Significant regional disparities in riverine microplastics.

Research on riverine microplastics has gradually increased, highlighting an area for further exploration: the lack of extensive, large-scale regional variations analysis due to methodological and spatiotemporal limitations. Herein, we constructed and applied a comprehensive framework for synthesizing and analyzing literature data on riverine microplastics to enable comparative research on the regional variations on a large scale. Research results showed that in 76 rivers primarily located in Asia, Europe, and North America, the microplastic abundance of surface water in Asian rivers was three times higher than that in Euro-America rivers, while sediment in Euro-American rivers was five times more microplastics than Asia rivers, indicating significant regional variations (p < 0.001). Additionally, based on the income levels of countries, rivers in lower-middle and upper-middle income countries had significantly (p < 0.001) higher abundance of microplastics in surface water compared to high-income countries, while the opposite was true for sediment. This phenomenon was preliminarily attributed to varying levels of urbanization across countries. Our proposed framework for synthesizing and analyzing microplastic literature data provides a holistic understanding of microplastic disparities in the environment, and can facilitate broader discussions on management and mitigation strategies.

A Naturally Active Spy Transposon Discovered from the Insect Genome of Colletes gigas as a Promising Novel Gene Transfer Tool.

Novel active DNA transposons, such as Spy transposons from the PHIS superfamily, are identified through bioinformatics in this study. The native transposases cgSpy and cvSpy displayed transposition activities of approximately 85% and 35% compared to the hyperactive piggyBac transposase (hyPB). The cgSpy transposon showed unique characteristics, including a lack of overproduction inhibition and reduced efficiency for insertion sizes between 3.1 to 8.5 kb. Integration preferences of cgSpy are found in genes and regulatory regions, making it suitable for genetic manipulation. Evaluation in T-cell engineering demonstrated that cgSpy-mediated chimeric antigen receptor (CAR) modification is comparable to the PB system, indicating its potential utility in cell therapy. This study unveils the promising application of the active native transposase, Spy, from Colletes gigas, as a valuable tool for genetic engineering, particularly in T-cell manipulation.

Characterising global antimicrobial resistance research explains why One Health solutions are slow in development: An application of AI-based gap analysis.

The global health crisis posed by increasing antimicrobial resistance (AMR) implicitly requires solutions based a One Health approach, yet multisectoral, multidisciplinary research on AMR is rare and huge knowledge gaps exist to guide integrated action. This is partly because a comprehensive survey of past research activity has never performed due to the massive scale and diversity of published information. Here we compiled 254,738 articles on AMR using Artificial Intelligence (AI; i.e., Natural Language Processing, NLP) methods to create a database and information retrieval system for knowledge extraction on research perfomed over the last 20 years. Global maps were created that describe regional, methodological, and sectoral AMR research activities that confirm limited intersectoral research has been performed, which is key to guiding science-informed policy solutions to AMR, especially in low-income countries (LICs). Further, we show greater harmonisation in research methods across sectors and regions is urgently needed. For example, differences in analytical methods used among sectors in AMR research, such as employing culture-based versus genomic methods, results in poor communication between sectors and partially explains why One Health-based solutions are not ensuing. Therefore, our analysis suggest that performing culture-based and genomic AMR analysis in tandem in all sectors is crucial for data integration and holistic One Health solutions. Finally, increased investment in capacity development in LICs should be prioritised as they are places where the AMR burden is often greatest. Our open-access database and AI methodology can be used to further develop, disseminate, and create new tools and practices for AMR knowledge and information sharing.

Local CO Generator Enabled by a CO-Producing Core for Kinetically Enhancing Electrochemical CO2 Reduction to Multicarbon Products.

