Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report ...that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H
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and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases.
Circular RNA ciRS-7 has been reported to be involved in the progression of various cancers. However, ciRS-7 expression and its role in clear cell renal cell carcinoma (ccRCC) progression remains ...unclear. This study aimed to investigate the effect of ciRS-7 expression on ccRCC and the related signaling pathway.
ciRS-7 expression was analyzed using quantitative reverse transcription polymerase chain reaction in 87 pairs of ccRCC and matched adjacent normal tissues. The role of ciRS-7 in ccRCC cell proliferation and invasion was determined using the cell counting kit-8 and invasion assays, respectively. Potential mechanisms underlying the role of ciRS-7 in promoting ccRCC progression were explored by Western blotting. The relationship between the expression of ciRS-7 and features of ccRCC was analyzed by the Chi-square test and progression-free survival was determined using a Kaplan-Meier plot.
ciRS-7 was overexpressed in ccRCC tissues compared with that in matched adjacent normal tissues. In addition, ciRS-7 up-regulation was closely associated with tumor diameter (P = 0.050), clinical stage (P = 0.009), and distant metastasis (P = 0.007). ciRS-7 knockdown in 786O and 769P cells markedly inhibited their proliferative and invasive abilities. In addition, ciRS-7 inhibition reduced phosphorylated epidermal growth factor receptor (p-EGFR) and phosphorylated serine/threonine kinase (p-Akt) levels.
ciRS-7 up-regulation could promote ccRCC cell proliferation and invasion, which may be related with the EGFR/Akt signaling pathway. ciRS-7 might be a potential ccRCC therapeutic target.
Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan.
This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect.
27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2–16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0–1 years were significantly more likely to be infected than children aged 2–5 years (odds ratio OR 2·20, 95% CI 1·40–3·44) and children aged 6–12 years (1·53, 1·01–2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28–1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14–0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30–1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 95% CI 0·24–0·26 to 0·12 0·10–0·13) and by 63% among secondary cases (from 0·17 0·16–0·18 to 0·063 0·057–0·070).
Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.
National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.
Interface strains and lattice distortion are inevitable issues during perovskite crystallization. Silane as a coupling agent is a popular connector to enhance the compatibility between inorganic and ...organic materials in semiconductor devices. Herein, a protonated amine silane coupling agent (PASCA‐Br) interlayer between TiO2 and perovskite layers is adopted to directionally grasp both of them by forming the structural component of a lattice unit. The pillowy alkyl ammonium bromide terminals at the upper side of the interlayer provide well‐matched growth sites for the perovskite, leading to mitigated interface strain and ensuing lattice distortion; meanwhile, its superior chemical compatibility presents an ideal effect on healing the under‐coordinated Pb atoms and halogen vacancies of bare perovskite crystals. The PASCA‐Br interlayer also serves as a mechanical buffer layer, inducing less cracked perovskite film when bending. The developed molecular‐level flexible interlayer provides a promising interfacial engineering for perovskite solar cells and their flexible application.
A protonated amino silane coupling agent as an interlayer is exploited on rigid and flexible substrates, which not only sets up well‐matched growth underlay but also serves as a structural component of the lattice units, leading to less‐distorted perovskite films, resulting in an obvious advance in device performance, stability, and mechanical tolerance in the corresponding flexible device.
The chemical composition engineering of lead halide perovskites via a partial or complete replacement of toxic Pb with tin has been widely reported as a feasible process due to the suitable ionic ...radius of Sn and its possibility of existing in the +2 state. Interestingly, a complete replacement narrows the bandgap while a partial replacement gives an anomalous phenomenon involving a further narrowing of bandgap relative to the pure Pb and Sn halide perovskite compounds. Unfortunately, the merits of this anomalous behavior have not been properly harnessed. Although promising progress has been made to advance the properties and performance of Sn‐based perovskite systems, their photovoltaic (PV) parameters are still significantly inferior to those of the Pb‐based analogs. This review summarizes the current progress and challenges in the preparation, morphological and photophysical properties of Sn‐based halide perovskites, and how these affect their PV performance. Although it can be argued that the Pb halide perovskite systems may remain the most sought after technology in the field of thin film perovskite PV, prospective research directions are suggested to advance the properties of Sn halide perovskite materials for improved device performance.
