Due to a labor shortage, the mechanical harvesting of tea plantations has become a focal point. However, mechanical harvest efficiency was hampered by droopy leaves, leading to a high rate of broken tea shoots and leaves. Here, we dissected the genetic structure of leaf droopiness in tea plants using genome-wide association studies (GWAS) on 146 accessions, combined with transcriptome from two accessions with contrasting droopy leaf phenotypes. A set of 16 quantitative trait loci (QTLs) containing 54 SNPs and 34 corresponding candidate genes associated with droopiness were then identified. Among these, CsEXL3 (EXORDIUM-LIKE 3) from Chromosome 1 emerged as a candidate gene. Further investigations revealed that silencing CsEXL3 in tea plants resulted in weaker vascular cell malformation and brassinosteroid-induced leaf droopiness. Additionally, brassinosteroid signal factor CsBES1.2 was proved to participate in CsEXL3-induced droopiness and vascular cell malformation via using the CsBES1.2-silencing tea plant. Notably, CsBES1.2 bound on the E-box of CsEXL3 promoter to transcriptionally activate CsEXL3 expression as CUT&TAG based ChIP-qPCR and ChIP-seq suggested in vivo as well as EMSA and Y1H indicated in vitro. Furthermore, CsEXL3 instead of CsBES1.2 decreased lignin content and the expressing levels of lignin biosynthesis genes. Overall, our findings suggest that CsEXL3 regulates droopy leaves, partially through the transcriptional activation of CsBES1.2, with the potential to improve mechanical harvest efficiency in tea plantations.
OBJECTIVE: This article focused on the correlation between the changes of serum total Immunoglobulin E (IgE) and Fractional exhaled Nitric Oxide (FeNO) and idiosyncratic reactions in children with bronchiolitis. METHODS: One hundred children with bronchiolitis and fifty healthy children were enrolled. Serum total IgE and FeNO were assessed, and the diagnostic value for bronchiolitis and the correlation with the severity of bronchiolitis were analyzed. Bronchiolitis children were divided into idiosyncratic + bronchiolitis and non-idiosyncratic + bronchiolitis groups, the relationship between serum total IgE and FeNO and idiosyncratic reaction was determined, and the diagnostic value of serum total IgE and FeNO for idiosyncratic bronchiolitis was examined. RESULTS: FeNO in bronchiolitis children was lower than that in healthy children but there was no significant difference in serum total IgE levels between the two populations. Serum total IgE increased while FeNO decreased with the aggravation of bronchiolitis in bronchiolitis children. The serum total IgE was positively correlated while FeNO was negatively correlated with the severity of bronchiolitis. Serum total IgE was higher in children with idiosyncratic bronchiolitis, but serum total IgE and FeNO were not the risk factors for idiosyncratic bronchiolitis; Area Under the Curve (AUC) of serum total IgE and FeNO for the diagnosis of idiosyncratic bronchiolitis was less than 0.7. CONCLUSION: Serum total IgE and FeNO in children with bronchiolitis are related to disease severity and idiosyncratic reaction. FeNO has a diagnostic value for bronchiolitis, but not for idiosyncratic bronchiolitis.
Introduction: In recent decades, widespread multi-drug resistant (MDR) bacteria have become a serious problem in healthcare facilities. Methods: To systematically summarize and investigate the prevalence and genomic features of clinical MDR Acinetobacter baumannii (A. baumannii) clinical isolates recovered from the first hospital of Lanzhou University, we collected 50 MDR A. baumannii isolates isolated in the first quarter of 2022 and using whole-genome sequencing investigate the genotypic characteristics. Results: All of these isolates were generally resistant to the common ß-lactamase antibiotics. Resistance to cefoperazone-sulbactam varies greatly between different clones. The proportion of CC208 isolates resistant and mediated to cefoperazone-sulbactam is as high as 84.6%. There were no isolates resistant to tigecycline and colistin. The presence of blaOXA - 23 (94.0%) and blaOXA - 66 (98.0%) were the most frequent determinants for carbapenem resistance. Two main endemic clones were identified, one (ST469oxf) was predominantly circulating in ICUs and carried the same resistance genes, virulence genes and transposons, and the other clone (CC208) carried more resistance genes and had more widely disseminated. Discussion: Our study showed that clinical MDR A. baumannii isolates circulating in our hospital exhibited highly similar genetic features. We should take timely and effective measures to control the further epidemic of these isolates.
