Admix-kit: an integrated toolkit and pipeline for genetic analyses of admixed populations.

SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations. AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available at https://github.com/UW-GAC/admix-kit_workflow.

Neuropsychological insights into exercise addiction: the role of brain structure and self-efficacy in middle-older individuals.

This study aimed to investigate the relationship between exercise addiction and brain structure in middle-older individuals, and to examine the role of self-efficacy in mediating physiological changes associated with exercise addiction. A total of 133 patients exhibiting symptoms of exercise addiction were recruited for this study (male = 43, age 52.86 ± 11.78 years). Structural magnetic resonance imaging and behavioral assessments were administered to assess the study population. Voxel-based morphological analysis was conducted using SPM12 software. Mediation analysis was employed to explore the potential neuropsychological mechanism of self-efficacy in relation to exercise addiction. The findings revealed a positive correlation between exercise addiction and gray matter volume in the right inferior temporal region and the right hippocampus. Conversely, there was a negative correlation with gray matter volume in the left Rolandic operculum. Self-efficacy was found to indirectly influence exercise addiction by affecting right inferior temporal region gray matter volume and acted as a mediating variable in the relationship between the gray matter volume of right inferior temporal region and exercise addiction. In summary, this study elucidates the link between exercise addiction and brain structure among middle-older individuals. It uncovers the intricate interplay among exercise addiction, brain structure, and psychological factors. These findings enhance our comprehension of exercise addiction and offer valuable insights for the development of interventions and treatments.

The sequence kernel association test for multicategorical outcomes.

Disease heterogeneity is ubiquitous in biomedical and clinical studies. In genetic studies, researchers are increasingly interested in understanding the distinct genetic underpinning of subtypes of diseases. However, existing set-based analysis methods for genome-wide association studies are either inadequate or inefficient to handle such multicategorical outcomes. In this paper, we proposed a novel set-based association analysis method, sequence kernel association test (SKAT)-MC, the sequence kernel association test for multicategorical outcomes (nominal or ordinal), which jointly evaluates the relationship between a set of variants (common and rare) and disease subtypes. Through comprehensive simulation studies, we showed that SKAT-MC effectively preserves the nominal type I error rate while substantially increases the statistical power compared to existing methods under various scenarios. We applied SKAT-MC to the Polish breast cancer study (PBCS), and identified gene FGFR2 was significantly associated with estrogen receptor (ER)+ and ER- breast cancer subtypes. We also investigated educational attainment using UK Biobank data ( N = 127 , 127 $N=127,127$ ) with SKAT-MC, and identified 21 significant genes in the genome. Consequently, SKAT-MC is a powerful and efficient analysis tool for genetic association studies with multicategorical outcomes. A freely distributed R package SKAT-MC can be accessed at https://github.com/Zhiwen-Owen-Jiang/SKATMC.

Increased mutations in lipopolysaccharide biosynthetic genes cause time-dependent development of phage resistance in Salmonella.

Understanding how bacteria evolve resistance to phages has implications for phage-based therapies and microbial evolution. In this study, the susceptibility of 335 Salmonella isolates to the wide host range Salmonella phage BPSELC-1 was tested. Potentially significant gene sets that could confer resistance were identified using bioinformatics approaches based on phage susceptibility phenotypes; more than 90 potential antiphage defense gene sets, including those involved in lipopolysaccharide (LPS) biosynthesis, DNA replication, secretion systems, and respiratory chain, were found. The evolutionary dynamics of Salmonella resistance to phage were assessed through laboratory evolution experiments, which showed that phage-resistant mutants rapidly developed and exhibited genetic heterogeneity. Most representative Salmonella hosts (58.1% of 62) rapidly developed phage resistance within 24 h. All phage-resistant mutant clones exhibited genetic heterogeneity and observed mutations in LPS-related genes (rfaJ and rfaK) as well as other genes such as cellular respiration, transport, and cell replication-related genes. The study also identified potential trade-offs, indicating that bacteria tend to escape fitness trade-offs through multi-site mutations, all tested mutants increased sensitivity to polymyxin B, but this does not always affect their relative fitness or biofilm-forming capacity. Furthermore, complementing the rfaJ mutant gene could partially restore the phage sensitivity of phage-resistant mutants. These results provide insight into the phage resistance mechanisms of Salmonella and the complexity of bacterial evolution resulting from phage predation, which can inform future strategies for phage-based therapies and microbial evolution.

