bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tilianin suppresses NLRP3 inflammasome activation in myocardial ischemia/reperfusion injury via inhibition of TLR4/NF-κB and NEK7/NLRP3
Authors: Yin Suyue , Han Kaixi , Wu Di , Wang Zihan , Zheng Ruifang , Fang Lianhua , Wang Shoubao , Xing Jianguo , Du Guanhua 
Published: October 2024

Tilianin, a flavonoid compound derived from Dracocephalum moldavica L., is recognized for its diverse biological functionalities, in particular alleviating myocardial ischemia-reperfusion injury (MIRI). There is ample evidence suggesting that the NLRP3 inflammasome has a significant impact on the development of MIRI. In this study, rats undergoing the ligation and subsequent release of the left anterior descending (LAD) coronary artery and H9c2 cardiomyocytes subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate the effects of tilianin on NLRP3 inflammasome and its anti-MIRI mechanisms. Upon reperfusion, the rats were intraperitoneally injected with tilianin at doses of 3, 10, 30 mg/kg. H9c2 cells were treated with tilianin at concentrations of 10, 30, and 50 μg/mL. Echocardiography, TTC staining and TUNEL staining demonstrated that tilianin remarkably improved cardiac function and mitigated myocardial damage in MIRI rats. Additionally, notable inflammatory response reduction by tilianin was evidenced by subsequent hematatoxylin-eosin (HE) staining, inflammatory cytokines assay, and quantitative proteomics. Further western blotting analysis and immunofluorescence staining showed tilianin decreased the levels of TLR4, p-NF-κB, NLRP3, and ASC in MIRI rats and H9c2 cells exposed to OGD/R, alongside a significant reduction in cleaved gasdermin D, mature IL-1β and IL-18. Molecular docking, cellular thermal shift assay (CETSA) and co-immunoprecipitation (co-IP) assay revealed that tilianin impeded the interaction between NLRP3 and NEK7. Taken together, tilianin protects cardiomyocytes from MIRI by suppressing NLRP3 inflammasome through the inhibition of the TLR4/NF-κB signaling pathway and the disruption of the NEK7/NLRP3 interface. These findings underscore the potential of tilianin as a promising therapeutic candidate for MIRI.
CDKN1A as a target of senescence in heart failure: insights from a multiomics study
Authors: Bian Rutao , Zhang Li , Li Dongyu , Xu Xuegong 
Published: October 2024

BackgroundCardiomyocyte senescence plays a crucial role as a pathological mechanism in heart failure (HF). However, the exact triggering factors and underlying causes of HF onset and progression are still not fully understood.ObjectivesBy integrating multi-omics data, this study aimed to determine the genetic associations between cardiomyocyte and HF using cell senescence-related genes (SRGs).MethodsThe study utilized the CellAge database and the SenMayo dataset, combined with high-resolution single-cell RNA sequencing (scRNA-seq) data, to identify SRG and examine differences in cardiac cell expression. To explore the causal relationship with HF using Mendelian Randomization (MR). Genetic variations influencing gene expression, DNA methylation, and protein expression (cis-eQTL, cis-mQTL, and cis-pQTL) were analyzed using the two-sample MR (TSMR) and summary-data-based MR (SMR). Additionally, Bayesian colocalization analysis, germline genetic variation, and bulk RNA data were employed to strengthen the reliability of the results. The application potential of therapeutic targets is ultimately assessed by evaluating their druggability.ResultsThe expression of 39 SRGs in cardiomyocytes was identified. In the discovery set revealed that CDKN1A (OR = 1.09, 95% confidence interval (CI) 1.02–1.15, FDR = 0.048) could be causally related to HF, and the results are also replicated in the validation set (OR = 1.20, 95% confidence interval (CI) 1.10–1.30, FDR &lt;0.0001). Based on the SMR method, CDKN1A was confirmed as a candidate pathogenic gene for HF, and its methylation (cg03714916, cg08179530) was associated with HF risk loci. The result is validated by Bayesian colocalization analysis, genetic variations, and bulk RNA data. The druggability analysis identified two potential therapeutic drugs.ConclusionBased on multi-omics data, this study uncovered the reciprocal regulation of cardiomyocyte senescence through CDKN1A, providing potential targets for HF drug development.
Effect of fermentation on the constituents in the branches and leaves of Taxus media and non-small cell lung cancer
Authors: Guo Xing , Wang Rui-Sheng , Zhang Zhen-Ling , Zhang Hong-Wei , Wang Sheng-Chao , Zhang Shuai , Wu Ya-Ning , Li Ya-Jing , Yuan Jun 
Published: October 2024

