CRISPR-Cas13 Inhibitors Block RNA Editing in Bacteria and Mammalian Cells.

Cas13 has demonstrated unique and broad utility in RNA editing, nucleic acid detection, and disease diagnosis; however, a constantly active Cas enzyme may induce unwanted effects. Bacteriophage- or prophage-region-encoded anti-CRISPR (acr) gene molecules provide the potential to control targeting specificity and potency to allow for optimal RNA editing and nucleic acid detection by spatiotemporally modulating endonuclease activities. Using integrated approaches to screen acrVI candidates and evaluate their effects on Cas13 function, we discovered a series of acrVIA1-7 genes that block the activities of Cas13a. These VI-A CRISPR inhibitors substantially attenuate RNA targeting and editing by Cas13a in human cells. Strikingly, type VI-A anti-CRISPRs (AcrVIAs) also significantly muffle the single-nucleic-acid editing ability of the dCas13a RNA-editing system. Mechanistically, AcrVIA1, -4, -5, and -6 bind LwaCas13a, while AcrVIA2 and -3 can only bind the LwaCas13-crRNA (CRISPR RNA) complex. These identified acr molecules may enable precise RNA editing in Cas13-based application and study of phage-bacterium interaction.

Light recovery after maize harvesting promotes soybean flowering in a maize-soybean relay strip intercropping system.

Moving from sole cropping to intercropping is a transformative change in agriculture, contributing to yield. Soybeans adapt to light conditions in intercropping by adjusting the onset of reproduction and the inflorescence architecture to optimize reproductive success. Maize-soybean strip intercropping (MS), maize-soybean relay strip intercropping (IS), and sole soybean (SS) systems are typical soybean planting systems with significant differences in light environments during growth periods. To elucidate the effect of changes in the light environment on soybean flowering processes and provide a theoretical basis for selecting suitable varieties in various planting systems to improve yields, field experiments combining planting systems (IS, MS, and SS) and soybean varieties (GQ8, GX7, ND25, and NN996) were conducted in 2021 and 2022. Results showed that growth recovery in the IS resulted in a balance in the expression of TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) in the meristematic tissues of soybeans, which promoted the formation of new branches or flowers. IS prolonged the flowering time (2-7 days) and increased the number of forming flowers compared with SS (93.0 and 169%) and MS (67.3 and 103.3%) at the later soybean flowering stage. The higher carbon and nitrogen content in the middle and bottom canopies of soybean contributed to decreased flower abscission by 26.7 and 30.2%, respectively, compared with SS. Canopy light environment recovery promoted branch and flower formation and transformation of flowers into pods with lower flower-pod abscission, which contributed to elevating soybean yields in late-maturing and multibranching varieties (ND25) in IS.

Mapping of cytosol-facing organelle outer membrane proximity proteome by proximity-dependent biotinylation in living Arabidopsis cells.

The cytosol-facing outer membrane (OM) of organelles communicates with other cellular compartments to exchange proteins, metabolites, and signaling molecules. Cellular surveillance systems also target OM-resident proteins to control organellar homeostasis and ensure cell survival under stress. However, the OM proximity proteomes have never been mapped in plant cells since using traditional approaches to discover OM proteins and identify their dynamically interacting partners remains challenging. In this study, we developed an OM proximity labeling (OMPL) system using biotin ligase-mediated proximity biotinylation to identify the proximity proteins of the OMs of mitochondria, chloroplasts, and peroxisomes in living Arabidopsis (Arabidopsis thaliana) cells. Using this approach, we mapped the OM proximity proteome of these three organelles under normal conditions and examined the effects of the ultraviolet-B (UV-B) or high light (HL) stress on the abundances of OM proximity proteins. We demonstrate the power of this system with the discovery of cytosolic factors and OM receptor candidates potentially involved in local protein translation and translocation. The candidate proteins that are involved in mitochondrion-peroxisome, mitochondrion-chloroplast, or peroxisome-chloroplast contacts, and in the organellar quality control system are also proposed based on OMPL analysis. OMPL-generated OM proximity proteomes are valuable sources of candidates for functional validation and suggest directions for further investigation of important questions in cell biology.