CO plays a crucial role as an intermediate in electrochemical CO2 conversion to generate multicarbon (C2+) products. However, optimizing the coverage of the CO intermediate (*CO) to improve the selectivity of C2+ products remains a great challenge. Here, we designed a hierarchically structured double hollow spherical nanoreactor featuring atomically dispersed nickel (Ni) atoms as the core and copper (Cu) nanoparticles as the shell, which can greatly improve the catalytic activity and selectivity for C2+ compounds. Within this configuration, CO generated at the active Ni sites on the inner layer accumulates in the cavity before spilling over neighboring Cu sites on the outer layer, thus enhancing CO dimerization within the cavity. Notably, this setup achieves a sustained faradaic efficiency of 74.4% for C2+ production, with partial current densities reaching 337.4 mA cm-2. In situ Raman spectroscopy and finite-element method (FEM) simulations demonstrate that the designed local CO generator can effectively increase the local CO concentration and restrict CO evolution, ultimately boosting C-C coupling. The hierarchically ordered architectural design represents a promising solution for achieving highly selective C2+ compound production in the electroreduction of CO2.

Surface-Diffusion-Induced Amorphization of Pt Nanoparticles over Ru Oxide Boost Acidic Oxygen Evolution.

Phase transformation offers an alternative strategy for the synthesis of nanomaterials with unconventional phases, allowing us to further explore their unique properties and promising applications. Herein, we first observed the amorphization of Pt nanoparticles on the RuO2 surface by in situ scanning transmission electron microscopy. Density functional theory calculations demonstrate the low energy barrier and thermodynamic driving force for Pt atoms transferring from the Pt cluster to the RuO2 surface to form amorphous Pt. Remarkably, the as-synthesized amorphous Pt/RuO2 exhibits 14.2 times enhanced mass activity compared to commercial RuO2 catalysts for the oxygen evolution reaction (OER). Water electrolyzer with amorphous Pt/RuO2 achieves 1.0 A cm-2 at 1.70 V and remains stable at 200 mA cm-2 for over 80 h. The amorphous Pt layer not only optimized the *O binding but also enhanced the antioxidation ability of amorphous Pt/RuO2, thereby boosting the activity and stability for the OER.

Ensemble Extreme Learning Machine Method for Hemoglobin Estimation Based on PhotoPlethysmoGraphic Signals.

Non-invasive detection of hemoglobin (Hb) concentration is of great clinical value for health screening and intraoperative blood transfusion. However, the accuracy and stability of non-invasive detection still need to be improved to meet clinical requirement. This paper proposes a non-invasive Hb detection method using ensemble extreme learning machine (EELM) regression based on eight-wavelength PhotoPlethysmoGraphic (PPG) signals. Firstly, a mathematical model for non-invasive Hb detection based on the Beer-Lambert law is established. Secondly, the captured eight-channel PPG signals are denoised and fifty-six feature values are extracted according to the derived mathematical model. Thirdly, a recursive feature elimination (RFE) algorithm is used to select the features that contribute most to the Hb prediction. Finally, a regression model is built by integrating several independent ELM models to improve prediction stability and accuracy. Experiments conducted on 249 clinical data points (199 cases as the training dataset and 50 cases as the test dataset) evaluate the proposed method, achieving a root mean square error (RMSE) of 1.72 g/dL and a Pearson correlation coefficient (PCC) of 0.76 (p < 0.01) between predicted and reference values. The results demonstrate that the proposed non-invasive Hb detection method exhibits a strong correlation with traditional invasive methods, suggesting its potential for non-invasive detection of Hb concentration.

Discovery of 2,3-Dihydro[1,4]dioxino[2,3-g]benzofuran Derivatives as Protease Activated Receptor 4 (PAR4) Antagonists with Potent Antiplatelet Aggregation Activity and Low Bleeding Tendency.

Patients with arterial embolic disease have benefited greatly from antiplatelet therapy. However, hemorrhage risk of antiplatelet agents cannot be ignored. Herein, we describe the discovery of 2,3-dihydro[1,4]dioxino[2,3-g]benzofuran compounds as novel PAR4 antagonists. Notably, the isomers 36 and 37 with the chemotype of phenoxyl methylene substituted on the 2,3-dihydro-1,4-dioxine ring exhibited potent in vitro antiplatelet activity (IC50 = 26.13 nM for 36 and 14.26 nM for 37) and significantly improved metabolic stability in human liver microsomes (T1/2 = 97.6 min for 36 and 11.1 min for BMS-986120). 36 also displayed good oral PK profiles (mice: T1/2 = 7.32 h and F = 45.11%). Both of them showed overall potent ex vivo antiplatelet activity at concentrations of 6 and 12 mg/kg, with no impact on the coagulation system and low bleeding liability. Our work will facilitate development of novel PAR4 antagonists as a safer therapeutic option for arterial embolism.

