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1.
J Youth Adolesc ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740645

ABSTRACT

Interest in socioeconomic differences in academic motivation has been longstanding. However, previous research has often treated both low- and high-SES students as homogenous groups. This study aims to address this gap by investigating the developmental trajectory profiles of mathematics motivation during early adolescence, with a focus on variations within and across SES groups. Multigroup latent class growth analysis was used on a sample of 3718 early adolescents in China (initial Mage was 9.40 ± 0.52 years; 48.0% girls) across 2 years from grades 4 through 6. The analysis identified three distinct self-determined mathematics motivation trajectory profiles within each SES group: a good-quality profile (i.e., initially high autonomous but low controlled), a high-quantity profile (i.e., initially high both autonomous and controlled), and a low-quantity profile (i.e., initially low both autonomous and controlled). A greater proportion of low-SES students were observed within the low-quantity profile than within the good-quality profile. The study found that the failure-is-enhancing view was a protective factor against two relatively maladaptive motivational trajectory profiles (i.e., high-quantity profile and low-quantity profile), irrespective of socioeconomic background. These findings emphasize the importance of implementing motivational interventions for early adolescents that consider both structural factors (e.g., socioeconomic backgrounds) and psychological factors (e.g., failure beliefs), to foster students' academic development.

2.
Int J Oral Sci ; 16(1): 30, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38622128

ABSTRACT

Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.


Subject(s)
Bacterial Infections , Nucleic Acids , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Nucleic Acids/pharmacology , Hydrogels/pharmacology , Hydrogels/chemistry , Wound Healing , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology
3.
Acta Pharmacol Sin ; 45(4): 815-830, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38066346

ABSTRACT

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.


Subject(s)
Diabetes Mellitus, Experimental , Luteolin , Wound Healing , Animals , Humans , Rats , Autophagy/drug effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Luteolin/pharmacology , Luteolin/therapeutic use , Quality of Life , Sirtuin 1/genetics , Sirtuin 1/metabolism , Wound Healing/drug effects
5.
Front Cell Dev Biol ; 11: 1268646, 2023.
Article in English | MEDLINE | ID: mdl-37771377

ABSTRACT

Pulmonary arterial hypertension (PAH) is a severe disease resulting from progressive increases in pulmonary vascular resistance and pulmonary vascular remodeling, ultimately leading to right ventricular failure and even death. Hypoxia, inflammation, immune reactions, and epigenetic modifications all play significant contributory roles in the mechanism of PAH. Increasingly, epigenetic changes and their modifying factors involved in reprogramming through regulation of methylation or the immune microenvironment have been identified. Among them, histone lactylation is a new post-translational modification (PTM), which provides a novel visual angle on the functional mechanism of lactate and provides a promising diagnosis and treatment method for PAH. This review detailed introduces the function of lactate as an important molecule in PAH, and the effects of lactylation on N6-methyladenosine (m6A) and immune cells. It provides a new perspective to further explore the development of lactate regulation of pulmonary hypertension through histone lactylation modification.

6.
Front Microbiol ; 14: 1128057, 2023.
Article in English | MEDLINE | ID: mdl-36891380

ABSTRACT

Introduction: Cyanogenic glycosides (CNglcs) are bioactive plant products involving in plant defense against herbivores by virtue of their abilities to release toxic hydrogen cyanide (HCN). Aspergillus niger has been shown to be effective in producing ß-glucosidase, which could degrade CNglcs. However, whether A. niger could remove CNglcs under ensiling conditions is still unknown. Methods: In this study, we first investigated the HCN contents in ratooning sorghums for two years, then the sorghums were ensiled with or without the addition of A. niger. Results: Two years' investigation indicated that the contents of HCN in fresh ratooning sorghum were larger than 801 mg/kg FW (fresh weight), which could not be reduced by silage fermentation under safety threshold (200 mg/kg FW). A. niger could produce ß-glucosidase over a range of pH and temperature, which degraded the CNglcs and removed the hydrogen cyanide (HCN) at early days of ratooning sorghum fermentation. The addition of A. niger (2.56 × 107 CFU/ml) altered the microbial community, increased bacterial diversity, improved the nutritive qualities, and reduced the HCN contents in ensiled ratooning sorghum lower than 100 mg/kg FW after 60 days of fermentation. Overall, the addition of 150 ml A. niger + 50 ml sterile water per 3 kg silage could efficiently remove CNglcs from ratooning sorghum silage. Conclusion: In conclusion, A. niger could produce ß-glucosidase which degraded the CNglcs during the early days of fermentation, benefiting the ensiling process and improving the utilization of ratooning sorghum.

