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Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit's response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit's sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit's defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.
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Chemoresistance is a main cause of chemotherapy failure and tumor recurrence. The effects of global protein SUMOylation on chemoresistance in colorectal cancer (CRC) remains to be investigated. Herein, we have proposed that the elevated SUMO2/3-modified proteins confer 5-fluorouracil (5-FU) chemoresistance acquisition in CRC. The SUMOylation levels of global proteins in CRC cell lines were elevated compared with normal colon cell line NCM460. 5-FU treatment obviously reduced SUMOylation of global proteins in 5-FU-sensitive CRC cells including HT29, HCT116 and HCT-8. However, in 5-FU-resistant HCT-8/5-FU cells, the expression level of SUMO2/3-modified proteins was increased under 5-FU exposure in a concentration-dependent manner. 5-FU treatment combined with SUMOylation inhibitor ML-792 significantly increased the sensitivity of 5-FU-resistant cells to 5-FU and reduced colony formation numbers in HCT-8/5-FU cells. And UBC9-mediated SUMOylation elevation contributes to 5-FU resistance in HCT116 cells. Moreover, we also identified RREB1 as a regulator of SUMOylation profiling of global cellular proteins via directly binding to the promoter of UBC9. Overexpression of RREB1 promoted 5-FU resistance in CRC, which was partially abolished by treatment of inhibitor ML-792. In conclusion, RREB1-enhanced protein SUMOylation contributes to 5-FU resistance acquisition in CRC.
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Nickel-catalyzed aqueous cyanation of allylic alcohols is herein described. This catalytic protocol provided environmentally friendly and operationally simple access to a variety of allylic nitriles in good yields. For chiral allylic alcohols, the reaction gave chiral allylic nitriles with a high degree of chiral inversion. The accelerated release of cyanide in H2O was crucial for the success of this reaction.
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Protein-protein interaction studies using proximity labeling techniques, such as biotin ligase-based BioID, have become integral in understanding cellular processes. Most studies utilize conventional 2D cell culture systems, potentially missing important differences in protein behavior found in 3D tissues. In this study, we investigated the protein-protein interactions of a protein, Bcl-2 Agonist of cell death (BAD), and compared conventional 2D culture conditions to a 3D system, wherein cells were embedded within a 3D extracellular matrix (ECM) mimic. Using BAD fused to the engineered biotin ligase miniTurbo (BirA*), we identified both overlapping and distinct BAD interactomes under 2D and 3D conditions. The known BAD binding proteins 14-3-3 isoforms and Bcl-XL interacted with BAD in both 2D and 3D. Of the 131 BAD-interactors identified, 56% were specific to 2D, 14% were specific to 3D, and 30% were common to both conditions. Interaction network analysis demonstrated differential associations between 2D and 3D interactomes, emphasizing the impact of the culture conditions on protein interactions. The 2D-3D overlap interactome encapsulated the apoptotic program, which is a well-known role of BAD. The 3D unique pathways were enriched in ECM signaling, suggestive of hitherto unknown functions for BAD. Thus, exploring protein-protein interactions in 3D provides novel clues into cell behavior. This exciting approach has the potential to bridge the knowledge gap between tractable 2D cell culture and organoid-like 3D systems.
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Técnicas de Cultivo de Célula , Proteína Letal Asociada a bcl , Humanos , Proteína Letal Asociada a bcl/metabolismo , Técnicas de Cultivo de Célula/métodos , Mapas de Interacción de Proteínas , Matriz Extracelular/metabolismo , Mapeo de Interacción de Proteínas/métodos , Proteínas 14-3-3/metabolismo , Ligasas de Carbono-Nitrógeno/metabolismo , Ligasas de Carbono-Nitrógeno/genética , Unión Proteica , Proteína bcl-X/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas RepresorasRESUMEN
OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.
