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Objective: The association between myopia and diabetic retinopathy (DR) is unclear, with inconsistent results reported, and whether the association represents causality remains unknown. This study aimed to investigate the causal associations of genetically determined myopia with DR, and further explore specific mechanisms. Methods: We conducted two-sample mendelian randomization (MR) analyses of any myopia and high myopia on six DR phenotypes, including any DR, background DR, severe background DR, proliferative DR (PDR), diabetic maculopathy and unspecific DR in the primary study. Mechanism exploration of spherical equivalent refraction (SER), corneal curvature (CC) and axial length (AL) on any DR was carried out subsequently. Single-nucleotide polymorphisms (SNPs), used as genetic instruments, were derived from UK Biobank, Genetic Epidemiology Research on Adult Health and Aging cohort (GERA) and FinnGen. The inverse variance weighted (IVW) method was mainly used to assess the causality, and was complemented with sensitivity analyses and causality direction analyses. Results: Using SNPs that have excluded possible confounders, we discovered suggestive and positive causal associations of any myopia with any DR (IVW: odds ratio [OR] ​= ​1.133, 95% confidence interval [95%CI]: 1.070–1.201, P ​= ​1.91×10−5) and PDR (IVW: OR ​= ​1.182, 95% CI: 1.088–1.285, P ​= ​8.31×10−5). Similar but more significant associations were found of high myopia with any DR and PDR (IVW: OR ​= ​1.107, 95%CI: 1.051–1.166, P ​= ​1.39×10−4; OR ​= ​1.163, 95%CI: 1.088–1.244, P ​= ​8.76×10−6, respectively). Further mechanism analyses found only AL, rather than SER or CC, was strongly and significantly associated with any DR. These associations were robust in sensitivity analyses and causality direction analyses. Conclusions: We found significant and positive causal associations of any myopia and high myopia with the risk of DR and PDR, which might be related with AL, indicating the significance of myopia control for preventing DR development and progression.

Abstract Background Veno-arterial (V-A) and veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) are crucial support modalities during lung transplantation, yet their comparative effectiveness remains unclear. Methods We conducted an 8-year retrospective analysis of 62 lung transplant recipients who received intraoperative ECMO (29 V-A, 33 V-V). Baseline characteristics, surgical parameters, and clinical outcomes were compared. To address potential selection bias, we employed entropy weighted inverse probability of treatment weighting (IPTW-EW). Results After IPTW-EW adjustment, V-A ECMO was associated with superior hemodynamic and respiratory parameters, including lower systolic pulmonary artery pressure (30 vs. 37 mmHg, p = 0.007), higher arterial oxygen partial pressure (119 vs. 78 mmHg, p = 0.002), and less severe pulmonary edema (Grade 1: 50% vs. 3%, Grade 2: 45% vs. 38%, Grade 3: 5% vs. 59%, p

Abstract The size of InGaN micro-LEDs is continuously decreasing to meet the demands of various emerging applications, especially in tiny micro-displays such as AR/VR. However, the conventional pixel definition based on plasma etching significantly damages the mesa sidewalls, leading to a severe reduction in efficiency as the micro-LED size decreases. This seriously impedes the development and application of micro-LEDs. In this work, we comprehensively explain the origin of micro-LED sidewall effects and corresponding physical models. Subsequently, we systematically review recent progress in micro-LED fabrication aiming at suppressing sidewall effects. Furthermore, we discuss advancements in micro-LED fabrication with “damage-free” techniques, which hold the potential to fundamentally address the issue of plasma damage in the micro-LED process. We believe this review will deepen the understanding of micro-LED sidewall effects and provide a better insight into the latest associated fabrication technologies for high-efficient InGaN micro-LEDs.

Abstract Cataract is the leading ocular disease of blindness and visual impairment globally. Deep neural networks (DNNs) have achieved promising cataracts recognition performance based on anterior segment optical coherence tomography (AS-OCT) images; however, they have poor explanations, limiting their clinical applications. In contrast, visual features extracted from original AS-OCT images and their transform forms (e.g., AS-OCT-based histograms) have good explanations but have not been fully exploited. Motivated by these observations, an explainable machine learning framework to recognize cataracts severity levels automatically using AS-OCT images was proposed, consisting of three stages: visual feature extraction, feature importance explanation and selection, and recognition. First, the intensity histogram and intensity-based statistical methods are applied to extract visual features from original AS-OCT images and AS-OCT-based histograms. Subsequently, the SHapley Additive exPlanations and Pearson correlation coefficient methods are applied to analyze the feature importance and select significant visual features. Finally, an ensemble multi-class ridge regression method is applied to recognize the cataracts severity levels based on the selected visual features. Experiments on a clinical AS-OCT-NC dataset demonstrate that the proposed framework not only achieves competitive performance through comparisons with DNNs, but also has a good explanation ability, meeting the requirements of clinical diagnostic practice.

Abstract Objectives Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC. Methods Paired liver metastatic tissue samples and peripheral blood from 32 liver oligometastatic NSCLC patients were concurrently collected for comprehensive genomic analysis using next-generation sequencing. Results A total of 206 mutated genes in 32 patients were detected, with a median of 4 mutations per sample. The most frequent alterations (> 10%) in liver oligometastasis were TP53 (72%), EGFR (50%), RB1 (19%) and SMARCA4 (12%). The co-occurrence rate of TP53 and RB1 in our cohort was significantly higher than that in the TCGA-LUAD cohort. Age, APOBEC, homologous recombination deficiency (HRD) and deficient mismatch repair (dMMR) established the mutational signature of liver oligometastatic NSCLC. The median tumor mutation burden (TMB) was 4.8 mutations/Mb. A total of 78.12% patients harbored at least one potentially actionable molecular alteration that may guide further targeted therapy according to the OncoKB evidence. Conclusions Our study comprehensively delineated the genomic characteristics of liver oligometastatic NSCLC - such findings were helpful to better understand the distinct clinic-biological features of oligometastasis and optimize personalized treatment of this population.

Abstract Background HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention. Methods The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA. This therapeutic effect was substantiated in various models: HEK 293 T cell, the HD 140Q-KI mouse, and the HD-KI pig model. The efficiency of the knockdown was analyzed through Western blot and RT-qPCR. Additionally, neuropathological changes were examined using Western blot, immunostaining, and RNA sequencing. The impact on motor abilities was assessed via behavioral experiments, providing a comprehensive evaluation of the treatment's effectiveness. Results CRISPR/CasRx system can significantly reduce HTT mRNA levels across various models, including HEK 293 T cells, HD 140Q-KI mice at various disease stages, and HD-KI pigs, and resulted in decreased expression of mHTT. Utilizing the CRISPR/CasRx system to knock down HTT RNA has shown to ameliorate gliosis in HD 140Q-KI mice and delay neurodegeneration in HD pigs. Conclusions These findings highlight the effectiveness of the RNA-targeting CRISPR/CasRx as a potential therapeutic strategy for HD. Furthermore, the success of this approach provides valuable insights and novel avenues for the treatment of other genetic disorders caused by gene mutations.

