RESUMEN
Incense-burning smoke is a deleterious air pollutant that initiates cytotoxic effects by inducing apoptosis in lung epithelial cells and also acts as a risk factor for lung cancers. Auramine, an ingredient of incense smoke, has been implicated in tumor progression and cellular sensitivity in non-small cell lung cancer (NSCLC) towards anti-cancer agents through unclear mechanisms. Tumor protein p53 (TP53)-activated long intergenic non-coding RNA-p21 (lincRNA-p21) undertakes a pivotal role in regulating cell apoptosis and chemosensitivity. TP53 mutations prevalent in 50% of NSCLC, contribute to diminished therapeutic efficacy. However, the influence of auramine on chemotherapy-induced lincRNA-p21 expression and apoptosis in NSCLC with different TP53 genetic statuses remains unexplored. This study disclosed that both wild-type p53 (wtp53) and mutant p53 (mutp53) mediate lincRNA-p21 expression, albeit through distinct promoter enhancers, p53-response element (p53RE) and non-B DNA structure G-quadruplex (GQ), respectively. Intriguingly, auramine functions as an effective stabilizer of the GQ structure, augmenting mutp53-mediated lincRNA-p21 expression and enhancing apoptosis and cellular sensitivity to chemotherapy in mutp53-expressing NSCLC cells. These findings suggest a mechanism by which mutp53, in the presence of auramine, is endowed with tumor-suppressing function akin to wtp53, thereby aiding in combating chemoresistance in NSCLC cells harboring TP53 mutations.
RESUMEN
Surface plasmonic detectors have the potential to be key components of miniaturized chip-scale spectrometers. Graphene plasmons, which are highly confined and gate-tunable, are suitable forin situlight detection. However, the tuning of graphene plasmonic photodetectors typically relies on the complex and high operating voltage based on traditional dielectric gating technique, which hinders the goal of miniaturized and low-power consumption spectrometers. In this work, we report a tunable mid-infrared (MIR) photodetector by integrating of patterned graphene with non-volatile ferroelectric polarization. The polarized ferroelectric thin film provides an ultra-high surface electric field, allowing the Fermi energy of the graphene to be manipulated to the desired level, thereby exciting the surface plasmon polaritons effect, which is highly dependent on the free carrier density of the material. By exciting intrinsic graphene plasmons, the light transmittance of graphene is greatly enhanced, which improves the photoelectric conversion efficiency of the device. Additionally, the electric field on the surface of graphene enhanced by the graphene plasmons accelerates the carrier transfer efficiency. Therefore, the responsivity of the device is greatly improved. Our simulations show that the detectors have a tunable resonant spectral response of 9-14µm by reconstructing the ferroelectric domain and exhibit a high responsivity to 5.67 × 105A W-1at room temperature. Furthermore, we also demonstrate the conceptual design of photodetector could be used for MIR micro-spectrometer application.
RESUMEN
BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.
