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The pathogenesis of complex diseases is intricately linked to various genes and network medicine has enhanced understanding of diseases. However, most network-based approaches ignore interactions mediated by noncoding RNAs (ncRNAs) and most databases only focus on the association between genes and diseases. Based on the mentioned questions, we have developed DisGeNet, a database focuses not only on the disease-associated genes but also on the interactions among genes. Here, the associations between diseases and various genes, as well as the interactions among these genes are integrated into a disease-centric network. As a result, there are a total of 502 688 interactions/associations involving 6697 diseases, 5780 lncRNAs (long noncoding RNAs), 16 135 protein-coding genes, and 2610 microRNAs stored in DisGeNet. These interactions/associations can be categorized as protein-protein, lncRNA-disease, microRNA-gene, microRNA-disease, gene-disease, and microRNA-lncRNA. Furthermore, as users input name/ID of diseases/genes for search, the interactions/associations about the search content can be browsed as a list or viewed in a local network-view. Database URL: https://disgenet.cn/., (© The Author(s) 2025. Published by Oxford University Press.)

Deterioration of a patient's state of consciousness is among the most concerning signs encountered in clinical practice. The evaluation of this finding carries a broad initial differential diagnosis and must account for any relevant medical history. We describe the case of a 41-year-old male with known retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) who presented with progressive mental status decline and acute onset intractable headache. Head computed tomography (CT) revealed extensive vasogenic edema, resulting in right to left shift of 11 millimeters at the level of the lateral ventricles, with associated uncal and subfalcine herniation. He was treated with a 5-day course of methylprednisolone, leading to resolution of his lethargy and headache. Follow up neuroimaging with magnetic resonance (MRI) brain demonstrated interval improvement with the midline shift reduced to 3 millimeters after completion of high dose corticosteroids. Neurosurgical intervention was considered, but ultimately not required given his improvement. This case describes the management of life-threatening cerebral edema as a complication of RVCL-S disease progression. Due to the rarity of this disease, there are no standardized guidelines for treatment and the care for such patients relies on expert opinion, case studies, and extrapolation of principles learned from related conditions. Our intention is that the reporting of this case will contribute to the limited body of literature and aid those affected by this condition., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The poor remediation performance of groundwater circulation well (GCW) on semi-volatile organic contaminants (such as aniline) has severely limited its practical application. To address the challenges posed by the low volatility and solubility of these contaminants, an innovative integration of GCW with in-situ thermal remediation (ISTR) was proposed to create a thermal enhanced circulation well (GCW-ISTR) in this study. Laboratory experiments and model simulations were performed to evaluate the heat transfer and enhanced remediation effect by GCW-ISTR. Results demonstrate that the heat transfer process is controlled by the water circulation around GCW-ISTR and is influenced by factors such as aeration flow rate, groundwater velocity and aquifer permeability. Heating area is directly proportional to the seepage velocity of groundwater which can be analyzed by multiplying the water head difference between the upper and lower screens with the aquifer permeability. Therefore, the heat transfer model, based on Darcy's seepage theory and the energy conservation equation, effectively simulates the heat transfer with an error margin of less than 10%. Compared to individual GCW, GCW-ISTR exhibits a 25.8% improvement in aniline remediation efficiency, resulting in a decrease in the average concentration from 97.95 mg/L to 0.168 mg/L within 48 h, effectively mitigating the occurrence of tailing phenomena. This study provides a feasible method of enhancing the remediation of GCW on semi-volatile contaminants and is anticipated to broaden the applicability of GCW in site application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The striped hamster, often parasitized by ectoparasites in nature, is an ideal model for studying host-ectoparasite molecular interactions. Investigating the response to ectoparasites under laboratory conditions helps elucidate the mechanism of host adaptations to ectoparasite pressure., Methods: Using transcriptome sequencing, we analyzed gene expression in striped hamsters after short-term (3 days) and long-term (28 days) flea ( Xenopsylla cheopis ) parasitism. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were pinpointed using protein-protein interaction (PPI) network analysis and the MCODE in Cytoscape. Gene Set Enrichment Analysis (GSEA) was used to further clarify the functional pathways of these hub genes. Validation of DEGs was performed via RT-qPCR. Additionally, the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined using specific enzyme-linked immunosorbent assay (ELISA) detection kits for hamsters., Results: GO analysis revealed that during early parasitism, hosts primarily responded to the ectoparasites by adjusting the expression of genes related to metabolic functions. As parasitism persisted, the immune response became prominent, activating various immune pathways against ectoparasites. KEGG analysis confirmed the ongoing roles of metabolism and immunity. Notably, the chemical carcinogenesis - reactive oxygen species pathway was upregulated during flea parasitism, with downregulation of hub genes ATP5MC1 and ATP5MC2, highlighting the importance of mitochondrial function in oxidative stress. ELISA findings revealed that on day 3, flea parasitism groups showed elevated ROS expression and reduced SOD and CAT levels compared to the control group. By day 28, only SOD expression showed a significant decrease in both parasitism groups., Conclusion: This study uncovered the dynamic changes in metabolism and immune responses of striped hamsters parasitized by Xenopsylla cheopis . Hosts adjust their physiological and immune states to optimize survival strategies during different ectoparasite stages, enhancing our understanding of host-ectoparasite interactions. This also paves the way for further research into how hosts regulate complex biological processes in response to ectoparasite challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lun, Wang, Zhao, Yue, Meng, Liu, Song, Liang and Lu.)