Our previous studies found that Sea Buckthorn polyphenols (SBP) extract inhibits fatty acid synthase (FAS) in vitro. Thus, we continued to explore possible effects and underlying mechanisms of SBP on complicated metabolic disorders in long-term high-fat-diet (HFD)-fed mice. To reveal that, an integrated approach was developed in this study. Targeted quantitative lipidomics with a total of 904 unique lipids mapping contributes to profiling the comprehensive features of disarranged hepatic lipid homeostasis and discovering a set of newfound lipid-based biomarkers to predict the occurrence and indicate the progression of metabolic disorders beyond current indicators. On the other hand, technologies of intermolecular interactions characterization, especially surface plasmon resonance (SPR) assay, contribute to recognizing targeted bioactive constituents present in SBP. Our findings highlight hepatic lipid homeostasis maintenance and constituent-FAS enzyme interactions, to provide new insights that SBP as a functional food alleviates HFD-induced metabolic disorders in mice via reprograming hepatic lipid homeostasis caused by targeting FAS, owing to four polyphenols directly interacting with FAS and cinaroside binding to FAS with good affinity.
Hippophae , Metabolic Diseases , Mice , Animals , Polyphenols/metabolism , Liver/metabolism , Diet, High-Fat/adverse effects , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Lipids/pharmacology , Metabolic Diseases/metabolism , Homeostasis , Mice, Inbred C57BL , Lipid Metabolism
Edwardsiella piscicida, a significant intracellular pathogen, is widely distributed in aquatic environments and causes systemic infection in various species. Therefore, it's essential to develop a rapid, uncomplicated and sensitive method for detection of E. piscicida in order to control the transmission of this pathogen effectively. The recombinase-aided amplification (RAA) assay is a newly developed, rapid detection method that has been utilized for various pathogens. In the present study, a real-time RAA (RT-RAA) assay, targeting the conserved positions of the EvpP gene, was successfully established for the detection of E. piscicida. This assay can be performed in a one-step single tube reaction at a temperature of 39°C within 20 min. The RT-RAA assay exhibited a sensitivity of 42 copies per reaction at a 95% probability, which was comparable to the sensitivity of real-time quantitative PCR (qPCR) assay. The specificity assay confirmed that the RT-RAA assay specifically targeted E. piscicida without any cross-reactivity with other important marine bacterial pathogens. Moreover, when clinical specimens were utilized, a perfect agreement of 100% was achieved between the RT-RAA and qPCR assays, resulting a kappa value of 1. These findings indicated that the established RT-RAA assay provided a viable alternative for the rapid, sensitive, and specific detection of E. piscicida.
Edwardsiella , Recombinases , Nucleic Acid Amplification Techniques/methods , Edwardsiella/genetics , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive system that poses a significant threat to human life and health. It is crucial to thoroughly investigate the mechanisms of esophageal carcinogenesis and identify potential key molecular events in its carcinogenesis. Single-cell transcriptome sequencing is an emerging technology that has gained prominence in recent years for studying molecular mechanisms, which may help to further explore the underlying mechanisms of the ESCC tumor microenvironment in depth. The single-cell dataset was obtained from GSE160269 in the Gene Expression Omnibus database, including 60 tumor samples and four paracancer samples. The single-cell data underwent dimensional reduction clustering analysis to identify clusters and annotate expression profiles. Subcluster analysis was conducted for each cellular taxon. Copy number variation analysis of tumor cell subpopulations was performed to primarily identify malignant cells within them. A proposed chronological analysis was performed to obtain the process of cell differentiation. In addition, cell communication, transcription factor analysis, and tumor pathway analysis were also performed. Relevant risk models and key genes were established by univariate COX regression and LASSO analysis. The key genes obtained from the screen were subjected to appropriate silencing and cellular assays, including CCK-8, 5-ethynyl-2'-deoxyuridine, colony formation, and western blot. Single-cell analysis revealed that normal samples contained a large number of fibroblasts, T cells, and B cells, with fewer other cell types, whereas tumor samples exhibited a relatively balanced distribution of cell types. Subclassification analysis of immune cells, fibroblasts, endothelial cells, and epithelial cells revealed their specific spatial characteristics. The prognostic risk model, we constructed successfully, achieved accurate prognostic stratification for ESCC patients. The screened key gene, UPF3A, was found to be significantly associated with the development of ESCC by cellular assays. This process might be linked to the phosphorylation of ERK and P38. Single-cell transcriptome analysis successfully revealed the distribution of cell types and major expressed factors in ESCC patients, which could facilitate future in-depth studies on the therapeutic mechanisms of ESCC.
