Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

A Label-Free Fluorescent Amplification Strategy for High-Sensitive Detection of Pseudomonas aeruginosa based on Protective-EXPAR (p-EXPAR) and Catalytic Hairpin Assembly.

This study presents a fluorescent mechanism for two-step amplification by combining two widely used techniques, exponential amplification reaction (EXPAR) and catalytic hairpin assembly (CHA). Pseudomonas aeruginosa (P. aeruginosa) engaged in competition with the complementary DNA in order to attach to the aptamer that had been fixed on the magnetic beads. The unbound complementary strand in the liquid above was utilized as a trigger sequence to initiate the protective-EXPAR (p-EXPAR) process, resulting in the generation of a substantial quantity of short single-stranded DNA (ssDNA). The amplified ssDNA can initiate the second CHA amplification process, resulting in the generation of many double-stranded DNA (dsDNA) products. The CHA reaction was initiated by the target/trigger DNA, resulting in the release of G-quadruplex sequences. These sequences have the ability to bond with the fluorescent amyloid dye thioflavin T (ThT), generating fluorescence signals. The method employed in this study demonstrated a detection limit of 16 cfu/mL and exhibited a strong linear correlation within the concentration range of 50 cfu/mL to 105 cfu/mL. This method of signal amplification has been effectively utilized to create a fluorescent sensing platform without the need for labels, enabling the detection of P. aeruginosa with high sensitivity.

Electroencephalographic insights into the pathophysiological mechanisms of emergence delirium in children and corresponding clinical treatment strategies.

Emergence delirium is a common postoperative complication in patients undergoing general anesthesia, especially in children. In severe cases, it can cause unnecessary self-harm, affect postoperative recovery, lead to parental dissatisfaction, and increase medical costs. With the widespread use of inhalation anesthetic drugs (such as sevoflurane and desflurane), the incidence of emergence delirium in children is gradually increasing; however, its pathogenesis in children is complex and unclear. Several studies have shown that age, pain, and anesthetic drugs are strongly associated with the occurrence of emergence delirium. Alterations in central neurophysiology are essential intermediate processes in the development of emergence delirium. Compared to adults, the pediatric nervous system is not fully developed; therefore, the pediatric electroencephalogram may vary slightly by age. Moreover, pain and anesthetic drugs can cause changes in the excitability of the central nervous system, resulting in electroencephalographic changes. In this paper, we review the pathogenesis of and prevention strategies for emergence delirium in children from the perspective of brain electrophysiology-especially for commonly used pharmacological treatments-to provide the basis for understanding the development of emergence delirium as well as its prevention and treatment, and to suggest future research direction.

Advances and perspectives on pharmacological activities and mechanisms of the monoterpene borneol.

BACKGROUND: Borneol, a highly lipid-soluble bicyclic terpene mainly extracted from plants, is representative of monoterpenoids. Modern medicine has established that borneol exhibits a range of pharmacological activities and used in the treatment of many diseases, particularly Cardio-cerebrovascular diseases (CVDs). The crucial role in enhancing drug delivery and improving bioavailability has attracted much attention. In addition, borneol is also widely utilized in food, daily chemicals, fragrances, and flavors industries. PURPOSE: This review systematically summarized the sources, pharmacological activities and mechanisms, clinical trial, pharmacokinetics, toxicity, and application of borneol. In addition, this review describes the pharmacological effects of borneol ester and the combination of borneol with nanomaterial. This review will provide a valuable resource for those pursuing researches on borneol inspiring the pharmacological applications in the medicine, food and daily chemical products, and developing of new drugs containing borneol or its derivatives. METHODS: This review searched the keywords ("borneol" or "bornyl esters") and ("pharmacology" or "Traditional Chinese medicine" or "Cardio-cerebrovascular diseases" or "blood-brain barrier" or "ischemic stroke" or "nanomaterials" or "neurodegenerative diseases" or "diabetes" or "toxicity") in Web of Science, PubMed, Google Scholar and China National Knowledge Infrastructure (CNKI) from January 1990 to May 2024. The search was limited to articles published in English and Chinese. RESULTS: Borneol exhibits extensive pharmacological activities including anti-inflammatory effects, analgesia, antioxidation, and has the property of crossing biological barriers and treating CVDs. The intrinsic molecular mechanisms are involved in multiple components, such as regulation of various key factors (including Tumor necrosis factor-α, Nuclear factor kappa-B, Interleukin-1ß, Malondialdehyde), inhibiting transporter protein function, regulating biochemical levels, and altering physical structural changes. In addition, this review describes the pharmacological effects of borneol ester and the combination of borneol with nanomaterial. CONCLUSION: The pharmacological properties and applications of borneol are promising, including anti-inflammatory, analgesic, antimicrobial, and antioxidant properties, as well as enhancing drug delivery and treating CVDs. However, its clinical application is hindered by the limited research on safety, efficacy, and pharmacokinetics. Therefore, this review systemically summarized the advances on pharmacological activities and mechanisms of the borneol. Standardized clinical trials and exploration of synergistic effects with other drugs were also are outlined.

