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Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth-associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.
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Sinapsis , Transmisión Sináptica , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Mitocondrias/metabolismo , Plasticidad Neuronal/fisiología , AutofagiaRESUMEN
Oligoasthenoteratozoospermia (OAT) is a common type of male infertility; however, its genetic causes remain largely unknown. Some of the genetic determinants of OAT are gene defects affecting spermatogenesis. BCORL1 (BCL6 corepressor like 1) is a transcriptional corepressor that exhibits the OAT phenotype in a knockout mouse model. A hemizygous missense variant of BCORL1 (c.2615T > G:p.Val872Gly) was reported in an infertile male patient with non-obstructive azoospermia (NOA). Nevertheless, the correlation between BCORL1 variants and OAT in humans remains unknown. In this study, we used whole-exome sequencing to identify a novel hemizygous nonsense variant of BCORL1 (c.1564G > T:p.Glu522*) in a male patient with OAT from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Further population screening identified four BCORL1 missense variants in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%), but no pathogenic BCORL1 variants among 362 fertile subjects. In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1.
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Secuenciación del Exoma , Infertilidad Masculina , Proteínas Represoras , Masculino , Humanos , Proteínas Represoras/genética , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Oligospermia/genética , Oligospermia/patología , Adulto , Linaje , Azoospermia/genética , Azoospermia/patología , Mutación con Pérdida de Función/genética , Predisposición Genética a la Enfermedad , Proteína-Arginina N-Metiltransferasas/genética , Mutación Missense/genética , Espermatogénesis/genéticaRESUMEN
This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.
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We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from â¼7.1 to â¼1.7â nm, corresponding to a pulse-width-tuning range from â¼350â fs to â¼1.56â ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of â¼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.
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We demonstrate a compact ultrafast fiber laser system that can deliver 1.87â GHz pulse train at 1550â nm with a pulse energy of 52â pJ and an ultrashort pulse duration of 57â fs. While an acousto-optic mode-locking fiber laser was used as the seed light source at GHz rate, a stage of Er-doped fiber amplifier boosted the laser power to â¼320â mW, giving a pulse energy of â¼170â pJ. Then, a pulse compression setup was constructed, providing a high compression ratio of â¼10 with a total efficiency of â¼32%. In the cascaded compression configuration, multiple fiber samples with alternately normal and anomalous dispersion were fused together, providing efficient nonlinear spectral broadening while suppressing excessive pulse broadening over propagation. This GHz-rate ultrafast fiber laser, with compact configuration, broad optical spectrum, and high time-resolving ability could be used as the seed light source for constructing high-rate, high-power ultrafast laser systems and may find a few applications in optical measurements and microwave photonics.
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Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.
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PURPOSE: The preimplantation genetic testing for aneuploidy (PGT-A) platform is not currently available for small copy-number variants (CNVs), especially those < 1 Mb. Through strategies used in PGT for monogenic disease (PGT-M), this study intended to perform PGT for families with small pathogenic CNVs. METHODS: Couples who carried small pathogenic CNVs and underwent PGT at the Reproductive and Genetic Hospital of CITIC-Xiangya (Hunan, China) between November 2019 and April 2023 were included in this study. Haplotype analysis was performed through two platforms (targeted sequencing and whole-genome arrays) to identify the unaffected embryos, which were subjected to transplantation. Prenatal diagnosis using amniotic fluid was performed during 18-20 weeks of pregnancy. RESULTS: PGT was successfully performed for 20 small CNVs (15 microdeletions and 5 microduplications) in 20 families. These CNVs distributed on chromosomes 1, 2, 6, 7, 13, 15, 16, and X with sizes ranging from 57 to 2120 kb. Three haplotyping-based PGT-M strategies were applied. A total of 89 embryos were identified in 25 PGT cycles for the 20 families. The diagnostic yield was 98.9% (88/89). Nineteen transfers were performed for 17 women, resulting in a 78.9% (15/19) clinical pregnancy rate after each transplantation. Of the nine women who had healthy babies, eight accepted prenatal diagnosis and the results showed no related pathogenic CNVs. CONCLUSION: Our results show that the extended haplotyping-based PGT-M strategy application for small pathogenic CNVs compensated for the insufficient resolution of PGT-A. These three PGT-M strategies could be applied to couples with small pathogenic CNVs.