A systematic assessment of deep learning methods for drug response prediction: from in vitro to clinical applications.

Drug response prediction is an important problem in personalized cancer therapy. Among various newly developed models, significant improvement in prediction performance has been reported using deep learning methods. However, systematic comparisons of deep learning methods, especially of the transferability from preclinical models to clinical cohorts, are currently lacking. To provide a more rigorous assessment, the performance of six representative deep learning methods for drug response prediction using nine evaluation metrics, including the overall prediction accuracy, predictability of each drug, potential associated factors and transferability to clinical cohorts, in multiple application scenarios was benchmarked. Most methods show promising prediction within cell line datasets, and TGSA, with its lower time cost and better performance, is recommended. Although the performance metrics decrease when applying models trained on cell lines to patients, a certain amount of power to distinguish clinical response on some drugs can be maintained using CRDNN and TGSA. With these assessments, we provide a guidance for researchers to choose appropriate methods, as well as insights into future directions for the development of more effective methods in clinical scenarios.

A primer on the use of machine learning to distil knowledge from data in biological psychiatry.

Applications of machine learning in the biomedical sciences are growing rapidly. This growth has been spurred by diverse cross-institutional and interdisciplinary collaborations, public availability of large datasets, an increase in the accessibility of analytic routines, and the availability of powerful computing resources. With this increased access and exposure to machine learning comes a responsibility for education and a deeper understanding of its bases and bounds, borne equally by data scientists seeking to ply their analytic wares in medical research and by biomedical scientists seeking to harness such methods to glean knowledge from data. This article provides an accessible and critical review of machine learning for a biomedically informed audience, as well as its applications in psychiatry. The review covers definitions and expositions of commonly used machine learning methods, and historical trends of their use in psychiatry. We also provide a set of standards, namely Guidelines for REporting Machine Learning Investigations in Neuropsychiatry (GREMLIN), for designing and reporting studies that use machine learning as a primary data-analysis approach. Lastly, we propose the establishment of the Machine Learning in Psychiatry (MLPsych) Consortium, enumerate its objectives, and identify areas of opportunity for future applications of machine learning in biological psychiatry. This review serves as a cautiously optimistic primer on machine learning for those on the precipice as they prepare to dive into the field, either as methodological practitioners or well-informed consumers.

Tungsten Nitride (W5N6): An Ultraresilient 2D Semimetal.

Two-dimensional transition metal nitrides offer intriguing possibilities for achieving novel electronic and mechanical functionality owing to their distinctive and tunable bonding characteristics compared to other 2D materials. We demonstrate here the enabling effects of strong bonding on the morphology and functionality of 2D tungsten nitrides. The employed bottom-up synthesis experienced a unique substrate stabilization effect beyond van-der-Waals epitaxy that favored W5N6 over lower metal nitrides. Comprehensive structural and electronic characterization reveals that monolayer W5N6 can be synthesized at large scale and shows semimetallic behavior with an intriguing indirect band structure. Moreover, the material exhibits exceptional resilience against mechanical damage and chemical reactions. Leveraging these electronic properties and robustness, we demonstrate the application of W5N6 as atomic-scale dry etch stops that allow the integration of high-performance 2D materials contacts. These findings highlight the potential of 2D transition metal nitrides for realizing advanced electronic devices and functional interfaces.

Exceptional Hole-Selective Properties of Ta2O5 Films via Sn4+ Doping for High Performance Silicon Heterojunction Solar Cells.

