ABSTRACT
As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.
Subject(s)
Actinidia , Drought Resistance , Actinidia/genetics , Actinidia/physiology , Drought Resistance/genetics , Fruit/genetics , Fruit/physiology , Genotype , Multivariate Analysis , Plant Roots/physiology , Plant Roots/genetics , Stress, Physiological/geneticsABSTRACT
Cross-coupling reactions represent an indispensable tool in chemical synthesis. An intriguing challenge in this field is to achieve selective cross-coupling between two precursors with similar reactivity or, to the limit, the identical molecules. Here we report an unexpected dehydrobrominative cross-coupling between 1,3,5-tris(2-bromophenyl)benzene molecules on silver surfaces. Using scanning tunneling microscopy, we examine the reaction process at the single-molecular level, quantify the selectivity of the dehydrobrominative cross-coupling, and reveal the modulation of selectivity by substrate lattice-related catalytic activity or molecular assembly effect. Theoretical calculations indicate that the dehydrobrominative cross-coupling proceeds via regioselective C-H bond activation of debrominated TBPB and subsequent highly selective C-C coupling of the radical-based intermediates. The reaction kinetics plays an important role in the selectivity for the cross-coupling. This work not only expands the toolbox for chemical synthesis but also provides important mechanistic insights into the selectivity of coupling reactions on the surface.
ABSTRACT
Inborn errors of metabolism (IEM) such as lysosomal storage disorders (LSDs) are conditions caused by deficiency of one or more key enzymes, cofactors, or transporters involved in a specific metabolic pathway. Enzyme replacement therapy (ERT) provides an exogenous source of the affected enzyme and is one of the most effective treatment options for IEMs. In this paper, we review the first-in-human (FIH) protocols for ERT drug development programs supporting 20 Biologic License Applications (BLA) approved by the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration (FDA) in the period of May 1994 to September 2023. We surveyed study design elements across these FIH protocols including study population, dosage form, dose selection, treatment duration, immunogenicity, biomarkers, and study follow-up. A total of 18 FIH trials from 20 BLAs were identified and of those, 72% (13/18) used single ascending dose (SAD) and/or multiple ascending dose (MAD) study design, 83% (15/18) had a primary objective of assessing the safety and tolerability, 72% (13/18) included clinical endpoint assessments, and 94% (17/18) included biomarker assessments as secondary or exploratory endpoints. Notably, the majority of ERT products tested the approved route of administration and the approved dose was tested in 83% (15/18) of FIH trials. At last, we offer considerations for the design of FIH studies.
ABSTRACT
PURPOSE: Breast cancer survivors face dual challenges: long-term sequelae of treatment and the risk of recurrent disease. Furthermore, obesity and a sedentary lifestyle can complicate both challenges. We aimed to assess the effect of a 12-week exercise-based weight-management program in overweight/obese breast cancer survivors. METHODS: A two-arm, single-blinded, randomized controlled trial was conducted among 60 overweight/obese, stage 0-III breast cancer survivors. During the 12-week program, the intervention group received weekly information support, fortnightly exercise prescriptions, including aerobic and resistance exercises to perform at home, and one dietary instruction. The control group received information support about weight management and exercise. Weight, body composition, and physical fitness data were collected at baseline, postintervention, and the 3-month follow-up. RESULTS: The intervention group showed significant improvements in body weight and all adiposity indices, including body mass index, waist circumference, and %body fat, in comparison with baseline (P < 0.001) and the control group (P < 0.05). Both groups showed no significant changes in fat-free mass during the 6-month period (P > 0.05). International Physical Activity Questionnaire scores and left grip strength increased significantly in the intervention group in comparison with the baseline (P < 0.01) and the control group (P < 0.05). Right grip strength, lower-body strength, and aerobic endurance showed no significant intergroup differences (P > 0.05). CONCLUSIONS: A combination of exercise prescription and weight-loss interventions yielded clinically meaningful weight loss in overweight/obese breast cancer survivors. These findings may facilitate the incorporation of home-based exercise and weight management into breast cancer treatment and survivorship care.