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Aborto Espontáneo , Diagnóstico Preimplantación , Embarazo , Humanos , Femenino , Diagnóstico Preimplantación/métodos , Pruebas Genéticas/métodos , Índice de Embarazo , Aborto Espontáneo/genética , Nacimiento Vivo , AneuploidiaRESUMEN
AIMS: To identify the contaminated areas of the hand collection and analyse the distribution characteristics of bacteria in the hand after swab collection. DESIGN: This study used a cross-sectional design. METHODS: A cross-sectional study sampling 50 pairs of hands (sampling hand and auxiliary hand) of healthcare workers was performed. Ten samples were collected from each participant. The optimal hand hygiene rates and bacterial colony counts of the whole hand and different hand sections without hand hygiene were identified as the primary outcomes. RESULTS: The optimal hand hygiene rates of the sampling hand and auxiliary hand were 88.8% (222/250) and 91.6% (229/250), respectively. The lowest optimal hand hygiene rates for the sampling hand and the auxiliary hand were both on the dorsal side of the finger and the dorsum of the hand (86.0%, 86.0% vs. 90.0%, 86.0%); the optimal hand hygiene rates for both sites of the sampling hand were 86.0% (43/50), and the optimal hand hygiene rates for the auxiliary hand were 90.0% (45/50) and 86.0% (43/50). The bacteria colony counts did not differ between the sampling hands and auxiliary hand. CONCLUSIONS: The dorsal side of the finger and dorsum of the hand were the most likely to be contaminated during oropharyngeal swab collection. Therefore, it is essential to pay extra attention to hand hygiene care of these two sites during the collection process to minimize the risk of cross-contamination. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were adopted in this study.
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BACKGROUND: During the brewing of soy sauce, the conversion of multiple substances is driven by various microorganisms and their secreted enzyme systems. Soy sauce mash is an important source of enzyme systems during moromi fermentation, but the changes of enzyme systems in soy sauce mash during moromi fermentation are poorly understood. In order to explore the predominant enzyme systems existing during moromi fermentation and to explain the characteristics of the enzyme system changes, an enzymatic activities assay and 4D-label-free proteomics analysis were conducted on soy sauce mash at different stages of fermentation. RESULTS: The activities of hydrolytic enzymes in soy sauce mash decreased continuously throughout the fermentation process, while most of the characteristic physicochemical substances in soy sauce mash supernatant had already accumulated at the early stage of fermentation. Four hydrolytic enzymes were found to be positively correlated with important physicochemical indexes by principal component analysis and Pearson correlation analysis. The proteomics analysis revealed three highly upregulated enzymes and two enzymes that were present in important metabolic pathways throughout the fermentation process. Furthermore, it was found that Aspergillus oryzae was able to accumulate various nutrients in the soy sauce mash by downregulating most of its metabolic pathways. CONCLUSION: Enzymes present with excellent properties during the moromi fermentation period could be obtained from these results. Meanwhile, the characterization of the metabolic pathways of microorganisms during the moromi fermentation period was revealed. The results provide a basis for more scientific and purposeful improvement of moromi fermentation in the future. © 2024 Society of Chemical Industry.
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Fermentación , Proteómica , Alimentos de Soja , Alimentos de Soja/análisis , Alimentos de Soja/microbiología , Proteínas Fúngicas/metabolismo , Aspergillus oryzae/metabolismo , Aspergillus oryzae/enzimologíaRESUMEN
This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.