Carrier-selective passivating contacts using transition metal oxides (TMOs) have attracted great attention for crystalline silicon (c-Si) heterojunction solar cells recently. Among them, tantalum oxide (Ta2O5) exhibits outstanding advantages, such as a wide bandgap, good surface passivation, and a small conduction band offset with c-Si, which is typically used as an electron-selective contact layer. Interestingly, it is first demonstrated that solution-processed Ta2O5 films exhibit a high hole selectivity, which blocks electrons and promotes hole transport simultaneously. Through the ozone pre-treatment of Ta2O5/p-Si interface and optimization of the film thickness (≈9 nm), the interfacial recombination is suppressed and the contact resistivity is reduced from 178.0 to 29.3 mΩ cm2. Moreover, the Sn4+ doping increases both the work function and oxygen vacancies of the film, contributing to the improved hole-selective contact performance. As a result, the photoelectric conversion efficiencies of Ta2O5/p-Si heterojunction solar cells are significantly improved from 14.84% to 18.47%, with a high thermal stability up to 300 °C. The work has provided a feasible strategy to explore new features of TMOs for carrier-selective contact applications, that is, bipolar carrier transport properties.

Single-cell and spatially resolved transcriptomics for liver biology.

Single-cell transcriptomics enables the identification of rare cell types and the inference of state transitions, whereas spatially resolved transcriptomics allows the quantification of cells and genes in the context of tissues. The recent progress in these new technologies is improving our understanding of the cell landscape and its roles in diseases. Here, we review key biological insights into liver homeostasis, development, regeneration, chronic liver disease, and cancer obtained from single-cell and spatially resolved transcriptomics. We highlight recent progress in the liver cell atlas that characterizes the comprehensive cellular composition; diversity and function; the spatial architecture such as liver zonation, cell communication, and proximity; the cell identity conversion and cell-specific alterations that are associated with liver pathology; and new therapeutic targets. We further discuss outstanding challenges, advanced experimental technologies, and computational methods that help to address these challenges.

Exploring the causal association between uric acid and lung cancer in east Asian and European populations: a mendelian randomization study.

BACKGROUND: Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer. METHODS: Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association. RESULTS: A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer. CONCLUSIONS: The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.

ZNF32 prevents the activation of cancer-associated fibroblasts through negative regulation of TGFB1 transcription in breast cancer.

Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related deaths in women worldwide. Cancer-associated fibroblasts (CAFs) are one of the fundamental cellular components of the tumor microenvironment and play a critical role in the initiation, progression, and therapy resistance of breast cancer. However, the detailed molecular mechanisms of CAFs activation from normal fibroblasts (NFs) are still not well understood. In the present study, we reported that ZNF32 expression in breast cancer cells was negatively correlated with CAF-related markers (FSP1, α-SMA, and FAP) in stromal fibroblasts, and loss of ZNF32 promoted the activation of CAFs, as evidenced by the enhanced proliferation and contractility of CAFs. ZNF32 deficiency-mediated fibroblast activation promoted the growth and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, we demonstrated that ZNF32 inhibited TGFB1 transcription by directly binding to the -1968/-1962 region of the TGFB1 promoter, leading to the prevention of fibroblast activation. Altogether, our findings reveal an important mechanism by which ZNF32 suppression increases the transcription of the TGFB1 gene in breast cancer cells, and subsequently, elevated levels of secretory TGF-ß stimulate NFs transformation into CAFs, which in turn facilitates the malignant progression of breast cancer. Our data implicated ZNF32 as a potential therapeutic strategy against breast cancer.

Silk Protein-Based Nanoporous Microsphere for Controllable Drug Delivery through Self-Assembly in Ionic Liquid System.