Subject(s)
Breast Carcinoma In Situ , Breast Neoplasms , Cancer Survivors , Humans , Female , Breast Neoplasms/complications , Breast Neoplasms/therapy , Overweight/therapy , Breast , Obesity/therapyABSTRACT
Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process is a promising wastewater treatment technology, but the slow microbial growth rate greatly hinders its practical application. Although high-level nitrogen removal and excellent biomass accumulation have been achieved in n-DAMO granule process, the formation mechanism of n-DAMO granules remains unresolved. To elucidate the role of functional microbes in granulation, this study attempted to cultivate granules dominated by n-DAMO microorganisms and granules coupling n-DAMO with anaerobic ammonium oxidation (Anammox). After long-term operation, dense granules were developed in the two systems where both n-DAMO archaea and n-DAMO bacteria were enriched, whereas granulation did not occur in the other system dominated by n-DAMO bacteria. Extracellular polymeric substances (EPS) measurement indicated the critical role of EPS production in the granulation of n-DAMO process. Metagenomic and metatranscriptomic analyses revealed that n-DAMO archaea and Anammox bacteria were active in EPS biosynthesis, while n-DAMO bacteria were inactive. Consequently, more EPS were produced in the systems containing n-DAMO archaea and Anammox bacteria, leading to the successful development of n-DAMO granules. Furthermore, EPS biosynthesis in n-DAMO systems is potentially regulated by acyl-homoserine lactones and c-di-GMP. These findings not only provide new insights into the mechanism of granule formation in n-DAMO systems, but also hint at potential strategies for management of the granule-based n-DAMO process.
Subject(s)
Archaea , Bacteria , Oxidation-Reduction , Archaea/metabolism , Archaea/genetics , Anaerobiosis , Bacteria/metabolism , Bacteria/genetics , Methane/metabolism , Waste Disposal, Fluid/methods , Nitrates/metabolism , Ammonium Compounds/metabolism , Nitrites/metabolism , Extracellular Polymeric Substance Matrix/metabolism , Bioreactors/microbiology , Wastewater/microbiologyABSTRACT
Structural colors produced from nanostructures have attracted much attention due to their promising advantages of long-term stability and high resolution. Many nanostructures like metasurfaces have been demonstrated to generate color information in the transmission or reflection mode. Here, a strategy of combining polarization-insensitive and polarization-sensitive transmissive structural color is proposed to realize convenient and diverse encrypted pattern designs. A two-dimensional metasurface, whose polarization characteristics are determined by the size of a nanobrick unit, is embedded inside an optical cavity to produce transmissive structural color. The polarization-insensitive transmissive structural color exhibits a wide color gamut and high excitation purity in all polarization states, while the polarization-sensitive transmissive structural color maintains the similar color appearance in x-direction polarization but appears nearly black in y-direction polarization. Combining these two transmissive structural colors can achieve diverse images designed at different polarizations instead of simply hiding the image in a specific polarization state. An image of "flower and flowerpot" using the generated colors is visually illustrated, which shows that the proposed transmissive structural colors would have great potential in the areas of security information encryption.
ABSTRACT
BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.
Subject(s)
Malaria , Humans , Reproducibility of Results , Malaria/epidemiology , Risk Assessment , China/epidemiology , Machine LearningABSTRACT
Diabetic nephropathy (DN) is a serious complication of diabetes, and its progression is influenced by factors like oxidative stress, inflammation, cell death, and fibrosis. Compared to drug treatment, exercise offers a cost-effective and low-risk approach to slowing down DN progression. Through multiple ways and mechanisms, exercise helps to control blood sugar and blood pressure and reduce serum creatinine and albuminuria, thereby alleviating kidney damage. This review explores the beneficial effects of exercise on DN improvement and highlights its potential mechanisms for ameliorating DN. In-depth understanding of the role and mechanism of exercise in improving DN would pave the way for formulating safe and effective exercise programs for the treatment and prevention of DN.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Humans , Diabetic Nephropathies/prevention & control , Albuminuria , Blood Glucose , Blood Pressure , Cell DeathABSTRACT
The U.S. Food and Drug Administration recently approved lonafarnib as the first treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies. This approval was primarily based on a comparison of patients with HGPS treated with lonafarnib in 2 open-label trials with an untreated patient cohort. With up to 11 years of follow-up, it was found that the lonafarnib treated patients with HGPS had a survival benefit of 2.5 years compared with the untreated patients with HGPS. This large treatment effect on the objective endpoint of mortality using a well-matched comparator group mitigated potential sources of bias and together with other evidence, established compelling evidence of a drug effect with benefits that outweighed the risks. This approval is an example of U.S. Food and Drug Administration's regulatory flexibility for a rare disease while ensuring that standards for drug approval are met.
