IL-2, IL-17A and TNF-α hold potential as biomarkers for predicting acute mountain sickness prior to ascent.

BACKGROUND: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes. METHODS: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity. RESULTS: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n = 17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-α at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-α and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.. CONCLUSION: We posited that the levels of TNF-α, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude. NEW & NOTEWORTHY: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-α could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m.

Characterization of three novel stem rot pathogens and their antagonistic endophytic bacteria associated with Cistanche deserticola.

Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.

Macrosemiafengi Wang sp. nov. from Yunnan and Guizhou, China (Hemiptera, Cicadidae, Cicadinae).

Background: The genus Macrosemia Kato, 1925 (Hemiptera, Cicadidae, Cicadinae, Dundubiini, Dundubiina) currently includes 16 species (excluding subspecies and varieties), mainly occurring in the Oriental Region. More than half of them, 10 species, are known from China, including one new species, described in the present study. New information: A new species of cicada, Macrosemiafengi Wang sp. nov., is described from Yunnan and Guizhou, southwest China. Colour plates are presented to illustrate its diagnostic characters. The distribution map of the new species is also given.

A new species of Tanna Distant, 1905 from Yunnan, China (Hemiptera, Cicadidae, Cicadinae).

Background: The genus Tanna Distant, 1905 (Hemiptera, Cicadidae, Cicadinae, Leptopsaltriini, Leptopsaltriina) currently includes 23 species (three tentatively placed), with its actual geographical distribution in China, Japan, Nepal, Bhutan, Cambodia, Thailand and Vietnam. Most of them, 16 species, are known from China, including one new species here described. New information: A new species of cicada, Tannafengi Wang sp. nov., is described from Yunnan, southwest China. Colour plates are presented to illustrate all diagnostic characters. An updated list of Tanna species occurring in China is provided.

Simultaneous determination of inflammatory factors SAA and LTF based on stable element labeling and inductively coupled plasma mass spectrometry to aid in the diagnosis of infection.

OBJECTIVE: The clinical value of Serum amyloid A (SAA) and Lactoferrin (LTF) has received significant attention, but their detection methods are inadequate, which limits their application. This study aims to develop a dual detection method based on stable element labeling strategies and inductively coupled plasma mass spectrometry (ICP-MS) for SAA/LTF and to assess whether it can be widely used in clinical practice. METHODS: A duplex immunoassay system based on sandwich method was constructed. After optimization, methodological evaluation was performed with the guidelines of Clinical Laboratory Standards Institute (CLSI). Finally, 131 plasma samples were collected to analyze whether the new method is suitable for clinical detection. RESULTS: The LoB, LLoQ, ULoQ, and linear range of the assay were 1.09 ng/mL, 3 ng/mL, 1500 ng/mL, 3-1500 ng/mL for SAA and 0.85 ng/mL, 2 ng/mL, 1200 ng/mL, 2-1200 ng/mL for LTF respectively. The recovery rates were 95.01% to 106.26%, the intra-batch precision of low, intermediate, and high-level samples was <8%, and the inter-batch of them was <11%, the deviation of interference test results was less than±10%. The Area Under the Curve (AUC) was 0.9809 for SAA, 0.8599 for LTF, and 0.9986 for combination. CONCLUSION: The quantitative duplex immunoassay for SAA/LTF has high accuracy, good precision, and high specificity, which meets the clinical testing requirements and can be widely used in clinical practice.

The Protective Effect of Melatonin on LPS-Induced Myocardial Injury via the Caspase-11/GSDMD Pathway.

