Predominance of A2063G mutant strains in the Mycoplasma pneumoniae epidemic in children-a clinical and epidemiological study in 2023 in Wuhan, China.

OBJECTIVES: The prevalence of respiratory infectious diseases has changed in the post Covid-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention. METHODS: Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung CT imaging. RESULTS: Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in year 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MPP treatment. CONCLUSION: A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.

Low-dose cadmium induces lymphangiogenesis through activation of the STAT3 signaling pathway.

Cadmium (Cd) is a widespread environmental toxicant that poses significant threat to public health. After intake, Cd is distributed throughout the body via blood and lymphatic circulation. However, the effect of Cd on lymphatic vessels has not been revealed. In this study, mice were exposed to 10 µM cadmium chloride through drinking water immediately after corneal alkali burn. In vivo analyses showed that Cd treatment enhances the alkali burn-induced corneal lymphangiogenesis, which is characterized by increased expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero-related homeobox 1 (PROX-1) and vascular endothelial growth factor receptor 3 (VEGFR3). In vitro, the proliferation and migration of human dermal lymphatic endothelial cells (HDLECs) are increased by 1 µM Cd treatment, while inhibited by 10 µM Cd treatment. At a concentration of 1 µM, Cd specifically induces phosphorylation of signal transducer and activator of transcription 3 (STAT3), but has no effect on the MAPK, AKT, or NF-κB signaling pathway. In the presence of the STAT3 inhibitor STATTIC, Cd fails to induce HDLECs proliferation and migration. In addition, Cd upregulates VEGFR3 expression and its gene promoter activity in a STAT3-dependent manner. Our study suggests that low-dose Cd promotes lymphangiogenesis through activation of the STAT3 signaling pathway.

Residual inflammatory risk and vulnerable plaque in the carotid artery in patients with ischemic stroke.

Objective: Inflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke. Methods: Patients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C <2.6 mmol/L and hsCRP ≥2 mg/L), residual cholesterol risk (RCR) only (LDL-C ≥2.6 mmol/L and hsCRP <2 mg/L), both risk or residual cholesterol and inflammatory risk (RCIR) (LDL-C ≥2.6 mmol/L and hsCRP ≥2 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <2 mg/L). Vulnerable plaques were determined if it had a low attenuated plaque CT value of <35 Hounsfield Units (HU) and a remodeling index of >1.1, which indicated a positive remodeling. Results: Out of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13-3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08-6.77, P = 0.034). Conclusions: In patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

Comparative genomic analysis provides insights into the genetic diversity and pathogenicity of the genus Brucella.

Some Brucella spp. are important pathogens. According to the latest prokaryotic taxonomy, the Brucella genus consists of facultative intracellular parasitic Brucella species and extracellular opportunistic or environmental Brucella species. Intracellular Brucella species include classical and nonclassical types, with different species generally exhibiting host preferences. Some classical intracellular Brucella species can cause zoonotic brucellosis, including B. melitensis, B. abortus, B. suis, and B. canis. Extracellular Brucella species comprise opportunistic or environmental species which belonged formerly to the genus Ochrobactrum and thus nowadays renamed as for example Brucella intermedia or Brucella anthropi, which are the most frequent opportunistic human pathogens within the recently expanded genus Brucella. The cause of the diverse phenotypic characteristics of different Brucella species is still unclear. To further investigate the genetic evolutionary characteristics of the Brucella genus and elucidate the relationship between its genomic composition and prediction of phenotypic traits, we collected the genomic data of Brucella from the NCBI Genome database and conducted a comparative genomics study. We found that classical and nonclassical intracellular Brucella species and extracellular Brucella species exhibited differences in phylogenetic relationships, horizontal gene transfer and distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes, showing the close relationship between the genetic variations and prediction of phenotypic traits of different Brucella species. Furthermore, we found significant differences in horizontal gene transfer and the distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes between the two chromosomes of Brucella, indicating that the two chromosomes had distinct dynamics and plasticity and played different roles in the survival and evolution of Brucella. These findings provide new directions for exploring the genetic evolutionary characteristics of the Brucella genus and could offer new clues to elucidate the factors influencing the phenotypic diversity of the Brucella genus.

