Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling.

Polygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from China Medical University Hospital. Logistic regression models assessed polygenic scores' ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. Notably, hyperplasia of the prostate exhibited the highest disease prediction ability (P value = 1.01 × 10-19, AUC = 0.874), highlighting the potential of these polygenic scores in preventive medicine and diagnosis. This study offers a comprehensive evaluation of polygenic scores performance across diverse human traits, identifying promising applications for precision medicine and personalized healthcare, thereby inspiring further research and development in this field.

A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis.

Background: Patients with osteoarthritis (OA) are exposed to an increased risk of adverse outcomes of COVID-19, and they tend to experience disruption in access to healthcare services and exercise facilities. However, a deep understanding of this comorbidity phenomenon and the underlying genetic architecture of the two diseases is still unclear. In this study, we aimed to untangle the relationship between OA and COVID-19 outcomes by conducting a large-scale genome-wide cross-trait analysis. Methods: Genetic correlation and causal relationships between OA and COVID-19 outcomes (critical COVID-19, COVID-19 hospitalization, and COVID-19 infection) were estimated by linkage disequilibrium score regression and Mendelian Randomization approaches. We further applied Multi-Trait Analysis of GWAS and colocalization analysis to identify putative functional genes associated with both OA and COVID-19 outcomes. Results: Significant positive genetic correlations between OA susceptibility and both critical COVID-19 (rg=0.266, P=0.0097) and COVID-19 hospitalization (rg=0.361, P=0.0006) were detected. However, there was no evidence to support causal genetic relationships between OA and critical COVID-19 (OR=1.17[1.00-1.36], P=0.049) or OA and COVID-19 hospitalization OR=1.08[0.97-1.20], P=0.143). These results were robustly consistent after the removal of obesity-related single nucleotide polymorphisms (SNPs). Moreover, we identified a strong association signal located near the FYCO1 gene (lead SNPs: rs71325101 for critical COVID-19, Pmeta=1.02×10-34; rs13079478 for COVID-19 hospitalization, Pmeta=1.09×10-25). Conclusion: Our findings further confirmed the comorbidity of OA and COVID-19 severity, but indicate a non-causal impact of OA on COVID-19 outcomes. The study offers an instructive perspective that OA patients did not generate negative COVID-19 outcomes during the pandemic in a causal way. Further clinical guidance can be formulated to enhance the quality of self-management in vulnerable OA patients.

Heterocyclic Functionalized Donor-Acceptor Hole-Transporting Materials for Inverted Perovskite Solar Cells.

Hole transport materials (HTMs) with appropriate energy levels and comprehensive passivation effects help to obtain highly efficient and stable perovskite solar cells (PSCs). Electron-deficient character-induced HTMs can generate varying energy level alignments near the HTM/perovskite interface. Herein, we report the synthesis and investigation of two new dipolar HTMs, WWC103 and WWC105, based on 2-(1,1-dicyanomethylene)rhodamine and 4-cynophenylacetonitrile acceptors, enabling high-efficiency mixed-cation mixed-halide perovskite solar cells. Apart from having different acceptors, these HTMs are built on a heterocyclic frame, which can provide passivation effects and improve the morphology of the perovskite layer. As a result, these dopant-free HTM-based solar cells show a high open-circuit voltage and good power conversion efficiency. Among both, the solar cell based on the HTM with 2-(1,1-dicyanomethylene)rhodamine exhibits a high open-circuit voltage of 1.09 V with a champion power conversion efficiency of over 20.51%. The improved performance of WWC103 over WWC105 (19.74%) is attributed to the new acceptor, which, in addition to providing good energy-level alignments and hole mobility, also holds the ability to passivate the defects. The findings suggest a new acceptor unit for constructing dopant-free HTMs for efficient PSCs.

Effective Induction of Fertile Gametes in Oriental × Trumpet (OT) Lily by High Temperatures.

