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OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.
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Aflatoxin B1 , Ferroptosis , Flavonoids , Hepatocytes , Tumor Suppressor Protein p53 , Flavonoids/pharmacology , Aflatoxin B1/toxicity , Ferroptosis/drug effects , Hepatocytes/drug effects , Animals , Tumor Suppressor Protein p53/metabolism , Rats , Oxidative Stress/drug effects , DNA Damage/drug effects , Male , Protective Agents/pharmacology , Rats, Sprague-Dawley , Humans , Reactive Oxygen Species/metabolismABSTRACT
Zebrafish serve as valuable models for research on growth, immunity, and gut microbiota due to their genomic similarities with mammals, transparent embryos developed in a relatively clean chorion environment, and extremely rapid development of larvae compared to rodent models. Germ-free (GF) zebrafish (Danio rerio) are crucial for evaluating pollutant toxicity and establishing human-like disease models related to microbial functions. In comparison to conventionally raised (CR) models (fish in common husbandry), GF zebrafish allow for more accurate manipulation of the host microbiota, aiding in determining the causal relationship between microorganisms and hosts. Consequently, they play a critical role in advancing our understanding of these relationships. However, GF zebrafish models are typically generated and researched during the early life stages (from embryos to larvae) due to limitations in immune function and nutrient absorption. This study optimizes the generation, maintenance, and identification of early GF zebrafish models without feeding and with long-term feeding using GF food (such as Artemia sp., brine shrimp). Throughout the process, daily sampling and culture were performed and identified through multiple detections, including plates and 16S rRNA sequencing. The aseptic rate, survival, and developmental indexes of GF zebrafish were recorded to ensure the quality and quantity of the generated models. Importantly, this study provides details on bacterial isolation and infection techniques for GF fish, enabling the efficient creation of GF fish models from larvae to juvenile stages with GF food support. By applying these procedures in biomedical research, scientists can better understand the relationships between intestinal bacterial functions and host health.
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Germ-Free Life , Larva , Models, Animal , Zebrafish , Animals , Zebrafish/microbiology , Larva/microbiology , Larva/growth & development , Female , MaleABSTRACT
The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.
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Fagopyrum , Lignin , Seeds , Lignin/metabolism , Lignin/genetics , Fagopyrum/genetics , Fagopyrum/metabolism , Seeds/genetics , Seeds/metabolism , MethyltransferasesABSTRACT
PURPOSE: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration. METHODS: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis. RESULTS: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K1 (p < 0.001), hepatic impairment (p = 0.014), and Cmin ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy. CONCLUSION: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone Cmin ≥ 87.765 mg/l. Vitamin K1 is effective in preventing this adverse reaction.
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Blood Coagulation Disorders , Liver Diseases , Humans , Cefoperazone/adverse effects , Case-Control Studies , Retrospective Studies , Critical Illness , Risk Factors , Blood Coagulation Disorders/chemically induced , Vitamin K , Intensive Care UnitsABSTRACT
High-quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi-C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein-coding genes and 1265 non-coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship with Salvia splendens and Salvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole-genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi-omics (integrated transcriptome and metabolome) analysis showed the tissue-specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up-regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments.
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Chromosomes, Plant , Genome, Plant , Genome, Plant/genetics , Chromosomes, Plant/genetics , Adaptation, Physiological/genetics , Salvia/genetics , Salvia/metabolism , Antioxidants/metabolism , Rosmarinus/genetics , Rosmarinus/metabolism , Transcriptome/genetics , Gene Expression Regulation, Plant , Depsides/metabolism , MultiomicsABSTRACT
It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.