Mitochondrial programmed cell death (PCD) plays a critical role in the pathogenesis of diabetic foot ulcers (DFU). In this study, we performed a comprehensive transcriptome analysis to identify potential hub genes and key cell types associated with PCD and mitochondria in DFU. Using intersection analysis of PCD- and mitochondria-related genes, we identified candidate hub genes through protein-protein interaction and random forest analysis. At the single-cell level, key cell types were further validated based on the expression of hub genes. Additionally, we explored the transcription factors (TFs) regulating hub gene expression and the cellular heterogeneity of DFU. Finally, the expression of key hub genes and TFs was validated in clinical specimens. Our results identified BCL2 and LIPT1 as significantly downregulated hub genes in DFU, with Keratinocytes, as the key cell type. Immunohistochemistry confirmed downregulation of BCL2 and LIPT1 in DFU samples (p < 0.05). Additionally, TFs CEBPD and IRF1 were significantly upregulated in DFU, as confirmed by real-time polymerase chain reaction analysis (p < 0.05)., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Alterations in ileal Paneth cell (PC) density have been described in gut inflammatory diseases such as Crohn's disease (CD) and could be used as a biomarker for disease prognosis. However, quantifying PCs is time-intensive, a barrier for clinical workflow. Deep learning (DL) has transformed the development of robust and accurate tools for complex image evaluation. Our aim was to use DL to quantify PCs for use as a quantitative biomarker., Methods: A retrospective cohort of whole slide images (WSI) of ileal tissue samples from patients with/without inflammatory bowel disease (IBD) was used for the study. A pathologist-annotated training set of WSI were used to train a U-net two-stage DL model to quantify PC number, crypt number, and PC density. For validation, a cohort of 48 WSIs were manually quantified by study pathologists and compared to the DL algorithm, using root mean square error (RMSE) and the coefficient of determination (r 2 ) as metrics. To test the value of PC quantification as a biomarker, resection specimens from patients with CD (n = 142) and without IBD (n = 48) patients were analysed with the DL model. Finally, we compared time to disease recurrence in patients with CD with low versus high DL-quantified PC density using Log-rank test., Findings: Initial one-stage DL model showed moderate accuracy in predicting PC density in cross-validation tests (RMSE = 1.880, r 2  = 0.641), but adding a second stage significantly improved accuracy (RMSE = 0.802, r 2  = 0.748). In the validation of the two-stage model compared to expert pathologists, the algorithm showed good performance up to RMSE = 1.148, r 2  = 0.708. The retrospective cross-sectional cohort had mean ages of 62.1 years in the patients without IBD and 38.6 years for the patients with CD. In the non-IBD cohort, 43.75% of the patients were male, compared to 49.3% of the patients with CD. Analysis by the DL model showed significantly higher PC density in non-IBD controls compared to the patients with CD (4.04 versus 2.99 PC/crypt). Finally, the algorithm quantification of PCs density in patients with CD showed patients with the lowest 25% PC density (Quartile 1) have significantly shorter recurrence-free interval (p = 0.0399)., Interpretation: The current model performance demonstrates the feasibility of developing a DL-based tool to measure PC density as a predictive biomarker for future clinical practice., Funding: This study was funded by the National Institutes of Health (NIH)., Competing Interests: Declaration of interests The authors have no conflict of interest to declare in relation to the work presented., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Boron Neutron Capture Therapy is being promoted with the development of accelerator neutron sources, and many new accelerator-based BNCT facilities are being built. In Particle Accelerator Facility project of Sun Yat-sen University, we plan to build a terminal for BNCT research based on an 8 MeV, CW 3 mA proton accelerator. In this paper, we present a beam-shaping assembly for this proton accelerator with such low 24 kW beam power, using composite moderator materials composed of five elements: Mg, Al, F, O, and Li. The calculation result of FLUKA with ENDF/B and JENDL libraries shows that the epithermal neutron beam flux is 1.57×10 9 n/cm 2 /s with the CW 3 mA proton beam. The fast neutron component and the gamma ray component under free-air condition are 1.49×10 -13 Gy∙cm 2 and 8.12×10 -14 Gy∙cm 2 respectively, in line with IAEA-TECDOC-1223 design recommendations. The thermal analysis shows that the maximum temperature of beryllium target is 706.5 K, and the structure materials of BSA do not melt., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Magnetic solid-phase extraction (MSPE) technology for tetracycline (TCC) was developed by employing the novel and pre-designed Fe 3 O 4 -COOH@hydrogen-bonded organic frameworks (HOFs) adsorbents in complex food samples. The HOF shell was grown onto the Fe 3 O 4 -COOH core by in-situ self-assembled method. The excellent MSPE performances with less solvent, less adsorbent and time consumption were derived from the hydrogen bonding, π-π and hydrophobic interactions between HOF shell and TCC. Combined with HPLC analysis, Fe 3 O 4 @ HOFs adsorbent reduced matrix effects and the established MSPE-HPLC method for TCC gave the linearity of 0.001-6 μg mL -1 with the limit of detection 0.0003 μg mL -1 . The recoveries in pure milk, canned yellow peach and carrot were 82.4-103.7 %. The method provided a simple, efficient and dependable alternative to monitor trace TCC antibiotics in food or environmental samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Morpholines are widespread in many biologically and catalytically active agents, thus being an important aim of pharmaceutical and synthetic chemists. However, efficient strategies for the catalytic asymmetric synthesis of chiral morpholines bearing crowded stereogenic centers still remain elusive. Herein, we disclose a Cu-catalyzed asymmetric propargylic amination/desymmetrization strategy to help resolve this challenge. As a result, two kinds of structurally various chiral morpholines bearing rich functional groups and N-α-quaternary stereocenters were produced with high efficiency and selectivity (42 examples, up to 91% yield, 97:3 er and > 19:1 dr). In addition, a series of transformations were performed to demonstrate the synthetic utility of this methodology. In particular, a hit compound for new antitumor drugs was identified through cellular evaluation. Furthermore, mechanistic investigations reveal that, hydrogen bonding in the key copper-allenylidene intermediate together with π-π stacking aids remote enantioinduction., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

This study investigates the effects of integrating carbon nanofibers (CNF) into concrete to enhance the mechanical properties and reversed cyclic behavior of framed shear walls, addressing the need for improved seismic performance and durability. Despite the known benefits of CNF in improving concrete properties and enabling structural health monitoring, its application in framed shear walls has been limited. Through the design and testing of nineteen CNFC formulations, this research established a constitutive relationship allowing the Cyclic Softened Membrane Model (CSMM) to be applied to CNFC. Finite element analysis of shear walls under reversed cyclic loading revealed notable improvements in shear force capacity and ductility when CNF was incorporated. These findings highlight the dual role of CNFC in advancing both material performance and structural resilience, offering a significant contribution to the fields of material science and earthquake engineering.

Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology., (© 2024 Wiley-VCH GmbH.)