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Isquemia Encefálica , FN-kappa B , Ratas , Masculino , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Quinasa I-kappa B/metabolismo , Quinasa I-kappa B/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Interleucina-6/genética , Péptido Relacionado con Gen de Calcitonina/farmacología , Ratas Sprague-Dawley , Transducción de Señal , Isquemia Encefálica/tratamiento farmacológico , ComprimidosRESUMEN
BACKGROUND: As a newly defined regulated cell death, ferroptosis is a potential biomarker in ovarian cancer (OV). However, its underlying mechanism in tumor microenvironment (TME) and clinical prediction significance in OV remained to be elucidated. METHODS: The transcriptome data of high-grade serous OV from The Cancer Genome Atlas (TCGA) database were downloaded. Molecular subtypes were classified based on ferroptosis-correlated genes from the FerrDb database by performing consensus clustering analysis. The associations between the subtypes and clinicopathologic characteristics, mutation, regulatory pathways and immune landscape were assessed. A ferroptosis-related prognostic model was constructed and verified using International Cancer Genome Consortium (ICGC) cohort and GSE70769. RESULTS: Three molecular subtypes of OV were defined. Patients in subtype C3 tended to have the most favorable prognosis, while subtype C1 showing more mesenchymal cells, increased immune infiltration of Macrophages_M2, lower tumor purity, and epithelial-to-mesenchymal transition (EMT) features had the poorest prognosis. A ferroptosis-related risk model was constructed using 8 genes (PDP1, FCGBP, EPHA4, GAS1, SLC7A11, BLOC1S1, SPOCK2, and CXCL9) and manifested a strong prediction performance. High-risk patients had enriched EMT pathways, more Macrophages_M2, less plasma cells and CD8 cell infiltration, greater tendency of immune escape and worse prognosis. The risk score has negatively correlated relation with LAG3, TIGIT, CTLA4, IDO1, CD27, ICOS, and IL2RB but positively correlated with PVR, CD276, and CD28. Moreover, low-risk patients were more sensitive to Cisplatin and Gefitinib, Gemcitabine. CONCLUSIONS: Our results could improve the understanding of ferroptosis in OV, providing promising insights for the clinical targeted therapy for the cancer.
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Ferroptosis , Neoplasias Ováricas , Microambiente Tumoral , Ferroptosis/genética , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Pronóstico , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Transcriptoma , Transición Epitelial-Mesenquimal/genética , Clasificación del TumorRESUMEN
BACKGROUND: Ice and snow sports, which are inherently high risk due to their physically demanding nature, pose significant challenges in terms of participant safety. These activities increase the likelihood of injuries, largely due to reduced bodily agility and responsiveness in cold, often unpredictable winter environments. The critical need for effective injury prevention in these sports is emphasized by the considerable impact injuries have on the health of participants, alongside the economic and social costs associated with medical and rehabilitative care. In the context of ice and snow sports environments, applying the E principles of injury prevention to evaluate intervention measures can guide the implementation of future sports safety and other health promotion intervention measures in this field. When well executed, this approach can substantially reduce both the frequency and severity of injuries, thereby significantly enhancing the safety and long-term viability of these challenging sports. OBJECTIVE: The objective of this study was to rigorously assess and statistically substantiate the efficacy of diverse injury prevention strategies in ice and snow sports, aiming to bolster future safety measures with solid empirical evidence. DESIGN: Systematic review and meta-analysis. METHODS: The overarching aim of this research was to meticulously aggregate and scrutinize a broad spectrum of scholarly literature, focusing on the quantifiable efficacy of diverse, multicomponent intervention strategies in mitigating the incidence of injuries within the realm of ice and snow sports. This endeavour entailed an exhaustive extraction of data from esteemed academic databases, encompassing publications up to September 30, 2023. In pursuit of methodological excellence and analytical rigor, the study employed advanced bias assessment methodologies, notably the AMSTAR 2 and GRADE approaches, alongside sophisticated random-effects statistical modelling. This comprehensive approach was designed to ensure the utmost validity, reliability, and scholarly integrity of the study's findings. RESULTS: Fifteen papers, including 9 randomized controlled trials, 3 caseâcontrol studies, and 3 cohort studies with 26,123 participants and 4,382 injuries, were analysed. The findings showed a significant reduction in injury rates through various interventions: overall injury prevention (RR = 0.50, 95% CI 0.42-0.63), educational training (RR = 0.50, 95% CI 0.34-0.73), educational videos (RR = 0.53, 95% CI 0.34-0.81), protective equipment (RR = 0.64, 95% CI 0.46-0.87), and policy changes (RR = 0.28, 95% CI 0.16-0.49). Subgroup analysis revealed potential heterogeneity in compliance (p = 0.347). Compared to controls, multicomponent interventions effectively reduced injury rates. CONCLUSION: This systematic review and meta-analysis demonstrated that multicomponent interventions significantly prevent injuries in ice and snow sports. By applying the E principles of injury prevention and constructing a framework for practical injury prevention research in ice and snow sports, we can gradually shift towards a systemic paradigm for a better understanding of the development and prevention of sports injuries. Moreover, sports injury prevention is a complex and dynamic process. Therefore, high-quality experiments in different scenarios are needed in future research to provide more reliable evidence, offer valuable and relevant prevention information for practitioners and participants, and help formulate more effective preventive measures in practice.