Preliminary investigation on the effect of Vibrio splendidus stimulation on the intestinal flora of Strongylocentrotus intermedius.

To better understand the effect of Vibrio splendidus infection on Strongylocentrotus intermedius, 16S rRNA sequencing was carried out to investigate the intestinal flora of S. intermedius stimulated by 0 CFU/mL (Con), 1.5 × 107 CFU/mL (Vib1) and 1.5 × 108 CFU/mL (Vib2) concentrations of V. splendidus. The results showed that there was significant difference in intestinal flora diversity between Con group and Vib1 group, but no significant difference between Con group and Vib2 group. However, there were significant differences in the composition of intestinal flora among all groups. Bacteroidota, Proteobacteria and Firmicutes were the dominant phylum in the Con group. The abundance of Bacteroidota and Firmicutes decreased and Proteobacteria increased in Vib1 and Vib2 groups. The relative abundance of the potential probiotic bacteria Muribaculaceae and Alloprevotella was significantly lower in the Vib1 and Vib2 groups. In addition, the opportunistic pathogen Desulfovibrio was found in Vib1 and Vib2 groups. It is evident that V. splendidus infection not only alters the composition of the microbial community in the intestinal tract of S. intermedius, but may also lead to the production of opportunistic pathogens, which could be potentially harmful to the health of S. intermedius. The results of this study provide a foundation for exploring the diseases caused by V. splendidus stimulation leading to an imbalance in the intestinal flora of S. intermedius, and contribute to our further understanding of the role of Vibrio on the health of S. intermedius.

One-Step Fabricated Sn0 Particle on S-Vacancies SnS2 to Accelerate Photoelectron Transfer for Sterling Photocatalytic CO2 Reduction in Pure Water Vapor Environment.

Promoting the proton-coupled electron transfer process in order to solve the sluggish carrier migration dynamics is an efficient way to accelerate the photocatalytic CO2 reduction (PCR) process. Herein, through the reduction of Sn4+ by amino and sulfhydryl groups, Sn0 particles are lodged in S-vacancies SnS2 nanosheets. The high conductance of Sn0 particles expedites the collection and transport of photogenerated electrons, activating the surrounding surface of unsaturated sulfur (Sx 2- ) and thus lowering the energy barrier for generation of *COOH. Meanwhile, S-vacancies boost H2 O adsorption while Sx 2- increases CO2 adsorption, as demonstrated by density functional theory (DFT), obtaining a selectivity of 97.88% CO and yield of 295.06 µmol g-1 h-1 without the addition of co-catalysts and sacrificial agents. This work provides a new approach to building a fast electron transfer interface between metal particles and semiconductors, which works in tandem with S-vacancies and Sx 2- to boost the efficiency of photocatalytic CO2 reduction to CO in pure water vapor environment.

Magnesium Ions Promote the Induction of Immunosuppressive Bone Microenvironment and Bone Repair through HIF-1α-TGF-ß Axis in Dendritic Cells.

The effect of immunoinflammation on bone repair during the recovery process of bone defects needs to be further explored. It is reported that Mg2+ can promote bone repair with immunoregulatory effect, but the underlying mechanism on adaptive immunity is still unclear. Here, by using chitosan and hyaluronic acid-coated Mg2+ (CSHA-Mg) in bone-deficient mice, it is shown that Mg2+ can inhibit the activation of CD4+ T cells and increase regulatory T cell formation by inducing immunosuppressive dendritic cells (imDCs). Mechanistically, Mg2+ initiates the activation of the MAPK signaling pathway through TRPM7 channels on DCs. This process subsequently induces the downstream HIF-1α expression, a transcription factor that amplifies TGF-ß production and inhibits the effective T cell function. In vivo, knock-out of HIF-1α in DCs or using a HIF-1α inhibitor PX-478 reverses inhibition of bone inflammation and repair promotion upon Mg2+-treatment. Moreover, roxadustat, which stabilizes HIF-1α protein expression, can significantly promote immunosuppression and bone repair in synergism with CSHA-Mg. Thus, the findings identify a key mechanism for DCs and its HIF-1α-TGF-ß axis in the induction of immunosuppressive bone microenvironment, providing potential targets for bone regeneration.

