We demonstrate high-performance, air-stable, low-temperature processed (≤100 °C) semitransparent (ST) perovskite solar cells (PSCs) by the applications of atomic layer deposition (ALD) technology to ...deposit ZnO and Al2O3 films as cathode buffer layer (CBL) and encapsulation layer, respectively. The application of ALD ZnO film as CBL in PSCs delivers several remarkable features, including fine-tunability of the work function of the electrode, low deposition temperature (80 °C), high charge selectivity, good electron-transporting ability (filed-effect mobility = 16.1 cm2 V–1 s–1), and excellent film coverage. With these desired interfacial properties, the device with opaque Ag electrode delivers high power conversion efficiency (PCE) up to 16.5%, greatly outperforming the device with state-of-the-art CBL ZnO nanoparticles film (10.8%). For ST PSCs employing Ag nanowires as transparent top electrode, a remarkable PCE of 10.8% with a corresponding average visible transmittance (AVT) of 25.5% is demonstrated, which represents the highest PCE ever reported for ST PSCs with similar AVT. More significantly, the insufficient ambient stability of ST device is significantly improved by employing excellent gas-barrier performance of ALD Al2O3-based encapsulation layer with an oxygen transmission rate of 1.9 × 10–3 cm3 m–2 day–1 and a water vapor transmittance rate of 9.0 × 10–4 g m–2 day–1.
Healing of large calvarial bone defects remains challenging. An RNA‐guided Split dCas12a system is previously harnessed to activate long non‐coding RNA H19 (lncRNA H19, referred to as H19 thereafter) ...in bone marrow‐derived mesenchymal stem cells (BMSCs). H19 activation in BMSCs induces chondrogenic differentiation, switches bone healing pathways, and improves calvarial bone repair. Since adipose‐derived stem cells (ASCs) can be harvested more easily in large quantity, here it is aimed to use ASCs as an alternative cell source. However, H19 activation alone using the Split dCas12a system in ASCs failed to elicit evident chondrogenesis. Therefore, split dCas12a activators are designed more to co‐activate other chondroinductive transcription factors (Sox5, Sox6, and Sox9) to synergistically potentiate differentiation. It is found that co‐activation of H19/Sox5/Sox6 in ASCs elicited more potent chondrogenic differentiation than activation of Sox5/Sox6/Sox9 or H19 alone. Co‐activating H19/Sox5/Sox6 in ASCs significantly augmented in vitro cartilage formation and in vivo calvarial bone healing. These data altogether implicated the potentials of the Split dCas12a system to trigger multiplexed gene activation in ASCs for differentiation pathway reprogramming and tissue regeneration.
A new Split dCas12a activator is designed for delivery into ASCs to co‐activate long non‐coding RNA H19, Sox5, and Sox6. The split dCas12a spontaneously dimerizes in ASCs and activates H19, Sox5, and Sox6, hence enhancing chondrogenesis, suppressing adipogenesis, and augmenting calvarial bone healing in rats.
Single‐crystalline silicon (sc‐Si) is the dominant semiconductor material for the modern electronics industry. Despite their excellent photoelectric and electronic properties, the rigidity, ...brittleness, and nontransparency of commonly used silicon wafers limit their application in transparent flexible optoelectronics. In this study, a new type of Si microstructure, named single‐crystalline Si frameworks (sc‐SiFs), is developed, through a combination of wet‐etching and microfabrication technologies. The sc‐SiFs are self‐supported, flexible, lightweight, tailorable, and highly transparent. They can withstand a small bending radius of less than 0.5 mm and have a transparency of up to 96% in all wavelength ranges, owing to the hollowed‐out framework structures. Thus, the sc‐SiFs provide a new platform for high‐performance transparent flexible optoelectronics. Taking transparent flexible photodetectors (TFPDs) as an example, substrate‐free and self‐driven TFPDs are achieved based on the sc‐SiFs. The devices exhibit superior performance compared to other reported TFPDs and reveal the great potential for integrated optoelectronic applications. The development of sc‐SiFs paves the way toward the fabrication of high‐performance transparent flexible devices for a host of applications, including e‐skins, the Internet of Things, transparent flexible displays, and artificial visual cortexes.