Shuzhe Xiao,1,* Yue Ding,1,* Chen Du,1,* Yiting Lv,1 Shumei Yang,1,2 Qi Zheng,3 Zhiqiu Wang,3 Qiaoli Zheng,3 Meifang Huang,1 Qingyan Xiao,1 Zhuxiao Ren,2 Guangliang Bi,1 Jie Yang1,2 1Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, 511442, People’s Republic of China; 3The First Clinical Medical College of Southern Medical University, Guangzhou, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Yang; Guangliang Bi, Email Jieyang0830@126.com; bader515@163.comBackground: Autophagy and immunity play important regulatory roles in lung developmental disorders. However, there is currently a lack of bioinformatics analysis on autophagy-related genes (ARGs) and immune infiltration in bronchopulmonary dysplasia (BPD). We aim to screen and validate the signature genes of BPD by bioinformatics and in vivo experiment.Methods: GSE8586 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the R program. Using cell-type identification with CIBERSORT to analyze the inflammatory and immune status of BPD. Subsequently, the hub genes were identified by Lasso and Cytoscape with three machine-learning algorithms (MCC, Degree and MCODE). In addition, hub genes were validated with ROC, single-cell sequence and IHC in hyperoxia mice. Finally, we searched the drug targets of these hub genes, and established a nomogram model for predicting the risk of BPD.Results: There were 73 the differentially expressed and autophagy-related genes (DE-ARGs) by overlapping the DEGs in GSE8586 and ARGs. Five hub genes, BRIX1, JUN, PES1, NR4A1 and RRP9, were lowly expressed in the BPD group and had high diagnostic value in the diagnostic model. All hub genes are mainly located in B cell, epithelial cell, fibroblast, endothelial cell, smooth muscle cell and pneumocyte in lung single-cell sequencing. Moreover, immune infiltration analysis showed immune cells were higher in the BPD group and were closely associated with hub genes. We also predict the drug targets of the genes. Finally, the IHC result in mice showed that expression of PES1, BRX1, RRP9, JUN, NR4A1 was lower in the hyperoxia group compared to the normoxia group.Conclusion: BRIX1, JUN, PES1, NR4A1, RRP9, may be promising therapeutic targets for BPD. Our findings provided researchers and clinicians with more evidence regarding immunotherapeutic strategies for BPD treatment.Keywords: BPD, autophagy, immune cell infiltration, single cell sequencing, biomarkers

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

The primary function of terminators is to terminate transcription in gene expression. Although some studies have suggested that terminators also contribute positively to upstream gene expression, the extent and underlying mechanism of this effect remain largely unexplored. Here, the correlation between terminating strength and upstream mRNA stability was investigated by constructing a terminator mutation library through randomizing 5 nucleotides, assisted by FlowSeq technology, terminator variants were categorized based on the downstream fluorescence intensity, followed by high-throughput sequencing. To examine the impact of terminators on mRNA stability, the abundance of downstream gene transcripts for each terminator variant was quantified through cDNA sequencing. The results revealed that the transcript abundance controlled by strong terminators was, on average 2.2 times greater than those controlled by weak terminators on average. Moreover, several distinct features could be ascribed to high relative abundance of upstream gene transcript, including a high GC content at the base region of hairpin, and a high AT content in downstream of the U-tract. Additionally, these terminators showed a free energy between −28 and −22 kcal/mol, and a stem length of 14 nt. Finally, these features ascribed the upstream beneficial terminator were validated across various expression systems. By incorporating the optimal terminator downstream of RSF, GSH and HIS in three different strains, the fermentation productions-NMN SAM and VD13 exhibited a remarkable enhancement of 30 %–70 %. The findings presented here uncovered the terminator characteristics contributed to the upstream mRNA stability, providing guiding principles for gene circuit design.

Shiraia-related species are well-known bambusicolous fungi in Dothideomycetes class, with high value in traditional medicine for producing hypocrellin, as an anticipated photosensitiser. The complete mitogenomes of hypocrellin-producing Pseudoshiraia conidialis strains were analysed in the present study, with functional gene variations through comparative genomics and transcriptomics. Five strains (ZZZ816, CNUCC1353PR, JAP103846, CNUCC C72, CNUCC C151) were sequenced, which indicated similar genome characteristics. Two of them possess an extra atp6 gene, and the associated variable fragment “HSP1-HSP2-atp6_2” correlates closely with hypocrellin production capacity. Therefore, these five strains were divided into three groups: ZZZ816 and CNUCC1353PR possessing high production efficiency, CNUCC C72 and JAP103846 with low yield and CNUCC C151 as a transition type. The gene expression changes were screened under various conditions. ZZZ816-related species showed significant changes in mitochondrial genes, especially HSP1, HSP2 and atp6_2, linked closely to hypocrellin synthesis and stress response; rps3 expression also consistently correlated with hypocrellin production. JAP103846 group showed a stable expression pattern divergently, except for rps3 suppression by blue light. These findings would provide new insights into secondary metabolite regulation and ROS resistance. Above all, this study conducted the comprehensive analysis of Shiraia-like fungi mitogenomes and functional gene expression, which can update the understanding of fungal evolution and potential for improved hypocrellin production.

Abstract Background We established and validated an innovative two-phase pipeline for automated detection and segmentation on multi-parametric cervical cancer magnetic resonance imaging (MRI) and investigated the clinical efficacy. Methods The retrospective multicenter study included 125 cervical cancer patients enrolled in two hospitals for 14,547 two-dimensional images. All the patients underwent pelvic MRI examinations consisting of diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI), and contrast-enhanced T1-weighted imaging (CE-T1WI). The deep learning framework involved a multiparametric detection module utilizing ConvNeXt blocks and a subsequent segmentation module utilizing 3-channel DoubleU-Nets. The pipeline was trained and tested (80:20 ratio) on 3,077 DWI, 2,990 T2WI, and 8,480 CE-T1WI slices. Results In terms of reference standards from gynecologic radiologists, the first automated detection module achieved overall results of 93% accuracy (95% confidence interval 92–94%), 93% precision (92–94%), 93% recall (92–94%), 0.90 κ (0.89–0.91), and 0.93 F1-score (0.92–0.94). The second-stage segmentation exhibited Dice similarity coefficients and Jaccard values of 83% (81–85%) and 71% (69–74%) for DWI, 79% (75–82%), and 65% (61–69%) for T2WI, 74% (71–76%) and 59% (56–62%) for CE-T1WI. Conclusion Independent experiments demonstrated that the pipeline could get high recognition and segmentation accuracy without human intervention, thus effectively reducing the delineation burden for radiologists and gynecologists. Relevance statement The proposed pipeline is potentially an alternative tool in imaging reading and processing cervical cancer. Meanwhile, this can serve as the basis for subsequent work related to tumor lesions. The pipeline contributes to saving the working time of radiologists and gynecologists. Key Points An AI-assisted multiparametric MRI-based pipeline can effectively support radiologists in cervical cancer evaluation. The proposed pipeline shows high recognition and segmentation performance without manual intervention. The proposed pipeline may become a promising auxiliary tool in gynecological imaging. Graphical Abstract