Ionic liquids (ILs) showed a promising application prospect in the field of biomedicine due to their unique recyclability, modifiability, and structure adjustability. In this study, nanoporous microsphere of silk protein and blending with poly(d,l-lactic acid) as model drug delivery was fabricated, respectively, through an IL-induced self-assembly method. Their morphology, structure, and thermal properties were comparably investigated through scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, differential scanning calorimetry, X-ray diffraction, and thermogravimetric analyses, and the interaction mechanisms were also discussed to elucidate the effect of structure on drug delivery kinetics. The pure protein exhibited a bigger nanopore size in the microsphere compared to the composite one, facilitating more effective drug loading up to 88.7%. However, drug release was over 53.5% for the composite during initial 4 h, while pure protein was only about half of the composite. Both of them exhibited sustained slow release after 24 h and anticancer efficacy. Furthermore, the favorable compatibility between drug and microsphere vehicle was found and experienced improved thermal stability upon encapsulation, which could protect the drug molecules in high temperature at 200 °C. When the protein and its composite self-assembled to microspheres in ILs due to electrostatic and hydrophobic interaction, the drug could be infiltrated into the nanoporous matrix through biophysical action, and the protein structure displayed reversible transition during delivery. The sustained slow release from pure SF was attributed to the high ß-sheet block action and strong drug-protein interactions, whose strength could be tuned through blending poly(d,l-lactic acid) with protein. These findings indicated that the SF-based nanoporous microspheres formed from IL self-assembled system are an ideal and potential drug delivery vehicle which can be incorporated into various biomaterials in the future.

LINC00472 Regulates Ferroptosis of Neurons in Alzheimer's Disease via FOXO1.

INTRODUCTION: The objective of the study was to explore the molecular mechanism of long noncoding RNA (lncRNA) LINC00472 in Alzheimer's disease (AD) and identify potential novel targets for AD therapy. METHOD: Ferroptosis-related lncRNAs were screened by GEO database. AD mouse model was constructed for in vivo experiments. The content of Aß protein and tau protein hyperphosphorylation were examined in hippocampal tissue samples of mice. Subsequently, HT22 cells were induced with Aß25-35 to establish a neuronal injury model of AD in vitro. The expression of FOXO1, a key gene for ferroptosis, was verified by overexpressing/knocking down the LINC00472. The effects of LINC00472 on ROS and lipid peroxidation content, GPX4, and tau protein in AD model cells were examined by ROS assay, MDA assay, Western blot, and qRT-PCR. Subsequently, the expression of iron ion, FTH, TfRC, and Fpn protein were detected in AD cells. RESULTS: The level of FOXO1 was positively correlated with the degree of AD. In vivo experiments showed that the expression of Aß and tau hyperphosphorylated were significantly reduced in the inhibitor group and iron was significantly reduced relative to the AD group. In the AD cell model, the content of lipid peroxide was upregulated, GPX4 protein and mRNA were decreased, and phosphorylation of tau protein was enhanced in the AD cell model relative to the control group. Whereas knocking down LINC00472 inhibited the upregulation of lipid peroxide, decreased the level of GPX4, and enhanced tau protein phosphorylation, and reduced iron accumulation in AD cells. CONCLUSIONS: LINC00472 affects ferroptosis in AD by regulating iron accumulation in neuronal cells.

The Mini Nutritional Assessment combined with body fat for detecting the risk of sarcopenia and sarcopenic obesity in metabolic syndrome.

Malnutrition is a key factor in metabolic syndrome (MS) and sarcopenia, assessing the nutritional status of these patients is a pressing issue. The purpose of this study was to clarify sarcopenia and sarcopenic obesity in patients with MS based on nutritional status. This was a case-control study between MS/non-MS. Body composition was measured by dual-energy X-ray absorptiometry. Muscle function was assessed by handgrip strength, five times sit-to-stand test, gait speed test and short physical performance battery (SPPB). The Mini Nutritional Assessment (MNA) was performed to assess the nutritional status in the participants in this study. Overall, a total of 56 % and 13 % of participants suffered from possible sarcopenia and sarcopenia, respectively. There was a higher rate of possible sarcopenic obesity in the MS group than in the non-MS group (48·9 % v. 24·7 %, P < 0·01), and all the sarcopenia participants in the MS group had sarcopenic obesity. MNA score was significantly associated with sarcopenia status (P < 0·01). The MNA combined with body fat score showed better acceptable discrimination for detecting sarcopenic obesity and sarcopenia in MS (AUC = 0·70, 95 % CI 0·53, 0·86). In summary, there was a higher prevalence of possible sarcopenic obesity in MS, and all the MS patients with sarcopenia had sarcopenic obesity in the present study. We suggest that the MNA should be combined with body fat percentage to assess the nutritional status of MS participants, and it also serves as a good indicator for sarcopenia and sarcopenic obesity in MS.