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Background: Preliminary evidence provides support for the proposition that there is a dissociative subtype of Complex posttraumatic stress disorder (CPTSD). Research on this proposition would extend our knowledge on the association between CPTSD and dissociation, guide contemporary thinking regarding placement of dissociation in the nosology of CPTSD, and inform clinically useful assessment and intervention.Objectives: The present study aimed to investigate the co-occurring patterns of CPTSD and dissociative symptoms in a large sample of trauma exposed adolescents from China, and specify clinical features covariates of such patterns including childhood trauma, comorbidities with major depressive disorder (MDD) and generalized anxiety disorder (GAD), and functional impairment.Methods: Participants included 57,984 high school students exposed to the coronavirus disease 2019 (COVID-19) pandemic. CPTSD and dissociative symptoms, childhood traumatic experience, and functional impairment were measured with the Global Psychotrauma Screen for Teenagers (GPS-T). Major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. Latent class analysis (LCA) was employed to test the co-occurring patterns of CPTSD and dissociative symptoms. Analysis of covariance (ANCOVA) and chi-square tests were respectively used to examine between-class differences in continuous and categorical clinical covariates.Results: A 5-class model emerged as the best-fitting model, including resilience, predominantly PTSD symptoms, predominantly disturbances in self-organization (DSO)symptoms, predominantly CPTSD symptoms, and CPTSD dissociative subtype classes. The CPTSD dissociative subtype class showed the lowest level of functioning and the highest rates of MDD, GAD and childhood trauma.Conclusions: Our findings provide initial empirical evidence supporting the existence of a dissociative subtype of CPTSD, and inform for further research and clinical practice on traumatized individuals.
The present study identified a dissociative subtype of ICD-11 CPTSD among trauma exposed youth.The dissociative subtype of ICD-11 CPTSD was associated with poorer mental health outcomes.Findings of this study provide initial empirical evidence supporting the existence of a dissociative subtype of CPTSD.
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Trastornos de Ansiedad , COVID-19 , Trastorno Depresivo Mayor , Trastornos Disociativos , Análisis de Clases Latentes , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Adolescente , China , Masculino , Femenino , Trastornos Disociativos/psicología , Trastornos Disociativos/epidemiología , COVID-19/psicología , COVID-19/epidemiología , Trastorno Depresivo Mayor/epidemiología , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , SARS-CoV-2 , Comorbilidad , Pueblos del Este de AsiaRESUMEN
The efficacy of nanoencapsulation as a technology for enhancing the solubility of active substances has been demonstrated. In this particular investigation, Ganoderic acid DM (GA-DM) was encapsulated within sodium alginate nanoparticles (NPs) using the ionic crosslinking method. The confirmation of the successful loading of GA-DM was ascertained through the analysis of Fourier transform infrared spectrum (FTIR). Empirical evidence derived from the examination of scanning electron microscope (SEM) images, transmission electron microscope (TEM) images, atomic force microscope (AFM) images, and dynamic light scattering (DLS) demonstrated a regular distribution and spherical morphology, with an average particle size of approximately 133 nm. The investigation yielded an encapsulation efficiency of 95.27 ± 0.11 % and a drug loading efficiency of 21.17 ± 0.02 % for the prepared sample. The release kinetics of SGPN was fitted with the Korsmeyer-Peppas kinetic model corresponding to diffusion-controlled release. The incorporation of GA-DM into sodium alginate nanocarriers exhibited a mitigating effect on the cytotoxicity of HaCat and B16, while also demonstrating inhibitory properties against tyrosinase activity and melanin formation.
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Alginatos , Melaninas , Monofenol Monooxigenasa , Nanopartículas , Triterpenos , Alginatos/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Nanopartículas/química , Humanos , Triterpenos/química , Triterpenos/farmacología , Tamaño de la Partícula , Liberación de Fármacos , Animales , Ratones , Portadores de Fármacos/química , Cinética , Composición de Medicamentos , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A Pd-catalyzed highly regio- and stereoselective hydrocyanation was developed, providing a novel approach to the stereodivergent synthesis of ß-cyano-substituted acrylates in good yields with a wide substrate scope. The judicious selection of ligands was crucial for elegant control over the stereodivergence. Furthermore, the success of the E-hydrocyanation hinges on the right matching of Pd and L1, which not only ensured the catalytic activity but also prevented the formation of α-cyanation products.
