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Abstract Background Treacher Collins syndrome (TCS, MIM #154500), a severe congenital disorder, predominantly involves dysplasia of craniofacial bones and is characterized by features such as downslanting palpebral fissures, lower eyelid colobomas, microtia, and other craniofacial anomalies. Despite its clinical importance, the underlying pathogenic mutations in TCS remain largely uncharacterized, representing a critical knowledge gap for researchers in the field. Results To address this, we performed mutation screening on a familial TCS case (trio) and 11 sporadic cases from a Chinese population. We identified 11 mutations predominantly localized to the central repeat domain (CRD) and the C-terminal domain (CTD, including the nuclear localization sequence) of TCOF1. The de novo frameshift mutation identified in the trio led to TCOF1 truncation, disrupting the central repeat domain crucial for binding transcriptional factors. Immunoprecipitation assays revealed that this pathogenic mutation attenuates the interaction between TCOF1 and transcription-related proteins, such as Pol II. Furthermore, cellular luciferase assays demonstrated that the mutation compromises the nuclear localization capability of TCOF1. Conclusions Our findings establish TCOF1 as the primary pathogenic gene in this Chinese TCS cohort, with mutations predominantly in the CRD and CTD, thereby expanding the known mutation spectrum of TCS and informing its prevention strategies.

Abstract Genetic alterations play a pivotal role in leukemic clonal transformation, significantly influencing disease pathogenesis and clinical outcomes. Here, we report a novel fusion gene and investigate its pathogenic role in acute lymphoblastic leukemia (ALL). We engineer a transposon transfection system expressing the TOP2B::AFF2 transcript and introduce it into Ba/F3 cells. Functional studies, including proliferation, cell cycle, and apoptosis assays, were conducted to assess the fusion gene’s impact. In vitro assays reveal that the TOP2B::AFF2 fusion significantly enhances Ba/F3 cell proliferation and G1/S phase transition while suppressing differentiation and apoptosis. This study identifies TOP2B::AFF2 as a potential oncogenic driver. However, further validation through in vivo studies are warranted to fully elucidate the fusion gene’s role in leukemogenesis.

Abstract Urinary proteomics is emerging as a potent tool for detecting sensitive and non-invasive biomarkers. At present, the comparability of urinary proteomics data across diverse liquid chromatography−mass spectrometry (LC-MS) platforms remains an area that requires investigation. In this study, we conduct a comprehensive evaluation of urinary proteome across multiple LC-MS platforms. To systematically analyze and assess the quality of large-scale urinary proteomics data, we develop a comprehensive quality control (QC) system named MSCohort, which extracted 81 metrics for individual experiment and the whole cohort quality evaluation. Additionally, we present a standard operating procedure (SOP) for high-throughput urinary proteome analysis based on MSCohort QC system. Our study involves 20 LC-MS platforms and reveals that, when combined with a comprehensive QC system and a unified SOP, the data generated by data-independent acquisition (DIA) workflow in urine QC samples exhibit high robustness, sensitivity, and reproducibility across multiple LC-MS platforms. Furthermore, we apply this SOP to hybrid benchmarking samples and clinical colorectal cancer (CRC) urinary proteome including 527 experiments. Across three different LC-MS platforms, the analyses report high quantitative reproducibility and consistent disease patterns. This work lays the groundwork for large-scale clinical urinary proteomics studies spanning multiple platforms, paving the way for precision medicine research.

Abstract Neuroinflammation is a key factor in the pathogenesis of Parkinson’s disease (PD). Activated microglia in the central nervous system (CNS) and infiltration of peripheral immune cells contribute to dopaminergic neuron loss. However, the role of peripheral immune responses, particularly triggering receptor expressed on myeloid cells-1 (TREM-1), in PD remains unclear. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD mouse model, we examined TREM-1 expression and monocyte infiltration in the substantia nigra pars compacta (SNpc). We found that MPTP increased peripheral monocytes, and deletion of peripheral monocytes protected against MPTP neurotoxicity in the SNpc. TREM-1 inhibition, both genetically and pharmacologically, reduced monocyte infiltration, alleviated neuroinflammation, and preserved dopaminergic neurons, resulting in improved motor function. Furthermore, adoptive transfer of TREM-1-expressing monocytes from PD model mice to naive mice induced neuronal damage and motor deficits. These results underscore the critical role of peripheral monocytes and TREM-1 in PD progression, suggesting that targeting TREM-1 could be a promising therapeutic approach to prevent dopaminergic neurodegeneration and motor dysfunction in PD. Schematic diagram of monocyte TREM-1-mediated dopaminergic neuron damage. The figure illustrates that in experimental MPTP-induced PD model mice, the number of inflammatory monocytes in the peripheral blood increases, after which the monocytes infiltrate the CNS through the Blood-Brain Barrier(BBB). These infiltrating monocytes increase the release of inflammatory cytokines and eventually cause neuronal injury. TREM-1 gene deletion and pharmacological blockade limit inflammatory monocyte recruitment into the SNpc and ameliorate neuroinflammatory events and the loss of dopaminergic neurons.

Abstract Deep phenotyping can enhance the power of genetic analysis, including genome-wide association studies (GWAS), but the occurrence of missing phenotypes compromises the potential of such resources. Although many phenotypic imputation methods have been developed, the accurate imputation of millions of individuals remains challenging. In the present study, we have developed a multi-phenotype imputation method based on mixed fast random forest (PIXANT) by leveraging efficient machine learning (ML)-based algorithms. We demonstrate by extensive simulations that PIXANT is reliable, robust and highly resource-efficient. We then apply PIXANT to the UKB data of 277,301 unrelated White British citizens and 425 traits, and GWAS is subsequently performed on the imputed phenotypes, 18.4% more GWAS loci are identified than before imputation (8710 vs 7355). The increased statistical power of GWAS identified some additional candidate genes affecting heart rate, such as RNF220, SCN10A, and RGS6, suggesting that the use of imputed phenotype data from a large cohort may lead to the discovery of additional candidate genes for complex traits.