Asunto(s)
Actinas , Meiosis , Oocitos , Proteína de Unión al GTP cdc42 , Animales , Oocitos/metabolismo , Ratones , Femenino , Actinas/metabolismo , Actinas/genética , Proteína de Unión al GTP cdc42/metabolismo , Proteína de Unión al GTP cdc42/genética , Fosforilación , Huso Acromático/metabolismoRESUMEN
SUMMARY: Intracranial aneurysm is a common cerebrovascular disease with high mortality. Neurosurgical clipping for the treatment of intracranial aneurysms can easily lead to serious postoperative complications. Studies have shown that intraoperative monitoring of the degree of cerebral ischemia is extremely important to ensure the safety of operation and improve the prognosis of patients. Aim of this study was to probe the application value of combined monitoring of intraoperative neurophysiological monitoring (IONM)-intracranial pressure (ICP)-cerebral perfusion pressure (CPP) in craniotomy clipping of intracranial aneurysms. From January 2020 to December 2022, 126 patients in our hospital with intracranial aneurysms who underwent neurosurgical clipping were randomly divided into two groups. One group received IONM monitoring during neurosurgical clipping (control group, n=63), and the other group received IONM-ICP-CPP monitoring during neurosurgical clipping (monitoring group, n=63). The aneurysm clipping and new neurological deficits at 1 day after operation were compared between the two groups. Glasgow coma scale (GCS) score and national institutes of health stroke scale (NIHSS) score were compared before operation, at 1 day and 3 months after operation. Glasgow outcome scale (GOS) and modified Rankin scale (mRS) were compared at 3 months after operation. All aneurysms were clipped completely. Rate of new neurological deficit at 1 day after operation in monitoring group was 3.17 % (2/63), which was markedly lower than that in control group of 11.11 % (7/30) (P0.05). Combined monitoring of IONM-ICP-CPP can monitor the cerebral blood flow of patients in real time during neurosurgical clipping, according to the monitoring results, timely intervention measures can improve the consciousness state of patients in early postoperative period and reduce the occurrence of early postoperative neurological deficits.
El aneurisma intracraneal es una enfermedad cerebrovascular común con alta mortalidad. El clipaje neuroquirúrgico para el tratamiento de aneurismas intracraneales puede provocar complicaciones posoperatorias graves. Los estudios han demostrado que la monitorización intraoperatoria del grado de isquemia cerebral es extremadamente importante para garantizar la seguridad de la operación y mejorar el pronóstico de los pacientes. El objetivo de este estudio fue probar el valor de la aplicación de la monitorización combinada de la monitorización neurofisiológica intraoperatoria (IONM), la presión intracraneal (PIC) y la presión de perfusión cerebral (CPP) en el clipaje de craneotomía de aneurismas intracraneales. Desde enero de 2020 hasta diciembre de 2022, 126 pacientes de nuestro hospital con aneurismas intracraneales que se sometieron a clipaje neuroquirúrgico se dividieron aleatoriamente en dos grupos. Un grupo recibió monitorización IONM durante el clipaje neuroquirúrgico (grupo de control, n=63) y el otro grupo recibió monitorización IONM-ICP-CPP durante el clipaje neuroquirúrgico (grupo de monitorización, n=63). Se compararon entre los dos grupos el recorte del aneurisma y los nuevos déficits neurológicos un día después de la operación. La puntuación de la escala de coma de Glasgow (GCS) y la puntuación de la escala de accidentes cerebrovasculares de los institutos nacionales de salud (NIHSS) se compararon antes de la operación, 1 día y 3 meses después de la operación. La escala de resultados de Glasgow (GOS) y la escala de Rankin modificada (mRS) se compararon 3 meses después de la operación. Todos los aneurismas fueron cortados por completo. La tasa de nuevo déficit neurológico 1 día después de la operación en el grupo de seguimiento fue del 3,17 % (2/63), que fue notablemente inferior a la del grupo de control del 11,11 % (7/30) (P 0,05). La monitorización combinada de IONM-ICP-CPP puede controlar el flujo sanguíneo cerebral de los pacientes en tiempo real durante el corte neuroquirúrgico; de acuerdo con los resultados de la monitorización, las medidas de intervención oportunas pueden mejorar el estado de conciencia de los pacientes en el período postoperatorio temprano y reducir la aparición de problemas postoperatorios tempranos y déficits neurológicos.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/fisiopatología , Circulación Cerebrovascular , Procedimientos Neuroquirúrgicos/métodos , Electroencefalografía/métodos , Presión Sanguínea , Presión Intracraneal , Escala de Coma de Glasgow , Aneurisma Intracraneal/patología , Estudios de Seguimiento , Resultado del Tratamiento , Craneotomía , Escala de Consecuencias de Glasgow , Monitoreo Fisiológico/métodosRESUMEN
Background: To analyzes the changes in serum levels of matrix metalloproteinase-9 (MMP-9), neuroenolase (NSE), myeloperoxidase (MPO) and prognostic factors in patients with intracranial aneurysm (IA) undergoing interventional embolization at different treatment times. Methods: A retrospective analysis was made of 200 IA patients admitted to our department from January 2018 to June 2021 was performed. All patients underwent interventional embolization. According to the timing of surgery, the patients were divided into an early group (n=120, onset to surgery ≤72 h) and a delayed group (n=80, onset to surgery >72 h). The effect of embolization, complications and neurological deficit scale (NDS) scores were compared between the two groups. Serum MMP-9, NSE and MPO levels were compared before and after surgery, and the prognosis of all patients within 2 years after surgery was assessed by the Glasgow outcome scale (GOS) and divided accordingly into the good prognosis group (n=147) and the poor prognosis group (n=53) accordingly, and the prognostic factors influencing the patients were analyzed univariately and multifactorially.