Conventional antibiotics are limited by drug resistance, poor penetration, and inadequate targeting in the treatment of bacterial biofilm-associated infections. Microbubble-based ultrasound (US)-responsive drug delivery systems can disrupt biofilm structures and enhance antibiotic penetration through cavitation effects. However, currently developed US-responsive microbubbles still depend on antibiotics and lack targeting capability. In this work, magnetic field/ultrasound (MF/US)-responsive Fe 3 O 4 microbubbles (FMB) were constructed based on Fe 3 O 4 nanoparticles (NPs) with superparamagnetic and peroxidase-like catalytic properties. In vitro experiments demonstrated that FMB can be targeted to methicillin-resistant Staphylococcus aureus (MRSA) biofilms by the direction of MF. Upon US irradiation, FMB collapse due to inertial cavitation and generate mechanical forces to disrupt the structure of MRSA biofilms and releases Fe 3 O 4 NPs, which catalyze the generation of reactive oxygen species (ROS) from H 2 O 2 in the biofilm microenvironment and kill the bacteria within the biofilm. In a mouse biofilm infection model, FMB efficiently destroyed MRSA biofilms grown in subcutaneous catheters with the MF and US. Magnetic-targeted mechanical/catalytic therapy based on FMB provides a promising strategy for effectively combating bacterial biofilm infection.

Correlophus ciliatus, or the crested gecko, is widely kept as a pet in many countries around the world due to its ease to care and bred and its high survival rate. However, there is limited number of genomic studies on the crested gecko. In this study, we generated a high-quality chromosome-level genome assembly of the crested gecko by combining Nanopore, Illumina, and Hi-C data. The genome assemble has a size of 1.66 Gb, with scaffold N50 of 109.97 Mb, and 99.52% of the scaffold anchored on 19 chromosomes. The BUSCO analysis indicated a gene completeness of 90.3% (n=7,480), including 6,673 (89.2%) single-copy genes and 84 (1.1%) duplicated genes. Additionally, we identified 21,065 protein-coding genes using the MAKER3 annotation toolkit, with 41.98% (697.51 Mb) consisting of repetitive elements. Among these, 21,037 genes were validated through InterProScan5. Our study is the first to report a chromosome-level genome for the crested gecko. It provides valuable genomic resources for understanding molecular mechanisms under many interesting traits of the species., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10 -15  mol/L and 1.56 × 10 -14  mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

After prolonged space operations, astronauts showed maladaptive atrophy within mostly left-ventricular myocardium, resulting in cardiac dysfunction. However, the mechanism of cardiac dysfunction under microgravity conditions is unclear, and the relevant prevention and treatment measures also need to be explored. Through simulating the microgravity environment with a tail suspension (TS) model, we found that long-term exposure to microgravity promotes aging of mouse hearts, which is closely related to cardiac dysfunction. The intravenous administration of adipose-derived mesenchymal stem cells (ADSCs) emerged preventive and therapeutic effect against myocardial senescence and the decline in cardiac function. Plasma metabolomics analysis suggests the loss of NAD+ in TS mice and motivated myocardial NAD + metabolism and utilization in ADSCs-treated mice, likely accounting for ADSCs' function. Oral administration of nicotinamide mononucleotide (NMN, a NAD + precursor) showed similar therapeutic effect to ADSCs treatment. Collectively, these data implicate the effect of ADSCs in microgravity-induced cardiac dysfunction and provide new therapeutic ideas for aging-related maladaptive cardiac remodeling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Long-term inflammation can cause chronic pain and trigger patients' anxiety by sensitizing the central nervous system. However, effective drugs with few side effects for treating chronic pain-induced anxiety are still lacking. The anxiolytic and anti-inflammatory effects of ruscogenin (RUS), an important active compound in Ophiopogon japonicus, were evaluated in a mouse model of chronic inflammatory pain and N9 cells. RUS (5, 10, or 20 mg/kg/day, i.g.) was administered once daily for 7 days after CFA injection; pain- and anxiety-like behaviors were assessed in mice. Anti-inflammatory effect of RUS (0.1, 1, 10 μM) on N9 microglia after LPS treatment was evaluated. Inflammatory markers (TNF-α, IL-1β, IL-6, CD86, IL-4, ARG-1, and CD206) were measured using qPCR. The levels of IBA1, ROS, NF-κB, TLR4, P-IKK, P-IκBα, and P65, MAPKs (ERK, JNK, and P38), NLRP3 (caspase-1, ASC, and NLRP3) were detected by Western blotting or immunofluorescence staining. The potential target of RUS was validated by molecular docking and adeno-associated virus injection. Mice in CFA group exhibited allodynia and anxiety-like behaviors. LPS induced neuroinflammation in N9 cells. Both CFA and LPS increased the levels of IBA1, ROS, and inflammatory markers. RUS (10 mg/kg in vivo and 1 μM in vitro) alleviated these alterations through NF-κB/MAPKs/NLRP3 signaling pathways but had no effect on pain hypersensitivity. TLR4 strongly interacted with RUS, and TLR4 overexpression abolished the effects of RUS on anxiety and neuroinflammation. RUS exerts anti-inflammatory and anxiolytic effects via TLR4-mediated NF-κB/MAPKs/NLRP3 signaling pathways, which provides a basis for the treatment of chronic pain-induced anxiety., (© 2024 John Wiley & Sons, Ltd.)

Parasite-mediated selection is widely believed to play a crucial role in maintaining the diversity of the major histocompatibility complex (MHC) genes, which is thought to be maintained through heterozygote advantage, rare-allele advantage, and fluctuating selection. However, the relationship between parasite pressure and MHC diversity has yielded inconsistent findings. These inconsistencies may arise from the influence of environmental factors and individual variations in traits on host-parasite interactions. To address these issues, our study extensively investigated populations of striped hamsters inhabiting regions characterized by environmental heterogeneity. The primary objective was to examine the universality of parasite-mediated selection mechanisms. Our observations revealed the presence of multiple parasite infections, accompanied by spatial and temporal variations in parasite communities and infection patterns among individual hamsters. Specifically, the temperature was found to influence all four parasite indices, while the presence of gamasid mites and parasite richness decreased with increasing precipitation. We also noted significant seasonal variation in parasite dynamics. Moreover, a significant sexual dimorphism was observed with males exhibiting a considerably higher parasite burden compared to their female counterparts. Lastly, we identified the maintenance of MHC polymorphism in striped hamsters as being driven by the heterozygote advantage and fluctuating selection mechanisms. This study underscores the significance of ecological processes in comprehending host-parasite systems and highlights the necessity of considering environmental factors and individual traits when elucidating the mechanisms underlying MHC diversity mediated by parasites., (© 2023 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