Lily is a very important bulb crop, and interspecific distant hybridization is a crucial method of lily breeding. However, F1 interspecific hybrids tend to be highly sterile due to low levels of genetic homozygosity. This can be addressed by meiotic polyploidization, which has the advantage of reducing breeding time and being able to promote genetic recombination resulting in many variant progenies. High temperatures have been proven to induce 2n gametes via hindering a spindle formation in several plants, but little has been reported in lilies. In the present study, after observing the correlation between the development of the pollen mother cells (PMCs) and the length of the buds, 28-31 mm long buds were selected as the experimental material, which were at the stage of prophase I-metaphase I. Individual buds were induced at different temperatures (40 °C, 42 °C, and 44 °C) and durations (4 h and 6 h) using self-made multiwire heating equipment, and successfully induced fertile male gametes.. The best results were achieved with treatment of 42 °C for 4 h, reaching a maximum fertile pollen induction rate of 36.64%, while bud mortality was 40%. Two chemicals, colchicine and oryzalin, were also used by injection, and only the treatment with oryzalin obtained fertile gametes, with the highest fertile gamete rate of 15.39% at a concentration of 0.005%, while the bud mortality was 36.67%. This suggests that high temperatures have a superior effect on lily 2n gamete induction. In addition, the pollen obtained from the 6 h induction of high temperature was significantly larger than that from the 4 h induction, with an average diameter of 138.64 µm and 107.88 µm, respectively, 2.35 and 1.84 times wider than haploid pollen. The fertile pollen was crossed with four cultivars and two species, and a total of 267 embryonic seeds were obtained, with the highest embryonic rate of 4.52% in OT lily 'Mister Cas' as the parent, which had a germination rate of 26.27%. This suggests that the method of high-temperature induction for fertile gametes probably has important significance for ploidy and distant hybrid breeding in lilies.

Arthritis and incident pulmonary diseases in middle-aged and elderly Chinese: a longitudinal population-based study.

BACKGROUND: The coexistence of arthritis and pulmonary abnormalities has long been observed, but the causal inter-relationships among them are still uncertain especially in elderly adults. METHODS: We extracted data from The China Health and Retirement Longitudinal Study (CHARLS). A total of 7534 participants without chronic lung diseases or/and asthma at the baseline and have complete follow-up information were included. Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) for developing chronic lung diseases or asthma. We also utilized generalized linear models to examine the association between arthritis and baseline peak expiratory flow (PEF). RESULTS: During 50,615 and 51,975 person-years of follow-up, 629 and 188 participants incident chronic lung diseases and asthma, respectively. Compared to those without arthritis, participants with arthritis had a higher risk of chronic lung diseases (HR = 1.54, 95%CI = 1.31-1.81, P = 1.23 × 10-7) and asthma (HR = 1.70, 95%CI = 1.27-2.28, P = 3.78 × 10-4). Arthritis subjects demonstrated significantly lower PEF than those without arthritis [ß = - 11.85 (95%CI = - 17.56, - 6.14), P = 4.81 × 10-5]. The results were stable after excluding these participates who incident chronic lung diseases or asthma in the first 1 year of follow-up. CONCLUSION: Arthritis increased the risk of pulmonary diseases among middle-aged and elderly Chinese. Early detection and treatment of pulmonary abnormalities among arthritis patients could help decrease the mortality and reduce the global burden of arthritis. Key Points • The coexistence of arthritis and pulmonary abnormalities has long been observed, but whether arthritis status can trigger pulmonary disorders is still uncertain. • Arthritis status are associated with increased risk of pulmonary diseases (chronic lung diseases/asthma) among middle-aged and elderly Chinese. • Early detection and treatment of pulmonary abnormalities among arthritis patients could help decrease the mortality and reduce the global burden of arthritis.

Identification of trehalose-6-phosphate synthase (TPS)-coding genes involved in flowering induction of Lilium× formolongi.

Lilium × formolongi, a facultative long-day (LD) plant, can complete the floral transition within one year after sowing under LD conditions. In addition to the photoperiod, the molecular mechanisms by which other flowering regulators, such as sugar, participate in juvenile development and flowering induction in L. × formolongi remain elusive. Therefore, based on the investigation of seedling development under different day length conditions, we explored the growth and nonstructural carbohydrate (NSC) contents of leaves and underground bulbs. Furthermore, the expression profiles of trehalose-6-phosphate synthase (TPS)-coding genes, LfTPSs, and miR156 were also determined. Three putative LfTPS genes, LfTPS1, LfTPS3 and LfTPS5, displayed high expression levels at the juvenile vegetative stage under different day length conditions. Among them, LfTPS1 maintained gradually elevated expression until the visible bud stage under short-day (SD) conditions. Additionally, the expression levels of LfTPS3 and LfTPS5 increased with the exogenous sucrose concentration. In contrast, the expression of miR156 rapidly decreased under the same sucrose treatments. Overexpression of LfTPS1/3/5 hastened flowering and the decline in miR156 expression levels to varying degrees in transgenic Arabidopsis. Taken together, the results demonstrate that LfTPS1, LfTPS3 and LfTPS5 modulate both juvenile vegetative development and flowering induction controlled by sugars in L. × formolongi.

