Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment: A prospective study.

BACKGROUND: Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques. AIM: To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). METHODS: This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment. RESULTS: The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment. CONCLUSION: UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Establishment of a reverse transcription-recombinase polymerase amplification-lateral flow dipstick method for the dual detection of Israeli acute paralysis virus and chronic bee paralysis virus.

Introduction: As an important social insect, honey bees play crucial roles in agricultural production, sustainable development of agricultural production, and the balance of the natural environment. However, in recent years, Israeli acute paralysis virus (IAPV) and chronic bee paralysis virus (CBPV), the main pathogens of bee paralysis, have continuously harmed bee colonies and caused certain losses to the beekeeping industry. Some beekeeping farms are located in wild or remote mountainous areas, and samples from these farms cannot be sent to the laboratory for testing in a timely manner, thereby limiting the accurate and rapid diagnosis of the disease. Methods and results: In this study, we used a reverse transcription-recombinase polymerase amplification-lateral flow dipstick (RT-RPA-LFD) method for the dual detection of IAPV and CBPV. RPA primers and LFD detection probes were designed separately for their conserved genes. Primers and probes were screened, and the forward and reverse primer ratios, reaction times, and temperatures were optimized. According to the results of the optimization tests, the optimal reaction temperature for RT-RPA is 37°C, and when combined with LFD, detection with the naked eye requires <20 min. The developed RPA-LFD method specifically targets IAPV and CBPV and has no cross-reactivity with other common bee viruses. In addition, the minimum detection limit of the RT-RPA-LFD method is 101 copies/µL. Conclusion: Based this study, this method is suitable for the detection of clinical samples and can be used for field detection of IAPV and CBPV.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

The Barthel Index predicts surgical textbook outcomes following hepatectomy for elderly patients with hepatocellular carcinoma: A multicenter cohort study.

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

An international, multicenter, survey-based analysis of practice and management of acute liver failure.

INTRODUCTION: Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and hepatic encephalopathy in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. METHODS: An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. RESULTS: A total of 267 physicians completed the survey with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians were specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred and fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver- or transplant- intensive care unit (p<0.001). Median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, one week in 37.6%, and more than one week in 9.6% (p<0.001). Deceased-donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of ALF patients, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring hepatic encephalopathy and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. DISCUSSION: In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare multicenter studies are valuable to identify global practice.

A review of the research progress on Artemisia argyi Folium: botany, phytochemistry, pharmacological activities, and clinical application.

As a kind of well-known moxibustion material across the world, Artemisia argyi Folium (AAF) has a definite curative effect. From 1996 to now, various studies on AAF have been increasing year by year. That is why this paper is conducted because of no comprehensive summary except for an essential oil review recently published in 2023. Using "AAF" and "mugwort" as keywords, the related literature was summarized in four internationally recognized databases: PubMed, Web of Science, ACS, and ScienceDirect, mainly include four aspects such as botany, phytochemistry, pharmacology, and clinical application. Four traditional identification methods and two new ones were reported. A total of 136 compounds were identified, among which 23 new terpenoids and two new flavonoids were discovered. The pharmacological effects of AAF mainly focus on anti-inflammatory, anti-tumor, antioxidant, antibacterial, and other aspects. Clinically, it is mainly used in respiratory, immune, digestive, and nervous systems in addition to gynecology. The current research mainly focuses on the composition and pharmacology of AAF. Future studies should thoroughly establish the quality criteria and pharmacokinetics of AAF. According to the different application fields, the corresponding quality standards should be formulated to ensure the efficacy of drugs in the actual treatment.

Sleep quality during pregnancy and fetal growth: A prospective cohort study.