Self‐supported, flexible, and highly transparent single‐crystalline silicon frameworks (sc‐SiFs) are fabricated from commonly used Si wafers by combining wet‐etching and microfabrication technologies. They provide a new platform for transparent flexible optoelectronics, enabling the construction of high‐performance transparent flexible Si‐based devices.
Crispr/CAS9‐enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context‐dependent promoter activity that complicate analysis of gene ...expression and protein accumulation patterns. However, there have been few reports examining whether such gene targeting/gene tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1‐pyrroline‐5‐carboxylate synthetase 1 (P5CS1) is key for stress‐induced proline synthesis and drought resistance, yet its expression pattern and protein localisation have been difficult to assay. We used GT to insert YFP in frame with the 5′ or 3′ ends of the endogenous P5CS1 and At14a‐Like 1 (AFL1) coding regions. Insertion at the 3′ end of either gene generated homozygous lines with expression of the gene‐YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT‐generated P5CS1‐YFP plants revealed new information about P5CS1 localisation and tissue‐specific expression. In contrast, insertion of YFP at the 5′ end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene.
Summary statement
Gene tagging (GT) of Arabidopsis thaliana P5CS1 and AFL1 shows the potential of GT for functional analysis of stress‐related genes, but also provides examples of how GT can dramatically disrupt expression of the target gene.
Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20-30% pathologic complete response. Because miRNAs ...are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Understanding the role and mechanism of dysregulated miRNAs in TNBC may help to develop novel diagnostic and prognostic strategy for TNBC patients.
The miRNA array profiles of 1299 breast cancer patients were collected from the Metabric database and subjected to analysis of the altered miRNAs between TNBC and non-TNBC. In Student's t-test and Kaplan-Meier analysis, four upregulated miRNAs correlated with poor survival in TNBC but not in non-TNBC. Four miRNAs were manipulated in multiple cell lines to investigate their functional role in carcinogenesis. From these results, we studied miR-105 and miR-93-3p in greater detail. The level of miR-105 and miR-93-3p were evaluated in 25 breast cancer tumor tissues. In addition, the diagnostic utility of circulating miR-105 and miR-93-3p were examined in 12 normal and 118 breast cancer plasma samples by ROC curve construction.
miR-105 and miR-93-3p were upregulated and correlated with poor survival in TNBC patients. Both miR-105 and miR-93-3p were found to activate Wnt/β-catenin signaling by downregulation of SFPR1. By this action, stemness, chemoresistance, and metastasis were promoted. Importantly, the combination of circulating miR-105/93-3p may serve as a powerful biomarker for TNBC, even in early-stage disease.
miR-105/93-3p activates Wnt/β-catenin signaling by downregulating SFRP1 and thereby promotes stemness, chemoresistance, and metastasis in TNBC cells. Most importantly, combined circulating miR-105/93-3p levels represent a prime candidate for development into a diagnostic biomarker for both early- and late-stage TNBC.
Several cross-sectional studies have reported risk factors for metabolic syndrome (MetS). However, these studies did not focus on sex differences in middle-aged and senior populations or employ a ...longitudinal design. These study design differences are important, as there are sex differences in lifestyle habits associated with MetS, and middle-aged and senior individuals have increased MetS susceptibility. Therefore, the purpose of this study was to examine whether sex differences influenced MetS risk over a ten-year follow-up period among middle-aged and senior hospital employees.
This population-based and prospective cohort study enrolled 565 participants who did not have MetS in 2012 for a ten-year repeated-measurement analysis. Data were retrieved from the hospital's Health Management Information System. Analyses included Student's t tests, χ
tests and Cox regression. P < 0.05 indicated statistical significance.