The replacement of lead with tin in halide perovskites is feasible due to suitable ionic radius and valency. However, easy oxidation, high cost and toxicity concerns in Sn halide perovskite systems may limit the consideration of Sn as a suitable alternative to Pb.
The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying the ...attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair.
Using bioinformatics and initial analysis, we identified an lncRNA, named CPR (cardiomyocyte proliferation regulator), that has a potential regulatory role in cardiomyocyte proliferation. For in vivo experiments, we generated CPR knockout and cardiac-specific CPR-overexpressing mice. In isolated cardiomyocytes, we used adenovirus for silencing (CPR-small interfering RNA) or overexpressing CPR. To investigate the mechanisms of CPR function in cardiomyocyte proliferation, we performed various analyses including quantitative reverse transcription-polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), transcriptome analyses (microarray assay), RNA pull-down assay, and chromatin immunoprecipitation assay.
CPR level is comparatively higher in the adult heart than in the fetal stage. The silencing of CPR significantly increased cardiomyocyte proliferation in postnatal and adult hearts. Moreover, CPR deletion restored the heart function after myocardial injury, which was evident from increased cardiomyocyte proliferation, improvement of myocardial function, and reduced scar formation. In contrast, the neonatal cardiomyocyte proliferation and cardiac regeneration were remarkably suppressed in CPR-overexpressing mice or adeno-associated virus serotype 9-CPR-overexpressing heart. These results indicate that CPR acts as a negative regulator of cardiomyocyte proliferation and regeneration. Next, we found that CPR targets minichromosome maintenance 3, an initiator of DNA replication and cell cycle progression, to suppress cardiomyocyte proliferation. CPR silenced minichromosome maintenance 3 expression through directly interacting and recruiting DNMT3A to its promoter cysteine-phosphate-guanine sites, as evident from decreased minichromosome maintenance 3 promoter methylation and increased minichromosome maintenance 3 expression in CPR knocked-down cardiomyocytes and CPR knockout mouse heart. These results were confirmed in CPR-overexpressing cardiomyocytes and CPR-overexpressing mouse heart.
Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation and indicated that lncRNAs take part in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration.
Through simultaneously enhancing the power factor by engineering the extra light band and enhancing phonon scatterings by introducing a high density of stacking faults, a record figure‐of‐merit over ...2.0 is achieved in p‐type AgSbTe2−xSex alloys. Density functional theory calculations confirm the presence of the light valence band with large degeneracy in AgSbTe2, and that alloying with Se decreases the energy offset between the light valence band and the valence band maximum. Therefore, a significantly enhanced power factor is realized in p‐type AgSbTe2−xSex alloys. In addition, transmission electron microscopy studies indicate the appearance of stacking faults and grain boundaries, which together with grain boundaries and point defects significantly strengthen phonon scatterings, leading to an ultralow thermal conductivity. The synergetic strategy of simultaneously enhancing power factor and strengthening phonon scattering developed in this study opens up a robust pathway to tailor thermoelectric performance.
The extra light valence band and dense stacking faults ensure a figure‐of‐merit over 2 in AgSbTe1.85Se0.15. Alloying with Se decreases the energy offset between the light and the primary valence bands, leading to an enhanced power factor. Transmission electron microscopy studies reveal the dense stacking faults and grain boundaries, which significantly strengthen phonon scatterings, generating an ultralow thermal conductivity.
Smartphones are becoming a daily necessity for most undergraduates in Mainland China. Because the present scenario of problematic smartphone use (PSU) is largely unexplored, in the current study we ...aimed to estimate the prevalence of PSU and to screen suitable predictors for PSU among Chinese undergraduates in the framework of the stress-coping theory.