Adaptive locating foveated ghost imaging based on affine transformation.

Ghost imaging (GI) has been widely used in the applications including spectral imaging, 3D imaging, and other fields due to its advantages of broad spectrum and anti-interference. Nevertheless, the restricted sampling efficiency of ghost imaging has impeded its extensive application. In this work, we propose a novel foveated pattern affine transformer method based on deep learning for efficient GI. This method enables adaptive selection of the region of interest (ROI) by combining the proposed retina affine transformer (RAT) network with minimal computational and parametric quantities with the foveated speckle pattern. For single-target and multi-target scenarios, we propose RAT and RNN-RAT (recurrent neural network), respectively. The RAT network enables an adaptive alteration of the fovea of the variable foveated patterns spot to different sizes and positions of the target by predicting the affine matrix with a minor number of parameters for efficient GI. In addition, we integrate a recurrent neural network into the proposed RAT to form an RNN-RAT model, which is capable of performing multi-target ROI detection. Simulations and experimental results show that the method can achieve ROI localization and pattern generation in 0.358 ms, which is a 1 × 105 efficiency improvement compared with the previous methods and improving the image quality of ROI by more than 4 dB. This approach not only improves its overall applicability but also enhances the reconstruction quality of ROI. This creates additional opportunities for real-time GI.

Modulation format recognition in a UVLC system based on an ultra-lightweight model with communication-informed knowledge distillation.

Modulation format recognition (MFR) is a key technology for adaptive optical systems, but it faces significant challenges in underwater visible light communication (UVLC) due to the complex channel environment. Recent advances in deep learning have enabled remarkable achievements in image recognition, owing to the powerful feature extraction of neural networks (NN). However, the high computational complexity of NN limits their practicality in UVLC systems. This paper proposes a communication-informed knowledge distillation (CIKD) method that achieves high-precision and low-latency MFR with an ultra-lightweight student model. The student model consists of only one linear dense layer under a communication-informed auxiliary system and is trained under the guidance of a high-complexity and high-precision teacher model. The MFR task involves eight modulation formats: PAM4, QPSK, 8QAM-CIR, 8QAM-DIA, 16QAM, 16APSK, 32QAM, and 32APSK. Experimental results show that the student model based on CIKD can achieve comparable accuracy to the teacher model. After knowledge transfer, the prediction accuracy of the student model can be increased by up to 87%. Besides, it is worth noting that CIKD's inference accuracy can reach up to 100%. Moreover, the parameters constituting the student model in CIKD correspond to merely 18% of the parameters found in the teacher model, which facilitates the hardware deployment and online data processing of MFR algorithms in UVLC systems.

Discovery of non-sulfonamide carbonic anhydrase IX inhibitors through structure-based virtual screening.

Carbonic anhydrase IX (CA IX) is a subtype of the human carbonic anhydrase (hCA) family and exhibits high expression in various solid tumors, rendering it a promising target for tumor therapy. Currently, marketed carbonic anhydrase inhibitors (CAIs) are primarily composed of sulfonamides derivatives, which may have impeded their potential for further expansion. Therefore, we have developed a structure-based virtual screening approach to explore novel CAIs exhibiting distinctive structures and anti-tumor potential in the FDA database. In vitro experiments demonstrated that 3-pyridinemethanol (0.42 µM), procodazole (8.35 µM) and pamidronic acid (8.51 µM) exhibited inhibitory effects on CA IX activity. The binding stability and interaction mode between the CA IX and the hit compounds are further investigated through molecular dynamics simulations and binding free energy calculations. Furthermore, the ADME/Tox prediction results indicated that these compounds exhibited favorable pharmacological properties and minimal toxic side effects. Our study successfully applied computational strategies to discover three non-sulfonamide inhibitors of carbonic anhydrase IX (CA IX) that demonstrate inhibitory activity in vitro. These findings have significant implications for the development of CA IX inhibitors and anti-tumor drugs, contributing to their progress in the field.

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction.