Abstract Background Varicella-zoster virus (VZV) is highly transmissible; however, there are limited studies in China. Methods The clinical symptoms, disease progression, and laboratory test results of varicella patients among children and adults diagnosed at Ganzhou Fifth People’s Hospital from August 2021 to December 2022 were analysed retrospectively. Genetic polymorphisms in the open reading frame (ORF) 22 and ORF62 fragments of VZV isolates were analysed using molecular epidemiological methods. Results Thirty-nine varicella patients were included in this study, 26 of them were children and 13 of them were adults. The incidence of discomfort and complications was significantly greater in adults than in children (P

Abstract Background Immune checkpoint inhibitors (ICIs) therapy has revolutionized anti-cancer therapy, with lung cancer exhibiting sustained clinical responses to it. However, there remains a lack of research into the risk factors of serious infections in patients with lung cancer following ICIs therapy. Therefore, we aimed to investigate the incidence and risk factors of serious infections in these patients. Methods Medical records were retrospectively collected and reviewed from 710 patients with lung cancer receiving ICIs therapy at Zhongshan Hospital between January 2021 and February 2023. Serious infections were defined as infections requiring hospitalization or parenteral antimicrobials occurring at any time from the initiation of the ICIs therapy to 3 months after its discontinuation. Results Among the study population, 191 patients had suffered from serious infections, with an overall infection rate of 26.90% during an average follow-up period of (432.62 ± 377.09) days. The predominant site of infection was the lung (75.61%), and the most prevalent pathogens were bacteria (85.07%), followed by Mycobacterium tuberculosis (6.47%), viruses (4.98%), and fungi (3.48%). In addition to chronic obstructive pulmonary disease (COPD), asthma, and systemic glucocorticoids use, low lymphocyte count and CD4/CD8 ratio were identified as independent risk factors (all p

Abstract The tumor microenvironment (TME) is pivotal in non-small cell lung cancer (NSCLC) progression, influencing drug resistance and immune cell behavior through complex ligand-receptor (LR) interactions. This study developed an epithelial LR-related prognostic risk score (LRrisk) to identify biomarkers and targets in NSCLC. We identified twenty epithelial LRs with significant prognostic implications and delineated three molecular NSCLC subtypes with distinct outcomes, pathological characteristics, biological pathways, and immune profiles. The LRrisk model was constructed using twelve differentially expressed ligand-receptor interaction-related genes (LRGs), with a focus on POPDC3 (popeye domain-containing protein 3), which was overexpressed in NSCLC cells. Functional assays revealed that POPDC3 knockdown reduced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while its overexpression promoted cancerous activities. In vivo, POPDC3 silencing hindered, and its overexpression accelerated the growth of NSCLC xenografts in nude mice. Additionally, high expression levels of POPDC3 in NSCLC tissues were associated with enhanced CD4+ T cell infiltration and increased PD-1 expression within the TME. Moreover, ectopic POPDC3 overexpression in C57BL/6 J mouse Lewis lung carcinoma (LLC) xenografts enhanced CD4+ T cell infiltration and PD-1 expression in the TME. This research establishes a robust epithelial LR-related signature, highlighting POPDC3 as a critical facilitator of NSCLC progression and a potential therapeutic target.

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) was associated with diabetes and cardiovascular diseases (CVD). However, the effect of CHIP on CVD have not been evaluated among patients with diabetes, and whether maintaining the healthy indictors could mitigate the adverse influence was also unclear. Methods A total of 22,239 adults from the UK Biobank with diabetes and available whole-exome sequence data, and free of CVD were included. Multivariable-adjusted Cox regressions were used to explore the associations of any CHIP (variant allele fraction ≥ 2%), large CHIP (variant allele fraction ≥ 10%), and the top 10 commonly mutated driver genes for CHIP and with risk of CVD. The joint associations between health indicators (body mass index [BMI], HbA1c, blood pressure [BP], and low-density lipoprotein cholesterol [LDL]) and CHIP were further investigated. Results Over a median follow-up of 13.2 years, 5366 participants with diabetes developed CVD events. The hazard ratios (HRs) (95% confidence intervals [CIs]) of any CHIP and large CHIP were (1.21, 1.08–1.36) and (1.25, 1.09–1.43) for incident CVD, respectively. Significant associations between any CHIP and coronary heart disease (HR, 95%CI: 1.18, 1.03–1.36) and heart failure (1.73, 1.46–2.06) were observed, but not for stroke (1.14, 0.89–1.48). Gene-specific analyses suggested that the greatest association were for SF3B1 (HR, 95%CI: 2.50, 1.25–5.01) and TET2 (HR, 95%CI: 1.36, 1.07–1.77) with risk of CVD. There was no significant interaction between the four health indicators and CHIP in relation to incident CVD. Compared to patients without CHIP, those with any CHIP and ideal health indicators still exhibited significantly or nonsignificantly higher HRs (BMI: 1.18, 0.82–1.68; HbA1c: 1.12, 0.96–1.30; BP: 1.24, 1.03–1.49; LDL: 1.29, 1.09–1.53). Similar results were demonstrated using large CHIP. Conclusions CHIP is independently associated with an increased risk of CVD in patients with diabetes, regardless of health indicator levels. Diabetic patients with CHIP but ideal health indicators still exhibited higher CVD risk compared with diabetic patients without CHIP. Graphic abstract

Abstract Imaging flow cytometry (IFC) combines the imaging capabilities of microscopy with the high throughput of flow cytometry, offering a promising solution for high-precision and high-throughput cell analysis in fields such as biomedicine, green energy, and environmental monitoring. However, due to limitations in imaging framerate and real-time data processing, the real-time throughput of existing IFC systems has been restricted to approximately 1000-10,000 events per second (eps), which is insufficient for large-scale cell analysis. In this work, we demonstrate IFC with real-time throughput exceeding 1,000,000 eps by integrating optical time-stretch (OTS) imaging, microfluidic-based cell manipulation, and online image processing. Cells flowing at speeds up to 15 m/s are clearly imaged with a spatial resolution of 780 nm, and images of each individual cell are captured, stored, and analyzed. The capabilities and performance of our system are validated through the identification of malignancies in clinical colorectal samples. This work sets a new record for throughput in imaging flow cytometry, and we believe it has the potential to revolutionize cell analysis by enabling highly efficient, accurate, and intelligent measurement.

Abstract Metal halide perovskites are attractive for optoelectronic applications, but the existing solution-based synthetic methods rely on hazardous solvents and lack reproducibility. To overcome these challenges, solvent-free mechanochemical synthesis of perovskites can be conducted, although traditional opaque ball milling equipment hinder real-time monitoring of the reaction progress. Herein, mechanochemistry was performed with time-lapsed in situ (TLIS) measurements to elucidate the optical properties during the synthesis. The TLIS spectrometer enabled real-time observation of the impact of varying the compositions on the absorption properties of formamidinium/methylammonium lead iodide (FA x MA1-x PbI3, x = 0 to 1) and facilitated optimization of the synthesis duration. Moreover, we can accelerate the evaluation and directly observe the effects of different synthetic strategies for enhancing the photoluminescence quantum yield and stability of the perovskites, providing near-infrared (NIR) emitting tin-based perovskites FASnI z Br3-z (where z = 0 to 3) with core-shell structures. Intriguingly, halide ion migration was deduced in lead-free double perovskites Cs2Na y Ag1-y BiCl6 (y = 0 to 1.0) at room temperature during aging after mechanochemical activation. Our work provides insights into the mechanochemistry of compounds with low thermodynamic barriers.

