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The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.
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Bacterias , Bacteriófagos , Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Bacterias/virología , Bacterias/genética , Bacterias/inmunología , Bacteriófagos/genética , Bacteriófagos/inmunología , Chryseobacterium/genética , Chryseobacterium/inmunología , Chryseobacterium/virología , Proteína 9 Asociada a CRISPR/química , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Sistemas CRISPR-Cas/inmunología , División del ADN , Sitios Genéticos/genética , Modelos Moleculares , Dominios ProteicosRESUMEN
Magnetic skyrmions are swirl-like spin configurations that present topological properties, which have great potential as information carriers for future high-density and low-energy-consumption devices. The optimization of skyrmion-hosting materials that can be integrated with semiconductor-based circuits is the primary challenge for their industrialization. Two-dimensional van der Waals ferromagnets are emerging materials that have excellent carrier mobility and compatibility with integrated circuits, making them an ideal candidate for spintronic devices. Here, we report the realization of skyrmions at above room temperature in the 2D ferromagnet Fe3GaTe2. The thickness tunability of their skyrmion size and the formation of the skyrmion lattice are revealed. Furthermore, we demonstrate that the skyrmions can be moved by a low-density current at room temperature, together with an apparent skyrmion Hall effect, which is consistent with our quantitative micromagnetic simulation. Our work offers a promising 2D material platform for harnessing magnetic skyrmions in practical device applications.
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Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.
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Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Humanos , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Atrofia de Múltiples Sistemas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Anciano , Imagen por Resonancia Magnética/métodos , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiopatología , Electromiografía , Neuroimagen/métodosRESUMEN
In populations in China, colorectal cancer (CRC) screening can be mainly accessed through organized screening, opportunistic screening, and physical examination. This screening intervention is found to be effective but the exact coverage rate is difficult to measure. Based on data from published articles, official websites, and available program reports, the screening coverage rate and related indicators were quantified. A rapid review was then conducted to estimate the overall and the breakdown coverage rates of the sub-type screening services, by leveraging the numbers of articles and the by-type median sample sizes. Up to 2020, two central government-funded and four provincial/municipal-level organized CRC screening programs have been initiated and included in this analysis. For populations aged 40-74, the estimated coverage rate of organized programs in China was 2.7% in 2020, and the 2-year cumulative coverage rate in 2019-2020 was 5.3% and the 3-year cumulative coverage rate in 2018-2020 was 7.7%. The corresponding coverage rates of 50-74-year-olds were estimated to be 3.4%, 7.1%, and 10.3%, respectively. Based on the rapid review approach, the overall screening coverage rate for 40-74 years, considering organized screening programs, opportunistic screening, and physical examinations, was then estimated to be 3.0% in China in 2020. However, comparing the findings of this study with the number of health check-ups reported in the local national health statistics yearbooks suggests that the number of CRC physical examinations may be underestimated in this study. The findings suggest that further efforts are needed to improve population access to CRC screening in China. Furthermore, evidence for access to opportunistic CRC screening and physical examination is limited, and more quantitative investigation is needed.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Accesibilidad a los Servicios de Salud , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , China/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Femenino , Masculino , Tamizaje Masivo/estadística & datos numéricos , Tamizaje Masivo/métodosRESUMEN
Radiotherapy, one of the most fundamental cancer treatments, is confronted with the dilemma of treatment failure due to radioresistance. To predict the radiosensitivity and improve tumor treatment efficiency in pan-cancer, we developed a model called Radiation Intrinsic Sensitivity Evaluation (RISE). The RISE model was built using cell line-based mRNA sequencing data from five tumor types with varying radiation sensitivity. Through four cell-derived datasets, two public tissue-derived cohorts, and one local cohort of 42 nasopharyngeal carcinoma patients, we demonstrated that RISE could effectively predict the level of radiation sensitivity (area under the ROC curve [AUC] from 0.666 to 1 across different datasets). After the verification by the colony formation assay and flow cytometric analysis of apoptosis, our four well-established radioresistant cell models successfully proved higher RISE values in radioresistant cells by RT-qPCR experiments. We also explored the prognostic value of RISE in five independent TCGA cohorts consisting of 1137 patients who received radiation therapy and found that RISE was an independent adverse prognostic factor (pooled multivariate Cox regression hazard ratio [HR]: 1.84, 95% CI 1.39-2.42; p < 0.01). RISE showed a promising ability to evaluate the radiotherapy benefit while predicting the prognosis of cancer patients, enabling clinicians to make individualized radiotherapy strategies in the future and improve the success rate of radiotherapy.