The aim of this study is to investigate the association between sleep quality during pregnancy and fetal growth. Pregnant women and their fetuses at 16-20 gestational weeks in Nantong Maternal and Child Health Hospital were recruited. Women were classified as having "good sleep quality" (Pittsburgh Sleep Quality Index score ≤ 5) and "poor sleep quality" (Pittsburgh Sleep Quality Index score > 5) according to the Pittsburgh Sleep Quality Index scores. The fetal growth was evaluated by three ultrasonographic examinations, birth weight and birth length. We used general linear model and multiple linear regression models to estimate the associations. A total of 386 pairs of mother and infant were included in the data analysis. After adjusting for gestational weight gain, anxiety and depression, fetuses in the good sleep quality group had greater abdominal circumference (p = 0.039 for 28-31+6 weeks gestation, p = 0.012 for 37-40+6 weeks gestation) and femur length (p = 0.014 for 28-31+6 weeks gestation, p = 0.041for 37-40+6 weeks gestation) at 28-31+6 weeks gestation and 37-40+6 weeks gestation, and increased femur length (p = 0.007) at 28-31+6 weeks gestation. Birth weights (p = 0.018) were positively associated with sleep quality. Poor sleep quality was associated with poor intrauterine physical development, decreased abdominal circumference and femur length, and lower birth weight after adjusting for confounding factors. Attention to the fetal growth of pregnant women with poor sleep quality has the potential to decrease the risk of adverse fetal outcomes.

Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy.

BACKGROUND: Renal allograft interstitial fibrosis/tubular atrophy (IF/TA) constitutes the principal histopathological characteristic of chronic allograft dysfunction (CAD) in kidney-transplanted patients. While renal vascular endothelial-mesenchymal transition (EndMT) has been verified as an important contributing factor to IF/TA in CAD patients, its underlying mechanisms remain obscure. Through single-cell transcriptomic analysis, we identified Rictor as a potential pivotal mediator for EndMT. This investigation sought to elucidate the role of Rictor/mTORC2 signalling in the pathogenesis of renal allograft interstitial fibrosis and the associated mechanisms. METHODS: The influence of the Rictor/mTOR2 pathway on renal vascular EndMT and renal allograft fibrosis was investigated by cell experiments and Rictor depletion in renal allogeneic transplantation mice models. Subsequently, a series of assays were conducted to explore the underlying mechanisms of the enhanced mitophagy and the ameliorated EndMT resulting from Rictor knockout. RESULTS: Our findings revealed a significant activation of the Rictor/mTORC2 signalling in CAD patients and allogeneic kidney transplanted mice. The suppression of Rictor/mTORC2 signalling alleviated TNFα-induced EndMT in HUVECs. Moreover, Rictor knockout in endothelial cells remarkably ameliorated renal vascular EndMT and allograft interstitial fibrosis in allogeneic kidney transplanted mice. Mechanistically, Rictor knockout resulted in an augmented BNIP3-mediated mitophagy in endothelial cells. Furthermore, Rictor/mTORC2 facilitated the MARCH5-mediated degradation of BNIP3 at the K130 site through K48-linked ubiquitination, thereby regulating mitophagy activity. Subsequent experiments also demonstrated that BNIP3 knockdown nearly reversed the enhanced mitophagy and mitigated EndMT and allograft interstitial fibrosis induced by Rictor knockout. CONCLUSIONS: Consequently, our study underscores Rictor/mTORC2 signalling as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis progression, exerting its impact through regulating BNIP3-mediated mitophagy. This insight unveils a potential therapeutic target for mitigating renal allograft interstitial fibrosis.

Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

Statin-Associated Liver Dysfunction and Muscle Injury: epidemiology, Mechanisms, and Management Strategies.

Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.

Enhancing the Solubility, Stability, and Bioavailability of Retinol Acetate through Mechanochemistry.

This study utilizes mechanochemistry to prepare retinol acetate (RA) solid dispersion (RA-sodium starch octenyl succinate (SSOS)), resulting in improved solubility, stability, and bioavailability compared with raw RA and commercial RA microcapsules. RA, poloxamer 188, SSOS, and milling beads (8 mm) were mixed in a ratio of 2:1:8:220 (w/w) and ball-milled at 100 rpm for 3 h. RA-SSOS exhibited a solubility of 1020.35 µL/mL and a 98.09% retention rate after aging at 30 °C. Rats fed with RA-SSOS showed an ∼30% increase in organ RA content. Characterization analysis attributed the solubility and stabilization of RA-SSOS to hydrogen bonding between RA and SSOS, along with an amorphous state. RA-SSOS offers significant advantages for the pharmaceutical and food industries, leveraging mechanochemistry to enhance solid dispersions for hydrophobic compounds and optimize drug delivery.

