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Abstract Background Leaves are important sites for photosynthesis and can convert inorganic substances into organic matter. Photosynthetic performance is an important factor affecting crop yield. Leaf colour is closely related to photosynthesis, and leaf colour mutants are considered an ideal material for studying photosynthesis. Results We obtained a yellow-green leaf mutant jym165, using ethyl methane sulfonate (EMS) mutagenesis. Physiological and biochemical analyses indicated that the contents of chlorophyll a, chlorophyll b, carotenoids, and total chlorophyll in the jym165 mutant decreased significantly compared with those in Jiyu47 (JY47). The abnormal chloroplast development of jym165 led to a decrease in net photosynthetic rate and starch content compared with that of JY47. However, quality traits analysis showed that the sum of oil and protein contents in jym165 was higher than that in JY47. In addition, the regional yield (seed spacing: 5 cm) of jym165 increased by 2.42% compared with that of JY47 under high planting density. Comparative transcriptome analysis showed that the yellow-green leaf phenotype was closely related to photosynthesis and starch and sugar metabolism pathways. Genetic analysis suggests that the yellow-green leaf phenotype is controlled by a single recessive nuclear gene. Using Mutmap sequencing, the candidate regions related of leaf colour was narrowed to 3.44 Mb on Chr 10. Conclusions Abnormal chloroplast development in yellow-green mutants leads to a decrease in the photosynthetic pigment content and net photosynthetic rate, which affects the soybean photosynthesis pathway and starch and sugar metabolism pathways. Moreover, it has the potentiality to increase soybean yield under dense planting conditions. This study provides a useful reference for studying the molecular mechanisms underlying photosynthesis in soybean.

Abstract Presenilin-associated protein (PSAP) is a mitochondrial proapoptotic protein as established in cell biology studies. It remains unknown whether it involves in neurodegenerative diseases. Here, we explored PASP expression in adult and aged human brains and its alteration relative to Alzheimer-disease (AD)-type neuropathology. In pathology-free brains, light PASP immunoreactivity (IR) occurred among largely principal neurons in the cerebrum and subcortical structures. In the brains with AD pathology, enhanced PSAP IR occurred in neuronal and neuritic profiles with a tangle-like appearance, with PSAP and pTau protein levels elevated in neocortical lysates relative to control. Neuronal/neuritic profiles with enhanced PSAP IR partially colocalized with pTau, but invariably with Amylo-Glo labelled tangles. The neuronal somata with enhanced PASP IR also showed diminished IR for casein kinase 1 delta (Ck1δ), a marker of granulovacuolar degeneration; and diminished IR for sortilin, which is normally expressed in membrane and intracellular protein sorting/trafficking organelles. In old 3xTg-AD mice with β-amyloid and pTau pathologies developed in the brain, PSAP IR in the cerebral sections exhibited no difference relative to wildtype mice. These findings indicate that PSAP upregulation is involved in the course of tangle formation especially in the human brain during aging and in AD pathogenesis.

Abstract Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; P

Biosafety hazards can trigger a host immune response after infection, invasion, or contact with the host. Whether infection with a microorganism results in disease or biosafety concerns depends to a large extent on the immune status of the population. Therefore, it is essential to investigate the immunological characteristics of the host and the mechanisms of biological threats and agents to protect the host more effectively. Emerging and re-emerging infectious diseases, such as the current coronavirus disease 2019 (COVID-19) pandemic, have raised concerns regarding both biosafety and immunology worldwide. Interdisciplinary studies involved in biosafety and immunology are relevant in many fields, including the development of vaccines and other immune interventions such as monoclonal antibodies and T-cells, herd immunity (or population-level barrier immunity), immunopathology, and multispecies immunity, i.e., animals and even plants. Meanwhile, advances in immunological science and technology are occurring rapidly, resulting in important research achievements that may contribute to the recognition of emerging biosafety hazards, as well as early warning, prevention, and defense systems. This review provides an overview of the interdisciplinary field of biosafety and immunology. Close collaboration and innovative application of immunology in the field of biosafety is becoming essential for human health.

Polydiacetylene (PDA) liposomes have been widely applied for detection due to their distinctive optical properties. However, the liquid phase in which PDA liposomes are dispersed generates several drawbacks, for instance, instability, compromise of detection sensitivity induced by dilution, and separation of target sampling and detection, making it inconvenient for application. In this paper, various functionalized PDA liposomes for detecting target were prepared, which were also immobilized into swelling microneedles to construct a solid-phase detection system. The PDA liposomes-complexed microneedles (PDA/MNs) enable the integration of target sampling and detection in one platform. The effects of the dispersing matrix phase on the detection sensitivity of PDA liposomes were systematically investigated from both environmental and chemical perspectives. PDA/MNs exhibited higher sensitivity than their counterparts in liquid phase. PDA/MNs were optimized and validated for lead ion (Pb2+) and sialic acid (SA) detections. For Pb2+ detection, the limit of detection (LOD) of the PDA/MNs was 13.7 μM and 2.5 times lower than the liquid phase. For SA detection, the LOD of the PDA/MNs was 0.83 μM and 1.7 times lower than the liquid phase. The results suggested that such PDA/MNs were validated to provide a label-free, stable, sensitive, and convenient tool in an all-in-one manner for physiologic target detection.