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Neoplasias , Tolerancia a Radiación , Humanos , Tolerancia a Radiación/genética , Pronóstico , Neoplasias/radioterapia , Neoplasias/genética , Neoplasias/patología , Línea Celular Tumoral , Femenino , Masculino , Apoptosis/efectos de la radiación , Persona de Mediana Edad , Curva ROC , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologíaRESUMEN
BACKGROUND AND AIMS: Cholesterol ester (CE) biosynthesis and homeostasis play critical roles in many cancers, including HCC, but their exact mechanistic contributions to HCC disease development require further study. APPROACH AND RESULTS: Here, we report on a proposed role of tumor suppressor P53 in its repressing ubiquitin-specific peptidase 19 (USP19) and sterol O-acyltransferase (SOAT) 1, which maintains CE homeostasis. USP19 enhances cholesterol esterification and contributes to hepatocarcinogenesis (HCG) by deubiquitinating and stabilizing SOAT1. Loss of either SOAT1 or USP19 dramatically attenuates cholesterol esterification and HCG in P53-deficient mice fed with either a normal chow diet or a high-cholesterol, high-fat diet (HCHFD). SOAT1 inhibitor avasimibe has more inhibitory effect on HCC progression in HCHFD-maintained P53-deficient mice when compared to the inhibitors of de novo cholesterol synthesis. Consistent with our findings in the mouse model, the P53-USP19-SOAT1 signaling axis is also dysregulated in human HCCs. CONCLUSIONS: Collectively, our findings demonstrate that SOAT1 participates in HCG by increasing cholesterol esterification, thus indicating that SOAT1 is a potential biomarker and therapeutic target in P53-deficient HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Esterificación , Carcinoma Hepatocelular/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias Hepáticas/genética , Colesterol , EndopeptidasasRESUMEN
BACKGROUND: Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. METHODS: A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. RESULTS: TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. CONCLUSION: Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.
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Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.
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Regulación Neoplásica de la Expresión Génica , Linfoma de Células B Grandes Difuso , Proteínas Proto-Oncogénicas c-myc , Proteínas Supresoras de Tumor , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Masculino , Pronóstico , Línea Celular Tumoral , Femenino , Persona de Mediana Edad , Metilación de ADN , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Anciano , Proliferación Celular , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.
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Cistanche , Bacterias/genética , Ambiente , Granjas , Tallos de la PlantaRESUMEN
Prosocial behaviors are central to individual and societal well-being. Although the relationship between effort and prosocial behavior is increasingly studied, the impact of effort-based self-interested motivation on prosocial behavior has received less attention. In the current study, we carried out two experiments to examine the effect of motivation to obtain a reward for oneself on donation behavior and brain response. We observed that individuals who accumulated more money in the effort-expenditure rewards task (EEfRT) donated a lower proportion of their earnings. The sigmoid model fitted participants' choices in the EEfRT task, and the effort-reward bias and sigma parameters negatively correlated with the amount of money donated in the donation task. Additionally, the effort-reward bias and sigma parameters negatively predicted N2 amplitude during processing of charitable donation-related information. We propose that individuals who exhibit a lower level of effort-based self-interest motivation may allocate more cognitive control or attentional resources when processing information related to charitable donations. Our work adds weight to understanding the relationship between effort-based self-interest motivation and prosocial behavior and provides electrophysiological evidence.
