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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.

Rolling bearings are the core transmission components of large-scale equipment. Once a fault occurs, the consequences may be catastrophic, posing a serious threat to life and the safety of the property. Aimed at the problem of rolling bearing faults, this paper analyzes the characteristics of different fault signals and proposes a fault diagnosis method based on fuzzy signals. Based on the definition of an incomplete mapping of a new connotation, this paper proposes a fuzzy fault diagnosis method by fuzzy mapping, gives a fuzzy signal processing algorithm, and discusses two judgment principles. Further, it carries out a vibration signal analysis of the rolling bearing. According to the fault diagnosis method in this paper, the fault rolling bearing is diagnosed. The experimental results show that the proposed method can effectively diagnose rolling bearing faults closer to their natural attributes and solves the problem of traditional generator bearing fault diagnosis that requires complex models and poor diagnosis speed. Further, it can be seen that the average time consumption of this method is reduced and the fault recognition accuracy rate is increased. Compared with the existing related methods, this proposed diagnosis method is superior to that of several existing methods. It not only has higher precision, stronger anti-noise capacity, and faster diagnosis speed, but also has lower effective information loss.

Arginine methylation by PRMTs is dysregulated in cancer. Here, the authors use functional genomics screens and identify PRMT1 as a vulnerability in pancreatic ductal adenocarcinoma, and further show that PRMT1 regulates RNA metabolism and coordinates expression of genes in cell cycle progression, maintaining genomic stability and tumour growth.

Abstract Background Coronavirus disease 2019 (COVID-19) is closely associated with physical and mental health problems; however, little is known about the severity of stigma caused by COVID-19 among its survivors. Thus, the aim of this study was to compare differences in stigma experiences of COVID-19 survivors versus healthy controls after the COVID-19 outbreak peak in China. Methods This cross-sectional study comprised 154 COVID-19 survivors and 194 healthy controls recruited through consecutive and convenience sampling methods, respectively. COVID-19 related stigma was measured by the Social Impact Scale (SIS). Stigma differences between the two groups were compared with analysis of covariance (ANCOVA) and a generalized linear model (GLM) was used to identify independent correlates of COVID-19-related stigma in this study. Results Compared with healthy controls, COVID-19 survivors reported more overall stigma (F (1,347) = 60.82, p

Background: Prevalence estimates of major depressive disorder (MDD) among adults in China have varied widely between studies. In this systematic review and meta-analysis, the overall prevalence of MDD in the Chinese population was estimated from published epidemiological studies and potential moderators that account for variability in estimates were assessed.Methods: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, PsycINFO, China National Knowledge Internet (CNKI), and WanFang databases to identify relevant studies. Data analyses were conducted using the Comprehensive Meta-Analysis Version 2.0.Results: Forty studies comprising 1,024,087 subjects were included. The pooled point, 12-month, and lifetime prevalence rates of MDD in China were 1.1% (95% CI: 0.9–1.4%), 1.6% (95% CI: 1.0–2.5%), and 1.8% (95% CI: 1.5–2.2%), respectively. Subgroup and meta-regression analyses revealed gender, marital status, survey year, being published in English language, use of the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic systems and age as significant moderators of MDD prevalence.Conclusion: The overall prevalence of MDD in the Chinese population appears to be lower than that of most countries, but the rates have been increasing over time and are elevated in particular demographic subgroups. Due to the negative consequences of MDD, effective preventive measures, early identification, and timely treatments are still important and should be offered to those in need.

BackgroundDepressive symptoms are common in empty-nest elderly in China, but the reported prevalence rates across studies are mixed. This is a meta-analysis of the pooled prevalence of depressive symptoms (depression hereafter) in empty-nest elderly in China.MethodsTwo investigators independently conducted a systematic literature search in both English (PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Library) and Chinese (CNKI and Wan Fang) databases. Data were analyzed using the Comprehensive Meta-Analysis program.ResultsA total of 46 studies with 36,791 subjects were included. The pooled prevalence of depression was 38.6% (95%CI: 31.5–46.3%). Compared with non-empty-nest elderly, empty-nest elderly were more likely to suffer from depression (OR=2.0, 95%CI: 1.4 to 2.8, P