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PURPOSE: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). CONCLUSION: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.
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With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.
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Equol , Isoflavonas , Animales , Humanos , Ratones , Ratas , Porcinos , Equol/genética , Equol/metabolismo , Racemasas y Epimerasas , Pollos/metabolismo , Isoflavonas/metabolismo , Oxidorreductasas/metabolismoRESUMEN
PURPOSE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP. METHODS: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group. RESULTS: Baseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population. CONCLUSIONS: ICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.
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BACKGROUND: Endoscopic submucosal dissection (ESD) and surgical resection are the standard of care for cT1N0M0 esophageal cancer (EC), whereas definitive chemoradiotherapy (d-CRT) is a treatment option. Nevertheless, the comparative efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC remain unclear. AIM: To compare the efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC. METHODS: We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th, 2022. We analyzed demographic, medical recorded, histopathologic characteristics, imaging and endoscopic, and follow-up data. The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments. Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors. RESULTS: We retrospectively analyzed patients who underwent ESD (n = 99) or surgery (n = 220) or d-CRT (n = 16) at the Sun Yat-sen University Cancer Center from 2017 to 2019. The median follow-up time for the ESD group, the surgery group, and the d-CRT group was 42.0 mo (95%CI: 35.0-60.2), 45.0 mo (95%CI: 34.0-61.75) and 32.5 mo (95%CI: 28.3-40.0), respectively. After adjusting for background factors using IPTW, the highest 3-year overall survival (OS) rate and 3-year recurrence-free survival (RFS) rate were observed in the ESD group (3-year OS: 99.7% and 94.7% and 79.1%; and 3-year RFS: 98.3%, 87.4% and 79.1%, in the ESD, surgical, and d-CRT groups, respectively). There was no difference of severe complications occurring between the three groups (P ≥ 0.05). Multivariate analysis showed that treatment method, histology and depth of infiltration were independently associated with OS and RFS. CONCLUSION: For cT1N0M0 EC, ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery, with a similar rate of severe complications occurring.
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Background: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) comorbidity occurs through exposure to trauma with genetic susceptibility. Neuropeptide-Y (NPY) and dopamine are neurotransmitters associated with anxiety and stress-related psychiatry through receptors. We attempted to explore the genetic association between two neurotransmitter receptor systems and the PTSD-MDD comorbidity. Methods: Four groups were identified using latent profile analysis (LPA) to examine the patterns of PTSD and MDD comorbidity among survivors exposed to earthquake-related trauma: low symptoms, predominantly depression, predominantly PTSD, and PTSD-MDD comorbidity. NPY2R (rs4425326), NPY5R (rs11724320), DRD2 (rs1079597), and DRD3 (rs6280) were genotyped from 1,140 Chinese participants exposed to earthquake-related trauma. Main, gene-environment interaction (G × E), and gene-gene interaction (G × G) effects for low symptoms, predominantly depression, and predominantly PTSD were tested using a multinomial logistic model with PTSD-MDD comorbidity as a reference. Results: The results demonstrated that compared to PTSD-MDD comorbidity, epistasis (G × G) NPY2R-DRD2 (rs4425326 × rs1079597) affects low symptoms (ß = -0.66, OR = 0.52 [95% CI: 0.32-0.84], p = 0.008, pperm = 0.008) and predominantly PTSD (ß = -0.56, OR = 0.57 [95% CI: 0.34-0.97], p = 0.037, pperm = 0.039), while NPY2R-DRD3 (rs4425326 × rs6280) impacts low symptoms (ß = 0.82, OR = 2.27 [95% CI: 1.26-4.10], p = 0.006, pperm = 0.005) and predominantly depression (ß = 1.08, R = 2.95 [95% CI: 1.55-5.62], p = 0.001, pperm = 0.001). The two G × G effects are independent. Conclusion: NPY and dopamine receptor genes are related to the genetic etiology of PTSD-MDD comorbidity, whose specific mechanisms can be studied at multiple levels.