The impact of continuous cultivation of Ganoderma lucidum on soil nutrients, enzyme activity, and fruiting body metabolites.

To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0-15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend. Conversely, in the deeper soil layer (15-30 cm), organic matter, ammonium nitrogen, available potassium, alkaline phosphatase, and sucrase demonstrated a decreasing trend, while nitrate nitrogen, available phosphorus, pH, EC, salt content, polyphenol oxidase, and soil peroxidase showed an increasing trend. Metabolomic analysis of Ganoderma lucidum fruiting bodies distinguished 64 significantly different metabolites between the GCK and GT groups, with 39 components having markedly higher relative contents in GCK and 25 components having significantly lower relative contents in GCK compared to GT. Moreover, among these metabolites, there were more types with higher contents in the fruiting bodies harvested in the first year (GCK) compared to those harvested in the second year (GT), with pronounced differences. KEGG pathway analysis revealed that GCK exhibited more complex metabolic pathways compared to GT. The metabolites of Ganoderma lucidum fruiting bodies were predominantly influenced by soil physicochemical factors and soil enzyme activity. In the surface soil layer (0-15 cm), the metabolome was significantly affected by soil pH, soil organic matter, available phosphorus, and soil alkaline phosphatase, while in the deeper soil layer (15-30 cm), differences in the Ganoderma lucidum metabolome were more influenced by soil alkaline phosphatase, soil catalase, pH, nitrate nitrogen, and soil sucrase.

Freeprotmap: waiting-free prediction method for protein distance map.

BACKGROUND: Protein residue-residue distance maps are used for remote homology detection, protein information estimation, and protein structure research. However, existing prediction approaches are time-consuming, and hundreds of millions of proteins are discovered each year, necessitating the development of a rapid and reliable prediction method for protein residue-residue distances. Moreover, because many proteins lack known homologous sequences, a waiting-free and alignment-free deep learning method is needed. RESULT: In this study, we propose a learning framework named FreeProtMap. In terms of protein representation processing, the proposed group pooling in FreeProtMap effectively mitigates issues arising from high-dimensional sparseness in protein representation. In terms of model structure, we have made several careful designs. Firstly, it is designed based on the locality of protein structures and triangular inequality distance constraints to improve prediction accuracy. Secondly, inference speed is improved by using additive attention and lightweight design. Besides, the generalization ability is improved by using bottlenecks and a neural network block named local microformer. As a result, FreeProtMap can predict protein residue-residue distances in tens of milliseconds and has higher precision than the best structure prediction method. CONCLUSION: Several groups of comparative experiments and ablation experiments verify the effectiveness of the designs. The results demonstrate that FreeProtMap significantly outperforms other state-of-the-art methods in accurate protein residue-residue distance prediction, which is beneficial for lots of protein research works. It is worth mentioning that we could scan all proteins discovered each year based on FreeProtMap to find structurally similar proteins in a short time because the fact that the structure similarity calculation method based on distance maps is much less time-consuming than algorithms based on 3D structures.

Layered BaV6O16·3H2O@GO as a high performance cathode material for calcium ion batteries.

The lack of suitable cathode materials has hampered the further development of calcium-ion batteries (CIBs). A novel composite cathode material, namely BaV6O16·3H2O@GO, was fabricated, which delivers a high specific capacity of 285.72 mA h g-1 at 50 mA g-1 after 50 cycles and a long cycle life, benefiting from a large layer spacing and robust structure. This study provides guidance for the development of vanadium-based cathode materials for CIBs.

The Resource Utilization of Poplar Leaves for CO2 Adsorption.