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ETHNOPHARMACOLOGICAL RELEVANCE: Some species of Codonopsis (local name in Shanxi: Ludang) have long demonstrated high medicinal and economic value. Radix Codonopsis, the dried root of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. modesta (Nannf.) L.D.Shen (C. pilosula var. modesta), or Codonopsis pilosula subsp. tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), was recorded as a traditional Chinese medicine back in the Qing Dynasty in Ben Cao Cong Xin. Radix Codonopsis, a valuable medicinal herb certified by the Chinese National Geographic Indication, is known for invigorating the spleen, nourishing the lungs, promoting blood circulation, and generating fluid properties. Given that chronic cerebral ischemia (CCI) is often associated with the symptoms of qi and blood deficiencies and fluid depletion, we explored the potential of Codonopsis decoction in the treatment of CCI. STUDY AIMS: We investigated the effects of Codonopsis decoction on cerebral blood flow (CBF) and cognitive function in rats with bilateral carotid artery occlusion after surgery; explored whether Codonopsis decoction alleviates pathological injuries in brain tissue of rats after 2-VO surgery; and assessed the impact of Codonopsis decoction on the expression of chemokines, hypoxia-inducible factors, and inflammatory mediators in rats after 2-VO surgery. MATERIALS AND METHODS: We used a 2-VO rat model to simulate CCI. We used a laser speckle imaging (LSI) system to observe changes in CBF before and after surgery. The goal was to examine variations in CBF at different time points after 2-VO surgery. For 4 weeks, the rats were orally administered Codonopsis decoction at doses of 2.7, 5.4, and 10.8 g/kg/day, or Ginaton at a dose of 43.2 mg/kg/day. To assess the effect of Codonopsis on cerebral hypoperfusion symptoms in rats, we conducted the Morris water maze (MWM), Barnes maze (BM), and forelimb grip strength tests. Additionally, pathological experiments including hematoxylin and eosin, Nissl, and Luxol fast blue staining were conducted. Furthermore, we used western blotting to detect changes in the levels of proteins such as the chemotactic factor CKLF1 and hypoxia-inducible actor 1-alpha (HIF-1α). RESULTS: One week after 2-VO surgery, cerebral arterial blood supply in the rats rapidly reduced to approximately 43.39% ± 3.53% of the preoperative level. Cerebral cortex perfusion reached its nadir within 24 h of surgery, gradually recovering and stabilizing by the fourth week after surgery. An integration of the results from the BM, MWM, and grip strength tests, which assessed cognitive function and forelimb strength in rats after 2-VO surgery, unequivocally revealed that Codonopsis treatment significantly reduced the latency period and increased the number of platform crossings in the MWM test. Ginaton exhibited a comparable effect. Moreover, both Codonopsis and Ginaton decreased the number of errors and the time required to locate the target hole in the BM test. Histopathological staining revealed that Codonopsis and Ginaton could ameliorate pathological damage in rats after CCI and reduce the release of factors such as CKLF1 and HIF-1α. CONCLUSION: Codonopsis decoction exerted its protective effects on CCI rats possibly by modulating the levels of chemokines, hypoxia-inducible factors, and neuroinflammatory mediators.
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Isquemia Encefálica , Codonopsis , Ratas , Animales , Isquemia Encefálica/tratamiento farmacológico , Cognición , Circulación Cerebrovascular , Quimiocinas , HipoxiaRESUMEN
Socioeconomic status' (SES) impact on depressive symptoms has been extensively examined; however, previous studies have generally used variable-centered approaches and cross-sectional designs. Therefore, this study explored the subtypes of depression and examined the degree of association between SES and latent transition probabilities. We used latent profile and latent transition analyses with the 2015 and 2018 waves of data from the China Health and Retirement Longitudinal Study (N = 4904). Three subtypes of depression were identified based on symptoms: severe symptom (SS), low symptom (LS), and sub-health (MS). The SS subtype had the highest probability of staying within the original subtype. Individuals in the MS subtype were more likely to move to the SS subtype than those in the LS subtype. The heterogeneity analysis also showed that the effect of SES on latent transition probabilities is heterogeneous to the satisfaction with their relationship with their children, as well as the number of children. Additionally, decision tree analysis found SES and gender can predict transitioning. These findings add to literature on the effects of SES on the heterogeneity of depression and have implications for depression screening and identifying individuals in need of targeted interventions.
