Early-life inflammation increases ethanol consumption in adolescent male mice.

Recent studies have demonstrated that stress during the critical windows of development can evoke a cascade of neurological changes that can result in neuropsychiatric disorders later in life. In this study, we examined the effect of early-life inflammation on ethanol consumption in adolescent mice. C57BL/6J mice were assigned to either the control or Lipopolysaccharide (LPS) group on postnatal day 14 (P14). In the latter group, LPS at a dose of 50 µg/kg was injected intraperitoneally. The mice were weaned at P21, and behavior tests were performed at P45. Ethanol consumption was assessed using a two-bottle choice drinking paradigm. Anxiety-like behaviors were assessed by marble burying test (MBT), open field (OF), and elevated plus maze (EPM). Ethanol-induced loss of righting reflex (LORR), hypothermia and ethanol metabolism were assessed to evaluate ethanol intoxication. P14 LPS-injected adolescent male mice exhibited significantly increased ethanol preference and consumption, with a similar taste preference for saccharin and avoidance of quinine. The adolescent male mice showed increased anxiety-like behaviors in the OF and EPM tests, and an increased duration of LORR, without affecting the hypothermic effects of ethanol and ethanol metabolism. Interestingly, these behavioral changes were not obvious in female mice. In conclusion, our data indicate that early-life inflammation may be a risk factor for ethanol consumption in adolescents with greater changes observed in male mice. SIGNIFICANCE STATEMENT: Our study is the first preclinical model to report the enhancement effect of early-life inflammation on ethanol consumption in adolescent male mice and our findings provide a valuable mouse model to examine the neurobiological mechanisms mediating the long-lasting effects of early-life inflammation on alcohol use disorders vulnerability.

Single-cell analysis defines highly specific leukemia-induced neutrophils and links MMP8 expression to recruitment of tumor associated neutrophils during FGFR1 driven leukemogenesis.

BACKGROUND: Leukemias driven by activated, chimeric FGFR1 kinases typically progress to AML which have poor prognosis. Mouse models of this syndrome allow detailed analysis of cellular and molecular changes occurring during leukemogenesis. We have used these models to determine the effects of leukemia development on the immune cell composition in the leukemia microenvironment during leukemia development and progression. METHODS: Single cell RNA sequencing (scRNA-Seq) was used to characterize leukemia associated neutrophils and define gene expression changes in these cells during leukemia progression. RESULTS: scRNA-Seq revealed six distinct subgroups of neutrophils based on their specific differential gene expression. In response to leukemia development, there is a dramatic increase in only two of the neutrophil subgroups. These two subgroups show specific gene expression signatures consistent with neutrophil precursors which give rise to immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Analysis of gene expression in these precursor cells identified pathways that were specifically upregulated, the most pronounced of which involved matrix metalloproteinases Mmp8 and Mmp9, during leukemia progression. Pharmacological inhibition of MMPs using Ilomastat preferentially restricted in vitro migration of neutrophils from leukemic mice and led to a significantly improved survival in vivo, accompanied by impaired PMN-MDSC recruitment. As a result, levels of T-cells were proportionally increased. In clinically annotated TCGA databases, MMP8 was shown to act as an independent indicator for poor prognosis and correlated with higher neutrophil infiltration and poor pan-cancer prognosis. CONCLUSION: We have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.

A Comparative Study of Prevalence and Associated Factors of Social Support Among Chinese Shidu Parents and Non-Shidu Parents.

The number of parents in China who have lost their only child, referred to as shidu parents, currently exceeds one million and is increasing by approximately 76,000 annually. Shidu parents face a unique challenge in long-term care, primarily stemming from the sudden and tragic loss of their only child, which leads to a substantial decrease in their social support network. A multi-stage, stratified, and cluster sampling method was employed across various economic belts. Linear regression analysis was utilized to examine factors associated with the social support status of shidu and non-shidu parents. The level of social support decreases as the severity of depression increases. Shidu parents with grandchildren tend to have good social support. The city of Hangzhou exhibits relatively high levels of social support. Married individuals typically report higher levels of social support. It is recommended to prioritize shidu parents without grandchildren as a primary focus for government and societal support. Key recommendations include strengthening social skills training and developing social support networks. Drive economic development, particularly in relatively underdeveloped regions. Strengthen social organizations and community development. Enhancing access to support services, leveraging technology, and encouraging volunteerism for non-married parents.

Optimizing Triage: Assessing Shock Index, Pediatric Age-Adjusted as an Adjunct to Improve Emergency Severity Index Mistriage.

OBJECTIVE: We investigated the diagnostic value of shock index, pediatric age-adjusted (SIPA) in predicting Emergency Severity Index level 3 patients' outcomes. Secondary objectives included exploring the impact of fever and participant variables on SIPA's predictive ability. METHODS: A retrospective chart review identified children aged 1 to 15 years triaged as a level 3 in the emergency department between January 2018 and December 2021. Shock index, pediatric age-adjusted thresholds based on age, 1 to 6 years (>1.2), 7 to 12 years (>1.0), and 13 to 17 years (>0.9), were used. We assessed elevated SIPA and SIPA corrected for fever to evaluate associations with outcomes and interventions. RESULTS: Our findings, involving 192 patients, revealed that elevated SIPA demonstrated enhanced discrimination relative to nonelevated SIPA. Patients with elevated SIPA had more average interventions: 1.14 versus 0.74, P < 0.016; average interventions using SIPA corrected for fever: 1.14 versus 0.77, P < 0.006; average interventions controlling for race and sex: 1.15 versus 0.71, P < 0.001; hospital admission: 64.4% versus 42.9%, P = 0.004; hospital length of stay (LOS): 3.06 days (SE, 0.42) versus 1.46 days (SE, 0.23); hospital LOS using SIPA corrected for fever: 2.75 days (SE, 0.44) versus 1.72 days (SE, 0.24); ventilatory support: 16.44% versus 3.36%, P < 0.002; fluid bolus: 28.77% versus 14.29%, P < 0.015; intravenous medications (antibiotics, antiepileptics, immune globulin, albumin): 45.21% versus 30.25%, P < 0.036. There was no difference between other interventions, pediatric intensive care admission, and LOS between the 2 groups. Importantly, SIPA was unaffected by fever, race, or sex. CONCLUSIONS: Shock index, pediatric age-adjusted identifies level 3 Emergency Severity Index pediatric patients more likely to require hospital admission, longer LOS, and a lifesaving intervention especially ventilatory support, intravenous fluids, or specific intravenous medications. Shock index, pediatric age-adjusted's predictive ability remained unaffected by fever, race, or sex, making it a valuable tool in preventing mistriage and justifying inclusion in the Emergency Severity Index danger zone vitals criteria for up-triage.

Synthesis of cobalt phosphide hybrid for simultaneous electrochemical detection of ascorbic acid, dopamine, and uric acid.

Ascorbic acid (AA), dopamine (DA), and uric acid (UA) are important biomarkers for the clinical screening of diseases. However, the simultaneous determination of these three analytes is still challenging. Herein, we report a facile metal-organic framework (MOF)-derived method to synthesize a cobalt phosphide (Co2P) hybrid for the simultaneous electrochemical detection of AA, DA and UA. The introduction of highly dispersed Co2P nanoparticles onto a P, N-doped porous carbon matrix is responsible for providing abundant active sites and facilitating electron transfer, thereby contributing to the improved electrocatalytic performance of the hybrid. Well-resolved oxidation peaks and an enhanced current response for the simultaneous oxidation of AA, DA, and UA were achieved using a Co2P hybrid-modified screen-printed electrode (Co2P hybrid-SPE) with the differential pulse voltammetry (DPV) method. The detection limits for AA, DA, and UA in simultaneous detection were calculated as 17.80 µM, 0.018 µM, and 0.068 µM (S/N = 3), respectively. Furthermore, the feasibility of using Co2P hybrid-SPE for the simultaneous detection of AA, DA, and UA in real serum samples was also confirmed.

Allelochemicals of Alexandrium tamarense and its algicidal mechanism for Prorocentrum donghaiense and Heterosigma akashiwo.

The effects of culture filtrate of Alexandrium tamarense on Prorocentrum donghaiense and Heterosigma akashiwo were investigated, including determination of algal density, photosynthesis, intracellular enzyme content and activity. The filtrate of A. tamarense had a stronger inhibitory effect on P. donghaiense than H. akashiwo, and the inhibitory effect decreased with higher temperature treatment of the filtrate. Instantaneous fluorescence (Ft) and maximum quantum yield of photosystem II (Fv/Fm) values of both kinds of target algae were reduced as exposed to the filtrate of A. tamarense, which proved that allelopathy could inhibit the normal operation of photosynthetic system. The increase of Malondialdehyde (MDA) content of the two kinds of target algae indicated that the cell membrane was seriously damaged by allelochemicals released by A. tamarense. The different responses of Superoxide Dismutase (SOD) and Catalase (CAT) activity in two kinds of target algae demonstrated the complexity and diversity of allelopathic mechanism. The filtrate of A. tamarense also influenced the metabolic function (ATPases) of P. donghaiense and H. akashiwo, and the influence on P. donghaiense was greater. Liquid-liquid extraction was used to extract and isolate allelochemicals from the filtrate of A. tamarense. It was found that only component I with molecular weight of 424.2573 and 434.2857 could inhibit the growth of P. donghaiense by HPLC-MS.

Bta-miR-365-3p-targeted FKBP5 participates in the AMPK/mTOR signaling pathway in the regulation of preadipocyte differentiation in cattle.

Objective: MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods: We identified bta-miR-365-3p, which specifically targets the 3'untranslated region (3'UTR) of the FK506-binding protein 5 (FKBP5),and verified its mechanisms for regulating expression and involvement in adipogenesis. Results: In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-365-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by qRT-PCR and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. AMPK/mTOR signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion: In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Antimicrobial resistance profiles of common mastitis pathogens on large Chinese dairy farms.

The primary objective of this study was to determine the antimicrobial resistance (AMR) profile of common mastitis pathogens on large Chinese dairy farms. A total of 673 isolates, including Staphylococcus aureus (14.41%, 97/673), coagulase-negative staphylococci (CNS, 52.30%, 352/673), Streptococcus agalactiae (5.64%, 38/673), non-agalactiae streptococci (7.42%, 50/673), Acinetobacter spp. (7.72%, 52/673), Escherichia spp. (6.39%, 43/673), and Klebsiella spp. (6.09%, 41/673), were collected from 15 large Chinese dairy farms in 12 provinces. The AMR profiles were measured using a microdilution method. Our results showed that more than 75% of Staph. aureus (87/97) and CNS (291/352) were resistant to penicillin (PEN). More than 30% of Escherichia spp. (15/43) showed resistance to ampicillin (AMP). However, less than 10% CNS and non-agalactiae streptococci showed resistance to amoxicillin/clavulanate (AMC; 1/352; 0/50), cephalexin (LEX; 1/352; 0/50), ceftiofur (EFT; 10/352; 0/50), and rifaximin (RIX; 21/352; 2/50); less than 10% Staph. aureus showed resistance to AMC (1/97), oxacillin (OX; 3/97), LEX (1/97), EFT (2/97), and RIX (2/97); less than 10% Strep. agalactiae showed resistance to PEN (3/38), AMC (0/38), LEX (0/38), EFT (0/38), and RIX (0/38); and less than 10% Escherichia spp. showed resistance to AMC (1/43) and EFT (4/43). These results suggested that most mastitis pathogens were susceptible to most antimicrobials with exceptions of Staph. aureus tested against penicillin or ampicillin and CNS against penicillin or oxacillin. To control the AMR threat in Chinese dairy farms, a nationwide surveillance program for AMR of bovine mastitis pathogens is needed.

Overexpression of YTHDF3 increases the specific productivity of the recombinant protein in CHO cells by promoting the translation process.

Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host cells for the production of recombinant therapeutic proteins in the biomedical field. Previous studies have shown that the m6A reader YTHDF3, which contains the YTH domain, can affect a variety of biological processes by regulating the translation and stability of target mRNAs. This study investigates the effect of YTHDF3 on transgenic CHO cells. The results indicate that stable overexpression of YTHDF3 significantly enhances recombinant protein expression without affecting host cell growth. Transcriptome sequencing indicated that several genes, including translation initiation factor, translation extension factor, and ribosome assembly factor, were upregulated in CHO cells overexpressing YTHDF3. In addition, cycloheximide experiments confirmed that YTHDF3 enhanced transgene expression by promoting translation in CHO cells. In conclusion, the findings in this study provide a novel approach for mammalian cell engineering to increase protein productivity by regulating m6A.

Omics-based approaches for discovering active ingredients and regulating gut microbiota of Actinidia arguta exosome-like nanoparticles.

Exosome-like nanoparticles (ELNs) are novel naturally occurring plant ultrastructures and contain unique bioactive components. However, the potential applications and biological functions of plant ELNs, especially in the context of health promotion and disease prevention, remain largely unexplored. This study aimed to explore the biological activities and functional mechanisms of Actinidia arguta-derived exosome-like nanoparticles (AAELNs). We reported the development of AAELNs, which possess particle sizes of 157.8 nm and a negative surface charge of -23.07 mV, uptaking by RAW264.7 cells, and reduction of oxidative stress by decreasing the activity of GSH-Px and T-SOD and increasing the content of MDA. Through the use of high-throughput sequencing technology, 12 known miRNA families and 23 additional miRNAs were identified in AAELNs, GO and KEGG term enrichment analysis revealed the potential of AAELNs-miRNAs in modulating neural-relevant behaviors. Additionally, LC-MS/MS analysis detected a total of 32 major lipid classes, 430 lipid subclasses, and 1345 proteins in AAELNs. Furthermore, in vivo fluorescence disappearance and in vitro fermentation experiments demonstrated that AAELNs were able to enter the colon and improve the microbial structure. These findings suggest that AAELNs could serve as nanoshuttles in food, potentially offering health-enhancing properties.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Exploring local and global stability of COVID-19 through numerical schemes.

Respiratory sensitivity and pneumonia are possible outcomes of the coronavirus (COVID-19). Surface characteristics like temperature and sunshine affect how long the virus survives. This research article analyzes COVID-19 mathematical model behavior based on symptomatic and non-symptomatic individuals. In the reproductive model, the best result indicates the intensity of the epidemic. Our model remained stable at a certain point under controlled conditions after we evaluated a specific element. This approach is in place of traditional approaches such as Euler's and Runge-Kutta's. An unusual numerical approach known as the non-standard finite difference (NSFD) scheme is used in this article. This numerical approach gives us positivity. A dependable numerical analysis allowed us to evaluate different approaches and verify our theoretical results. Unlike the widely used Euler and RK4 approaches, we investigated the benefits of implementing NSFD schemes. By numerically simulating COVID-19 in a variety of scenarios, we demonstrated how our theoretical concepts work. The simulation findings support the usefulness of both approaches.

A Novel Nomogram for Predicting Early Rebleeding After Endoscopic Treatment of Esophagogastric Variceal Hemorrhage.

BACKGROUND: Early rebleeding is a significant complication of endoscopic treatment for esophagogastric variceal hemorrhage (EGVH). However, a reliable predictive model is currently lacking. AIMS: To identify risk factors for rebleeding within 6 weeks and establish a nomogram for predicting early rebleeding after endoscopic treatment of EVGH. METHODS: Demographic information, comorbidities, preoperative evaluation, endoscopic features, and laboratory tests were collected from 119 patients who were first endoscopic treatment for EGVH. Independent risk factors for early rebleeding were determined through least absolute shrinkage and selection operator logistic regression. The discrimination, calibration, and clinical utility of the nomogram were assessed and compared with the model for end-stage liver disease (MELD), Child-Pugh, and albumin-bilirubin (ALBI) scores using receiver-operating characteristic (ROC) curves, calibration plots, and decision curve analyses (DCA). RESULTS: Early rebleeding occurred in 39 patients (32.8%) within 6 weeks after endoscopic treatment. Independent early rebleeding factors included gastric variceal hemorrhage (GVH), concomitant hepatocellular carcinoma (HCC), international normalized ratio (INR), and creatinine. The nomogram demonstrated exceptional calibration and discrimination capability. The area under the curve for the nomogram was 0.758 (95% CI 0.668-0.848), and it was validated at 0.71 through cross-validation and bootstrapping validation. The DCA and ROC curves demonstrated that the nomogram outperformed the MELD, Child-Pugh, and ALBI scores. CONCLUSIONS: Compared with existing prediction scores, the nomogram demonstrated superior discrimination, calibration, and clinical applicability for predicting rebleeding in patients with EGVH after endoscopic treatment. Therefore, it may assist clinicians in the early implementation of aggressive treatment and follow-up.

Earthquake supercycles and fault interaction over the past 32 ka in the Lake Ebinur area, Xinjiang, China.

Earthquake prediction and disaster assessment in tectonically active regions require a continuous and complete regional seismic archive, which is commonly difficult to obtain, especially for prehistoric records. Here, high-resolution analysis of the sedimentary sequence from Lake Ebinur in Xinjiang revealed a detailed history of environment evolution since 32 ka ago. Both the Cl content and ultrafine proportion revealed the changing climate: the climate was relatively dry with low lake-water volumes from 32 to 12 ka, while the climate became warmer and wetter since 12 ka. In addition, eight earthquakes were identified by comprehensive analysis of grain size and geochemical element proxies, showing more than two seismic supercycles, with gaps of ∼10.4 ka; these gaps are much larger than those inferred previously (∼4-7 ka). Notably, these seismic events exhibited a pattern of mutual transmittance between the BoA and Jinghenan faults. Such fault interaction can occur in the Lake Ebinur area because it is dominated by weak lithosphere in which strain is easily accumulated and released; the interaction can also be attributed to the unique spatial distribution and immature nature of both faults. Combined with trenching investigations, our high-resolution analysis of lacustrine sediments can reveal a complete history of tectonic activity, which can efficiently serve regional earthquake prediction and disaster assessment.

Engineering Matrix-Free Drug Protein Nanoparticles with Promising Penetration through Biobarriers for Treating Corneal Neovascularization.

Protein drugs have been widely used in treating various clinical diseases because of their high specificity, fewer side effects, and favorable therapeutic effect, but they greatly suffer from their weak permeability through tissue barriers, high sensitivity to microenvironments, degradation by proteases, and rapid clearance by the immune system. Herein, we disrupted the standard protocol where protein drugs must be delivered as the cargo via a delivery system and innovatively developed a free entrapping matrix strategy by simply mixing bevacizumab (Beva) with zinc ions to generate Beva-NPs (Beva-Zn2+), where Beva is coordinatively cross-linked by zinc ions with a loading efficiency as high as 99.2% ± 0.41%. This strategy was universal to generating various protein NPs, with different metal ions (Cu2+, Fe3+, Mg2+, Sr2+). The synthetic conditions of Beva-NPs were optimized, and the generated mechanism was investigated in detail. The entrapment, releasing profile, and the bioactivities of released Beva were thoroughly studied. By using in situ doping of the fourth-generation polyamindoamine dendrimer (G4), the Beva-G4-NPs exhibited extended ocular retention and penetration through biobarriers in the anterior segment through transcellular and paracellular pathways, effectively inhibiting corneal neovascularization (CNV) from 91.6 ± 2.03% to 13.5 ± 1.87% in a rat model of CNV. This study contributes to engineering of protein NPs by using a facile strategy for overcoming the weaknesses of protein drugs and protein NPs, such as weak tissue barrier permeability, low encapsulation efficiency, poor loading capacity, and susceptibility to inactivation.