RESUMEN
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, posttranscriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1,547 RNA-binding proteins on cell motility in colon cancer cells and identified multiple core components of P-bodies (PB) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multiomics analysis revealed that PBs could repress the translation of the EMT driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in the regulation of EMT in cancer. SIGNIFICANCE: Systematic investigation of the influence of posttranscriptional regulation on cancer cell motility established a connection between P-body-mediated translational control and EMT, which could be therapeutically exploited to attenuate metastasis formation.
Asunto(s)
Neoplasias del Colon , Cuerpos de Procesamiento , Humanos , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Detección Precoz del Cáncer , Factores de Transcripción/metabolismo , Transición Epitelial-Mesenquimal/genética , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Línea Celular Tumoral , Proteínas/genéticaRESUMEN
Zinc metal is widely considered as the primary option for constructing various aqueous batteries due to its cost-effectiveness, safety, and environmental friendliness. However, the Zn anode continues to be plagued by parasitic reactions and dendrite growth in aqueous electrolytes, limiting the practical implementation of zinc ion batteries (ZIBs) for large-scale energy storage. Herein, a foveolate ZnTe nanoarray is developed as a protective layer to enhance the chemical reversibility during Zn plating/stripping. The semi-conductive ZnTe with excellent ionic conductivity and hydrophobicity can effectually prevent the corrosion reactions, hydrogen generation and dendritic growth on the surface of the Zn anode. As a result, the Zn@ZnTe symmetrical cells achieve ultrahigh cycling stability (over 2800 h at 2 mA cm-2 and 1 mA h cm-2) and simultaneously deliver a low voltage hysteresis of 28 mV. Additionally, the durable Zn@ZnTe//V2O5 cells exhibit a remarkable capacity retention of 96.7% after 3000 cycles, surpassing that of the Zn//V2O5 cells. This work provides a straightforward and low-cost strategy to regulate the interface chemistry of the Zn anode, which may open a way for the development of practical ZIBs.
RESUMEN
MoS2 has long been considered a promising catalyst for hydrogen production. At present, there are many strategies to further improve its catalytic performance, such as edge engineering, defect engineering, phase engineering, and so on. However, at present, there is still a great deal of controversy about the mechanism of MoS2 catalytic hydrogen production. For example, it is generally believed that the base plane of MoS2 is inert; however, it has been reported that the inert base plane can undergo a transient phase transition in the catalytic process to play the catalytic role, which is contrary to the common understanding that the catalytic activity only occurs at the edge. Therefore, it is necessary to further understand the mechanism of MoS2 catalytic hydrogen production. In this article, we summarized the latest research progress on the catalytic hydrogen production of MoS2, which is of great significance for revisiting the mechanism of MoS2 catalytic hydrogen production.
RESUMEN
Ru(II)-catalyzed condition-controlled divergent coupling between 3-aryl-2H-benzoxazin-2-ones and benzoquinones has been realized under operationally simple conditions, affording a series of structurally stable spiropyrans and valuable arylquinones. The potential of this method is also demonstrated by scale-up synthesis and derivatization. Additionally, an unprecedented cycloruthenated complex has been identified as a key intermediate.