IntroductionNon-small cell lung cancer (NSCLC) is a prominent lung cancer disease worldwide. Currently, commonly used methods, such as surgery and radiotherapy, have significant side effects. Traditional Chinese medicine (TCM) has become a research hotspot because of its safe and effective characteristics. The branches and leaves of Taxus media are abundant in antitumor active compounds, and there has been no research conducted as yet regarding its anti–lung cancer molecular mechanism.ObjectiveThe aim of this study is to investigate the antitumor activity of two samples before and after fermentation of T. media, and to research the molecular mechanism of its inhibitory effect on NSCLC.MethodsThe chemical composition of pre-fermentation T. media (TM) and post-fermentation T. media qu (TMQ) were investigated using UHPLC-Q-Qrbitrap HRMS and high-performance liquid chromatography (HPLC). The anti-lung cancer activities of TM and TMQ were compared using an A549-induced tumor mouse model. An enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&amp;E) staining, immunohistochemistry, and immunofluorescence were used to determine the of TMQ mechanism of action.ResultsThe results indicated that TM and TMQ contained 83 compounds, consisting primarily of flavonoids, organic acids, and taxanes. Both taxanes and flavonoids in TMQ were higher than that in TM. Both TM and TMQ effectively inhibited the tumor growth in non-small cell lung cancer (NSCLC), and the inhibition rate was greater in TMQ (57.24%) than in TM (49.62%). TMQ administration downregulated the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the glutathione (GSH) level and upregulated interferon-γ (IFN-γ), reactive oxygen species (ROS), and malondialdehyde (MDA) levels in the serum of tumor mice. TMQ treatment also increased the protein expression of Bax, Caspase-3, and Beclin-1 in tumor tissues. In contrast, the bcl-2, PI3K, Ki67, ULK1, and mTOR protein levels were suppressed by TMQ. Protein assay analyses reemphasized the superior antitumor effect of TMQ over TM. These cumulative findings demonstrated that the mechanism of action of TMQ was closely related to the activation of transcriptional misregulation in the cancer pathway that inhibited the cholinergic synaptic, AMPK, and PI3K/Akt/mTOR signaling pathways.ConclusionThis study demonstrated that fermentation increased the active ingredient contents and antitumor effects of T. media. In addition, post-fermentation TMQ was superior to TM as a herbal medicine for NSCLC treatment.
Trends and predictions of maternal sepsis and other maternal infections among women of childbearing age: a systematic analysis for the global burden of disease study 2019
Authors: Qian Hang , Shang Weifeng , Zhang Sheng , Pan Xiaojun , Huang Sisi , Li Hui , Wen Zhenliang , Liu Jiao , Chen Dechang 
Published: October 2024

BackgroundMaternal sepsis and other maternal infections (MSMIs) are major public health concerns worldwide. However, comprehensive data on their global burden and evolving trends remain sparse. This study aims to explore the epidemiological trends of MSMIs in women of childbearing age (WCBA) from 1990 to 2019, investigate the relationship between disease burden and age, period, and birth cohorts, and then provide a prediction of MSMIs incidence and deaths.MethodsThe estimates and 95% uncertainty intervals (UIs) for the incidence and death number of MSMIs in seven age groups (15–19, 20–24, 25–29, 30–34, 35–39, 40–44, 45–49 years) were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The age-standardized incidence and mortality rates of MSMIs in WCBA were estimated utilizing the age standardization by direct method. Joinpoint regression analysis was employed to investigate the changing trends of age-standardized incidence and mortality rates from 1990 to 2019. Age-period-cohort analysis was utilized to estimate the independent effects of age, period, and birth cohorts. Furthermore, a Nordpred age-period-cohort analysis was implemented to predict the global epidemiological trends through 2044.ResultsIn 2019, the estimated global age-standardized incidence and mortality rates of MSMIs in WCBA were 1072.90 (95% UI: 725.93 to 1483.46) and 0.86 (95% UI: 0.69 to 1.05), respectively. The highest disease burden existed in the African Region. From 1990 to 2019, the estimated global age-standardized incidence and mortality rates of MSMIs (AAPC: -1.32, 95% CI: −1.34 to −1.30; AAPC: -3.39, 95% CI: −4.28 to −2.48) in WCBA both demonstrated significant declining trends. The changing trends varied significantly across 6 regions and 204 countries. The effects of age, period, and cohort on incidence and mortality rates differed. From 2020 to 2044, the global age-standardized incidence rate of MSMIs in WCBA was predicted to decrease whereas the case number increases slowly.ConclusionThe global trends in MSMIs incidence and mortality generally showed a decline with considerable heterogeneity, indicating both the effectiveness and unevenness of global management of MSMIs. Moreover, the predicted increased case number highlights prominent challenges in the control of MSMIs.
Child and adolescent sleep disturbances and psychopathology in a mental health clinic sample
Authors: Blacher Aviva , McKenzie Katarina N. A. , Stewart Shannon L. , Reid Graham J. 
Published: October 2024