BACKGROUND: Bronchial asthma is closely related to the occurrence of attention-deficit hyperactivity disorder (ADHD) in children, which can easily have adverse effects on children's learning and social interactions. Studies have shown that childhood asthma can increase the risk of ADHD and the core symptoms of ADHD. Compared with children with ADHD alone, children with asthma and ADHD are more likely to show high levels of hyperactivity, hyperactive-impulsive and other externalizing behaviors and anxiety in clinical practice and have more symptoms of somatization and emotional internalization. AIM: To explore the relationship between ADHD in children and bronchial asthma and to analyze its influencing factors. METHODS: This retrospective cohort study was conducted at Dongying People's Hospital from September 2018 to August 2023. Children diagnosed with ADHD at this hospital were selected as the ADHD group, while healthy children without ADHD who underwent physical examinations during the same period served as the control group. Clinical and parental data were collected for all participating children, and multivariate logistic regression analysis was employed to identify risk factors for comorbid asthma in children with ADHD. RESULTS: Significant differences were detected between the ADHD group and the control group in terms of family history of asthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergy medications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationship status (P < 0.05). Out of the 183 children in the ADHD group, 25 had comorbid asthma, resulting in a comorbidity rate of 13.66% (25/183), compared to the comorbidity rate of 2.91% (16/549) among the 549 children in the control group. The difference in the asthma comorbidity rate between the two groups was statistically significant (P < 0.05). The results of the multivariate logistic regression analysis indicated that family history of asthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergy medications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationship status are independent risk factors increasing the risk of comorbid asthma in children with ADHD (P < 0.05). CONCLUSION: Children with ADHD were more likely to have comorbid asthma than healthy control children were. A family history of asthma, adverse maternal factors during pregnancy, and parental relationship status were identified as risk factors influencing the comorbidity of asthma in children with ADHD. Clinically, targeted interventions based on these factors can be implemented to reduce the risk of comorbid asthma. This information is relevant for results sections of abstracts in scientific articles.
Metallic wood combines the unique structural benefits of wood and the properties of metals and is thus promising for applications ranging from heat transfer to electromagnetic shielding to energy conversion. However, achieving metallic wood with full use of wood structural benefits such as anisotropy and multiscale porosity is challenging. A key reason is the limited mass transfer in bulk wood where fibers have closed ends. In this work, programmed removal of cell-wall components (delignification and hemicellulose extraction) was introduced to improve the accessibility of cell walls and mass diffusion in wood. Subsequent low-temperature electroless Cu plating resulted in a uniform continuous Cu coating on the cell wall, and, furthermore, Cu nanoparticles (NPs) insertion into the wood cell wall. A novel Cu NPs-embedded multilayered cell-wall structure was created. The unique structure benefits compressible metal-composite foam, appealing for stress sensors, where the multilayered cell wall contributes to the compressibility and stability. The technology developed for wood metallization here could be transferred to other functionalizations aimed at reaching fine structure in bulk wood.