RESUMEN
Non-suicidal self-injury behavior (NSSI) is a serious public health concern that requires immediate attention. Despite the high prevalence of NSSI among the Chinese population, there is a significant gap in research on the comprehensive picture of this field. Therefore, a scoping review was conducted to investigate the prevalence, methods, risk factors, and preventive intervention programs related to NSSI in China. The review found that the estimated lifetime prevalence of NSSI among Chinese youth population is alarmingly high at 24.7% (N = 1,088,433). Common methods of NSSI include scratching, hitting, and biting. Additionally, the review synthesized 249 risk factors based on the biopsychosocial-ecological framework, highlighting the urgent need for intervention. However, only 12 empirical studies focus on NSSI prevention or intervention programs were included. These findings underscore the necessity for more clinical practices and larger studies to identify effective interventions and ultimately alleviate the burden of NSSI on the Chinese population. Funding: This review was supported by Humanity and Social Science Youth foundation of Ministry of Education (22YJCZH018), Science and Technology Innovation 2030 (STI2030-Major Projects:2021ZD0200702), National Natural Science Foundation of China (81825009), and Shuimu Tsinghua Scholar. No funding agencies were involved in the data collection, data analysis, and writing of this paper.
RESUMEN
BACKGROUND: Circulating tumor cells (CTCs) have been a non-invasive technique which allows investigation of tumor characteristics. The purpose of this study was to investigate the relationship between circulating tumor cells and colorectal cancer. METHODS: The clinical data of 617 patients with colorectal cancer from October 2019 to March 2022 were retrospectively collected to analyze the correlation between CTCs and clinicopathologic characteristics. RESULTS: The CTCs value increased with the progression of Tumor(T) stage,Metastasis(M) stage and Tumor Node Metastasis(TNM) stage (P < 0.05), but not with Node (N) stage (P > 0.05). Binary logistic regression analysis showed that CTCs, CEA, CA125 and CA199 were independent risk factors for CRC metastasis. Compared with CTCs, CEA, CA125 and CA199, the Logistic model had the highest AUC (AUC = 0.778,95%CI: 0.732-0.824), and the specificity and sensitivity were 82.9% and 63.2%, respectively. After operation, chemo-radiotherapy and other treatment for CRC, CTCs and CEA were significantly decreased compared with before treatment (P < 0.05). In addition, Spearman Correlation showed significant correlation between CTCs and IgG (P = 0.000). CONCLUSION: CTCs, CEA, CA125 and CA199 were independent risk factors for CRC metastasis.CTCs can be used for the prediction of tumur metastasis, and the evaluation of therapeutic effect.
Asunto(s)
Neoplasias Colorrectales , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Estudios Retrospectivos , Pueblos del Este de Asia , Neoplasias Colorrectales/patología , Antígeno Ca-125 , Biomarcadores de TumorRESUMEN
Intracranial epidermoid cysts are benign lesions and are rarely seen in clinical practice. Owing to similarities in imaging findings to those of common cystic lesions, the preoperative diagnosis is rendered challenging. Here, we present a case report of an epidermoid cyst at the right oculomotor nerve, which was initially misdiagnosed as a common cyst. A 14-year-old female child was admitted to our department due to a previous magnetic resonance imaging scan of a cystic lesion on the right side of the saddle that was suspected to be an oculomotor nerve cyst. In our department, this patient underwent a complete surgical resection of the tumor, and the pathology results revealed an epidermoid cyst. This is the first study that reported an epidermoid cyst at the right oculomotor nerve entering the orbit, mimicking a common cyst in imaging. We hope that this study would allow clinicians to consider this type of lesion as a differential diagnosis. Moreover, we suggest that specific diffusion-weighted imaging scan should be performed to aid in the diagnosis.