IntroductionChildren and adolescents treated in specialty mental health services are more likely to have sleep disturbances than those without mental health problems. Few studies have investigated the relationship between sleep and psychopathology in broad clinical samples of children. We examined the relationship between sleep disturbance and age on internalizing and externalizing psychopathology in a sample who sought treatment at children's mental health centers.MethodsSecondary data analyses were completed on a sample of children (N = 13,472; aged 4 to 18; 55% male) from 39 children's mental health agencies in Ontario, Canada, who completed a semi-structured assessment, the interRAI Children and Youth Mental Health (ChYMH). A split-half sample approach was utilized (S1 n = 6,773, S2 n = 6,699). Hierarchical regressions examined the effects of sleep disturbances (i.e., difficulty falling asleep, staying asleep, night waking, bedtime resistance, falling asleep during the day) on internalizing and externalizing symptoms, above and beyond established child- (i.e., age, sex, sensory sensitivity, pain) and family-level variables (family functioning, caregiver distress, parenting strengths). Age was tested as a moderator for sleep disturbances on both outcome variables.ResultsOverall, 6.7% of children had clinically significant sleep disturbance scores (≥10 out of 16) on the interRAI ChYMH. In both samples, sleep disturbances predicted internalizing (S1 ΔR2 = 10%, S2 ΔR2 = 10%) and externalizing symptoms (S1 ΔR2 = 2%, S2 ΔR2 = 1%), above and beyond child and family variables. Age moderated the relationship between sleep disturbances and internalizing symptoms (S1 ß = 0.07; S2 ß = 0.07; ΔR2 = 0.004 in both samples), but not externalizing symptoms; sleep disturbance was more strongly related to internalizing symptoms amongst adolescents (ß = 0.98) than children (ß = 0.62).DiscussionThe relationship between sleep and internalizing symptoms appears to change as children move through development. Further, sleep was a stronger predictor of internalizing problems in adolescents than children, suggesting an additional focus of clinician efforts in this age group. These findings strengthen the importance of routine assessment of sleep, as is done with the interRAI ChYMH.
Herd-Level Risk Factors Associated with Mycoplasma bovis Serostatus in Youngstock on Irish Dairy Farms
Authors: McCarthy Marie-Claire , O’Grady Luke , McAloon Conor G. , Mee John F. 
Published: October 2024

Mycoplasma bovis is a globally significant pathogen of cattle associated with a wide range of clinical syndromes, including respiratory disease, mastitis, arthritis, otitis, and reproductive failure. Since its detection in Ireland in 1994, M. bovis has become a significant contributor to morbidity and mortality in Irish cattle. This study aimed to investigate herd-level risk factors associated with M. bovis seropositivity in replacement dairy heifers, using data from 105 Irish dairy herds. Ten heifers per herd were sampled on three occasions: spring 2018, spring 2019, and autumn 2019. Seropositivity was evaluated using two thresholds: ≥1 positive heifer (Model ≥ 1POS) and ≥3 positive heifers (Model ≥ 3POS). M. bovis seropositivity varied over time, with at least one positive heifer in 50.4% (95% confidence interval (CI): 40.5–60.3) of herds in spring 2018, 35.2% (95% CI: 26.2–45.1) in spring 2019, and 45.7% (95% CI: 36.0–55.7) in autumn 2019. Herds with three or more positive heifers increased from 31.4% (95%CI: 22.7–41.2) in spring 2018 to 42.9% (95% CI: 33.2–52.9) by autumn 2019. Risk factors for M. bovis seropositivity included the purchase of cattle, which significantly raised the odds of seropositivity across multiple visit periods (Model ≥ 1POS: Odds ratio (OR) 3.84, p = 0.02; Model ≥ 3POS: OR 3.69, p = 0.02). Managing more than three land parcels, housing heifer calves separately from bull calves, and sharing airspace between calves and older animals also increased seropositivity risks. Conversely, more colostrum feeds reduced the risk of seropositivity (Model ≥ 1POS: OR 0.81, p = 0.05), while colostrum quality assessment and feeding waste milk showed a trend toward increased risk. These findings suggest the importance of robust biosecurity measures, including limiting cattle purchases, improving calf management, and enhancing colostrum feeding practices, to control the spread of M. bovis. This study provides valuable insights into the epidemiology of M. bovis in Irish dairy herds, emphasising the need for targeted biosecurity and surveillance to safeguard herd productivity.
New Occurrence of Nigrospora oryzae Causing Leaf Blight in Ginkgo biloba in China and Biocontrol Screening of Endophytic Bacteria
Authors: Tao Yuan , Yang Chun , Yu Sinong , Fu Fangfang , Dai Tingting 
Published: October 2024