Urokinase in the treatment of tuberculous pleurisy: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). METHODS: We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias. RESULTS: Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (- 7.77, - 3.87); P<0.00001] and the residual pleural thickness [MD-1.31, 95%CI (- 1.70, - 0.91); P<0.00001], pleural effusion drainage volume [MD 822.81, 95%CI (666.46,977.96); P<0.00001], FVC%pred [MD 7.95, 95%CI (4.51,11.40); P<0.00001], FEV1%pred [MD 12.67, 95%CI (10.09,15.24); P<0.00001] were significantly different. CONCLUSION: The clinical effect of urokinase is better than that of antituberculous therapy alone: it can increase total pleural effusion, decrease residual pleural thickness, improve the pulmonary function, and shorten the time of pleural effusion absorption.

Automated diagnosis of schizophrenia based on spatial-temporal residual graph convolutional network.

BACKGROUND: Schizophrenia (SZ), a psychiatric disorder for which there is no precise diagnosis, has had a serious impact on the quality of human life and social activities for many years. Therefore, an advanced approach for accurate treatment is required. NEW METHOD: In this study, we provide a classification approach for SZ patients based on a spatial-temporal residual graph convolutional neural network (STRGCN). The model primarily collects spatial frequency features and temporal frequency features by spatial graph convolution and single-channel temporal convolution, respectively, and blends them both for the classification learning, in contrast to traditional approaches that only evaluate temporal frequency information in EEG and disregard spatial frequency features across brain regions. RESULTS: We conducted extensive experiments on the publicly available dataset Zenodo and our own collected dataset. The classification accuracy of the two datasets on our proposed method reached 96.32% and 85.44%, respectively. In the experiment, the dataset using delta has the best classification performance in the sub-bands. COMPARISON WITH EXISTING METHODS: Other methods mainly rely on deep learning models dominated by convolutional neural networks and long and short time memory networks, lacking exploration of the functional connections between channels. In contrast, the present method can treat the EEG signal as a graph and integrate and analyze the temporal frequency and spatial frequency features in the EEG signal. CONCLUSION: We provide an approach to not only performs better than other classic machine learning and deep learning algorithms on the dataset we used in diagnosing schizophrenia, but also understand the effects of schizophrenia on brain network features.

Evaluation of ventricular repolarization in dermatomyositis and relationship with inflammation and autoimmunity.

Dermatomyositis (DM) is a chronic multi-systemic inflammatory disorder of autoimmune origin, which has been associated with cardiovascular complications, including ventricular arrhythmias and sudden cardiac death. The Tp-e interval and Tp-e/QT ratio have been accepted as new markers for the assessment of myocardial repolarization and ventricular arrhythmogenesis. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with DM, and to assess the relation with inflammation and autoimmunity. This study included 281 DM patients (180 females, 101 males; mean age 52.73 ± 15.80 years) and 281 control subjects (180 females, 101 males; mean age 53.38 ± 15.72 years). QTc, Tp-e interval and Tp-e/QT ratio were measured from the 12-lead ECG. The plasma level of blood routine test, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) was measured. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QTc, Tp-e interval and Tp-e/QT ratio were significantly increased in DM patients compared to the control group (441.44 ± 26.62 ms vs 422.72 ± 11.7 ms, 104.16 ± 24.34 ms vs 77.23 ± 16.25 ms and 0.27 ± 0.06 ms vs 0.20 ± 0.04 ms, all P value < 0.01). QTc, Tp-e interval and Tp-e/QT were positively correlated with NLR, CRP, and ESR (all P values < 0.01), and were increased in anti-Ro/SSA-52kD positive patients compared to those negative (452.33 ± 24.89 ms vs 438.55 ± 26.37 ms, 114.05 ± 22.68 ms vs 101.53 ± 24.13 ms, and 0.29 ± 0.06 ms vs 0.27 ± 0.05 ms, all P value < 0.01). Our study demonstrated that QTc, Tp-e interval, and Tp-e/QT ratio were increased in DM patients and were associated with inflammatory markers and anti-Ro/SSA-52kD positivity.