Every late autumn, fluttering poplar leaves scatter throughout the campus and city streets. In this work, poplar leaves were used as the raw material, while H3PO4 and KOH were used as activators and urea was used as the nitrogen source to prepare biomass based-activated carbons (ACs) to capture CO2. The pore structures, functional groups and morphology, and desorption performance of the prepared ACs were characterized; the CO2 adsorption, regeneration, and kinetics were also evaluated. The results showed that H3PO4 and urea obviously promoted the development of pore structures and pyrrole nitrogen (N-5), while KOH and urea were more conductive to the formation of hydroxyl (-OH) and ether (C-O) functional groups. At optimal operating conditions, the CO2 adsorption capacity of H3PO4- and KOH-activated poplar leaves after urea treatment reached 4.07 and 3.85 mmol/g, respectively, at room temperature; both showed stable regenerative behaviour after ten adsorption-desorption cycles.

Influence of Socioeconomic Status on Functional Outcomes After Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: This review aimed to quantify the impact of socioeconomic status on functional outcomes from stroke and identify the socioeconomic status indicators that exhibit the highest magnitude of association. METHODS AND RESULTS: We performed a systematic literature search across Medline and Embase from inception to May 2022, to identify observational studies (n≥100, and in English). Risk of bias was assessed using the modified Newcastle Ottawa Scale. Random effects meta-analysis was used to pool data. We included 19 studies (157 715 patients, 47.7% women) reporting functional outcomes measured with modified Rankin Scale or Barthel index, with 10 assessed as low risk of bias. Measures of socioeconomic status reported were education (11 studies), income (8), occupation (4), health insurance status (3), and neighborhood socioeconomic deprivation (3). Pooled data suggested that low socioeconomic status was significantly associated with poor functional outcomes, including incomplete education or below high school level versus high school attainment and above (odds ratio [OR], 1.66 [95% CI, 1.40-1.95]), lowest income versus highest income (OR, 1.36 [95% CI, 1.02-1.83]), a manual job/being unemployed versus a nonmanual job/working (OR, 1.62 [95% CI, 1.29-2.02]), and living in the most disadvantaged socioeconomic neighborhood versus the least disadvantaged (OR, 1.55 [95% CI, 1.25-1.92]). Low health insurance status was also associated with an increased risk of poor functional outcomes (OR, 1.32 [95% CI, 0.95-1.84]), although this was association was not statistically significant. CONCLUSIONS: Despite great strides in stroke treatment in the past decades, social disadvantage remains a risk factor for poor functional outcome after an acute stroke. Further research is needed to better understand causal mechanisms and disparities.

The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Genome-wide identification of bHLH transcription factors and expression analysis under drought stress in Pseudoroegneria libanotica at germination.

The basic helix-loop-helix (bHLH) transcription factor family is the second largest in plants. bHLH transcription factor is not only universally involved in plant growth and metabolism, including photomorphogenesis, light signal transduction, and secondary metabolism, but also plays an important role in plant response to stress. However, the function of bHLH TFs in Pseudoroegneria species has not been studied yet. Pseudoroegneria (Nevski) Á. Löve is a perennial genus of the Triticeae. Pseudoroegneria species are mostly distributed in arid/semi-arid areas and they show good drought tolerance. In this study, we identified 152 PlbHLH TFs in Pseudoroegneria libanotica, which could be classified into 15 groups. Collinearity analysis indicates that 122 PlbHLH genes share homology with wbHLH genes in wheat, and it has lower homology with AtbHLH genes in Arabidopsis. Based on transcriptome profiling under an experiment with three PEG concentrations (0%, 10%, and 20%), 10 up-regulated genes and 11 down-regulated PlbHLH genes were screened. Among them, PlbHLH6, PlbHLH55 and PlbHLH64 as candidate genes may be the key genes related to drought tolerance response at germination, and they have been demonstrated to respond to drought, salt, oxidative, heat, and heavy metal stress in yeast. This study lays the foundation for an in-depth study of the biological roles of PlbHLHs in Pse. libanotica, and discovered new drought-tolerance candidate genes to enhance the genetic background of Triticeae crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01433-w.

Mixed exposure to haloacetaldehyde disinfection by-products exacerbates lipid aggregation in the liver of mice.