The throughput of mass spectrometers and the amount of publicly available metabolomics data are growing rapidly, but analysis tools such as molecular networking and Mass Spectrometry Search Tool do not scale to searching and clustering billions of mass spectral data in metabolomics repositories. To address this limitation, we designed MASST+ and Networking+, which can process datasets that are up to three orders of magnitude larger than those processed by state-of-the-art tools., Competing Interests: Competing interests H.M. and B.B. are cofounders of and have equity interests in Chemia.ai, LLC. P.C.D. is an advisor of and holds equity in Cybele, consulted for MSD Animal Health in 2023 and is a cofounder of, holds equity in and is scientific advisor for Ometa Labs, Arome and Enveda with prior approval by the University of California San Diego. The remaining authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Bartonella grahamii is one of the most prevalent Bartonella species in wild rodents and has been associated with human cases of neuroretinitis. The structure and distribution of genomic diversity in natural B. grahamii is largely unexplored. Here, we have applied a comprehensive population genomic and phylogenomic analysis to 172 strains of B. grahamii to unravel the genetic differences and influencing factors that shape its populations. The findings reveal a remarkable genomic diversity within the species, primarily in the form of single- nucleotide polymorphisms. The open pangenome of B. grahamii indicates a dynamic genomic evolution influenced by its ecological niche. Whole-genome data allowed us to decompose B. grahamii diversity into six phylogroups, each characterized by a unique "mosaic pattern" of hosts and biogeographic regions. This suggests a complex interplay between host specificity and biogeography. In addition, our study suggests a possible origin of European strains from Asian lineages, and host factors have a more significant impact on the genetic differentiation of B. grahamii than geographical factors. These insights contribute to understanding the evolutionary history of this pathogen and provide a foundation for future epidemiological research and public health strategies., Importance: Bartonella grahamii has been reported worldwide and shown to infect humans. Up to now, an effective transmission route of B. grahamii to humans has not been confirmed. The genetic evolution of B. grahamii and the relationship between B. grahamii and its host need to be further studied. The factors driving the genetic diversity of B. grahamii are still controversial. The results showed that the European isolates shared a common ancestor with the Chinese isolates. Host factors were shown to play an important role in driving the genetic diversity of B. grahamii . When host factors were fixed, geographic barriers drove B. grahamii microevolution. Our study emphasizes the importance of characterizing isolate genomes derived from hosts and geographical locations and provides a new reference for the origin of B. grahamii ., Competing Interests: The authors declare no conflict of interest.

Lumbar spinal stenosis (LSS) is a degenerative spinal condition characterized by the narrowing of the spinal canal, resulting in low back pain (LBP) and limited leg mobility. Twin and family studies have suggested that genetics contributes to disease progression. However, the genetic causes of familial LSS remain unclear. We performed whole-exome and direct sequencing on seven female patients from a Han Chinese family with LBP, among whom four developed LSS. Based on our genetic findings, we performed gene knockdown studies in human chondrocytes to study possible pathological mechanisms underlying LSS. We found a novel nonsense mutation, c.417C > G (NM&#95;002183, p.Y139X), in IL3RA , shared by all the LBP/LSS cases. Knockdown of IL3RA led to a reduction in the total collagen content of 81.6% in female chondrocytes and 21% in male chondrocytes. The expression of MMP-1 , -3 , and/or -10 significantly increased, with a more pronounced effect observed in females than in males. Furthermore, EsRb expression significantly decreased following IL3RA knockdown. Moreover, the knockdown of EsRb resulted in increased MMP-1 and -10 expression in chondrocytes from females. We speculate that IL3RA deficiency could lead to a reduction in collagen content and intervertebral disk (IVD) strength, particularly in females, thereby accelerating IVD degeneration and promoting LSS occurrence. Our results illustrate, for the first time, the association between IL3RA and estrogen receptor beta, highlighting their importance and impact on MMPs and collagen in degenerative spines in women.

A Pd-catalyzed asymmetric higher-order dipolar cycloaddition between allenyl carbonates and azadienes is achieved by exploiting novel alkylidene-π-allyl-Pd dipoles. This research provides a modular platform for the synthesis of challenging chiral endocyclic allenes bearing a medium-sized heterocyclic motif and a centrally chiral stereocenter in good yields with high enantio- and diastereoselectivities (29 examples, up to 97% yield, 97:3 er and >19:1 dr). Experimental and computational studies elucidate the possible reaction mechanism and the observed stereochemical results. Based on the mechanistic understanding, a new π-propargyl-Pd dipole was designed to further extend the success of the higher order dipolar cycloaddition strategy to the synthesis of 10-membered endocyclic alkynes from propargyl carbonates and azadienes (13 examples, up to 98% yield and 94.5:5.5 er).

Background Clinical outcome prediction based on acute-phase ischemic stroke data is valuable for planning health care resources, designing clinical trials, and setting patient expectations. Existing methods require individualized features and often involve manually engineered, time-consuming postprocessing activities. Purpose To predict the 90-day modified Rankin Scale (mRS) score with a deep learning (DL) model fusing noncontrast-enhanced CT (NCCT) and clinical information from the acute phase of stroke. Materials and Methods This retrospective study included data from six patient datasets from four multicenter trials and two registries. The DL-based imaging and clinical model was trained by using NCCT data obtained 1-7 days after baseline imaging and clinical data (age; sex; baseline and 24-hour National Institutes of Health Stroke Scale scores; and history of hypertension, diabetes, and atrial fibrillation). This model was compared with models based on either NCCT or clinical information alone. Model-specific mRS score prediction accuracy, mRS score accuracy within 1 point of the actual mRS score, mean absolute error (MAE), and performance in identifying unfavorable outcomes (mRS score, >2) were evaluated. Results A total of 1335 patients (median age, 71 years; IQR, 60-80 years; 674 female patients) were included for model development and testing through sixfold cross validation, with distributions of 979, 133, and 223 patients across training, validation, and test sets in each of the six cross-validation folds, respectively. The fused model achieved an MAE of 0.94 (95% CI: 0.89, 0.98) for predicting the specific mRS score, outperforming the imaging-only (MAE, 1.10; 95% CI: 1.05, 1.16; P < .001) and the clinical information-only (MAE, 1.00; 95% CI: 0.94, 1.05; P = .04) models. The fused model achieved an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.92) for predicting unfavorable outcomes, outperforming the clinical information-only model (AUC, 0.88; 95% CI: 0.87, 0.90; P < .001) and the imaging-only model (AUC, 0.85; 95% CI: 0.84, 0.87; P < .001). Conclusion A fused DL-based NCCT and clinical model outperformed an imaging-only model and a clinical-information-only model in predicting 90-day mRS scores. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Lee in this issue.

