RESUMEN
Understanding how life's essential homochiral biopolymers arose from racemic precursors is a challenging quest. Herein, we present a groundbreaking approach involving hierarchical chiral assembly-driven stereoselective ring-opening polymerization of ε-benzyloxycarbonyl-l/d-lysine N-carboxyanhydrides assisted by ultrasonication in an aqueous medium. This method enabled a narrow dispersity within a few minutes and the achievement of high molecular weight for polypeptides, employing a living polymerization mechanism. The polymerization of l and d enantiomers yielded predominantly right- and left-handed superhelical assemblies in a one-pot preparation, respectively. Notably, stereoselective polypeptide segments were efficiently prepared through hierarchical assembly-driven polymerization of racemic monomers in the absence of a catalyst. This research offers an innovative strategy for the convenient preparations of stereoenriched polypeptides and, more importantly, sheds light on the plausible emergence of homochiral peptides in the origin of life.
RESUMEN
BACKGROUND: COVID-19 has triggered a global public health crisis, and had an impact on economies, societies, and politics around the world. Based on the pathogen prevalence hypothesis suggested that residents of areas with higher infection rates are more likely to be collectivists as compared with those of areas with lower infection rates. Many researchers had studied the direct link between infectious diseases and individualism/collectivism (infectious diseasesâ cultural values), but no one has focused on the specific psychological factors between them: (infectious diseasesâ cognition of the pandemicâ cultural values). To test and develop the pathogen prevalence hypothesis, we introduced pandemic mental cognition and conducted an empirical study on social media (Chinese Sina Weibo), hoping to explore the psychological reasons behind in cultural value changes in the context of a pandemic. METHODS: We downloaded all posts from active Sina Weibo users in Dalian during the pandemic period (January 2020 to May 2022) and used dictionary-based approaches to calculate frequency of words from two domains (pandemic mental cognition and collectivism/individualism), respectively. Then we used the multiple log-linear regression analysis method to establish the relationship between pandemic mental cognition and collectivism/individualism. RESULTS: Among three dimensions of pandemic mental cognition, only the sense of uncertainty had a significant positive relationship with collectivism, and also had a marginal significant positive relationship with individualism. There was a significant positive correlation between the first-order lag term AR(1) and individualism, which means the individualism tendency was mainly affected by its previous level. CONCLUSIONS: The study found that more collectivist regions are associated with a higher pathogen burden, and recognized the sense of uncertainty as its underlying cause. Results of this study validated and further developed the pathogen stress hypothesis in the context of the COVID-19 pandemic.
Asunto(s)
COVID-19 , Enfermedades Transmisibles , Medios de Comunicación Sociales , Humanos , COVID-19/epidemiología , Pandemias , Cognición , Enfermedades Transmisibles/epidemiologíaRESUMEN
The electric double layer governs the processes of all charged surfaces in aqueous solutions; however, elucidating the structure of the water molecules is challenging for even the most advanced spectroscopic techniques. Here, we present the individual Stern layer and diffuse layer OH stretching spectra at the silica/water interface in the presence of NaCl over a wide pH range using a combination of vibrational sum frequency generation spectroscopy, heterodyned second harmonic generation, and streaming potential measurements. We find that the Stern layer water molecules and diffuse layer water molecules respond differently to pH changes: unlike the diffuse layer, whose water molecules remain net-oriented in one direction, water molecules in the Stern layer flip their net orientation as the solution pH is reduced from basic to acidic. We obtain an experimental estimate of the non-Gouy-Chapman (Stern) potential contribution to the total potential drop across the insulator/electrolyte interface and discuss it in the context of dipolar, quadrupolar, and higher order potential contributions that vary with the observed changes in the net orientation of water in the Stern layer. Our findings show that a purely Gouy-Chapman (Stern) view is insufficient to accurately describe the electrical double layer of aqueous interfaces.