BACKGROUND: The effects of air pollution on endothelial function remain unclear across populations. We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of air pollution exposure on endothelial dysfunction. METHODS: We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter < 2.5 µm aerodynamic diameter (PM2.5), inhalable particulate matter < 10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratification by age and sex. RESULTS: This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 µg/m3 increase in 7-day exposure to PM2.5 and PM10 was significantly linearly associated with a 0.07% (ß = -0.07, 95% CI: -0.13 to -0.004) and 0.05% (ß = -0.05, 95% CI: -0.10 to -0.004) decrease in FMD in the fully adjusted model. After full adjustment, long-term exposure to all air pollutants was significantly associated with impaired FMD. Each 10 µg/m3 increase in long-term exposure to PM2.5 and PM10 was significantly associated with a -0.18% (95% CI: -0.34 to -0.03) and - 0.23% (95% CI: -0.40 to -0.06) change in FMD, respectively. After stratification, the associations of lower FMD with long-term exposure to PM2.5, PM10, SO2, NO2, and CO significantly persisted in men and participants younger than 65 years instead of women or older participants. For short-term exposure, we observed differences consistent with long-term exposure and a stronger effect of 7-day exposure to SO2 in men due to a significant interaction effect. CONCLUSION: Short- and long-term exposure to different air pollutants are strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex.

Minimally invasive palliative treatment of malignant tracheoesophageal fistula using cardiac septal occluder.

INTRODUCTION: Tracheoesophageal fistula (TEF) especially malignant TEF (mTEF) is an uncommon yet critical medical condition necessitating immediate intervention. This life-threatening condition frequently manifests in critically ill patients who are dependent on prolonged mechanical ventilation and are unsuitable candidates for thoracotomy due to their compromised health status. The Management of these mTEF patients remain a significant challenge.This study aimed to evaluate the safety and efficacy of using a cardiac septal occluder for the closure of mTEF. METHODS: 8 patients with mTEF underwent closure surgery using atrial/ventricular septal defect (ASD/VSD) septal occluders at the Respiratory Department of HuBei Yichang Central People's Hospital from 2021 to 2023. The procedure involved percutaneous placement of the occluder through the fistula to achieve closure. RESULTS: The placement of the cardiac septal occluder was successfully achieved with ease and efficiency in all patients. The study demonstrated that the use of cardiac septal occluder therapy in patients with mTEF can alleviate symptoms, improve quality of life, and enhance survival rates, with no significant complications observed. Furthermore, the study provided comprehensive details on surgical indications, preoperative evaluation and diagnosis, selection of occluder, methods of occlusion, and postoperative care. CONCLUSIONS: The application of cardiac septal occluder in the treatment of mTEF is a safe and effective palliative treatment. This approach may be particularly beneficial for patients with a high risk of complications and mortality associated with traditional surgical interventions.

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.

[Factors associated with the care needs of the older adults based on different disability levels].

OBJECTIVE: To identify the factors associated with the care needs of the older adults aged 65-105 by age groups, and to compare these factors across different age groups. METHODS: A total of 12 244 older adults from the Chinese longitudinal healthy longevity survey (CLHLS) conducted in 2018 were included in the analyses. The participants were categorized into three age groups: young-old (aged 65-79), middle-old (aged 80-89), and oldest-old (aged 90-105). The level of disability was measured by the disability index (DI) in four dimensions, reflecting their care needs. Potential factors associated with care needs were selected based on the health ecological model (HEM), including perspectives of personal characteristics, behavioral characteristics, interpersonal network, living and working conditions, and policy environment. Multifactor analysis was performed using multinomial Logistic regression. RESULTS: Among China ' s 12 244 older adults, 43.4% had medium or high care needs. Factors for higher care needs of older adults included higher age, higher number of chronic diseases, no exercise habit, excessive sleep duration (≥9 h/d), depressive tendency, living with children or spouse, and uneducated (all P < 0.05). In addition, the young-old group who were past smokers (OR=2.009, 95% CI: 1.019-3.959), were past drinkers (OR=2.213, 95% CI: 1.141-4.291), and reported self-perceived poverty (OR=2.051, 95% CI: 1.189-3.540), had higher level of care needs. The middle-old group who were female (OR=1.373, 95% CI: 1.038-1.817), never drank alcohol (OR=1.551, 95% CI: 1.059-2.269), and were lack of medical insurance (OR=1.598, 95% CI: 1.053-2.426), and had higher level of care needs. The oldest-old group who were female (medium care needs vs. low care needs: OR=1.412, 95% CI: 1.062-1.878; high care needs vs. low care needs: OR=1.506, 95% CI: 1.137-1.993), reported self-perceived poverty (OR=2.064, 95% CI: 1.282-3.323), and were lack of medical insurance (OR=1.621, 95% CI: 1.148-2.291), and had higher level of care needs. CONCLUSION: The identical factors associated with care needs across different age groups include age, chronic disease, exercise, sleep, depression, living arrangement, and education. Smoking, alcohol consumption, and economic status are specific factors among the young-old group of the older adults, while gender and medical insurance are specific factors among the middle-old and the oldest-old group of the older adults. We recommend conducting prospective cohort studies and intervention studies among specific age groups on the above factors to provide reliable evidence for policy formulation.