BACKGROUND: Melatonin (MT) has been demonstrated to have cardioprotective effects. Nevertheless, the precise mechanism through which MT provides protection against the etiology of LPS-induced myocardial injury remains uncertain. In this investigation, our objective was to explore the impact of MT on LPS-induced myocardial injury in an in vitro setting. METHODS: H9C2 cells were categorized into four groups: a control group (H9C2 group), an MT group, an LPS group, and an MT + LPS group. The H9C2 group received treatment with sterile saline solution, the LPS group was exposed to 5 µg/mL LPS for 24 hours, the MT + LPS group underwent pretreatment with 150 µmol/L MT for 2 hours, followed by exposure to 5 µg/mL LPS for 24 hours, and the MT group received only 150 µmol/L MT for 2 hours. Cell viability and lactate dehydrogenase (LDH) release were assessed using the CCK-8 assay and LDH activity assay, respectively. The levels of reactive oxygen species (ROS) were quantified in each group of cells, and the percentage of propidium iodide (PI)-stained apoptotic cells was determined by flow cytometry. The mRNA levels of caspase11, GSDMD, and IL-18 in each group of cells were quantified. RESULTS: MT treatment significantly protected H9C2 cells from LPS-induced damage, as evidenced by decreased LDH release. LPS treatment markedly increased ROS levels in H9C2 cells, which were subsequently reduced by MT. LPS caused a substantial decrease in superoxide dismutase (SOD) activity and a significant increase in malondialdehyde (MDA) levels, while MT treatment significantly reversed these effects. Additionally, MT markedly enhanced the proportion of viable H9C2 cells compared to LPS-treated controls, as evidenced by the PI staining assay. LPS upregulated both mRNA levels and protein levels of IL-18 in H9C2 cells. However, MT treatment effectively mitigated this LPS-induced increase. Furthermore, MT significantly decreased LPS-induced protein levels of cleaved-caspase 11 and GSDMD-N in H9C2 cells. CONCLUSION: Overall, our findings suggest that MT inhibits the Caspase11-GSDMD signaling pathway via pyroptosis-related proteins (caspase-11 and GSDMD-N) and reduces the expression of inflammation-related cytokines (IL-18), thereby exerting a protective effect on H9C2 cells after LPS injury.

A α-L-rhamnosidase from Echinacea purpurea endophyte Simplicillium sinense EFF1 and its application in production of Calceorioside B.

Calceorioside B, a multifunctional phenylethanol glycosides (PhGs) derivative, exhibits a variety of notable properties, such as antithrombotic, anti-tumorigenic, anti-neocoronavirus, anti-inflammatory, and neuroprotective effects. However, the large-scale production of calceorioside B is routinely restricted by its existence as an intermediary compound derived from plants, and still unachieved through excellent and activity chemical synthesis. Here, a total of 51 fungal endophytes were isolated from four PhGs-producing plants, and endophyte Simplicillium sinense EFF1 from Echinacea purpurea was identified with the ability to de-rhamnosing isoacteoside to generate calceorioside B. According to the RNA-transcription of EFF1 under the various substrates, a key gene CL1206.Contig2 that undertakes the hydrolysis function was screened out and charactered by heterologous expression. The sequence alignment, phylogenetic tree construction and substrate specificity analysis revealed that CL1206 was a novel α-L-rhamnosidase that belongs to the glycosyl hydrolase family 78 (GH78). The optimum catalytic conditions for CL1206 were at pH 6.5 and 55 °C. Finally, the enzyme-catalyzed approach to produce calceorioside B from 50 % crude isoacteoside extract was explored and optimized, with the maximum conversion rate reaching 69.42 % and the average producing rate reaching 0.37 g-1.L-1.h-1, which offered a great biocatalyst for potential industrial calceorioside B production. This is the first case for microorganism and rhamnosidase to show the hydrolysis ability to caffeic acid-modified PhGs.

miR-29a activates expression of α-cardiac myosin heavy chain via ß1 thyroid hormone receptor in neonatal rats.

Introduction: MicroRNAs (miRs) are small noncoding RNAs which are regulators of gene expression and also regulate the genes in heart tissues. The aim of the study was to evaluate the effect of miRs on the expression level of myosin heavy chain (MHC), which is responsible for regulation of cardiac functions in neonatal rat ventricular myocytes and mice. Material and methods: The miRs were suppressed in neonatal rat ventricular myocytes using small interfering RNAs (siRNAs) against Dicer followed by evaluation of MHC levels. For in vivo study the C57 black/6 Jacksonian mice were subjected to the transverse aortic constriction (TAC) procedure. Results: The Dicer siRNA suppressed the endogenous miRs and the α-MHC gene but failed to down-regulate the ß-MHC. Among the 17 selected miRs, miR-29a was found to up-regulate the α-MHC gene significantly but not ß-MHC. The expression of α-MHC was suppressed by silencing the expression of miR-29a. Bioinformatics study done by TargetScan suggested thyroid hormone receptor-ß1 (TR-ß1) as a potential target of miR-29a. Additionally, miR-29a was found to regulate the expression of α-MHC via TR-ß1 signaling. Conclusions: The findings of the present study indicated that miR-29a modulates expression of α-the MHC gene by targeting TR-ß1 in cardiac cells. The study may provide a new direction for treating cardiac failure and cardiac hypertrophy.

Erianin induces ferroptosis in GSCs via REST/LRSAM1 mediated SLC40A1 ubiquitination to overcome TMZ resistance.

