Search

Abstract Owing to the ability to parallel manipulate micro-objects, dynamic holographic optical tweezers (HOTs) are widely used for assembly and patterning of particles or cells. However, for simultaneous control of large-scale targets, potential collisions could lead to defects in the formed patterns. Herein we introduce the artificial potential field (APF) to develop dynamic HOTs that enable collision-avoidance micro-manipulation. By eliminating collision risks among particles, this method can maximize the degree of parallelism in multi-particle transport, and it permits the implementation of the Hungarian algorithm for matching the particles with their target sites in a minimal pathway. In proof-of-concept experiments, we employ APF-empowered dynamic HOTs to achieve direct assembly of a defect-free 8 × 8 array of microbeads, which starts from random initial positions. We further demonstrate successive flexible transformations of a 7 × 7 microbead array, by regulating its tilt angle and inter-particle spacing distances with a minimalist path. We anticipate that the proposed method will become a versatile tool to open up new possibilities for parallel optical micromanipulation tasks in a variety of fields.

Digital in-line holographic microscopy (DIHM) is a widely used interference technique for real-time reconstruction of living cells’ morphological information with large space-bandwidth product and compact setup. However, the need for a larger pixel size of detector to improve imaging photosensitivity, field-of-view, and signal-to-noise ratio often leads to the loss of sub-pixel information and limited pixel resolution. Additionally, the twin-image appearing in the reconstruction severely degrades the quality of the reconstructed image. The deep learning (DL) approach has emerged as a powerful tool for phase retrieval in DIHM, effectively addressing these challenges. However, most DL-based strategies are data-driven or end-to-end net approaches, suffering from excessive data dependency and limited generalization ability. Herein, a novel multi-prior physics-enhanced neural network with pixel super-resolution (MPPN-PSR) for phase retrieval of DIHM is proposed. It encapsulates the physical model prior, sparsity prior and deep image prior in an untrained deep neural network. The effectiveness and feasibility of MPPN-PSR are demonstrated by comparing it with other traditional and learning-based phase retrieval methods. With the capabilities of pixel super-resolution, twin-image elimination and high-throughput jointly from a single-shot intensity measurement, the proposed DIHM approach is expected to be widely adopted in biomedical workflow and industrial measurement.

The tumor microenvironment, particularly the hypoxic property and glutathione (GSH) overexpression, substantially inhibits the efficacy of cancer therapy. In this article, we present the design of a magnetic nanoplatform (MNPT) comprised of a photosensitizer (Ce6) and an iron oxide (Fe3O4)/manganese oxide (MnO2) composite nanozyme. Reactive oxygen species (ROS), such as singlet oxygen (1O2) radicals produced by light irradiation and hydroxyl radicals (·OH) produced by catalysis, are therapeutic species. These therapeutic substances stimulate cell apoptosis by increasing oxidative stress. This apoptosis then triggers the immunological response, which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer. Furthermore, MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

BackgroundRacial disparities in COVID-19 incidence and outcomes have been widely reported. Non-Hispanic Black patients endured worse outcomes disproportionately compared with non-Hispanic White patients, but the epidemiological basis for these observations was complex and multifaceted. ObjectiveThis study aimed to elucidate the potential reasons behind the worse outcomes of COVID-19 experienced by non-Hispanic Black patients compared with non-Hispanic White patients and how these variables interact using an explainable machine learning approach. MethodsIn this retrospective cohort study, we examined 28,943 laboratory-confirmed COVID-19 cases from the OneFlorida Research Consortium’s data trust of health care recipients in Florida through April 28, 2021. We assessed the prevalence of pre-existing comorbid conditions, geo-socioeconomic factors, and health outcomes in the structured electronic health records of COVID-19 cases. The primary outcome was a composite of hospitalization, intensive care unit admission, and mortality at index admission. We developed and validated a machine learning model using Extreme Gradient Boosting to evaluate predictors of worse outcomes of COVID-19 and rank them by importance. ResultsCompared to non-Hispanic White patients, non-Hispanic Blacks patients were younger, more likely to be uninsured, had a higher prevalence of emergency department and inpatient visits, and were in regions with higher area deprivation index rankings and pollutant concentrations. Non-Hispanic Black patients had the highest burden of comorbidities and rates of the primary outcome. Age was a key predictor in all models, ranking highest in non-Hispanic White patients. However, for non-Hispanic Black patients, congestive heart failure was a primary predictor. Other variables, such as food environment measures and air pollution indicators, also ranked high. By consolidating comorbidities into the Elixhauser Comorbidity Index, this became the top predictor, providing a comprehensive risk measure. ConclusionsThe study reveals that individual and geo-socioeconomic factors significantly influence the outcomes of COVID-19. It also highlights varying risk profiles among different racial groups. While these findings suggest potential disparities, further causal inference and statistical testing are needed to fully substantiate these observations. Recognizing these relationships is vital for creating effective, tailored interventions that reduce disparities and enhance health outcomes across all racial and socioeconomic groups.

Summary: ATP-citrate lyase (ACLY) is a critical metabolic enzyme and promising target for drug development. The structure determinations of ACLY have revealed its homotetramer states with various subunit symmetries, but catalytic mechanism of ACLY tetramer and the importance of subunit symmetry have not been clarified. Here, we constructed the free energy landscape of ACLY tetramer with arbitrary subunit symmetries and investigated energetic and conformational coupling of subunits during citryl-CoA synthesis process. The optimal conformational pathway indicates that ACLY tetramer encounters three critical conformational barriers and undergoes a loss of rigid-D2 symmetry to gain an energetic advantage. Energetic coupling of conformational changes and biochemical reactions suggests that these biological events are not independent but rather coupled with each other, showing a comparable energy barrier to the experimental data for the rate-limiting step. These findings could contribute to further research on catalytic mechanism, functional modulation, and inhibitor design of ACLY.