7.
Neuron ; 111(10): 1637-1650.e5, 2023 05 17.
Article in English | MEDLINE | ID: mdl-36917980

ABSTRACT

The Ras GTPase-activating protein SYNGAP1 plays a central role in synaptic plasticity, and de novo SYNGAP1 mutations are among the most frequent causes of autism and intellectual disability. How SYNGAP1 is regulated during development and how to treat SYNGAP1-associated haploinsufficiency remain challenging questions. Here, we characterize an alternative 3' splice site (A3SS) of SYNGAP1 that induces nonsense-mediated mRNA decay (A3SS-NMD) in mouse and human neural development. We demonstrate that PTBP1/2 directly bind to and promote SYNGAP1 A3SS inclusion. Genetic deletion of the Syngap1 A3SS in mice upregulates Syngap1 protein and alleviates the long-term potentiation and membrane excitability deficits caused by a Syngap1 knockout allele. We further report a splice-switching oligonucleotide (SSO) that converts SYNGAP1 unproductive isoform to the functional form in human iPSC-derived neurons. This study describes the regulation and function of SYNGAP1 A3SS-NMD, the genetic rescue of heterozygous Syngap1 knockout mice, and the development of an SSO to potentially alleviate SYNGAP1-associated haploinsufficiency.


Subject(s)
Alternative Splicing , Intellectual Disability , Humans , Mice , Animals , Up-Regulation , Alternative Splicing/genetics , Neurons/metabolism , Mice, Knockout , Intellectual Disability/genetics , ras GTPase-Activating Proteins/genetics , ras GTPase-Activating Proteins/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Polypyrimidine Tract-Binding Protein/genetics
8.
Heliyon ; 9(2): e13185, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36747547

ABSTRACT

Background: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. Methods: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package "limma". Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. Results: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. Conclusion: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA.

10.
Waste Manag ; 157: 141-148, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36538835

ABSTRACT

Annually increasing electric vehicles will undoubtedly end in tremendous amount of waste LiFePO4 (LFP) batteries. In this work, a highly-efficient and easy-going solid-phase method is proposed for direct regeneration of the waste LFP cathode material (W-LFP). The W-LFP is successfully regenerated via heat treatment with the addition of Li2CO3, CNTs and glucose. After activation, the dispersibility of CNTs in water is improved, making it easier to mix well with other materials. Also, the hydroxyl and carboxyl groups on CNTs have a certain degree of reducibility, which is conducive to the reduction of Fe3+ to Fe2+. After subsequent heat treatment, the three-dimensional conductive network composed of CNTs greatly enhances the conductivity and the ionic diffusion coefficient of LFP, thereby improving its electrochemical performance. Meanwhile, the decay and regeneration mechanisms of LFP are investigated by characterization and electrochemical testing. The regenerated LFP achieves an excellent specific capacity of 155.47 mAh/g at 0.05 C, which is around 99% that of new LFP. Additionally, the costs of main consumption in the regeneration process only account for 33.7% the price of new LFP. This low-cost, high-value-added and solid-phase direct regeneration process is proved to have great economic and energy-saving potential, which is promising for recycling the waste LFP cathode materials.


Subject(s)
Electric Power Supplies , Lithium , Lithium/chemistry , Electrodes , Recycling , Ions/chemistry , Waste Products
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-993325

ABSTRACT

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008876

ABSTRACT

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.


Subject(s)
Humans , Drugs, Chinese Herbal/therapeutic use , Inflammation/drug therapy , Medicine, Chinese Traditional , Respiratory Tract Infections/drug therapy , Treatment Outcome
13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008735

ABSTRACT

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.