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In February 2022, leaf zonate spot disease afflicted Aloe vera L. in Yunnan, China, endangering the $39 billion industry with 0.33ha under cultivation (Wan 2015). The disease manifested with watery spots progressing into oval or circular necrosis lesions, characterized by a dark center surrounded by a gray-brown zone. In the late stage of the disease, lesions regress in size and several small dark picnidia dots appeared on the gray-brown zone. The disease incidence ranged from 10% to 15% in three commercial plantations. If left uncontrolled, the disease could diminish the commercial value of Aloe vera plants. Eighteen symptomatic leaf samples underwent morphological and genetic identification. The samples were carefully washed with distilled water and 1×1 cm2 sections of tissue were excised using a sterile scalpel. The sections underwent surface-disinfection with 3% NaOCl for 3 min and 75% ethanol for 30 s. After three sterile water rinses the sections were air-dried. Subsequently, they were transferred to potato dextrose agar (PDA) before being incubated at 25 â in the dark. Of the 18 samples, eight produced the colonies with similar morphological characteristics, named LH7. Isolate LH7 had downy to woolly aerial mycelia, initially pinkish white on the surface, and gradually turned greenish-olivaceous from the middle, and eventually turned dark brown to black after seven days. The fungus formed arthric chains in the aerial mycelium on PDA but did not produce conidiomata. The conidia, which occurred in arthric chains were 5.50-9.9 × 4.08-7.51 µm (mean 7.09× 5.26 µm, n=50) in size, cylindrical, brown, and 0-1 septate. To ascertain LH7's pathogenicity, three healthy one-year old aloe plants were surface-sanitized with a 1% aqueous chlorine solution, rinsed with sterile water, and dried. Three leaves from each plant were punctuated and inoculated using conidial suspension (100 µl of 1x 106 conidial mL-1), while three control plants were inoculated with sterile distilled water. The pathogenicity tests were repeated twice. The inoculated plants were kept at 25 â with a 12-hour light/12-hour dark cycle. After seven days, symptoms observed in the field appeared in the plants, while no disease occurred in the control plants. After 21 days, conidiomata formed on the inoculated leaves, averaging 116.92 µm (n=20) in diameter. These conidiomata were globose to subglobose, and brown to sub-brown. The fungus was successfully re-isolated from symptomatic tissue and the resulting colonies were morphologically consistent with isolate LH7. Based on the characteristics, the fungus was identified as Neoscytalidium dimidiatum (Philips et al. 2013). The specimen was deposited in China Center for Type Culture Collection ( CCTCC AF 2024001). This identification was confirmed through sequencing of ITS gene region of rDNA using ITS1/ITS4 (Imran et al. 2022). The sequence was submitted into GenBank database (ON878059). BLAST analysis of the LH7's ITS amplicon showed 100% similarity with that of JN093303.1. A phylogenetic tree constructed using the maximum likelihood method revealed that ON878059 was clustered with JN093303.1. Previous studies have documented that pathogens such as Colletotrichum gloeosporioides (Penz.), Fusarium spp. and Rhizopus oryzae can also cause diseases in A. vera in China (Zhou et al. 2008; Ding et al. 2015). Additinonally, Cladosporium sphaerospermum, Pseudopestalotiopsis theae, and Lasiodiplodia theobromae have been identified as causal agents of aloe leaf spot diseases in India, Bangladesh and Malaysia (Avasthi et al. 2016; Ahmmed et al. 2022; Khoo et al. 2022). To our knowledge, this is the first report of N. dimidiatum causing leaf necrosis of aloe in China. Vigilant surveillance and disease control measures are imperative to mitigate potential losses in this region.