In recent studies, erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has exhibited notable anticancer properties. Ferroptosis, a novel form of programmed cell death, holds potential as a strategy to overcome Temozolomide (TMZ) resistance in glioma by inducing ferroptosis in TMZ-resistant glioma cells. Here, utilizing various phenotyping experiments, including cell counting kit-8 (CCK-8) assays, EdU assays, transwell assays, neurosphere formation assays and extreme limiting dilution (ELDA) assays, we demonstrated that erianin exerts its anticancer activity on both TMZ sensitive and TMZ-resistant glioma stem cells (GSCs). Furthermore, we made an exciting discovery that erianin enhances TMZ sensitivity in TMZ-resistant GSCs. Subsequently, we demonstrated that erianin induced ferroptosis in TMZ-resistant GSCs and enhances TMZ sensitivity through inducing ferroptosis, which was confirmed by intracellular measurements of ROS, GSH, and MDA, as well as through the use of BODIPY (581/591) C11 and transmission electron microscopy. Conversely, the ferroptosis inhibitor ferrostatin-1 (Fer-1) blocked the effects of erianin. The underlying mechanism of ferroptosis induced by erianin was further explored through co-immunoprecipitation (Co-IP) assays, ubiquitination assays, protein stability assessments, chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. We found that erianin specifically targets REST, inhibiting its transcriptional repression function without altering its expression levels. Consequently, this suppression of REST's role leads to an upregulation of LRSAM1 expression. In turn, LRSAM1 ubiquitinates and degrades SLC40A1, a protein that inhibits ferroptosis by exporting ferrous ions. By downregulating SLC40A1, erianin ultimately induces ferroptosis in TMZ-resistant GSCs. Taken together, our research demonstrates that the natural product erianin inhibits the malignant phenotype of GSCs and increases the sensitivity of TMZ in TMZ-resistant GSCs by inducing ferroptosis. These findings suggest erianin as a prospective compound for the treatment of TMZ-resistant glioma.

Antimicrobial Resistance and the Genomic Epidemiology of Multidrug-Resistant Salmonella enterica serovar Enteritidis ST11 in China.

BACKGROUND: With the recent evolution of multidrug-resistant strains, the genetic characteristics of foodborne Salmonella enterica serovar Enteritidis and clinical isolates have changed. ST11 is now the most common genotype associated with S. Enteritidis isolates. METHODS: A total of 83 strains of S. Enteritidis were collected at the General Hospital of the People's Liberation Army. Of these, 37 were from aseptic sites in patients, 11 were from the feces of patients with diarrhea, and the remaining 35 were of chicken-origin. The minimum inhibitory concentration of S. Enteritidis was determined by the broth microdilution method. Genomic DNA was extracted using the QiAamp DNA Mini Kit, and whole-genome sequencing (WGS) was performed using an Illumina X-ten platform. Prokka was used for gene prediction and annotation, and bioinformatic analysis tools included Resfinder, ISFinder, Virulence Factor Database, and PlasmidFinder. IQ-TREE was used to build a maximum likelihood phylogenetic tree. The phylogenetic relationship and distribution of resistance genes was displayed using iTOL. Comparative population genomics was used to analyze the phenotypes and genetic characteristics of antibiotic resistance in clinical and chicken-origin isolates of S. Enteritidis. RESULTS: The chicken-origin S. Enteritidis isolates were more resistant to antibiotics than clinical isolates, and had a broader antibiotic resistance spectrum and higher antibiotic resistance rate. A higher prevalence of antibiotic-resistance genes was observed in chicken-origin S. Enteritidis compared to clinical isolates, along with distinct patterns in the contextual characteristics of these genes. Notably, genes such as blaCTX-M and dfrA17 were exclusive to plasmids in clinical S. Enteritidis, whereas in chicken-origin S. Enteritidis they were found in both plasmids and chromosomes. Additionally, floR was significantly more prevalent in chicken-origin isolates than in clinical isolates. Careful analysis revealed that the delayed isolation of chicken-origin S. Enteritidis contributes to accelerated gene evolution. Of note, certain resistance genes tend to integrate seamlessly and persist steadfastly within the chromosome, thereby expediting the evolution of resistance mechanisms against antibiotics. Our comparative analysis of virulence genes in S. Enteritidis strains from various sources found no substantial disparities in the distribution of other virulence factors. In summary, we propose that chicken-origin S. Enteritidis has the potential to cause clinical infections. Moreover, the ongoing evolution and dissemination of these drug-resistant genes poses a formidable challenge to clinical treatment. CONCLUSIONS: Constant vigilance is needed to monitor the dynamic patterns of drug resistance in S. Enteritidis strains sourced from diverse origins.

Unveiling research trends in the prognosis of osteosarcoma: A bibliometric analysis from 2000 to 2022.

Background: Osteosarcoma (OSA) is the most prevalent form of malignant bone tumor in children and adolescents, producing osteoid and immature bone. Numerous high quality studies have been published in the OSA field, however, no bibliometric study related to this area has been reported thus far. Therefore, the present study retrieved the published data from 2000 to 2022 to reveal the dynamics, development trends, hotspots and future directions of the OSA. Methods: Publications regard to osteogenic sarcoma and prognosis were searched in the core collection on Web of Science database. The retrieved publications were analyzed by publication years, journals, categories, countries, citations, institutions, authors, keywords and clusters using the two widely available bibliometric visualization tools, VOS viewer (Version 1.6.16), Citespace (Version 6.2. R1). Results: A total of 6260 publications related to the current topic were retrieved and analyzed, revealing exponential increase in the number of publications with an improvement in the citations on the OSA over time, in which China and the USA are the most productive nations. Shanghai Jiao Tong University, University of Texas System and Harvard University are prolific institutions, having highest collaboration network. Oncology Letters and Journal of Clinical Oncology are the most productive and the most cited journals respectively. The Wang Y is a prominent author and articles published by Bacci G had the highest number of citations indicating their significant impact in the field. According to keywords analysis, osteosarcoma, expression and metastasis were the most apparent keywords whereas the current research hotspots are biomarker, tumor microenvironment, immunotherapy and DNA methylation. Conclusion: Our findings offer valuable information for researchers to understand the current research status and the necessity of future research to mitigate the mortality of the OS patients.

The critical roles of lnc-GLYATL2-2/PD-L1 axis in immune microenvironment and the clinical value of intracranial chordomas.

Intracranial chordomas (ICs) are associated with a poor prognosis due to low total resection rates and high recurrence rates. However, the role of immunotherapy in ICs remains unknown. RNA sequencing and immunohistochemical staining were performed on IC tissues and normal tissues, and the long noncoding RNA (lncRNA) lnc-GLYATL2-2 was identified. The results indicated that high expression of lnc-GLYATL2-2 was positively correlated with the tumor-infiltrating lymphocyte (TIL) markers CD4 and Foxp3, negatively correlated with CD8, and positively correlated with the expression of the immune checkpoint molecules programmed death receptor-1 (PD-1) and programmed death ligand 1 (PD-L1). Additionally, Kaplan-Meier and univariate or multivariate Cox regression analyses revealed the predictive value of lnc-GLYATL2-2 for survival based on clinical data from patients with ICs. A high expression level of lnc-GLYATL2-2 is potentially correlated with a suppressive tumor immune microenvironment and adverse clinical outcomes in IC patients. Mechanistically, the upregulation of lnc-GLYATL2-2 can result in increased cytoplasmic levels of ELAVL1, leading to enhanced binding to the 3'-UTR of PD-L1 mRNA and maintenance of its stability. In contrast, lnc-GLYATL2-2 can directly interact with the PD-L1 protein to prevent degradation, thereby promoting high levels of PD-L1 expression simultaneously at the transcriptional and translational levels in chordoma cells. These results provide a new perspective on the diagnosis and prognosis of ICs and provide theoretical evidence for immunotherapy in patients with ICs.

A diagnostic model for distinguishing between active tuberculosis and latent tuberculosis infection based on the blood expression profiles of autophagy-related genes.

BACKGROUND: Autophagy is closely involved in the control of mycobacterial infection. OBJECTIVES: Here, a diagnostic model was developed using the levels of autophagy-related genes (ARGs) in the blood to differentiate active tuberculosis (ATB) and latent tuberculosis infection (LTBI). DESIGN: Secondary data analysis of three prospective cohorts. METHODS: The expression of ARGs in patients with ATB and LTBI were analyzed using the GSE37250, GSE19491, and GSE28623 datasets from the GEO database. RESULTS: Twenty-two differentially expressed ARGs were identified in the training dataset GSE37250. Using least absolute shrinkage and selection operator and multivariate logistic regression, three ARGs (FOXO1, CCL2, and ITGA3) were found that were positively associated with adaptive immune-related lymphocytes and negatively associated with myeloid and inflammatory cells. A nomogram was constructed using the three ARGs. The accuracy, consistency, and clinical relevance of the nomogram were evaluated using receiver operating characteristic curves, the C-index, calibration curves, and validation in the datasets GSE19491 and GSE28623. The nomogram showed good predictive performance. CONCLUSION: The nomogram was able to accurately differentiate between ATB and LTBI patients. These findings provide evidence for future study on the pathology of autophagy in tuberculosis infection.