Subject(s)
Child , Humans , Drugs, Chinese Herbal/therapeutic use , Treatment Outcome , Clinical Trials as Topic , Respiratory Tract Infections/drug therapy
14.
Aquat Toxicol ; 253: 106328, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36302320

ABSTRACT

As a typical type of persistent organic pollutant, perfluorooctanoic acid (PFOA) is pervasive in the environment. Multiple studies have found that PFOA has hepatotoxicity, but the mechanism remains poorly understood. In this study, the toxic effects of different concentrations of PFOA on zebrafish liver cells were systematically assessed by recording cell survival, ultrastructural observations, and transcriptome analyses. The results showed that the inhibition of cell viability and the massive accumulation of autophagic vacuoles were observed at 400 µM PFOA, while transcriptomic changes occurred with treatments of 1 and 400 µM PFOA. The transcription levels of 1055 (977 up- and 78 down-regulated genes) and 520 (446 up- and 74 down-regulated genes) genes were significantly changed after treatment with 1 and 400 µM PFOA, respectively. Based on Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, significant expression changes were observed in autophagy, tight junction, signal transduction, immune system, endocrine system, and metabolism-related pathways, indicating that such processes were greatly affected by PFOA exposure. The findings of this study will provide a scientific basis for the toxic effects and potential toxic mechanisms of PFOA on zebrafish, and provide information for ecological risk assessments.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/metabolism , Water Pollutants, Chemical/toxicity , Caprylates/toxicity , Caprylates/metabolism , Liver
15.
Front Synaptic Neurosci ; 14: 939793, 2022.
Article in English | MEDLINE | ID: mdl-36176941

ABSTRACT

Synapses are the basic units for information processing and storage in the nervous system. It is only when the synaptic connection is established, that it becomes meaningful to discuss the structure and function of a circuit. In humans, our unparalleled cognitive abilities are correlated with an increase in the number of synapses. Additionally, genes involved in synaptogenesis are also frequently associated with neurological or psychiatric disorders, suggesting a relationship between synaptogenesis and brain physiology and pathology. Thus, understanding the molecular mechanisms of synaptogenesis is the key to the mystery of circuit assembly and neural computation. Furthermore, it would provide therapeutic insights for the treatment of neurological and psychiatric disorders. Multiple molecular events must be precisely coordinated to generate a synapse. To understand the molecular mechanisms underlying synaptogenesis, we need to know the molecular components of synapses, how these molecular components are held together, and how the molecular networks are refined in response to neural activity to generate new synapses. Thanks to the intensive investigations in this field, our understanding of the process of synaptogenesis has progressed significantly. Here, we will review the molecular mechanisms of synaptogenesis by going over the studies on the identification of molecular components in synapses and their functions in synaptogenesis, how cell adhesion molecules connect these synaptic molecules together, and how neural activity mobilizes these molecules to generate new synapses. Finally, we will summarize the human-specific regulatory mechanisms in synaptogenesis and results from human genetics studies on synaptogenesis and brain disorders.

16.
Science ; 377(6614): eabo7257, 2022 09 30.
Article in English | MEDLINE | ID: mdl-36007006

ABSTRACT

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.


Subject(s)
Dorsolateral Prefrontal Cortex , Evolution, Molecular , Primates , Somatostatin , Tyrosine 3-Monooxygenase , Adult , Animals , Dopamine/metabolism , Dorsolateral Prefrontal Cortex/cytology , Dorsolateral Prefrontal Cortex/metabolism , Humans , Pan troglodytes , Primates/genetics , Single-Cell Analysis , Somatostatin/genetics , Somatostatin/metabolism , Transcriptome , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolism
17.
Sheng Li Xue Bao ; 74(3): 489-494, 2022 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-35770646

ABSTRACT

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.