Abstract Uterine Corpus Endometrial Carcinoma (UCEC) represents a common malignant neoplasm in women, with its prognosis being intricately associated with available therapeutic interventions. In the past few decades, there has been a burgeoning interest in the role of mitochondria within the context of UCEC. Nevertheless, the development and application of prognostic models predicated on mitochondrial-related genes (MRGs) in UCEC remains in the exploratory stages. This study utilized RNA sequencing data and clinical information from the TCGA database to identify differentially expressed MRGs (DEMRGs) between UCEC and normal groups that are associated with overall survival (OS). Patients were randomly assigned to training and testing cohorts in a 1:1 ratio. In the training cohort, a risk model based on DEMRGs was developed using Lasso Cox regression analysis. Subsequently, patients in both cohorts were stratified into high-risk and low-risk groups based on their median risk scores. The prognostic performance of the model was validated through Kaplan-Meier survival analysis, ROC curves, and nomograms. Additionally, further analyses including functional enrichment, immune landscape assessment, prediction of response to ICB therapy, mutation profiling, and drug sensitivity analysis elucidated biological distinctions between the identified risk groups. We established a risk model incorporating eight MRGs. Patients classified within he high-risk group exhibited significantly poorer prognoses relative to those in the low-risk group. Functional enrichment analysis identified substantial differences in biological processes and signaling pathways between the high-risk and low-risk cohorts. Immune landscape analysis showed that patients with elevated risk scores exhibited significant immunosuppressive and immune evasion mechanisms. Conversely, low-risk patients exhibited higher expression of human leukocyte antigen (HLA) family members and immune checkpoint genes (ICGs) compared to their high-risk counterparts.Consequently, low-risk patients showed greater responsiveness to immunotherapy and potential small molecule drugs, whereas high-risk patients were more susceptible to chemotherapy. The mitochondrial-related risk model formulated in this study demonstrates efficacy in predicting both prognosis and response to immunotherapy in patients with UCEC, thereby providing a scientific basis for personalized treatment strategies. Future research endeavors should focus on further validating the clinical utility of this model and investigate the specific mechanisms of the identified MRGs in UCEC.

Abstract The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is an intronic G4C2 repeat expansion in C9orf72. The repeats undergo bidirectional transcription to produce sense and antisense repeat RNA species, which are translated into dipeptide repeat proteins (DPRs). As toxicity has been associated with both sense and antisense repeat-derived RNA and DPRs, targeting both strands may provide the most effective therapeutic strategy. CRISPR-Cas13 systems mature their own guide arrays, allowing targeting of multiple RNA species from a single construct. We show CRISPR-Cas13d variant CasRx effectively reduces overexpressed C9orf72 sense and antisense repeat transcripts and DPRs in HEK cells. In C9orf72 patient-derived iPSC-neuron lines, CRISPR-CasRx reduces endogenous sense and antisense repeat RNAs and DPRs and protects against glutamate-induced excitotoxicity. AAV delivery of CRISPR-CasRx to two distinct C9orf72 repeat mouse models significantly reduced both sense and antisense repeat-containing transcripts. This highlights the potential of RNA-targeting CRISPR systems as therapeutics for C9orf72 ALS/FTD.

Abstract The molecular mechanism underlying the role of hippocampal hilar interneuron degeneration in temporal lobe epilepsy (TLE) remains unclear. Especially, very few studies have focused on the role of neuronal nitric oxide synthase (nNOS, encoded by Nos1) containing hilar interneurons in TLE. In the present study, Nos1 conditional knockout mice were constructed, and we found that selective deletion of Nos1 in hilar interneurons rather than dentate granular cells (DGCs) triggered epileptogenesis. The level of nNOS was downregulated in patients and mice with TLE. Nos1 deletion led to excessive epilepsy-like excitatory input circuit formation and hyperexcitation of DGCs. Replenishment of hilar nNOS protein blocked epileptogenic development and memory impairment in pilocarpine-induced TLE mice. Moreover, chronic treatment with DETA/NONOate, a slowly released exogenous nitric oxide (NO) donor, prevented aberrant neural circuits of DGCs and the consequent epileptogenesis without acute antiseizure effects. Therefore, we concluded that NO donor therapy may be a novel anti-epileptogenesis strategy, different from existing antiseizure medications (ASMs), for curing TLE.

Abstract Background Stroke ranks as the second leading cause of death worldwide. Meanwhile, headaches are considered the second leading cause of disability, and they often occur as a stroke complication. However, insufficient attention has been given to the treatment and rehabilitation of headaches among stroke patients, and the research on the epidemiology and risk factors of headaches in stroke patients in China is limited. Therefore, in this study, China Health and Retirement Longitudinal Study (CHARLS) data were utilized for a cross-sectional analysis to estimate the prevalence of headaches in stroke patients and identify the associated risk factors. Method This study utilized data, which included those of participants aged 45 and above from 28 provinces across China, from the nationally representative CHARLS 2018 database. A total of 876 stroke patients and 17,469 nonstroke patients were considered in this work. Stroke diagnosis and headache status were determined based on self-reported questionnaire responses. Cross-sectional analysis determined the prevalence of headaches in patients with strokes and those without through quantification of individuals diagnosed with headaches. Categorical variables were presented as percentages and counts, and univariate and multivariate logistic regression models were used to calculate the odds ratios (OR) for the risk factors associated with headaches in stroke patients. Results In the 2018 data, 328 individuals with stroke-related headaches were screened and compared with 4,249 individuals without the condition. Overall, a cross-sectional survey revealed that the headache prevalence among stroke patients reached 37.44% (95% confidence interval (CI): 34.23%-40.74%), which was higher than the overall headache prevalence among nonstroke patients 24.32% (95% CI: 23.69%-24.97%). Headaches were considerably more common in women (45.95%; 95% CI: 41.31%-50.58%) than in men (26.70%; 95% CI: 24.44%-32.97%; gender difference, p

Abstract Objective This study aims to assess the significance of monitoring temperature change trends at various wound sites in the healing process of diabetic foot ulcers after microcirculation reconstruction surgery. Methods A retrospective analysis was conducted on individuals with diabetic foot ulcers who had been admitted to the Department of Orthopedics at the Second Hospital of Shanxi Medical University between July 2020 and February 2022. Temperature changes were regularly monitored at the center of the wound and the distal tibia of the ipsilateral lower leg to assess microcirculatory blood perfusion. Wound, ischemia, and foot infection (WIFi) grading was performed at admission and the final follow-up was to determine the value of temperature monitoring at various sites. Additionally, the formation of collateral microarterial vessels was monitored to determine their consistency with the observed trends in temperature differences. Follow-up assessments included the recurrence of ulcers, development of ulcers at different locations, re-amputation of the toe or limb, and diabetes-related mortality. Results A total of 29 patients were included in the follow-up, with an average age of 57.14 ± 14.75 years and a follow-up period of 9.79 ± 4.13 months. Following microcirculation reconstruction surgery, as the microvascular network formed, the temperature difference between the center of the wound and the distal tibia on the same side gradually decreased, with no statistical difference observed at 4 weeks postoperatively. At both admission and the final follow-up, there was a significant reduction in the wound (W) and ischemia (I) grades within the WIFi classification. The temperature at the wound center showed progressive improvement as collateral microarterial vessels developed. During the follow-up period, there were 2 cases of ulcer recurrence, 1 case of an ulcer appearing at a different location, no cases of re-amputation of the toe or limb, and 2 diabetes-related fatalities. Conclusion Skin temperature monitoring offers a direct and reliable indication of microcirculatory blood perfusion. Its simplicity and cost-effectiveness make it a valuable tool for widespread use in evaluating wound healing following microcirculation reconstruction surgery.

In present study, the mitogenome of Rosa laevigata was assembled and characterized, with a total length of 281,693 bp and a GC content of 45.4%. The genome encompasses 53 genes, including 32 protein-coding genes, 3 rRNA genes and 18 tRNA genes. Furthermore, 19 MTPTs were identified, ranging from 48 to 1585 bp, covering 3.1% (8764 bp) of the mitogenome. Phylogenetic analysis of 34 Rosaceae species based on 21 common conserved protein-coding genes detected the monophyly of Rosa, with R. laevigata and R. chinensis forming a sister clade to R. rugosa. The mitogenome provides valuable genetic resources for R. laevigata utilization and for further phylogeny reconstruction of Rosa and Rosaceae.

A new species from China, Elymus multiramosus Y.C. Zhang, sp. nov. is described and illustrated herein, based on morphological characters and molecular phylogenetic analysis. The taxonomic descriptions of E. multiramosus and the comparison with related species are presented. The taxonomic distinctiveness of this new species was inferred by Maximum Likelihood (ML) analysis and Bayesian phylogenetic analysis, based on the complete chloroplast genome sequence. It is assigned to the Elymus section and bears similarity to Elymus nutans Griseb. However, it can be easily distinguished from other species by its compound spike, in contrast to the simple spike inflorescence typical of those species. The compound spike is characterised by rhachillas that are extended at the base of the main axis, giving rise to 3–6 mini-spike-like branches. Notably, these branches significantly increase in length from the top towards the bottom of the compound spike. In the molecular phylogeny, Elymus multiramosus from Qinghai, north-western China, is phylogenetically positioned as a distinct lineage. The lineage comprising Elymus sinosubmuticus from Sichuan, east of the Tibetan Plateau and Elymus nutans from the Himalayas forms a sister group to Elymus multiramosus, suggesting that these three species share a common ancestor that is distinct from the lineage leading to Elymus atratus from Gansu, north of the Tibetan Plateau.

Purpose: Low back pain (LBP) has a significant impact on the general population, especially on military personnel. This study aimed to systematically review the relevant literature to determine the prevalence and risk factors of low back pain among military personnel from different military occupational categories. Methods: For this systematic review, we searched Embase, PubMed, and Cochrane. We performed study selection, data extraction, and assessed the quality of the evidence using the adapted risk of bias assessment tool by Hoy et al. This review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This study is registered on the Center for Open Science, registration DOI: 10.17605/OSF.IO/HRGE8. Results: Out of 860 papers, 19 studies met the inclusion criteria. More than 360 000 military people with lumbar pain situation were considered for inclusion in this systematic review. The 1-year prevalence of LBP could be up to 81.7% in the Army, 5.2% in the Marines, and 48.1% in the Air Force. Age (OR = 0.494–2.89), history of LBP (OR = 2.2–8.91), and sedentary position (OR = 0.55–3.63) were the most common physical, sociodemographic, and occupational risk factors, respectively. Conclusions: Low back pain was prevalent among military personnel. There was heterogeneity in studies and a significant difference in prevalence and incidence across various occupational categories. Physical, sociodemographic, and occupational risk factors were researched more than psychological risk factors in the military.

Abstract Background Recent studies have established a correlation between ADAMTSL2 (ADAMTS-like 2) and the development of various cancers. This study aims to conduct a comprehensive pan-cancer analysis in 37 cancer types and investigate its potential role in colon and rectal adenocarcinoma (COADREAD). Method Pan-cancer and mutation data were sourced from The Cancer Genome Atlas (TCGA) database and analyzed using Sangerbox analysis platform. We explored the expression patterns and prognostic implications of ADAMTSL2, and investigated its relationships with tumor heterogeneity, stemness, immune checkpoint genes, immune cell infiltration, RNA modifications, and mutational profiles across different cancers. Additionally, with Ethics Committee approval, we conducted immunohistochemical (IHC) analysis on 120 COADEAD samples to evaluate ADAMTSL2 expression and its association with clinicopathological parameters. Results ADAMTSL2 expression was positively correlated with the hazard ratio of OS, DSS, DFI and PFI for ESCA and COADREAD. A negative correlation was observed between ADAMTSL2 expression and NEO levels in COAD. Gene alterations in ADAMTSL2 were observed, with a mutation frequency of 5.0% in COAD. There is a significant correlation between ADAMTSL2 expression and immune cell infiltration in a variety of cancers. The expression level of ADAMTSL2 protein was associated with T stage, N stage, M stage (p

Objective At present, due to the lack of early observation methods, the effect of the ‘accordion’ technique on the treatment of nonunion of the docking site varies greatly. In this study, color Doppler ultrasound was used to observe the docking site's local changes and investigate the relationship between local microenvironment changes and bone healing after the accordion technique. Methods 30 patients with tibial bone transport treated at the Department of Orthopedics, Second Hospital of Shanxi Medical University, from May 2018 to June 2022, were analyzed retrospectively. Paired‐sample t‐tests were used for data that conformed to a normal distribution, and paired rank‐sum tests were used for before‐and‐after comparisons that did not conform to a normal distribution. There were 26 males and 4 females, aged 47.3 ± 11.7 years. Before bone transport, the defect gap between tibial bone ends was 6.80 ± 3.61 cm. The steps of the accordion technique were as follows: compression for 7 days, ultrasonic study of the microenvironment at the docking site, distraction for 12 days, latency for 7 days, compression for 14 days, then static fixation and radiological study until complete bone healing. Ultrasound was used to detect the size of the hematoma after 7 days of pressure, and the changes in blood flow before and after the ‘accordion' operation. Results All patients were followed up for 11.9 ± 1.9 months. At the last follow‐up, 22 patients achieved bone healing at the docking site after the treatment of the ‘accordion’ technique. There was a linear negative correlation between the size of the hematoma and the time of bone healing at the docking site (r = −0.639, p

Abstract Background Case-based learning (CBL) utilizing three-dimensional (3D) printed hip joint models is a problem-solving teaching method that combines the tactile and visual advantages of 3D-printed models with CBL. This study aims to investigate the impact of integrating 3D printing with CBL on learning developmental dysplasia of the hip (DDH). Methods We conducted a prospective study from 2022 to 2023, including 120 fourth-year clinical medical students at Xuzhou Medical University. Students were randomly allocated into two groups of 60 participants each. The CBL group received conventional CBL teaching methods, while the 3D + CBL group utilized 3D-printed models in conjunction with CBL. Post-teaching, we analyzed and compared the theoretical and practical achievements of both groups. A questionnaire was designed to assess the impact of the educational approach on orthopedic surgery learning. Results The theory scores of the CBL group (62.88 ± 7.98) and 3D + CBL group (66.35 ± 8.85) were significantly different (t = 2.254, P = 0.026); the practical skills scores of the CBL group (57.40 ± 8.80) and 3D + CBL group (63.42 ± 11.14) were significantly different (t = 3.283, P = 0.001). The questionnaire results showed that the 3D + CBL group was greater than the CBL group in terms of hip fundamentals, ability to diagnose cases and plan treatments, interesting teaching content, willingness to communicate with the instructor and satisfaction. Conclusions The integration of 3D printing with case-based learning has yielded positive outcomes in teaching DDH, providing valuable insights into the use of 3D-printed orthopedic models in clinical education.

Abstract Background Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration. Methods We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD. Results All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent. Conclusion Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis.

Penicillium citrinum is one of the most prevalent tobacco spoilage fungi. However, the mechanisms underlying fungal growth on tobacco leaves remain largely unknown. In this study, transcriptomic analyses were performed to reveal the genome-wide expression profiles of P. citrinum growing on tobacco leaves. First, a comparative analysis was conducted between two sets of transcriptomic data from P. citrinum growing on chemically defined media and tobacco leaves. Enrichment analyses showed that differentially regulated genes were mainly associated with carbohydrate degradation (e.g., cellulose, pectin, and xylan) and the catabolism of fatty acids and aromatic compounds. Comparative transcriptomic analyses between different time points indicated that the fungal transcriptome varied dynamically during the spoilage process, and the enriched terms were associated with small-molecule degradation and fungal development. Enrichment analyses indicated that more up-regulated genes appeared in all enriched Gene Ontology terms. Notably, more organelles significantly contributed to further fungal growth on tobacco leaves. In conclusion, P. citrinum activates a comprehensive transcriptome that changes dynamically when causing tobacco mildew.

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. Methods In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch’s tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman’s correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. Results It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from − 0.228 to -0.385. Further regression analysis presented β values between − 0.954 and − 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. Conclusions The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. Trial registration NCT05644548, December 1, 2022.

Dryas octopetala L. var. asiatica (Nakai) Nakai 1918 is a dwarf shrub that mainly grow in alpine and arctic zones of the Northern Hemisphere, representing an endemic variety in Asia. In the present study, the complete chloroplast (cp) genome of D. octopetala var. asiatica was first characterized and used for its phylogenetic analysis. The cp genome span 158,271 bp with an overall GC content of 36.5%. A total of 129 genes were identified, including 84 protein-coding genes (PCGs), 37 tRNA genes, and 8 rRNA genes. In addition, repetitive sequences and microsatellites were detected within this species. Phylogenetic analysis involving 39 cp genomes from Rosaceae family indicated that D. octopetala var. asiatica was sister to the clade of Amygdaloideae. This study contributes fundamental insights into the cp genome of Dryas octopetala var. asiatica, which will have expanded its use in photosynthesis and evolutionary study.

Abstract Background Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear. Methods This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies. Results A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB

Abstract The small genera Allaeanthus and Malaisia within the Moraceae have important edible, medicinal, and economic value. However, complete plastome blueprints and a well-resolved evolutionary history of these two genera are still lack, thereby limiting their conservation and application. The recent discovery of a new distribution of Allaeanthus kurzii in Hainan, China, marked by the collection of two unique samples, alongside three samples of Malaisia scandens, has opened new avenues for research. This study aimed to compare the Allaeanthus and Malaisia plastomes of Hainan Province samples with those of samples from other regions, focusing on plastome structure, codon usage bias, natural selection, and the evolutionary history of A. kurzii and M. scandens. The results showed that both species had a quadripartite plastome structure, with sizes ranging from 162,134 to 162,170 bp for A. kurzii and 161,235 to 162,134 bp for M. scandens. Both species displayed loss of the infA gene and reduction of the rpl22 gene. Two highly variable regions (petD-trnD-GUC and rpl20-clpP) and three highly variable genes (rpl20, petB, and rpl16) were identified in A. kurzii, while two highly variable regions (ycf2-ndhB and ccsA-ndhE) and three highly variable genes (psbT, rpl36, and ycf2) were found in M. scandens. The protein-coding sequences (CDSs) of the Allaeanthus and Malaisia plastomes exhibited similar patterns of adaptive indices and codon usage frequencies. The genes associated with photosynthesis underwent strong purifying selection. Phylogenetic analysis revealed that Allaeanthus, Broussonetia, and Malaisia constituted a monophyletic group, with Malaisia being more closely related to Broussonetia. Broussonetia diversified approximately 19.78 million years ago, Malaisia approximately 4.74 million years ago, and Allaeanthus approximately 16.18 million years ago. These new plastome-based discoveries will guide conservation planners and medicinal plant breeders and genetic resource development for these species in the region.

Abstract With a large number of film capacitors being deployed in critical locations in electrical and electronic systems, artificial intelligence (AI) technology is also expected to address the problems encountered in this process. According to our findings, AI applications can cover the entire lifecycle of film capacitors. However, the AI safety hazards in these applications have not received the attention they deserve. To meet this, the authors argue, with specific examples, risks that flawed, erratic, and unethical AI can introduce in the design, operation, and evaluation of film capacitors. Human‐AI common impact and more multi‐dimensional evaluation for AI are proposed to better cope with unknown, ambiguity, and known risks brought from AI in film capacitors now and in the future.

We report on the optical spectroscopic observations of the host galaxy of the hyperactive repeating fast radio burst (FRB) FRB 20240114A. The host galaxy is a dwarf galaxy at a redshift of z = 0.1306 ± 0.0002. With a rest-frame coverage of 4300–7900 Å, we have detected H α , H β , [O iii ] λλ 4959,5007, [N ii ] λλ 6548,6583, and [S ii ] λ 6716 emission lines. The emission line ratios suggest that the ionization in the host galaxy is dominated by star formation. The star formation rate (SFR) derived from the H α emission line is (0.06 ± 0.01) M _⊙ yr ^−1 , and the spectral energy distribution fitting suggests the lower limit of the SFR(UV) is 0.09 M _⊙ yr ^−1 . The stellar mass is (4.0 ± 1.8) × 10 ^8 M _⊙ , making the specific SFR ${\rm{log}}\,{\rm{sSFR}}({\rm{H}}\alpha )=-9.17\pm 0.07\,{{\rm{yr}}}^{-1}$ . The line ratios indicate an upper limit of a metallicity of 12 + log _10 ([O/H]) ∼ 8.5. As the nearest dwarf host galaxy with a repeating FRB, the activity of FRB 20240114A and the properties of this host galaxy closely resemble those of FRB 20121102A and FRB 20190520B. The H α -traced dispersion measure provided by the ionized gas of the host galaxy has a moderate contribution of ∼200 pc cm ^−3 , assuming a warm ionized gas. We found that the distributions of the stellar mass versus SFR are significantly different between repeating and one-off FRBs, as determined by the MANOVA test with p = 0.0116.

BackgroundIntertrochanteric fractures are one of the most common types of hip fractures, with delayed surgical treatment beyond 48 h associated with increased postoperative complications and mortality, especially in older adults. This study aimed to develop a predictive model for delayed preoperative waiting times in intertrochanteric fracture cases, based on previous research, to offer a valuable reference for clinical decision-making.MethodsA retrospective analysis was conducted on 1,116 patients with intertrochanteric fractures admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine for internal fixation surgery from January 2017 to January 2024. Patient demographic data and clinical examination results were collected. A logistic regression model was used to construct a predictive model, which was then visualized through a nomogram. The model’s performance was subsequently validated.ResultsThe predictive model developed from 728 patients in the training cohort, identified key predictors, including age, sex, lower extremity deep vein thrombosis, injury location, and biochemical markers. The model demonstrated strong discriminative ability, with an area under the receiver operating characteristic curve of 0.749 (95% confidence interval: 0.621–0.801) for the training set, and 0.745 in the validation set. Calibration curves indicated that the predicted risk of surgical delay closely aligned with observed outcomes. Furthermore, decision curve analysis verified the model’s clinical utility, demonstrating its effectiveness in guiding treatment decisions.ConclusionThe nomogram model developed in this study provides a reliable tool for predicting delayed surgical intervention in patients with intertrochanteric femur fractures. It offers clinicians a valuable reference to anticipate delays in surgical treatment and aids in the formulation of more timely and appropriate treatment strategies, potentially improving patient outcomes.

Polycystic ovary syndrome (PCOS) is a primary endocrine disorder affecting premenopausal women involving metabolic dysregulation. We aimed to screen serum biomarkers in PCOS patients using untargeted lipidomics and ensemble machine learning. Serum from PCOS patients and non-PCOS subjects were collected for untargeted lipidomics analysis. Through analyzing the classification of differential lipid metabolites and the association between differential lipid metabolites and clinical indexes, ensemble machine learning, data preprocessing, statistical test pre-screening, ensemble learning method secondary screening, biomarkers verification and evaluation, and diagnostic panel model construction and verification were performed on the data of untargeted lipidomics. Results indicated that different lipid metabolites not only differ between groups but also have close effects on different corresponding clinical indexes. PI (18:0/20:3)-H and PE (18:1p/22:6)-H were identified as candidate biomarkers. Three machine learning models, logistic regression, random forest, and support vector machine, showed that screened biomarkers had better classification ability and effect. In addition, the correlation of candidate biomarkers was low, indicating that the overlap between the selected biomarkers was low, and the combination of panels was more optimized. When the AUC value of the test set of the constructed diagnostic panel model was 0.815, the model's accuracy in the test set was 0.74, specificity was 0.88, and sensitivity was 0.7. This study demonstrated the applicability and robustness of machine learning algorithms to analyze lipid metabolism data for efficient and reliable biomarker screening. PI (18:0/20:3)-H and PE (18:1p/22:6)-H showed great potential in diagnosing PCOS.

The FSH-FSHR pathway has been considered an essential regulator in reproductive development and fertility. But there has been emerging evidence of FSHR expression in extragonadal organs. This poses new questions and long-term debates regarding the physiological role of the FSH-FSHR, and underscores the need for reliable, in vivo analysis of FSHR expression in animal models. However, conventional methods have proven insufficient for examining FSHR expression due to several limitations. To address this challenge, we developed Fshr-ZsGreen reporter mice under the control of Fshr endogenous promoter using CRISPR-Cas9. With this novel genetic tool, we provide a reliable readout of Fshr expression at single-cell resolution level in vivo and in real time. Reporter animals were also subjected to additional analyses,to define the accurate expression profile of FSHR in gonadal and extragonadal organs/tissues. Our compelling results not only demonstrated Fshr expression in intragonadal tissues but also, strikingly, unveiled notably increased expression in Leydig cells, osteoblast lineage cells, endothelial cells in vascular structures, and epithelial cells in bronchi of the lung and renal tubes. The genetic decoding of the widespread pattern of Fshr expression highlights its physiological relevance beyond reproduction and fertility, and opens new avenues for therapeutic options for age-related disorders of the bones, lungs, kidneys, and hearts, among other tissues. Exploiting the power of the Fshr knockin reporter animals, this report provides the first comprehensive genetic record of the spatial distribution of FSHR expression, correcting a long-term misconception about Fshr expression and offering prospects for extensive exploration of FSH-FSHR biology.

Background: Neuropathic pain (NP) constitutes a significant burden for individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous research has suggested that the analgesic effects of NP are mediated by dopamine (DA) neurons in the ventral tegmental region (VTA) through projections to various brain regions. A decrease in VTA dopamine neurons following NP may contribute to prolonged pain. It has been revealed that inflammatory activation triggers necroptosis by stimulating mixed lineage kinase domain-like protein (MLKL), leading to progressive neuronal demise. Recent research from many studies has revealed that IL-17-induced necroptosis plays an important role in neuroinflammation and neuronal damage. To our knowledge, few studies have hitherto investigated how IL-17-induced necroptosis may contribute to neuropathic pain. Hydrogen sulfide (H2S) treatment is commonly used for neuropathic pain, although the exact mechanisms remain unclear. Sodium hydrosulfide (NaHS), a common H2S delivery method in medicine, has also been shown to exert neuroprotective effects against neuropathic pain. This study aimed to investigate the link between IL-17-induced necroptosis of dopamine neurons in the VTA and neuropathic pain. Additionally, we explored whether H2S treatment could reduce the loss of VTA dopamine neurons, thereby lowering neuropathic pain in a chronic constriction injury (CCI) model. Methods: This study employed a CCI animal model created using a sciatic nerve ligation approach. To investigate the effect of H2S treatment on neuropathic pain, NaHS was injected intrathecally into CCI model mice. The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were evaluated to assess the mice's pain thresholds. Additional experiments, including electrophysiological studies and immunofluorescence assays, western blotting, real-time quantitative Polymerase Chain Reaction (PCR) were conducted to elucidate the precise mechanism underlying the analgesic effects of H2S therapy on neuropathic pain. Results: In mice exposed to CCI, there was a significant decrease in dopamine neurons, a reduction in MWT and TWL, decreased expression of tyrosine hydroxylase (TH) protein and TH mRNA and an increase in VTA firing rate and MLKL colocalization with DA neurons (all p

In a world grappling with the overuse of pesticides, China emerges as a key consumer and producer, facing substantial challenges in environmental and agricultural sustainability. This study investigates how agricultural services can foster eco-friendly pesticide use among farmers. It leverages data from the ‘China Land Economic Survey’ (2020-2021) by Nanjing Agricultural University, covering 52 villages and 2600 households. Using a multi-dimensional fixed effects model and propensity score matching, the research addresses biases inherent in the data. Results show that agricultural business services significantly boost green pesticide adoption, outperforming agricultural technology and input sectors. These services increase the use of safer pesticides and the recycling of their containers by 11.6% and 6%, respectively. Farmer satisfaction and regular internet use also play a role in reinforcing this trend. Based on these insights, it recommends enhancing support for low-toxicity pesticides and recycling programmes, creating tailored policies for diverse agricultural needs, and implementing resource management and incentive mechanisms to promote sustainable practices. These strategies aim to bolster sustainable agriculture, balancing environmental health with economic viability.

Objective To investigate the changes in liver and kidney function, red blood cell (RBC) count and hemoglobin (HGB) levels in patients undergoing ultrasound-guided percutaneous microwave ablation (UPMWA) for uterine fibroids on postoperative day 1.Methods The changes in liver and kidney function, RBC count and HGB levels in 181 patients who underwent selective UPMWA in the Second Affiliated Hospital of Shantou University Medical College, China, between August 2017 and January 2023 were retrospectively analyzed.Results All patients underwent UPMWA for uterine fibroids; 179 patients had multiple uterine fibroids and 2 patients had single uterine fibroids. The maximum fibroid diameter ranged from 18 to 140 mm, with an average of 68.3 mm. Ultrasound imaging was used to confirm that the blood flow signal within the mass had disappeared in all patients, indicating that the ablation was effective. Within 24 h, compared with before UPMWA, levels of total bilirubin, direct bilirubin, indirect bilirubin and aspartate aminotransferase had significantly increased (p

Soil alkalization is a major challenge for global crop production. This study reveals a novel defense mechanism in rice seedlings against alkaline stress, involving methyl jasmonate (MeJA) and auxin pathways. Under alkaline stress (15 mM Na2CO3), rice seedlings exhibited elevated levels of endogenous MeJA and upregulation of JA-responsive genes. Pre-treatment with MeJA (50 µM) significantly improved seedling survival, growth, and mitigated root damage under alkaline stress. This treatment also upregulated genes associated with cell death suppression (OsBI1) and stress tolerance (OsJRL, OsNAC). Notably, MeJA pre-treatment increased auxin (indole-3-acetic acid, IAA) levels in roots, and upregulated genes involved in IAA synthesis (OASA1, OASA2) and auxin signaling (Aux/IAA, ARFs). Blocking auxin transport with N-1-naphthylphthalamic acid intensified root damage under alkaline stress and diminished the protective effect of MeJA. These results highlight the crucial role of MeJA-induced activation of auxin pathway in enhancing rice tolerance to alkaline stress, and provide valuable insights for developing strategies to improve crop resilience in alkaline soils.

Purpose: In the military, neck pain is second to low back pain among musculoskeletal disorders. However, the prevalence and related factors of neck pain in military personnel have not been systematically investigated, which may lead to the lack of neck pain prevention and the generation of additional medical expenses, posing challenges to medical care. This review aimed to obtain the prevalence and related factors for neck pain in military personnel in an attempt to provide directions for prevention and intervention. Methods: We searched PubMed, Embase, and Cochrane databases in December 2021. Two researchers independently screened studies according to eligibility criteria and assessed study quality. Results: We screened titles and abstracts of 503 articles, and 17 articles met the inclusion criteria. Sixteen articles received moderate to high-quality evaluations. Neck pain is common in the military, with 1-year prevalence as high as 83% and lifetime prevalence as high as 78%. Old age (OR = 5.0), poor neck mobility (OR = 3.61), shoulder pain (OR = 4.9), low back pain (OR = 2.3), high-G pilots (OR = 1.6), longer flight time (OR = 2.53), type of aircraft (OR = 3.93), and use of helmets and night vision systems (OR = 1.9) may be associated with the prevalence of neck pain. Conclusion: Neck pain is highly prevalent in military personnel and exhibits a substantial lifetime prevalence rate. The high prevalence rate of neck pain in the military is related to many individual-related factors and work-related factors. The in-depth assessment and prevention of specific factors is an important direction of future research.

Singerocybe alboinfundibuliformis (Seok et al.) Yang, Qin & Takah 2014 is an edible mushroom distributed in several East or Southeast Asian countries. Herein, we report the mitochondrial genome of S. alboinfundibuliformis based on Illumina sequencing data. The overall length of the mitochondrial genome is 64,279 bp, with a GC content of 29.0%. It contains 14 typical protein-coding genes, 27 tRNA genes, two rRNA genes, and 13 intergenic ORFs. Most of these genes (39 out of 56) are transcribed at the forward strand, and few (17 out of 56) are transcribed at the reverse strand. Among these genes, only the rnl gene is invaded by an intron, and all other genes are intron-free. Phylogenetic analysis based on mitochondrial amino acid sequences supports the phylogenetic position of S. alboinfundibuliformis in Clitocybaceae, being close to Lepista sordida (Schumach.) Singer 1951. This study serves as a springboard for future investigation on fungal evolution in Clitocybaceae.

Bird’s nest fungi involve six different genera, but only one of these genera (i.e. Cyathus) have available mitochondrial genomes (mitogenomes) to date. In this study, we report the first mitogenome in the genus Nidula with Nidula shingbaensis K. Das & R.L. Zhao 2013 as a representative. The mitogenome is a circular molecule of 65,793 bp with a GC content of 26.2%. There are a total of 43 genes, including 14 typical protein-coding genes, 26 tRNA genes, two rRNA genes, and one free-standing intergenic open reading frame (ORF). Three introns (two in cox1 and one in cob) are present in the mitogenome, with each containing an ORF encoding for a LAGLIDADG endonuclease. Phylogenetic analysis based on mitochondrial amino acid sequences confirms the phylogenetic placement of N. shingbaensis in Nidulariaceae in Agaricales. This study serves as a springboard for future investigation on fungal evolution in Nidulariaceae.

With the rapid development of nuclear energy, uranium as the main element of nuclear energy production, its source has been widely explored. At present, uranium resources mainly come from uranium mining, and a lot of radioactive uranium containing wastewater is produced in the process of uranium mining. Until now, the treatment technology of uranium mine wastewater is still in the research and development stage in China, which leads to the storage of a large amount of uranium mine wastewater and the discharge of nuclear waste liquid, which poses a threat to human health and the environment due to the comprehensive effect of chemical toxicity and radiation toxicity. On the other hand, other metal cations in uranium wastewater, such as Ca2+ and Mg2+, compete with U(Ⅵ) for active sites, making it difficult for most treatment methods to effectively recover uranium resources from uranium wastewater. Therefore, how to effectively treat radioactive uranium mine wastewater is full of challenges. Photocatalysis is a kind of green environmental protection technology with natural selectivity to non-variable valence ions, which can precipitate the soluble U(Ⅵ) in wastewater. The photocatalysis technology is expected to overcome the competition between metal cations and uranium for active sites, and realize the efficient extraction of U(Ⅵ) in uranium mine wastewater. In this study, ZIF-8-derived Zinc@iron oxide(D-ZnO@FexOy) heterostructures were prepared by impregnation of metal salt solution and high-temperature pyrolysis using ZIF-8 as a precursor for photoassisted reduction of U(Ⅵ) in uranium ore wastewater. The electron transport mode of D-ZnO@FexOy in S-scheme heterojunction is deduced by calculating the work function and band structure. Under photoexcitation, the direction of electron flow changes, the useless electrons and holes recombine at the interface, and the electrons and holes with strong redox ability are retained and participate in the photocatalytic reaction. Compared with D-ZnO and FexOy, this kind of spatially separated photogenerated electrons and holes have stronger redox ability and longer electron lifetime. Meanwhile, the internal electric field formed at the heterojunction interface can effectively enhance the directional electron migration, providing a strong power for promoting the photoassisted reduction of uranium. Therefore, compared with iron oxide(FexOy) and ZIF-8-derived ZnO(D-ZnO), the S-type heterostructure D-ZnO@FexOy exhibits stronger photoassisted uranium reduction ability(>95%) in the presence of multiple competing ions, and the material has good anti-interference and stability. High U(Ⅵ) removal performance(above 86%) is maintained after 5 cycles. The mechanism study shows that hydroxyl radical and superoxide radical are the main active species of photocatalytic reduction of U(Ⅵ). U(Ⅵ) is deposited on the surface of the material in the form of (UO2)O2•2H2O crystals. This study provides a valuable way to explore the photocatalyst with high efficiency photoelectron separation to reduce U(Ⅵ).