Abstract The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

ObjectiveThis retrospective study aims to investigate the treatment of tic disorder (TD) in Dongfang Hospital affiliated with Beijing University of Chinese Medicine, explore its underlying mechanism, and provide valuable insights for future research and clinical management of TD.MethodsThe electronic medical records of children with TD, from 2015 to 2021, were extracted from the information system of Dongfang Hospital affiliated with Beijing University of Chinese Medicine. The clinical characteristics of TD, utilization patterns of Chinese herbal medicine and synthetic drugs in prescriptions, as well as their pharmacological effects, were statistically described and categorized. In addition, association rules and network pharmacology were employed to identify core prescriptions (CPs) and elucidate their microscopic molecular mechanisms in treating TD.ResultsThe age range of the children was from 6 to 11 years, with a higher proportion of male participants than female ones. The average duration of treatment was 6 weeks. Regimen Z for the treatment of TD can be summarized as follows: Chinese herbal medicine [Saposhnikoviae Radix (FangFeng), Puerariae Lobatae Radix (GeGen), Uncariae Ramulus cum Uncis (GouTeng), Acori Tatarinowii Rhizoma (ShiChangPu), Chuanxiong Rhizoma (ChuanXiong)] and vitamins [lysine, inosite, and vitamin B12 oral solution] form the basic treatment, combined with immunomodulators, antibiotics, electrolyte-balancing agents, and antiallergic agents. CPs primarily exerted their effects through the modulation of gene expression (transcription), the immune system, and signal transduction pathways, with interleukin-4 and interleukin-13 pathways being particularly crucial. Among the lysine synthetic drugs used, inosite and vitamin B12 oral solution were the most frequently prescribed.ConclusionThe regimen Z drug treatment holds significant importance in the field, as it exerts its therapeutic effects through a multitude of pathways and intricate interventions. Chinese herbal medicine primarily regulates immune system–related pathways, while synthetic drugs predominantly consist of vitamins.

BackgroundInfluenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in the intestine and glycolysis in the lung tissues. In the clinical guidelines for pneumonia treatment in China, Ma Xing Shi Gan Decoction (MXSG) is a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism of action is related to the regulation of intestinal microbiota structure and lung tissue glycolysis.ObjectiveThis study aimed to investigate the mechanism of action of MXSG in an animal model of influenza virus-induced pneumonia. Specifically, we aimed to elucidate how MXSG modulates intestinal microbiota structure and lung tissue glycolysis to exert its therapeutic effects on pneumonia.MethodsWe established a mouse model of influenza virus-induced pneumoni, and treated with MXSG. We observed changes in inflammatory cytokine levels and conducted 16S rRNA gene sequencing to assess the intestinal microbiota structure and function. Additionally, targeted metabolomics was performed to analyze lung tissue glycolytic metabolites, and Western blot and enzyme-linked immunosorbent assays were performed to assess glycolysis-related enzymes, lipopolysaccharides (LPSs), HIF-1a, and macrophage surface markers. Correlation analysis was conducted between the LPS and omics results to elucidate the relationship between intestinal microbiota and lung tissue glycolysis in pneumonia animals under the intervention of Ma Xing Shi Gan Decoction.ResultsMXSG reduced the abundance of Gram-negative bacteria in the intestines, such as Proteobacteria and Helicobacter, leading to reduced LPS content in the serum and lungs. This intervention also suppressed HIF-1a activity and lung tissue glycolysis metabolism, decreased the number of M1-type macrophages, and increased the number of M2-type macrophages, effectively alleviating lung damage caused by influenza virus-induced pneumonia.ConclusionMXSG can alleviate glycolysis in lung tissue, suppress M1-type macrophage activation, promote M2-type macrophage activation, and mitigate inflammation in lung tissue. This therapeutic effect appears to be mediated by modulating gut microbiota and reducing endogenous LPS production in the intestines. This study demonstrates the therapeutic effects of MXSG on pneumonia and explores its potential mechanism, thus providing data support for the use of traditional Chinese medicine in the treatment of respiratory infectious diseases.

Objective: To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis. Methods: Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot. Results: GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1. Conclusion: The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

Extensive regulation of microRNAs (miRNAs) that belong to a type of endogenous small noncoding RNAs on gene expression in sheep has been recognised. Meanwhile, utilisation of water extract of Allium mongolicum Regel (WEA) in diet of sheep has been proved to regulate fatty acid composition and flavour in mutton. However, the regulatory mechanism remains unclear. We conducted miRNA and mRNA sequencing in this study. Briefly, 30 male small-tailed Han sheep (4.5 months old) were randomly assigned to two groups. A basal diet with 3.4 g·sheep−1·d−1 WEA supplementation (WEA group) or with no WEA supplementation (CON group) was fed to sheep, respectively. Subcutaneous and visceral adipose tissue samples were collected during slaughter after 75-day feeding experiment. We obtained 30 differentially expressed miRNAs (DE-miRNAs) after application of WEA in diet of sheep in subcutaneous adipose tissue. Likewise, 15 DE-miRNAs in visceral adipose tissue were identified. A total of 746 differentially expressed mRNAs (DE-mRNAs) with 90 lipid-related DE-mRNAs in subcutaneous adipose tissue and 569 DE-mRNAs with 73 lipid-related DE-mRNAs in visceral adipose tissue were identified after WEA supplementation. The intersection genes from predicted target genes of DE-miRNAs by databases and actual DE-mRNAs by mRNA sequencing were enriched in several lipid-related pathways both in subcutaneous adipose and in visceral adipose tissue. We constructed differential miRNAs-mRNAs networks by Cytoscape software. Our results will help to explain regulatory mechanism of fatty acid composition in mutton by dietary WEA and will provide a theoretical basis for rational use of the plant extract in diet of sheep.HIGHLIGHTS Utilisation of Allium mongolicum Regel water extract led to alterations of endogenous miRNA and gene expression profiles in subcutaneous and visceral adipose tissue of sheep. Allium mongolicum Regel water extract improved nutritional value and flavour of mutton by changing fatty acid composition in adipose tissue. Establishment of miRNA-mRNA regulatory network with regard to manipulation of fatty acid composition in mutton by Allium mongolicum Regel water extract, and provided a theoretical basis for rational utilisation of this plant extract in diet of sheep.

BackgroundThe efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy.MethodsBy conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM’s effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database.ResultsTwenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = −1.08, 95% CI (-1.30, −0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, −0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, −0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, −0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance.ConclusionChinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM’s therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.

BackgroundThe use of Intra-aortic Balloon Pump (IABP) and Impella devices as a bridge to heart transplantation (HTx) has increased significantly in recent times. This study aimed to create and validate an explainable machine learning (ML) model that can predict the failure of status two listings and identify the clinical features that significantly impact this outcome.MethodsWe used the UNOS registry database to identify HTx candidates listed as UNOS Status 2 between 2018 and 2022 and supported with either Impella (5.0 or 5.5) or IABP. We used the eXtreme Gradient Boosting (XGBoost) algorithm to build and validate ML models. We developed two models: (1) a comprehensive model that included all patients in our cohort and (2) separate models designed for each of the 11 UNOS regions.ResultsWe analyzed data from 4,178 patients listed as Status 2. Out of them, 12% had primary outcomes indicating Status 2 failure. Our ML models were based on 19 variables from the UNOS data. The comprehensive model had an area under the curve (AUC) of 0.71 (±0.03), with a range between 0.44 (±0.08) and 0.74 (±0.01) across different regions. The models' specificity ranged from 0.75 to 0.96. The top five most important predictors were the number of inotropes, creatinine, sodium, BMI, and blood group.ConclusionUsing ML is clinically valuable for highlighting patients at risk, enabling healthcare providers to offer intensified monitoring, optimization, and care escalation selectively.