Background: Epidemiology has demonstrated that plasma free fatty acids (FFAs) can prevent the development of cancer. Our study sought to evaluate the relationship between plasma (FFA) levels and cervical cancer. Methods: In recent years, metabolomics-based approaches have been recognized as an emerging tool, so we examined the plasma FFA profiles of 114 patients with cervical cancer and 151 healthy people using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results: The data results were analyzed by multifactorial binary logistic regression analysis, and it was found that palmitic acid, docosahexaenoic acid (DHA), and total ω-3 fatty acids were negatively correlated with the risk of cervical cancer; whereas tetracosanoic acid was positively correlated with the risk of cervical cancer (OR, 1.026; 95% CI, 1.013-1.040; p < 0.001). Dynamic follow-up of 40 cervical cancer patients who successfully completed CCRT revealed that most fatty acid levels tended to increase after the end of treatment, except for palmitic and stearic acid levels, which were lower than before treatment. Conclusion: Plasma FFA profiles were altered in cervical cancer patients, which may be related to abnormal fatty acid metabolism in cervical cancer. The described changes in fatty acid profiles during CCRT may be related to the good functioning of CCRT. Further studies on plasma FFA composition and its changes due to CCRT in patients with cervical cancer are warranted.
Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.
Brain Neoplasms , Glioblastoma , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Oncolytic Viruses/genetics , Glioblastoma/genetics , Glioblastoma/therapy , CD8-Positive T-Lymphocytes , Brain Neoplasms/genetics , Brain Neoplasms/therapy
Phase-sensitive measurements on a composite ring made of a superconductor of interest connected by a known singlet s-wave superconductor can unambiguously determine its pairing symmetry. In composite rings with epitaxial ß-Bi_{2}Pd and s-wave Nb, we have observed half-integer-quantum flux when Nb is connected to the opposite crystalline ends of ß-Bi_{2}Pd and integer-quantum flux when Nb is connected to the same crystalline ends of ß-Bi_{2}Pd. With ascending temperature, the half-integer-flux quantization transits to integer-flux quantization, before the eventual loss of phase coherence. These findings point to odd-parity pairing symmetry in superconducting ß-Bi_{2}Pd.
BACKGROUND: The growing demand for electrophysiology (EP) treatment in China presents a challenge for current EP care delivery systems. This study constructed a discrete event simulation (DES) model of an inpatient EP care delivery process, simulating a generalized inpatient journey of EP patients from admission to discharge in the cardiology department of a tertiary hospital in China. The model shows how many more patients the system can serve under different resource constraints by optimizing various phases of the care delivery process. METHODS: Model inputs were based on and validated using real-world data, simulating the scheduling of limited resources among competing demands from different patient types. The patient stay consists of three stages, namely: the pre-operative stay, the EP procedure, and the post-operative stay. The model outcome was the total number of discharges during the simulation period. The scenario analysis presented in this paper covers two capacity-limiting scenarios (CLS): (1) fully occupied ward beds and (2) fully occupied electrophysiology laboratories (EP labs). Within each CLS, we investigated potential throughput when the length of stay or operative time was reduced by 10%, 20%, and 30%. The reductions were applied to patients with atrial fibrillation, the most common indication accounting for almost 30% of patients. RESULTS: Model validation showed simulation results approximated actual data (137.2 discharges calculated vs. 137 observed). With fully occupied wards, reducing pre- and/or post-operative stay time resulted in a 1-7% increased throughput. With fully occupied EP labs, reduced operative time increased throughput by 3-12%. CONCLUSIONS: Model validation and scenario analyses demonstrated that the DES model reliably reflects the EP care delivery process. Simulations identified which phases of the process should be optimized under different resource constraints, and the expected increases in patients served.