Asunto(s)
Quiste Epidérmico , Niño , Femenino , Humanos , Adolescente , Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Nervio Oculomotor/diagnóstico por imagen , Imagen por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética , Diagnóstico DiferencialRESUMEN
BACKGROUND: Mental health problems are a crucial global public health concern. Owing to their cost-effectiveness and accessibility, conversational agent interventions (CAIs) are promising in the field of mental health care. OBJECTIVE: This study aims to present a thorough summary of the traits of CAIs available for a range of mental health problems, find evidence of efficacy, and analyze the statistically significant moderators of efficacy via a meta-analysis of randomized controlled trial. METHODS: Web-based databases (Embase, MEDLINE, PsycINFO, CINAHL, Web of Science, and Cochrane) were systematically searched dated from the establishment of the database to October 30, 2021, and updated to May 1, 2022. Randomized controlled trials comparing CAIs with any other type of control condition in improving depressive symptoms, generalized anxiety symptoms, specific anxiety symptoms, quality of life or well-being, general distress, stress, mental disorder symptoms, psychosomatic disease symptoms, and positive and negative affect were considered eligible. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data were extracted by 2 independent reviewers, checked by a third reviewer, and pooled using both random effect models and fixed effects models. Hedges g was chosen as the effect size. RESULTS: Of the 6900 identified records, a total of 32 studies were included, involving 6089 participants. CAIs showed statistically significant short-term effects compared with control conditions in improving depressive symptoms (g=0.29, 95% CI 0.20-0.38), generalized anxiety symptoms (g=0.29, 95% CI 0.21-0.36), specific anxiety symptoms (g=0.47, 95% CI 0.07-0.86), quality of life or well-being (g=0.27, 95% CI 0.16-0.39), general distress (g=0.33, 95% CI 0.20-0.45), stress (g=0.24, 95% CI 0.08-0.41), mental disorder symptoms (g=0.36, 95% CI 0.17-0.54), psychosomatic disease symptoms (g=0.62, 95% CI 0.14-1.11), and negative affect (g=0.28, 95% CI 0.05-0.51). However, the long-term effects of CAIs for the most mental health outcomes were not statistically significant (g=-0.04 to 0.39). Personalization and empathic response were 2 critical facilitators of efficacy. The longer duration of interaction with conversational agents was associated with the larger pooled effect sizes. CONCLUSIONS: The findings show that CAIs are research-proven interventions that ought to be implemented more widely in mental health care. CAIs are effective and easily acceptable for those with mental health problems. The clinical application of this novel digital technology will conserve human health resources and optimize the allocation of mental health services. TRIAL REGISTRATION: PROSPERO CRD42022350130; https://tinyurl.com/mvhk6w9p.
Asunto(s)
Salud Mental , Calidad de Vida , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ansiedad/terapiaRESUMEN
The first germanimidoyl chloride MsFluindtBu-Ge(Cl)îNMes (2, where MsFluindtBu is a bulky hydrindacene skeleton) was synthesized through the reaction of MsFluindtBu-GeCl (1) and mesityl azide (MesN3). In contrast, treatment of 1 with a less bulky azide ArN3 (Ar = 4-tBuC6H4) produced a germatetrazole chloride MsFluindtBu-Ge(Cl)N4Ar2 (3), and a salt [MsFluindtBu-GeN4Ar2]+[BArF4]- (4; ArF = 3,5-(CF3)2C6H3) followed by chloride abstraction with NaBArF4, both bearing a five-membered GeN4 ring. Functionalization of 2 with Ar'Li (Ar' = 3,5-tBu2C6H3) or MeLi furnished a germanimine MsFluindtBu-Ge(Ar')îNMes (5) or an amide lithium salt MsFluindtBu-Ge(Me)2-N(Mes)Li(thf) (6).