Asphalt pavement is widely applied to the surface in high-grade highway tunnels due to its prominent preponderance in road performance. However, asphalt is flammable as the binder material to adhere the aggregates and other additives, resulting that a fire in the semi-closed space of the tunnel can ignite and burn asphalt pavement to generate a large amount of heat and smoke. Therefore, further promoting the advance of flame-retardant asphalt pavement is essential to ensure security in tunnels. We gathered the relevant standards or regulations of diverse nations and test methods concerning flame retardancy of asphalt. Then we reviewed the research status of flame-retardant asphalt mixture, including thermal characteristics of the asphalt and four fractions, the flame retardants applicable to asphalt, and effects on other components. This review demonstrated that establishing universal standards and test methods is a research basis specifically for flame-retardant asphalt pavement. To optimize the flame retardancy of asphalt pavement, it should focus on the synergy with diversified aspects such as asphalt binders, multiple flame retardants, aggregates, mineral powders, fibers, and other additives.

Abstract Background Engelhardia (Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of Engelhardia, the maternal genome evolution and phylogeny of Engelhardia in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight Engelhardia species and the outgroup Rhoiptelea chiliantha, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of Engelhardia and the whole Juglandaceae family. Results The 13 Engelhardia plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (TrnK-rps16, ndhF-rpl32, and ycf1) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only rpl22 and psaI genes showed positive selection (Ka/Ks > 1). Phylogenetic results fully supported Engelhardia as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The Engelhardia originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn’t support rapid radiation occurred in the evolution history of Engelhardia. Conclusion Our study fully supported the taxonomic treatment of at the section for Engelhardia species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of Engelhardia and the whole Juglandaceae family.

Abstract Long-read sequencing, exemplified by PacBio, revolutionizes genomics, overcoming challenges like repetitive sequences. However, the high DNA requirement ( > 1 µg) is prohibitive for small organisms. We develop a low-input (100 ng), low-cost, and amplification-free library-generation method for PacBio sequencing (LILAP) using Tn5-based tagmentation and DNA circularization within one tube. We test LILAP with two Drosophila melanogaster individuals, and generate near-complete genomes, surpassing preexisting single-fly genomes. By analyzing variations in these two genomes, we characterize mutational processes: complex transpositions (transposon insertions together with extra duplications and/or deletions) prefer regions characterized by non-B DNA structures, and gene conversion of transposons occurs on both DNA and RNA levels. Concurrently, we generate two complete assemblies for the endosymbiotic bacterium Wolbachia in these flies and similarly detect transposon conversion. Thus, LILAP promises a broad PacBio sequencing adoption for not only mutational studies of flies and their symbionts but also explorations of other small organisms or precious samples.

Abstract Traditional catalytic techniques often encounter obstacles in the search for sustainable solutions for converting CO2 into value-added products because of their high energy consumption and expensive catalysts. Here, we introduce a contact-electro-catalysis approach for CO2 reduction reaction, achieving a CO Faradaic efficiency of 96.24%. The contact-electro-catalysis is driven by a triboelectric nanogenerator consisting of electrospun polyvinylidene fluoride loaded with single Cu atoms-anchored polymeric carbon nitride (Cu-PCN) catalysts and quaternized cellulose nanofibers (CNF). Mechanistic investigation reveals that the single Cu atoms on Cu-PCN can effectively enrich electrons during contact electrification, facilitating electron transfer upon their contact with CO2 adsorbed on quaternized CNF. Furthermore, the strong adsorption of CO2 on quaternized CNF allows efficient CO2 capture at low concentrations, thus enabling the CO2 reduction reaction in the ambient air. Compared to the state-of-the-art air-based CO2 reduction technologies, contact-electro-catalysis achieves a superior CO yield of 33 μmol g−1 h−1. This technique provides a solution for reducing airborne CO2 emissions while advancing chemical sustainability strategy.

Abstract The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/β-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.

Abstract Background Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. Results Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. Conclusions This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish. Video Abstract

Abstract Background As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups. Methods The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC). Results One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes. Conclusions CMWI, calculated based on primary care’s routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients’ health risks in primary care.

Abstract Film capacitors are playing an increasingly important role in power‐related fields, driven by the continuous development of dielectric materials and practical needs. Long‐term accumulation has also led to an increasing wealth of data related to film capacitors. Sonification opens up a new way for people to make good use of data from film capacitors. A framework for sonifying film capacitors data based on TwoTone is presented. Based on the analysis and discussion, it is clear that the sonification results can easily represent the monotonic variation pattern of film capacitors data. What's more, the sonification results increase the possibility that people pay attention to the changing trend of film capacitors data when there is no significant difference in the visual perception of the data. In addition to providing a new way of music generation of electrical equipment, the method proposed is expected to contribute to theory reference in typical scenarios, such as factory calibration of film capacitors, monitoring of film capacitor operation status, and presentation of statistical data of film capacitors' dielectric materials, which will help us to better understand the distribution characteristics of polymer films.

We explore a class of nonlocal Schrödinger equations that include not only fractional Schrödinger equations but also other nonlocal Schrödinger equations studied in the literature. We prove the existence of least energy solutions to this class of equations by the variational method, which extends the results obtained by Gu et al. (2018) and Xiang et al. (2019).