Abstract Background Families are faced with enormous challenges in caring for children with autism spectrum disorder (ASD) over a lifetime. As the main caregiver of children, mothers who have children with autism are in poor health compared to the mothers of typically developing (TD) children. Previous studies have revealed that the mental health of mothers has a direct impact on children. On the other hand, attention bias (AB) can be an important indicator of the mental status. Therefore, the characteristic of AB of mothers who have children with autism can be a window into the treatment of autism. Methods In this study, 28 mothers who have children with autism and 31 mothers of typically developing children completed the modified dot-probe task to explore the attention bias. Results We found that there was a significant difference of AB between mothers who have children with autism and mothers of typically developing children, which indicated that mothers who have children with autism tend to avoid negative emotional words. Conclusions The current study illuminates the attentional characteristics of mothers who have children with autism toward emotional words, which provides a new starting point for the intervention of mothers of children with autism.

Abstract Background Osteoarthritis (OA) is considered an advancing chronic degenerative joint disease, leading to severe physical functional impairment of patients. Its development is closely related to increased inflammation and oxidative stress within the joint. Ginkgetin (GK), a natural non-toxic chemical, has proven anti-inflammatory, antioxidant, anti-tumor, and neuroprotective effects. Methods First, this study utilizes network pharmacology to explore the intrinsic connection between GK and OA. In vitro, SW1353 human cartilage cells were stimulated with Tert-butyl hydrogen peroxide (TBHP), and different GK concentrations were pre-treated to evaluate its protective effects. GK's anti-inflammatory and antioxidative effects were comprehensively assessed via MTT assay, western blot, cell immunofluorescence, ELISA, and transcriptome sequencing. Potential underlying mechanisms were also explored. In vivo, OA was induced in rats via anterior cruciate ligament transection (ACLT), and GK's impact on cartilage protection was further assessed via histological analysis and western blot. Results Network pharmacology has revealed that GK regulates OA via several key pathways, especially NF-κB, HIF-1, PI3K-AKT, and substances like reactive oxygen species. In vitro experiments showed GK effectively reverses oxidative stress damage from TBHP, inhibits inflammatory factor release, and protects Extracellular matrix (ECM) from degradation. These functions may be achieved via the NF-κB and MAPK signaling pathways. In vivo experiments showed GK significantly reduced proteoglycan loss from ACLT and inhibited matrix metalloproteinase 13 (MMP13) and ADAMTS5 (A disintegrin and metalloproteinase with thrombospondin motifs 5) production, effectively preventing cartilage degeneration in rats. Conclusion These findings suggest that GK has potential as a therapeutic agent for OA, offering new strategies and directions for OA treatment.

Plants and their interaction partners offer unparalleled views of evolutionary ecology. Nectar larceny, entailing nectar extraction without pollinating, is thought to be an example of a harmful, antagonistic behavior, but the precise consequences of floral larceny on plant reproductive success remain contentious. We conducted a comprehensive meta-analysis of 153 studies across 120 plant species, using 14 moderators to assess the effects of floral larceny on plant reproductive success and examine the key moderators. We found that floral larceny negatively impacts flower traits, pollinator visitation, pollen deposition, and fruit set, while having a neutral effect on critical female fitness indicators, such as seed set and seed quality, as well as on male fitness. By altering pollinator behavior, floral larceny may reduce geitonogamy, potentially enhancing genetic diversity. Additionally, factors such as pollinator type, plant mating system, and pollen limitation were identified as key moderators of these effects. Our analysis reveals an ultimately neutral effect of floral larceny on plant reproductive success, with potential benefits in certain contexts. These findings suggest that floral larceny plays a complex and multifaceted role within plant-pollinator interactions, facilitating the evolutionary stability and coexistence of floral larcenists and host plants.

Abstract Badminton-related injury is thought to happen with increasing incidence among badminton players. Literature shown injury incidence across age is scarce. The objective was to investigate the epidemiological characteristics of badminton-related injuries among badminton players broken down by age and sex. This epidemiology study is a retrospective design in 7–22-year-old badminton players at a national competitive tournament with a questionnaire from 2018 to 2023. An injury was defined as somatic complaint with time loss and/or medical care. Badminton-related injuries were normalized to rate per 1000 training-hours calculated by Poisson distribution in the collected data according to age and gender. Among all the 711 badminton players, 60.3% (429 players) suffered from at least one badminton-related injury. Regardless of gender, the most frequently injured anatomical site was knee (male: 18.8%, female: 18.6%), followed by ankle (male: 13.4%, female: 13.4%) and lower back (male: 12.3%, female: 10.0%). In male badminton players, the shoulder (7.6%) ranked fourth as the plantar (6.7%) ranked fourth in female badminton players. The rate per 1000 training-hours of badminton-related injuries showed that male players peaked at age 15–16 years and female players peaked at age 17–18 years, with 3.24 injuries and 3.52 injuries per 1000 training-hours, respectively. In 7–22-year-old badminton players, knee, lower back, and shoulder injuries frequently occurred and were significantly associated with the incidence of badminton-related injuries. The peak incidence of badminton-related injuries was in 15–16-year-old male badminton players while the peak incidence was in 17–18-year-old female badminton players. These data have the potential to help target the most at-risk anatomical sites and the most at-risk badminton players precisely for injury prevention programs.

Abstract We use an effective Lagrangian approach to investigate the production of the anticharmed pentaquark state $$P_{\bar{c}s}^{(*)-}$$ P c ¯ s ( ∗ ) - with the minimal quark content $$\bar{c}sudd$$ c ¯ s u d d in the $$\Lambda _b^0$$ Λ b 0 decay. In our calculation, the $$P_{\bar{c}s}^{(*)-}$$ P c ¯ s ( ∗ ) - is considered as the molecule state of the $$nD_{s0(s1)}^{-}$$ n D s 0 ( s 1 ) - in an S wave, and its production and decay occur via triangle loops at the hadron level. With the moderate model parameters, the computed results suggest that the branching fractions of $$\Lambda _b^0\rightarrow P_{\bar{c}s}^{(*)-} D^+ $$ Λ b 0 → P c ¯ s ( ∗ ) - D + can reach approximately $$10^{-4}$$ 10 - 4 . The possible decay modes $$ P_{\bar{c}s}^{(*)-} \rightarrow \Lambda D^{(*)-}$$ P c ¯ s ( ∗ ) - → Λ D ( ∗ ) - and $$ P_{\bar{c}s}^{(*)-} \rightarrow \Sigma D^{(*)-}$$ P c ¯ s ( ∗ ) - → Σ D ( ∗ ) - are also investigated. It is hoped that these predictions could be helpful in searching for the anticharmed-strange pentaquark candidates in future LHCb experiments.