Abstract Myeloid cells are pivotal in the inflammatory and remodeling phases of fracture repair. Here, we investigate the effect of periostin expressed by myeloid cells on bone regeneration in a monocortical tibial defect (MTD) model. In this study, we show that periostin is expressed by periosteal myeloid cells, primarily the M2 macrophages during bone regeneration. Knockout of periostin in myeloid cells reduces cortical bone thickness, disrupts trabecular bone connectivity, impairs repair impairment, and hinders M2 macrophage polarization. Mechanical stimulation is a regulator of periostin in macrophages. By activating transforming growth factor-β (TGF-β), it increases periostin expression in macrophages and induces M2 polarization. This mechanosensitive effect also reverses the delayed bone repair induced by periostin deficiency in myeloid cells by strengthening the angiogenesis-osteogenesis coupling. In addition, transplantation of mechanically conditioned macrophages into the periosteum over a bone defect results in substantially enhanced repair, confirming the critical role of macrophage-secreted periostin in bone repair. In summary, our findings suggest that mechanical stimulation regulates periostin expression and promotes M2 macrophage polarization, highlighting the potential of mechanically conditioned macrophages as a therapeutic strategy for enhancing bone repair.

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract The expression and biological function of junctional adhesion molecule-like protein (JAML) in colorectal cancer (CRC) remain unclear. Paraffin tissue samples from 50 cases of CRC were collected to determine the expression of JAML. JAML was overexpressed or knock-down in CRC cells to evaluated the proliferation, migration and invasion in vitro and in vivo. Western-blot and others were applied to explore the mechanisms. The study showed that JAML was highly expressed within cancer tissues in 50% (25/50) of patients with CRC, and was correlated with higher TNM stage (p

Abstract Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

Abstract Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. Graphical Abstract

The orchid Calanthe discolor, which has high ornamental and medicinal value, is mainly distributed in Zhejiang, Jiangsu, and southeast Hubei Provinces of China, as well as in Japan and the southern Korean peninsula. In this study, the whole chloroplast genome sequence of C. discolor was first assembled using high-throughput Illumina paired-end technology, providing data to evaluate the evolution of this species. The C. discolor chloroplast genome was158,286 bp long, including a large single-copy region of 87,095 bp, a small single-copy region of 18,407 bp, and two copies of a repeat region (26,392-bp each). The overall G + C content was 41.2%. A total of 133 genes were predicted from the genome, including 87 protein-coding genes, eight ribosomal RNAs, 38 transfer RNAs. Phylogenetic analysis indicated a close relationship between C. discolor and C. bicolor.

Abstract We addressed fundamental questions about the influence of metabolites on the development of Diabetic retinopathy (DR), and explored the related pathological mechanism. Genome-wide association study (GWAS) database data for metabolites and DR were used to perform Mendelian randomization (MR) studies. The inverse variance weighting (IVW) was chosen as the primary analysis method. Sensitivity analysis was conducted using MR-PRESSO, leave-one-out and Cochran’s Q test. Confounding factors were eliminated to ensure robustness. We also conducted metabolic pathway analysis. In vivo experimental validation was conducted using Sprague Dawley rats. The serum metabolites of the DR group rats and normal group rats were examined to evaluate the MR results. The screen identified eighteen metabolites associated with DR risk, twelve of which were known components. Seven metabolites were positively correlated with DR risk, while five could reduce it. Eight metabolites associated with proliferative DR (PDR) risk were identified, four of which are known components. Three of these were positively associated with PDR risk and one metabolite reduced PDR risk. Additionally, two possible metabolic pathways involved in the biological mechanism of DR were identified. The ELISA results showed that the serum levels of isoleucine and 4-HPA were significantly increased in DR rats, while the level of inosine was decreased. This study offers novel insights into the biological mechanisms underlying DR. Metabolites that are causally linked to DR may serve as promising biomarkers and therapeutic targets.

Abstract Keratoconus (KC) is an irreversible blinding eye disease; therefore, early screening of KC suspects (KCS) is crucial for protecting patients’ quality of life. Scheimpflug imaging is a commonly used screening device in clinical practice. We aimed to evaluate the diagnostic ability of a Scheimpflug imaging device (Scansys) for KC and KCS and compared it with other Scheimpflug-based devices (Pentacam and Corvis ST). This prospective case-control study included 107 normal eyes, 72 KCS, and 57 KC. Scansys screening index Keratoconus probability (KCP) showed excellent performance in diagnosing KC at a cutoff value of 16.4 (area under the receiver operating characteristic [AUROC] = 1.000), with 100% sensitivity and 98.11% specificity. KCP had a better KCS diagnostic ability at a cutoff value of 8.9 (AUROC = 0.813) than Corvis biomechanical index (CBI, AUROC = 0.764), reaching 67.61% sensitivity and 85.85% specificity. Pentacam screening index Belin/Ambrósio enhanced ectasia display deviation (BAD-D) showed the best performance with 92.96% sensitivity and 89.62% specificity at a cutoff value of 1.525 (AUROC = 0.970) in diagnosing KCS. Scansys provides accurate KCP parameters in diagnosing KC; however, the efficiency of diagnosing KCS should be further optimized.

Abstract Background The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk. Methods We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups. Results Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for “CC” started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort. Conclusion The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice.