Evolution of Endogenous Retroviruses in the Subfamily of Caprinae.

The interest in endogenous retroviruses (ERVs) has been fueled by their impact on the evolution of the host genome. In this study, we used multiple pipelines to conduct a de novo exploration and annotation of ERVs in 13 species of the Caprinae subfamily. Through analyses of sequence identity, structural organization, and phylogeny, we defined 28 ERV groups within Caprinae, including 19 gamma retrovirus groups and 9 beta retrovirus groups. Notably, we identified four recent and potentially active groups prevalent in the Caprinae genomes. Additionally, our investigation revealed that most long noncoding genes (lncRNA) and protein-coding genes (PC) contain ERV-derived sequences. Specifically, we observed that ERV-derived sequences were present in approximately 75% of protein-coding genes and 81% of lncRNA genes in sheep. Similarly, in goats, ERV-derived sequences were found in approximately 74% of protein-coding genes and 75% of lncRNA genes. Our findings lead to the conclusion that the majority of ERVs in the Caprinae genomes can be categorized as fossils, representing remnants of past retroviral infections that have become permanently integrated into the genomes. Nevertheless, the identification of the Cap_ERV_20, Cap_ERV_21, Cap_ERV_24, and Cap_ERV_25 groups indicates the presence of relatively recent and potentially active ERVs in these genomes. These particular groups may contribute to the ongoing evolution of the Caprinae genome. The identification of putatively active ERVs in the Caprinae genomes raises the possibility of harnessing them for future genetic marker development.

Population genetic analysis based on the polymorphisms mediated by transposons in the genomes of pig.

Transposable elements (TEs) mobility is capable of generating a large number of structural variants (SVs), which can have considerable potential as molecular markers for genetic analysis and molecular breeding in livestock. Our results showed that the pig genome contains mainly TE-SVs generated by short interspersed nuclear elements (51,873/76.49%), followed by long interspersed nuclear elements (11,131/16.41%), and more than 84% of the common TE-SVs (Minor allele frequency, MAF > 0.10) were validated to be polymorphic. Subsequently, we utilized the identified TE-SVs to gain insights into the population structure, resulting in clear differentiation among the three pig groups and facilitating the identification of relationships within Chinese local pig breeds. In addition, we investigated the frequencies of TEs in the gene coding regions of different pig groups and annotated the respective TE types, related genes, and functional pathways. Through genome-wide comparisons of Large White pigs and Chinese local pigs utilizing the Beijing Black pigs, we identified TE-mediated SVs associated with quantitative trait loci and observed that they were mainly involved in carcass traits and meat quality traits. Lastly, we present the first documented evidence of TE transduction in the pig genome.

Spatial distribution pattern and correlation of dominant populations in the shrub layer of Fengshui forest in Leizhou Peninsula, China.

To elucidate the spatial patterns of understory species in fragmented forests adjacent to human settlements, we examined the spatial distribution and intraspecific correlations of three dominant species Mallotus philippensis, Dasymashalon trichophorum, and Psychotria rubra by employing point pattern analysis, which were the top three in terms of importance value in the shrub layer of Fengshui forest in Leizhou Peninsula, Guangdong. The results showed that all the three species were mainly aggregated at the scale of 0-25 m, especially for young trees. The degree of aggregation gradually diminished with increasing age class. The spatial distribution patterns of three species were predominantly influenced by habitat heterogeneity, negative density dependence, and dispersal limitation. They showed positive association among different age classes, especially between young trees and middle age trees and between young trees and adult trees. Therefore, in the ecological restoration process of Leizhou Peninsula, M. philippensis, D. trichophorum, and P. rubra should be planted in clusters at a small scale within the range of 0-25 m, with the degree of clusters depending on plant morphology. For larger scales, a dispersed cultivation approach was advocated.

Lung transcriptomics reveals the underlying mechanism by which aerobic training enhances pulmonary function in chronic obstructive pulmonary disease.