Atrial Fibrillation , Humans , Computer Simulation , Tertiary Care Centers , Electrophysiology , China
Nitrogen fertilizer can affect the seed quality of mung bean. However, the effects of nitrogen fertilizer on the properties of mung bean protein (MBP) remain unclear. We investigated the effects of four nitrogen fertilization levels on the physicochemical, structural, functional, thermal, and rheological properties of MBP. The results showed that the amino acid and protein contents of mung bean flour were maximized under 90 kg ha-1 of applied nitrogen treatment. Nitrogen fertilization can alter the secondary and tertiary structure of MBP. The main manifestations are an increase in the proportion of ß-sheet, the exposure of more chromophores and hydrophobic groups, and the formation of loose porous aggregates. These changes improved the solubility, oil absorption capacity, emulsion activity, and foaming stability of MBP. Meanwhile, Thermodynamic and rheological analyses showed that the thermal stability, apparent viscosity, and gel elasticity of MBP were all increased under nitrogen fertilizer treatment. Correlation analysis showed that protein properties are closely related to changes in structure. In conclusion, nitrogen fertilization can improve the protein properties of MBP by modulating the structure of protein molecules. This study provides a theoretical basis for the optimization of mung bean cultivation and the further development of high-quality mung bean protein foods.
Fabaceae , Vigna , Vigna/chemistry , Fertilizers , Nitrogen/pharmacology , Fabaceae/chemistry , Amino Acids
Subcutaneous (s.c.) administration of monoclonal antibodies (mAbs) can reduce treatment burden for patients and healthcare systems compared with intravenous (i.v.) infusion through shorter administration times, made possible by convenient, patient-centric devices. A deeper understanding of clinical pharmacology principles related to efficacy and safety of s.c.-administered mAbs over the past decade has streamlined s.c. product development. This review presents learnings from key constituents of the s.c. mAb development pathway, including pharmacology, administration variables, immunogenicity, and delivery devices. Restricted mAb transportation through the hypodermis explains their incomplete absorption at a relatively slow rate (pharmacokinetic (PK)) and may impact mAb-cellular interactions and/or onset and magnitude of physiological responses (pharmacodynamic). Injection volumes, formulation, rate and site of injection, and needle attributes may affect PKs and the occurrence/severity of adverse events like injection-site reactions or pain, with important consequences for treatment adherence. A review of immunogenicity data for numerous compounds reveals that incidence of anti-drug antibodies (ADAs) is generally comparable across i.v. and s.c. routes, and complementary factors including response magnitude (ADA titer), persistence over time, and neutralizing antibody presence are needed to assess clinical impact. Finally, four case studies showcase how s.c. biologics have been clinically developed: (i) by implementation of i.v./s.c. bridging strategies to streamline PD-1/PD-L1 inhibitor development, (ii) through co-development with i.v. presentations for anti-severe acute respiratory syndrome-coronavirus 2 antibodies to support rapid deployment of both formulations, (iii) as the lead route for bispecific T cell engagers (BTCEs) to mitigate BTCE-mediated cytokine release syndrome, and (iv) for pediatric patients in the case of dupilumab.
Antibodies, Monoclonal , Subcutaneous Tissue , Humans , Child , Antibodies, Monoclonal/adverse effects , Antibodies, Neutralizing , Administration, Intravenous
Lipid monitoring plays a crucial role in biomedical research, particularly in the areas of cardiovascular health, metabolic disorders and nutrition. However, direct and highly sensitive detection of lipids poses significant challenges due to the interference of high SERS background noise in lipid samples. In this study, we present a SERS platform for the quantitative analysis of lipids. By harnessing the Surface Plasmon Resonance (SPR) effect of nanostructured grooves and leveraging deuterium oxide, a remarkable enhancement of in-situ Raman signals originating from cholesterol is achieved. This approach yielded an impressive average enhancement factor of 7.3 × 105 and a detection limit of 1.9 × 10-4 mg/mL, highlighting the exceptional sensitivity and precision of our method. We have obtained high quality, in-situ SERS signals for six distinct lipid molecules. Rapid identification of lipid samples in mixed systems has been achieved through the combination of characteristic peak analysis and PCA-LDA, including the detection of SERS signals from lipids in milk. Notably, univariate monitoring of in-situ cholesterol in human serum was successfully achieved for the first time using deuterium water as an internal standard. In addition, silver substrate demonstrated outstanding reproducibility, maintaining consistent SERS activity even after more than 10 repetitions. Therefore, this platform offers the distinct advantages of high sensitivity, specificity and cost-effectiveness for lipid detection. These findings enable dietary management and blood lipid monitoring, and therefore hold crucial implications for the early prevention of lipid-related disorders and diseases.
Metal Nanoparticles , Surface Plasmon Resonance , Humans , Surface Plasmon Resonance/methods , Silver/chemistry , Reproducibility of Results , Spectrum Analysis, Raman/methods , Metal Nanoparticles/chemistry , Lipids , Cholesterol
BACKGROUND: Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug's safety profile and effectiveness. AIM: To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS: A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS: A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION: The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.
Ferroptosis and cuproptosis are both novel types of cell death. Long noncoding RNAs (lncRNAs) are associated with multiple cancers. Notably, bioinformatics study of ferroptosis- and cuproptosis-related lncRNAs (FCLs) in lung adenocarcinoma (LUAD) has not been elucidated. In this study, we used univariate Cox, multivariate Cox, and least absolute shrinkage and selection operator Cox (LASSO-Cox) analyses to screen three FCLs, namely AC079193.2, AC090559.1, and AL512363.1. We then showed that these three FCLs were tumor-specific and correlated with ferroptosis and cuproptosis using qRT-PCR. Next, a prognostic risk model consisting of high- and low-risk cohorts was successfully constructed based on The Cancer Genome Atlas-LUAD data. The high-risk group consistently demonstrated poor prognosis. The accuracy of the model was evaluated using AUC, C-index curves, and nomograms. Furthermore, KEGG and GO analysis with R software showed significant enrichment in immune functions and metabolic pathways. Hereto, the immune function and immune cell expression results were more pronounced in the low-risk versus high-risk group. In conclusion, the prognostic risk model comprised of three FCLs effectively predicted patient outcomes and is associated with the immune microenvironment in LUAD.
Understanding human disease on a molecular level, and translating this understanding into targeted diagnostics and therapies are central tenets of molecular medicine1. Realizing this doctrine requires an efficient adaptation of molecular discoveries into the clinic. We present an approach to facilitate this process by describing the Imageable Genome, the part of the human genome whose expression can be assessed via molecular imaging. Using a deep learning-based hybrid human-AI pipeline, we bridge individual genes and their relevance in human diseases with specific molecular imaging methods. Cross-referencing the Imageable Genome with RNA-seq data from over 60,000 individuals reveals diagnostic, prognostic and predictive imageable genes for a wide variety of major human diseases. Having both the critical size and focus to be altered in its expression during the development and progression of any human disease, the Imageable Genome will generate new imaging tools that improve the understanding, diagnosis and management of human diseases.
Diagnostic Imaging , Genome , Humans
Background: Conducting an up-to-date analysis on the genomic diversity and evolution patterns of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for elucidating the underlying mechanisms of its emergency and pathogenicity, as well as assessing the extent of its threat to public health. Methods: Complete genome sequences of SFTSV were obtained from GenBank until December 19, 2022. A thorough phylogenetic analysis was conducted using comprehensive bioinformatics methods to estimate the genomic diversity and evolution. Results: The phylogenetic classification of SFTSV strains yielded seven lineages (A-G) for each genome segment. SFTSV displayed notable variations in evolutionary patterns among different regions and segments, without a linear accumulation of nucleotide substitutions within segments and regions. The comprehensive analysis revealed 54 recombination events and 17 reassortment strains, including the first discovery of recombination events involving sea-crossing and species-crossing. Selection analysis identified three positive sites (2, 671, 1353) in RNA-dependent RNA polymerase, three positive sites (22, 298, 404) in glycoprotein, and two positive sites (9, 289) in nonstructural protein. No positive selection sites were found in nucleoprotein. Conclusion: Our study unveiled the existence of multiple evolutionary forces influencing SFTSV, contributing to its increasing genetic diversity, which had the potential to modify its antigenicity and pathogenicity. Furthermore, our study highlights the importance of tracking the spread of SFTSV across regions and species.