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Altruismo , Electroencefalografía , Potenciales Evocados , Motivación , Recompensa , Humanos , Motivación/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Potenciales Evocados/fisiologíaRESUMEN
Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.
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Anemia Ferropénica , Hierro , Saccharomyces cerevisiae , Animales , Anemia Ferropénica/tratamiento farmacológico , Masculino , Ratones , Saccharomyces cerevisiae/metabolismo , Hierro/metabolismo , Modelos Animales de Enfermedad , Animales no ConsanguíneosRESUMEN
PURPOSE: To explore the behavioral intention of breast cancer patients undergoing chemotherapy to prevent PICC-related thrombosis based on the theory of planned behavior (TPB). METHODS: This qualitative study employed purposive sampling and conducted semi-structured interviews with 14 breast cancer patients undergoing chemotherapy in the outpatient chemotherapy ward of a tertiary A-level comprehensive hospital in Beijing from July to August 2023. Data were analyzed using Colaizzi's descriptive analysis framework. RESULTS: Data analysis identified 10 themes that were derived from 4 aspects. Regarding behavioral attitude, three themes were condensed: (1) Considering the benefits of preventive measures, (2) Simple and easy preventive measures, and (3) Underestimating the importance of PICC-related thrombosis prophylaxis. Subjective norms yielded two main themes and five sub-themes: (1) Support from those close to the patient motivates adherence to prophylaxis (support from the patient's family, healthcare professionals, and other patients) and (2) Patients are influenced by personal factors to form an internal driving force (physical symptoms, fear of PICC-related thrombosis). Regarding perceived behavioral control, three main themes and four sub-themes were extracted: (1) Obstacles before actual prevention exercise (prevention information, hard-to-remember information), (2) Forgetfulness is the main obstacle factor, and (3) Wanting to overcome barriers to adhere to regular prevention (confidence to overcome obstacles, hope to get support). CONCLUSIONS: The impediments and facilitators identified in this study may provide a scientific foundation for subsequent targeted non-pharmacological preventive interventions for PICC-related thrombosis based on TPB in breast cancer patients undergoing chemotherapy. Special interventions should be designed for the patients in three areas: the patients themselves, the supporters around the patient, and the healthcare professionals.
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Neoplasias de la Mama , Intención , Investigación Cualitativa , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Trombosis/prevención & control , Trombosis/etiología , Anciano , Entrevistas como Asunto , Teoría del Comportamiento PlanificadoRESUMEN
BACKGROUND: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a rare leukemia subtype first classified by the World Health Organization in 2016. The incidence of Ph+ AML is approximately 0.5 - 3%, and its prognosis is poor. Ph+ AML with additional chromosomal abnormalities in children has rarely been reported, and its treatment and prognosis remain uncertain. METHODS: We retrospectively analyzed 649 patients with AML from 2006 - 2021. Six (0.9%) patients with Ph+ AML were identified and treated with conventional chemotherapy. The clinical features and prognoses were retrospectively analyzed. RESULTS: Six cases of AML with a Ph chromosome were reported. One of the six individuals exhibited a biphenotypic immunophenotype, one exhibited a simple myeloid immunophenotype, and the other four exhibited myeloid and lymphoid expression. Karyotypic analysis (R banding) was performed in six cases, four of which were classical Ph chromosomal abnormalities, two of which had additional abnormalities outside the Ph chromosome. Fluorescence in situ hybridization (FISH) analysis using the BCR/ABL fusion gene distinguished that the BCR major breakpoint break in three cases was type P210 and the BCR minor breakpoint break in three cases was type P190. The complete remission rate of the six patients in this study using conventional chemotherapy was 60%, with a median survival time of 7.5 months. CONCLUSIONS: In summary, Ph+ AML is a heterogeneous disease often associated with additional chromosomal abnormalities. Ph+ AML is seen with a lymphoid immunophenotype and alterations in associated genes such as the IGH gene. Adults were predominantly P210 and two cases in children were both P190. Conventional treatments are less effective, and there are no standard treatment regimens.