A sample of 1062 undergraduate smartphone users was recruited by means of the stratified cluster random sampling strategy between April and May 2015. The Problematic Cellular Phone Use Questionnaire was used to identify PSU. We evaluated five candidate risk factors for PSU by using logistic regression analysis while controlling for demographic characteristics and specific features of smartphone use.
The prevalence of PSU among Chinese undergraduates was estimated to be 21.3%. The risk factors for PSU were majoring in the humanities, high monthly income from the family (≥1500 RMB), serious emotional symptoms, high perceived stress, and perfectionism-related factors (high doubts about actions, high parental expectations).
PSU among undergraduates appears to be ubiquitous and thus constitutes a public health issue in Mainland China. Although further longitudinal studies are required to test whether PSU is a transient phenomenon or a chronic and progressive condition, our study successfully identified socio-demographic and psychological risk factors for PSU. These results, obtained from a random and thus representative sample of undergraduates, opens up new avenues in terms of prevention and regulation policies.
In this article, deep learning (DL) has attracted increasing attention for remaining useful life (RUL) prediction. However, most DL-based prognostics methods only provide deterministic RUL values ...while ignoring the associated epistemic and aleatoric uncertainties. In practice, it is important to know the exact confidence in model predictions for decision making. In this article, a Bayesian deep learning (BDL) framework for RUL prediction incorporating uncertainty quantification and calibration is proposed. First, the epistemic and aleatoric uncertainties, which account for the ignorance about the model and the noise inherent in the observations, respectively, are characterized by integrating both types of uncertainties into a BDL framework. Second, to avoid under- and over-confident predictions, a novel iterative calibration method is proposed to jointly calibrate epistemic, aleatoric, and predictive uncertainties by combining isotonic regression with standard deviation scaling. The effectiveness of the proposed method is demonstrated by the case study of turbofan engines and lithium-ion batteries datasets.
Although immune checkpoint inhibitor (ICI) is regarded as a breakthrough in cancer therapy, only a limited fraction of patients benefit from it. Cancer stemness can be the potential culprit in ICI ...resistance, but direct clinical evidence is lacking.
Publicly available scRNA-Seq datasets derived from ICI-treated patients were collected and analyzed to elucidate the association between cancer stemness and ICI response. A novel stemness signature (Stem.Sig) was developed and validated using large-scale pan-cancer data, including 34 scRNA-Seq datasets, The Cancer Genome Atlas (TCGA) pan-cancer cohort, and 10 ICI transcriptomic cohorts. The therapeutic value of Stem.Sig genes was further explored using 17 CRISPR datasets that screened potential immunotherapy targets.
Cancer stemness, as evaluated by CytoTRACE, was found to be significantly associated with ICI resistance in melanoma and basal cell carcinoma (both P < 0.001). Significantly negative association was found between Stem.Sig and anti-tumor immunity, while positive correlations were detected between Stem.Sig and intra-tumoral heterogenicity (ITH) / total mutational burden (TMB). Based on this signature, machine learning model predicted ICI response with an AUC of 0.71 in both validation and testing set. Remarkably, compared with previous well-established signatures, Stem.Sig achieved better predictive performance across multiple cancers. Moreover, we generated a gene list ranked by the average effect of each gene to enhance tumor immune response after genetic knockout across different CRISPR datasets. Then we matched Stem.Sig to this gene list and found Stem.Sig significantly enriched 3% top-ranked genes from the list (P = 0.03), including EMC3, BECN1, VPS35, PCBP2, VPS29, PSMF1, GCLC, KXD1, SPRR1B, PTMA, YBX1, CYP27B1, NACA, PPP1CA, TCEB2, PIGC, NR0B2, PEX13, SERF2, and ZBTB43, which were potential therapeutic targets.
We revealed a robust link between cancer stemness and immunotherapy resistance and developed a promising signature, Stem.Sig, which showed increased performance in comparison to other signatures regarding ICI response prediction. This signature could serve as a competitive tool for patient selection of immunotherapy. Meanwhile, our study potentially paves the way for overcoming immune resistance by targeting stemness-associated genes.
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