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Peppers globally renowned for their distinctive spicy flavor, have attracted significant research attention, particularly in understanding spiciness regulation. While the activator MYB's role in spiciness regulation is well-established, the involvement of repressor MYB factors remains unexplored. This study identified the MYB4 transcription factor through RNA-seq and genome-wide analysis as being associated with spiciness. Consequently, CcMYB4-2 and CcMYB4-12 were cloned from Hainan Huangdenglong peppers, both exhibiting nuclear subcellular localization. qRT-PCR analysis revealed that CcMYB4-2/4-12 had high expression levels during the accumulation period of capsaicin, but there were differences in their peak expression levels, which may be related to the formation of pepper spiciness. Heterologous expression in Arabidopsis thaliana resulted in significantly elevated CcMYB4-2/4-12 expression levels and reduced lignin content. In CcMYB4-2 silenced plants, PAL expression remained unchanged, while PAL expression significantly increased in CcMYB4-12 silenced plants, leading to elevated lignin content and reduced capsaicin content. Yeast one-hybrid (Y1H) and dual luciferase reporter assays (DLR) demonstrated that CcMYB4-2/4-12 inhibited the transcription of CcPAL2 by binding to its promoter. Notably, CcMYB4-12 exhibited more pronounced inhibition. Therefore, it is hypothesized that CcMYB4-12 plays a pivotal role in regulating lignin and capsaicin biosynthesis. This study elucidates the molecular mechanism of MYB4 binding to the PAL promoter, providing a foundational understanding for analyzing phenylpropanoid metabolism and its diverse branches. KEY MESSAGE: Through functional verification analysis of the repressor CcMYB4, transcriptional regulation experiments revealed that CcMYB4 can bind to the CcPAL2 promoter, negatively regulating the capsaicin biosynthesis in Capsicum chinense fruits., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Citrus diseases caused by fungal pathogens drastically decreased the yield and quality of citrus fruits, leading to huge economic losses. Given the threats of chemical pesticides on the environment and human health, biocontrol agents have received considerable attention worldwide as ecofriendly and sustainable alternative to chemical fungicides. In the present study, we isolated a Bacillus velezensis strain TZ01 with potent antagonistic effect against three citrus pathogenic fungi: Diaporthe citri , Colletotrichum gloeosporioides and Alternaria alternata. The culture supernatant of this strain exhibited remarkable antifungal activity on potato dextrose agar plates and detached leaves of five citrus varieties. Treatment with TZ01 culture supernatant obviously affected the hyphal morphology and caused nucleic acid leakage. The crude lipopeptides (LPs) extracted from the culture supernatant were found as the major active ingredients, and could maintain the activity under a wide range of temperature and pH and ultraviolet radiation. Furthermore, the type of LPs, produced in vitro , were explored. Whole-genome sequencing of TZ01 revealed secondary metabolite gene clusters encoding synthetases for non-ribosomal peptides and polyketide production, and gene clusters responsible for the synthesis of three important LPs (surfactin, iturin, and fengycin) were identified in the genome. The liquid chromatography-mass spectrometry analysis confirmed the presence of various homologs of surfactin A, bacillomycin D, and fengycin A in the extracted LPs. Taken together, these results contribute to the possible biocontrol mechanisms of B. velezensis strain TZ01, as well as providing a promising new candidate strain as a biological control agent for controlling citrus fungal pathogens., 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 An, Du, Huang, Pu, Lv, Zhu, Liu, Zhang, Chen and Lu.)

P-type hydrogenated nanocrystalline silicon (nc-Si:H) has been used as a hole-selective layer for efficient n-type crystalline silicon heterojunction (SHJ) solar cells. However, the presence of an additional valence band offset at the interface between intrinsic amorphous hydrogenated silicon and p-type nc-Si:H films will limit the hole carrier transportation. In this work, it has been found that when a heavily boron-doped silicon oxide layer deposited with high hydrogen dilution to silane (p B ) was inserted into their interface, the fill factor of SHJ solar cells increases 3% absolutely because of the reduced valence band offset and the increased opportunity to provide a hopping tunnel assisted by the doping energy level and valence band tail states. Furthermore, the additional boron incorporation in intrinsic amorphous silicon adjacent to p B helps to enhance the built-in electric field, thus increasing the hole selectivity. By these means, the power conversion efficiency was improved from 23.9% to approximately 25%.