Asunto(s)
Electrólitos , Agua , Electricidad , Electrólitos/química , Dióxido de Silicio , Propiedades de Superficie , Agua/químicaRESUMEN
CONTEXT: The Chinese herbal prescription JieZe-1 (JZ-1) is effective against HSV-2 (Herpes simplex virus type 2) infection. However, its mechanism remains unclear. OBJECTIVE: To explore the mechanism of JZ-1 in protecting against HSV-2 infection. MATERIALS AND METHODS: Using the methods of network pharmacology, the hub components and targets were screened and functionally enriched. We established a genital herpes (GH) mouse model and observe the disease characteristics. Then, the GH mice in different groups (10 per/group) were treated with 20 µL JZ-1 gel (2.5, 1.5, and 0.5 g/mL), acyclovir gel (0.03 g/mL), or plain carbomer gel twice a day. The symptom score, vulvar histomorphology, and virus load were measured. The critical proteins of caspase-1-dependent pyroptosis were analysed by microscopy, co-immunoprecipitation, western blotting, and ELISA. Molecular docking was also performed. RESULTS: Network pharmacology analysis identified 388 JZ-1 targets related to HSV-2 infection, with 36 hub targets and 21 hub components screened. The TCID50 of HSV-2 was 1 × 10-7/0.1 mL. JZ-1 gel (2.5 g/mL) can effectively reduce the symptom score (81.23%), viral load (98.42%) and histopathological changes, and significantly inhibit the proteins expression of caspase-1-dependent pyroptosis in GH mice (p< 0.05). The molecular docking test showed a good binding potency between 11 components and caspase-1 or interleukin (IL)-1ß. DISCUSSION AND CONCLUSIONS: The present study demonstrated that JZ-1 protected mice from HSV-2 infection and inhibit the caspase-1-dependent pyroptosis in GH mice. It is of significance for the second development of JZ-1 and the exploration of new drugs.
Asunto(s)
Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Herpes Genital/tratamiento farmacológico , Herpesvirus Humano 2/efectos de los fármacos , Aciclovir/farmacología , Animales , Antivirales/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Herpes Genital/virología , Ratones , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , Farmacología en Red , Piroptosis/efectos de los fármacosRESUMEN
BACKGROUND: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. OBJECTIVE: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. METHODS: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. RESULTS: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. CONCLUSIONS: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.
Asunto(s)
Depresión , Salud Mental , China , Grupos Focales , Humanos , Encuestas y CuestionariosRESUMEN
The loss of an only child is one of the most painful life events and creates tremendous change in its parents' lives. Analyzing parents' online language use may help to better understand their loss, especially their psychological process. This study compared the online word use of 228 lost-only-child (LOC) parents to that of their peers. We also tracked the change in word use for a subset of these parents (n = 36) quarterly during the first 2 years following their bereavement. The implications of the word use of Chinese LOC parents for mood, parent-child bond, and lifestyle are then discussed.
Asunto(s)
Aflicción , Hijo Único , China , Humanos , Lenguaje , Lingüística , PadresRESUMEN
BACKGROUND: Abnormalities in vocal expression during a depressed episode have frequently been reported in people with depression, but less is known about if these abnormalities only exist in special situations. In addition, the impacts of irrelevant demographic variables on voice were uncontrolled in previous studies. Therefore, this study compares the vocal differences between depressed and healthy people under various situations with irrelevant variables being regarded as covariates. METHODS: To examine whether the vocal abnormalities in people with depression only exist in special situations, this study compared the vocal differences between healthy people and patients with unipolar depression in 12 situations (speech scenarios). Positive, negative and neutral voice expressions between depressed and healthy people were compared in four tasks. Multiple analysis of covariance (MANCOVA) was used for evaluating the main effects of variable group (depressed vs. healthy) on acoustic features. The significances of acoustic features were evaluated by both statistical significance and magnitude of effect size. RESULTS: The results of multivariate analysis of covariance showed that significant differences between the two groups were observed in all 12 speech scenarios. Although significant acoustic features were not the same in different scenarios, we found that three acoustic features (loudness, MFCC5 and MFCC7) were consistently different between people with and without depression with large effect magnitude. CONCLUSIONS: Vocal differences between depressed and healthy people exist in 12 scenarios. Acoustic features including loudness, MFCC5 and MFCC7 have potentials to be indicators for identifying depression via voice analysis. These findings support that depressed people's voices include both situation-specific and cross-situational patterns of acoustic features.