The intratumoral microbiota biomarkers for predicting survival and efficacy of immunotherapy in patients with ovarian serous cystadenocarcinoma.

BACKGROUND: Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need. METHODS: In this study, we analyzed the microbial contents of 453 ovarian serous cystadenocarcinoma and 68 adjacent non-cancerous samples. A univariate Cox regression model was used to identify microorganisms significantly associated with survival and a prognostic risk score model constructed using LASSO Cox regression analysis. Patients were subsequently categorized into high-risk and low-risk groups based on their risk scores. RESULTS: Survival analysis revealed that patients in the low-risk group had a higher overall survival rate. A nomogram was constructed for easy visualization of the prognostic model. Analysis of immune cell infiltration and immune checkpoint gene expression in both groups showed that both parameters were positively correlated with the risk level, indicating an increased immune response in higher risk groups. CONCLUSION: Our findings suggest that microbial profiles in ovarian serous cystadenocarcinoma may serve as viable clinical prognostic indicators. This study provides novel insights into the potential impact of intratumoral microbial communities on disease prognosis and opens avenues for future therapeutic interventions targeting these microorganisms.

Compared with other methods, cyanoacrylate and lauromacrogol in treating esophagogastric varices did not increase the risk of postoperative infection.

BACKGROUND: Patients with cirrhosis commonly undergo endoscopic cyanoacrylate injection for gastric and esophageal variceal bleeding. However, postoperative infections can increase the risk of rebleeding and mortality. AIM: This study aimed to determine the risk of postoperative infections and its associated factors following cyanoacrylate injection treatment in these patients. METHODS: A retrospective analysis was conducted on 57 patients treated with ligation (ligation group), 66 patients treated with cyanoacrylate injection (injection group), and 91 patients treated with conservative treatment (control group) at the Nanchong Central Hospital. RESULTS: The rate of postoperative infection was similar among the cyanoacrylate, ligation, and conservative treatment groups, with no significant statistical difference observed (P = 0.97). Multivariate analysis identified postoperative Child-Pugh score and renal insufficiency as two independent risk factors for postoperative infection. The rebleeding rate in the injection group was significantly lower than in the other groups (P = 0.01). Mortality was significantly higher in the control group compared with the ligation and injection groups (P = 0.01). CONCLUSION: Cyanoacrylate combined with lauromacrogol injection did not significantly increase the risk of infection compared with ligation and conservative treatments, and it was more effective in reducing the risk of rebleeding. This method is safe, effective, and holds clinical value for broader application.

Chinese FDI outflows and host country environment.

This study provides first evidence on the effects of Chinese FDI (Foreign Direct Investment) outflows on host country environments. The study draws upon a comprehensive dataset covering aggregate Chinese FDI outflows and sector specific data into 65 host nations over the 2007-2019 period. Employing a STIRPAT (Stochastic Regression on Population, Affluence and Technology) model and several different techniques including DID (Difference-in-Difference), pooled OLS (Ordinary Least Squares), quantile regression, IV (Instrumental Variable) estimation, threshold and Tobit regression, the findings suggest that Chinese FDI leads to an increase in host country CO2 (Carbon Dioxide) emissions, aligning with the pollution haven hypothesis at the aggregate level. A closer investigation at the development regime and sectoral levels indicates that in the low development regime, FDI inflows into the financial and real estate sector increase emissions. Conversely in the high-income regime, Chinese FDI into the entertainment sector is associated with an increase in carbon emissions. Chinese FDI is further found to lead to an increase in emissions in countries with a per capita GDP (Gross Domestic Product) of below USD72041.7. However, as per capita income rises above USD72041.7, FDI leads to a fall in carbon emissions.

Ursolic acid improves necroptosis via STAT3 signaling in intestinal ischemia/reperfusion injury.