Haloacetaldehyde disinfection by-products (HAL-DBPs) are among the top three unregulated DBPs found in drinking water. The cytotoxicity and genotoxicity of HALs are much higher than that of the regulated trihalomethanes and haloacetic acids. Previous studies have mainly focused on the toxic effects of single HAL, with few examining the toxic effects of mixed exposures to HALs. The study aimed to observe the effects of mixed exposures of 1∼1000X the realistic level of HALs on the hepatotoxicity and lipid metabolism of C57BL/6J mice, based on the component and concentration of HALs detected in the finished water of Shanghai. Exposure to realistic levels of HALs led to a significant increase in phosphorated acetyl CoA carboxylase 1 (p-ACC1) in the hepatic de novo lipogenesis (DNL) pathway. Additionally, exposure to 100X realistic levels of HALs resulted in significant alterations to key enzymes of DNL pathway, including ACC1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2), as well as key proteins of lipid disposal such as carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator activated receptor α (PPARα). Exposure to 1000X realistic levels of HALs significantly increased hepatic and serum triglyceride levels, as well as total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase levels, significantly decreased high-density lipoprotein. Meanwhile, histopathological analysis demonstrated that HALs exacerbated tissue vacuolization and inflammatory cell infiltration in mice livers, which showed the typical phenotypes of non-alcoholic fatty liver disease (NAFLD). These results suggested that the HALs mixture is a critical risk factor for NAFLD and is significantly highly toxic to C57BL/6J mice.

Association between body mass index and tic disorders in school-age children.

OBJECTIVE: To explore the relationship between body mass index (BMI ) and the severity of tic disorders (TDs) in children 6-14 years old. METHODS: A total of 86 children diagnosed with TDs in a hospital between Jan. 2023 and Sept. 2023 were collected by convenient sampling method, and the general data and TD-specific data were collected and analyzed. RESULTS: Univariate analysis showed that patients with different Yale Global Tic Severity Scale (YGTSS) grades had statistically significant differences in age, BMI, residence, snacking pattern, weekly physical exercise frequency, weekly physical exercise time, and proportion of cesarean birth. Multiple linear regression analysis showed that the YGTSS score grades were related to BMI, snacking pattern, and cesarean birth of the patients. Correlation analysis revealed a positive correlation between BMI grades and the YGTSS score grades, with a higher BMI indicating more severe TDs. Predictive value evaluation showed that BMI, snacking pattern, and cesarean birth had predictive values for TD severity, and the highest value was found in the combined prediction. CONCLUSION: BMI, snacking pattern, and cesarean birth are of predictive values for the severity of TDs. In addition, BMI is positively correlated with the severity of TDs, and a higher BMI suggests more severe TDs.

[Preliminary Study on the Identification of Aerobic Vaginitis by Artificial Intelligence Analysis System]. / 人工智能分析系统对需氧菌性阴道炎的判读方法初探.

Objective: To develop an artificial intelligence vaginal secretion analysis system based on deep learning and to evaluate the accuracy of automated microscopy in the clinical diagnosis of aerobic vaginitis (AV). Methods: In this study, the vaginal secretion samples of 3769 patients receiving treatment at the Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University between January 2020 and December 2021 were selected. Using the results of manual microscopy as the control, we developed the linear kernel SVM algorithm, an artificial intelligence (AI) automated analysis software, with Python Scikit-learn script. The AI automated analysis software could identify leucocytes with toxic appearance and parabasal epitheliocytes (PBC). The bacterial grading parameters were reset using standard strains of lactobacillus and AV common isolates. The receiver operating characteristic (ROC) curve analysis was used to determine the cut-off value of AV evaluation results for different scoring items were obtained by using the results of manual microscopy as the control. Then, the parameters of automatic AV identification were determined and the automatic AV analysis scoring method was initially established. Results: A total of 3769 vaginal secretion samples were collected. The AI automated analysis system incorporated five parameters and each parameter incorporated three severity scoring levels. We selected 1.5 µm as the cut-off value for the diameter between Lactobacillus and common AV bacterial isolates. The automated identification parameter of Lactobacillus was the ratio of bacteria ≥1.5 µm to those <1.5 µm. The cut-off scores were 2.5 and 0.5, In the parameter of white blood cells (WBC), the cut-off value of the absolute number of WBC was 103 µL－1 and the cut-off value of WBC-to-epithelial cell ratio was 10. The automated identification parameter of toxic WBC was the ratio of toxic WBC toWBC and the cut-off values were 1% and 15%. The parameter of background flora was bacteria<1.5 µm and the cut-off values were 5×103 µL－1 and 3×104 µL－1. The parameter of the parabasal epitheliocytes was the ratio of PBC to epithelial cells and the cut-off values were 1% and 10%. The agreement rate between the results of automated microscopy and those of manual microscopy was 92.5%. Out of 200 samples, automated microscopy and manual microscopy produced consistent scores for 185 samples, while the results for 15 samples were inconsistent. Conclusion: We developed an AI recognition software for AV and established an automated vaginal secretion microscopy scoring system for AV. There was good overall concordance between automated microscopy and manual microscopy. The AI identification software for AV can complete clinical lab examination with rather high objectivity, sensitivity, and efficiency, markedly reducing the workload of manual microscopy.