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CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.
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Proteína CapZ , Discapacidades del Desarrollo , Epilepsia , Heterocigoto , Hipotonía Muscular , Mutación , Preescolar , Femenino , Humanos , Masculino , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Epilepsia/genética , Secuenciación del Exoma , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Fenotipo , Empalme del ARN/genética , Proteína CapZ/genéticaRESUMEN
Background: Social isolation can be particularly challenging for individuals with high autistic traits who struggle with social interactions. The COVID-19 pandemic led to increased isolation, exacerbating stress for those who may have difficulty in connecting with others. This study aimed to explore the relationship between autistic traits and stress associated with social isolation. Methods: A sample of 1597 Chinese adults completed measures of autistic traits, the stress of social isolation, psychological inflexibility and core self-evaluation, during an epidemic prevention and control period of COVID-19 in Chongqing, China. Measures included the Autism-Spectrum Quotient, Coronavirus Stress Measure, Acceptance and Action Questionnaire-II, and Core Self-Evaluation Scale. Results: Autistic traits were positively correlated with the stress of social isolation, which was mediated by the chain effect of core self-evaluation and psychological inflexibility. individuals with high autistic traits reported significantly higher stress than individuals with low autistic traits. Limitations: This was a cross-sectional study, which limits causal inference. In addition, data were self-reported, which may cause methodological effects. Finally, this study was conducted during China's quarantine policy and external validation of the findings is required. Conclusions: Autistic traits are positively associated with the stress of social isolation. Autistic traits affected core self-evaluation first, and psychological inflexibility subsequently, leading to the stress of social isolation. individuals with high autistic traits tended to experience higher levels of stress during pandemic quarantines. The findings provide useful evidence for developing interventions and implementing preventive measures to reduce stress in individuals with high autistic traits and autism spectrum disorder.
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PURPOSE: This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people. METHODS: (1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software. RESULTS: Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research. CONCLUSION: Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.
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Puntos de Acupuntura , Estreñimiento , Humanos , Anciano , Reproducibilidad de los Resultados , Estreñimiento/tratamiento farmacológico , Medicina Tradicional China , Resultado del TratamientoRESUMEN
BACKGROUND: The COVID-19 pandemic and related policies have amplified the vulnerability of adolescents to the development of posttraumatic stress disorder (PTSD) and dissociation symptoms. This study sought to explore the profile patterns and psychopathological characteristics of co-occurring PTSD and dissociation symptoms in Chinese adolescents. METHODS: A total of 57,984 junior and senior high school students in Deyang City, China were recruited between July 13 and July 19, 2020. PTSD and dissociation symptoms, risk factors, and functional impairment variables were assessed using the Global Psychotrauma Screen for Teenagers (GPS-T) instrument. Latent class analysis (LCA) was employed to examine the phenomenology and risk factors of co-occurring PTSD and dissociation symptoms. Analysis of Variance (ANOVA) was utilized to investigate differences in COVID-19 pandemic-related exposure and functional impairment across distinct symptom profiles. RESULTS: A 4-class model was selected as the optimal solution, comprising subgroups of low symptom, predominant PTSD symptom, predominant dissociation symptom, and PTSD-dissociation symptom. Class membership could be significantly predicted by other stressful experiences, social support, childhood maltreatment and psychiatric histories. The PTSD-dissociation symptom class exhibited the most severe COVID-19 pandemic-related exposure and functional impairment among all classes. LIMITATIONS: The cross-sectional design, Chinese cultural background, online survey method and oversimple measurements were the limitations. CONCLUSIONS: Our findings extend existing knowledge about the coexisting patterns of PTSD and dissociation symptoms in adolescents, which could assist in identifying high-risk youths. Furthermore, our findings offer recommendations for shaping public health policies and formulating effective clinical interventions for adolescents following the COVID-19 pandemic and lockdown.