Subject(s)
Progeria , United States , Humans , Progeria/drug therapy , Progeria/genetics , Lamin Type A/genetics , Piperidines/therapeutic use , Pyridines/therapeutic useABSTRACT
Enhancing soil organic carbon (SOC) sequestration and food supply are vital for human survival when facing climate change. Site-specific best management practices (BMPs) are being promoted for adoption globally as solutions. However, how SOC and crop yield are related to each other in responding to BMPs remains unknown. Here, path analysis based on meta-analysis and machine learning was conducted to identify the effects and potential mechanisms of how the relationship between SOC and crop yield responds to site-specific BMPs in China. The results showed that BMPs could significantly enhance SOC and maintain or increase crop yield. The maximum benefits in SOC (30.6%) and crop yield (79.8%) occurred in mineral fertilizer combined with organic inputs (MOF). Specifically, the optimal SOC and crop yield would be achieved when the areas were arid, soil pH was ≥7.3, initial SOC content was ≤10 g kg-1 , duration was >10 years, and the nitrogen (N) input level was 100-200 kg ha-1 . Further analysis revealed that the original SOC level and crop yield change showed an inverted V-shaped structure. The association between the changes in SOC and crop yield might be linked to the positive role of the nutrient-mediated effect. The results generally suggested that improving the SOC can strongly support better crop performance. Limitations in increasing crop yield still exist due to low original SOC level, and in regions where the excessive N inputs, inappropriate tillage or organic input is inadequate and could be diminished by optimizing BMPs in harmony with site-specific conditions.
Subject(s)
Agriculture , Soil , Humans , Soil/chemistry , Agriculture/methods , Carbon/analysis , Carbon Sequestration , China , Crops, AgriculturalABSTRACT
Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.
Subject(s)
Ileus , Plants, Medicinal , Humans , TRPA1 Cation Channel , Ileus/drug therapy , Pain , Plant Extracts , TRPV Cation Channels/physiologyABSTRACT
Several randomized controlled trials (RCTs) have investigated the effects of fermented foods on metabolic outcomes in adult patients suffering from diabetes and prediabetes. However, the results of these RCTs are conflicting. This systematic review and meta-analysis was carried out on data from RCTs to evaluate the effects of fermented foods in patients with diabetes and prediabetes. The PubMed, Web of Science, Embase, the Cochrane Library and Scopus databases were searched up to 21 June, 2022. English-language RCTs of fermented foods consumption were included which gave metabolic outcomes on body composition, glucose control, insulin sensitivity, lipid profile, as well as blood pressure. Eighteen RCTs met the inclusion criteria and 843 participants were included in the final analysis. The pooled results showed a significant reduction of fasting blood glucose (FBG), the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), low density lipid cholesterol (LDL-C) and diastolic blood pressure (DBP) in the intervention group versus the control group. The results of this research showed that fermented foods have the potential to improve some metabolic outcomes, including FBG, HOMA-IR, TC, LDL-C, and DBP in patients with diabetes and prediabetes.
ABSTRACT
BACKGROUND: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP. METHODS: The clinical records of 324 SAP patients admitted within 48 h after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin (PCT) concentration on the 1st, 4th, and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5-7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the receiver operating characteristic curve analyses. RESULTS: NLR, PCT, body mass index, and MCTSI were significantly higher in the IPN group (p < 0.001) compared to the control, among which NLR, PCT, and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded significant predicting values with an area under curve of 0.92, sensitivity of 97.2%, and specificity of 77.2% in receiver operating characteristic curve analysis. CONCLUSION: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients.