Sporisorium reilianum polysaccharides improve DSS-induced ulcerative colitis by regulating intestinal barrier function and metabolites.

This study investigated the regulatory effects of Sporisorium reilianum polysaccharides (SRPS) on metabolism and the intestinal barrier in mice with colitis induced by dextran sulfate sodium (DSS). SRPS were resistant to the digestion of saliva, gastric juices, and intestinal fluid. SRPS significantly reduced the disease activity index and inhibited DSS-induced colon shortening. The expression of proinflammatory cytokines in the colon was normal (P < 0.05). Acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid contents increased. Moreover, 64 biomarker metabolites were affected, including 42 abnormal decreases and 22 abnormal increases caused by DSS, which targeted amino acid biosynthesis; tryptophan metabolism; protein digestion and absorption; aminoacyl-tRNA biosynthesis; and glycine, serine, and threonine metabolism. In addition, SRPS reduced goblet cell loss and increased mucin secretion. The short-chain fatty acid receptor GPR41 was activated, and zonula occludens-1 and occludin expression levels were upregulated. Epithelial cell apoptosis was inhibited by increased Bcl-2 and decreased Bax expression NLRP3, ASC, and caspase-1 protein levels decreased. Intestinal barrier damage improved, and colon inflammation was reduced. Thus, our preliminary findings reveal that SRPS regulates metabolism and has the potential to protect the intestinal barrier in ulcerative colitis mice.

Association of Calcium and Vitamin D Supplements with Fractures in Persons with a Traumatic SCI.

Background: Osteoporotic fractures occur in almost half of patients with a spinal cord injury (SCI) and are associated with significant morbidity and excess mortality. Paralyzed Veterans Administration (PVA) guidelines suggest that adequate calcium and vitamin D intake is important for skeletal health, however, the association of these supplements with osteoporotic fracture risk is unclear. Objectives: To determine the association of filled prescriptions for calcium and vitamin D with fracture risk in Veterans with an SCI. Methods: The 5897 persons with a traumatic SCI of at least 2 years' duration (96% male; 4% female) included in the VSSC SCI/D Registry in FY2014 were followed from FY2014 to FY2020 for incident upper and lower extremity fractures. Filled daily prescriptions for calcium or vitamin D supplements for ≥6 months with an adherence ≥80% were examined. Results: Filled prescriptions for calcium (hazard ratio [HR] 0.65; 95% CI, 0.54-0.78) and vitamin D (HR 0.33; 95% CI, 0.29-0.38) supplements were associated with a significantly decreased risk for incident fractures. Conclusion: Calcium and vitamin D supplements are associated with decreased risk of fracture, supporting PVA guidelines that calcium and vitamin D intake are important for skeletal health in persons with an SCI.

Individualized anti-thrombotic therapy for acute myocardial infarction complicated with left ventricular thrombus: A case report.

BACKGROUND: Presently, there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). While vitamin K antagonists are the preferred choice for oral blood thinning, determining the best course of blood-thinning medication remains challenging. It is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating LVT. This study significantly contributes to the medical community. CASE SUMMARY: The blood-thinning treatment of a patient with AMI and LVT was analyzed. Triple blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g, daily clopidogrel hydrogen sulfate at 75 mg, and dabigatran etexilate at 110 mg twice daily. After 15 d, the patient's LVT did not decrease but instead increased. Clinical pharmacists comprehensively analyzed the cases from the perspective of the patient's disease status and drug interaction. The drug regimen was reformulated for the patient, replacing dabigatran etexilate with warfarin, and was administered for six months. The clinical pharmacist provided the patient with professional and standardized pharmaceutical services. The patient's condition was discharged after meeting the international normalized ratio value (2-3) criteria. The patient fully complied with the follow-up, and the time in the therapeutic range was 78.57%, with no serious adverse effects during pharmaceutical monitoring. CONCLUSION: Warfarin proves to be an effective drug for patients with AMI complicated by LVT, and its blood-thinning course lasts for six months.

Distribution of rhizosphere fungi of Kobresia humilis on the Qinghai-Tibet Plateau.