The hardness recognition is of great significance to tactile sensing and robotic control. The hardness recognition methods based on deep learning have demonstrated a good performance, however, a huge amount of manually labeled samples which require lots of time and labor costs are necessary for the training of deep neural networks. In order to alleviate this problem, a semi-supervised generative adversarial network (GAN) which requires less manually labeled samples is proposed in this paper. First of all, a large number of unlabeled samples are made use of through the unsupervised training of GAN, which is used to provide a good initial state to the following model. Afterwards, the manually labeled samples corresponding to each hardness level are individually used to train the GAN, of which the architecture and initial parameter values are inherited from the unsupervised GAN, and augmented by the generator of trained GAN. Finally, the hardness recognition network (HRN), of which the main architecture and initial parameter values are inherited from the discriminator of unsupervised GAN, is pretrained by a large number of augmented labeled samples and fine-tuned by manually labeled samples. The hardness recognition result can be obtained online by importing the tactile data captured by the robotic forearm into the trained HRN. The experimental results demonstrate that the proposed method can significantly save the manual labeling work while providing an excellent recognition precision for hardness recognition.

We previously demonstrated that multipotent mesenchymal stromal cells (MSCs) that overexpress microRNA 133b (miR-133b) significantly improve functional recovery in rats subjected to middle cerebral artery occlusion (MCAO) compared with naive MSCs and that exosomes generated from naive MSCs mediate the therapeutic benefits of MSC therapy for stroke. Here we investigated whether exosomes isolated from miR-133b-overexpressing MSCs (Ex-miR-133b + ) exert amplified therapeutic effects. Rats subjected to 2 h of MCAO were intra-arterially injected with Ex-miR-133b + , exosomes from MSCs infected by blank vector (Ex-Con), or phosphate-buffered saline (PBS) and were sacrificed 28 days after MCAO. Compared with the PBS treatment, both exosome treatment groups exhibited significant improvement of functional recovery. Ex-miR-133b + treatment significantly increased functional improvement and neurite remodeling/brain plasticity in the ischemic boundary area compared with the Ex-Con treatment. Treatment with Ex-miR-133b + also significantly increased brain exosome content compared with Ex-Con treatment. To elucidate mechanisms underlying the enhanced therapeutic effects of Ex-miR-133b + , astrocytes cultured under oxygen- and glucose-deprived (OGD) conditions were incubated with exosomes harvested from naive MSCs (Ex-Naive), miR-133b downregulated MSCs (Ex-miR-133b − ), and Ex-miR-133b + . Compared with the Ex-Naive treatment, Ex-miR-133b + significantly increased exosomes released by OGD astrocytes, whereas Ex-miR-133b − significantly decreased the release. Also, exosomes harvested from OGD astrocytes treated with Ex-miR-133b + significantly increased neurite branching and elongation of cultured cortical embryonic rat neurons compared with the exosomes from OGD astrocytes subjected to Ex-Con. Our data suggest that exosomes harvested from miR-133b-overexpressing MSCs improve neural plasticity and functional recovery after stroke with a contribution from a stimulated secondary release of neurite-promoting exosomes from astrocytes.

Sublethal effects of chlorantraniliprole to Helicoverpa armigera (Hbner) larvae were evaluated through exposure of third instar larvae to the insecticide incorporated into an artificial diet. When larvae were fed on the insecticide-containing diet for 7 d, the LC10, LC20, LC40, and LC50 values were 3.790, 7.977, 21.577, and 33.121 μg active ingredient L−1, respectively. Chlorantraniliprole at sublethal concentrations significantly reduced the larval body mass, emergence ratio, adult longevity and egg hatching rate in both the parental and offspring generations. The pupation and copulation rate in the parental generation and the pupal mass in the offspring also strongly decreased. Reproduction was seriously disturbed in both the parental and offspring groups even when only one of the partners was exposed to chlorantraniliprole at larval stages. However, at the lowest concentration of exposure (LC10), offspring fecundity was strongly reduced only when both partners were exposed. The net reproductive rate (R0), intrinsic rate of increase (rm), and gross reproduction rate (GRR) at LC20, LC40 concentrations were significantly lower than that of the control. Post-exposure effects also included an extended larval developmental time and increased male proportion in both generations. The doubling time (Dt) at LC20, LC40 concentrations as well as gross reproduction rate (GRR) at LC10 concentration were also significantly increased. Chlorantraniliprole might have significant effects on H. armigera population dynamics even at sublethal concentrations on both parental and offspring generations.