Background: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated., Objective: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms., Methods: A total of twenty male participants were recruited and followed up after 3 months' natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected., Results: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back, tail and paws upon lysine supplementation. Furthermore, lysine supplementation increased the level of histone H3K18cr and promoted the gene and protein expression of Cpt1a, Cpt2 and Cyp27a1 in liver., Conclusion: Our work identified lysine as a critical amino acid for the remodeling of hepatic histone crotonylation that facilitates cold acclimation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies have yielded conflicting results regarding the link between maternal perinatal depression and asthma in children. To provide a clearer understanding of this relationship, a comprehensive meta-analysis was carried out to evaluate the association mentioned above., Methods: A comprehensive review of observational studies was conducted by searching electronic databases including Medline, Embase, and Web of Science. The data were combined using a randomized-effects model taking into account potential variations. Subgroup analyses were performed to evaluate the possible impact of study characteristics on outcomes., Results: Ten cohort studies, which included 833,230 mother-child pairs, were examined in the analysis. Maternal depressive symptoms during the perinatal period were associated with an increased risk of asthma in offspring (risk ratio [RR]: 1.24, 95% confidence interval [CI]: 1.19 to 1.30, p < 0.001; I2 = 0%). Further sensitivity analyses restricted to multivariate studies (RR: 1.24, 95% CI: 1.19 to 1.30, p < 0.001; I2 = 0%) or studies where asthma was diagnosed in children aged three years or older (RR: 1.24, 95% CI: 1.19 to 1.30, p < 0.001; I2 = 0%) revealed consistent outcomes. Subgroup analyses according to study design, methods for the diagnosis of maternal depression, timing for the evaluation of maternal depression, methods for the validation of asthma in offspring, adjustment of maternal smoking during pregnancy and of maternal asthma, or study quality score showed similar results (p for subgroup difference all > 0.05)., Conclusions: Maternal perinatal depression appears to be significantly linked to a higher occurrence of childhood asthma in children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Histone deacetylation, one of most important types of post-translational modification, plays multiple indispensable roles in plant growth and development and abiotic stress responses. However, little information about the roles of histone deacetylase in regulating inflorescence architecture, fruit yield, and stress responses is available in tomato. Functional characterization revealed that SlHDT1 participated in the control of inflorescence architecture and fruit yield by regulating auxin signalling, and influenced tolerance to drought and salt stresses by governing abscisic acid (ABA) signalling. More inflorescence branches and higher fruit yield, which were influenced by auxin signalling, were observed in SlHDT1-RNAi transgenic plants. Moreover, tolerance to drought and salt stresses was decreased in SlHDT1-RNAi transgenic lines compared with the wild type (WT). Changes in parameters related to the stress response, including decreases in survival rate, chlorophyll content, relative water content (RWC), proline content, catalase (CAT) activity and ABA content and an increase in malonaldehyde (MDA) content, were observed in SlHDT1-RNAi transgenic lines. In addition, the RNA-seq analysis revealed varying degrees of downregulation for genes such as the stress-related genes SlABCC10 and SlGAME6 and the pathogenesis-related protein P450 gene SlCYP71A1, and upregulation of the pathogenesis-related protein P450 genes SlCYP94B1, SlCYP734A7 and SlCYP94A2 in SlHDT1-RNAi transgenic plants, indicating that SlHDT1 plays an important role in the response to biotic and abiotic stresses by mediating stress-related gene expression. In summary, the data suggest that SlHDT1 plays essential roles in the regulation of inflorescence architecture and fruit yield and in the response to drought and salt stresses., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: In recent years, genetic algorithms have been applied in the field of nuclear technology design, producing superior optimization results compared to traditional methods. They can be employed in the design and optimization of beam shaping assemblies (BSA) BSA to obtain the desired neutron beams. But it should be noted that the direct combination of Monte Carlo methods with genetic algorithms requires a significant amount of computational resources and time., Purpose: Design and optimize BSA more efficiently to achieve neutron beams that meet specified recommendations., Methods: We propose an approach of NSGA II with crucial variables which are identified by multivariate statistical techniques. This approach significantly reduces the problem sizes, thus reducing the time required for optimization. We illustrate this methodology using the example of BSA design for AB-BNCT., Results: The computational efficiency has tripled with crucial variables. By using NSGA II, we obtained optimized models conforming to both the new and old version IAEA BNCT guidelines through a single optimization process and subjected them to phantom analysis. The results demonstrate that models obtained through this method can meet the IAEA recommendations with deep advantage depth (AD) and high absorbed ratio (AR)., Conclusion: The genetic algorithm with crucial variables displays tremendous potential in addressing BSA optimization challenges., (© 2024 American Association of Physicists in Medicine.)