Abstract Due to the relatively brief domestication history of sugar beet (Beta vulgaris ssp. vulgaris), our understanding of the genomic diversity and functional genes in its cultivars is limited, resulting in slow breeding progress. To address this issue, a total of 306 germplasm materials of major cultivars and breeding lines from China, the USA, and Europe were selected for genome resequencing. We investigated population structure and genetic diversity and performed selective scanning of genomic regions, identifying six novel genes associated with important agronomic traits: the candidate genes DFAX2 and P5CS for skin roughness; the candidate genes FRO5, GL24, and PPR91 for root yield and sugar yield, and the pleiotropic candidate gene POLX for flourishing growth vigour, plant height, crown size, flesh coarseness, and sugar yield. In addition, we constructed a protein–protein interaction network map and a phenotype-gene network map, which provide valuable information for identifying and characterizing functional genes affecting agronomic traits in sugar beet. Overall, our study sheds light on the future improvement of sugar beet agronomic traits at the molecular level.

Abstract The application of lithium‐based batteries is challenged by the safety issues of leakage and flammability of liquid electrolytes. Polymer electrolytes (PEs) can address issues to promote the practical use of lithium metal batteries. However, the traditional preparation of PEs such as the solution‐casting method requires a complicated preparation process, especially resulting in side solvents evaporation issues. The large thickness of traditional PEs reduces the energy density of the battery and increases the transport bottlenecks of lithium‐ion. Meanwhile, it is difficult to fill the voids of electrodes to achieve good contact between electrolyte and electrode. In situ polymerization appears as a facile method to prepare PEs possessing excellent interfacial compatibility with electrodes. Thus, thin and uniform electrolytes can be obtained. The interfacial impedance can be reduced, and the lithium‐ion transport throughput at the interface can be increased. The typical in situ polymerization process is to implant a precursor solution containing monomers into the cell and then in situ solidify the precursor under specific initiating conditions, and has been widely applied for the preparation of PEs and battery assembly. In this review, we focus on the preparation and application of in situ polymerization method in gel polymer electrolytes, solid polymer electrolytes, and composite polymer electrolytes, in which different kinds of monomers and reactions for in situ polymerization are discussed. In addition, the various compositions and structures of inorganic fillers, and their effects on the electrochemical properties are summarized. Finally, challenges and perspectives for the practical application of in situ polymerization methods in solid‐state lithium‐based batteries are reviewed.

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that “one-size-fits-all” for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

The natural color of biological specimens plays a crucial role in body protection, signaling, physiological adaptations, etc. Full-color optical sectioning structured illumination microscopy (OS-SIM) color is a promising approach that can reconstruct biological specimens in three-dimension meanwhile maintaining their natural color. Full-color OS-SIM takes the advantages of rapid imaging speed, compatibility with fluorescence and non-fluorescence samples, compact configuration, and low cost. However, the commonly used HSV-RMS reconstruction algorithm for full-color OS-SIM faces two issues to be improved. One is the RMS (root-mean-square) OS reconstruction algorithm is prone to background noise, and the other is the reconstruction is bound in RGB and HSV color spaces, consuming more reconstructing time. In this paper, we propose a full-color Fourier-OS-SIM method that allows for the OS reconstruction using the high-frequency spectrum of the sample and thus is immune to the low-frequency background noise. The full-color Fourier-OS-SIM directly runs in the RGB color space, providing an easy way to restore the color information. Simulation and experiments with various samples (pollen grains and tiny animals) demonstrate that the full-color Fourier-OS-SIM method is superior to the HSV-RMS method regarding background noise suppression. Moreover, benefiting from the background noise suppression merit, the quantitative morphological height map analysis with the full-color Fourier-OS-SIM method is more accurate. The proposed full-color Fourier-OS-SIM method is expected to find broad applications in biological and industrial fields where the 3D morphology and the color information of objects both need to be recovered.

Background: Mitral valve repair (MVr) is an effective treatment for degenerative mitral regurgitation (DMR).And the outcomes and repair rates for posterior leaflet prolapse (PLP), anterior leaflet prolapse (ALP), and bileaflet prolapse (BLP) vary. This study aimed to compare the outcomes of mitral valve repair for patients with PLP, ALP, and BLP. Methods: From 2010 to 2019, 1192 patients with degenerative mitral valve regurgitation underwent surgery at our hospital. And 1069 patients were identified. The average age of all patients was (54.74 ± 12.17) years old for all patients. 273 patients (25.5%) had ALP, 148 patients (13.8%) had BLP, and 648 patients (60.6%) had PLP. All patients were followed up for an average duration of 5.1 years. We compared the outcomes of patients with ALP, PLP, and BLP. Results: Patients with ALP were the youngest of the 3 groups and had the highest prevalence of atrial fibrillation. Patients with PLP had the highest prevalence of hypertension, whereas patients with BLP and ALP had larger left ventricular end-diastolic and left ventricular end-systolic diameters. ALP and BLP repairs had a longer cardiopulmonary bypass and aortic cross-clamp time.10 patients dead in-hospital, 5 patients had PLP, 3 had ALP, and 2 had BLP. The 10-year survival cumulative incidences of reoperation among ALP, BLP, and PLP repairs were not significantly different. ALP repair still had higher cumulative incidences of recurrent mitral regurgitation (MR) compared to PLP. Conclusions: The rates of long-term survival and freedom from reoperation were not significantly different among patients with ALP, BLP, and PLP. ALP repair has higher cumulative incidences of recurrent MR compared to PLP.

The objective of this study was to evaluate the potential modulating effects of Allium mongolicum regel ethanol extract (AME) on rumen fermentation and biohydrogenation (BH) bacteria in vitro. Four Holstein cows were used as donors for the rumen fluid used in this study. In experiment 1, five treatments (supplemented with 0 mg/g, 1 mg/g, 2 mg/g, 3 mg/g, and 4 mg/g of AME based on fermentation substrate, respectively) were conducted to evaluate the effects of different levels of AME on fermentation status in vitro. The results showed that after 24 h of fermentation, MCP was reduced with AME supplementation (p

The COVID-19 pandemic has caused a worldwide health crisis and economic recession. Effective prevention and treatment methods are urgently required to control the pandemic. However, the emergence of novel SARS-CoV-2 variants challenges the effectiveness of currently available vaccines and therapeutic antibodies. In this study, through the assessment of binding free energies, we analyzed the mutational effects on the binding affinity of the coronavirus spike protein to neutralizing antibodies, patient-derived antibodies, and artificially designed antibody mimics. We designed a scoring method to assess the immune evasion ability of viral variants. We also evaluated the differences between several targeting sites on the spike protein of antibodies. The results presented herein might prove helpful in the development of more effective therapies in the future.