Asunto(s)
Trastorno Depresivo Mayor/fisiopatología , Acústica del Lenguaje , Calidad de la Voz , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Listeria monocytogenes is a facultative anaerobic Gram-positive bacterium. It is well adapted to external environments and able to infect both humans and animals. To understand the impacts of ncRNA Rli60 on the adaptability of L. monocytogenes to environmental stresses and biofilm formation, a rli60 deletion strain of L. monocytogenes (LM-Δrli60) was constructed using splicing by overlap extension PCR (SOE-PCR) and homologous recombination and then compared it with wild-type strain L. monocytogenes EGD-e in the aspects of adaptability to environmental stresses by measuring their growth under stresses of different temperatures, and acidic, alkaline, hypertonic and alcoholic conditions, and capability of biofilm formation by using crystal violet staining, as well as the transcriptional levels of genes (gltB and gltC) related to the biofilm formation by real-time quantitative PCR (qRT-PCR). The results showed that (1) the growth of LM-Δrli60 strain was significantly slower under environmental stresses of low temperature (30 °C), high temperature (42 °C), as well as alkaline and alcoholic conditions, (2) the amount of biofilm formed by LM-Δrli60 was attenuated, and (3) the transcriptional levels of gltB and gltC genes at 24 h and 48 h in LM-Δrli60 revealed a significant reduction. Overall, the results confirmed that ncRNA Rli60 plays important roles in regulating the adaptability of L. monocytogenes to environmental stresses and biofilm formation possibly through impacting the expression of gltB and gltC genes.
Asunto(s)
Biopelículas , Regulación Bacteriana de la Expresión Génica , Listeria monocytogenes/fisiología , ARN Bacteriano/metabolismo , ARN Largo no Codificante/metabolismo , Adaptación Fisiológica , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Humanos , Listeria monocytogenes/genética , ARN Bacteriano/genética , ARN Largo no Codificante/genética , Estrés FisiológicoRESUMEN
The nematode-trapping fungi possess a unique capability of predating and invading nematodes. As a representative nematode-trapping fungus, Arthrobotrys oligospora has been widely used to study the interactions between nematode-trapping fungi and their hosts. Serine proteinase is one of the important virulence factors during process of invasion of the nematode-trapping fungi into nematodes. In this study, using reverse transcription polymerase chain reaction, we amplified the gene sequence of serine proteinase 186 from A. oligospora, cloned it into pPIC9K vector and expressed it in the yeast Pichia pastoris. The expressed recombinant serine proteinase186 (reP186) was purified via Ni-affinity chromatography. The in vitro nematode-degrading activity of reP186 was analyzed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis revealed that reP186 with molecular weight of 33 kDa was successfully obtained. ReP186 was capable of degrading a series of protein substrates including casein, gelatin, bovine serum albumin, denatured collagen and nematode cortical layer. The reP186 exhibited the maximal activity at pH 8.0 and 55 °C and was highly sensitive to the inhibitor, phenylmethanesulfonylfluoride. Treatment of Caenorhabditis elegans and Haemonchus contortus with reP186 for 12, 24 and 36 h, respectively, resulted in 62, 88 and 100 % of killing rates for C. elegans, and 52, 65 and 84 % of killing rates for H. contortus, respectively, indicating a relatively strong nematode-degrading bioactivity of reP186.