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COVID-19 , Trastornos por Estrés Postraumático , Humanos , Adolescente , Trastornos por Estrés Postraumático/psicología , Estudios Transversales , Análisis de Clases Latentes , Pandemias , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Trastornos Disociativos/psicología , China/epidemiologíaRESUMEN
BACKGROUND: Malignant melanoma is a kind of tumor derived from melanocytes, which has the characteristics of drug resistance and distant metastasis. Accumulating evidence has demonstrated that circular RNAs (circRNAs) are involved in the pathogenesis of melanoma. Our current study aimed to investigate the role and mechanism of circRTTN in melanoma progression. METHODS: The levels of circRTTN, microRNA-890 (miR-890) and EPH receptor A2 (EPHA2) were examined via quantitative real-time PCR (qRT-PCR) and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to estimate the effects of circRTTN on growth, apoptosis, migration, invasion and angiogenesis of melanoma cells. Western blot was used to measure related marker protein levels. The interaction between miR-890 and circRTTN or EPHA2 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circRTTN in vivo. RESULTS: CircRTTN and EPHA2 levels were up-regulated, while miR-890 was down-regulated in melanoma tissues and cells. CircRTTN knockdown restrained cell proliferation, migration, invasion and angiogenesis, but promoted cell apoptosis in vitro. CircRTTN was an effective molecular sponge for miR-890, and negatively regulated miR-890 expression. The suppressive role of circRTTN knockdown on cell growth, metastasis and angiogenesis in vitro was abated by blocking miR-890. MiR-890 directly targeted EPHA2. MiR-890 overexpression elicited a similar anti-tumor role in melanoma cells, which was abrogated by overexpression of EPHA2. In addition circRTTN knowdown markedly attenuated xenograft tumor growth in vivo. CONCLUSION: Our findings demonstrated that circRTTN mediated melanoma progression via regulating the miR-890/ EPHA2 axis.
Asunto(s)
Melanoma , MicroARNs , Neoplasias Cutáneas , Humanos , Melanoma/genética , Neoplasias Cutáneas/genética , Melanocitos , Apoptosis , Proliferación Celular , MicroARNs/genética , Línea Celular TumoralRESUMEN
ABSTRACT: Background: Sepsis is a life-threatening systemic inflammatory disease that can cause many diseases, including acute kidney injury (AKI). Increasing evidence showed that a variety of circular RNAs were considered to be involved in the development of the disease. In this study, we aimed to elucidate the role and potential mechanism of circUSP42 in sepsis-induced AKI. Methods: HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. The expression levels of circUSP42, microRNA-182-5p (miR-182-5p), and DUSP1 in LPS-treated HK2 cells were measured by quantitative real-time polymerase chain reaction or Western blot. Functional experiments were performed by using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, oxidative stress assay, and enzyme-linked immunosorbent assay. The potential target binding site between miR-182-5p and CircUSP42 or DUSP1 was verified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: CircUSP42 and DUSP1 were downregulated in serum samples from patients with AKI and LPS-treated HK2 cells, while miR-182-5p was upregulated. Functionally, overexpression of CircUSP42 promoted cell proliferation and inhibited apoptosis, inflammation, and oxidative stress in LPS-triggered HK2 cells. Further mechanism analysis showed that miR-182-5p had potential binding sites with circUSP42 and DUSP1, and circUSP42 regulated LPS-induced cell damage by targeting miR-182-5p. At the same time, miR-182-5p knockdown inhibited LPS-treated HK2 cell damage by regulating DUSP1. In addition, circUSP42 induced DUSP1 expression via sponging miR-182-5p to ameliorate LPS-induced HK2 cell damage. Conclusion : Our results showed that circUSP42 overexpression might attenuate LPS-induced HK2 cell injury by regulating miR-182-5p/DUSP1 axis. This might provide therapeutic strategy for the treatment of sepsis.