Abstract Small-cell lung cancer (SCLC) transformation accounts for 3–14% of resistance in EGFR-TKI relapsed lung adenocarcinomas (LUADs), with unknown molecular mechanisms and optimal treatment strategies. We performed transcriptomic analyses (including bulk and spatial transcriptomics) and multiplex immunofluorescence on pre-treated samples from LUADs without transformation after EGFR-TKI treatment (LUAD-NT), primary SCLCs (SCLC-P) and LUADs with transformation after EGFR-TKI treatment (before transformation: LUAD-BT; after transformation: SCLC-AT). Our study found that LUAD-BT exhibited potential transcriptomic characteristics for transformation compared with LUAD-NT. We identified several pathways that shifted during transformation, and the transformation might be promoted by epigenetic alterations (such as HDAC10, HDAC1, DNMT3A) within the tumor cells instead of within the tumor microenvironment. For druggable pathways, transformed-SCLC were proved to be less dependent on EGF signaling but more relied on FGF signaling, while VEGF-VEGFR pathway remained active, indicating potential treatments after transformation. We also found transformed-SCLC showed an immuno-exhausted status which was associated with the duration of EGFR-TKI before transformation. Besides, SCLC-AT exhibited distinct molecular subtypes from SCLC-P. Moreover, we constructed an ideal 4-marker model based on transcriptomic and IHC data to predict SCLC transformation, which obtained a sensitivity of 100% and 87.5%, a specificity of 95.7% and 100% in the training and test cohorts, respectively. We provided insights into the molecular mechanisms of SCLC transformation and the differences between SCLC-AT and SCLC-P, which might shed light on prevention strategies and subsequent therapeutic strategies for SCLC transformation in the future.

Improving plant resistance to Verticillium wilt (VW), which causes massive losses in Gossypium hirsutum, is a global challenge. Crop plants need to efficiently allocate their limited energy resources to maintain a balance between growth and defense. However, few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in cotton. In this study, we found that the that expression of most R2R3-MYB members in cotton is significantly changed by V. dahliae infection relative to the other MYB types. One novel R2R3-MYB transcription factor (TF) that specifically responds to V. dahliae, GhMYB3D5, was identified. GhMYB3D5 was not expressed in 15 cotton tissues under normal conditions, but it was dramatically induced by V. dahliae stress. We functionally characterized its positive role and underlying mechanism in VW resistance. Upon V. dahliae infection, the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated GhADH1 expression. In addition, GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of GhADH1. Consequently, the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis (GhPAL, GhC4H, Gh4CL, and GhPOD/GhLAC) in cotton, thereby enhancing cotton VW resistance. Our results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation, which can be regarded as an effective way to orchestrate plant immunity and growth.

To support the "people-centered" chronic disease health management work, Shanghai has developed a community chronic disease health management information system. This system provides an efficient tool for achieving integrated medical care and disease prevention, as well as collaborative management between doctors and patients, through functions such as information registration and management, risk assessment, chronic disease screening, patient evaluation, and categorized follow-up. It delivers comprehensive, precise, and high-quality health management services for various chronic diseases, effectively promoting the implementation of comprehensive chronic disease prevention and control strategies and the transformative development of chronic disease health management services. However, the system currently requires the inclusion of a broader range of chronic diseases and the enhancement of interactive integration between clinic-based doctor follow-ups and home-based self-management. Future improvements may include the integration of additional disease types and the fusion of complex interaction scenarios to continuously adapt to the new situations and challenges in chronic disease prevention and control.

Abstract Accurate monitoring of wheat phenological stages is essential for effective crop management and informed agricultural decision-making. Traditional methods often rely on labour-intensive field surveys, which are prone to subjective bias and limited temporal resolution. To address these challenges, this study explores the potential of near-surface cameras combined with an advanced deep-learning approach to derive wheat phenological stages from high-quality, real-time RGB image series. Three deep learning models based on three different spatiotemporal feature fusion methods, namely sequential fusion, synchronous fusion, and parallel fusion, were constructed and evaluated for deriving wheat phenological stages with these near-surface RGB image series. Moreover, the impact of different image resolutions, capture perspectives, and model training strategies on the performance of deep learning models was also investigated. The results indicate that the model using the sequential fusion method is optimal, with an overall accuracy (OA) of 0.935, a mean absolute error (MAE) of 0.069, F1-score (F1) of 0.936, and kappa coefficients (Kappa) of 0.924 in wheat phenological stages. Besides, the enhanced image resolution of 512 × 512 pixels and a suitable image capture perspective, specifically a sensor viewing angle of 40° to 60° vertically, introduce more effective features for phenological stage detection, thereby enhancing the model’s accuracy. Furthermore, concerning the model training, applying a two-step fine-tuning strategy will also enhance the model’s robustness to random variations in perspective. This research introduces an innovative approach for real-time phenological stage detection and provides a solid foundation for precision agriculture. By accurately deriving critical phenological stages, the methodology developed in this study supports the optimization of crop management practices, which may result in improved resource efficiency and sustainability across diverse agricultural settings. The implications of this work extend beyond wheat, offering a scalable solution that can be adapted to monitor other crops, thereby contributing to more efficient and sustainable agricultural systems.