RESUMEN
Vinylarenes represent an important class of core skeleton embedded in natural products, organic materials, and pharmaceutical molecules. Therefore, numerous efforts have been devoted to developing efficient methods for their preparation. Among them, transition-metal-catalyzed oxidative coupling of arenes and alkenes has proved to be a powerful method due to its high atom and step economy. Although a wide range of oxidative alkenylations of arenes have been developed, the alkenes employed in most cases are still limited to electron-deficient alkenes. Reported herein is a Rh(III)-catalyzed C-H cross-coupling of benzoxazinones and simple unactivated styrenes to furnish a variety of vinylarene scaffolds. This established protocol is characterized by wide functional group compatibility, high yields, and excellent regio- and chemo-selectivity. Mechanistic studies and gram-scale experiments on this high-value conversion are disclosed. Moreover, the potential utility of this method was highlighted by a series of further transformations.
RESUMEN
Carbynes (R-[Formula: see text]), species that bear a monovalent carbon atom with three non-bonding valence electrons, are important intermediates and potentially useful in organic synthetic chemistry. However, free species of the type R-[Formula: see text] of any group 14 element (E) have eluded isolation in the condensed phase due to their high reactivity. Here we report the isolation, characterization and reactivity of a crystalline germylyne radical by using a sterically hindered hydrindacene ligand. The germylyne radical bears an essentially one-coordinate germanium atom as shown by single-crystal X-ray diffraction analysis. Electron paramagnetic resonance spectroscopic studies and theoretical calculations show that the germylyne radical features a doublet ground state, and the three non-bonding valence electrons at the germanium atom contribute to the lone pair of electrons as the highest occupied molecular orbital-3 and one unpaired electron as the singly occupied molecular orbital.
RESUMEN
BACKGROUND: According to data from the National Health Commission in 2018, more than 30 million children and adolescents in China suffered from mental health problems of varying degrees, with depression accounting for the largest proportion. Life events occur at every stage of child and adolescent development. Many studies have found a relationship between life events and depression in children and adolescents, but few studies have further explored the mediating and moderating variables that influence this relationship. Based on theoretical and empirical research on social support and cognitive styles, this study established a two-stage moderated mediating model to test whether social support mediates life events to depression, and cognitive style moderates the two mediating pathways. METHODS: We recruited 3540 participants from primary and secondary schools in Chongqing and collected 2814 valid data. All the participants completed self-report measures of life events, depression, social support and cognitive styles. The moderated mediation model was examined using SPSS PROCESS model 58. RESULTS: (1) There were significant positive correlations between life events and depression. (2) Social support mediates the relationship between life events and depression in children and adolescents. (3) Cognitive style moderates life events to social support and social support to depression. LIMITATIONS: This is a cross-sectional study and the questionnaire is self-reported. CONCLUSIONS: In children and adolescents, life events can influence depression through the mediating role of social support and cognitive styles could moderate its two mediating pathways.
Asunto(s)
Depresión , Apoyo Social , Humanos , Niño , Adolescente , Depresión/psicología , Estudios Transversales , China , CogniciónRESUMEN
RUNX proteins are highly conserved in metazoans and perform critical functions during development. Dysregulation of RUNX proteins through various molecular mechanisms facilitates the development and progression of various cancers, where different RUNX proteins show tumor type-specific functions and regulate different aspects of tumorigenesis by cross-talking with different signaling pathways such as Wnt, TGF-ß, and Hippo. Molecularly, they could serve as transcription factors (TFs) to activate their direct target genes or interact with many other TFs to modulate chromatin architecture globally. Here, we review the current knowledge on the functions and regulations of RUNX proteins in different cancer types and highlight their potential role as epigenetic modulators in cancer.