Phototherapeutic keratectomy for corneal epithelial-stromal dystrophies in pediatric patients.

Corneal dystrophies may develop gradually from early onset in childhood and persist for years to decades. Visual impairment or repeated ocular irritations caused by corneal dystrophies severely affect the quality of life. Although various surgical treatment options are indicated for adult patients, the treatment plan for pediatric patients remains unclear. Herein we describe clinical observations of phototherapeutic keratectomy for corneal epithelial-stromal dystrophies in three pediatric patients (five eyes). Corneal opacities were successfully removed, and visual acuity was greatly improved in all operated eyes. The procedure of phototherapeutic keratectomy seems to be feasible in the treatment of corneal epithelial-stromal dystrophies in c hildren, with advantages of minimal invasion and good visual outcomes.

Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients. METHODS: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years. RESULTS: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 µm compared to that of 51.7 ± 2.6 µm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels. CONCLUSIONS: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.

Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 and human coronaviruses.

Gene-editing technologies, including the widespread usage of CRISPR endonucleases, have the potential for clinical treatments of various human diseases. Due to the rapid mutations of SARS-CoV-2, specific and effective prevention and treatment by CRISPR toolkits for coronavirus disease 2019 (COVID-19) are urgently needed to control the current pandemic spread. Here, we designed Type III CRISPR endonuclease antivirals for coronaviruses (TEAR-CoV) as a therapeutic to combat SARS-CoV-2 infection. We provided a proof of principle demonstration that TEAR-CoV-based RNA engineering approach leads to RNA-guided transcript degradation both in vitro and in eukaryotic cells, which could be used to broadly target RNA viruses. We report that TEAR-CoV not only cleaves SARS-CoV-2 genome and mRNA transcripts, but also degrades live influenza A virus (IAV), impeding viral replication in cells and in mice. Moreover, bioinformatics screening of gRNAs along RNA sequences reveals that a group of five gRNAs (hCoV-gRNAs) could potentially target 99.98% of human coronaviruses. TEAR-CoV also exerted specific targeting and cleavage of common human coronaviruses. The fast design and broad targeting of TEAR-CoV may represent a versatile antiviral approach for SARS-CoV-2 or potentially other emerging human coronaviruses.

Relative and absolute inequalities in cerebrovascular disease mortality rates: exploring the influence of socioeconomic status and urbanization levels in Taiwan.

BACKGROUND/OBJECTIVE: Limited evidence exists regarding the socioeconomic inequalities in cerebrovascular disease (CBD) mortality at different urbanization levels. Therefore, this study was conducted to assess the socioeconomic inequalities and urbanization levels in township-based CBD mortality in Taiwan. METHODS: Socioeconomic variables, including the percentages of low-income households, individuals with a university education and above, and tax payments, were measured at the township level from 2011 to 2020. Urbanization was also determined by the national survey and divided into seven levels. Age-standardized mortality rate (ASMR) of CBD was calculated using a Geographic Information System (GIS) in 358 townships. The effects of socioeconomic variables and urbanization levels on relative and absolute inequalities in township-based CBD mortality rates were examined. RESULTS: Significant differences in ASMR of CBD were observed across all socioeconomic status indicators over the years. Higher proportions of low-income households were associated with higher ASMR of CBD. Conversely, there were negative correlations between higher proportions of individuals with a university education and above and tax payments with ASMR of CBD. The regression analysis indicated significant impacts of relative and absolute socioeconomic inequalities on ASMR of CBD. Additionally, a moderation effect of socioeconomic variables and urbanization on CBD mortality rates was observed, with rural areas showing sensitivity to these factors. CONCLUSION: Although ASMR of CBD showed significant decreases over time, socioeconomic inequalities in CBD mortality rates persist. Interventions targeting socioeconomic inequalities in health outcomes, especially in rural areas, are needed to address this issue.