Objective: To evaluate the feasibility of the production of ethephon in the freezing thawing and fresh keeping of fresh walnut, and to provide theoretical basis and technical support for fresh walnut freezing thawing and fresh keeping technology system. Methods: The late fruiting walnut variety 'Qingxiang' from Longnan county of Gansu province was used as the experimental material, and then the green walnut was picked by hand and then peeled by Ethephon. Meanwhile, the artificial peeling was used as the control （CK）. The fresh walnut was peeled and stored in a constant temperature freezer with temperature of -7~-5 ℃ and humidity of 85%~95%, the effects of ethephon on sensory quality （seed shell color, seed coat color, seed coat browning index, peeling difficulty and seed kernel flavor）, nutritional quality （water content, total fat content） and oil quality （acid value, iodine value, peroxide value and saponification value） of fresh walnut kernel after freezing thawing were studied. Results: Under the conditions of -7~-5 ℃ frozen storage, Ethrel accelerated the browning rate of peeled fresh kernels in the early stage of frozen storage to a certain extent. After 10 months of frozen storage, the scores of shell color, shell color and kernel flavor were 73.48, 74.56 and 77.26, respectively; The kernel water content, total fat content, acid value, iodine value, peroxide value and saponification value were 22.07%, 49.74%, 0.62 mg/g, 145.31 g/100 g, 3.62 meq/kg and 169.53 mg/g, respectively. There was no significant difference compared with the artificial peeled fresh walnut, which could maintain better flavor and nutritional quality. Conclusion: Ethephon accelerated ripening and peeling had no adverse effect on the quality of fresh walnut after freezing thawing. Ethephon could be used in the pretreatment process of fresh walnut frozen storage.

BackgroundMyopic corneal refractive surgery is one of the most prevalent ophthalmic procedures for correcting ametropia. This study aimed to perform a bibliometric analysis of research in the field of corneal refractive surgery over the past 40 years in order to describe the current international status and to identify most influential factors, while highlighting research hotspots.MethodsA bibliometric analysis based on the Web of Science Core Collection (WoSCC) was used to analyze the publication trends in research related to myopic corneal refractive surgery. VOSviewer v.1.6.10 was used to construct the knowledge map in order to visualize the publications, distribution of countries, international collaborations, author productivity, source journals, cited references, keywords, and research hotspots in this field.ResultsA total of 4,680 publications on myopic corneal refractive surgery published between 1979 and 2022 were retrieved. The United States has published the most papers, with Emory University contributing to the most citations. The Journal of Cataract and Refractive Surgery published the greatest number of articles, and the top 10 cited references mainly focused on outcomes and wound healing in refractive surgery. Previous research emphasized “radial keratotomy (RK)” and excimer laser-associated operation methods. The keywords containing femtosecond (FS) laser associated with “small incision lenticule extraction (SMILE)” and its “safety” had higher burst strength, indicating a shift of operation methods and coinciding with the global trends in refractive surgery. The document citation network was clustered into five groups: (1) outcomes of refractive surgery: (2) preoperative examinations for refractive surgery were as follows: (3) complications of myopic corneal refractive surgery; (4) corneal wound healing and cytobiology research related to photorefractive laser keratotomy; and (5) biomechanics of myopic corneal refractive surgery.ConclusionThe bibliometric analysis in this study may provide scholars with valuable to information and help them better understand the global trends in myopic corneal refractive surgery research frontiers. Two stages of rapid development occurred around 1991 and 2013, shortly after the innovation of PRK and SMILE surgical techniques. The most cited articles mainly focused on corneal wound healing, clinical outcomes, ocular aberration, corneal ectasia, and corneal topography, representing the safety of the new techniques.

Optical waveguides play a vital role in the manufacture of various optical devices due to their unique performances and high-degree integration. We report on the preparation and characterization of the planar waveguides in the Dy3+/Tm3+-codoped GeS2–Ga2S3–PbI2 chalcohalide glass. The waveguide was formed by the 400 keV H+-ion implantation with a dose of 8 × 1016 ions/cm2. Its thermal stability was studied by annealing at 260°C for 1 h. The changes in the nuclear energy loss with the implantation depth were simulated by the stopping and range of ions in matter (SRIM 2013). The dark-mode characteristics of the waveguide were measured by the prism coupling method. The refractive index distribution of the optical waveguide was reconstructed by the reflectivity calculation method. The modal profile of the waveguide structure was calculated by the finite-difference beam propagation method (FD-BPM). The thermally stable proton-implanted Dy3+/Tm3+-codoped GeS2–Ga2S3–PbI2 chalcohalide glass waveguide is expected to be applied in mid-infrared integrated optical devices.

Summary: Grain size is a key component of grain yield and quality in crops. Several core players of auxin signaling have been revealed to modulate grain size; however, to date, few genetically defined pathways have been reported, and whether phosphorylation could boost degradation of Aux/IAA proteins is uncertain. Here, we show that TGW3 (also called OsGSK5) interacts with and phosphorylates OsIAA10. Phosphorylation of OsIAA10 facilitates its interaction with OsTIR1 and subsequent destabilization, but this modification hinders its interaction with OsARF4. Our genetic and molecular evidence identifies an OsTIR1-OsIAA10-OsARF4 axis as key for grain size control. In addition, physiological and molecular studies suggest that TGW3 mediates the brassinosteroid response, the effect of which can be relayed through the regulatory axis. Collectively, these findings define a auxin signaling pathway to regulate grain size, in which phosphorylation of OsIAA10 enhances its proteolysis and potentiates OsIAA10-OsARF4-mediated auxin signaling.

GPR88 is an orphan GPCR and regulates diverse brain functions. Here, the authors report two structures of the human GPR88-Gi complex, showing an allosteric ligand directly involved in the interaction interface between the receptor and G-protein, and a density which may represent an endogenous ligand of GPR88.

Abstract The Jarzynski identity can describe small-scale nonequilibrium systems through stochastic thermodynamics. The identity considers fluctuating trajectories in a phase space. The complexity geometry frames the discussions on quantum computational complexity using the method of Riemannian geometry, which builds a bridge between optimal quantum circuits and classical geodesics in the space of unitary operators. Complexity geometry enables the application of the methods of classical physics to deal with pure quantum problems. By combining the two frameworks, i.e., the Jarzynski identity and complexity geometry, we derived a complexity analog of the Jarzynski identity using the complexity geometry. We considered a set of geodesics in the space of unitary operators instead of the trajectories in a phase space. The obtained complexity version of the Jarzynski identity strengthened the evidence for the existence of a well-defined resource theory of uncomplexity and presented an extensive discussion on the second law of complexity. Furthermore, analogous to the thermodynamic fluctuation-dissipation theorem, we proposed a version of the fluctuation-dissipation theorem for the complexity. Although this study does not focus on holographic fluctuations, we found that the results are surprisingly suitable for capturing their information. The results obtained using nonequilibrium methods may contribute to understand the nature of the complexity and study the features of the holographic fluctuations.