Subject(s)
Circadian Rhythm , Hearing Loss, Noise-Induced , Animals , Auditory Threshold , Cochlea , Evoked Potentials, Auditory, Brain Stem/physiology , Hair Cells, Auditory , Noise/adverse effects
18.
Exp Appl Acarol ; 86(3): 343-356, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35239074

ABSTRACT

Vitellogenin (Vg) is an important factor that impacts oocyte maturation, egg formation and embryonic development in Arthropoda. Two orthologs of Vg gene were obtained from the genome of Phytoseiulus persimilis and termed as PpVg1 and PpVg2. Both orthologs belong to the large lipid transfer protein superfamily. The expression of PpVg1 and PpVg2 was low in immatures and male adults, and increased rapidly in female adults after mating, and reached a peak before the first egg was laid (168×  and 20.5×  the level in virgin females, respectively). When PpVg1 and PpVg2 were interfered with dsRNA, the relative expression decreased by 81.0 and 30.9%, respectively, and 7.8 and 31.4% interfered individuals died within 24 h. Among surviving individuals, ca. 51.1 and 44.8% are infertile. Factors that might be related to expression of Vg genes are also discussed.


Subject(s)
Mites , Vitellogenins , Animals , Female , Male , Reproduction , Vitellogenins/genetics , Vitellogenins/metabolism
19.
Front Cell Infect Microbiol ; 12: 827643, 2022.
Article in English | MEDLINE | ID: mdl-35223552

ABSTRACT

Fluoride-containing toothpaste is daily used in toothbrush. Some compounds derived from natural herbs that have antibacterial and anti-inflammatory activities has attracted increasing attention as potential supplements for the control of oral diseases. In this paper, a natural product mixture (NPM-8) containing eight herbs extracts was added to toothpaste, and its antibacterial and anti-inflammatory effects were investigated. The results showed that NPM-8-containing toothpaste exhibited superior and faster inhibitory and bactericidal effects against S. mutans, S. sanguinis and P. gingivalis than that of the NPM-8-free toothpaste. NPM-8-containing toothpaste significantly reduced the biomass of single-species or three-species biofilms. The cytotoxicity of the NPM-8-containing toothpaste was similar to that of the conventional fluoride toothpaste and CHX. The NPM-8-containing toothpaste could significantly inhibit IL-1ß and IL-6 production in HGE cells and exhibited a better anti-inflammatory effect than that of the NPM-8-free toothpaste. In conclusion, NPM-8-containing fluoride toothpaste is superior to conventional fluoride toothpaste in regard to their antibacterial, antibiofilm, and anti-inflammatory properties. NPM-8-containing toothpaste also has good biocompatibility and is safe for daily use. It indicates that NPM-8 is a promising natural product mixture in oral health.


Subject(s)
Biological Products , Toothpastes , Anti-Bacterial Agents/pharmacology , Biological Products/pharmacology , Fluorides/pharmacology , Sodium Fluoride/pharmacology , Toothpastes/pharmacology
20.
Genet Med ; 24(2): 319-331, 2022 02.
Article in English | MEDLINE | ID: mdl-34906466

ABSTRACT

PURPOSE: Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown. METHODS: We used exome sequencing to uncover ADD1 variants associated with intellectual disability (ID) and brain malformations. We studied ADD1 splice isoforms in mouse and human neocortex development with RNA sequencing, super resolution imaging, and immunoblotting. We investigated 4 variant ADD1 proteins and heterozygous ADD1 cells for protein expression and ADD1-ADD2 dimerization. We studied Add1 functions in vivo using Add1 knockout mice. RESULTS: We uncovered loss-of-function ADD1 variants in 4 unrelated individuals affected by ID and/or structural brain defects. Three additional de novo copy number variations covering the ADD1 locus were associated with ID and brain malformations. ADD1 is highly expressed in the neocortex and the corpus callosum, whereas ADD1 splice isoforms are dynamically expressed between cortical progenitors and postmitotic neurons. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. CONCLUSION: Our human and mouse genetics results indicate that pathogenic ADD1 variants cause corpus callosum dysgenesis, ventriculomegaly, and/or ID.


Subject(s)
Hydrocephalus , Intellectual Disability , Agenesis of Corpus Callosum/genetics , Agenesis of Corpus Callosum/pathology , Animals , DNA Copy Number Variations , Humans , Hydrocephalus/genetics , Intellectual Disability/genetics , Mice , Phenotype
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