[Objective] To explore the clinical significance and application value of establishing a database for red blood cell alloantibody detection. [Methods] Patients who were scheduled for blood transfusion in our hospital from January 1, 2020 to May 1, 2024 were selected as the research subjects. A red blood cell alloantibody detection database was established using Microsoft Office Excel software to register the detection data of patients' alloantibodies and antibodies of undetermined specificity (AUS). A retrospective analysis was conducted on the clinical characteristics, antibody distribution, antibody decay and repeat positivity of the patients in the database. The LISS-IAT method was routinely used for antibody screening and identification. [Results] Among the alloantibodies, the Rh blood group system had the highest detection rate, followed by antibodies of the MNS blood group system and the Lewis blood group system. The predominant antibody in the Rh blood group system was anti-E. In the univariate analysis, the positivity of antibody was significantly associated with the patient's gender, age, blood transfusion history, pregnancy history and type of disease (all P

Background: Distraction osteogenesis(DO) is a valuable bone regeneration technique, yet its prolonged consolidation phase often entails pain, high costs, infection risks, and lifestyle disruptions. Finding adjunctive approaches to shorten treatment duration is thus of clinical significance. Long noncoding RNAs have been demonstrated to play pivotal roles in regulating bone formation, and homeobox transcript antisense intergenic RNA(HOTAIR) was also reported to regulate osteogenesis and bone formation. However, its role in DO remains unclear. Methods: The effects of HOTAIR on osteogenesis were examined in rat bone marrow-derived mesenchymal stem cells(BMSCs) by asssessing ALP activity, calcification, and osteogenic gene expression with HOTAIR knockdown or overexpression. Using a tibial DO model, HOTAIR-stably silenced BMSCs or control cells were locally injected into the percutaneous distraction gap, and the effects were evaluated by micro-CT, dual-energy X-ray examination, mechanical testing, hematoxylin and eosin staining, and immunohistochemistry. Results: In the present study, it was found that HOTAIR silence promoted while its overexpression suppressed the osteogenic differentiation of BMSCs. The Mechanistic study revealed that HOTAIR physically interacted with FTO, and disrupted FTO ubiquitination and degradation, leading to FTO up-regulation and suppressing osteogenesis. Using DO animal model, HOTAIR-silenced BMSCs stimulated new bone formation and accelerated DO healing in vivo. Conclusion: Silence of HOTAIR enhanced osteogenesis in BMSCs and facilitated DO healing by recruiting FTO and inducing its degradation. Translational potential: The findings generated from this study suggest that inhibitor of HOTAIR may be developed as a promising strategy for DO patients.

Abstract A Gemini cationic surfactant was synthesized through an aldehyde-amine condensation reaction to address challenges related to bacterial corrosion and foaming during shale gas extraction. This treatment agent exhibits sterilization, corrosion mitigation, and foaming properties. The mechanism of action was characterized through tests measuring surface tension, particle size, sterilization efficacy, corrosion mitigation efficiency, and foaming behavior. Results from the surface tension test indicate that at 60 °C, surfactants with a low carbon chain structure achieve the lowest surface tension of 32.61 mN/m at the critical micelle concentration. Particle size distribution (PSD) tests reveal that within the 1–10 critical micelle concentration range, three types of surfactants can form aggregates through self-assembly, with a PSD range of 100–400 nm. Antibacterial performance tests demonstrate that a concentration of 0.12 mmol/L at 20–60 °C achieves a bactericidal rate exceeding 99%, maintained even after 24 h of contact. The bactericidal effect is enhanced under acidic and alkaline conditions. Corrosion mitigation tests show that at 50 °C, the corrosion mitigation rate reaches an optimal value of over 70%. Bubble performance evaluation results suggest that the optimal surfactant concentration is 1 mmol/L at 60 °C, exhibiting resistance to mineralization up to 200 g/L. The development of this surfactant establishes a foundation for effectively addressing issues related to bacterial corrosion and wellbore fluid encountered in shale gas wells.

Abstract Background Abdominal aortic calcification (AAC) is considered as a strong predictor of cardiovascular disease (CVD) events. Our study aimed to investigate whether the predicted risk for cardiac death with the Framingham risk score (FRS) could be further improved with the addition of AAC score in general population aged ≥ 40 years. Methods A total of 2971 participants aged ≥ 40 years in the National Health and Nutrition Examination Surveys (NHANES) 2013–2014 were followed up. The Spearman’s rank correlation was performed to explore the correlation between the AAC score and FRS. the Kaplan-Meier method was used to make cumulative cardiac death curve. Predictors of cardiac death was identified by multivariate Cox regression. Additionally, the predictive value of FRS alone and combined with AAC score was estimated by comparing the area under the receiver-operating characteristic (ROC) curve (AUC) and calculating Integrated Discrimination Improvement (IDI). Results During a median of 70.50 months (interquartile range 58.43–82.57 months), 49 (1.649%) experienced cardiac death in the follow-up. The FRS was positively associated with AAC score. Both FRS and AAC score were independent predictors of cardiac death (hazard ratio 1.216; 95%CI 1.135 to 1.302; p

Abstract Understanding human endometrial dynamics in the establishment of endometrial receptivity remains a challenge, which limits early diagnosis and treatment of endometrial-factor infertility. Here, we decode the endometrial dynamics of fertile women across the window of implantation and characterize the endometrial deficiency in women with recurrent implantation failure. A computational model capable of both temporal prediction and pattern discovery is used to analyze single-cell transcriptomic data from over 220,000 endometrial cells. The time-series atlas highlights a two-stage stromal decidualization process and a gradual transitional process of the luminal epithelial cells across the window of implantation. In addition, a time-varying gene set regulating epithelium receptivity is identified, based on which the recurrent implantation failure endometria are stratified into two classes of deficiencies. Further investigation uncovers a hyper-inflammatory microenvironment for the dysfunctional endometrial epithelial cells of recurrent implantation failure. The holistic characterization of the physiological and pathophysiological window of implantation and a computational tool trained on this temporal atlas provide a platform for future therapeutic developments.

Abstract The lack of high-efficiency platinum (Pt)-based nanomaterials remains a formidable and exigent challenge in achieving high formic acid oxidation reaction (FAOR) and membrane electrode assembly (MEA) catalysis for direct formic acid fuel cell (DFAFC) technology. Herein, we report 16 Pt-based heterophase nanotrepang with rare earth (RE)-doped face-centered cubic Pt (fcc-Pt) and trigonal Pt-tellurium (t-PtTe2) configurations ((RE-Pt)-PtTe2 HPNT). Yttrium (Y) is identified as the optimal dopant, existing as single sites and clusters on the surface. The (Y-Pt)-PtTe2 HPNT/C demonstrates the superior mass and specific activities of 6.4 A mgPt −1 and 5.4 mA cm-2, outperforming commercial Pt/C by factors of 49.2 and 25.7, respectively. Additionally, it achieves a normalized MEA power density of 485.9 W gPt −1, tripling that of Pt/C. Density functional theory calculations further reveal that Y doping enhances HCOO* intermediate adsorption and suppresses CO intermediate formation, thereby promoting FAOR kinetics. This work highlights the role of RE metals in heterostructure regulation of Pt-based anodic nanomaterials for achieving the efficient direct formic acid electrocatalysis.