Facile Synthesis and First Antifungal Exploration of Tetracyclic Meroterpenoids: (+)-Aureol, (-)-Pelorol, and Its Analogs.

As an important bioactive molecular backbone, drimane meroterpenoids have drawn a great deal of attention from both pharmacologists and chemists. Inspired by the prevalidated success of conformational restriction in the discovery of novel pharmaceutical leads, two distinct tetracyclic drimane meroterpenoids, (-)-pelorol and (+)-aureol, were synthesized from the inexpensive starting material (-)-sclareol through 10 and 8 steps with 5.6% and 5.4% overall yield, respectively. The mild conditions, operational facility, and scalability enabled the expedient synthesis and biological exploration of not only natural products themselves but also their mimics. The first agrochemical exploration showed (-)-pelorol and (+)-aureol possessed good antifungal activity against Rhizoctonia solani, with EC50 values of 7.7 and 6.9 µM, respectively. This revealed that tetracyclic drimane meroterpenoids are valuable models for antifungal lead discovery.

Identification of receptors and factors associated with human coronaviruses in the oral cavity using single-cell RNA sequencing.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ravaged the world, and Coronavirus Disease 2019 (COVID-19) exhibited highly prevalent oral symptoms that had significantly impacted the lives of affected patients. However, the involvement of four human coronavirus (HCoVs), namely SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E, in oral cavity infections remained poorly understood. We integrated single-cell RNA sequencing (scRNA-seq) data of seven human oral tissues through consistent normalization procedure, including minor salivary gland (MSG), parotid gland (PG), tongue, gingiva, buccal, periodontium and pulp. The Seurat, scDblFinder, Harmony, SingleR, Ucell and scCancer packages were comprehensively used for analysis. We identified specific cell clusters and generated expression profiles of SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) in seven oral regions, providing direction for predicting the tropism of four HCoVs for oral tissues, as well as for dental clinical treatment. Based on our analysis, it appears that various SCARFs, including ACE2, ASGR1, KREMEN1, DPP4, ANPEP, CD209, CLEC4G/M, TMPRSS family proteins (including TMPRSS2, TMPRSS4, and TMPRSS11A), and FURIN, are expressed at low levels in the oral cavity. Conversely, BSG, CTSB, and CTSL exhibit enrichment in oral tissues. Our study also demonstrates widespread expression of restriction factors, particularly IFITM1-3 and LY6E, in oral cells. Additionally, some replication, assembly, and trafficking factors appear to exhibit broad oral tissues expression patterns. Overall, the oral cavity could potentially serve as a high-risk site for SARS-CoV-2 infection, while displaying a comparatively lower degree of susceptibility towards other HCoVs (including SARS-CoV, MERS-CoV and HCoV-229E). Specifically, MSG, tongue, and gingiva represent potential sites of vulnerability for four HCoVs infection, with the MSG exhibiting a particularly high susceptibility. However, the expression patterns of SCARFs in other oral sites demonstrate relatively intricate and may only be specifically associated with SARS-CoV-2 infection. Our study sheds light on the mechanisms of HCoVs infection in the oral cavity as well as gains insight into the characteristics and distribution of possible HCoVs target cells in oral tissues, providing potential therapeutic targets for HCoVs infection in the oral cavity.