Silicon heterojunction (SHJ) solar cells have set world-record efficiencies among single-junction silicon solar cells, accelerating their commercial deployment. Despite these clear efficiency advantages, the high costs associated with low-temperature silver pastes (LTSP) for metallization have driven the search for more economical alternatives in mass production. 2D transition metal carbides (MXenes) have attracted significant attention due to their tunable optoelectronic properties and metal-like conductivity, the highest among all solution-processed 2D materials. MXenes have emerged as a cost-effective alternative for rear-side electrodes in SHJ solar cells. However, the use of MXene electrodes has so far been limited to lab-scale SHJ solar cells. The efficiency of these devices has been constrained by a fill factor (FF) of under 73%, primarily due to suboptimal charge transport at the contact layer/MXene interface. Herein, a silver nanowire (AgNW)-assisted Ti 3 C 2 T x MXene electrode contact is introduced and explores the potential of this hybrid electrode in industry-scale solar cells. By incorporating this hybrid electrode into SHJ solar cells, 9.0 cm 2 cells are achieved with an efficiency of 24.04% (FF of 81.64%) and 252 cm 2 cells with an efficiency of 22.17% (FF of 76.86%), among the top-performing SHJ devices with non-metallic electrodes to date. Additionally, the stability and cost-effectiveness of these solar cells are discussed., (© 2024 Wiley‐VCH GmbH.)

The development of heterogeneous catalysts with well-defined uniform isolated or multiple active sites is of great importance for understanding catalytic performances and studying reaction mechanisms. Herein, we present a CoCu dual-atom catalyst (CoCu-DAC) where bonded Co-Cu dual-atom sites are embedded in N-doped carbon matrix with a well-defined Co(OH)CuN 6 structure. The CoCu-DAC exhibits higher catalytic activity and selectivity than the Co single-atom catalyst (Co-SAC) and Cu single-atom catalyst (Cu-SAC) counterparts in the catalytic oxidative esterification of alcohols and a variety of methyl and alkyl esters have been successfully synthesized. Kinetic studies reveal that the activation energy (29.7 kJ mol -1 ) over CoCu-DAC is much lower than that over Co-SAC (38.4 kJ mol -1 ) and density functional theory (DFT) studies disclose that two different mechanisms are regulated over CoCu-DAC and Co-SAC/Cu-SAC in three-step esterification of alcohols. The bonded Co-Cu and adjacent N species efficiently catalyze the elementary reactions of alcohol dehydrogenation, O 2 activation and ester formation, respectively. The stepwise alkoxy pathway (O-H and C-H scissions) is preferred for both alcohol dehydrogenation and ester formation over CoCu-DAC, while the progressive hydroxylalkyl pathway (C-H and O-H scissions) for alcohol dehydrogenation and simultaneous hemiacetal dehydrogenation are favored over Co-SAC and Cu-SAC. Characteristic peaks in the Fourier transform infrared spectroscopy analysis may confirm the formation of the metal-C intermediate and the hydroxylalkyl pathway over Co-SAC., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

To investigate and comprehend the evolving research hotspots, cutting-edge trends, and frontiers associated with defensive medicine. The original data was collected from the Web of Science core collection and then subjected to a preliminary retrieval process. Following screening, a total of 654 relevant documents met the criteria and underwent subsequent statistical analysis. Software CiteSpace was employed for conducting a customized visual analysis on the number of articles, keywords, research institutions, and authors associated with defensive medicine. The defensive medicine research network was primarily established in Western countries, particularly the United States, and its findings and conceptual framework have significantly influenced defensive medicine research in other regions. Currently, quantitative methods dominated most studies while qualitative surveys remained limited. Defensive medicine research mainly focused on high-risk medical specialties such as surgery and obstetrics. Research on defensive medicine pertained to the core characteristics of its conceptual framework. An in-depth investigation into the factors that give rise to defensive medicine is required, along with the generation of more generalizable research findings to provide valuable insights for improving and intervening in defensive medicine., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