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide Aguda , Adulto , Niño , Humanos , Cromosoma Filadelfia , Pronóstico , Hibridación Fluorescente in Situ , Estudios Retrospectivos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Aberraciones Cromosómicas , Proteínas de Fusión bcr-abl/genéticaRESUMEN
Previous clinical reports have shown that capecitabine, an oral prodrug of 5-fluorouracil (5-Fu), can induce peripheral neuropathy, resulting in numbness, paresthesia and hypoesthesia. However, the mechanism through which capecitabine causes peripheral nerve injury remains unclear. Here, we demonstrate that systemic administration of capecitabine leads to myelin abnormalities in the peripheral nerves of mice, which are possibly attributed to the death of Schwann cells, the myelinating cells in the peripheral nervous system. Furthermore, our results show that 5-Fu induces significant oxidative stress in Schwann cells by inhibiting the expression of the anti-oxidative protein DJ-1, leading to a decrease in Schwann cell markers. We found that the anti-oxidant dihydromyricetin (DMY) reverses 5-Fu-induced Schwann cell death and oxidative stress and alleviates capecitabine-induced myelin abnormalities. Taken together, our data indicate that capecitabine induces peripheral myelin dysfunction by regulating DJ-1-mediated oxidative stress in Schwann cells and reveal DMY as a potential therapeutic strategy for capecitabine-induced peripheral neuropathy.
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Flavonoles , Vaina de Mielina , Enfermedades del Sistema Nervioso Periférico , Ratones , Animales , Vaina de Mielina/metabolismo , Capecitabina/metabolismo , Estrés Oxidativo , Enfermedades del Sistema Nervioso Periférico/metabolismo , Fluorouracilo/toxicidadRESUMEN
BACKGROUND: Dyadic coping resources have been considered a potential explanatory mechanism of spousal interdependence in health, but the mediation of spousal collaboration for the relationship between self-rated health and depressive symptoms has yet to be examined. This study aimed to investigate the within- (actor effect) and between-partner effects of self-rated health on depressive symptoms in community-dwelling older couples facing physical functioning limitations and to examine the role of spousal collaboration in mediating the actor and cross-partner effects of self-rated health on depressive symptoms. METHOD: Data from 185 community-dwelling older Chinese married couples were analyzed using the actor-partner interdependence mediation model (APIMeM). Couples were interviewed through trained research assistants using the 5-item common dyadic coping subscale of the Dyadic Coping Inventory (DCI), the Visual Analog Scale (VAS) of the QoL questionnaire EQ-5D and the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Husbands' self-rated health had an actor effect on their own depressive symptoms and a partner effect on their wives' depressive symptoms. Wives' self-rated health had an actor effect on their own depressive symptoms. The actor effects between self-rated health and depressive symptoms were partially mediated by their own perception of spousal collaboration. Furthermore, husbands' self-rated health not only affects wives' depressive symptoms directly but also indirectly by influencing wives' perceptions of spousal collaboration. DISCUSSION: The findings from this study underscored the importance of viewing couples' coping processes from a dyadic and gender-specific perspective, since more (perceived) collaborative efforts have beneficial effects on both partners' mental health outcomes.