BACKGROUND: Aerobic training is the primary method of rehabilitation for improving respiratory function in patients with chronic obstructive pulmonary disease (COPD) in remission. However, the mechanism underlying this improvement is not yet fully understood. The use of transcriptomics in rehabilitation medicine offers a promising strategy for uncovering the ways in which exercise training improves respiratory dysfunction in COPD patients. In this study, lung tissue was analyzed using transcriptomics to investigate the relationship between exercise and lung changes. METHODS: Mice were exposed to cigarette smoke for 24 weeks, followed by nine weeks of moderate-intensity treadmill exercise, with a control group for comparison. Pulmonary function and structure were assessed at the end of the intervention and RNA sequencing was performed on the lung tissue. RESULTS: Exercise training was found to improve airway resistance and lung ventilation indices in individuals exposed to cigarette smoke. However, the effect of this treatment on damaged alveoli was weak. The pair-to-pair comparison revealed numerous differentially expressed genes, that were closely linked to inflammation and metabolism. CONCLUSIONS: Further research is necessary to confirm the cause-and-effect relationship between the identified biomarkers and the improvement in pulmonary function, as this was not examined in the present study.

Distinguishing schizophrenia and bipolar disorder through a Multiclass Classification model based on multimodal neuroimaging data.

This study aimed to identify neural biomarkers for schizophrenia (SZ) and bipolar disorder (BP) by analyzing multimodal neuroimaging. Utilizing data from structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), multiclass classification models were created for SZ, BP, and healthy controls (HC). A total of 113 participants (BP: 31, SZ: 39, and HC: 43) were recruited under strict enrollment control, from which 272, 200, and 1875 features were extracted from sMRI, DTI, and rs-fMRI data, respectively. A support vector machine (SVM) with recursive feature elimination (RFE) was employed to build the models using a one-against-one approach and leave-one-out cross-validation, achieving a classification accuracy of 70.8%. The most discriminative features were primarily from rs-fMRI, along with significant findings in sMRI and DTI. Key biomarkers identified included the increased thickness of the left cuneus cortex and decreased regional functional connectivity strength (rFCS) in the left supramarginal gyrus as shared indicators for BP and SZ. Additionally, decreased fractional anisotropy in the left superior fronto-occipital fasciculus was suggested as specific to BP, while decreased rFCS in the left inferior parietal area might serve as a specific biomarker for SZ. These findings underscore the potential of multimodal neuroimaging in distinguishing between BP and SZ and contribute to the understanding of their neural underpinnings.

Generation of induced pluripotent stem cells (ZZUCSBi001-A) from skin fibroblasts of a healthy donor.

Fibroblasts were extracted from the scalp of a healthy 55-year-old male and subsequently transformed into pluripotent stem cells by introducing episomal plasmids harboring essential reprogramming factors. These induced pluripotent stem cells exhibited a normal karyotype and demonstrated the capacity to differentiate into all three germ layers, as confirmed through teratoma assays. This specific cell line serves as a valuable reference for comparative investigations alongside other induced pluripotent stem cell lines generated from somatic cells of patients afflicted by genetic neurodegenerative disorders.

Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma.

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.

Retroviral Insertion Polymorphism (RIP) of Porcine Endogenous Retroviruses (PERVs) in Pig Genomes.

Endogenous retroviruses (ERVs) are one of the superfamilies of long terminal repeat retrotransposons (LTRs) in mice and humans. Approximately 8% of the pig genome is composed of sequences derived from LTRs. While the majority of ERVs in pigs have decayed, a small number of full-length copies can still mobilize within the genome. This study investigated the unexplored retroviral insertion polymorphisms (RIPs) generated by the mobilization of full-length ERVs (Fl-ERVs), and evaluated their impact on phenotypic variation to gain insights into the biological role of Fl-ERVs in pigs. Overall, 39 RIPs (insertions or deletions relative to the pig reference genome) generated by Fl-ERVs were predicted by comparative genomic analysis, and 18 of them were confirmed by PCR detection. Four RIP sites (D5, D14, D15, and D18) were further evaluated by population analysis, and all of them displayed polymorphisms in multiple breeds. The RIP site of ERV-D14, which is a Fl-ERV inserted in the STAB2-like gene, was further confirmed by sequencing. Population analysis of the polymorphic site of ERV-D14 reveals that it presents moderate polymorphism information in the Large White pig breed, and the association analysis reveals that the RIP of ERV-D14 is associated with age variations at 30 kg body weight (p < 0.05) and 100 kg body weight (p < 0.01) in the population of Large White pigs (N = 480). Furthermore, the ERV-D14 RIP is associated with changes in the expression of the target gene STAB2-like in the liver, backfat, and leaf fat in Sushan pigs. These data suggest that some Fl-ERVs are still mobilizing in the pig's genome, and contribute to genomic and phenotypic variations.