Asunto(s)
Subunidades alfa del Factor de Unión al Sitio Principal , Neoplasias , Humanos , Subunidades alfa del Factor de Unión al Sitio Principal/genética , Subunidades alfa del Factor de Unión al Sitio Principal/metabolismo , Neoplasias/metabolismo , Epigenómica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Epigénesis GenéticaRESUMEN
BACKGROUND: Depression has a high prevalence among young adults, especially during the COVID-19 pandemic. However, mental health services remain scarce and underutilized worldwide. Mental health chatbots are a novel digital technology to provide fully automated interventions for depressive symptoms. OBJECTIVE: The purpose of this study was to test the clinical effectiveness and nonclinical performance of a cognitive behavioral therapy (CBT)-based mental health chatbot (XiaoE) for young adults with depressive symptoms during the COVID-19 pandemic. METHODS: In a single-blind, 3-arm randomized controlled trial, participants manifesting depressive symptoms recruited from a Chinese university were randomly assigned to a mental health chatbot (XiaoE; n=49), an e-book (n=49), or a general chatbot (Xiaoai; n=50) group in a ratio of 1:1:1. Participants received a 1-week intervention. The primary outcome was the reduction of depressive symptoms according to the 9-item Patient Health Questionnaire (PHQ-9) at 1 week later (T1) and 1 month later (T2). Both intention-to-treat and per-protocol analyses were conducted under analysis of covariance models adjusting for baseline data. Controlled multiple imputation and δ-based sensitivity analysis were performed for missing data. The secondary outcomes were the level of working alliance measured using the Working Alliance Questionnaire (WAQ), usability measured using the Usability Metric for User Experience-LITE (UMUX-LITE), and acceptability measured using the Acceptability Scale (AS). RESULTS: Participants were on average 18.78 years old, and 37.2% (55/148) were female. The mean baseline PHQ-9 score was 10.02 (SD 3.18; range 2-19). Intention-to-treat analysis revealed lower PHQ-9 scores among participants in the XiaoE group compared with participants in the e-book group and Xiaoai group at both T1 (F2,136=17.011; P<.001; d=0.51) and T2 (F2,136=5.477; P=.005; d=0.31). Better working alliance (WAQ; F2,145=3.407; P=.04) and acceptability (AS; F2,145=4.322; P=.02) were discovered with XiaoE, while no significant difference among arms was found for usability (UMUX-LITE; F2,145=0.968; P=.38). CONCLUSIONS: A CBT-based chatbot is a feasible and engaging digital therapeutic approach that allows easy accessibility and self-guided mental health assistance for young adults with depressive symptoms. A systematic evaluation of nonclinical metrics for a mental health chatbot has been established in this study. In the future, focus on both clinical outcomes and nonclinical metrics is necessary to explore the mechanism by which mental health chatbots work on patients. Further evidence is required to confirm the long-term effectiveness of the mental health chatbot via trails replicated with a longer dose, as well as exploration of its stronger efficacy in comparison with other active controls. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052532; http://www.chictr.org.cn/showproj.aspx?proj=135744.
Asunto(s)
COVID-19 , Salud Mental , Humanos , Adulto Joven , Femenino , Adolescente , Masculino , Depresión/terapia , Método Simple Ciego , PandemiasRESUMEN
Immunoglobulins are key humoral immune molecules produced and secreted by B lymphocytes at various stages of differentiation. No research has reported whether immunoglobulins are present in the non-proliferative female germ cells-oocytes-and whether they are functionally important for oocyte quality, self-protection, and survival. Herein, we found that IgG was present in the oocytes of immunodeficient mice; the IgG-VDJ regions were highly variable between different oocytes, and H3K27Ac bound and regulated the IgG promoter region. Next, IgG mRNA and protein levels increased in response to LPS, and this increment was mediated by CR2 on the oocyte membrane. Finally, we revealed three aspects of the functional relevance of oocyte IgG: first, oocytes could upregulate IgG to counteract the increased ROS level induced by CSF1; second, oocytes could upregulate IgG in response to injected virus ssRNA to maintain mitochondrial integrity; third, upon bacterial infection, oocytes could secrete IgG, subsequently encompassing the bacteria, thus increasing survival compared to somatic cells. This study reveals for the first time that the female germ cells, oocytes, can independently adjust intrinsic IgG production to survive in adverse environments.