Subject(s)
Pancreatitis, Acute Necrotizing , Humans , Pancreatitis, Acute Necrotizing/diagnostic imaging , Procalcitonin , Acute Disease , Neutrophils , Retrospective Studies , ROC Curve , Lymphocytes , Tomography, X-Ray Computed , Prognosis , Severity of Illness IndexABSTRACT
Circulating tumor cells (CTCs) are cells shed from primary or metastatic tumors and spread into the peripheral bloodstream. Mutation detection in CTCs can reveal vital genetic information about the tumors and can be used for "liquid biopsy" to indicate cancer treatment and targeted medication. However, current methods to measure the mutations in CTCs are based on PCR or DNA sequencing which are cumbersome and time-consuming and require sophisticated equipment. These largely limited their applications especially in areas with poor healthcare infrastructure. Here we report a simple, convenient, and rapid method for mutation detection in CTCs, including an example of a deletion at exon 19 (Del19) of the epidermal growth factor receptor (EGFR). CTCs in the peripheral blood of NSCLC patients were first sorted by a double spiral microfluidic chip with high sorting efficiency and purity. The sorted cells were then lysed by proteinase K, and the E19del mutation was detected via real-time recombinase polymerase amplification (RPA). Combining the advantages of microfluidic sorting and real-time RPA, an accurate mutation determination was realized within 2 h without professional operation or complex data interpretation. The method detected as few as 3 cells and 1% target variants under a strongly interfering background, thus, indicating its great potential in the non-invasive diagnosis of E19del mutation for NSCLC patients. The method can be further extended by redesigning the primers and probes to detect other deletion mutations, insertion mutations, and fusion genes. It is expected to be a universal molecular diagnostic tool for real-time assessment of relevant mutations and precise adjustments in the care of oncology patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoplastic Cells, Circulating , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Microfluidics , Recombinases/genetics , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Mutation , Neoplastic Cells, Circulating/pathologyABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of noninvasive therapies in the treatment of central poststroke pain (CPSP) by network meta-analysis and to provide an evidence-based basis for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, Wanfang, and VIP were searched for clinical randomized controlled studies on noninvasive therapy for CPSP. The retrieval time limit was from the establishment of each database to July 2022. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included randomized controlled trials (RCTs). Stata 14.0 was used for network meta-analysis, and Review Manager 5.3 software was used for traditional meta-analysis. RESULTS: Twelve RCTs involving 8 treatment schemes and 641 patients were finally included. The results of the network meta-analysis showed the following rankings in visual analysis scale (VAS): super laser injury on stellate ganglia (SLI) > transcranial direct current stimulation (tDCS) > music therapy (MT) > repetitive transcranial magnetic stimulation (rTMS) > continuous theta burst stimulation (cTBS) > transcutaneous acupoint electrical stimulation (TAES) > common therapy (CT). The total clinical efficiency ranked as follows: psychological training of mindfulness (PT) > rTMS > CT. Clinical adverse reactions ranked as follows: rTMS > MT > CT > SLI. CONCLUSIONS: Noninvasive complementary therapy can effectively alleviate the pain of CPSP patients, and the efficacy and safety of SLI are relatively significant. However, due to the limitations of this study, the efficacy ranking cannot fully explain the advantages and disadvantages of clinical efficacy. In the future, more multicentre, large sample, double-blind clinical randomized controlled trials are needed to supplement and demonstrate the results of this study.
Subject(s)
Neuralgia , Transcranial Direct Current Stimulation , Humans , Network Meta-Analysis , Transcranial Magnetic Stimulation/adverse effects , Transcranial Magnetic Stimulation/methods , Transcranial Direct Current Stimulation/methods , Neuralgia/etiology , Pain Management/methods , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). RESULTS: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). CONCLUSIONS: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.