Constructing sulfur and oxygen super-coordinated main-group electrocatalysts for selective and cumulative H2O2 production.

Direct electrosynthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction presents a burgeoning alternative to the conventional energy-intensive anthraquinone process for on-site applications. Nevertheless, its adoption is currently hindered by inferior H2O2 selectivity and diminished H2O2 yield induced by consecutive H2O2 reduction or Fenton reactions. Herein, guided by theoretical calculations, we endeavor to overcome this challenge by activating a main-group Pb single-atom catalyst via a local micro-environment engineering strategy employing a sulfur and oxygen super-coordinated structure. The main-group catalyst, synthesized using a carbon dot-assisted pyrolysis technique, displays an industrial current density reaching 400 mA cm-2 and elevated accumulated H2O2 concentrations (1358 mM) with remarkable Faradaic efficiencies. Both experimental results and theoretical simulations elucidate that S and O super-coordination directs a fraction of electrons from the main-group Pb sites to the coordinated oxygen atoms, consequently optimizing the *OOH binding energy and augmenting the 2e- oxygen reduction activity. This work unveils novel avenues for mitigating the production-depletion challenge in H2O2 electrosynthesis through the rational design of main-group catalysts.

Biomarker Testing Journey Among Patients with Advanced Solid Tumors and Treatment Patterns by Homologous Recombination Repair Status: A Clinico-Genomic Database Study.

INTRODUCTION: Defects in the homologous recombination repair (HRR) pathway can include mutations in BRCA1 and BRCA2 (BRCAm) and other HRR genes (HRRm). These mutations are associated with a homologous recombination deficiency (HRD) phenotype. We evaluated testing journey and treatment patterns by BRCAm, HRRm, and HRD status in a real-world dataset. METHODS: Deidentified data for patients who had undergone comprehensive genomic profiling using FoundationOne®CDx were collected through December 31, 2020, from a real-world multi-tumor clinico-genomic database (CGDB) capturing data from clinics in the United States. Patients eligible for inclusion in this analysis had a confirmed diagnosis with advanced or metastatic disease between January 1, 2018, and December 31, 2019, for 1 of 15 solid tumor types. Objectives were to evaluate patient treatment patterns by BRCAm, HRRm, and HRD status and to describe the timing of when (throughout disease course) comprehensive genomic profiling was performed. RESULTS: Among 9457 patients included in the overall population with evaluable biomarker status, 7856 (83.1%) received ≥ 1 systemic therapy. Among the 7856 patients who received systemic therapy, 2324 (30.0%) underwent testing before first-line therapy, 4114 (52.4%) were tested after receiving first-line therapy and before receiving subsequent therapy (if any), 970 (12.3%) were tested after second-line therapy and before receiving subsequent therapy (if any), and 447 (5.7%) patients underwent testing after receiving third-line therapy. A higher proportion of patients with BRCAm, HRRm, or HRD-positive status were treated with poly(ADP-ribose) polymerase (PARP) inhibitors across all lines of therapy. There was no evidence of a meaningful difference in the proportion of patients who received other treatment (including chemotherapy and immunotherapy) by BRCAm, HRRm, or HRD status. CONCLUSION: The majority of patients from this real-world dataset underwent FoundationOne®CDx testing after initiation of first-line treatment. Testing appeared to influence treatment patterns, with a higher proportion of patients with BRCAm, HRRm, and HRD-positive disease receiving PARP inhibitors.

Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Real-world prevalence of homologous recombination repair mutations in advanced prostate cancer: an analysis of two clinico-genomic databases.

