as an example, this paper focuses on the theory and algorithm of 3D modeling of urban geology, the geological background of the demonstration area, the preparation and processing of 3D modeling data, and the research and demonstration application of 3D modeling technology for urban geology.

ObjectiveAcute aneurysmal rupture can be treated with endovascular therapy or surgical clipping. For patients with concurrent acute hydrocephalus, the placement of an external ventricular drainage (EVD) is required. This study aims to investigate the impact of pre-treatment EVD placement on rebleeding in ruptured aneurysms and to examine the influence of dual antiplatelet therapy and the sequencing of dual antiplatelet therapy with EVD placement on EVD-related hematomas.MethodsWe reviewed the clinical data of 83 patients with ruptured aneurysms who underwent EVD placement from a total of 606 aneurysm patients consecutively admitted between January 2018 and January 2023. The analysis focused on the impact of pre-treatment EVD placement on aneurysmal rebleeding and the effect of dual antiplatelet therapy and its sequencing with EVD placement on EVD-related hematomas.ResultsAmong the 503 patients with ruptured aneurysms, 83 required EVD placement. EVD was placed before aneurysm treatment in 63 patients and after treatment in 20 patients. The number of aneurysmal rebleeding cases in the pre-treatment EVD group and non-EVD group was 1 (1.6%) and 20 (4.8%), respectively (p = 0.406). 31 patients (37.3%) underwent stent-assisted embolization or flow diversion requiring dual antiplatelet therapy, while 52 patients (62.7%) underwent simple embolization or surgical clipping without antiplatelet therapy. EVD-related hematomas occurred in 14 patients (16.9%), with 10 cases (32.3%) in those receiving dual antiplatelet therapy and 4 cases (7.7%) in those not receiving antiplatelet therapy (p = 0.01). Among 16 patients who had EVD placed before dual antiplatelet therapy, 4 (25%) developed EVD-related hematomas. Of the 15 patients who had EVD placed after dual antiplatelet therapy, 6 (40%) developed EVD-related hematomas (p = 0.458).ConclusionIn patients with aneurysmal subarachnoid hemorrhage (aSAH) and acute hydrocephalus, the placement of EVD before aneurysm treatment does not increase the risk of rebleeding. However, dual antiplatelet therapy increases the risk of EVD-related hematoma, and the sequence of EVD placement relative to dual antiplatelet therapy does not appear to significantly affect the outcome of EVD-related hematoma.

Summary: Heart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery (n = 514) and validation (n = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 μmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 μmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.

Microalgae are a promising sustainable food source with high nutritional value and environmental benefits. This study investigated the presence of toxic metals and rare earth elements (REEs) in 68 microalgal-based food products and conducted a probabilistic risk assessment to evaluate potential health risks. The findings revealed high detection rates of REEs (80.96% to 100%) and heavy metals (83.82% to 100%), with REE concentrations ranging from 0.0055 to 0.5207 mg/kg. Heavy metals were detected at the following average concentrations: As (2.80 mg/kg) > Cr (1.27 mg/kg) > Pb (0.30 mg/kg) > Cd (0.20 mg/kg) > Hg (0.01 mg/kg). Carcinogenic risk analysis for Cd (3.004 × 10−3), Cr (1.484 × 10−3), and As (1.1283 × 10−2) indicated that 95th percentile values exceeded established safety thresholds (10−4). These findings highlight the critical need for stringent monitoring and the establishment of comprehensive regulatory frameworks for the safety of novel microalgae foods.

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate as a biomarker and its influence on immune cell dynamics, emphasizing its critical role in modulating immune responses during sepsis. Mechanistically, key lactate transporters like MCT1, MCT4, and the receptor GPR81 are crucial in mediating these effects. HIF-1α also plays a significant role in lactate-driven immune modulation. Additionally, lactate affects immune cell function through post-translational modifications such as lactylation, acetylation, and phosphorylation, which alter enzyme activities and protein functions. These interactions between lactate and immune cells are central to understanding sepsis-associated immune dysregulation, offering insights that can guide future research and improve therapeutic strategies to enhance patient outcomes.

Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.

BackgroundArtificial intelligence (AI) has increasingly been applied to computed tomography angiography (CTA) images to aid in the assessment of atherosclerotic plaque. Our aim was to explore the diagnostic accuracy of AI-assisted CTA for plaque diagnosis and classification through a systematic review and meta-analysis.MethodsA systematic literature review was performed by searching PubMed, EMBASE, and the Cochrane Library according to PRISMA guidelines. Original studies evaluating the diagnostic accuracy of radiomics, machine-learning, or deep-learning techniques applied to CTA images for detecting stenosis, calcification, or plaque vulnerability were included. The quality and risk of bias of the included studies were evaluated using the QUADAS-2 tool. The meta-analysis was conducted using STATA software (version 17.0) to pool sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) to determine the overall diagnostic performance.ResultsA total of 11 studies comprising 1,484 patients were included. There was low risk of bias and substantial heterogeneity. The overall pooled AUROC for atherosclerotic plaque assessment was 0.96 [95% confidence interval (CI) 0.94–0.97] across 21 trials. Of these, for ≥50% stenosis detection, the AUROC was 0.95 (95% CI 0.93–0.96) in five studies. For identifying ≥70% stenosis, the AUROC was 0.96 (95% CI 0.94–0.97) in six studies. For calcium detection, the AUROC was 0.92 (95% CI 0.90–0.94) in six studies.ConclusionOur meta-analysis demonstrates that AI-assisted CTA has high diagnostic accuracy for detecting stenosis and characterizing plaque composition, with optimal performance in detecting ≥70% stenosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO, identifier (CRD42023431410).