Wnt7a promotes muscle regeneration in branchiomeric orbicularis oris muscle.

BACKGROUND: The orbicularis oris muscle exhibits a deficiency in cleft lip patients. Compared with the somite-derived limb muscles, the regeneration performance of the branchiomeric orofacial muscle has seldom been investigated. OBJECTIVE: This study aims to explore the possibility of augmenting the orbicularis oris muscle through the stimulus of Wnt7a. METHODS: Adult rat orbicularis oris muscle and tibialis anterior muscle were injected with recombinant human Wnt7a protein. The muscles were harvested at different time points after Wnt7a delivery. Muscle regeneration-related activity, including cell proliferation, stem cell proportion, myofiber plasticity, and total fiber number, was examined. RESULTS: Adult rat orbicularis oris muscle and tibialis anterior muscle exhibit similar regeneration-related activities after Wnt7a administration. Recombinant human Wnt7a administration resulted in enhanced cell proliferation, stem cell expansion, and fiber type remodelling in rat orbicularis oris muscle. In addition, newly formed myofibers were detected, contributing to an increased total fiber number. CONCLUSION: Wnt7a induces vigorous regeneration in rat orbicularis oris muscle. This study helps lay a foundation for developing biotherapies to combat orofacial muscle deficiency.

Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 µg/mL and ~1 µL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.

Transcriptome profiling reveals the molecular processes for survival of Lysinibacillus fusiformis strain 15-4 in petroleum environments.

A bacterial strain designated Lysinibacillus fusiformis 15-4 was isolated from oil-free soil on the Qinghai-Tibet Plateau, which can grow well utilizing petroleum hydrocarbons as a carbon source at a lower temperature. To deeply characterize the molecular adaptations and metabolic processes of this strain when grown in a petroleum-containing environment, transcriptome analysis was performed. A total of 4664 genes and the expression of 3969 genes were observed in strain 15-4. When the strain was grown in petroleum-containing medium, 2192 genes were significantly regulated, of which 1312 (60%) were upregulated and 880 (40%) were downregulated. This strain degraded and adapted to petroleum via modulation of diverse molecular processes, including improvements in transporter activity, oxidoreductase/dehydrogenase activity, two-component system/signal transduction, transcriptional regulation, fatty acid catabolism, amino acid metabolism, and environmental stress responses. Many strain-specific genes were involved in the oxidation of hydrocarbon compounds, such as several luciferase family alkane monooxygenase genes, flavin-utilizing monooxygenase family genes, and flavoprotein-like family alkanesulfonate monooxygenase genes. Several cold shock protein genes were also induced suggesting adaptation to cold environments and the potential for petroleum degradation at low temperatures. The results obtained in this study may broaden our understanding of molecular adaptation of bacteria to hydrocarbon-containing environments and may provide valuable data for further study of L. fusiformis.

The impacts of maternal separation experience and its pattern on depression and dysfunctional attitude in middle school students in rural China.

BACKGROUND: In China, because of the growth of economically driven rural-to-urban migration, there are lots of children in rural area who are separating or have separation experience with their parents. Until now, few studies focused on solely maternal separation and no research studied whether its pattern will affect children's later psychological status. AIM: The aim of this study was to determine whether early or late maternal separation affects depression and dysfunctional attitude in middle school students and what is the role of cumulative duration and meeting frequency. METHODS: Maternal separation experience was obtained by using questionnaires. We got early maternal separation group first. Then, late maternal separation and control group were obtained with the same number by matching grade, sex and family socioeconomic status. All the students in the three groups completed the scales of Children's Depression Inventory (CDI) and Dysfunctional Attitude Scale (DAS). RESULTS: Both CDI and DAS scores of early separation group are higher than the other two groups. When we split the data by sex, only females presented the same results. When cumulative duration is short, there is significant difference in both scores of CDI and DAS among the three groups, which showed the scores of early separation group are higher than the other two groups. When the cumulative duration is long, there is no significant difference among the three groups. When meeting frequency is high, there is no significant difference among the three groups. When it is low, there is significant difference among the three groups, which showed the CDI and DAS scores of early separation group are higher than the other two groups. Furthermore, the same results are also found in females. CONCLUSION: Early maternal separation may exert negative influence on student's depression and dysfunctional attitude. The sex, cumulative duration and meeting frequency may also play important roles in the effect.