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Depresión , Clase Social , Humanos , Masculino , Femenino , Estudios Longitudinales , China , Anciano , Persona de Mediana Edad , Pueblos del Este de AsiaRESUMEN
Ginsenoside is the principal active ingredient in ginseng. Several investigations have found that ginsenosides have anti-inflammatory, antioxidant, anti-apoptotic, anti-cancer, and antiallergic activities. Ferroptosis is an iron-dependent, non-apoptotic form of cell-regulated death caused by lipid peroxidation. Iron, lipid, and amino acid metabolism orchestrate the complex ferroptosis response through direct or indirect regulation of iron accumulation or lipid peroxidation. More and more research has demonstrated that ginsenoside impacts illnesses via ferroptosis, implying that ferroptosis might be employed as a novel target of ginsenoside for disease therapy. This article examines the molecular mechanism of ferroptosis as well as the current advancement of ginsenoside in influencing disorders via ferroptosis.
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Ferroptosis , Ginsenósidos , Ginsenósidos/farmacología , Ginsenósidos/química , Ferroptosis/efectos de los fármacos , Humanos , Animales , Peroxidación de Lípido/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Hierro/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Panax/químicaRESUMEN
STUDY QUESTION: Are there other pathogenic genes for asthenoteratozoospermia (AT)? SUMMARY ANSWER: DNAH3 is a novel candidate gene for AT in humans and mice. WHAT IS KNOWN ALREADY: AT is a major cause of male infertility. Several genes underlying AT have been reported; however, the genetic aetiology remains unknown in a majority of affected men. STUDY DESIGN SIZE DURATION: A total of 432 patients with AT were recruited in this study. DNAH3 mutations were identified by whole-exome sequencing (WES). Dnah3 knockout mice were generated using the genome editing tool. The morphology and motility of sperm from Dnah3 knockout mice were investigated. The entire study was conducted over 3 years. PARTICIPANTS/MATERIALS SETTING METHODS: WES was performed on 432 infertile patients with AT. In addition, two lines of Dnah3 knockout mice were generated. Haematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunostaining, and computer-aided sperm analysis (CASA) were performed to investigate the morphology and motility of the spermatozoa. ICSI was used to overcome the infertility of one patient and of the Dnah3 knockout mice. MAIN RESULTS AND THE ROLE OF CHANCE: DNAH3 biallelic variants were identified in three patients from three unrelated families. H&E staining revealed various morphological abnormalities in the flagella of sperm from the patients, and TEM and immunostaining further showed the loss of the central pair of microtubules, a dislocated mitochondrial sheath and fibrous sheath, as well as a partial absence of the inner dynein arms. In addition, the two Dnah3 knockout mouse lines demonstrated AT. One patient and the Dnah3 knockout mice showed good treatment outcomes after ICSI. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This is a preliminary report suggesting that defects in DNAH3 can lead to asthenoteratozoospermia in humans and mice. The pathogenic mechanism needs to be further examined in a future study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that DNAH3 is a novel candidate gene for AT in humans and mice and provide crucial insights into the biological underpinnings of this disorder. The findings may also be beneficial for counselling affected individuals. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from National Natural Science Foundation of China (82201773, 82101961, 82171608, 32322017, 82071697, and 81971447), National Key Research and Development Program of China (2022YFC2702604), Scientific Research Foundation of the Health Committee of Hunan Province (B202301039323, B202301039518), Hunan Provincial Natural Science Foundation (2023JJ30716), the Medical Innovation Project of Fujian Province (2020-CXB-051), the Science and Technology Project of Fujian Province (2023D017), China Postdoctoral Science Foundation (2022M711119), and Guilin technology project for people's benefit (20180106-4-7). The authors declare no competing interests.