Abstract High intrinsic detection efficiency is as decisive as high energy resolution. Scaling up detector volume has presented great challenges, preventing perovskite semiconductors from reaching sufficient detection efficiency. We report a hole-only virtual-Frisch-grid CsPbBr3 detector up to 2.2 cm thick for efficient gamma-ray spectroscopy. By utilizing high-quality columnar CsPbBr3 single crystals up to ~1 cm3, we configure virtual-Frisch-grid detectors with optimized weighting potential distribution. These centimeter-thick detectors outperform ambipolar planar configuration, achieving a champion energy resolution of 1.9% at 662 keV. Time-of-flight analysis, stimulated by single gamma-ray photon, reveals hole carrier multiplication effect possibly caused by Auger recombination and space charge accumulation effect, collectively driving an anomalous stabilization process. Digital pulse measurements reduce the ballistic deficit, thereby improving the spectral response to 2.2% at 662 keV for 2.2 cm thick detector. The low-cost device fabrication and adequate detection efficiency of virtual-Frisch-grid detectors will surely foster the development of large-volume perovskite detectors.

Abstract Urban overheating significantly affects thermal comfort and livability, making it essential to understand the relationship between urban form and land surface temperature (LST). While the horizontal dimensions of urban form have been widely studied, the vertical structures and their impact on LST remain underexplored. This study investigates the influence of three-dimensional urban form characteristics on LST, using ECOSTRESS sensor data and four machine learning models. Six urban morphology variables—building density (BD), mean building height (MH), building volume (BVD), gross floor area (GFA), floor area ratio (FAR), and sky view factor (SVF)—are analyzed across different seasons and times of day. The results reveal that MH, BD, and FAR are season-stable factors, with higher MH correlated with lower LST ((e.g., an observed reduction of approximately 3 °C in spring), while higher BD is associated with higher LST (e.g., an increase of about 3.5 °C in autumn). In contrast, BVD, GFA, and SVF are season-varying factors with variable impacts depending on the time of year. Higher BVD is generally associated with elevated LST, while GFA and SVF are linked to lower LST. These associations reflect absolute changes in LST, measured directly from ECOSTRESS data. These findings offer valuable insights into the complex interactions between urban morphology and LST, helping to inform strategies for urban heat mitigation and sustainable planning.

Abstract Background To investigate the optimization of leadless pacemaker placement and to assess its impact on heart synchronization and tricuspid regurgitation. Results A clinical trial was conducted involving 53 patients who underwent leadless pacemaker implantation at the Second Affiliated Hospital of Zhejiang University School of Medicine and Hangzhou First People’s Hospital between March 2022 and February 2023. Implantation site localization was determined using the 18-segment method under RAO 30° imaging. Intraoperative and 1-month post-operative echocardiography was performed to assess cardiac electromechanical synchronization and tricuspid regurgitation; parameters of interest included interventricular mechanical delay (IVMD), pre-ejection period of the aorta (L-PEI), and septal-to-posterior wall motion delay (SPWMD). Pacing thresholds, sensing, and impedance exhibited no significant differences between the 8/9 zone and other sites (P > 0.05). In contrast, the 8/9 zone group manifested a significant reduction in L-PEI (128.24 ± 12.27 vs. 146.50 ± 18.17 ms, P

Abstract Objective We aimed to outline the experience with extracorporeal membrane oxygenation (ECMO) for respiratory and cardiac failure in neonates in our institution and compare our results with those from other countries. Method The clinical data of 28 neonates who required ECMO assistance were studied retrospectively. Results A total of 28 neonates underwent support with veno-arterial ECMO, including 14 cardiac support and 14 respiratory support. The neonates with a median age of 5 days (1–28 days) and a median weight of 3.3 kg (2.4–4.2 kg). Of these neonates, 4 were female, and 24 were male. Among the neonates. For neonates requiring ECMO support for cardiac conditions, 9 survived, resulting in a 64% survival rate. In contrast, for those requiring ECMO support for respiratory conditions, 6 survived, indicating a 42% survival rate. The survivors exhibited a significant reduction in lactic acid levels within the first 24 h. In the 15 successful weaning neonates, four neonates died at the end of the study; one was for the cardiac function failure; two were for the respiratory failure; one was given up for Bipedal necrosis; the other 11 neonates were successful discharge. Notably, two neonates underwent ECMO ventilation in the prone position without experiencing any complications. Conclusion The utilization of ECMO support in neonates experiencing severe respiratory and cardiac failure efficiently improves cardiopulmonary function and significantly reduces mortality rates among critically ill neonates. The neonates with a respiratory indication in our study have a lower survival rate than other reported in the literature. Monitoring the trend in lactate levels following ECMO support proves valuable in estimating the prognosis of affected children.

AIM: To investigate whether interleukin-17A (IL-17A) gets involved in the mechanisms of inflammation-related retinal pigment epithelium (RPE) cells injury and its significance in age-related macular degeneration (AMD). RESULTS: In the scenario of NaIO3 stimulation, RPE cells obviously tended to degenerate. Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice, whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/- mice. In addition, IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo. Meanwhile, the extracellular signal-regulated kinase (ERK) signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo, as IL-17A-induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway. CONCLUSION: IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway. Inhibition of IL-17A may be a new potential target for dry AMD treatment.

Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism Saccharomyces cerevisiae (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining β-carotene 15,15′-mono(di)oxygenase from different sources and identified two isoenzymes Mbblh and Ssbco with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from β-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from Homo sapiens was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing POS5Δ17 enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene Mbblh further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in S. cerevisiae was achieved in a 1-L bioreactor. This study unlocked the potential of S. cerevisiae for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.

Abstract Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC). Importantly, HSC-supporting ability of BM EPCs is partially recovered, whereas leukemia-supporting ability is decreased in CR patients. Mechanistically, the transcriptome characteristics of leukemia-modified BM EPCs return to near-normal after CR. In a classic AML mouse and chemotherapy model, BM vasculature and normal hematopoiesis are reversed after CR. In summary, we provide further insights into how leukemia-modified BM microenvironment can be remodeled to support normal hematopoiesis after CR, which can be further improved by NAC.

Abstract This study is to analyse the failure patterns and long-term survival after stereotactic body radiotherapy (SBRT) in patients with T1-3N0M0 inoperable non-small cell lung cancer (NSCLC). Early-stage NSCLC patitents who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary endpoint were the patterns of disease progression, which were divided into local recurrence, regional failure, and distant metastasis. Kaplan-Meier method survival analysis was used to calculate overall survival (OS), progression-free survival (PFS). Cox model was used for univariate analysis and multivariate analysis. A total of 215 patients with 224 lesions were enrolled. After the median follow-up time of 50.8 months (1.0-117.9 months), 76 (35.3%) patients progressed, with regional progression occurring in 4 cases (1.8%), local and local-regional progression in 17 cases (7.9%), various distant metastases developing in 55 cases (25.6%). The OS rates at 1, 3, and 5 years were 97.1%, 80.9%, and 63.8%, respectively, with a median OS of 92.2 months (95%CI, 61.5-122.9 months). The PFS rates at 1, 3, and 5 years were 87.5%, 65.9%, and 50.8%, respectively, with a median PFS of 62.2 months (95% CI, 45.0-59.4 months). There was no significant difference in OS (P = 0.832) and PFS (P = 0.672) between the two groups with or without pathology. Multivariate analysis showed that BED and patient age were independent prognostic factors affecting early-stage lung cancer survival (all P

The availability of civil aircraft cockpit display interface is related to pilot's satisfaction as well as flight safety and efficiency, but current indicator system in this field lacks target-oriented focus. Firstly, in this paper, the flight mission, pilots' senses, pilots' cognition, and flight interaction dimensions are obtained by executive process interactive control model(EPIC), and extracted usability indicators from these dimensions. Secondly, to tackle the problem of filtering multidimensional indicator datasets supported by small samples, an indicator clustering reduction algorithm is proposed based on hierarchical clustering-rough set information entropy(HC-CEBARKNC) which compared to K-means clustering and genetic algorithm. Finally, the support vector machine(SVM) classification model was employed to verify performance and reliability of both algorithms. The experimental result shows the HC-CEBARKNC algorithm proposed has better evaluation accuracy that contribute to practical indicators reduction and decision rules screening.