Intestinal ischemia/reperfusion injury (IRI) poses a serious threat to human survival and quality of life with high mortality and morbidity rates. The current absence of effective treatments for intestinal IRI highlights the urgent need to identify new therapeutic targets. Ursolic acid (UA), a pentacyclic triterpene natural compound, has been shown to possess various pharmacological properties including intestinal protection. However, its potential protective efficacy on intestinal IRI remains elusive. This study aimed to investigate the effect of UA on intestinal IRI and explore the underlying mechanisms. To achieve this, we utilized network pharmacology to analyze the mechanism of UA in intestinal IRI and assessed UA's effects on intestinal IRI using a mouse model of superior mesenteric artery occlusion/reperfusion and an in vitro model of oxygen-glucose deprivation and reperfusion-induced IEC-6 cells. Our results demonstrated that UA improved necroptosis through the RIP1/RIP3/MLKL pathway, reduced necroinflammation via the HMGB1/TLR4/NF-κB pathway, attenuated morphological damage, and enhanced intestinal barrier function. Furthermore, UA pretreatment downregulated the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). The effects of UA were attenuated by the STAT3 agonist Colivelin. In conclusion, our study suggests that UA can improve intestinal IRI by inhibiting necroptosis in enterocytes via the suppression of STAT3 activation. These results provide a theoretical basis for UA treatment of intestinal IRI and related clinical diseases.

Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension.

Herein, a series of novel arylpiperazine (piperidine) derivatives were designed, synthesized, and evaluated for mechanisms of action through in vitro and in vivo studies. The most promising compound, II-13 (later named as MT-1207), is a potent α1 and 5-HT2A receptor antagonist with remarkable IC50 in the picomolar level. Importantly, in the in vivo assay, II-13 achieved an effective blood pressure (BP) reduction in the 2K2C rat model without damaging renal function. Compound II-13, with its significant advantages in terms of pharmacological effects, pharmacokinetic parameters, and a large safety window, was extensively investigated. Moreover, data also showed that compound II-13 had fewer side effects in a postural BP assay and could prevent the onset of postural hypotension. Together, these results suggested that compound II-13 is a highly potent antihypertensive drug candidate with multitarget mechanisms of action in preclinical models. Currently, MT-1207 is in phase II hypertensive clinical trials in China.

The relationship between household income and prognosis of patients with cervical adenocarcinoma in the United States: A retrospective cohort study based on the SEER database.

OBJECTIVE: To investigate the association between household income and overall survival (OS) of patients with cervical adenocarcinoma. METHODS: We conducted a retrospective cohort study involving participants selected from the Surveillance, Epidemiology, and End Results (SEER) database. Data were collected on various variables, including demographic variables such as median household income and clinicopathological characteristics for all participants. Cox regression analysis was utilized to examine the association between household income and OS. Subgroup analysis, sensitivity analysis, and E-value were used to further confirm the association. RESULTS: A total of 2217 patients were included in the study. Compared with low-income (<$35,000-$54,999), middle-income (55,000-$69,999) or high-income (≥$70,000) was significantly associated with a higher 5-year OS (70.8 %, 58.7 % vs 50 %) in patients with cervical adenocarcinoma. The HR was 0.49, 95 % CI 0.41-0.58, p < 0.001 and 0.66 (0.55-0.78), p < 0.001 respectively, in the unadjusted model. After adjustment for potential confounders, the results were similar (adjusted HR 0.54 (0.45-0.65), p < 0.001) and 0.79 (0.66-0.94), p = 0.01), respectively. This significant association was also present in the various adjusted models. Subgroup and sensitivity analyses suggested that the relationship remained robust and reliable. The E-value analysis indicated robustness to unmeasured confounding. There was evidence of an interaction between age at diagnosis, race, primary site, tumor grade, T, N, M, or Scope Reg LN Sur, and household income on increasing the 5-year OS of cervical adenocarcinoma. CONCLUSIONS: Our study found that middle or high household income was significantly associated with a better 5-year OS compared with low household income in patients with cervical adenocarcinoma.

Characteristics of adult retroperitoneal lymphangioma: a single center Chinese cohort study of 15 cases.

BACKGROUND: Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease. METHODS: We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022. RESULTS: The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via computed tomography (CT) (n = 10, 66.67%) or magnetic resonance imaging (MRI) (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients. CONCLUSIONS: Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions.

Relationship between Sjogren's syndrome and gastroesophageal reflux: A bidirectional Mendelian randomization study.