Subject(s)
Drinking Water , Renal Insufficiency, Chronic , Animals , Drinking Water/analysis , Zebrafish , Sri Lanka , Renal Insufficiency, Chronic/etiology , MetabolomeABSTRACT
Background: Acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) carries a substantial risk of mortality, emphasizing the need for effective risk assessment and timely interventions. This study aimed to develop and validate a practical dynamic nomogram for predicting 3-month mortality in AIS patients with AF. Methods: AIS patients with AF were enrolled and randomly divided into training and validation cohorts. The nomogram was developed based on independent risk factors identified by multivariate logistic regression analysis. The prediction performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, decision curve analysis (DCA), and Kaplan-Meier survival analysis. Results: A total of 412 patients with AIS and AF entered final analysis, 288 patients in the training cohort and 124 patients in the validation cohort. The nomogram was developed using age, baseline National Institutes of Health Stroke Scale score, early introduction of novel oral anticoagulants, and pneumonia as independent risk factors. The nomogram exhibited good discrimination both in the training cohort (AUC, 0.851; 95% CI, 0.802-0.899) and the validation cohort (AUC, 0.811; 95% CI, 0.706-0.916). The calibration plots, DCA and Kaplan-Meier survival analysis demonstrated that the nomogram was well calibrated and clinically useful, effectively distinguishing the 3-month survival status of patients with AIS and AF, respectively. The dynamic nomogram can be obtained at the website: https://yanxiaodi.shinyapps.io/3-monthmortality/. Conclusion: The dynamic nomogram represents the first predictive model for 3-month mortality and may contribute to managing the mortality risk of patients with AIS and AF.
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OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: ⢠Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. ⢠Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. ⢠Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.
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Heart Failure , Humans , Stroke Volume/physiology , Hemodynamics , Cardiac Output/physiology , Pulmonary Wedge Pressure/physiology , Ventricular Function, Left/physiologyABSTRACT
Dystonia is characterized by sustained or intermittent involuntary muscle contractions. Psychiatric symptoms are essential non-motor features of dystonia, and higher risks of depressive and anxiety disorders have been reported. The precedence of psychiatric to motor symptoms in some patients and the dopaminergic and serotonergic system involvement in both the motor and psychiatric aspects suggest these psychiatric disorders may be intrinsic to the neurobiology of dystonia. Nevertheless, psychiatric comorbidities are often construed as secondary reactions to motor disabilities and the negative bio-psycho-social impacts of dystonia, leading to underdiagnosis and undertreatment. Research on antidepressant use in dystonia is scarce, especially in children and adolescents. This report presents a 17-year-old female with dystonia comorbid with depression with psychotic features, whose motor symptoms improved but psychiatric symptoms persisted with dopaminergic pharmacotherapy. Sertraline was finally added 5 years after the onset and successfully managed her psychotic depression without worsening motor symptoms. Early detection, prompt diagnosis, and timely holistic treatment with dopaminergic agents, antidepressants, and psychosocial interventions are critical for the mental health of dystonia patients.
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Bipolar Disorder , Depressive Disorder, Major , Dystonia , Humans , Adolescent , Female , Child , Sertraline/therapeutic use , Depressive Disorder, Major/drug therapy , Dystonia/drug therapy , Anxiety Disorders , Bipolar Disorder/drug therapy , Antidepressive Agents/therapeutic useABSTRACT
Objective:To establish an ultrasound prediction model of postoperative recurrence in patients with papillary thyroid carcinoma(PTC)after complete endoscopic radical surgery.Meth-ods:264 patients with PTC who underwent complete endoscopic radical surgery for the first time in our hospital from February 2017 to March 2020 were retrospectively collected.They were divided in-to recurrence group and non recurrence group according to whether there was recurrence after surgery.The clinical data,nodule diameter,nodule number,internal echo,microcalcification and other ultrasonic data of the two groups were compared.Single factor,Lasso and Logistic regression mod-els were used to analyze the influencing factors of postoperative recurrence of PTC patients,and an nomogram model was established based on the selected indicators.Results:Compared with the non recurrence group,the patients in the recurrence group had larger nodule diameter,irregular nod-ule edge,aspect ratio>1,microcalcification and capsule invasion(P<0.05).Nodular diameter>10 mm,irregular edge,aspect ratio>1,microcalcification and capsule invasion were independent risk factors for postoperative recurrence of PTC patients(P<0.05).The C-index of the constructed nomogram model was 0.756(95%Cl:0.684~0.830),and the AUC of the ROC curve was 0.895(95%Cl:0.866~0.915);The calibration curve results show that the average deviation is 0.027,and the predic-tion probability fits the actual probability well;The clinical decision curve is far away from the extreme curve and has good clinical applicability.Conclusion:The nomogram model based on nodule size,irregular margin,microcalcification,aspect ratio>1,and capsule invasion has good accuracy in pre-dicting the recurrence of PTC patients after complete endoscopic radical surgery,and has certain clinical significance.