Asunto(s)
Ascomicetos/enzimología , Caenorhabditis elegans/efectos de los fármacos , Haemonchus/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Serina Proteasas/metabolismo , Animales , Western Blotting , Caenorhabditis elegans/fisiología , Cromatografía de Afinidad , Clonación Molecular , Electroforesis en Gel de Poliacrilamida , Expresión Génica , Haemonchus/fisiología , Concentración de Iones de Hidrógeno , Peso Molecular , Pichia/genética , Pichia/metabolismo , Reacción en Cadena de la Polimerasa , Inhibidores de Proteasas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Serina Proteasas/química , Serina Proteasas/genética , Serina Proteasas/aislamiento & purificación , Análisis de Supervivencia , Temperatura , Compuestos de Tosilo/metabolismoRESUMEN
BACKGROUND: In recent years, women's fertility desire has attracted increasing attention in China. OBJECTIVE: This study aims to detect attitudes toward giving birth among young female users on Douban, a very popular Chinese social media platform. METHODS: A total of 2634 valid posts from 2489 users discussing the topic "What does childbirth mean to a woman" on Douban were crawled and retained for analysis. We utilized content and thematic analysis methods to capture users' concepts of childbirth. RESULTS: The findings reveal that a significant majority of users conveyed generally neutral (1060/2634, 40.24%) or negative (1051/2634, 39.90%) attitudes toward childbirth, while only about one-fifth of users expressed positive (523/2634, 19.86%) sentiments. Notably, posts with negative attitudes garnered more replies and likes, and the proportion of posts expressing negativity exhibited fluctuations over time. Health risk (339/2634, 12.87%) emerged as the most frequently cited aspect of childbirth cost, with subjective happiness and the fulfillment of mental needs identified as primary benefits. Surprisingly, only a minimal number of posts (10/2634, 0.38%) touched upon the traditional objective benefits of raising children for old-age care. Thematic analysis results suggest that discussions about fertility on social media platforms might contribute to an exaggerated perception of health risks among women. Additionally, a lack of knowledge about childbirth was observed, partially attributable to longstanding neglect and avoidance of communication on these matters, likely influenced by traditional cultural biases. Moreover, there is a prevailing assumption that women should naturally sacrifice themselves for childbirth and childcare, influenced by the idealization of the female figure. Consequently, women may harbor hesitations about having a baby, fearing the potential loss of their own identity in the process. CONCLUSIONS: The results indicate a shift in the perception of childbirth among modern Chinese women over time, influenced by their increasing social status and the pursuit of self-realization. Implementing strategies such as public education on the health risks associated with pregnancy and delivery, safeguarding women's rights, and creating a supportive environment for mothers may enhance women's willingness to undergo childbirth. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/preprints.50468.
RESUMEN
Objective: Genital herpes, primarily caused by HSV-2 infection, remains a widespread sexually transmitted ailment. Extracellular vesicles play a pivotal role in host-virus confrontation. Recent research underscores the influence of Chinese herbal prescriptions on extracellular vesicle production and composition. This study aims to probe the impact of JieZe-1 (JZ-1) on extracellular vesicle components, elucidating its mechanisms against HSV-2 infection via extracellular vesicles. Methods: The JZ-1's anti-HSV-2 effects were assessed using CCK-8 assay. Extracellular vesicles were precisely isolated utilizing ultracentrifugation and subsequently characterized through TEM, NTA, and Western Blot analyses. The anti-HSV-2 activity of extracellular vesicles was gauged using CCK-8, Western Blot, and immunofluorescence. Additionally, high-throughput sequencing was employed to detect miRNAs from extracellular vesicles, unraveling the potential antiviral mechanisms of JZ-1. Results: Antiviral efficacy of JZ-1 was shown in VK2/E6E7, HeLa, and Vero cells. The samples extracted from cell supernatant by ultracentrifugation were identified as extracellular vesicles. In VK2/E6E7 cells, extracellular vesicles from JZ-1 group enhanced cell survival rates and diminished the expression of intracellular viral protein gD, contrasting with the inert effect of control group vesicles. Extracellular vesicles from JZ-1 treated Vero cells demonstrated a weaker yet discernible anti-HSV-2 effect. Conversely, extracellular vesicles of HeLa cells exhibited no anti-HSV-2 effect from either group. High-throughput sequencing of VK2/E6E7 cell extracellular vesicles unveiled significant upregulation of miRNA-101, miRNA-29a, miRNA-29b, miRNA-29c, and miRNA-637 in JZ-1 group vesicles. KEGG pathway analysis suggested that these miRNAs may inhibit PI3K/AKT/mTOR signaling pathway and induce autophagy of host cells to protect against HSV-2. Western blot confirmed the induction of autophagy and inhibition of AKT/mTOR in VK2/E6E7 cells with JZ-1 group extracellular vesicles treatment. Conclusion: JZ-1 had an anti-HSV-2 efficacy. After JZ-1 stimulation, VK2/E6E7 cells secreted extracellular vesicles which protect host cells from HSV-2 infection. High-throughput sequencing showed that these extracellular vesicles contained a large number of miRNAs targeting PI3K/AKT/mTOR pathway. JZ-1 group extracellular vesicles could inhibit the activation of AKT/mTOR pathway and induce the host cells autophagy.