Kobresia humilis is a major species in the alpine meadow communities of the Qinghai-Tibet Plateau (QTP); it plays a crucial role in maintaining the ecological balance of these meadows. Nevertheless, little is known about the rhizosphere fungi associated with K. humilis on the Qinghai Tibet Plateau. In this study, we used Illumina Miseq to investigate the fungal diversity, community structure, and ecological types in the root and rhizosphere soil of K. humilis across eight areas on the QTP and analyzed the correlation between rhizosphere fungi of K. humilis and environmental factors. A total of 19,423 and 25,101 operational taxonomic units (OTUs) were obtained from the roots and rhizosphere soil of K. humilis. These were classified into seven phyla, 25 classes, 68 orders, 138 families, and 316 genera in the roots, and nine phyla, 31 classes, 76 orders, 152 families, and 407 genera in the rhizosphere soil. There were 435 and 415 core OTUs identified in root and rhizosphere soil, respectively, which were categorized into 68 and 59 genera, respectively, with 25 shared genera. Among them, the genera with a relative abundance >1% included Mortierella, Microscypha, Floccularia, Cistella, Gibberella, and Pilidium. Compared with the rhizosphere soil, the roots showed five differing fungal community characteristics, as well as differences in ecological type, and in the main influencing environmental factors. First, the diversity, abundance, and total number of OTUs in the rhizosphere soil of K. humilis were higher than for the endophytic fungi in the roots by 11.85%, 9.85%, and 22.62%, respectively. The composition and diversity of fungal communities also differed between the eight areas. Second, although saprotroph-symbiotrophs were the main ecological types in both roots and rhizosphere soil; there were 62.62% fewer pathotrophs in roots compared to the rhizosphere soil. Thirdly, at the higher altitude sites (3,900-4,410 m), the proportion of pathotroph fungi in K. humilis was found to be lower than at the lower altitude sites (3,200-3,690 m). Fourthly, metacommunity-scale network analysis showed that during the long-term evolutionary process, ZK (EICZK = 1) and HY (EICHY = 1) were critical sites for development of the fungal community structure in the roots and rhizosphere soil of K. humilis, respectively. Fifthly, canonical correspondence analysis (CCA) showed that key driving factors in relation to the fungal community were longitude (R2 = 0.5410) for the root community and pH (R2 = 0.5226) for the rhizosphere soil community. In summary, these results show that K. humilis fungal communities are significantly different in the root and rhizosphere soil and at the eight areas investigated, indicating that roots select for specific microorganisms in the soil. This is the first time that the fungal distribution of K. humilis on the QTP in relation to long-term evolutionary processes has been investigated. These findings are critical for determining the effects of environmental variables on K. humilis fungal communities and could be valuable when developing guidance for ecological restoration and sustainable utilization of the biological resources of the QTP.

Characterization of Two Gonadal Genes, zar1 and wt1b, in Hermaphroditic Fish Asian Seabass (Lates calcarifer).

Zygote arrest-1 (Zar1) and Wilms' tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, Lczar1 and Lcwt1b were identified in Asian seabass (Lates calcarifer), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of Lczar1 were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of Lcwt1b cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family. RT-qPCR analysis showed that Lczar1 mRNA was exclusively expressed in the ovary, while Lcwt1b mRNA was majorly expressed in the gonads in a higher amount in the testis than in the ovary. In situ hybridization results showed that Lczar1 mRNA was mainly concentrated in oogonia and oocytes at early stages in the ovary, but were undetectable in the testis. Lcwt1b mRNA was localized not only in gonadal somatic cells (the testis and ovary), but also in female and male germ cells in the early developmental stages, such as those of previtellogenic oocytes, spermatogonia, spermatocytes and spermatids. These results indicated that Lczar1 and Lcwt1b possibly play roles in gonadal development. Therefore, the findings of this study will provide a basis for clarifying the mechanism of Lczar1 and Lcwt1b in regulating germ cell development and the sex reversal of Asian seabass and even other hermaphroditic species.