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Objective The best evidence of respiratory muscle training for patients with mechanical ventilation in ICU after machine withdrawal was extracted and summarized to provide evidence-based evidence for respiratory muscle training for patients with mechanical ventilation after machine withdrawal.Methods We searched relevant guideline networks and association websites,as well as PubMed,Web of Science,Embase,CINAHL,CNKI,VIP,Wanfang and other databases to collect relevant guidelines,clinical decisions,evidence summaries,expert consensuses,systematic reviews and randomized controlled studies,and the search time limit is from the establishment of the databases to July 30,2023.There were 2 researchers who independently evaluated the literature quality and extracted data.Results A total of 13 articles were included,including 2 guidelines,2 clinical decisions,5 systematic reviews and 4 expert consensuses.There were 24 pieces of evidence being summarized in 7 categories,including training team,training evaluation,training methods,training frequency,training safety,training effect evaluation and health education.Conclusion This study summarizes the best evidence for respiratory muscle training in patients with mechanical ventilation after withdrawal,which can provide references for medical staffs to conduct respiratory muscle training for patients after withdrawal.It is recommended that medical staff should consider the clinical situation when applying the evidence,and selectively apply the best evidence.
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AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.
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The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional two-dimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized,in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.
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Objective To observe the clinical efficacy of Qigui Tongluo Oral Liquid(a hospital preparation developed by Guangdong Second Traditional Chinese Medicine Hospital and being composed of Astragali Radix,Angelicae Sinensis Radix,Notoginseng Radix et Rhizoma,Paeoniae Radix Rubra,Achyranthis Bidentatae Radix,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Pheretima,etc.)combined with moxibustion for the treatment of chronic fatigue syndrome(CFS)of qi deficiency and blood stasis type on the basis of qi-collateral theory.Methods A retrospective study was conducted in 60 CFS patients with qi deficiency and blood stasis type.The patients were divided into an observation group and a control group,with 30 patients in each group according to the therapy.The control group was treated with mild moxibustion on Shenque(CV8)point with moxa sticks,and the observation group was treated with Qigui Tongluo Oral Liquid on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,Fatigue Scale-14(FS-14)scores,serum immunoglobulin IgA,IgM,IgG levels,and cortisol(COR)level in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 96.67%(29/30),and that of the control group was 80.00%(24/30).The intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the TCM syndrome scores and FS-14 scores of patients in the two groups were significantly decreased compared with those before treatment(P<0.01),and the effect on decreasing TCM syndrome scores and FS-14 scores in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the serum IgA and IgG levels of the two groups as well as the serum IgM and COR levels of the observation group were significantly increased compared with those before treatment(P<0.01),and the effect of the observation group on increasing serum IgA,IgM,IgG,and COR levels was significantly superior to that of the control group(P<0.05 or P<0.01).(4)During the treatment,there were no significant adverse reactions occurring in the two groups.Conclusion Healthy-qi deficiency and collateral obstruction contribute to the core pathogenesis of CFS.Based on the TCM qi-collateral theory and following the therapeutic principle of replenishing deficiency and unblocking collaterals,Qigui Tongluo Oral Liquid combined with moxibustion for the treatment of CFS patients with qi deficiency and blood stasis type can achieve certain efficacy.The combined therapy could significantly alleviate the clinical symptoms,improve the immunity level,and regulate the neuro-endocrine-immune(NEI)network of the patients.