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Depresión , Calidad de Vida , Humanos , Depresión/psicología , Esposos/psicología , Encuestas y Cuestionarios , ChinaRESUMEN
Background Sexual transmission accounts for a substantial proportion of HIV infections. Although some countries are experiencing an upward trend in HIV infections, there has been a lack of studies assessing the global burden of HIV/AIDS acquired through sexual transmission. We assessed the global, regional, and national burdens of HIV/AIDS acquired through sexual transmission from 1990 to 2019. Methods Data on deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALY) of HIV/AIDS acquired through sexual transmission in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study (GBD) 2019. The burdens and trends were evaluated using the age-standardised rates (ASR) and estimated annual percentage change (EAPC). Results Globally, HIV/AIDS acquired through sexual transmission accounted for ~695.8 thousand (95% uncertainty interval 628.0-811.3) deaths, 33.0million (28.7-39.9) YLLs, 3.4million (2.4-4.6) YLDs, and 36.4million (32.2-43.1) DALYs in 2019. In 2019, Southern sub-Saharan Africa (11350.94), Eastern sub-Saharan Africa (3530.91), and Western sub-Saharan Africa (2037.74) had the highest ASR of DALYs of HIV/AIDS acquired through sexual transmission per 100,000. In most regions of the world, the burden of HIV/AIDS acquired through sexual transmission has been increasing from 1990 to 2019, mainly in Oceania (EAPC 17.20, 95% confidence interval 12.82-21.75), South Asia (9.00, 3.94-14.30), and Eastern Europe (7.09, 6.35-7.84). Conclusions HIV/AIDS acquired through sexual transmission results in a major burden globally, regionally, and nationally.
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Carga Global de Enfermedades , Salud Global , Infecciones por VIH , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Masculino , Femenino , Salud Global/estadística & datos numéricos , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/transmisión , Adulto , Años de Vida Ajustados por Discapacidad , Persona de Mediana EdadRESUMEN
BACKGROUND: In order to improve the tenderness of dried shrimp products as well as to reduce the hardness of the meat during the drying process, shrimp were treated with ultrasound combined with pineapple protease and the tenderization condition was optimized by measuring the texture and shear force of dried shrimp. In addition, the sulfhydryl content, myofibril fragmentation index (MFI) and microstructure were also examined to clarify the mechanisms of shrimp tenderization. RESULTS: The results showed UB1 group with ultrasonic power of 100 W, heating temperature of 50 °C and pineapple protease concentration of 20 U mL-1 were the optimum tenderization conditions, where shrimp showed the lowest hardness (490.76 g) and shear force (2006.35 gf). Microstructure as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis results suggested that during the tenderization process the muscle segments of shrimps were broken, degradation of myofibrillar proteins occurred, and MFI values and total sulfhydryl content increased significantly (P < 0.05) (MFI value = 193.6 and total sulfhydryl content = 93.93 mmol mg-1 protein for UB 1 group). CONCLUSION: Ultrasound combined with bromelain could be used as a simple and effective tenderization method for the production of tender dried shrimp. The best conditions were 100 W ultrasonic power, 50 °C ultrasonic temperature, and 20 U mL-1 bromelain. © 2024 Society of Chemical Industry.
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Ananas , Bromelaínas , Bromelaínas/análisis , Bromelaínas/metabolismo , Alimentos Marinos/análisis , Carne/análisis , Proteínas/metabolismo , Miofibrillas/químicaRESUMEN
Cancer can be considered one of the most threatening diseases to human health, and immunotherapy, especially T-cell immunotherapy, is the most promising treatment for cancers. Diet therapy is widely concerned in cancer because of its safety and fewer side effects. Many studies have shown that both the function of T cells and the progression of cancer can be affected by nutrients in the diet. In fact, it is challenging for T cells to infiltrate and eliminate cancer cells in tumor microenvironment, because of the harsh metabolic condition. The intake of different nutrients has a great influence on the proliferation, activation, differentiation and exhaustion of T cells. In this review, we summarize the effects of typical amino acids, lipids, carbohydrates and other nutritional factors on T cell functions and provide future perspectives for dietary treatment of cancer based on modifications of T cell functions.