Antimicrobial resistance characteristics and phylogenetic relationships of pleuromutilin-resistant Enterococcus isolates from different environmental samples along a laying hen production chain.

Antimicrobial resistance in the laying hen production industry has become a serious public health problem. The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified. 105 Enterococcus isolates were obtained from 115 environmental samples (air, dust, feces, flies, sewage, and soil) collected along the laying hen production chain (breeding chicken, chick, young chicken, and commercial laying hen). These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics, such as tetracycline (92.4%), streptomycin (92.4%), and erythromycin (91.4%), and all strains had multidrug resistance phenotypes. Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51 pleuromutilin-resistant Enterococcus isolates, and lsa(E), which mediates resistance to pleuromutilins, always co-occurred with lnu(B). Alignments with the Mobile Genetic Elements database identified four transposons (Tn554, Tn558, Tn6261, and Tn6674) with several ARGs (erm(A), ant(9)-la, fex(A), and optrA) that mediated resistance to many clinically important antibiotics. Moreover, we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492. A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms. Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention, and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain, thereby warranting effective disinfection.

"Whole-Body" Fluorination for Highly Efficient and Ultra-Stable All-Inorganic Halide Perovskite Quantum Dots.

Inherent "soft" ionic lattice nature of halide perovskite quantum dots (QDs), triggered by the weak Pb-X (X=Cl, Br, I) bond, is recognized as the primary culprit for their serious instability. A promising way is to construct exceedingly strong ionic interaction inside the QDs and increase their crystal cohesive energy by substituting the interior X- with highly electronegative F- , however, which is challenging and hitherto remains unreported. Here, a "whole-body" fluorination strategy is proposed for strengthening the interior bonding architecture of QDs, wherein the F- are uniformly distributed throughout the whole nanocrystal encompassing both the interior lattice and surface, successfully stabilizing their "soft" crystal lattice and passivating surface defects. This approach effectively mitigates their intrinsic instability issues including light-induced phase segregation. As a result, light-emitting devices based on these QDs exhibit exceptional efficiency and remarkable stability.

COVID-19 Spread Mapper: a multi-resolution, unified framework and open-source tool.

SUMMARY: Amidst the continuing spread of coronavirus disease-19 (COVID-19), real-time data analysis and visualization remain critical the general public to track the pandemic's impact and to inform policy making by officials. Multiple metrics permit the evaluation of the spread, infection and mortality of infectious diseases. For example, numbers of new cases and deaths provide easily interpretable measures of absolute impact within a given population and time frame, while the effective reproduction rate provides an epidemiological measure of the rate of spread. By evaluating multiple metrics concurrently, users can leverage complementary insights into the impact and current state of the pandemic when formulating prevention and safety plans for oneself and others. We describe COVID-19 Spread Mapper, a unified framework for estimating and quantifying the uncertainty in the smoothed daily effective reproduction number, case rate and death rate in a region using log-linear models. We apply this framework to characterize COVID-19 impact at multiple geographic resolutions, including by US county and state as well as by country, demonstrating the variation across resolutions and the need for harmonized efforts to control the pandemic. We provide an open-source online dashboard for real-time analysis and visualization of multiple key metrics, which are critical to evaluate the impact of COVID-19 and make informed policy decisions. AVAILABILITY AND IMPLEMENTATION: Our model and tool are publicly available as implemented in R and hosted at https://metrics.covid19-analysis.org/. The source code is freely available from https://github.com/lin-lab/COVID19-Rt and https://github.com/lin-lab/COVID19-Viz. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Foveated panoramic ghost imaging.