Abstract Background Increasing attention has been paid to the potential relationship between gut and lung. The bacterial dysbiosis in respiratory tract and intestinal tract is related to inflammatory response and the progress of lung diseases, and the pulmonary diseases could be improved by regulating the intestinal microbiome. This study aims to generate the knowledge map to identify major the research hotspots and frontier areas in the field of gut–lung axis. Materials and methods Publications related to the gut–lung axis from 2011 to 2021 were identified from the Web of Science Core Collection. CiteSpace 5.7.R2 software was used to analyze the publication years, journals, countries, institutions, and authors. Reference co-citation network has been plotted, and the keywords were used to analyze the research hotspots and trends. Results A total of 3315 publications were retrieved and the number of publications per year increased over time. Our results showed that Plos One (91 articles) was the most active journal and The United States (1035 articles) published the most articles. We also observed the leading institution was the University of Michigan (48 articles) and Huffnagle Gary B, Dickson Robert P and Hansbro Philip M, who have made outstanding contributions in this field. Conclusion The Inflammation, Infection and Disease were the hotspots, and the regulation of intestinal flora to improve the efficacy of immunotherapy in lung cancer was the research frontier. The research has implications for researchers engaged in gut–lung axis and its associated fields.

Pyrochlore has been extensively studied as one of the most ideal candidates for nuclear wastes immobilization, due to its excellent geological stability, radiation tolerance, low chemical leaching rate, and high thermal stability. However, the artificial pyrochlore has a relatively high selectivity for curing nuclides, which limits the types and quantity of its target species. To tackle the challenge, a variety of simulated nuclides(Eu, Sm and Nd) were successfully incorporated into the pyrochlore lattice by solid-state reactions. The experimental results show that the multi-pyrochlore exhibits a homogeneous structure with single phase. Leaching tests indicate that the multi-pyrochlore owns excellent leaching resistance and chemical stability, which enables multi-pyrochlore a promising immobilization material for high-level waste.

Background: Cognitive decline in older adults has become one of the critical challenges to global health. This study aims to examine both cross-sectional and longitudinal associations of levels of serum 25-hydroxyvitamin D3 (25(OH)D3) (briefed as VD3) concentration and sleep quality/duration, especially their interactions, with risk of cognitive impairment among older adults in China. Methods: We utilized a special subsample of adults aged 65–105 years (individuals = 3412, observations = 4816) from eight provinces in China derived from the 2011/2012 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Cognitive impairment was measured by the Mini-Mental State Examination scale. Sleep quality was classified as good versus fair/poor, and sleep duration was classified into short (3 sufficiency are positively associated with good cognitive function. VD3 sufficiency could enhance the associations between sleep and cognitive impairment.

Abstract Background Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. Methods We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2 −/− mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. Results Intra-cerebroventricular infection of Nos2 −/− mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2 −/− mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. Conclusions Intra-cerebroventricular infection of Nos2 −/− mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host–pathogen interactions and evaluate therapeutic agents for CNS-TB.

Scattering media, such as biological tissues and turbid liquids, scatter light randomly and introduce several challenges when imaging objects behind them. The transmission matrix (TM) describes the relation between the input and output of a beam transmitted through a medium, which can be used to reconstruct a target located behind a scattering medium. However, the current TM methods cannot easily retrieve the phase distribution of objects inside or behind a scattering medium. In this work, a compressive sensing (CS) method to identify the TM of a scatter contained in an imaging system was investigated. By calibrating the TM, the phase information of the object can be retrieved quantitatively. This method allows one to retrieve multilevel and dynamic phase objects behind different scatters. The influence of the calibration parameters on the reconstruction quality was investigated in detail. The proposed method, featuring noninterference measurements of the TM and exploiting a large field of view, can be used in phase imaging applications.

IntroductionArtificial intelligence can recognize complex patterns in large datasets. It is a promising technology to advance heart failure practice, as many decisions rely on expert opinions in the absence of high-quality data-driven evidence.MethodsWe searched Embase, Web of Science, and PubMed databases for articles containing “artificial intelligence,” “machine learning,” or “deep learning” and any of the phrases “heart transplantation,” “ventricular assist device,” or “cardiogenic shock” from inception until August 2022. We only included original research addressing post heart transplantation (HTx) or mechanical circulatory support (MCS) clinical care. Review and data extraction were performed in accordance with PRISMA-Scr guidelines.ResultsOf 584 unique publications detected, 31 met the inclusion criteria. The majority focused on outcome prediction post HTx (n = 13) and post durable MCS (n = 7), as well as post HTx and MCS management (n = 7, n = 3, respectively). One study addressed temporary mechanical circulatory support. Most studies advocated for rapid integration of AI into clinical practice, acknowledging potential improvements in management guidance and reliability of outcomes prediction. There was a notable paucity of external data validation and integration of multiple data modalities.ConclusionOur review showed mounting innovation in AI application in management of MCS and HTx, with the largest evidence showing improved mortality outcome prediction.

NADPH oxidase 1 (NOX1) is primarily expressed in epithelial cells and responsible for local generation of reactive oxygen species (ROS). By specifically manipulating the local redox microenvironment, NOX1 actively engages in epithelial immunity, especially in colorectal and pulmonary epithelia. To unravel the structural basis of NOX1 engaged epithelial immune processes, a predicted structure model was established using RaptorX deep learning models. The predicted structure model illustrates a 6-transmembrane domain structure, a FAD binding domain, and an NADPH binding/NOXO1 interacting region. The substrate/cofactor binding scheme with respect to this proposed model highly correlates with published reports and is verified in our site-directed mutagenesis assays. An electron transport chain, from NADPH to FAD and the two heme groups, was well supported by the predicted model. Through molecular docking analysis of various small molecule NOX1 inhibitors and subsequent experimental validation, we identified pronounced active sites for potent NOX1 inhibition. Specifically, LEU60, VAL71, MET181, LEU185, HIS208, PHE211, TYR214, and TYR280 in the transmembrane domain form an active pocket for insertion of the small molecule inhibitors to inhibit electron transfer between the heme groups, thus affecting extracellular ROS generation. Altogether, our study provides structural information to help elucidate the role of NOX1 in epithelial generation of ROS and sheds light on the development of therapeutics for NOX1 related illnesses.