Reservoirs play a critical role in terrestrial hydrological systems, but the contribution of small and medium-sized ones is rarely considered and recorded. Particularly in developing countries, there is a rapid increase of such reservoirs due to their quick construction. Accurately identifying these reservoirs is important for understanding social and economic development, but distinguishing them from other natural water bodies poses a significant challenge. Thus, we propose a method to identify reservoirs using high-resolution satellite images and deep learning algorithms. We trained models with various parameters and network structures, and You Only Look Once version 7 (YOLOv7) outperformed other algorithms and was selected to build the final model. The method was applied to a region in northwestern Iran, characterized by an abundance of reservoirs of various sizes. Evaluation results indicated that our method was highly accurate (mAP: 0.79, Recall: 0.76, Precision: 0.82). The YOLOv7 model was able to automatically identify 650 reservoirs in the entire study region, indicating that the proposed method can accurately detect reservoirs and has the potential for broader-scale surveys, even global applications.

Abstract The extracytoplasmic function (ECF) sigma factor AlgU is involved in the regulation of various virulence-related pathways in Pseudomonas syringae, especially alginate biosynthesis and motility, and the role of AlgU differs among P. syringae pathovars. However, to date, the mechanism of its regulation in virulence of P. syringae pv. actinidiae (Psa) is still unclear. ECF sigma factors are a class of alternative sigma factors that typically function with anti-sigma factors as part of cell-surface signaling systems. Under non-inducing conditions, AlgU remains inhibited by anti-sigma factors such as MucA and MucB. To investigate the function of AlgU in Psa, mutant strains lacking algU or lacking algU with mucA and mucB genes, as well as complementary and overexpression strains of algU were generated, respectively. The results showed that AlgU was highly conserved among P. syringae pathovars and positively regulated growth rate, pathogenicity, and resistance to osmotic and oxidative stress of Psa QSY6. While AlgU did not affect the motility and exopolysaccharide production of Psa, its abundant expression enhanced the swimming ability of QSY6 and reduced its production of extracellular polysaccharides. Furthermore, AlgU regulates a number of virulence-related factors, including the Hrp system, the type VI secretion system, and flagellar synthesis. Specifically, AlgU induced the expression of hrpL and hrpRS in vivo, and repressed the transcription of hrpL and tssC in vitro, while promoting the expression of hrpS, fliC, and tssJ. This study contributes to a better understanding of the mechanisms of virulence regulation of AlgU in Psa.

Abstract Background Pseudomonas syringae pv. actinidiae (Psa) is an important bacterial plant pathogen that causes severe damage to the kiwifruit industry worldwide. Three Psa strains were recently obtained from different kiwifruit orchards in Anhui Province, China. The present study mainly focused on the variations in virulence and genome characteristics of these strains based on the pathogenicity assays and comparative genomic analyses. Results Three strains were identified as biovar 3 (Psa3), along with strain QSY6 showing higher virulence than JZY2 and YXH1 in pathogenicity assays. The whole genome assembly revealed that each of the three strains had a circular chromosome and a complete plasmid. The chromosome sizes ranged from 6.5 to 6.6 Mb with a GC content of approximately 58.39 to 58.46%, and a predicted number of protein-coding sequences ranging from 5,884 to 6,019. The three strains clustered tightly with 8 Psa3 reference strains in terms of average nucleotide identity (ANI), whole-genome-based phylogenetic analysis, and pangenome analysis, while they were evolutionarily distinct from other biovars (Psa1 and Psa5). Variations were observed in the repertoire of effectors of the type III secretion system among all 15 strains. Moreover, synteny analysis of the three sequenced strains revealed eight genomic regions containing 308 genes exclusively present in the highly virulent strain QSY6. Further investigation of these genes showed that 16 virulence-related genes highlight several key factors, such as effector delivery systems (type III secretion systems) and adherence (type IV pilus), which might be crucial for the virulence of QSY6. Conclusion Three Psa strains were identified and showed variant virulence in kiwifruit plant. Complete genome sequences and comparative genomic analyses further provided a theoretical basis for the potential pathogenic factors responsible for kiwifruit bacterial canker.

Abstract This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (β = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (β = 0.147, FDR = 0.006), sensorimotor cortex (β = 0.153, FDR = 0.006), and entorhinal cortex (β = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).

Abstract Purpose We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC). Methods The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS). Results 133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012). Conclusions Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence.