Canagliflozin inhibits PASMCs proliferation via regulating SGLT1/AMPK signaling and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) was a devastating disease characterized by artery remodeling, ultimately resulting in right heart failure. The aim of this study was to investigate the effects of canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i) with mild SGLT1 inhibitory effects, on rats with PAH, as well as its direct impact on pulmonary arterial smooth muscle cells (PASMCs). PAH rats were induced by injection of monocrotaline (MCT) (40 mg/kg), followed by four weeks of treatment with CANA (30 mg/kg/day) or saline alone. Pulmonary artery and right ventricular (RV) remodeling and dysfunction in PAH were alleviated with CANA, as assessed by echocardiography. Hemodynamic parameters and structural of pulmonary arteriole, including vascular wall thickness and wall area, were reduced by CANA. RV hypertrophy index, cardiomyocyte hypertrophy, and fibrosis were decreased with CANA treatment. PASMCs proliferation was inhibited by CANA under stimulation by platelet-derived growth factor (PDGF)-BB or hypoxia. Activation of AMP kinase (AMPK) was induced by CANA treatment in cultured PASMCs in a time- and concentration-dependent manner. These effects of CANA were attenuated when treatment with compound C, an AMPK inhibitor. Abundant expression of SGLT1 was observed in PASMCs and pulmonary arteries, while SGLT2 expression was undetectable. SGLT1 increased in response to PDGF-BB or hypoxia stimulation, while PASMCs proliferation was inhibited and beneficial effects of CANA were counteracted by knockdown of SGLT1. Our research demonstrated for the first time that CANA inhibited the proliferation of PASMCs by regulating SGLT1/AMPK signaling and thus exerted an anti-proliferative effect on MCT-induced PAH.

Characterization of the metabolic contributions of cytochrome P450 isoforms to bicyclol using the relative activity factor method.

Bicyclol is a hepatoprotective agent widely used for treating chronic hepatitis and drug-induced liver injuries in clinics. The purpose of the study was to elucidate the contribution of CYP450 enzymes to the metabolism of bicyclol using the relative activity factor approach. After incubation with human liver microsomes and recombinant human liver CYP450 enzymes, the calculated contribution of CYP3A4 and 2C19 to the metabolism of bicyclol was 85.6-90.3% and 9.2-9.7%, respectively. The metabolism was interrupted in the presence of CYP3A4 and 2C19 selective inhibitors. These findings help to predict or avoid metabolic drug-drug interactions or toxicity in clinical applications of bicyclol.

Toosendanin induces hepatotoxicity via disrupting LXRα/Lipin1/SREBP1 mediated lipid metabolism.

Toosendanin (TSN) is the main active compound derived from Melia toosendan Sieb et Zucc with various bioactivities. However, liver injury was observed in TSN limiting its clinical application. Lipid metabolism plays a crucial role in maintaining cellular homeostasis, and its disruption is also essential in TSN-induced hepatotoxicity. This study explored the hepatotoxicity caused by TSN in vitro and in vivo. The lipid droplets were significantly decreased, accompanied by a decrease in fatty acid transporter CD36 and crucial enzymes in the lipogenesis including ACC and FAS after the treatment of TSN. It was suggested that TSN caused lipid metabolism disorder in hepatocytes. TOFA, an allosteric inhibitor of ACC, could partially restore cell survival via blocking malonyl-CoA accumulation. Notably, TSN downregulated the LXRα/Lipin1/SREBP1 signaling pathway. LXRα activation improved cell survival and intracellular neutral lipid levels, while SREBP1 inhibition aggravated the cell damage and caused a further decline in lipid levels. Male Balb/c mice were treated with TSN (5, 10, 20 mg/kg/d) for 7 days. TSN exposure led to serum lipid levels aberrantly decreased. Moreover, the western blotting results showed that LXRα/Lipin1/SREBP1 inhibition contributed to TSN-induced liver injury. In conclusion, TSN caused lipid metabolism disorder in liver via inhibiting LXRα/Lipin1/SREBP1 signaling pathway.

Risk Factors of Tuberculosis Destroyed Lung in Patients with Pulmonary Tuberculosis and Structural Lung Diseases: A Retrospective Observational Study.

Background: Tuberculosis destroyed lung constitutes a significant worldwide public health challenge, little is known about its associated risk factors and prognosis. Our study aimed to identify the risk factors of tuberculosis destroyed lung among pulmonary tuberculosis and structural lung diseases. Methods: Between January 2019 and December 2021, a case-control study was conducted at the Third People's Hospital of Shenzhen in China. We collected the clinical data among patients with pulmonary tuberculosis and structural lung diseases. Cases were defined as patients with tuberculosis destroyed lung. Controls were not diagnosed with the tuberculosis destroyed lung. A binary logistic regression was performed. Results: In our study, a total of 341 patients met the inclusion criteria, including 182 cases and 159 controls. We found that age ranges of 46-60 years (aOR: 4.879; 95% CI: 2.338-10.180), >60 years (aOR: 3.384; 95% CI: 1.481-7.735); history of TB treatment (aOR: 2.729; 95% CI: 1.606-4.638); malnutrition (aOR: 5.126; 95% CI: 1.359-19.335); respiratory failure (aOR: 5.080; 95% CI: 1.491-17.306); and bronchiarctia (aOR: 3.499; 95% CI: 1.330-9.209) were the independent risk factors for tuberculosis destroyed lung. Conversely, having a normal (aOR: 0.207; 95% CI: 0.116-0.371) or overweight BMI (aOR: 0.259; 95% CI: 0.090-0.747) emerged as a protective factor against tuberculosis destroyed lung. Conclusion: This study indicated that tuberculosis destroyed lung is a common condition among patients with pulmonary tuberculosis and structural lung diseases. The independent risk factors for tuberculosis destroyed lung were identified as being within the age groups of 46-60 and over 60 years, having a previous history of TB treatment, malnutrition, respiratory failure, and bronchiarctia. It is essential to closely monitor patients possessing these risk factors to prevent the progression towards tuberculosis destroyed lung.

Impact of organic matter molecular weight on hexavalent chromium enrichment in green microalgae.

In lightly polluted water containing heavy metals, organic matter, and green microalgae, the molecular weight of organic matter may influence both the growth of green microalgae and the concentration of heavy metals. This study elucidates the effects and mechanisms by which different molecular weight fractions of fulvic acid (FA), a model dissolved organic matter component, facilitate the bioaccumulation of hexavalent chromium (Cr(VI)) in a typical green alga, Chlorella vulgaris. Findings show that the addition of FA fractions with molecular weights greater than 10 kDa significantly enhances the enrichment of total chromium and Cr(VI) in algal cells, reaching 21.58%-31.09 % and 16.17 %-22.63 %, respectively. Conversely, the efficiency of chromium enrichment in algal cells was found to decrease with decreasing molecular weight of FA. FA molecular weight within the range of 0.22 µm-30 kDa facilitated chromium enrichment primarily through the algal organic matter (AOM) pathway, with minor contributions from the algal cell proliferation and extracellular polymeric substances (EPS) pathways. However, with decreasing FA molecular weight, the AOM and EPS pathways become less prominent, whereas the algal cell proliferation pathway becomes dominant. These findings provide new insights into the mechanism of chromium enrichment in green algae enhanced by medium molecular weight FA.

A machine learning-based predictive model of causality in orthopaedic medical malpractice cases in China.

PURPOSE: To explore the feasibility and validity of machine learning models in determining causality in medical malpractice cases and to try to increase the scientificity and reliability of identification opinions. METHODS: We collected 13,245 written judgments from PKULAW.COM, a public database. 963 cases were included after the initial screening. 21 medical and ten patient factors were selected as characteristic variables by summarising previous literature and cases. Random Forest, eXtreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM) were used to establish prediction models of causality for the two data sets, respectively. Finally, the optimal model is obtained by hyperparameter tuning of the six models. RESULTS: We built three real data set models and three virtual data set models by three algorithms, and their confusion matrices differed. XGBoost performed best in the real data set, with a model accuracy of 66%. In the virtual data set, the performance of XGBoost and LightGBM was basically the same, and the model accuracy rate was 80%. The overall accuracy of external verification was 72.7%. CONCLUSIONS: The optimal model of this study is expected to predict the causality accurately.

Rosmarinic acid alleviates toosendanin-induced liver injury through restoration of autophagic flux and lysosomal function by activating JAK2/STAT3/CTSC pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosmarinic acid (RA), a natural polyphenol abundant in numerous herbal remedies, has been attracting growing interest owing to its exceptional ability to protect the liver. Toosendanin (TSN), a prominent bioactive compound derived from Melia toosendan Siebold & Zucc., boasts diverse pharmacological properties. Nevertheless, TSN possesses remarkable hepatotoxicity. Intriguingly, the potential of RA to counteract TSN-induced liver damage and its probable mechanisms remain unexplored. AIM OF THE STUDY: This study is aimed at exploring whether RA can alleviate TSN-induced liver injury and the potential mechanisms involved autophagy. MATERIALS AND METHODS: CCK-8 and LDH leakage rate assay were used to evaluate cytotoxicity. Balb/c mice were intraperitoneally administered TSN (20 mg/kg) for 24 h after pretreatment with RA (0, 40, 80 mg/kg) by gavage for 5 days. The autophagic proteins P62 and LC3B expressions were detected using western blot and immunohistochemistry. RFP-GFP-LC3B and transmission electron microscopy were applied to observe the accumulation levels of autophagosomes and autolysosomes. LysoTracker Red and DQ-BSA staining were used to evaluate the lysosomal acidity and degradation ability respectively. Western blot, immunohistochemistry and immunofluorescence staining were employed to measure the expressions of JAK2/STAT3/CTSC pathway proteins. Dual-luciferase reporter gene was used to measure the transcriptional activity of CTSC and RT-PCR was used to detect its mRNA level. H&E staining and serum biochemical assay were employed to determine the degree of damage to the liver. RESULTS: TSN-induced damage to hepatocytes and livers was significantly alleviated by RA. RA markedly diminished the autophagic flux blockade and lysosomal dysfunction caused by TSN. Mechanically, RA alleviated TSN-induced down-regulation of CTSC by activating JAK2/STAT3 signaling pathway. CONCLUSION: RA could protect against TSN-induced liver injury by activating the JAK2/STAT3/CTSC pathway-mediated autophagy and lysosomal function.

Metabolic signatures of two scleractinian corals from the northern South China sea in response to extreme high temperature events.

Coral bleaching events are becoming increasingly common worldwide, causing widespread coral mortality. However, not all colonies within the same coral taxa show sensitivity to bleaching events, and the current understanding of the metabolic mechanisms underlying thermal bleaching in corals remains limited. We used untargeted metabolomics to analyze the biochemical processes involved in the survival of two bleaching phenotypes of the common corals Pavona decussata and Acropora pruinosa, during a severe bleaching event in the northern South China Sea in 2020. During thermal bleaching, P. decussata and A. pruinosa significantly accumulated energy products such as succinate and EPA, antioxidants and inflammatory markers, and reduced energy storage substances like glutamate and thymidine. KEGG analysis revealed enrichment of energy production pathways such as ABC transporters, nucleotide metabolism and lipid metabolism, suggesting the occurrence of oxidative stress and energy metabolism disorders in bleached corals. Notably, heat stress exerted distinct effects on metabolic pathways in the two coral species, e.g., P. decussata activating carbohydrate metabolism pathways like glycolysis and the TCA cycle, along with amino acid metabolism pathways, whereas A. pruinosa significantly altered the content of multiple small peptides affected amino acid metabolism. Furthermore, the osmoregulatory potential of corals correlates with their ability to survive in heat-stress environments in the wild. This study provides valuable insights into the metabolic mechanisms linked to thermal tolerance in reef-building corals, contributes to the understanding of corals' adaptive potential to heat stress induced by global warming and lays the foundation for developing targeted conservation strategies in the future.

Insights into the Impact of Trans-Zeatin Overproduction-Engineered Sinorhizobium meliloti on Alfalfa (Medicago sativa L.) Tolerance to Drought Stress.

Plant growth-promoting rhizobacteria have been shown to enhance plant tolerance to drought stress through various mechanisms. However, there is limited research on improving drought resistance in alfalfa by genetically modifying PGPR to produce increased levels of cytokinins. Herein, we employed synthetic biology approaches to engineer two novel strains of Sinorhizobium meliloti capable of overproducing trans-Zeatin and investigated their potential in enhancing drought tolerance in alfalfa. Our results demonstrate that alfalfa plants inoculated with these engineered S. meliloti strains exhibited reduced wilting and yellowing while maintaining higher relative water content under drought conditions. The engineered S. meliloti-induced tZ activated the activity of antioxidant enzymes and the accumulation of osmolytes. Additionally, the increased endogenous tZ content in plants alleviated the impact of drought stress on the alfalfa photosynthetic rate. However, under nondrought conditions, inoculation with the engineered S. meliloti strains had no significant effect on alfalfa biomass and nodule formation.

Research advances on molecular mechanism and natural product therapy of iron metabolism in heart failure.

The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.

Present situation of minimally invasive surgical treatment for early gastric cancer.

Minimally invasive surgery is a kind of surgical operation, which is performed by using professional surgical instruments and equipment to inactivate, resect, repair or reconstruct the pathological changes, deformities and wounds in human body through micro-trauma or micro-approach, in order to achieve the goal of treatment, its surgical effect is equivalent to the traditional open surgery, while avoiding the morbidity of conventional surgical wounds. In addition, it also has the advantages of less trauma, less blood loss during operation, less psychological burden and quick recovery on patients, and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer patients. Surgical minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer (EGC): endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR), endoscopic submucosal excavation (ESE), submucosal tunnel endoscopic resection), laparoscopic and endoscopic cooperative surgery (LECS); Among them, EMR, EFTR and LECS technologies have a wide range of applications and different modifications have been derived from their respective surgical operations, such as band-assisted EMR (BA-EMR), conventional EMR (CEMR), over-the-scope clip-assisted EFTR, no-touch EFTR, the inverted LECS, closed LECS, and so on. These new and improved minimally invasive surgeries are more precise, specific and effective in treating different types of EGC.

Forensic efficiency and population genetic construction of Guizhou Gelao minority from Southwest China revealed by a panel of 23 autosomal STR loci.

Short tandem repeats (STRs) are the most common genetic markers in forensic and human population genetics due to their high polymorphism, rapid detection, and reliable genotyping. To adapt the rapid growth of forensic DNA database and solve problems in disputed cases, a panel of 23 autosomal STR loci with high discriminating ability was constructed recently. The Tai-Kadai-speaking Gelao is the most ancient indigenous minority in Guizhou province, however, the forensic efficiency and population genetic structure remain poorly explored. Here, 490 Guizhou Gelao individuals from Southwest China were genotyped with the panel of 23 STRs using the Huaxia Platinum Kit. A total of 265 alleles were screened. The combined discrimination power and the combined probability of paternity were 0.9999 and 0.9999, respectively. This indicated the 23 loci had higher discrimination power in Guizhou Gelao and could be applied to forensic practice. Comprehensive population structures with reference populations from China and abroad using the neighbour-joining phylogenetic tree (N-J tree), multidimensional scaling, principal component analysis and heatmap demonstrated that Guizhou Gelao was genetically closer to Guizhou Han than other populations. Moreover, our results showed that a complex phylogenetic model was influenced by ethnic, geographic, and linguistic factors. Key points: The first batch of genetic data for 23 autosomal STRs in 490 Geolao individuals from Guizhou was provided.The 23 STR panel can afford high genetic polymorphisms and discrimination power and can be efficiently applied to forensic practice in Guizhou Gelao population.A complex phylogenetic model influenced by ethnic, geographic, and linguistic factors was uncovered.

Knowledge mapping and global trends of drug hypersensitivity from 2013 to 2023: A bibliometric analysis.

BACKGROUND: Drug hypersensitivity is a major global public health issue with a significant increase in prevalence in populations. Here, we provide a deep insight into the frontier hotspot and future direction in the field of drug hypersensitivity. METHODS: A knowledge map is portrayed based on publications related to drug hypersensitivity from Web of Science Core Collection using CiteSpace. Co-occurrence relationships of countries, institutes, authors, journals, references, and keywords are constructed. According to the co-occurrence relationships, hotspots and future trends are overviewed. RESULTS: The United States ranked first in the world and China with the second highest publications was the only developing country. Torres, Mayorga, and Blanca were highly productive authors. Harvard University was the institution with the most research publications. Keywords co-occurrence analysis suggested applications in emerging causes, potential mechanisms, and clinical diagnosis as the research hotspots and development frontiers. CONCLUSION: Research on drug hypersensitivity is in a rapid development stage and an emerging trend in reports of anaphylaxis to polyethylene glycols is identified. Developing algorithms for understanding the standardization process of culprit drugs, clinical manifestations, and diagnostic methods will be the focus of future direction. In addition, a better understanding of the mechanisms to culprit drugs with immunological precise phenotypic definitions and high-throughput platforms is needed.

An important issue of burnout among pre-hospital emergency medical personnel in Chengdu: a cross-sectional study.

OBJECTIVE: This survey aims to comprehensively understand occupational burnout among pre-hospital emergency medical personnel and explore associated risk factors. METHODS: A cross-sectional online survey using a census method was conducted between 15 July, 2023, and ends on 14 August, 2023, in Chengdu, SiChuan province, China. The questionnaire included general demographic information, the Maslach Burnout Inventory-General Survey (MBI-GS) with 15 items, and the Fatigue Scale-14 (FS-14) with 14 items. Univariate analysis was conducted on all variables, followed by multivariate logistic regression models to examine the associations between occupational burnout and the risk factors. RESULTS: A total of 2,299 participants,99.57% completed the survey effectively The participants were from 166 medical institutions in Chengdu, comprising 1,420 nurses (61.50%) and 889 clinical doctors (38.50%). A total of 33.36% participants experienced burnout, predominantly mild (30.27%), followed by moderate (2.78%) and severe (0.3%). Physicians, higher fatigue scores, age, work experience appeared to be related to burnout. Logistic regression models revealed that individuals aged over 50 were less prone to experience burnout compared to medical staff aged 18-30 (OR: 0.269, 95% CI: 0.115-0.627, p = 0.002). Physicians were more prone to experience burnout compared to nursing staff (OR: 0.690, 95% CI: 0.531-0.898, p = 0.006). Those with 0-5 years of experience were more prone to experience burnout compared to those with 6-10 years or over 15 years of experience (OR: 0.734, 95% CI: 0.547-0.986, p = 0.040; OR: 0.559, 95% CI: 0.339-0.924, p = 0.023). Additionally, for each 1-point increase in the fatigue score, the likelihood of burnout in medical staff increased by 1.367 times (OR: 1.367, 95% CI: 1.323-1.412, p < 0.0001). CONCLUSION: Pre-hospital emergency medical personnel demonstrate a notable prevalence of mild job burnout. These results provide a groundwork for future focus on the various stages of job burnout within pre-hospital emergency staff, alerting hospital and departmental managers to promptly address the mental well-being of their personnel and intervene as needed.

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

Exercise preconditioning inhibits doxorubicin-induced cardiotoxicity via YAP/STAT3 signaling.

Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague-Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.

Pharmacological effects and target analysis of Guipi wan in the treatment of cerebral ischemia-reperfusion injury.

Guipi wan (GPW) is a traditional Chinese medicine commonly used in clinical practice, typically to treat neurological diseases such as neurasthenia and traumatic brain injury. It may have positive effects on cerebral ischemia‒reperfusion injury (cI/R). This study aimed to assess the effects of GPW in a mouse model of cI/R and find its possible targets. C57BL/6J mice were used to establish the cI/R model, and the laser speckle doppler was used to determine the success of the model. GPW was administered intragastrically for 7 days, brain tissue sections were stained with TTC, HE, and TUNEL, Western blot assay was performed to detect the effect of apoptosis-related proteins. Furthermore, we screened active ingredients from the TCM Database and constructed a compound‒target network using the Cytoscape 3.8.0 software. Moreover, we employed protein‒protein interaction and component‒target‒pathway network analyses to determine the potential components of GPW and its target genes, the key target was verified through molecular docking. Finally, we detected the influence of the downstream signaling pathway of the target through Western blot. The results showed that GPW decreased the cerebral infarction area, neurological function scores, and neuronal apoptosis in mice by regulating PI3K/AKT signaling pathway. Network analysis indicated that gamma-aminobutyric acid B receptor 1 (GABBR1) might be a potential target for the treatment of cI/R. Molecular docking indicated that 9 active components in GPW could bind to GABBR1 with desirable binding energy. This study represented the demonstratable effect of GPW in the treatment of cI/R injury and suggested GABBR1 as a potential target using network analysis.

Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

Amide Modification of Glycolipid Biosurfactants as Promising Biocompatible Antibacterial Agents.

Discovering new antibacterial agents is crucial to addressing the increasing risk of bacterial infections induced by antimicrobial resistance in food and agricultural industries. Here, biocompatible acidic-type sophorolipids (ASLs) and glucolipids (GLs) prepared via chemical modification of natural sophorolipids from fermentation were functionalized via amide modification for use as potential antibacterial agents. It was found that the arginine methyl ester derivative of GLs (GLs-d-Arg-OMe) showed excellent antibacterial activity, killing more than 99.99% of Escherichia coli at 200 mg/L. The sterilization dosage of the GLs against Bacillus subtilis, Bacillus cereus, and Staphylococcus aureus was 16-64 mg/L, in contrast to 32-64 mg/L for the fungus Candida albicans. In particular, GLs-d-Arg-OMe showed the best biocompatibility with a therapeutic index of up to 18. It was shown that amide modification of glycolipids can effectively improve antibacterial activity while maintaining biocompatibility, which can be exploited for the development of novel antibiotics in food and agricultural fields.

Genome-Wide Analysis of C-Repeat Binding Factor Gene Family in Capsicum baccatum and Functional Exploration in Low-Temperature Response.

Capsicum baccatum is a close relative of edible chili peppers (Capsicum annuum) with high economic value. The CBF gene family plays an important role in plant stress resistance physiology. We detected a total of five CBF genes in the C. baccatum genome-wide sequencing data. These genes were scattered irregularly across four chromosomes. The genes were categorized into three groupings according to their evolutionary relationships, with genes in the same category showing comparable principles for motif composition. The 2000 bp upstream of CbCBF contains many resistance-responsive elements, hormone-responsive elements, and transcription factor binding sites. These findings emphasize the crucial functions of these genes in responding to challenging conditions and physiological regulation. Analysis of tissue-specific expression revealed that CbCBF3 exhibited the greatest level of expression among all tissues. Under conditions of low-temperature stress, all CbCBF genes exhibited different levels of responsiveness, with CbCBF3 showing a considerable up-regulation after 0.25 h of cold stress, indicating a high sensitivity to low-temperature response. The importance of the CbCBF3 gene in the cold response of C. baccatum was confirmed by the use of virus-induced gene silencing (VIGS) technology, as well as the prediction of its protein interaction network. To summarize, this study conducts a thorough bioinformatics investigation of the CbCBF gene family, showcases the practicality of employing VIGS technology in C. baccatum, and confirms the significance of the CbCBF3 gene in response to low temperatures. These findings provide significant references for future research on the adaptation of C. baccatum to low temperatures.