Incidence and Outcomes of Brucella Endocarditis in a High-Prevalence Area: A Single-Center Study.

OBJECTIVE: To analyze the clinical characteristics of Brucella endocarditis (BE) and observe the factors related to death to provide guidance for clinical treatment. METHODS: This study examined all patients with BE admitted to The First People's Hospital of Kashi Prefecture between January 2017 and November 2023. Clinical characteristics and follow-up outcomes were collected for analysis. RESULTS: This study revealed 774 cases of brucellosis and 14 cases of BE, with an overall incidence rate of 1.88%. Most of the patients were male (71.43%) and lived in areas where brucellosis is common. Patients ranged in age from 26 to 68 years. Common symptoms reported among patients included chest tightness and fatigue, and a significant portion also presented with congestive heart failure. Most patients exhibited normal white blood cell counts (WBC) but had elevated levels of C-reactive protein (CRP). Transthoracic ultrasound (TTE) revealed cardiac valve vegetation in all patients, along with positive blood cultures. Six patients (42.86%) completed heart surgery, and ten (71.43%) completed anti-infection treatment. Six patients died, five of whom did not undergo surgery. The other patient with Marfan syndrome died after surgery. Sex, WBC count, neutrophil (NEUT) and total bilirubin (TBIL) were significant factors associated with regression in BE patients (P < 0.05) according to univariate analysis. CONCLUSIONS: Patients with BE in Kashi have a severe clinical presentation at diagnosis, but early detection with improved cardiac ultrasound and aggressive treatment can improve the prognosis.

Characterization of a methyltransferase for iterative N-methylation at the leucinostatin termini in Purpureocillium lilacinum.

N-methyltransferase (NMT)-catalyzed methylation at the termini of nonribosomal peptides (NRPs) has rarely been reported. Here, we discover a fungal NMT LcsG for the iterative terminal N-methylation of a family of NRPs, leucinostatins. Gene deletion results suggest that LcsG is essential for leucinostatins methylation. Results from in vitro assays and HRESI-MS-MS analysis reveal the methylation sites as NH2, NHCH3 and N(CH3)2 in the C-terminus of various leucinostatins. LcsG catalysis yields new lipopeptides, some of which demonstrate effective antibiotic properties against the human pathogen Cryptococcus neoformans and the plant pathogen Phytophthora infestans. Multiple sequence alignments and site-directed mutagenesis of LcsG indicate the presence of a highly conserved SAM-binding pocket, along with two possible active site residues (D368 and D395). Molecular dynamics simulations show that the targeted N can dock between these two residues. Thus, this study suggests a method for increasing the variety of natural bioactivity of NPRs and a possible catalytic mechanism underlying the N-methylation of NRPs.

Can molecular hydrogen supplementation enhance physical performance in healthy adults? A systematic review and meta-analysis.

Background: Physical exertion during exercise often leads to increased oxidative stress and inflammatory responses, significantly affecting physical performance. Current strategies to mitigate these effects are limited by their effectiveness and potential side effects. Molecular hydrogen (H2) has gained attention for its antioxidant and anti-inflammatory properties. Studies have suggested that H2 supplementation contributes to antioxidant potential and anti-fatigue during exercise, but the variance in the observations and study protocols is presented across those studies. Objective: This systematic review and meta-analysis aimed to comprehensively characterize the effects of H2 supplementation on physical performance (i.e., endurance, muscular strength, and explosive power), providing knowledge that can inform strategies using H2 for enhancing physical performance. Methods: We conducted a literature search of six databases (PubMed, Web of Science, Medline, Sport-Discus, Embase, and PsycINFO) according to the PRISMA guidelines. The data were extracted from the included studies and converted into the standardized mean difference (SMD). After that, we performed random-effects meta-analyses and used the I 2 statistic to evaluate heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the quality of the evidence obtained from this meta-analysis. Results: In total, 27 publications consisting of 597 participants were included. The search finally included aerobic endurance, anaerobic endurance, muscular strength, lower limb explosive power, rating of perceived exertion (RPE), blood lactate (BLA), and average heart rate (HRavg) in the effect size (ES) synthesis. The ES of H2 on aerobic endurance, including V̇O2max (SMD = 0.09, p = 0.394; I 2 = 0%) and aerobic endurance exercise (SMD = 0.04, p = 0.687; I 2 = 0%), were not significant and trivial; the ES of H2 on 30 s maximal anaerobic endurance (SMD = 0.19, p = 0.239; I 2 = 0%) was not significant and trivial; the ES of H2 on muscular strength (SMD = 0.19, p = 0.265; I 2 = 0%) was not significant and trivial; but the ES of H2 on lower limb explosive power (SMD = 0.30, p = 0.018; I 2 = 0%) was significant and small. In addition, H2 reduces RPE (SMD = -0.37, p = 0.009; I 2 = 58.0%) and BLA (SMD = -0.37, p = 0.001; I 2 = 22.0%) during exercise, but not HRavg (SMD = -0.27, p = 0.094; I 2 = 0%). Conclusion: These findings suggest that H2 supplementation is favorable in healthy adults to improve lower limb explosive power, alleviate fatigue, and boost BLA clearance, but may not be effectively improving aerobic and anaerobic endurance and muscular strength. Future studies with more rigorous designs are thus needed to examine and confirm the effects of H2 on these important functionalities in humans. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO.