Association between short-term glucose fluctuations and cognition in patients with acute ischemic stroke complicated by type 2 diabetes mellitus.

OBJECTIVES: Glucose fluctuations are more harmful than persistent hyperglycemia for chronic complications of diabetes. However, the relationship between cognition and glucose fluctuations in patients with acute ischemic stroke (AIS) complicated by type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association between short-term glucose fluctuations and cognition in patients with AIS complicated by T2DM. DESIGN: A cohort study with a 2-year follow-up. SETTING AND PARTICIPANTS: We included 554 patients with mild AIS (mean age: 62 years; 170 females and 384 males). MEASUREMENTS: Glucose variability (GV) was evaluated using glycated hemoglobin (HbA1c), stress hyperglycemia (SHR), standard deviation of blood glucose (SDBG), mean postprandial blood glucose (MPBG), mean amplitude of glycemic excursion (MAGE), and time in range (TIR). We evaluated the relationship between GV, fasting blood glucose (FBG) and cognition during the acute phase using linear regression analysis. We evaluated the relationship between GV, FBG and the occurrence of post-stroke cognitive impairment (PSCI) using a logistic regression model. Mediation analyses were fitted to explore whether the relationships of HbA1c with cognition were mediated by cerebral small vessel disease (CSVD). RESULTS: A clear pattern of age-related GV was observed. Higher SHR in middle-aged participants; higher HbA1c, and lower TIR in older participants; and higher MAGE, MPBG, and SDBG across a broad age range (50-80 years) were associated with cognitive impairment in the acute phase of AIS. Higher SHR and SDBG together with lower TIR in middle-aged participants, higher HbA1c in older participants, and higher FBG, MPBG, and MAGE across a broad age range (50-80 years) were associated with the occurrence of PSCI. The association between HbA1c and cognition was partially mediated (proportion: 7-16%) by CSVD. CONCLUSIONS: Short-term glucose fluctuations are associated with cognition and a higher risk of PSCI in patients with AIS complicated by T2DM. CSVD might play an important role in the relationship between short-term glucose fluctuations and cognition.

Acetylation proteomics and metabolomics analyses reveal the involvement of starch synthase undergoing acetylation modification during UV-B stress resistance in Rhododendron Chrysanthum Pall.

BACKGROUND: Rhododendron chrysanthum Pall. (R. chrysanthum) is a plant that lives in high mountain with strong UV-B radiation, so R. chrysanthum possess resistance to UV-B radiation. The process of stress resistance in plants is closely related to metabolism. Lysine acetylation is an important post-translational modification, and this modification process is involved in a variety of biological processes, and affected the expression of enzymes in metabolic processes. However, little is known about acetylation proteomics during UV-B stress resistance in R. chrysanthum. RESULTS: In this study, R. chrysanthum OJIP curves indicated that UV-B stress damaged the receptor side of the PSII reaction center, with a decrease in photosynthesis, a decrease in sucrose content and an increase in starch content. A total of 807 differentially expressed proteins, 685 differentially acetylated proteins and 945 acetylation sites were identified by quantitative proteomic and acetylation modification histological analysis. According to COG and subcellular location analyses, DEPs with post-translational modification of proteins and carbohydrate metabolism had important roles in resistance to UV-B stress and DEPs were concentrated in chloroplasts. KEGG analyses showed that DEPs were enriched in starch and sucrose metabolic pathways. Analysis of acetylation modification histology showed that the enzymes in the starch and sucrose metabolic pathways underwent acetylation modification and the modification levels were up-regulated. Further analysis showed that only GBSS and SSGBSS changed to DEPs after undergoing acetylation modification. Metabolomics analyses showed that the metabolite content of starch and sucrose metabolism in R. chrysanthum under UV-B stress. CONCLUSIONS: Decreased photosynthesis in R. chrysanthum under UV-B stress, which in turn affects starch and sucrose metabolism. In starch synthesis, GBSS undergoes acetylation modification and the level is upregulated, promotes starch synthesis, making R. chrysanthum resistant to UV-B stress.