Abstract Among the existing research on the treatment of disorders of consciousness (DOC), deep brain stimulation (DBS) offers a highly promising therapeutic approach. This comprehensive review documents the historical development of DBS and its role in the treatment of DOC, tracing its progression from an experimental therapy to a detailed modulation approach based on the mesocircuit model hypothesis. The mesocircuit model hypothesis suggests that DOC arises from disruptions in a critical network of brain regions, providing a framework for refining DBS targets. We also discuss the multimodal approaches for assessing patients with DOC, encompassing clinical behavioral scales, electrophysiological assessment, and neuroimaging techniques methods. During the evolution of DOC therapy, the segmentation of central nuclei, the recording of single-neurons, and the analysis of local field potentials have emerged as favorable technical factors that enhance the efficacy of DBS treatment. Advances in computational models have also facilitated a deeper exploration of the neural dynamics associated with DOC, linking neuron-level dynamics with macroscopic behavioral changes. Despite showing promising outcomes, challenges remain in patient selection, precise target localization, and the determination of optimal stimulation parameters. Future research should focus on conducting large-scale controlled studies to delve into the pathophysiological mechanisms of DOC. It is imperative to further elucidate the precise modulatory effects of DBS on thalamo-cortical and cortico-cortical functional connectivity networks. Ultimately, by optimizing neuromodulation strategies, we aim to substantially enhance therapeutic outcomes and greatly expedite the process of consciousness recovery in patients.

Abstract Background Epithelial ovarian cancer (EOC) is a lethal form of gynecological malignancy. Some EOC patients experience relapse after standard primary debulking surgery (PDS) and adjuvant chemotherapy (ACT). Identifying molecular residual disease (MRD) by circulating tumor DNA (ctDNA) detection can timely signal the potential for relapse. However, research on the usage of ctDNA for MRD detection in EOC is limited. Methods Fifty-one EOC patients who received standard PDS and ACT were included. Targeted sequencing based on a panel of 1021 cancer-related genes, along with further validation using Enrich-rare-mutation sequencing, was performed on tumor tissues acquired during PDS and on plasma samples collected before and after PDS/ACT to identify variants reflecting tumor signals. Results Post-surgery MRD was associated with relapse (Log-rank p = 0.0006) and was identified as an independent prognostic factor (HR, 3.4; 95% CI, 1.02–11.42; p = 0.047). The negative and positive predictive values were 0.83 and 0.62 respectively. Additionally, post-surgery MRD outperformed CA125 in predicting relapse, and integrating both parameters could provide more accurate risk stratification. Post-ACT MRD detection identified the patients with ctDNA clearance who were still at risk of relapse. Furthermore, baseline ctDNA detection could help determine patients who are not suitable for further tests after surgery. Conclusions Post-surgery MRD is superior to CA125 in predicting relapse in EOC. Patients exhibiting transient ctDNA clearance, as evaluated by post-ACT MRD, may require longitudinal monitoring. Baseline ctDNA detection could help determine whether post-surgery ctDNA monitoring should be performed.

Abstract The prospective use of food additive titanium dioxide (E171 TiO2) in a variety of fields (food, pharmaceutics, and cosmetics) prompts proper cellular cytotoxicity and transcriptomic assessment. Interestingly, smaller-sized E171 TiO2 can translocate in bloodstream and induce a diverse immunological response by activating the immune system, which can be either pro-inflammatory or immune-suppressive. Nevertheless, their cellular or immunologic responses in a heterogeneous population of the immune system following exposure of food additive E171 TiO2 is yet to be elucidated. For this purpose, we have used male Sprague-Dawley rats to deliver E171 TiO2 (5 mg/kg bw per day) via non-invasive intratracheal instillation for 13 weeks. After the 4 weeks recovery period, 3 mL of blood samples from both treated and untreated groups were collected for scRNAseq analysis. Firstly, granulocyte G1 activated innate immune response through the upregulation of genes involved in pro-inflammatory cytokine mediated cytotoxicity. Whereas NK cells resulted in heterogeneity role depending on the subsets where NK1 significantly inhibited cytotoxicity, whereas NK2 and NK3 subsets activated pro-B cell population & inhibited T cell mediated cytotoxicity respectively. While NKT_1 activated innate inflammatory responses which was confirmed by cytotoxic CD8+ T killer cell suppression. Similarly, NKT_2 cells promote inflammatory response by releasing lytic granules and MHC-I complex inhibition to arrest cytotoxic T killer cell responses. Conversely, NKT_3 suppressed inflammatory response by release of anti-inflammatory cytokines suggesting the functional heterogeneity of NKT subset. The formation of MHC-I or MHC-II complexes with T-cell subsets resulted in neither B and T cell dysfunction nor cytotoxic T killer cell inhibition suppressing adaptive immune response. Overall, our research offers an innovative high-dimensional approach to reveal immunological and transcriptomic responses of each cell types at the single cell level in a complex heterogeneous cellular environment by reassuring a precise assessment of immunological response of E171 TiO2. Graphical Abstract

Bacillus mojavensis KRS009 was identified as an antagonistic strain with a strong inhibitory effect on various phytopathogenic fungi. To provide further insight into its biocontrol mechanisms and ability to improve plant salt tolerance, the high quality complete genome of KRS009 was sequenced by PacBio platform and assembled using PacBio-HiFiReads. The KRS009 genome consists of one circular chromosome of 4,089,687 bp with 43.5% GC content and 4,062 open reading frames, of which 3,920 protein-coding genes, 86 transfer RNA, 10 ribosomal RNA, and 26 small RNA were identified in this genome. Among them, genes related to compatible solutes, including treC, galU, proX, and proW, are involved in the synthesis of trehalose, proline, and betaine metabolism and play an important role in relieving osmotic stress. In addition, the KRS009 genome contains genes associated with high salinity tolerance, including those responsible for Na+/H+ antiporters, K+ transporters, TrkH thiamin phosphate synthase, K+-sensing histidine kinase, aryl-phospho-beta-D-glucosidase, flavoprotein CzcO associated with the cation diffusion facilitator CzcD, and chaperonin GroEL. Together, the high-quality genome resource of strain KRS009 would provide a molecular basis for further research on its biocontrol and plant salt tolerance mechanisms. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Receptor kinases play a pivotal role in detecting environmental signals, and consequently, gene pleiotropy is frequently observed within this family. However, the trade-off in trait expression resulting from gene pleiotropy poses a constraint on the utilization of such genes in agricultural breeding. In this study, we identified the receptor kinase gene FERONIA-Like Receptor 13 (FLR13) as a pleiotropic gene influencing plant height, tillering, grain yield, and disease resistance. Using promoter editing, we generated novel alleles (FLR13T5T6-1, FLR13T5T6-2) that confer resistance to rice blast and increase per-plant yield. The knockout of the T5T6 segment alleviates the inhibitory effects of two transcription factors, OsGBP1 and OsWRKY53, on FLR13 expression. In summary, our study presents a promising avenue for enhancing the pivotal attributes of receptor-like kinases through a promoter-editing strategy.