BACKGROUND: Homologous recombination repair mutation (HRRm) status may guide risk-stratification and treatment decisions, including polyadenosine diphosphate-ribose polymerase inhibitor use, in advanced prostate cancer. Although HRRm prevalence has been reported in single-institution studies or clinical trials, real-world HRRm prevalence in diverse populations is unknown. We describe HRRm in the clinical setting using two real-world clinicogenomic databases: the Flatiron Health and Foundation Medicine, Inc. Clinico-Genomic Database (CGDB), a national electronic health record-derived database, and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE). METHODS: This cross-sectional analysis included 3757 individuals diagnosed with prostate cancer who had next generation sequencing (NGS) as standard of care. The CGDB included men with advanced/metastatic prostate cancer and genetic data included both germline and somatic pathogenic mutations. The GENIE analysis included men with prostate cancer whose received NGS as standard of care, but the data were filtered to include somatic mutations only. Due to key differences among databases, direct comparisons were not possible. Overall prevalence of HRRm was calculated and stratified by demographic and clinical characteristics. RESULTS: HRRm prevalence (combined germline and somatic) in CGDB (n = 487) was 24.6% (95% CI 20.9-28.7%), with no major differences across demographic and disease characteristic subgroups. HRRm prevalence (somatic) in GENIE (n = 3270) was 11.0% (95% CI 10.0-12.1%), which varied between 9.5% and 18.4% across treatment centers. CONCLUSIONS: Approximately one-quarter of patients with advanced/metastatic prostate cancer in the CGDB had germline and/or somatic HRRm, which is consistent with clinical trials such as the PROfound study that used a similar NGS platform and algorithm to define HRRm. In the GENIE database, HRRm prevalence varied by treatment center or NGS platform. More research is needed to understand real-world HRRm prevalence variations.

Efficacy of prednisone combined with mycophenolate mofetil for immunoglobulin A nephropathy with moderate-to-severe renal dysfunction.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis. Currently, IgAN is one of the main causes of chronic renal failure in China; its prognosis varies greatly between patients, with renal function at the time of diagnosis and prognosis being strongly correlated. Mycophenolate mofetil (MMF) is a drug with a good immunomodulatory effect and is commonly used clinically. However, its effects in IgAN have not yet been clearly demonstrated. Therefore, herein, we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment. AIM: To evaluate the effectiveness and safety of prednisone and MMF in treating IgAN with moderate-to-severe renal dysfunction. METHODS: Between January 2011 and December 2020, 200 patients with moderate-to-severe IgAN were included in this study, all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University. All patients underwent a renal puncture biopsy, which revealed primary IgAN with a glomerular filtration rate (GFR) of 30-60 mL/min. The patients were divided into a glucocorticoid therapy group (GTG) and an immunosuppressive therapy group (ITG) according to the different treatment regimens, with 100 patients in each group. Based on general treatments, such as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers, patients in the GTG were administered prednisone 0.5-0.8 mg/ (kg·d-1) for 4-8 wk, which was reduced by 5 mg every two weeks until the maintenance(30 mg/d) dose was reached and maintained for 12 mo. In the ITG, MMF was administered at 1.0 g/d for 6-12 mo, followed by a maintenance dosage of 0.5 g/d for 12 mo. Age, sex, blood pressure, 24-h urinary egg white measurement, serum creatinine (Scr), blood uric acid, blood albumin, blood potassium (K), hemoglobin, GFR, alanine aminotransferase, total cholesterol (T-CHO), fasting blood glucose, and body mass index were recorded. The 24-h urinary protein, Scr, and GFR levels were recorded 3, 6, 9, and 12 mo after treatment. Follow-up data were also collected. RESULTS: No discernible differences existed between the two groups in terms of age, sex, blood pressure, creatinine, 24-h urinary protein level, GFR, or other biochemical indicators at the time of enrollment. Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function. Nine months after treatment, the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG. By the 12th month of treatment, the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month. In addition, the overall response rate in the ITG was significantly higher than that in the GTG. The occurrence of side effects did not vary significantly between the two regimens; however, endpoint events were significantly more common in the GTG than in the ITG. The follow-up time for the GTG was noticeably lower than that for the ITG. CONCLUSION: Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.