Panoramic ghost imaging (PGI) is a novel method by only using a curved mirror to enlarge the field of view (FOV) of ghost imaging (GI) to 360°, making GI a breakthrough in the applications with a wide FOV. However, high-resolution PGI with high efficiency is a serious challenge because of the large amount of data. Therefore, inspired by the variant-resolution retina structure of human eye, a foveated panoramic ghost imaging (FPGI) is proposed to achieve the coexistence of a wide FOV, high resolution and high efficiency on GI by reducing the resolution redundancy, and further to promote the practical applications of GI with a wide FOV. In FPGI system, a flexible variant-resolution annular pattern structure via log-rectilinear transformation and log-polar mapping is proposed to be used for projection, which can allocate the resolution of the region of interest (ROI) and the other region of non-interest (NROI) by setting related parameters in the radial and poloidal directions independently to meet different imaging requirements. In addition, in order to reasonably reduce the resolution redundancy and avoid the loss of the necessary resolution on NROI, the variant-resolution annular pattern structure with a real fovea is further optimized to keep the ROI at any position in the center of 360° FOV by flexibly changing the initial position of the start-stop boundary on the annular pattern structure. The experimental results of the FPGI with one fovea and multiple foveae demonstrate that, compared to the traditional PGI, the proposed FPGI not only can improve the imaging quality on the ROIs with a high resolution and flexibly remain a lower-resolution imaging on the NROI with different required resolution reduction; but also reduce the reconstruction time to improve the imaging efficiency due to the reduction of the resolution redundancy.

Discovery of novel bicyclic[3.3.0]proline peptidyl α-ketoamides as potent 3CL-protease inhibitors for SARS-CoV-2.

The outbreak of SARS-CoV-2 has caused global crisis on health and economics. The multiple drug-drug interaction risk associated with ritonavir warrants specialized assessment before using Paxlovid. Here we report a multiple-round SAR study to provide a novel bicyclic[3.3.0]proline peptidyl α-ketoamide compound 4a, which is endowed with excellent antiviral activities and pharmacokinetic properties. Also, in vivo HCoV-OC43 neonatal mice model demonstrated compound 4a has good in vivo efficacy. Based on these properties, compound 4a worth further SAR optimization with the goal to develop compounds with better pharmacokinetic properties and finally to realize single agent efficacy in human.

Association of vascular endothelial function and quality of life in patients with ischemia and non-obstructive coronary artery disease.

Improvements are required in the quality of life (QoL) of patients with ischemia and non-obstructive coronary artery disease (INOCA). Several patients with INOCA experience vascular endothelial dysfunction. However, the relationship between endothelial function and QoL remains unelucidated. This study aimed to initially investigate the relationship between endothelial function and QoL in patients with INOCA. This prospective observational study included 121 patients with INOCA (aged 31-85 years). Vascular endothelial function was assessed by flow-mediated dilatation (FMD) of the peripheral brachial artery. QoL was evaluated using the 36-Item Short-Form Health Survey (SF-36). Patients with INOCA were divided into two groups according to the median FMD change during the 1-year follow-up (group A, ≥ median FMD change cut-off; group B, < median FMD change cut-off). The median change in FMD was 0.92%. The mean baseline SF-36 scores were comparable between the two groups (53.95 ± 6.46 vs. 53.92 ± 4.29, p = 0.98). The QoL at follow-up was better in group A than in group B (56.61 ± 5.50 vs. 53.32 ± 5.58, p = 0.002). The change in FMD (r = 0.34, p < 0.01), rather than FMD at baseline (r = - 0.01, p = 0.89) or follow-up (r = 0.13, p = 0.15), was related to the follow-up SF-36 scores. FMD improvement was an independent predictor of increased QoL (odds ratio, 3.90; 95% confidence interval: 1.59-9.53, p = 0.003). Endothelial function change is associated with QoL, and patients with improved endothelial function have a better QoL than those without.