RESUMEN
Atherosclerosis is a leading cause of cardiovascular diseases, characterized by endothelial dysfunction and lipid accumulation. Long non-coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell behavior. This study aimed to investigate the role of lncRNA NORAD in endothelial cell proliferation and as a potential therapeutic target for atherosclerosis. A total of 75 CAD patients and 76 controls were recruited, and plasma NORAD levels were measured using qRT-PCR. HUVECs were transfected with si-NORAD to evaluate its effects on cell cycle, proliferation, migration, and apoptosis. Plasma NORAD levels were significantly elevated in CAD patients. The NORAD-miRNA-mRNA ceRNA regulatory network was constructed based on GEO database, and G1/S-specific cyclin-D1 (CCND1) was identified as one of the hub factors. NORAD deficiency suppressed cell migration and induced G1 cell cycle arrest in HUVECs by downregulating CCND1 in vitro. NORAD upregulated CCND1 in HUVECs via sponging miR-106a that inhibited cell migration. The dual-luciferase assay confirmed the direct targeting of miR-106a by NORAD, and overexpression of miR-106a inhibited HUVEC proliferation and migration. Si-NORAD transfection resulted in induced early apoptosis, increased intracellular ROS levels, decreased GSH levels, and reduced mitochondrial membrane potential. Additionally, si-NORAD decreased the expression of GPX4, FTH1, KEAP1, NCOA4, and Nrf2, while increasing Xct levels, confirming the involvement of ferroptosis. Our findings reveal that NORAD plays a critical role in endothelial cell proliferation, migration, and apoptosis, and its silencing induces ferroptosis. The regulatory network involving NORAD, miR-106a, and their target genes provides a potential therapeutic avenue for atherosclerosis.
Asunto(s)
Ciclina D1 , Células Endoteliales , Ferroptosis , MicroARNs , ARN Largo no Codificante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis/genética , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/sangre , Aterosclerosis/patología , Movimiento Celular , Proliferación Celular , Ciclina D1/metabolismo , Ciclina D1/genética , Ferroptosis/genética , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Células Endoteliales de la Vena Umbilical Humana/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/sangre , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , Células Endoteliales/metabolismoRESUMEN
Acute myeloid leukemia (AML) represents a highly malignant subtype of leukemia with limited therapeutic options. In this study, we propose a novel therapeutic strategy for treating AML by inhibiting SIRT3 to regulate mitochondrial metabolism network involved in energy metabolism and epigenetic modifications essential for AML survival. A series of thieno [3,2-d]pyrimidine-6-carboxamide derivatives were designed and synthesized by structure-based strategy, 17f was documented to be a potent and acceptable selective SIRT3 inhibitor with IC50 value of 0.043 µM and exhibited profound anti-proliferative activity in MOLM13, MV4-11, and HL-60 cells. Through CETSA assay and the degree of deacetylation of intracellular SIRT3 substrates, we confirmed that 17f could effectively bind and inhibit SIRT3 activity in AML cells. Mechanistically, 17f suppressed mitochondrial function, triggered the accumulation of ROS, and significantly inhibited the production of ATP in AML cells. With the breakdown of mitochondrial function, 17f eventually induced apoptosis of AML cells. In addition, 17f also showed excellent anti-AML potential in nude mouse tumor models of HL-60-Luc. Collectively, these results demonstrate that 17f is a potent and acceptable selective SIRT3 inhibitor with promising potential to treat AML.
Asunto(s)
Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Leucemia Mieloide Aguda , Sirtuina 3 , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Sitios de Unión/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones Desnudos , Estructura Molecular , NAD/metabolismo , Sirtuina 3/antagonistas & inhibidores , Sirtuina 3/metabolismo , Relación Estructura-ActividadRESUMEN
Peroxicedoxin 4 (PRDX4), a member of the peroxicedoxins (PRDXs), has been reported in many cancer-related studies, but its role in uterine corpus endometrial carcinoma (UCEC) is not fully understood. In the present study, we found that PRDX4 was highly expressed in UCEC tissues and cell lines through the combination of bioinformatics analysis and experiments, and elevated PRDX4 levels were associated with poor prognosis. Knockdown of PRDX4 significantly blocked the proliferation and migration of the UCEC cell line Ishikawa and reduced degree of cell confluence. These findings highlight the oncogenic role of PRDX4 in UCEC. In addition, genes that interact with PRDX4 in UCEC were MT-ATP8, PBK, and PDIA6, and we speculated that these genes interacted with each other to promote disease progression in UCEC. Thus, PRDX4 is a potential diagnostic biomarker for UCEC, and targeting PRDX4 may be a potential therapeutic strategy for patients with UCEC.
Asunto(s)
Biología Computacional , Neoplasias Endometriales , Humanos , Femenino , Línea Celular , Progresión de la Enfermedad , Neoplasias Endometriales/genética , Peroxirredoxinas/genéticaRESUMEN
PURPOSE: Illiterate people may frequently experience social discrimination and exclusion in our modern society. It has been suggested that social adversity increases risk of schizophrenia. The current study examines the relation between illiteracy and schizophrenia. METHODS: We utilized data on 1,909,205 representative Chinese people of age 18 years or older collected by the Second China National Sample Survey on Disability in 2006 (participation rate 99.8%). Experienced clinical psychiatrists diagnosed schizophrenia among those who were psychiatrically disabled with the ICD-10 symptom checklist. RESULTS: Strikingly high prevalence of schizophrenia was observed among the young illiterates aged 18-29 years (prevalence 1.64%, 95% confidence interval (CI) 1.35, 1.93) and 30-39 years (prevalence 1.51%, 95% CI 1.34, 1.68), much higher than the prevalence estimates for general Chinese population of similar age reported by any of the previous studies in mainland China. Among people aged less than 40 years, we found that the illiterates were 2.08 times more likely to develop schizophrenia than the literates with no school or primary school education (odds ratio (OR) = 2.08, 95% CI 1.84, 2.36). The association remained statistically significant after adjustment for age, gender, marital status, household income, and location of residence. Consistently, a strong association between illiteracy and schizophrenia (OR = 2.8, 95% CI 1.28, 6.11) was found in conditional logistic regression analysis among matched sibling sets aged less than 40 years that further adjusted for genetic confounding. CONCLUSION: The risk of schizophrenia may have increased among the socially disadvantaged illiterate people.
Asunto(s)
Escolaridad , Esquizofrenia/epidemiología , Adolescente , Adulto , Factores de Edad , China/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Adulto JovenRESUMEN
OBJECTIVE: JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis. METHODS: HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 µmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay. RESULTS: HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1ß (P < 0.001), and IL-18 levels (P < 0.001). CONCLUSION: JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.
Asunto(s)
Medicamentos Herbarios Chinos , Herpes Simple , Inflamasomas , Caspasa 1/metabolismo , Inflamasomas/metabolismo , Inflamasomas/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Simplexvirus/efectos de los fármacos , Simplexvirus/metabolismo , Medicamentos Herbarios Chinos/farmacología , Herpes Simple/tratamiento farmacológico , HumanosRESUMEN
Emodin is an anthraquinone derivative that is widely present in natural plants and has a wide spectrum of pharmacological effects, such as antibacterial, anti-inflammatory, anti-fibrotic and anticancer and so on. Through reviewing studies on antiviral effect of emodin in the past decades, we found that emodin exhibits ability of inhibiting the infection and replication of more than 10 viruses in vitro and in vivo, including herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), coxsackievirus B (CVB), hepatitis B virus (HBV), influenza A virus (IAV), SARS-CoV, viral haemorrhagic septicaemia rhabdovirus (VHSV), enterovirus 71 (EV71), dengue virus serotype 2 (DENV-2) and Zika virus (ZIKV). Therefore, this review aims to summarize the antiviral effect of emodin, in order to provide reference and hopes to support the further investigations.