IntroductionType 2 diabetes mellitus (T2DM) is a metabolic disease that has led to a significant global public health burden.MethodsIn this work, we investigated the effects of Lacticaseibacillus rhamnosus Hao9 on T2DM in mice with high-fat diet- and streptozotocin (STZ)-induced diabetes (diabetic mice) and explored the underlying mechanisms.ResultsWe found that 109 colony forming units (CFUs) of Hao9 per day significantly reduced fasting blood glucose and insulin levels (p < 0.001) in diabetic mice. Moreover, Hao9 enhanced liver antioxidant capacity and significantly decreased glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression in the livers of diabetic mice (p < 0.001). Hao9 also reduced the serum concentrations of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin-1β (IL1β), and IL6 (p < 0.05) and improved intestinal barrier function in diabetic mice. The composition of the gut microbiome was modulated by Hao9, with an increased abundance of Roseburia, Eubacterium, and Lacticaseibacillus, and decreased abundance of Escherichia/Shigella. Notably, Lacticaseibacillus was detected at both weeks 5 and 12 post-treatment, suggesting sustained colonization of the gut by Hao9.DiscussionThe supplementation of Hao9 improved gut microbiota, glucose metabolism, and insulin levels significantly in T2DM mice. That means Hao9 contributes to improving T2DM symptoms with its potential beneficial effects. Therefore, Hao9 is a promising dietary supplement for the treatment of T2DM.

Light-sheet fluorescence microscopy (LSFM) is a kind of volumetric imaging methodology suited for long term living specimens at high temporal-spatial resolution. A single Airy beam (SAB) light-sheet can extend the field of view of Light-sheet fluorescence microscopy benefiting from its non-diffracting nature, but at the cost of out-of-focus background and low imaging contrast caused by side lobes illumination. Here, we propose a method to generate a sort of multiple Airy beams (MAB), which are linearly superimposed of multiple single Airy beams with different scale factors. Compared to the SAB light-sheet, the energy of the multiple Airy beams light-sheet is more concentrated on the focal plane of the detection objective, which can improve the imaging contrast and decrease the photodamage effect. Furthermore, we combined the complementary beam subtraction (CBS) strategy to increase the axial resolution, termed as multiple Airy beams-complementary beam subtraction method, which enables the axial resolution of 1.2 μm while keeping the field of view of 450 μm × 450 μm. The effectiveness of the method is demonstrated by imaging of fluorescent beads and aspergillus conidiophores.

Sugar beet (Beta vulgaris L.) is an important sugar-producing and energy crop worldwide. The sugar beet pure line IMA1 independently bred by Chinese scientists is a standard diploid parent material that is widely used in hybrid-breeding programs. In this study, a high-quality, chromosome-level genome assembly for IMA1was conducted, and 99.1% of genome sequences were assigned to nine chromosomes. A total of 35,003 protein-coding genes were annotated, with 91.56% functionally annotated by public databases. Compared with previously released sugar beet assemblies, the new genome was larger with at least 1.6 times larger N50 size, thereby substantially improving the completeness and continuity of the sugar beet genome. A Genome-Wide Association Studies analysis identified 10 disease-resistance genes associated with three important beet diseases and five genes associated with sugar yield per hectare, which could be key targets to improve sugar productivity. Nine highly expressed genes associated with pollen fertility of sugar beet were also identified. The results of this study provide valuable information to identify and dissect functional genes affecting sugar beet agronomic traits, which can increase sugar beet production and help screen for excellent sugar beet breeding materials. In addition, information is provided that can precisely incorporate biotechnology tools into breeding efforts.

Hepatic ischemia-reperfusion injury (HIRI) is one of the major sources of mortality and morbidity associated with hepatic surgery. Ac2-26, a short peptide of Annexin A1 protein, has been proved to have a protective effect against IRI. However, whether it exerts a protective effect on HIRI has not been reported. The HIRI mice model and the oxidative damage model of H2O2-induced AML12 cells were established to investigate whether Ac2-26 could alleviate HIRI by regulating the activation of IL-22/IL-22R1/STAT3 signaling. The protective effect of Ac2-26 was measured by various biochemical parameters related to liver function, apoptosis, inflammatory reaction, mitochondrial function and the expressions of IL-22, IL-22R1, p-STAT3Tyr705. We discovered that Ac2-26 reduced the Suzuki score and cell death rate, and increased the cell viability after HIRI. Moreover, we unraveled that Ac2-26 significantly decreased the number of apoptotic hepatocytes, and the expressions of cleaved-caspase-3 and Bax/Bcl-2 ratio. Furthermore, HIRI increased the contents of malondialdehyde (MDA), NADP+/NADPH ratio and reactive oxygen species (ROS), whereas Ac2-26 decreased them significantly. Additionally, Ac2-26 remarkably alleviated mitochondria dysfunction, which was represented by an increase in the adenosine triphosphate (ATP) content and mitochondrial membrane potential, a decrease in mitochondrial DNA (mtDNA) damage. Finally, we revealed that Ac2-26 pretreatment could significantly inhibit the activation of IL-22/IL22R1/STAT3 signaling. In conclusion, this work demonstrated that Ac2-26 ameliorated HIRI by reducing oxidative stress and inhibiting the mitochondrial apoptosis pathway, which might be closely related to the inhibition of the IL-22/IL22R1/STAT3 signaling pathway.

The objective of this study was to evaluate the effect of Allium mongolicum Regel ethanol extract (AME) on the concentration of three branched-chain fatty acids (BCFAs) related to flavor, fermentation parameters and the bacteria and their correlations in the rumen of lambs. A total of thirty 3-month-old male, Small-tailed Han sheep (33.60 ± 1.23 kg) were randomly distributed into 2 groups as follows: control group (CON) was fed a basal diet and AME group was fed a basal diet supplemented with 2.8 g⋅lamb–1⋅d–1A. mongolicum Regel ethanol extract. AME supplementation decreased (P = 0.022) 4-methyloctanoic acid (MOA) content and tended to lower (P = 0.055) 4-methylnonanoic acid (MNA) content in the rumen. Compared to CON group, the ruminal concentrations of valerate and isovalerate were higher (P = 0.046 and P = 0.024, respectively), and propionate was lower (P = 0.020) in the AME group. At the phylum level, the AME group had a lower abundance of Bacteroidetes (P = 0.014) and a higher abundance of Firmicutes (P = 0.020) than the CON group. At the genus level, the relative abundances of Prevotella (P = 0.001), Christensenellaceae_R-7_group (P = 0.003), Succiniclasticum (P = 0.004), and Selenomonas (P = 0.001) were significantly lower in the AME group than in the CON group, while the relative abundances of Ruminococcus (P < 0.001), Quinella (P = 0.013), and Lachnospiraceae_XPB1014_group (P = 0.001) were significantly higher. The relative abundances of Prevotella (P = 0.029, R = 0.685; P = 0.009, R = 0.770), Christensenellaceae_R-7_group (P = 0.019, R = 0.721; P = 0.029, R = 0.685), and Succiniclasticum (P = 0.002, R = 0.842; P = 0.001, R = 0.879) was positively correlated with MOA and MNA levels, and the relative abundance of Lachnospiraceae_XPB1014_group (P = 0.033, R = −0.673) was negatively correlated with MOA. The relative abundance of Christensenellaceae_R-7_group (P = 0.014, R = −0.744) and Prevotellaceae_UCG-003 (P = 0.023, R = −0.706) correlated negatively with the EOA content. In conclusion, these findings suggest that the AME affected the concentration of BCFAs, fermentation parameters and the rumen bacteria in the rumen of lambs.