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Neoplasias , Linfocitos T , Humanos , Dieta , Estado Nutricional , Neoplasias/tratamiento farmacológico , Inmunoterapia , Microambiente TumoralRESUMEN
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality in patients with chronic liver disease. Chronic hepatitis B is the main cause of ACLF (HBV-ACLF) in China and other Asian countries. To improve disease management and survival for patients with ACLF, we aimed to discover novel biomarkers to enhance HBV-ACLF diagnosis and prognostication. METHODS: We performed a metabolomics profiling of 1,024 plasma samples collected from patients with HBV-related chronic liver disease with acute exacerbation at hospital admission in a multi-year and multi-center prospective study (367 ACLF and 657 non-ACLF). The samples were randomly separated into equal halves as a discovery set and a validation set. We identified metabolites associated with 90-day mortality in the ACLF group and the progression to ACLF within 28 days in the non-ACLF group (pre-ACLF) using statistical analysis and machine learning. We developed diagnostic algorithms in the discovery set and used these to assess the findings in the validation set. RESULTS: ACLF significantly altered the plasma metabolome, particularly in membrane lipid metabolism, steroid hormones, oxidative stress pathways, and energy metabolism. Numerous metabolites were significantly associated with 90-day mortality in the ACLF group and/or pre-ACLF in the non-ACLF group. We developed algorithms for the prediction of 90-day mortality in patients with ACLF (area under the curve 0.87 and 0.83 for the discovery set and validation set, respectively) and the diagnosis of pre-ACLF (area under the curve 0.94 and 0.88 for the discovery set and validation set, respectively). To translate our discoveries into practical clinical tests, we developed targeted assays using liquid chromatography-mass spectrometry. CONCLUSIONS: Based on novel metabolite biomarkers, we established tests for HBV-related ACLF with higher accuracy than existing methods. CLINICAL TRIAL NUMBER: NCT02457637 and NCT03641872. IMPACT AND IMPLICATIONS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality affecting 25% of patients hospitalized with cirrhosis. Chronic hepatitis B is the main etiology of ACLF in China and other Asian counties. There is currently no effective therapy. Early diagnosis and accurate prognostication are critical for improving clinical outcomes in patients with ACLF. Based on novel metabolite biomarkers, we developed liquid chromatography-mass spectrometry tests with improved accuracy for the early diagnosis and prognostication of HBV-related ACLF. The liquid chromatography-mass spectrometry tests can be implemented in clinical labs and used by physicians to triage patients with HBV-related ACLF to ensure optimized clinical management.
RESUMEN
BACKGROUND: Great progress has been made in studying the function of long non-coding RNA (lncRNA) in various tumors, including gastric cancer (GC). However, there are still numerous lncRNAs that have not yet been studied and explored for their roles in GC, and their important functions need to be further revealed. METHODS: Through analyzing The Cancer Genome Atlas (TCGA) database combined with bioinformatics survival tools, a novel GC-related lncRNA LGALS8-AS1 was identified. A quantitative real-time polymerase chain reaction and a series of in vitro or in vivo cell functional experiments were performed to determine the expression and the role of LGALS8-AS1/miR-138-5p/PLAGL2 in GC. RESULTS: LGALS8-AS1 was remarkably upregulated and correlated with the unfavorable prognosis in GC. Higher expression of LGALS8-AS1 was positively associated with higher lymph node metastasis rate, as well as larger tumor size. In addition, a series of cell functional experiments revealed that LGALS8-AS1 could facilitate GC cell proliferation, migration and metastasis in vitro or in vivo. A deeper mechanism exploration revealed that LGALS8-AS1 could function as the miR-138-5p molecular sponge and upregulate the PLAGL2 expression, thereby promoting the cell proliferation, migration and metastasis in GC. CONCLUSIONS: In brief, we revealed the tumor promoting role of the LGALS8-AS1/miR-138-5p/PLAGL2 molecular signaling axis in GC, and our findings provide enlightenment for further understanding of the mechanism of tumorigenesis and development of GC, making LGALS8-AS1 a possible new diagnostic or therapeutic target for GC.