Phytohormones possess unique chemical structures, and their physiological effects are regulated through intricate interactions or crosstalk among multiple phytohormones. MALDI-MSI enables the simultaneous detection and imaging of multiple hormones. However, its application for tracing phytohormones is currently restricted by low abundance of hormone in plant and suboptimal matrix selection. 2,4-Dihydroxy-5-nitrobenzoic acid (DHNBA) was reported as a new MALDI matrix for the enhanced detection and imaging of multiple phytohormones in plant tissues. DHNBA demonstrates remarkable sensitivity improvement when compared to the commonly used matrix, 2,5-dihydroxybenzoic acid (DHB), in the detection of isoprenoid cytokinins (trans-zeatin (tZ), dihy-drozeatin (DHZ), meta-topolin (mT), and N 6 -(Δ 2 -isopentenyl) adenine (iP)), jasmonic acid (JA), abscisic acid (ABA), and 1-aminocyclo-propane-1-carboxylic acid (ACC) standards. The distinctive properties of DHNBA (i.e. robust UV absorption, uniform matrix deposition, negligible background interference, and high ionization efficiency of phytohormones) make it as an ideal matrix for enhanced detection and imaging of phytohormones, including tZ, DHZ, ABA, indole-3-acetic acid (IAA), and ACC, by MALDI-MSI in various plant tissues, for example germinating seeds, primary/lateral roots, and nodules. Employing DHNBA significantly enhances our capability to concurrently track complex phytohormone biosynthesis pathways while providing precise differentiation of the specific roles played by individual phytohormones within the same category. This will propel forward the comprehensive exploration of phytohormonal functions in plant science., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Background and Aims: The monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients., Methods: A total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities., Results: Among the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group., Conclusions: In patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Novel magnetic covalent organic frameworks (COFs) were prepared by one-pot synthetic strategy and employed as an efficient adsorbent for magnetic solid-phase extraction (MSPE) of naphthaleneacetic acid (NAA) in food samples. Depending on the predesigned the hydrogen bonding, π-π and hydrophobic interactions of magnetic COFs, the efficient and selective extraction process for NAA was achieved within 15 min. The magnetic COFs adsorbent combined with HPLC-UV was devoted to develop a novel quantitative method for NAA in complex food. The method afforded good coefficient in range of 0.002-10.0 µg mL -1 and low limit of detection was 0.0006 µg mL -1 . And the newly established method afforded less adsorbent consumption, wider linearity and lower LODs than the reported analytical methods. Ultimately, the method was successfully applied to determine NAA in fresh pear, tomato and peach juice. The magnetic COFs based MSPE coupled with HPLC-UV method provided a simple, efficient and dependable alternative to monitor trace NAA in food samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quantum communication networks are crucial for both secure communication and cryptographic networked tasks. Building quantum communication networks in a scalable and cost-effective way is essential for their widespread adoption. Here, we establish a complete polarization entanglement-based fully connected network, which features an ultrabright integrated Bragg reflection waveguide quantum source, managed by an untrusted service provider, and a streamlined polarization analysis module, which requires only one single-photon detector for each user. We perform a continuously working quantum entanglement distribution and create correlated bit strings between users. Within the framework of one-time universal hashing, we provide the experimental implementation of source-independent quantum digital signatures using imperfect keys circumventing the necessity for private amplification. We further beat the 1/3 fault tolerance bound in the Byzantine agreement, achieving unconditional security without relying on sophisticated techniques. Our results offer an affordable and practical route for addressing consensus challenges within the emerging quantum network landscape.

Background: Studies have reported the adverse effects of cold events on influenza. However, the role of critical factors, such as characteristics of cold spells, and regional variations remain unresolved., Objective: We aimed to systematically evaluate the association between cold spells and influenza incidence in mainland China., Methods: This time series analysis used surveillance data of daily influenza from 325 sites in China in the 2014-2019 period. A total of 15 definitions of cold spells were adopted based on combinations of temperature thresholds and days of duration. A distributed lag linear model was used to estimate the short-term effects of cold spells on influenza incidence during the cool seasons (November to March), and we further explored the potential impact of cold spell characteristics (ie, intensity, duration, and timing during the season) on the estimated associations. Meta-regressions were used to evaluate the modification effect of city-level socioeconomic indicators., Results: The overall effect of cold spells on influenza incidence increased with the temperature threshold used to define cold spells, whereas the added effects were generally small and not statistically significant. The relative risk of influenza-associated with cold spells was 3.35 (95% CI 2.89-3.88), and the estimated effects were stronger during the middle period of cool seasons. The health effects of cold spells varied geographically and residents in Jiangnan region were vulnerable groups (relative risk 7.36, 95% CI 5.44-9.95). The overall effects of cold spells were positively correlated with the urban population density, population size, gross domestic product per capita, and urbanization rate, indicating a sterner response to cold spells in metropolises., Conclusions: Cold spells create a substantial health burden on seasonal influenza in China. Findings on regional and socioeconomic differences in the health effects of cold spells on seasonal influenza may be useful in formulating region-specific public health policies to address the hazardous effects of cold spells., (© Haitao Wang, Mengjie Geng, Tamara Schikowski, Ashtyn Tracey Areal, Kejia Hu, Wen Li, Micheline de Sousa Zanotti Stagliorio Coelho, Paulo Hilário Nascimento Saldiva, Wei Sun, Chengchao Zhou, Liang Lu, Qi Zhao, Wei Ma. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

5-methylcytosine (m 5 C) is a prevalent RNA modification crucial for gene expression regulation. However, accurate and sensitive m 5 C sites identification remains challenging due to severe RNA degradation and reduced sequence complexity during bisulfite sequencing (BS-seq). Here, we report m 5 C-TAC-seq, a bisulfite-free approach combining TET-assisted m 5 C-to-f 5 C oxidation with selective chemical labeling, therefore enabling direct base-resolution m 5 C detection through pre-enrichment and C-to-T transitions at m 5 C sites. With m 5 C-TAC-seq, we comprehensively profiled the m 5 C methylomes in human and mouse cells, identifying a substantially larger number of confident m 5 C sites. Through perturbing potential m 5 C methyltransferases, we deciphered the responsible enzymes for most m 5 C sites, including the characterization of NSUN5's involvement in mRNA m 5 C deposition. Additionally, we characterized m 5 C dynamics during mESC differentiation. Notably, the mild reaction conditions and preservation of nucleotide composition in m 5 C-TAC-seq allow m 5 C detection in chromatin-associated RNAs. The accurate and robust m 5 C-TAC-seq will advance research into m 5 C methylation functional investigation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Replica symmetry breaking (RSB) has been introduced in a random laser to investigate the interactions between disorder and fluctuations. In this work, the dynamic difference between four non-energy transfer and Förster resonance energy transfer (FRET)-assisted random laser systems is investigated based on RSB. It is found that FRET is one of the key factors influencing RSB, and it is demonstrated that RSB in a random laser is not robust. This dynamic difference can be attributed to the different disorders induced by the gain mechanism in different random laser systems. This provides experimental evidence and theoretical support for the classification feasibility of RL with different emission mechanisms employing RSB.

Cross-individual variability is considered the essence of biology, preventing precise mathematical descriptions of biological motion 1-7 like the physics law of motion. Here we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in-vivo electrophysiology and optogenetics in mice, we confirmed that deep cerebellar neurons encoded frequencies via populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism was consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform, or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validated the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating-current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for brain-computer interface for motor control., Competing Interests: Declaration of interests: All authors declare no competing interests.

Herein, we designed a reaction for the desymmetrization-addition of cyclopropenes to imines by leveraging the synergy between photoredox and asymmetric cobalt catalysis. This protocol facilitated the synthesis of a series of chiral functionalized cyclopropanes with high yield, enantioselectivity, and diastereoselectivity (44 examples, up to 93% yield and >99% ee). A possible reaction mechanism involving cyclopropene desymmetrization by Co-H species and imine addition by Co-alkyl species was proposed. This study provides a novel route to important chiral cyclopropanes and extends the frontier of asymmetric metallaphotoredox catalysis.