Molecular insights into the interactions of theaflavin and epicatechin with different lipid bilayer membranes by molecular dynamics simulation.

At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

Cell-Specific Impacts of Surface Coating Composition on Extracellular Vesicle Secretion.

Biomaterial properties have recently been shown to modulate extracellular vesicle (EV) secretion and cargo; however, the effects of substrate composition on EV production remain underexplored. This study investigates the impacts of surface coatings composed of collagen I (COLI), fibronectin (FN), and poly l-lysine (PLL) on EV secretion for applications in therapeutic EV production and to further understanding of how changes in the extracellular matrix microenvironment affect EVs. EV secretion from primary bone marrow-derived mesenchymal stromal cells (BMSCs), primary adipose-derived stem cells (ASCs), HEK293 cells, NIH3T3 cells, and RAW264.7 cells was characterized on the different coatings. Expression of EV biogenesis genes and cellular adhesion genes was also analyzed. COLI coatings significantly decreased EV secretion in RAW264.7 cells, with associated decreases in cell viability and changes in EV biogenesis-related and cell adhesion genes at day 4. FN coatings increased EV secretion in NIH3T3 cells, while PLL coatings increased EV secretion in ASCs. Surface coatings had significant effects on the capacity of EVs derived from RAW264.7 and NIH3T3 cells to impact in vitro macrophage proliferation. Overall, surface coatings had different cell-specific effects on EV secretion and in vitro functional capacity, thus highlighting the potential of substrate coatings to further the development of clinical EV production systems.

Characterization of the Apoptotic and Antimicrobial Activities of Two Initiator Caspases of Sea Cucumber Apostichopus japonicus.

Caspase (CASP) is a protease family that plays a vital role in apoptosis, development, and immune response. Herein, we reported the identification and characterization of two CASPs, AjCASPX1 and AjCASPX2, from the sea cucumber Apostichopus japonicus, an important aquaculture species. AjCASPX1/2 share similar domain organizations with the vertebrate initiator caspases CASP2/9, including the CARD domain and the p20/p10 subunits with conserved functional motifs. However, compared with human CASP2/9, AjCASPX1/2 possess unique structural features in the linker region between p20 and p10. AjCASPX1, but not AjCASPX2, induced marked apoptosis of human cells by activating CASP3/7. The recombinant proteins of AjCASPX2 and the CARD domain of AjCASPX2 were able to bind to a wide range of bacteria, as well as bacterial cell wall components, and inhibit bacterial growth. AjCASPX1, when expressed in Escherichia coli, was able to kill the host bacteria. Under normal conditions, AjCASPX1 and AjCASPX2 expressions were most abundant in sea cucumber muscle and coelomocytes, respectively. After bacterial infection, both AjCASPX1 and AjCASPX2 expressions were significantly upregulated in sea cucumber tissues and cells. Together, these results indicated that AjCASPX1 and AjCASPX2 were initiator caspases with antimicrobial activity and likely functioned in apoptosis and immune defense against pathogen infection.

Bacterial Lipopeptides Are Effective against Pear Fire Blight.