The clinical incidence of sjogren's syndrome combined with gastroesophageal reflux disease is high. Existing observational studies have shown inconsistent results in the association between gastroesophageal reflux disease (GERD) and Sjogren's syndrome (SS).We observed that the symptoms of SS patients also improved after receiving GERD-related treatment. Therefore, we aimed to investigate the relationship between GERD and SS through a bidirectional two-sample Mendelian randomization (MR) study. Independent SNPs associated with GERD and SS were selected from a genome-wide association study (GWAS) as instrumental variables to conduct a bidirectional two-sample Mendelian analysis of GERD and SS. Genetic data were obtained from two databases for the following two outcomes: Gastroesophageal reflux (IEU Open GWAS) [sample size = 602,604 (patients = 129,080; nonpatients = 473,524)] and SS (FinnGen) [sample size = 392,423 (patients = 2,495; nonpatients = 389,928)]. Statistical methods for the MR analysis included the inverse-variance weighting method, weighted median, simple mode and weighted mode, as well as heterogeneity and sensitivity analyses using the Cochran Q statistic, MR‒Egger regression, outlier detection methods (MR-PRESSO). In addition, Steiger Test was conducted to test the direction of causality. MR analysis showed a positive correlation between GERD and SS risk [odds ratio (OR) = 1.3279 (95% confidence interval 1.0312-1.7099, P = 0.0280)]. However, in contrast, no significant causal effect of SS on GERD was observed [OR = 1.0024 (95% CI 0.9651-1.0412; P = 0.8995)]. This bidirectional two-sample Mendelian randomization study confirmed a causal relationship between SS and GERD, and suggested that GERD is a risk factor for SS, while SS does not affect GERD.

A retrospective study of prognostic factors and treatment outcome in advanced-stage Mycosis Fungoides and Sezary Syndrome.

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs.Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023.Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, ß2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival.Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.

Built-In Positive Valence Space Shifting the Chemical Equilibrium Forward for Nitrate Reduction to Ammonia.

The electrochemical conversion of nitrate pollutants into value-added ammonia (NH3) is an appealing alternative synthetic route for sustainable NH3 production. However, the development of the electrocatalytic nitrate-to-ammonia reduction reaction (NO3RR) has been hampered by unruly reactants and products at the interface and the accompanied sluggish kinetic rate. In this work, a built-in positive valence space is successfully constructed over FeCu nanocrystals to rationally regulate interfacial component concentrations and positively shift the chemical equilibrium. With positive valence Cu optimizing the active surface, the space between the stern and shear layers becomes positive, which is able to continuously attract the negatively charged NO3- reactant and repulse the positively charged NH4+ product even under high current density, thus significantly boosting the NO3RR kinetics. The system with a built-in positive valence space affords an ampere-level NO3RR performance with the highest NH3 yield rate of 150.27 mg h-1 mg-1 at -1.3 V versus RHE with an outstanding NH3 current density of 189.53 mA cm-2, as well as a superior Faradaic efficiency (FE) of 97.26% at -1.2 V versus RHE. The strategy proposed here underscores the importance of interfacial concentration regulation and can find wider applicability in other electrochemical syntheses suffering from sluggish kinetics.

Spatial distribution pattern of immune cells is associated with patient prognosis in colorectal cancer.

BACKGROUND: The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients' clinical outcomes. However, the prognostic value of the TIIC spatial distribution is unknown. Thus, we aimed to investigate the association between TIICs in situ and patient prognosis in a large CRC sample. METHODS: We implemented multiplex immunohistochemistry staining technology in 190 CRC samples to quantify 14 TIIC subgroups in situ. To delineate the spatial relationship of TIICs to tumor cells, tissue slides were segmented into tumor cell and microenvironment compartments based on image recognition technology, and the distance between immune and tumor cells was calculated by implementing the computational pipeline phenoptr. RESULTS: MPO+ neutrophils and CD68+IDO1+ tumor-associated macrophages (TAMs) were enriched in the epithelial compartment, and myeloid lineage cells were located nearest to tumor cells. Except for CD68+CD163+ TAMs, other cells were all positively associated with favorable prognosis. The prognostic predictive power of TIICs was highly related to their distance to tumor cells. Unsupervised clustering analysis divided colorectal cancer into three subtypes with distinct prognostic outcomes, and correlation analysis revealed the synergy among B cells, CD68+IDO1+TAMs, and T lineage cells in producing an effective immune response. CONCLUSIONS: Our study suggests that the integration of spatial localization with TIIC abundance is important for comprehensive prognostic assessment.

Tagging large CNV blocks in wheat boosts digitalization of germplasm resources by ultra-low-coverage sequencing.