RESUMEN
Background: Coronavirus disease 2019 (COVID-19) threatens people's physical and mental health, globally, and it may even trigger suicide ideation and suicidal behavior. Aims: We aimed to examine the impact of COVID-19 on suicide risk by sampling Chinese Weibo users and analyzing their social media messages. Method: We predicted the probability of suicide (including hopelessness, suicidal ideation, negative self-evaluation, and hostility) of Weibo users in order to assess the changes in suicide probability at different times. Repeated-measures ANOVA was performed to examine the differences in suicide probability in different regions during different periods. Results: There was no significant difference in suicide probability between profoundly infected areas (PIAs) and less infected areas (LIAs) before the outbreak of COVID-19. LIAs had an increase in hopelessness during the COVID-19 growth period, while hopelessness and hostility in PIA increased during the COVID-19 decline period, indicating potential suicide probability. Limitations: Results should be interpreted with caution, and cross-cultural research may be considered in the future. Conclusion: COVID-19 has a dynamic impact on suicide probability. Using data from online social networks may help to understand the impact pattern of COVID-19 on people's suicide probability.
Asunto(s)
COVID-19 , Medios de Comunicación Sociales , China/epidemiología , Humanos , Probabilidad , Ideación SuicidaRESUMEN
During the COVID-19 pandemic, every day, updated case numbers and the lasting time of the pandemic became major concerns of people. We collected the online data (28 January to 7 March 2020 during the COVID-19 outbreak) of 16,453 social media users living in mainland China. Computerized machine learning models were developed to estimate their daily scores of the nine dimensions of the Symptom Checklist-90 (SCL-90). Repeated measures analysis of variance (ANOVA) was used to compare the SCL-90 dimension scores between Wuhan and non-Wuhan residents. Fixed effect models were used to analyze the relation of the estimated SCL-90 scores with the daily reported cumulative case numbers and lasting time of the epidemic among Wuhan and non-Wuhan users. In non-Wuhan users, the estimated scores for all the SCL-90 dimensions significantly increased with the lasting time of the epidemic and the accumulation of cases, except for the interpersonal sensitivity dimension. In Wuhan users, although the estimated scores for all nine SCL-90 dimensions significantly increased with the cumulative case numbers, the magnitude of the changes was generally smaller than that in non-Wuhan users. The mental health of Chinese Weibo users was affected by the daily updated information on case numbers and the lasting time of the COVID-19 outbreak.
RESUMEN
Conventionally, the photoelectrochemistry relies on freely diffusive signal molecules in solution to stimulate the photocurrent output, leading to limited sensing strategies. Herein, we showcase the methylene blue (MB) embedded duplex DNA for efficient signal stimuli and its application for ultrasensitive photoelectrochemical (PEC) bioassay. Specifically, the MB embedded duplex DNA scavenged the photogenerated holes of petal-like BiVO4 efficiently, and thus greatly augmented the anodic photocurrent output. Taking the miRNA-21 as a model target, whose biorecognition reaction was aided by the rolling circle amplification (RCA) reaction to finally produce an amplified amount of double-stranded DNA (dsDNA) with embedded MB on the photoelectrode's surface, a "label-free" and "signal-on" PEC biosensing platform was implemented with ultra-sensitivity and high selectivity. The proposed strategy could detect miRNA-21 in the concentration range of 5.0 fM to 10 nM, with the detection limit as low as 0.3 fM. This work opens up the utilization of redox substance intercalated duplex DNA for an efficient signal stimulator, which hints the prospect of other more intercalators embedded DNA for versatile biosensing purposes. Importantly, considering the large quantities of bioreactions that involve duplex DNA as reactants/products, the developed signal transduction strategy may further find wide applications in bioanalysis for targeting more analytes.