Abstract By analyzing e + e − annihilation data corresponding to an integrated luminosity of 2.93 fb −1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the semileptonic decays D 0 → K S 0 π − π 0 e + ν e $$ {D}^0\to {K}_S^0{\pi}^{-}{\pi}^0{e}^{+}{\nu}_e $$ and D + → K S 0 π + π − e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^{+}{\pi}^{-}{e}^{+}{\nu}_e $$ is reported. In the hypothesis that all events correspond to K 1(1270) decays, the branching fractions are measured to be B D 0 → K 1 1270 − → K S 0 π − π 0 e + ν e = 1.69 − 0.46 + 0.53 ± 0.15 × 10 − 4 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}\left(\to {K}_S^0{\pi}^{-}{\pi}^0\right){e}^{+}{\nu}_e\right)=\left({1.69}_{-0.46}^{+0.53}\pm 0.15\right)\times {10}^{-4} $$ and B D + → K ¯ 1 1270 0 → K S 0 π + π − e + ν e = 1.47 − 0.40 + 0.45 ± 0.14 × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0\left(\to {K}_S^0{\pi}^{+}{\pi}^{-}\right){e}^{+}{\nu}^e\right)=\left({1.47}_{-0.40}^{+0.45}\pm 0.14\right)\times {10}^{-4} $$ with statistical significance of 5.4σ and 5.6σ, respectively. When combined with measurements of the K 1(1270) → K + π − π decays, the absolute branching fractions are determined to be B D 0 → K 1 1270 − e + ν e = 1.08 − 0.13 − 0.10 + 0.14 + 0.08 ± 0.21 × 10 − 3 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}{e}^{+}{\nu}_e\right)=\left({1.08}_{-0.13-0.10}^{+0.14+0.08}\pm 0.21\right)\times {10}^{-3} $$ and B D + → K ¯ 1 1270 0 e + ν e = 1.70 − 0.23 + 0.26 ± 0.13 ± 0.35 × 10 − 3 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0{e}^{+}{\nu}_e\right)=\left({1.70}_{-0.23}^{+0.26}\pm 0.13\pm 0.35\right)\times {10}^{-3} $$ . The first and second uncertainties are statistical and systematic, respectively, and the third uncertainties originate from the assumed branching fractions of the K 1(1270) → Kππ decays.

Objective To evaluate the effect of empathic nursing combined with Lee Silverman voice treatment (LSVT) on negative emotion, swallowing function and compliance in elderly patients with cerebral infarction. Methods A total of 100 elderly patients with cerebral infarction admitted to General Hospital of Northern Theater Command and the First Affiliated Hospital of Air Force Medical University from December 2020 to December 2022 were selected as the research objects, and they were divided into two groups according to random number table method, with 50 cases in each group. The control group received routine nursing and routine speech intervention training, and the study group received empathic nursing combined with LSVT. The neurological function [simple test for evaluating hand function scale (STEF)], motor function [Fugl-Meyer motor assessment scale (FMA)], negative emotions [self rating anxiety scale (SAS), self-rating depression scale (SDS)], swallowing function (wata drinking water test), activities of daily living (Barthel scale), compliance and nursing satisfaction were compared between the two groups. Results Before intervention, between the two groups, there was no significant difference in STEF score, FMA score, SAS score, SDS score, drinking water test and Barthel scale score (P > 0.05) . After intervention, STEF scores, FMA scores and and Barthel scale score in both groups were higher than those before intervention (P < 0.05), and SAS score, SDS score were lower than those before intervention (P < 0.05) . After intervention, the STEF scores, FMA scores and and Barthel scale score in the observation group were higher than those in the control group (P < 0.05), the SAS score, SDS score and drinking water test in the observation group were lower than those in the control group (P < 0.05), and the drinking water test in the observation group was better than that in the control group (P < 0.05) . The total sequence rate and nursing satisfaction in observation group were higher than those in control group (P < 0.05) . Conclusion Empathic nursing combined with LSVT has a positive effect on the elderly patients with cerebral infarction, which can improve the neurological function, motor function and swallowing function, and reduce the negative emotion. In addition, patients have high compliance and satisfaction with this nursing method.

Abstract Background Understanding the role of cytokines in tooth development is critical for advancing dental tissue engineering. Fibroblast growth factor 9 (FGF9) is the only FGF consistently expressed throughout dental epithelial tissue, from the initiation of tooth bud formation to tooth maturation. However, mice lacking Fgf9 (Fgf9 −/− ) surprisingly show no obvious abnormalities in tooth development, suggesting potential compensation by other FGFs. Here we report findings from an Fgf9 S99N mutation mouse model, a loss-of-function mutation with a dominant negative effect. Our study reveals that Fgf9 is crucial for dental epithelial stem cell (DESC) survival and enamel formation. Methods To dissect the role of Fgf9 in tooth development, we performed the micro-CT, histomorphological analysis and gene expression assay in mice and embryos with S99N mutation. In addition, we assessed the effect of FGF9 on the DESC survival and dental epithelial differentiation by DESC sphere formation assay and tooth explant culture. Cell/tissue culture methods, gene expression analysis, specific inhibitors, and antibody blockage analysis were employed to explore how Fgf9 regulates enamel differentiation and DESC survival through both direct and indirect mechanisms. Results The Fgf9 S99N mutation in mice led to reduced ameloblasts, impaired enamel formation, and increased apoptosis in the cervical loop (CL). DESC sphere culture experiments revealed that FGF9 facilitated DESC survival via activating ERK/CREB signaling, without affecting cell proliferation. Furthermore, in vitro tissue culture experiments demonstrated that FGF9 promoted enamel formation in a manner dependent on the presence of mesenchyme. Interestingly, FGF9 stimulation inhibited enamel formation in isolated enamel epithelia and DESC spheres. Further investigation revealed that FGF9 supports DESC survival and promotes amelogenesis by stimulating the secretion of FGF3 and FGF10 in dental mesenchymal cells via the MAPK/ERK signaling pathway. Conclusions Our study demonstrates that Fgf9 is essential for DESC survival and enamel formation. Fgf9 performs as a dual-directional regulator of the dental enamel epithelium, not only inhibiting DESC differentiation into ameloblasts to preserve the stemness of DESC, but also promoting ameloblast differentiation through epithelial-mesenchymal interactions.