Multicenter registry study of cerebral venous thrombosis in china (RETAIN-CH): Rationale and design.

BACKGROUND AND RATIONALE: Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder that mainly affects young and middle-aged adults. Epidemiological data on the incidence, risk factors, diagnosis, treatment, and prognosis of CVT are lacking in China. In addition, there is a lack of evidence from large, multicenter, real-world studies on the efficacy and safety of endovascular. AIM: To understand the incidence, diagnosis and treatment status of CVT in China and to estimate the effectiveness and safety of endovascular treatment in the real-world. METHODS: A multicenter, retrospective observational cohort study will be conducted on CVT patient records from 104 hospitals, between January 1, 2018 and June 30, 2022, identified using a 2-stage cluster sampling design based on per capita gross domestic product. Each enrolled participant is required to complete a further follow-up, which includes the current situation and the assessment at 3 and 12 months after discharge. STUDY OUTCOMES: The outcomes of this study will include the current status of the incidence, pathogenesis, etiology, clinical symptoms, diagnosis, and treatment of CVT in China, as well as the effectiveness and safety of endovascular treatment in the real-world. DISCUSSION: Results from this study will provide evidence on the incidence, specific risk factors, symptomatic and imaging features, and clinical outcomes of CVT in China as well as indicate whether endovascular treatment is superior to medical management alone for patients with acute CVT in the real-world. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. IDENTIFIER: NCT05448248.

Cadmium aggravates liver injury by activating ferroptosis and neutrophil extracellular traps formation in Nile tilapia (Oreochromis niloticus).

Cadmium (Cd) is a pervasive environmental contaminant and a significant risk factor for liver injury. The present study was undertaken to evaluate the involvement of ferroptosis and neutrophil extracellular traps (NETs) in Cd-induced liver injury in Nile tilapia (Oreochromis niloticus), and to explore its underlying mechanism. Cd-induced liver injury was associated with increased total iron, malondialdehyde (MDA), and Acyl-CoA synthetase long-chain family member 4 (ACSL4), together with reduced levels of glutathione, glutathione peroxidase-4a (Gpx4a), and solute carrier family 7 member 11 (SLC7A11), which are all hallmarks of ferroptosis. Moreover, liver hyperemia, neutrophil infiltration, increased inflammatory factors and myeloperoxidase, as well as elevated serum DNA content in Cd-stimulated Nile tilapia suggested that a considerable number of neutrophils were recruited to the liver. Furtherly, in vitro experiments demonstrated that Cd induced the formation of NETs, and the possible mechanism was related to the generation of reactive oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, along with the P38 and extracellular regulated protein kinase (ERK) signaling pathways. We concluded that ferroptosis and NETs are the critical mechanisms contributing to Cd-induced liver injury in Nile tilapia. These findings will contribute to Cd toxicological studies in aquatic animals.

Purification of Photorhabdus Virulence Cassette (PVC) Protein Complexes from Escherichia coli for Artificial Translocation of Heterologous Cargo Proteins.

Contractile injection systems (CISs), one of the most important bacterial secretion systems that transport substrates across the membrane, are a collection of diverse but evolutionarily related macromolecular devices. Numerous effector proteins can be loaded and injected by this secretion complex to their specific destinations. One group of CISs called extracellular CIS (eCIS) has been proposed as secretory molecules that can be released from the bacterial cytoplasm and attack neighboring target cells from the extracellular environment. This makes them a potential delivery vector for the transportation of various cargos without the inclusion of bacterial cells, which might elicit certain immunological responses from hosts. We have demonstrated that the Photorhabdus virulence cassette (PVC), which is a typical eCIS, could be applied as an ideal vector for the translocation of proteinaceous cargos with different physical or chemical properties. Here, we describe the in-depth purification protocol of this mega complex from Escherichia coli. The protocol provided is a simpler, faster, and more productive way of generating the eCIS complexes than available methodologies reported previously, which can facilitate the subsequent applications of these nanodevices and other eCIS in different backgrounds.