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ObjectiveTo introduce the basic design, development plan and objectives of a population-based birth cohort in Shanghai, and further present the main data and baseline characteristics of enrolled participants in the cohort, and to provide key information for reproductive health-related studies. MethodsThe Shanghai population-based birth cohort initiated on January 1, 2005, included newborns born in Shanghai every year and their parents, and collected information on reproductive health, reproductive treatment, birth characteristics, growth and development status, as well as the incidence, treatment and death of diseases by employing data linkage technology and investigations. This formed a birth cohort spanning the entire life cycle. ResultsAs of October 2022, a total of 2 978 538 newborns and their parents were included in the cohort. Among them, 2 905 135 (97.54%) were naturally conceived (NC), and 73 403 (2.46%) were born through assisted reproductive technologies (ART). The average age of parents was (32.56±4.12) years old for females and (34.62±5.34) years old for males in the ART group, which was higher than (28.02±4.71) years and (30.07±5.54) years for parents in the NC group. Among parents, females and males aged 30 and above accounted for 77.12% and 85.08%, respectively, which were higher than that of parents (35.28% for females and 49.66% for males) in the NC group. Furthermore, the percentage of parents with a college degree or above in the ART group was 73.23% for females and 73.66% for males, which were higher than those in the NC group (49.98% and 50.91%, respectively). The multiple births rate in the ART group was 33.81%, which was higher than that in the NC group (1.88%). The incidence of premature birth and low birth weight in the ART group were 24.47% and 19.08%, respectively, which was higher than that in the NC group (5.47% and 3.73%). ConclusionThe comprehensive collection of reproductive health-related information in the birth cohort in Shanghai can provide essential resources to determine the influence of genetics, environment, reproductive treatment and other related factors on the health of offspring after birth.
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Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L
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Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that has grown vigorously in recent years. With noticeable attention, machine learning methods have also been applied to fNIRS. However, the current approach lacks interpretability of the results. In recent years, the utilization and investigation of fNIRS have experienced significant growth and are now being utilized in clinical research. However, the collection of clinical fNIRS data is limited in sample size. Therefore, our aim is to utilize the collected fNIRS data from all channels and achieve interpretable analysis results with minimal human manipulation, channel selection or feature extraction. We developed an fNIRS-based interpretable model and used class-specific gradient information to visualize the biomarkers captured by the model via locating the important region. The accuracy of our model's classification was 6% higher than that of the conventional SVM method under within-subject classification. The model focuses on signals from the left brain in the classification of right-hand finger tapping task, while in the task of classifying left-handed movements, the model relies on signals from the right brain. These results were consistent with current understanding of physiology.Clinical Relevance- The machine learning-based fNIRS model has the potential to be used for the diagnosis and prediction of therapeutic efficacy in clinical settings.
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Brain , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Brain/diagnostic imaging , Neural Networks, Computer , Hand , Cerebral CortexABSTRACT
The efficacy and safety of anticoagulant therapy in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) remain uncertain. This study enrolled 431 AIS and AF patients from Nanjing Drum Tower Hospital between January 2019 and December 2021 and followed for 365 days to determine the associations between anticoagulants and clinical outcomes by assessing modified Rankin Scale (mRS) score, recurrent ischemic stroke/systemic embolism (IS/SE), all-cause mortality, intracranial hemorrhage (ICH) and major bleeding. Final analysis included 400 eligible patients and divided them into antiplatelet group (n = 191) and anticoagulant group (n = 209). Anticoagulant therapy was associated with excellent (mRS 0-1; adjusted odds ratio (aOR), 2.63; 95% confidence interval (CI), 1.61-4.30) and favorable functional outcomes (mRS 0-2; aOR, 2.82; 95% CI, 1.69-4.70) and lower risk of all-cause mortality (adjusted hazard ratio (aHR), 0.35; 95% CI, 0.21-0.57), ICH (aHR, 0.45; 95% CI, 0.23-0.87) and major bleeding (aHR, 0.51; 95% CI, 0.28-0.94), without increasing the risk of recurrent IS/SE (aHR, 0.75; 95% CI, 0.45-1.24). In conclusion, anticoagulant therapy may be a more effective and safer option than antiplatelet therapy for AIS patients with AF.
Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Platelet Aggregation Inhibitors/adverse effects , Stroke/etiology , Stroke/complications , Ischemic Stroke/drug therapy , Anticoagulants/adverse effects , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Intracranial Hemorrhages/chemically induced , Administration, OralABSTRACT
Sporopollenin in the pollen cell wall protects male gametophytes from stresses. Phenylpropanoid derivatives, including guaiacyl (G) lignin units, are known to be structural components of sporopollenin, but the exact composition of sporopollenin remains to be fully resolved. We analyzed the phenylpropanoid derivatives in sporopollenin from maize and Arabidopsis by thioacidolysis coupled with nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS). The NMR and GC-MS results confirmed the presence of p-hydroxyphenyl (H), G, and syringyl (S) lignin units in sporopollenin from maize and Arabidopsis. Strikingly, H units account for the majority of lignin monomers in sporopollenin from these species. We next performed a genome-wide association study to explore the genetic basis of maize sporopollenin composition and identified a vesicle-associated membrane protein (ZmVAMP726) that is strongly associated with lignin monomer composition of maize sporopollenin. Genetic manipulation of VAMP726 affected not only lignin monomer composition in sporopollenin but also pollen resistance to heat and UV radiation in maize and Arabidopsis, indicating that VAMP726 is functionally conserved in monocot and dicot plants. Our work provides new insight into the lignin monomers that serve as structural components of sporopollenin and characterizes VAMP726, which affects sporopollenin composition and stress resistance in pollen.
Subject(s)
Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Genome-Wide Association Study , Hot Temperature , Lignin/chemistry , Lignin/genetics , Lignin/metabolism , Pollen/genetics , Pollen/metabolism , Ultraviolet Rays , Zea mays/genetics , Zea mays/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
OBJECTIVE: To assess the association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese from Guangxi, China. METHODS: From May 2017 to March 2020, 258 patients diagnosed with asthma and 244 healthy controls were recruited from the Affiliated Hospital of Youjiang Minzhu Medical College and the People's Hospital of Hechi. Genotypes of the c.*670T>G polymorphism were determined by Sanger sequencing. Flow cytometry was used in combination with an electrical impedance method for the counting and classification of peripheral blood cells. RESULTS: Compared with the T allele, the G allele of the c.*670T>G polymorphism was associated with the risk for asthma in the population (OR = 1.54, 95%CI = 1.15-2.06; P = 0.004). Compared with the GT and TT genotypes, homozygous GG genotype also comprised a risk factor (OR = 1.66, 95%CI = 1.16-2.38; P = 0.005). Stratification of the risk factors showed that the homozygous GG genotype has increased the risk of asthma in males and urban residents (P < 0.01). The erythrocyte, hemoglobin and platelet counts of the asthma group were significantly higher than the control group (P < 0.001). The GG, GT and TT genotypes have respectively accounted for 82.35%, 17.65% and 0% of the samples with platelets exceeding the normal value. The overall platelet level of GG genotype was higher than GT+TT genotype (P < 0.05). The significant association was verified by the false positive report probability, and at a prior probability level of 0.1, G vs. T false positive probability was 0.071, and GG vs. GT+TT false positive probability was 0.153. CONCLUSION: The GG genotype of the c.*670T>G polymorphism is associated with the risk for asthma among ethnic Zhuang Chinese from northwest Guangxi. Above finding has also enriched the genotypic data and peripheral blood phenotype for this polymorphism.