Abstract Background Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients’ quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. Purpose Investigate the effects of tDCS on pain and physical function in patients with KOA. Methods Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. Results Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. Conclusions The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

Abstract Using e + e − annihilation data sets corresponding to an integrated luminosity of 4.5 fb −1, collected with the BESIII detector at center-of-mass energies between 4.600 and 4.699 GeV, we report the first measurements of the absolute branching fractions B Λ c + → p K L 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0\right) $$ = (1.67 ± 0.06 ± 0.04)%, B Λ c + → p K L 0 π + π − $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^{+}{\pi}^{-}\right) $$ = (1.69 ± 0.10 ± 0.05)%, and B Λ c + → p K L 0 π 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^0\right) $$ = (2.02 ± 0.13 ± 0.05)%, where the first uncertainties are statistical and the second systematic. Combining with the known branching fractions of Λ c + → p K S 0 $$ {\Lambda}_c^{+}\to p{K}_S^0 $$ , Λ c + → p K S 0 π + π − $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^{+}{\pi}^{-} $$ , and Λ c + → p K S 0 π 0 $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^0 $$ , we present the first measurements of the K S 0 $$ {K}_S^0 $$ - K L 0 $$ {K}_L^0 $$ asymmetries R Λ c + K S , L 0 X = B Λ c + → K S 0 X − B Λ c + → K L 0 X B Λ c + → K S 0 X + B Λ c + → K L 0 X $$ R\left({\Lambda}_c^{+},{K}_{S,L}^0X\right)=\frac{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)-\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)}{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)+\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)} $$ in charmed baryon decays: R Λ c + p K S , L 0 = − 0.025 ± 0.031 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0\right)=-0.025\pm 0.031 $$ , R Λ c + p K S , L 0 π + π − = − 0.027 ± 0.048 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^{+}{\pi}^{-}\right)=-0.027\pm 0.048 $$ and R Λ c + p K S , L 0 π 0 = − 0.015 ± 0.046 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^0\right)=-0.015\pm 0.046 $$ . No significant asymmetries with statistical significance are observed.

Abstract Background The KT/HAK/KUP is the largest K+ transporter family in plants, playing crucial roles in K+ absorption, transport, and defense against environmental stress. Sweet watermelon is an economically significant horticultural crop belonging to the genus Citrullus, with a high demand for K+ during its growth process. However, a comprehensive analysis of the KT/HAK/KUP gene family in watermelon has not been reported. Results 14 KT/HAK/KUP genes were identified in the genomes of each of seven Citrullus species. These KT/HAK/KUPs in watermelon were unevenly distributed across seven chromosomes. Segmental duplication is the primary driving force behind the expansion of the KT/HAK/KUP family, subjected to purifying selection during domestication (Ka/Ks

Abstract Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection.

Abstract P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor’s ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3’s physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3β domain of the ICD. PSFL77 modulated pain perception in P2rx3 +/+, but not in P2rx3 −/−, mice, indicating that the 1α3β, a “tunable” region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.

Abstract Background Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family’s largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria’s taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system. Results This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK–rps16, trnC–petN, petN–psbM, accD–psaI, petA–psbJ, rpl32–trnL, ccsA–ndhD, rps15–ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics. Conclusions The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.

Abstract. Background:. Accurately and efficiently extracting microbial genomic sequences from complex metagenomic data is crucial for advancing our understanding in fields such as clinical diagnostics, environmental microbiology, and biodiversity. As sequencing technologies evolve, this task becomes increasingly challenging due to the intricate nature of microbial communities and the vast amount of data generated. Especially in intensive care units (ICUs), infections caused by antibiotic-resistant bacteria are increasingly prevalent among critically ill patients, significantly impacting the effectiveness of treatments and patient prognoses. Therefore, obtaining timely and accurate information about infectious pathogens is of paramount importance for the treatment of patients with severe infections, which enables precisely targeted anti-infection therapies, and a tool that can extract microbial genomic sequences from metagenomic dataset would be of help. Methods:. We developed MetaGeneMiner to help with retrieving specific microbial genomic sequences from metagenomes using a k-mer-based approach. It facilitates the rapid and accurate identification and analysis of pathogens. The tool is designed to be user-friendly and efficient on standard personal computers, allowing its use across a wide variety of settings. We validated MetaGeneMiner using eight metagenomic samples from ICU patients, which demonstrated its efficiency and accuracy. Results:. The software extensively retrieved coding sequences of pathogens Acinetobacter baumannii and herpes simplex virus type 1 and detected a variety of resistance genes. All documentation and source codes for MetaGeneMiner are freely available at https://gitee.com/sculab/MetaGeneMiner. Conclusions:. It is foreseeable that MetaGeneMiner possesses the potential for applications across multiple domains, including clinical diagnostics, environmental microbiology, gut microbiome research, as well as biodiversity and conservation biology. Particularly in ICU settings, MetaGeneMiner introduces a novel, rapid, and precise method for diagnosing and treating infections in critically ill patients. This tool is capable of efficiently identifying infectious pathogens, guiding personalized and precise treatment strategies, and monitoring the development of antibiotic resistance, significantly impacting the diagnosis and treatment of severe infections.

Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

The low-degree gravity field and rotation parameters of terrestrial planets are functions of the planet's interior structure, providing insights into their composition and evolution, which serves them as crucial targets throughout deep-space exploration. Particularly, the measurement of rotation state can directly reveal the density and size of most untouchable planetary core. With the accumulation of data and the recent high-precision deep-space missions, substantial scientific advances have been achieved in understanding the internal structure of terrestrial planets, especially the core, using the low-degree gravity field and rotation measurements. In this study, we provide a summary of the fundamental theory and method for determining the principal moment of inertia tensor of planets, and then the basic theory of planetary rotation dynamics and rotational normal modes closely related to internal structures, and the methods for solving principal moments of inertia tensors of planets using the low-degree gravitational potential coefficients. We review the up-to-date researches on determining the mean bulk density and mean moment of inertia factor through limited rotation observations and the low-degree gravity field measurements, and the basic approaches to invert interior structures. Finally, we present existing challenges in revealing interior structures from low-degree gravity field and rotation normal modes for terrestrial planets and asteroids with a hope to provide scientific references and theoretical support for Chinese future deep-space missions.

The effect of Zn/Mg ratio on the microstructure and properties of Al-Zn-Mg-Cu alloys under single-step and double-step aging processes were investigated by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron backscatter diffraction (EBSD), as well as hardness, room temperature tensile, and fracture toughness testing. During single-step aging, as the Zn/Mg ratio increases, the aging response of the alloys accelerates. However, the peak hardness and strength gradually decreased while the average size of precipitates increased. During double-step aging, as the secondary aging time increases, the strength and hardness of the alloys gradually decrease. Additionally, the higher the Zn/Mg ratio, the faster the strength and hardness decline. Under the T74 temper, the alloy with higher Zn/Mg ratios exhibits lower hardness and strength but better fracture toughness and larger precipitate sizes. A simple method was proposed to statistically determine the critical diameter size of GPII zone and η′ phase, which was approximately 4.47 nm. A strength model was developed to predict the yield strength of alloys, considering factors such as solid solution strengthening, grain boundary strengthening, and precipitation strengthening. The model demonstrates good predictive accuracy for both peak-aged and T74 temper alloys, providing valuable guidance for alloy design and microstructure regulation.

Currently, the rapid development of the industrial Internet has led to the creation of a massive number of intelligent agents that are widely and distributively applied in various edge scenarios. The work conditions in these edge scenarios are complex, uncertain, and random. Traditional manual updates or human judgments are used for task decision-making in large-scale distributive intelligent agent edge work scenarios, which lack dynamic perception and autonomous recognition capabilities for edge work conditions. This inevitably leads to low decision-making accuracy, poor reliability, and ultimately, task failure. To address this issue, this study proposes an adaptive task identification strategy based on cloud-edge collaboration. This method utilizes a cloud-edge collaborative industrial intelligent application architecture to achieve cloud-based training and encapsulation of the task model, with online calling at the edge-end. Then, edge-end intelligent agents identify edge work conditions through multi-source data fusion, enabling accurate task decision-making. Finally, the edge-end requests the cloud for task model matching. The effectiveness of the proposed method is validated in an industrial safety situation virtual detection system.

Abstract Background Grapes are highly valued for their nutritional and economic benefits, and have been widely studied for their biological attributes such as fruit development, quality formation, and stress resistance. One significant threat to grape quality is gray mold, caused by Botrytis cinerea, which can infect the flowers, fruits, leaves, and stems. The quantitative real-time PCR (qRT-PCR), known for its high sensitivity and quantitative accuracy, is an essential tool for analyzing gene expression related to the pathogenesis of gray mold, thereby providing deeper insights into the disease. Result In this study, we aim to identify stable internal reference genes crucial for accurate gene expression analysis via qRT-PCR. Utilizing transcriptome data from grapes under various disease stresses, we identified twelve candidate reference genes with consistently high expression levels. The stability of these genes was assessed through delta-CT, geNorm, NormFinder, BestKeeper, and RefFinder analyses after establishing the cycling thresholds (Ct) in different grape varieties treated with Botrytis cinerea. Conclusions Our findings reveal that VIT-17s0000g02750 and VIT-06s0004g04280 exhibit stable expression and are suitable as new reference genes. This foundational work supports further research into the molecular mechanisms of grape biological processes.