The perturbations of DNA methyltransferase 3 alpha (DNMT3A) may cause uncontrolled gene expression, resulting in cancers and tumors. The DNMT inhibitors Azacytidine (AZA) and Zebularine (ZEB) inhibit the DNMT family with no specificities, and consequently would bring side effects during the treatment. Therefore, it is vital to understand the inhibitory mechanisms in DNMT3A to inform the new inhibitor design for DNMTs. Herein, we carried out molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations to investigate the inhibitory mechanisms of the AZA and ZEB. The results were compared to the methyl transfer of cytosine. We showed how the AZA might stop the methyl transfer process, whereas the ZEB might be stuck in a methyl-transferred intermediate (IM3). The IM3 state then fails the elimination due to the unique protein dynamics that result in missing the catalytic water chain. Our results brought atomic-level insights into the mechanisms of the two drugs in DNMT3A, which could benefit the new generation of drug design for the DNMTs.

Abstract Background Sleep duration and vegetable consumption are associated with mortality at old age (termed as sleep-mortality linkage and vegetable-mortality linkage, respectively). Yet, little is known about the interplay of sleep duration and vegetable consumption on mortality. Methods A dataset of nationwide longitudinal survey with 13,441 participants aged 65 years or older recruited in 2008 and followed up till 2014 was used. Sleep duration was classified into five groups (≤5, 6, 7–8, 9, and ≥ 10 h/day). Vegetable consumption was classified as either high frequency (eating vegetables almost daily) or low frequency. We used parametric Weibull hazard regression models to estimate associations of sleep duration and frequency of vegetable consumption with mortality, adjusting for demographics, socioeconomic factors, family/social support, health practice, and health conditions. Results Over the six-year study period, when only demographics were present, participants sleeping ≤5, 6, 9, and ≥ 10 h/day had relative hazard (RH) of mortality 1.18 (p 0.1), and 1.30 (p

BackgroundThe impact of COVID-19 has most likely increased the prevalence of stunting. The study aimed to determine the prevalence of stunting among kindergarten children in the context of coronavirus disease 2019 (COVID-19) in Longgang District, Shenzhen, China, and its risk factors.MethodsA cross-sectional study was conducted to identify children from 11 sub districts of 481 kindergartens in the Longgang District of Shenzhen City from May to July 2021. In the context of COVID-19, an online survey was conducted to gather demographic information, height, birth information, and lifestyle. The prevalence of stunting was calculated, and the risk factors were analyzed using binary logistic regression with three stepwise models.ResultsA total of 118,404 subjects were included from May to July 2021, with a response and questionnaire effective rates of 85.75% and 95.03%, respectively. The prevalence of stunting and severe stunting were 3.3% and 0.8%, respectively. Model 3 showed that risk factors for stunting were male sex [odds ratio (OR) = 1.07], low birth weight (OR = 2.02), insufficient sleep time (OR = 1.08), less food intake than their peers (OR = 1.66), slower eating than their peers (OR = 1.16), accompanied by grandparents alone or non-lineal relatives (reference: parents accompanying) (OR = 1.23, 1.51), and children induced to eat (OR = 1.17). Protective factors included only-child status (OR = 0.66), reported high activity (OR = 0.37, 0.26, 0.23), parents with high education levels (father: OR = 0.87, 0.69; mother: OR = 0.69, 0.58), high monthly income per capita of the family (OR = 0.88, 0.74, 0.68), and allowing children to make food choices (OR = 0.82).ConclusionThe stunting rate of children in kindergartens in Longgang District is 3.3%, close to the level of developed countries but higher than the average level of developed cities in China. The relatively high stunting rate in children under 3 years old in 2021 may be associated with the influence of COVID-19. Appropriate policies should be formulated for individuals and families with children to help children establish good living habits and reduce stunting.

Abstract Allium mongolicum Regel (A. mongolicum) is a perennial and xerophytic Liliaceous allium plant in high altitude desert steppe and desert areas. Feeding A. mongolicum greatly reduced unpleasant mutton flavor and improves meat quality of sheep. We analyzed epigenetic regulatory mechanisms of water extracts of A. mongolicum (WEA) on sheep muscle and adipose using RNA-Seq and whole-genome Bisulfite sequencing. Feeding WEA reduced differentially expressed genes and long non-coding RNAs (lncRNAs) between two tissues but increased differentially methylation regions (DMRs). LncRNA and DMR targets were both involved in ATP binding, ubiquitin, protein kinase binding, regulation of cell proliferation, and related signaling pathways, but not unsaturated fatty acids metabolism. Besides, tissue specific targets were involved in distinct functional annotations, e.g., Golgi membrane and endoplasmic reticulum for muscle lncRNA, oxidative phosphorylation metabolism for adipose lncRNA, dsRNA binding for muscle DMRs. Epigenetic regulatory networks were also discovered to discovered essential co-regulated modules, e.g., co-regulated insulin secretion module (PDPK1, ATP1A2, CACNA1S and CAMK2D) in adipose. The results indicated that WEA induced distinct epigenetic regulation on muscle and adipose to diminish transcriptome differences between tissues, which highlights biological functions of A. mongolicum, tissue similarity and specificity, as well as regulatory mechanism of mutton odor.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, caused a global pandemic, and killed millions of people. The spike protein embedded in the viral membrane is essential for recognizing human receptors and invading host cells. Many nanobodies have been designed to block the interaction between spike and other proteins. However, the constantly emerging viral variants limit the effectiveness of these therapeutic nanobodies. Therefore, it is necessary to find a prospective antibody designing and optimization approach to deal with existing or future viral variants. Methods: We attempted to optimize nanobody sequences based on the understanding of molecular details by using computational approaches. First, we employed a coarse-grained (CG) model to learn the energetic mechanism of the spike protein activation. Next, we analyzed the binding modes of several representative nanobodies with the spike protein and identified the key residues on their interfaces. Then, we performed saturated mutagenesis of these key residue sites and employed the CG model to calculate the binding energies. Results: Based on analysis of the folding energy of the angiotensin-converting enzyme 2 (ACE2) -spike complex, we constructed a detailed free energy profile of the activation process of the spike protein which provided a clear mechanistic explanation. In addition, by analyzing the results of binding free energy changes following mutations, we determined how the mutations can improve the complementarity with the nanobodies on spike protein. Then we chose 7KSG nanobody as a template for further optimization and designed four potent nanobodies. Finally, based on the results of the single-site saturated mutagenesis in complementarity determining regions (CDRs), combinations of mutations were performed. We designed four novel, potent nanobodies, all exhibiting higher binding affinity to the spike protein than the original ones. Conclusions: These results provide a molecular basis for the interactions between spike protein and antibodies and promote the development of new specific neutralizing nanobodies.