Ginkgo biloba is a multifunctional composite tree species that has important ornamental, economic, medicinal, and scientific research value. In October 2023, the foliage of G. biloba on the campus of Nanjing Forestry University exhibited leaf blight. Black-brown necrotic spots were observed on a large number of leaves, with a disease incidence of 86%. After isolating a fungus from symptomatic leaves, pathogenicity was tested to satisfy Koch’s postulates. Using morphological features and multi-gene phylogenetic analyses of an internal transcribed spacer (ITS), elongation factor 1-alpha (EF1-α), and beta-tubulin (β-tub), the isolates YKB1-1 and YKB1-2 were identified as Nigrospora oryzae. N. oryzae was previously reported as an endophyte of G. biloba. However, this study shows it to be pathogenic to G. biloba, causing leaf spots. Two endophytic bacteria were isolated from asymptomatic leaves of diseased G. biloba trees, and their molecular identification was performed using 16S ribosomal DNA (16S rDNA). GBB1-2 was identified as Bacillus altitudinis, while GBB1-5 was identified as Bacillus amyloliquefaciens. The screening and verification of endophytic bacteria provide a new strategy for the control of N. oryzae.
Post-pandemic impact on a private University in Malaysia: adapting strategies for sustainable education in chemistry
Authors: Chong Sheau Huey , Wong Pei Ying 
Published: October 2024

The emergence of the COVID-19 pandemic marked an unprecedented disruption in global education systems, affecting a vast population of approximately 1.6 billion learners across over 200 countries. Specifically, within Malaysia, where private universities hold a significant role in shaping the educational sphere, the pandemic brought about notable shifts in higher education. This research focuses on the post-pandemic impact on a private university situated in the Malaysian capital, focusing on transformations in teaching and learning approaches, student engagement, and technological integration in chemistry education. Through an in-depth analysis of diverse data sources from students and literatire review, this study aims to shed light on the challenges faced by the teaching and learning process in chemistry and the strategies employed to mitigate the adverse effects. In addition, the study also discusses the potential long-term transformations in higher education that may persist beyond the pandemic and offers recommendations to ensure the resilience and adaptability of private universities in Malaysia. Understanding the post-pandemic impact on private universities is crucial for formulating effective policies and strategies to enhance the quality and accessibility of higher education in the evolving educational landscape.
A CASE OF DÜHRING'S DERMATITIS HERPETIFORMIS ASSOCIATED WITH SARS - COV - 2
Authors: N.K. Sultanova , N.K. Shaimardanov 
Published: October 2024

Clinical studies during the epidemic of a new coronavirus infection caused by SARS - CoV -2 confirm not only dermatropic skin lesions, but also complex immune-mediated skin complications of COVID -19, one of which is Dühring's herpetiform dermatitis. To present a clinical case of Dühring's dermatitis herpetiformis, which developed against the background of a coronavirus infection, probably caused by the SARS - CoV - 2 virus. Retrospective analysis of the medical history, interpretation of clinical and laboratory data in an 81-year-old patient with developed Duhring's dermatitis herpetiformis. Characteristic changes in the skin pathological process in a patient with Dühring's dermatitis herpetiformis made it possible to assume a tendency to a protracted severe course as a result of a coronavirus infection, leading to a protracted immunodeficiency state. The presented case will be of interest to therapists, infectious disease specialists, doctors of other specialties, as well as residents and students of medical universities.
Клинические исследования в период эпидемии новой коронавирусной инфекции, вызванной SARS-CoV-2 подтверждают не только дермотропное поражение кожи, но и сложные иммуноопосредованные кожные осложнения COVID-19, одним из которых является герпетиформный дерматит Дюринга. Представлен клинический случай герпетиформного дерматита Дюринга, у пациентки 81 года, развившегося на фоне коронавирусной инфекции, вероятно обусловленный вирусом SARS-CoV-2. Характерные изменения кожно-патологического процесса дали возможность предположить склонность к затяжному тяжелому течению, как следствие перенесенной коронавирусной инфекции, ведущей к затяжному иммунодефицитному состоянию. Представленный случай будет интересен для терапевтов, инфекционистов, врачей других специальностей, а также резидентов, студентов медицинских ВУЗов.
SARS-CoV-2 тудырған жаңа коронавирустық инфекцияның эпидемиясы кезіндегі клиникалық зерттеулер терінің дермотропты зақымдануын ғана емес, сонымен қатар COVID-19күрделі иммундық тері асқынуларын растайды, олардың бірі Дюринг ұшықтәрәзді дерматиті. SARS-CoV-2 вирусынан туындаған коронавирустық инфекцияның үстінен дамыған ұшықтәрізді Дюринг дерматитінің клиникалық жағдайының 81 жастағы науқаста презентациясы. Дюринг ұшықтәрізді дерматиті науқаста терінің патологиялық тән өзгерістері ұзаққа созылған ауыр ағымға бейімділік иммун тапшылығы жағдайына әкелетін коронавирустық инфекцияға байланысты деп болжауға мүмкіндік берді. Осы оқиға терапевт,инфекционист, басқа мамаң дәрігерлеріне және медициналық ЖОО студенттеріне, резиденттеріне қызығушылық көрсетеді.
ГРАНУЛЕМАТОЗНЫЙ ПОЛИАНГИИТ (ГРАНУЛЕМАТОЗ ВЕГЕНЕРА) В ПРАКТИКЕ РЕВМАТОЛОГА
Authors: Горемыкина М.В. , Ешмухамет М.М. , Ильяс Ж.А. , Берекенова А.М. , Жандарбекова Б.Б. 
Published: October 2024