Abstract Background Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts. Methods Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed. Results CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients (r = 0.462 ∼ 0.636, p

Abstract Insufficient cytotrophoblast (CTB) migration and invasion into the maternal myometrium leads to pregnancy related complications like Intra-uterus Growth Restriction (IUGR), and pre-eclampsia (PE). We previously found that hydrogen sulfide (H2S) enhanced CTB migration without knowing the mechanism(s) and the pathophysiological significance. By studying human samples and cell line, we found that H2S levels were lower in PE patients’ plasma; H2S synthetic enzyme cystathionine β-synthetase (CBS) was reduced in PE extravillious invasive trophoblasts. GYY4137 (H2S donor, 1 µM) promoted CBS/H2S translocation onto mitochondria, preserved mitochondria functions, enhanced cell invasion and migration. CBS knockdown hindered the above functions which were rescued by GYY4137, indicating the vital roles of CBS/H2S signal. Disturbance of mitochondria dynamics inhibited cell invasion and migration. The 185 and 504 cysteines of Mitochondrial Rho GTPase 2 (Miro2C185/C504) were highly sulfhydrated by H2S. Knockdown Miro2 or double mutation of Miro2C185/C504 to serine fragmented mitochondria, and inhibited cell invasion and migration which can’t be rescued by H2S. The present study showed that human cytotrophoblast receives low dose H2S regulation; CBS/H2S sustained mitochondria functions via Miro2C185/C504 sulfhydration to enhance cytotrophoblast mobility. These findings established a new regulatory pathway for cytotrophoblast functions, and provided new targets for IUGR and PE.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complication of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Abstract Objective To investigate indications and surgical procedures of keratoplasty in a tertiary comprehensive hospital in northern part of China over a 20-year period. Methods All patients undergoing keratoplasty between January 1, 2002 to December 31, 2021 in a tertiary comprehensive hospital in northern part of China were retrospectively reviewed. The annual proportion of keratoplasty indications and surgical procedures was recorded and analyzed. Results A total of 8266 keratoplasty procedures were included. Leading indications were keratoleukoma (n = 2108, 25.50%), followed by regraft (n = 1453 ,17.58%), corneal endothelial dysfunction (n = 1085, 13.13%), and keratoconus (n = 922,11.15%). A decreasing trend was observed for keratoleukoma (P

Abstract Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count

Abstract Background The cardiometabolic index (CMI) is a novel metric for assessing cardiometabolic health and type 2 diabetes mellitus (DM), yet its relationship with insulin resistance (IR) and prediabetes (preDM) is not well-studied. There is also a gap in understanding the nonlinear associations between CMI and these conditions. Our study aimed to elucidate these associations. Methods We included 13,142 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2020. CMI was calculated by multiplying the triglyceride-to-high density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Using weighted multivariable linear and logistic regression explored the relationships of CMI with glucose metabolism markers, IR, preDM, and DM. Nonlinear associations were assessed using generalized additive models (GAM), smooth curve fittings, and two-piecewise logistic regression. Results Multivariate regression revealed positive correlations between CMI and glucose metabolic biomarkers, including FBG (β = 0.08, 95% CI: 0.06–0.10), HbA1c (β = 0.26, 95% CI: 0.22–0.31), FSI (β = 4.88, 95% CI: 4.23–5.54), and HOMA-IR (β = 1.85, 95% CI: 1.56–2.14). There were also significant correlations between CMI and increased risk of IR (OR = 3.51, 95% CI: 2.94–4.20), preDM (OR = 1.49, 95% CI: 1.29–1.71), and DM (OR = 2.22, 95% CI: 2.00-2.47). Inverse nonlinear L-shaped associations were found between CMI and IR, preDM, and DM, with saturation inflection points at 1.1, 1.45, and 1.6, respectively. Below these thresholds, increments in CMI significantly correlated with heightened risks of IR, preDM, and DM. Conclusions CMI exhibited inverse L-shaped nonlinear relationships with IR, preDM, and DM, suggesting that reducing CMI to a certain level might significantly prevent these conditions.

Abstract Autophagy plays a dual role in coronavirus infection, facilitating the elimination of either proviral components (virophagy) or antiviral factors such as mitochondria (mitophagy), leading to complex mechanisms of immune evasion. Understanding the mechanisms that govern the switch between the autophagic degradation of deleterious or beneficial substrates in coronavirus infection is crucial for developing precise drug targets to treat virus-induced diseases. However, this switch remains largely unknown. Using a dual split-fluorescence assay, we identify PDPK1 as a negative regulator of innate immunity, directing the transition from virophagy to mitophagy through the phosphorylation of SQSTM1 at T138. Remarkably, a PDPK1-targeting peptide inhibits the replication of various RNA viruses by restoring innate immunity through enhanced virophagy and suppressed mitophagy, thereby protecting female mice from lethal infections. These findings underscore the detrimental role of PDPK1 in innate immunity by orchestrating the shift from virophagy to mitophagy, positioning PDPK1 as a promising pharmacological target for effectively combating a broad spectrum of virus infections.