The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial.

(1) Background: Hydrogen (H2) may be a potential therapeutic agent for managing Long COVID symptoms due to its antioxidant and anti-inflammatory properties. However, more scientific literature is needed to describe the effects of H2 administration on treating symptoms. A study aimed to investigate the impact of hydrogen-rich water (HRW) administration on the fatigue and dyspnea of Long-COVID patients for 14 consecutive days. (2) Methods: In this randomized, single-blind, placebo-controlled study, 55 participants were recruited, and 23 of them were excluded. A total of 32 eligible participants were randomized into a hydrogen-rich water (HRW) group (n = 16) and a placebo water (PW) group (n = 16) in which they were instructed to consume hydrogen-rich water or placebo water for 14 days, respectively. The participants completed the Fatigue Severity Scale (FSS), Six-Minute Walk Test (6MWT), 30 s Chair Stand Test (30s-CST), Modified Medical Research Council Dyspnea Rating Scale (mMRC), Pittsburgh Sleep Quality Index (PSQI), and depression anxiety stress scale (DASS-21) before and after the intervention. A linear mixed-effects model was used to analyze the effects of HRW. Cohen's d values were used to assess the effect size when significance was observed. The mean change with 95% confidence intervals (95% CI) was also reported. (3) Results: The effects of HRW on lowering FSS scores (p = 0.046, [95% CI = -20.607, -0.198, d = 0.696] and improving total distance in the 6WMT (p < 0.001, [95% CI = 41.972, 61.891], d = 1.010), total time for the 30s-CST (p = 0.002, [95% CI = 1.570, 6.314], d = 1.190), and PSQI scores (p = 0.012, [95% CI = -5.169, 0.742], d = 1.274) compared to PW were of a significantly moderate effect size, while there was no significant difference in mMRC score (p = 0.556) or DASS-21 score (p > 0.143). (4) Conclusions: This study demonstrates that HRW might be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality. Still, it does not ameliorate dyspnea among Long-COVID patients.

Can molecular hydrogen supplementation reduce exercise-induced oxidative stress in healthy adults? A systematic review and meta-analysis.

Objective: Exercise-induced oxidative stress affects multiple neurophysiological processes, diminishing the exercise performance. Hydrogen (H2) can selectively reduce excessive free radicals, but studies observed its "dual effects" on exercise-induced oxidative stress, that is, increasing or decreasing the oxidative stress. Therefore, we here conducted a systematic review and meta-analysis to quantitatively assess the influence of H2 on exercise-induced oxidative stress in healthy adults. Methods: We conducted a systematic review of publications across five databases. The following keywords were used for search strategy: ["hydrogen"[Mesh] or "molecular hydrogen" or "hydrogen rich water" or "hydrogen-rich water" or "hydrogen rich saline"] and ["Oxidative Stress"[Mesh] or "Antioxidative Stress" or "Oxidative Damage" or "Oxidative Injury" or "Oxidative Cleavage"] and ["randomized controlled trial"[Mesh] or "randomized" or "RCT"]. We included trials reporting the effects of H2 on exercise-induced oxidative stress and potential antioxidant capacity post-exercise in healthy adults. Additionally, subgroup analyses were conducted to explore how various elements of the intervention design affected those outcomes. Results: Six studies, encompassing seven experiments with a total of 76 participants, were included in our analysis. Among these studies, hydrogen-rich water, hydrogen bathing, and hydrogen-rich gas were three forms used in H2 administration. The H2 was applied in different timing, including before, during, or after exercise only, both before and after exercise, and repeatedly over days. Single-dose, multi-dose within 1 day and/or multiple-dose over days were implemented. It was observed that compared to placebo, the effects of H2 on oxidative stress (diacron-reactive oxygen metabolites, d-ROMs) was not significant (SMD = -0.01, 95%CI-0.42 to 0.39, p = 0.94). However, H2 induced greater improvement in antioxidant potential capacity (Biological Antioxidant Potential, BAP) (SMD = 0.29, 95% CI 0.04 to 0.54, p = 0.03) as compared to placebo. Subgroup analyses revealed that H2 supplementation showed greater improvement (SMD = 0.52, 95%CI 0.16 to 0.87, p = 0.02) in the antioxidant potential capacity of intermittent exercises than continuous exercise. Conclusion: H2 supplementation can help enhance antioxidant potential capacity in healthy adults, especially in intermittent exercise, but not directly diminish the levels of exercise-induced oxidative stress. Future studies with more rigorous design are needed to examine and confirm these findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364123, Identifier CRD42022364123.