BACKGROUND: The massive structural variations and frequent introgression highly contribute to the genetic diversity of wheat, while the huge and complex genome of polyploid wheat hinders efficient genotyping of abundant varieties towards accurate identification, management, and exploitation of germplasm resources. RESULTS: We develop a novel workflow that identifies 1240 high-quality large copy number variation blocks (CNVb) in wheat at the pan-genome level, demonstrating that CNVb can serve as an ideal DNA fingerprinting marker for discriminating massive varieties, with the accuracy validated by PCR assay. We then construct a digitalized genotyping CNVb map across 1599 global wheat accessions. Key CNVb markers are linked with trait-associated introgressions, such as the 1RS·1BL translocation and 2NvS translocation, and the beneficial alleles, such as the end-use quality allele Glu-D1d (Dx5 + Dy10) and the semi-dwarf r-e-z allele. Furthermore, we demonstrate that these tagged CNVb markers promote a stable and cost-effective strategy for evaluating wheat germplasm resources with ultra-low-coverage sequencing data, competing with SNP array for applications such as evaluating new varieties, efficient management of collections in gene banks, and describing wheat germplasm resources in a digitalized manner. We also develop a user-friendly interactive platform, WheatCNVb ( http://wheat.cau.edu.cn/WheatCNVb/ ), for exploring the CNVb profiles over ever-increasing wheat accessions, and also propose a QR-code-like representation of individual digital CNVb fingerprint. This platform also allows uploading new CNVb profiles for comparison with stored varieties. CONCLUSIONS: The CNVb-based approach provides a low-cost and high-throughput genotyping strategy for enabling digitalized wheat germplasm management and modern breeding with precise and practical decision-making.

The effect of agitating buffy coats on platelet quality before soft spin.

BACKGROUND: Platelet plays a vital role in both physiological and pathological processes. However, the limited storage time of platelet in vitro poses an immense challenge for its applications because of the increased risk of bacterial contamination and platelet storage lesions. Agitation can inhibit lesions by facilitating continuous oxygenation of platelets and permitting excess carbon dioxide to be removed during storage. However, it is still not known whether agitating BCs gives a positive effect on platelet quality. OBJECTIVES: To evaluate the quality difference between platelet concentrates (PCs) from buffy coats (BCs) held rest and agitation. METHODS: Samples were withdrawn for cell count, blood gas analysis, free hemoglobin level, hypotonic shock response, maximum aggregation rate, activation marker expression (CD62P and CD42b) and coagulation function. RESULTS: We found the PCs prepared from the agitating BCs had fewer residual WBCs, exhibited a better gas exchange ability, slower metabolism (higher pH, higher content glucose, and lower lactic acid levels), better hypotonic shock response, and lower levels of CD62P. The TEG-PC assays showed no difference in coagulation function. CONCLUSION: Our findings showed that BC can be agitated overnight before a soft spin.

Inhibition of Th17 cell differentiation by aerobic exercise improves vasodilatation in diabetic mice.

BACKGROUND: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. METHODS: db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. RESULTS: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. CONCLUSIONS: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.

Biological Evaluation of Lysionotin: a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma.

OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.

Triglyceride-glucose index is associated with the risk of impaired fasting glucose in Chinese elderly individuals.

The association between the triglyceride-glucose (TyG) index and impaired fasting glucose (IFG) in elderly individuals remains uncertain. Our study aimed to explore the association between the TyG index and the risk of future IFG in this population. This retrospective cohort study included 17,746 elderly individuals over 60. In this population, Cox regression models proportional to hazards, along with smooth curve fitting and cubic spline functions, were employed to examine the association between the baseline TyG index and the risk of IFG. Subgroup analyses and sensitivity were also performed to ensure the robustness of the study findings. After adjusting for covariates, a positive association between the TyG index and the risk of IFG was found (HR = 1.43, 95% CI 1.27-1.60, P < 0.0001). The likelihood of IFG rose steadily as the TyG index quartiles (from Q1 to Q4) increased, with Q4 demonstrating a 62% elevated risk compared to Q1 (adjusted HR = 1.62, 95% CI 1.37-1.90). Additionally, we found the association between TyG index and risk of IFG was a linear. Sensitivity and subgroup analyses confirmed the stability of the results. Our study observed a linear association between the TyG index and the development of IFG in elderly Chinese individuals. Recognizing this association can help clinicians identify high-risk individuals and implement targeted interventions to reduce their risk of progressing to diabetes.