Subject(s)
Adenomyosis , Intrauterine Devices, Medicated , Female , Humans , Levonorgestrel/therapeutic use , Adenomyosis/surgery , Adenomyosis/pathology , Dysmenorrhea/therapy , Uterus/pathology , MenstruationABSTRACT
Recommended management practices (RMPs, e.g., manuring, no-tillage, crop residue return) can increase soil organic carbon (SOC), reduce greenhouse gas emissions, and maintain soil health in croplands. However, there is no consensus on how RMPs affect the SOC storage potential of cropland soils for climate change mitigation. Here, based on 2301 comparisons from 158 peer-reviewed papers, a meta-analysis was conducted to explore management-induced SOC stock changes and their variations under different conditions. The results show that SOC stocks in the 0-20 cm layer were increased by 31.8% when chemical fertilization combined with manure application was compared with no fertilizer; 9.98% when no-tillage was compared with plow tillage; and 10.84% when straw return was compared with removal. The RMPs favorably increased SOC stock in arid areas, and in alkaline and fine-textured soils. Initial SOC, carbon-nitrogen ratio, and experimental duration could also affect SOC storage. Compared with the initial SOC stock, RMPs increased the SOC sequestration potential by 2.6-4.5% in the 0-20 cm soil depth, indicating that these practices can help China achieve targets to increase SOC by 4.0. Hence, it is essential to implement RMPs for climate change mitigation and soil fertility improvement.
Subject(s)
Agriculture , Soil , Soil/chemistry , Agriculture/methods , Carbon/analysis , Crops, Agricultural , China , Carbon Sequestration , Manure/analysisABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). Genetic factors might influence susceptibility to the SARS-CoV-2 infection or disease severity. Genome-wide association studies (GWASs) have identified multiple susceptible genes related to COVID-19 phenotypes, providing the scientific basis for the COVID-19 prevention and treatment. In this review, we summarize the recent progresses of COVID-19 susceptible genes, including the GWASs on multiple phenotypes of COVID-19, GWASs of COVID-19 in multiple ethnic populations, GWASs of COVID-19 based on multiple types of genetic variations, and the fine-mapping of the regions surrounding the susceptible genes.
Subject(s)
COVID-19 , Genetic Predisposition to Disease , Genome-Wide Association Study , SARS-CoV-2 , Humans , COVID-19/genetics , Genetic Predisposition to Disease/genetics , SARS-CoV-2/geneticsABSTRACT
This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P<0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P<0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P<0.01), and significantly increased levels of GABA(P<0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P<0.05, P<0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.
Subject(s)
Hippocampus , Receptors, Ionotropic Glutamate , Rats , Mice , Animals , Receptors, Ionotropic Glutamate/metabolism , Neuronal Plasticity , Receptors, N-Methyl-D-Aspartate/genetics , Anxiety/drug therapy , Anxiety/genetics , gamma-Aminobutyric AcidABSTRACT
OBJECTIVES: To study the moderating effect of mother-child relationship in the association between maternal parenting stress and emotional and behavioral problems in preschool children, and to provide reference for the prevention and control of emotional and behavioral problems in preschool children. METHODS: Using a stratified cluster sampling method, 2 049 preschool children were surveyed from November to December 2021, who sampled from 12 kindergartens in Wuhu City, Anhui Province. The emotional and behavioral problems of preschool children were assessed with the Strength and Difficulties Questionnaire. Pearson correlation analysis was used to evaluate the relationship of maternal parenting stress and mother-child relationship with children's emotional and behavioral problems. The PROCESS Macro was used to analyze the moderating effect of conflicted and dependent mother-child relationships in the association between maternal parenting stress and emotional and behavioral problems in these preschool children. RESULTS: Among these preschool children, maternal parenting stress was positively correlated with the scores of emotional symptoms, conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001); intimate mother-child relationships were negatively correlated with the scores of conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001); conflicted and dependent mother-child relationships were positively correlated with the scores of emotional symptoms, conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001). After controlling for relevant confounding factors, conflicted mother-child relationship (ß=0.05, P=0.001) and dependent mother-child relationship (ß=0.04, P=0.012) were found to have a moderating effect on the association between maternal parenting stress and total difficulty scores in these preschool children. CONCLUSIONS: Negative mother-child relationships play a moderating role in the association between maternal parenting stress and emotional and behavioral problems in preschool children. Prevention of emotional and behavioral problems in preschool children should focus on reducing maternal parenting stress and improving negative mother-child relationships.