Fire blight, a devastating disease caused by Erwinia amylovora, poses a significant threat to pear and apple trees in Xinjiang province, China. In an effort to combat this pathogen, we isolated 10 bacteria from various components of apple and crabapple trees and conducted screenings to assess their ability to inhibit E. amylovora in vitro. Through biochemical tests and partial 16S rRNA gene sequencing, we identified two promising strains, Priestia megaterium strain H1 and Bacillus subtilis strain I2. These strains were then evaluated for their efficacy in biocontrol under controlled laboratory conditions, focusing on immature fruits and leaves. Remarkably, all selected antagonists exhibited the capability to reduce the severity of the disease on both fruit and leaves. P. megaterium strain H1 and B. subtilis strain I2 exhibited significant reductions in disease incidence on both immature fruits and leaves compared to the control. Specifically, on immature fruits, they achieved reductions of 53.39% and 44.76%, respectively, while on leaves, they demonstrated reductions of 59.55% and 55.53%, respectively. Furthermore, during the study, we detected the presence of lipopeptides, including surfactin, iturins, bacillomycin D, and fengycins, in the methanol extract obtained from these two antagonistic bacteria using thin-layer chromatography (TLC). Based on the results obtained, B. subtilis strain I2 and P. megaterium strain H1 exhibit considerable potential for controlling fire blight. However, further evaluation of their efficacy under natural field conditions is essential to validate their practicality as a biocontrol method.

Efficacy and safety of Ferrous iron on the prevention of Vascular cOgnitive impaiRment among patients with cerebral Infarction/TIA (FAVORITE): rationale and design of a multicentre randomised trial.

BACKGROUND: The incidence of vascular cognitive impairment (VCI) is high in patients suffering from ischaemic stroke or transient ischaemic attack (TIA) or with vascular risk factors. Effective prevention strategies for VCI remain limited. Anaemia or low haemoglobin was found as an independent risk factor for adverse outcomes after acute stroke. Anaemia or low haemoglobin was possibly associated with an increased risk of poststroke cognitive impairment. Whether supplement of ferrous iron to correct anaemia reduces the risk of VCI and improves adverse outcomes in patients with ischaemic cerebrovascular disease remains uncertain. AIM: We aim to introduce the design and rationale of the safety and efficacy of Ferrous iron on the prevention of Vascular cOgnitive impaiRment in patients with cerebral Infarction or TIA (FAVORITE) trial. DESIGN: FAVORITE is a randomised, placebo-controlled, double-blind, multicentre trial that compares supplement of ferrous iron with placebo for recent minor stroke/TIA patients complicated with mild anaemia or iron deficiency: Ferrous succinate sustained-release tablet 0.2 g (corresponding to 70 mg of elemental iron) once daily after or during breakfast for 12 weeks or placebo with much the same colour, smell and size as ferrous iron once daily during or after breakfast for 12 weeks. All paticipants will be followed within the next year. STUDY OUTCOMES: The primary effective outcome is the incidence of VCI at 3 months after randomisation and the primary safety outcome includes any gastrointestinal adverse event during 3 months. DISCUSSION: The FAVORITE trial will clarify whether supplement of ferrous iron to correct low haemoglobin reduces the risk of VCI in patients with recent ischaemic stroke or TIA complicated with mild anaemia or iron deficiency compared with placebo. TRIAL REGISTRATION NUMBER: NCT03891277.

Combination of UPLC-Q-TOF/MS and network pharmacology to reveal the mechanism of Chaihu-jia-Longgu-Muli decoction for treating vertigo with anxiety disorder.

Chaihu-jia-Longgu-Muli decoction (CLMD) has been proven clinically effective in treating vertigo with anxiety disorder. However, the mechanism is not clear. This study aimed to explore the mechanism of CLMD in treating vertigo with anxiety disorder based on ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology. UPLC-Q-TOF/MS was performed to identify the compounds in blood and the targets of compounds of CLMD in vertigo and anxiety were searched using databases. A protein-protein interaction network was built to screen the core targets. The core targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, the vertigo with anxiety rat model was used to verify the results. A total of 22 compounds were absorbed into the blood. Eighty-one potential targets associated with CLMD for vertigo with anxiety disorder were identified through network pharmacological analysis. Subsequently, GO and KEGG analysis showed that CLMD treatment for vertigo with anxiety disorder is associated with neurotransmitter levels and other pertinent physiological processes. The results of the animal experiments showed that CLMD decreased the levels of serotonin, norepinephrine and dopamine, alleviating the symptoms of vertigo and anxiety disorder in model rats. The study revealed CLMD could alleviate vertigo and anxiety symptoms through reducing the levels of neurotransmitters.