Male middle-aged and senior hospital employees had an elevated MetS risk (hazard ratio (HR) = 1.936, p < 0.001). Men with more than four family history risk factors had an increased risk of MetS (HR = 1.969, p = 0.010). Women who worked shift duty (HR = 1.326, p = 0.020), had more than two chronic diseases (HR = 1.513, p = 0.012), had three family history risk factors (HR = 1.623, p = 0.010), or chewed betel nuts (HR = 9.710, p = 0.002) had an increased risk of MetS.
The longitudinal design of our study improves the understanding of sex differences in MetS risk factors in middle-aged and senior adults. A significantly elevated risk of MetS over the ten-year follow-up period was associated with male sex, shift work, the number of chronic diseases, the number of family history risk factors, and betel nut chewing. Women who chewed betel nuts had an especially increased risk of MetS. Our study indicates that population-specific studies are important for the identification of subgroups susceptible to MetS and for the implementation of hospital-based strategies.
We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor ...(VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11). The intravitreal faricimab group showed numerically lower CST WMD = - 5.96; 95% CI = (- 7.11, - 4.82), total CNV area WMD = - 0.49; 95% CI = (- 0.68, - 0.30), and total lesion leakage WMD = - 0.88; 95% CI = (- 1.08, - 0.69) after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49) and serious adverse events (SAEs) pooled OR = 0.84; 95% CI = (0.37, 1.90). The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
Genetic co-expression network (GCN) analysis augments the understanding of breast cancer (BC). We aimed to propose GCN-based modeling for BC relapse-free survival (RFS) prediction and to discover ...novel biomarkers. We used GCN and Cox proportional hazard regression to create various prediction models using mRNA microarray of 920 tumors and conduct external validation using independent data of 1056 tumors. GCNs of 34 identified candidate genes were plotted in various sizes. Compared to the reference model, the genetic predictors selected from bigger GCNs composed better prediction models. The prediction accuracy and AUC of 3 ~ 15-year RFS are 71.0-81.4% and 74.6-78% respectively (rfm, ACC 63.2-65.5%, AUC 61.9-74.9%). The hazard ratios of risk scores of developing relapse ranged from 1.89 ~ 3.32 (p < 10
) over all models under the control of the node status. External validation showed the consistent finding. We found top 12 co-expressed genes are relative new or novel biomarkers that have not been explored in BC prognosis or other cancers until this decade. GCN-based modeling creates better prediction models and facilitates novel genes exploration on BC prognosis.
The aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for advanced fibrosis in chronic hepatitis C (CHC) patients. ...However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. We sought to investigate the optimal cutoff values of the two compound surrogates for predicting cirrhosis stratified by AST level.
This retrospective study enrolled 1716 treatment-naive CHC patients who underwent liver biopsy prior to interferon therapy from 1997-2010. Fibrosis was scored according to the modified Knodell classification. The upper limit for normal AST in our hospital is 37 IU/L. We stratified the enrolled patients into the categories of AST≤37 IU/L (N = 132), 37<AST≤74, (N = 501), 74<AST≤148 IU/L (N = 737), and AST>148 IU/L (N = 346).
436 patients had cirrhosis (F4). The area under receiver operating characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non-cirrhosis (F0-F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST≤37 IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37<AST≤74IU/L; 0.72 for APRI and 0.73 for FIB-4 in patients with 74<AST≤148 IU/L; and 0.68 for APRI and 0.70 for FIB-4 in patients with AST>148 IU/L. The optimal cutoff values of APRI and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in patients with AST≤37 IU/L; 1.1 and 2.2, respectively, in patients with 37<AST≤74 IU/L; 2.2 and 3.4, respectively, in patients with 74<AST≤148 IU/L; and 3.4 and 5.5, respectively, in patients with AST>148 IU/L.
We provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis stratified by AST levels, which should be more feasible compared with the single cutoff values proposed in previous studies.
Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome ...Coronavirus 2 (SARS-CoV-2).
Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors.
Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity.
IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs).
Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001) and CCGSFPOR20002. ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR.
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