Background: The metastatic vascular patterns of hepatocellular carcinoma (HCC) are mainly microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC). However, most existing VETC-related radiological studies still focus on the prediction of VETC status., Purpose: This study aimed to build and compare VETC-MVI related models (clinical, radiomics, and deep learning) associated with recurrence-free survival of HCC patients., Study Type: Retrospective., Population: 398 HCC patients (349 male, 49 female; median age 51.7 years, and age range: 22-80 years) who underwent resection from five hospitals in China. The patients were randomly divided into training cohort (n = 358) and test cohort (n = 40)., Field Strength/sequence: 3-T, pre-contrast T1-weighted imaging spoiled gradient recalled echo (T1WI SPGR), T2-weighted imaging fast spin echo (T2WI FSE), and contrast enhanced arterial phase (AP), delay phase (DP)., Assessment: Two radiologists performed the segmentation of HCC on T1WI, T2WI, AP, and DP images, from which radiomic features were extracted. The RFS related clinical characteristics (VETC, MVI, Barcelona stage, tumor maximum diameter, and alpha fetoprotein) and radiomic features were used to build the clinical model, clinical-radiomic (CR) nomogram, deep learning model. The follow-up process was done 1 month after resection, and every 3 months subsequently. The RFS was defined as the date of resection to the date of recurrence confirmed by radiology or the last follow-up. Patients were followed up until December 31, 2022., Statistical Tests: Univariate COX regression, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier curves, log-rank test, C-index, and area under the curve (AUC). P < 0.05 was considered statistically significant., Results: The C-index of deep learning model achieved 0.830 in test cohort compared with CR nomogram (0.731), radiomic signature (0.707), and clinical model (0.702). The average RFS of the overall patients was 26.77 months (range 1-80 months)., Data Conclusion: MR deep learning model based on VETC and MVI provides a potential tool for survival assessment., Evidence Level: 3 TECHNICAL EFFICACY: Stage 3., (© 2023 International Society for Magnetic Resonance in Medicine.)

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

Background: Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites., Methods: RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein-protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR)., Results: A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable., Conclusions: Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites., (© 2024. The Author(s).)

While soybean (Glycine max L.) provides the most important source of vegetable oil and protein, it is sensitive to salinity, which seriously endangers the yield and quality during soybean production. The application of Plant Growth-Promoting Rhizobacteria (PGPR) to improve salt tolerance for plant is currently gaining increasing attention. Streptomycetes are a major group of PGPR. However, to date, few streptomycetes has been successfully developed and applied to promote salt tolerance in soybean. Here, we discovered a novel PGPR strain, Streptomyces lasalocidi JCM 3373 T , from 36 strains of streptomycetes via assays of their capacity to alleviate salt stress in soybean. Microscopic observation showed that S. lasalocidi JCM 3373 T does not colonise soybean roots. Chemical analysis confirmed that S. lasalocidi JCM 3373 T secretes indole-3-carboxaldehyde (ICA1d). Importantly, IAC1d inoculation alleviates salt stress in soybean and modulates its root architecture by regulating the expression of stress-responsive genes GmVSP, GmPHD2 and GmWRKY54 and root growth-related genes GmPIN1a, GmPIN2a, GmYUCCA5 and GmYUCCA6. Taken together, the novel PGPR strain, S. lasalocidi JCM 3373 T , alleviates salt stress and improves root architecture in soybean by secreting ICA1d. Our findings provide novel clues for the development of new microbial inoculant and the improvement of crop productivity under salt stress., (© 2024 John Wiley & Sons Ltd.)

Purpose: Female infertility is a global health concern. The aim of this study was to investigate the relationship between regulatory T (Treg) cells and helper T cells 17 (Th17) in peripheral blood and unexplained infertility (UI). In addition, we explored potential valuable diagnostic biomarkers for patients with UI and ascertained whether Treg and Th17 cells are associated with primary and secondary UI., Patients and Methods: The patients underwent standard fertility evaluation test, including blood tests, ultrasound examination, fallopian tube tests, ovulation assessment, and male partner's semen analysis. According to the inclusion and exclusion criteria, this study enrolled 37 patients with UI (30 with primary UI and 7 with secondary UI) and 26 age-matched healthy volunteers as the control group. Flow cytometry was used to detect the frequency of Treg and Th17 cells. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was used to assess the diagnostic performance. An AUC > 0.800 indicated good diagnostic performance., Results: The percentage of Treg decreased significantly, whereas the percentage and absolute count of Th17 cells increased. Moreover, the Th17/Treg ratio in patients with UI increased significantly. As a diagnostic biomarker for UI, the Th17/Treg ratio exhibited remarkable diagnostic performance (AUC: 0.813 (95% CI = 0.709-0.917)). However, the percentages and absolute counts of Treg and Th17 cells in the peripheral blood of women with primary and secondary UI, as well as their Th17/Treg ratios, did not differ significantly., Conclusion: The distribution of Treg and Th17 cells is imbalanced in patients with UI. Therefore, the Th17/Treg ratio may be a promising indicator of UI. However, there were no significant differences in the distribution of Treg and Th17 cells between women with primary and secondary UI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Lu et al.)

Objective: This study aimed to clarify the association between suboptimal health status and health-related productivity loss among primary healthcare workers in China., Material and Methods: A field questionnaire survey was conducted with a multistage sampling among primary healthcare workers. The data on sub-health and health-related productivity loss were collected using the Sub-health Measurement Scale Version 1.0 and Work Productivity and Activity Impairment Questionnaire: General Health, respectively. Ordinary least squares regression was used to evaluate the association of the suboptimal health and health-related productivity loss. Subgroup analyses were performed by occupation (physician and nurse)., Results: Front-line primary healthcare workers (N = 1709) from 31 provinces in China responded to the survey. Of all participants, 73.43% experienced suboptimal health. The status of being in physical suboptimal health (Coef. = 0.050, p < 0.001, 95% CI = [0.031,0.070]) and mental suboptimal health (Coef. = 0.040, p < 0.001, 95% CI = [0.020,0.059]) status exerted significant effect on the extent of health-related productivity loss among primary healthcare workers in China. Nurses in social adaptation suboptimal health status (Coef. = 0.030, p = 0.027, 95% CI = [0.003,0.057]) had significant effect on health-related productivity loss., Conclusion: The prevalence of suboptimal health is high among the respondents. Providing support for primary healthcare workers from bio-psycho-social aspects is an effective measure to promote their occupational health and improve their productivity., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lu and Chen.)

Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2 dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.

Hepeviruses have been identified in a broad range of animal hosts, including mammals, birds, and fish. In this study, rodents ( n =91) from seven different species and ten pikas ( Ochotona curzoniae ) were collected in Qinghai Province, China. Using transcriptomic sequencing and confirmatory molecular testing, hepeviruses were detected in 27 of 45 (60 %) long-tailed dwarf hamsters ( Cricetulus longicaudatus ) and were undetected in other rodents and pika. The complete genome sequences from 14 representative strains were subsequently obtained, and phylogenetic analyses suggested that they represent a novel species within the genus Rocahepevirus , which we tentatively designated as Cl-2018QH. The virus was successfully isolated in human hepatoma (Huh-7) and murine fibroblast (17 Cl-1) cell lines, though both exhibited limited replication as assayed by detection of negative-sense RNA intermediates. A129 immunodeficient mice were inoculated with Cl-2018QH and the virus was consistently detected in multiple organs, despite relatively low viral loads. In summary, this study has described a novel rodent hepevirus, which enhances our knowledge of the genetic diversity of rodent hepeviruses and highlights its potential for cross-species transmission.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients., Methods: A total of 58 female patients (aged 20-60 years, ASAⅠ-Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis., Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group., Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Wheat Fusarium crown rot (FCR) is a serious problem primarily caused by Fusarium pseudograminearum, a pathogenic agent known to produce mycotoxins, including deoxynivalenol (DON). Cyclobutrifluram, a novel succinate dehydrogenase inhibitor devised by Syngenta, has immense potential to control both nematodes and Fusarium diseases. However, its efficacy in combating Fusarium species, its ability to prevent and reverse the detrimental effects of FCR, and its impact on the production of DON by F. pseudograminearum are yet to be fully ascertained., Results: Cyclobutrifluram exhibited substantial inhibitory activity against Fusarium species, with half-maximal effective concentration values ranging from 0.0021-0.0647 μg mL -1 . It demonstrated significant inhibitory activity toward three developmental stages of F. pseudograminearum, F. graminearum and F. asiaticum. Furthermore, cyclobutrifluram showed both protective and curative activities against FCR and was rapidly absorbed by roots and transported to wheat stems and leaves. Cyclobutrifluram could also decrease DON production by F. pseudograminearum., Conclusion: This investigation has revealed the potential of cyclobutrifluram as a formidable candidate fungicide, particularly in its ability to effectively combat FCR and other Fusarium-related ailments. This novel compound has exceptional pathogen-fighting capabilities, coupled with remarkable systemic translocation properties and a notable ability to reduce the production of DON. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed., (© 2024 Wiley-VCH GmbH.)

Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics., (© 2024. The Author(s).)

Flexible engineering of the complex shapes of the surface nanoscale axial photonics (SNAP) bottle microresonators (SBMs) is challenging for future nanophotonic technology applications. Here, we experimentally propose a powerful approach for the one-step fabrication of SBMs with simultaneous negative and positive radius variations, exhibiting a distinctive "bump-well-bump" profile. It is executed by utilizing two focused and symmetrical CO 2 laser beams exposed on the fiber surface for only several hundred milliseconds. The spectral characteristics of different eigenmodes are analyzed, providing deep insights into the complex physical processes during the CO 2 laser exposure. The shapes of the SBMs can be flexibly adjusted by the exposure time, laser power, and applied pre-strains. As a proof of this technique, the developed approach enables the efficient production of a bat SBM, ensuring a uniform field amplitude of the bat mode over the length exceeding 120 µm with 7% deviation. Our proposed technique provides a powerful technique for the efficient fabrication of SBMs with predetermined shapes, laying the groundwork for its applications on microscale optical signal processing, quantum computing, and so on.

The toxic effects of excessive manganese (Mn) levels in the environment have led to a severe public health concern. Ferroptosis is a newly form of cell death relying on iron, inherent to pathophysiological processes of psychiatric disorders, such as anxiety and depression-like behaviors. Excessive Mn exposure causes various neurological effects, including neuronal death and mood disorders. Whether Mn exposure causes anxiety and depression-like behaviors, and the underlying mechanisms of Mn-induced ferroptosis have yet to be determined. Here, Mn-exposed mice showed anxiety-like behavior. We also confirmed the accumulation of ferrous ion (Fe 2+ ), lipid peroxidation, and depletion of antioxidant defense system both in vitro and in vivo Mn-exposed models, suggesting that Mn exposure can induce ferroptosis. Furthermore, Mn exposure downregulated the expression of miR-125b-2-3p. In turn, overexpression of miR-125b-2-3p alleviated the Mn-induced ferroptosis by targeting Transferrin receptor protein 1 (TFR1). In summary, this novel study established the propensity of Mn to cause anxiety-like behavior, an effect that was regulated by miR-125b-2-3p and ensuing ferroptosis secondary to the targeting of TFR1. These results offer promising targets for the prevention and treatment of Mn-induced neurotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Herein, we aimed to develop an easily available and efficient screening method for diabetic peripheral neuropathy (DPN) suitable for primary care settings, emphasizing simplicity, speed, and accuracy. Nerve conduction studies were conducted on 214 patients with diabetes, encompassing the outcomes of five distinct assessments: diabetic neuropathy symptom (DNS), vibration perception threshold (VPT), and nerve screening. The diagnostic accuracy of the VPT and nerve screening was evaluated by comparing them with that of the nerve conduction study. To assess diagnostic efficacy, various combinations were examined, including DNS combined with VPT, pain, temperature, touch, and ankle reflex. The diagnostic performance of DNS was superior to that of the five neurological screening items and VPT, with sensitivity, specificity, and accuracy of 0.68, 0.81, and 0.73, respectively. Among the two combined methods, "DNS + ankle reflex" was identified as having the highest diagnostic value, with an area under the curve, a sensitivity, a specificity, and an accuracy of 0.81, 0.89, 0.70, and 0.80, respectively. Furthermore, a combination of "DNS + ankle reflex + touch + pain + VPT" achieved the best performance among the five combinations, with an area under the curve, sensitivity, specificity, and accuracy of 0.85, 0.93, 0.68, and 0.81, respectively. The combination of DNS, ankle reflex, touch, pain, and VPT methods showed the highest diagnostic value for DPN. However, considering factors including accuracy, time, and economic cost, we recommend using a simpler combination of DNS and ankle reflex for large-scale screening of patients with DPN.