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Using the daily average temperature data of 125 national meteorological observation stations and NCAR/NCEP reanalysis data from 1961 to 2022, the main patterns of Asian circulation changes in winter and their impact on low-temperature events in Yunnan province were analyzed. The results show that there are two patterns of atmospheric circulation at 500 hPa in Asia during winter, namely zonal and meridional patterns, and the impact of the two patterns on low-temperature events in Yunnan province is significantly different. During the zonal circulation pattern, the stronger cold air flows directly southward from Lake Baikal to low latitudes, mainly affecting the eastern part of East Asia. The low-temperature events in Yunnan province also mainly occur in the eastern region. At this time, the low-temperature process is closely related to the strengthening of the Ural Mountains High and the Siberian High, as well as the wave trains at mid-to-high latitudes in Eurasia. During the meridional circulation pattern, the cold air flows southward along the eastern coast of the East Asian continent with the northerly airflow of the eastern side of the anomalous anticyclone in Lake Baikal, and moves southeast in the form of backflow in mid-to-low latitude areas. The activity is located southward and westward, which is beneficial for the low temperature of Yunnan province, the Tibet Plateau, and low latitude areas in Southeast Asia. At this time, the low-temperature events are mainly related to the changes in the subtropical wave train and the strengthening of positive surface level pressure (SLP) anomalies on the Tibet Plateau, but not closely related to the strengthening of High pressure in the Ural Mountain and the Siberian.

Abstract Background The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients. Methods In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA. Results A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20–3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84–1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar. Conclusion OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population. Trial registration Clinicaltrials.gov; No: NCT03362385.

Abstract Growing research has suggested an association between chronic inflammation and Intervertebral disc degeneration (IVDD), but whether there is a causal effect remains unknown. This study adopted two-sample Mendelian randomization (MR) approach to explore the etiological role of chronic inflammation in IVDD risk. Here, summary statistics for C-reactive protein (CRP), interleukin (IL)-1 $$\mathcal {\alpha }$$ α , IL-1 $$\mathcal {\beta }$$ β , IL-6 expression and IVDD were obtained from genome-wide association studies (GWAS) of European ancestry. MR analyses were conducted by using inverse variance weighted (IVW), Wald Ratio, weighted median, and MR-Egger method. Sensitivity analyses were conducted to assess the robustness of the results. The MR analyses suggested a lack of causal association of CRP, IL-6 , and IL-1 $$\mathcal {\alpha }$$ α levels on IVDD (CRP-IVDD: odds ratio [OR] = 0.97, 95% confidence interval [CI] 0.86–1.09, P = 0.583; IL-6-IVDD: OR = 1.04, 95% CI 0.86–1.27, P = 0.679; IL-1 $$\mathcal {\alpha }$$ α -IVDD: OR = 1.09, 95%CI 1.00–1.18, P = 0.058). However, there was a sign of a connection between genetically elevated IL-1 $$\mathcal {\beta }$$ β levels and a decreased IVDD incidence (OR = 0.87, 95%CI 0.77–0.99, P = 0.03). Our findings suggest a connection between IL-1 $$\mathcal {\beta }$$ β levels and the risk of IVDD. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, the specific underlying mechanisms warrant further investigation.

Abstract Background The purpose of the study was to evaluate renal quality and predict posttransplant graft function using ex vivo sound touch elastography (STE). Methods In this prospective study, 106 donor kidneys underwent ex vivo STE examination and biopsy from March 2022 to August 2023. The mean stiffness of the superficial cortex (STEsc), deep cortex (STEdc), and medulla (STEme) was obtained and synthesized into one index (STE) through the factor analysis method. Additionally, 100 recipients were followed up for 6 months. A random forest algorithm was employed to explore significant predictive factors associated with the Remuzzi score and allograft function. The performance of parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). Results STE had AUC values of 0.803 for diagnosing low Remuzzi and 0.943 for diagnosing high Remuzzi. Meanwhile, STE had an AUC of 0.723 for diagnosing moderate to severe ATI. Random forest algorithm identified STE and Remuzzi score as significant predictors for 6-month renal function. The AUC for STE in predicting postoperative allograft function was 0.717, which was comparable with that of the Remuzzi score (AUC = 0.756). Nevertheless, the specificity of STE was significantly higher than that of Remuzzi (0.913 vs 0.652, p

Abstract Background The ability of socially assistive robots (SARs) to treat dementia and Alzheimer’s disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots. Objective This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures. Design This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines. Methods The PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence. Results Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = − 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use. Conclusions The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions. Trial registration The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Abstract Congenital long QT syndrome (LQTS) is a genetic heart disorder, which may lead to life-threatening arrhythmias, especially in children. Here, we reported two children who were initially misdiagnosed with epilepsy and experienced Torsades de Pointes (TdP) cardiac electrical storm (ES). Through whole exome sequencing (WES), we identified two Potassium voltage-gated channel subfamily H member 2 (KCHN2) mutations (c.1841 C > T and c.1838 C > T) respectively in a 6-year-old boy and a 13-year-old girl. Clinical data indicated that the QT interval was significantly prolonged, the T-wave pattern of chest V5-V6 leads and limb leads were inverted. Our study suggests that patients with epilepsy, especially those refractory epilepsy with atypical features, need comprehensive evaluation of cardiovascular function. KCNH2 mutation in pore region, QT interval prolongation and T wave inversion are high risk factors for ES. For LQT2 patients with ES, Nadolol and left cardiac sympathetic denervation are indicated, sometimes with an ICD.