В данной публикации приводится описание пациента с диагнозом Гранулематозный полиангиит (гранулематоз Вегенера), который длительное время наблюдался и лечился у врачей разных специальностей. В виду неэффективности многолетней терапии заболевания был проведен тщательный комплексный анализ клинико-лабораторных и инструментальных данных с целью верификации диагноза. Данные, приведенные в статье, будут полезны представителям практического здравоохранения, ревматологам, врачам визуальной диагностики и врачам общей практики.
This publication describes a patient diagnosed with Granulomatous polyangiitis (Wegener's granulomatosis), who was observed and treated for a long time by doctors of different specialties. Due to the ineffectiveness of long-term therapy for the disease, a thorough comprehensive analysis of clinical, laboratory and instrumental data was carried out in order to verify the diagnosis. The data presented in the article will be useful to representatives of practical healthcare, rheumatologists, visual diagnostic doctors and general practitioners.
Бұл басылымда гранулематозды полиангиит (Вегенер гранулематозы) диагнозы қойылған науқасты әртүрлі мамандықтағы дәрігерлер ұзақ уақыт бойы бақылап, емдеген. Аурудың ұзақ мерзімді терапиясының тиімсіздігіне байланысты диагнозды нақтылау мақсатында клиникалық, зертханалық және аспаптық мәліметтерге жан-жақты талдау жүргізілді. Мақалада келтірілген деректер практикалық денсаулық сақтау өкілдеріне, ревматологтарға, визуалды диагностикалық дәрігерлерге және жалпы тәжірибелік дәрігерлерге пайдалы болады.
ИННОВАЦИОННОЕ УПРАВЛЕНИЕ РЕСУРСОСБЕРЕЖЕНИЕМ В АГРАРНОМ СЕКТОРЕ
Authors: БАНДУРИНА И.П. , ПИСАРЕВА М.А. , САРКИСЯН М.С. , СТАРИЧЕНКО А.В. 
Published: October 2024

Развитие современного сельского хозяйства в значительной степени зависит от эффективного использования ресурсов в сельскохозяйственном секторе. В этой статье рассматривается внедрение передовых технологий и стратегий управления, направленных на максимальное использование природных ресурсов. Особое внимание уделяется эффективным методам управления земельными, водными и энергетическими ресурсами, а также внедрению цифровых технологий и автоматизации в сельскохозяйственные операции. Рассматривается влияние новых идей на финансовую и экологическую устойчивость сельскохозяйственных предприятий, а также примеры их успешного применения. Анализируются возможности для дополнительного роста и необходимость поддержки со стороны государственных и коммерческих структур для эффективной реализации креативных сельскохозяйственных проектов.
The development of modern agriculture largely depends on the efficient use of resources in the agricultural sector. This article discusses the introduction of advanced technologies and management strategies aimed at maximizing the use of natural resources. Special attention is paid to effective methods of managing land, water and energy resources, as well as the introduction of digital technologies and automation in agricultural operations. The impact of new ideas on the financial and environmental sustainability of agricultural enterprises is considered, as well as examples of their successful application. The possibilities for additional growth and the need for support from government and commercial structures for the effective implementation of creative agricultural projects are analyzed.