Abstract Background Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. This study included mild, moderate, severe, and critical COVID-19 patients to evaluate azvudine’s effectiveness across different severity levels. Methods We conducted a retrospective cohort study of patients with COVID-19 admitted to our hospital from December 1, 2022, to March 31, 2023. Patients were divided into retrospective cohorts receiving azvudine antiviral therapy and standard treatment, and were followed-up for up to 28 days. Results Prior to data processing, azvudine treatment was associated with reduced mortality rates at 7 days (1.09/1000 persons vs. 5.06/1000 persons, P

Abstract With the advancement of precise hepatobiliary surgery concepts, the diagnostic and therapeutic approaches for hepatic echinococcosis have undergone significant transformations. However, whether these changes have correspondingly improved patient outcomes remains unclear. A retrospective analysis of these changes will provide crucial guidance for the prevention and treatment of hepatic echinococcosis. Clinical data from 6 hospitals in Xinjiang region of China from January 2009 to December 2023 were collected and systematically random sampling was conducted. The study was divided into the first stage (2009–2013), the second stage (2014–2018), and the third stage (2019–2023) with a 5-year time node to compare the changes in diagnosis and treatment mode and clinical features. There was no significant difference in the age of onset among patients across different phases (P = 0.759). The frequency of open cystectomy gradually decreased [302 (62.3%), 223 (53.0%), 165 (55.7%), P = 0.015], while the rate of total cystectomy increased steadily [82 (16.9%), 88 (20.9%), 94 (23.7%), P = 0.040]. The proportion of patients admitted due to screening also increased [367 (75.7%), 373 (88.6%), 364 (91.9%), P

ABSTRACT Background Cancer cachexia significantly contributes to morbidity and mortality in patients with non‐small‐cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin‐6 (IL‐6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL‐6‐elevated cachexia. Methods In this retrospective study, data were collected from patients with NSCLC and concurrent IL‐6‐elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C‐reactive protein (CRP) and mGPS. Qualitative improvements in patient self‐rated appetite and fatigue were reported as exploratory analysis. Results The study included 49 patients diagnosed with NSCLC and IL‐6‐elevated cachexia, Eastern Cooperative Oncology Group performance status of 2–4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08–0.38; p

Abstract Strong light-matter interaction provides opportunities for tailoring the physical properties of quantum materials on the ultrafast timescale by forming photon-dressed electronic states, i.e., Floquet-Bloch states. While the light field can in principle imprint its symmetry properties onto the photon-dressed electronic states, so far, how to experimentally detect and further engineer the symmetry of photon-dressed electronic states remains elusive. Here by utilizing time- and angle-resolved photoemission spectroscopy (TrARPES) with polarization-dependent study, we directly visualize the parity symmetry of Floquet-Bloch states in black phosphorus. The photon-dressed sideband exhibits opposite photoemission intensity to the valence band at the Γ point, suggesting a switch of the parity induced by the light field. Moreover, a “hot spot” with strong intensity confined near Γ is observed, indicating a momentum-dependent modulation beyond the parity switch. Combining with theoretical calculations, we reveal the light-induced engineering of the wave function of the Floquet-Bloch states as a result of the hybridization between the conduction and valence bands with opposite parities, and show that the “hot spot” is intrinsically dictated by the symmetry properties of black phosphorus. Our work suggests TrARPES as a direct probe for the parity of the photon-dressed electronic states with energy- and momentum-resolved information, providing an example for engineering the wave function and symmetry of such photon-dressed electronic states via Floquet engineering.

Abstract Cancer cells secrete extracellular vesicles (EV) encapsulating bioactive cargoes to facilitate inter-organ communication in vivo and are emerging as critical mediators of tumor progression and metastasis, a condition which is often accompanied by a dysregulated cholesterol metabolism. Whether EVs are involved in the control of cholesterol homeostasis during tumor metastasis is still undefined and warrant further investigation. Here, we find that breast cancer-derived exosomal miR-9-5p induces the expression of HMGCR and CH25H, two enzymes involved in cholesterol synthesis and the conversion of 25-hydroxycholesterol from cholesterol by targeting INSIG1, INSIG2 and ATF3 genes in the liver. Notably, in vivo miR-9-5p antagomir treatment and genetic CH25H ablation prevents tumor metastasis in a mouse model of breast cancer. Thus, our findings reveal the regulatory mechanism of tumor-derived miR-9-5p in liver metastasis by linking oxysterol metabolism and Kupffer cell polarization, shedding light on future applications for cancer diagnosis and treatment.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic and is continuously spreading globally. The continuous emergence of new SARS-CoV-2 variants keeps posing threats, highlighting the need for fast-acting, mutation-resistant broad-spectrum therapeutics. Protein translation is vital for SARS-CoV-2 replication, producing early non-structural proteins for RNA replication and transcription, and late structural proteins for virion assembly. Targeted blocking of viral protein translation is thus a potential approach to developing effective anti-SARS-CoV-2 drugs. SARS-CoV-2, as an obligate parasite, utilizes the host’s translation machinery. Translation-blocking strategies that target the SARS-CoV-2 mRNA, especially those that target its conserved elements are generally preferred. In this review, we discuss the current understanding of SARS-CoV-2 translation, highlighting the important conserved motifs and structures involved in its regulation. We also discuss the current strategies for blocking SARS-CoV-2 translation through viral RNA degradation or RNA element dysfunction.

Computational modeling has earned significant interest as an alternative to animal testing of toxicity assessment. However, the process of selecting an appropriate algorithm and fine-tuning hyperparameters for the developing of optimized models takes considerable time, expertise, and an intensive search. The recent emergence of automated machine learning (autoML) approaches, available as user-friendly platforms, has proven beneficial for individuals with limited knowledge in ML-based predictive model development. These autoML platforms automate crucial steps in model development, including data preprocessing, algorithm selection, and hyperparameter tuning. In this study, we used seven previously published and publicly available datasets for oxides and metals to develop nanotoxicity prediction models. AutoML platforms, namely Vertex AI, Azure, and Dataiku, were employed and performance measures such as accuracy, F1 score, precision, and recall for these autoML-based models were then compared with those of conventional ML-based models. The results demonstrated clearly that the autoML platforms produced more reliable nanotoxicity prediction models, outperforming those built with conventional ML algorithms. While none of the three autoML platforms significantly outperformed the others, distinctions exist among them in terms of the available options for choosing technical features throughout the model development steps. This allows users to select an autoML platform that aligns with their knowledge of predictive model development and its technical features. Additionally, prediction models constructed from datasets with better data quality displayed, enhanced performance than those built from datasets with lower data quality, indicating that future studies with high-quality datasets can further improve the performance of those autoML-based prediction models.