A Novel Coacervate Embolic Agent for Tumor Chemoembolization.

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.

Basic concepts, recent advances, and future perspectives in the diagnosis of bovine mastitis.

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated . Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.

Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer-specific evolutionary pattern contributing to high oxidative metabolism.

BACKGROUND: Epithelial ovarian cancer (EOC) heavily relies on oxidative phosphorylation (OXPHOS) and exhibits distinct mitochondrial metabolic reprogramming. Up to now, the evolutionary pattern of somatic mitochondrial DNA (mtDNA) mutations in EOC tissues and their potential roles in metabolic remodelling have not been systematically elucidated. METHODS: Based on a large somatic mtDNA mutation dataset from private and public EOC cohorts (239 and 118 patients, respectively), we most comprehensively characterised the EOC-specific evolutionary pattern of mtDNA mutations and investigated its biological implication. RESULTS: Mutational profiling revealed that the mitochondrial genome of EOC tissues was highly unstable compared with non-cancerous ovary tissues. Furthermore, our data indicated the delayed heteroplasmy accumulation of mtDNA control region (mtCTR) mutations and near-complete absence of mtCTR non-hypervariable segment (non-HVS) mutations in EOC tissues, which is consistent with stringent negative selection against mtCTR mutation. Additionally, we observed a bidirectional and region-specific evolutionary pattern of mtDNA coding region mutations, manifested as significant negative selection against mutations in complex V (ATP6/ATP8) and tRNA loop regions, and potential positive selection on mutations in complex III (MT-CYB). Meanwhile, EOC tissues showed higher mitochondrial biogenesis compared with non-cancerous ovary tissues. Further analysis revealed the significant association between mtDNA mutations and both mitochondrial biogenesis and overall survival of EOC patients. CONCLUSIONS: Our study presents a comprehensive delineation of EOC-specific evolutionary patterns of mtDNA mutations that aligned well with the specific mitochondrial metabolic remodelling, conferring novel insights into the functional roles of mtDNA mutations in EOC tumourigenesis and progression.

The comparison between effects of Taichi and conventional exercise on functional mobility and balance in healthy older adults: a systematic literature review and meta-analysis.

Background: Taichi is beneficial for functional mobility and balance in older adults. However, such benefits of Taichi when comparing to conventional exercise (CE) are not well understood due to large variance in study protocols and observations. Methods: We reviewed publications in five databases. Eligible studies that examined the effects of Taichi on the outcomes of functional mobility and balance in healthy older adults as compared to CE were included. Subgroup analyses compared the effects of different types of CE (e.g., single and multiple-type exercise) and different intervention designs (e.g., Taichi types) on those outcomes (Registration number: CRD42022331956). Results: Twelve studies consisting of 2,901 participants were included. Generally, compared to CE, Taichi induced greater improvements in the performance of Timed-Up-and-Go (SMD = -0.18, [-0.33 to -0.03], p = 0.040, I2 = 59.57%), 50-foot walking (MD = -1.84 s, [-2.62 to -1.07], p < 0.001, I2 = 0%), one-leg stance with eyes open (MD = 6.00s, [2.97 to 9.02], p < 0.001, I2 = 83.19%), one-leg stance with eyes closed (MD = 1.65 s, [1.35 to 1.96], p < 0.001, I2 = 36.2%), and functional reach (SMD = 0.7, [0.32 to 1.08], p < 0.001, I2 = 86.79%) tests. Subgroup analyses revealed that Taichi with relatively short duration (<20 weeks), low total time (≤24 h), and/or using Yang-style, can induce significantly greater benefits for functional mobility and balance as compared to CE. Uniquely, Taichi only induced significantly greater improvements in Timed-Up-and-Go compared to single- (SMD = -0.40, [-0.55 to -0.24], p < 0.001, I2 = 6.14%), but not multiple-type exercise. A significant difference between the effects of Taichi was observed on the performance of one-leg stance with eyes open when compared to CE without balance (MD = 3.63 s, [1.02 to 6.24], p = 0.006, I2 = 74.93%) and CE with balance (MD = 13.90s, [10.32 to 17.48], p < 0.001, I2 = 6.1%). No other significant difference was shown between the influences of different CE types on the observations. Conclusion: Taichi can induce greater improvement in functional mobility and balance in older adults compared to CE in a more efficient fashion, especially compared to single-type CE. Future studies with more rigorous design are needed to confirm the observations here.