The nucleosome, which organizes the long coil of genomic DNA in a highly condensed, polymeric way, is thought to be the basic unit of chromosomal structure. As the most important protein–DNA complex, its structural and dynamic features have been successively revealed in recent years. However, its regulatory mechanism, which is modulated by multiple factors, still requires systemic discussion. This study summarizes the regulatory factors of the nucleosome’s dynamic features from the perspective of histone modification, DNA methylation, and the nucleosome-interacting factors (transcription factors and nucleosome-remodeling proteins and cations) and focuses on the research exploring the molecular mechanism through both computational and experimental approaches. The regulatory factors that affect the dynamic features of nucleosomes are also discussed in detail, such as unwrapping, wrapping, sliding, and stacking. Due to the complexity of the high-order topological structures of nucleosomes and the comprehensive effects of regulatory factors, the research on the functional modulation mechanism of nucleosomes has encountered great challenges. The integration of computational and experimental approaches, the construction of physical modes for nucleosomes, and the application of deep learning techniques will provide promising opportunities for further exploration.

An analytic model was provided for the conventional distributed queueing (DQ) and its back-off tree operations, followed by a design of improving algorithm based on depth first traversal.Combing the specific analysis of complete binary tree with generalized extension by random tree reconstruction, the performance of proposed algorithm was evaluated on the throughput in both theory and simulation experiment.A theoretic optimal solution of contention slots of DQ frame and a brief description of simulation extension based on the open source NS-3 were presented.The simulation results show that the maximum stationary throughput by the proposed algorithm reaches 70% of the physical capacity of channel.

Objective: To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet, as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction (YD) and its effects on inflammation-related metabolic pathways. Methods: Lipopolysaccharides (LPS) and a special high-calorie diet were used to induce Sprague Dawley (SD) rats to simulate the intestinal state of infant pneumonia. Liquid chromatography-mass spectrometry technology (LC-MS/MS) was used to detect metabolites in each group. Supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model values were used for the detection results to find the differential metabolites. The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis. Finally, the T cell receptor signaling pathway (TCR) signal conversion was analyzed by the network pharmacology method. Results: In the high-calorie diet combined with pneumonia group (M3), a total of 55 metabolites were determined to be different from the normal group (N). A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group (T1). YD had a regulatory effect on glutathione metabolism, arginine and proline metabolism, ascorbic acid and aldehyde metabolism and phenylalanine metabolism. And the small molecule metabolites could act on the FYN and lymphocyte-specific protein tyrosine kinase (LCK) target proteins in the TCR signaling pathway, thereby affecting the immune function of the lungs. Conclusion: A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats, thereby creating chronic lung inflammation in young rats. YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets. Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.

With the increase in the installed capacity of wind power systems, the fault diagnosis and condition monitoring of wind turbines (WT) has attracted increasing attention. In recent years, machine learning (ML) has played a crucial role as an emerging technology for fault diagnosis in wind power systems has played a crucial role. Even though ML methods have shown great potential in dealing with the issues related to the fault diagnosis of WT, there are still some challenges encountered in many aspects. In this paper, typical fault diagnosis methods based on ML methods for wind power systems are thoroughly reviewed in terms of both theoretical fundamentals and industrial applications, including traditional machine learning (TML), artificial neural networks (ANN), deep learning (DL) and transfer learning (TL), in the development line of ML technologies. The advantages and disadvantages of various methods are analyzed and discussed. Meanwhile, a distribution diagram is provided for the discussions of ML methods applied for WT fault diagnosis, and the existing challenges on the applications for fault diagnosis based on ML for wind power generation systems are presented. Moreover, some prospects for future research directions are provided.

Abstract As pulmonary arterial hypertension associated with congenital heart disease (PAH‐CHD) may increase maternal and fetal risk, this study explored the pregnancy outcomes of Chinese women with PAH‐CHD. The clinical data of pregnant women with PAH‐CHD admitted to the Beijing Anzhen Hospital from 2010 to 2019 were retrospectively analyzed; these patients and their offspring were followed up, with a mean period of 5.9 ± 2.7 years. Overall, 260 patients with PAH‐CHD were included. The mean maternal age was 27.7 ± 4.1 years, and 205 (78.8%) patients were nulliparous. The estimated systolic pulmonary artery pressure was 40–50 mmHg in 34.6% of the patients, 50–70 mmHg in 23.1%, and >70 mmHg in 42.3%. More than 96% of patients were diagnosed with PAH‐CHD before pregnancy. During pregnancy, heart failure occurred in 19.2% of the patients. Cesarean delivery was performed in 88.1% (15.0% emergency) of the patients. Complications included fetal distress (5.8%), preterm delivery (34.2%), and low birth weight (33.8%). A total of 15 mothers (5.8%) died, with the highest mortality rate in those with Eisenmenger syndrome (10/43, 23.3%), and 10 offspring died (3.8%), two (0.8%) following hospital discharge and eight (3.1%) while in hospital. Although most pregnant women with PAH‐CHD were able to have children, PAH increased the maternal and fetal risk. Thus, an individualized risk‐based approach with shared decision‐making may be more appropriate in pregnant women with PAH‐CHD.

The etiology of acute lung injury (ALI) is not clear, and the treatment of ALI presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-κB subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-κB activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-κB signaling activation and binding of NF-κB to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment.

Optical sectioning structured illumination microscopy (OS-SIM) has been attracting considerable interest in fast 3D microscopy. The reconstruction of optical sectioning images in the conventional method employs the root-mean-square (RMS) algorithm in the spatial domain, which is prone to residual background noise. To overcome this problem, we propose a Fourier domain based optical sectioning image reconstruction algorithm (termed Fourier-OS-SIM), which has an improved background noise suppression capability compared to the RMS algorithm. The experimental results verified the feasibility and the effectiveness of the algorithm. The improved performance of the Fourier-OS-SIM may find more applications in biomedical or industrial fields.

Abstract Background Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet. Methods In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia. Results Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target. Conclusion Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.