HIV-1 chronically infects host CD4 + T lymphocytes and further affects a variety of immune cells, including CD8 + T cells. In our previous study, by analyzing unbiased high-dimensional single-cell RNA-seq data (scRNA-seq), we found that the frequency of GZMK + CD8 + T cells expressing granzyme K (GZMK) was increased in people living with HIV-1 (PLWHs). However, the phenotypic and functional characteristics of these cells in chronic HIV-1 infection and their correlation with disease are not well understood. In this study, we conducted a comprehensive analysis of scRNA-seq and matched T-cell receptor repertoire (TCR) sequencing data to delve into the characterizations of GZMK + CD8 + T cells, which was further validated by flow cytometry. We observed heterogeneity within the GZMK + CD8 + T cells, which could be further subdivided into a GZMK + GZMB - subset and a GZMK + GZMB + subset, with the latter being significantly enriched in PLWHs. The GZMK + GZMB + cells are a unique subset within CD8 + T cells, characterized by high proliferation, activation, inflammatory response, clone transition, etc., and are one of the differentiation endpoints by pseudotemporal analysis of CD8+αβ T cells. Despite being predominantly composed of effector memory T cells (Tem), similar to the GZMK + GZMB - subset, the GZMK + GZMB + subset exhibits differentiation at a later stage than the GZMK + GZMB - subset. We also observed that the frequency/count of GZMK + GZMB + CD8 + T cells was negatively correlated with CD4/CD8 ratio, and positively correlated with HIV DNA, IP-10, and MIG levels in PLWHs. In vitro experiments demonstrate that GZMK can potentiate the stimulatory effects of lipopolysaccharide (LPS) on THP-1 macrophages via the TLR-4 pathway, significantly enhancing the secretion of IP-10, MIG, and MCP-1, as well as increasing the proportion of TNF-α + cells. In conclusion, in PLWHs, GZMK + GZMB + CD8 + T cells are a highly reactive and inflammatory-inducing subset that may be associated with systemic inflammation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To identify distinct trajectories of psychological resilience among Chinese patients with maintenance hemodialysis, explore influencing factors and inform the formulation of corresponding interventions., Methods: This was a multi-center longitudinal study with a 6-month follow-up. With convenience sampling, a total of 231 patients with maintenance hemodialysis were recruited between September 2020 and July 2021. Patients' characteristics, including sociodemographic information, social support and family resilience was collected through structured questionnaires as potential baseline influencing factors of psychological resilience trajectories. Psychological resilience was evaluated using the 25-item Chinese version of the Conner and Davidson resilience scale. Latent class growth modeling was conducted to identify homogeneous subgroups with distinct trajectories of psychological resilience. Univariable and multinomial logistic regression analysis were used to examine whether baseline influencing factors were associated with trajectories in patients with maintenance hemodialysis., Results: Five distinct psychological resilience trajectory groups were identified: declining group (n = 20, 8.7 %), rising group (n = 17, 7.4 %), moderate-stable group (n = 128, 55.4 %), high-stable group (n = 7, 3.0 %) and low-stable group (n = 59, 25.5 %). High-stable group and moderate-stable group were combined into the well-psychological resilience group for multinomial logistic regression analysis. The multinomial logistic regression analysis showed that influencing factors associated with trajectories of psychological resilience were age, religion, monthly household income per capita, and baseline family resilience., Conclusions: The results highlight the heterogeneity in the development of psychological resilience among Chinese patients with maintenance hemodialysis. There is a need for healthcare professionals to screen for trajectories of psychological resilience in Chinese maintenance hemodialysis patients and prepare individual mental healthcare interventions., 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.)

Salt stress imposes significant plant limitations, altering their molecular, physiological, and biochemical functions. Pepper, a valuable herbaceous plant species of the Solanaceae family, is particularly susceptible to salt stress. This study aimed to elucidate the physiological and molecular mechanisms that contribute to the development of salt tolerance in two pepper species ( Capsicum baccatum (moderate salt tolerant) and Capsicum chinense (salt sensitive)) through a transcriptome and weighted gene co-expression network analysis (WGCNA) approach to provide detailed insights. A continuous increase in malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 ) levels in C. chinense and higher activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) in C. baccatum indicated more tissue damage in C. chinense than in C. baccatum. In transcriptome analysis, we identified 39 DEGs related to salt stress. Meanwhile, KEGG pathway analysis revealed enrichment of MAPK and hormone signaling pathways, with six DEGs each. Through WGCNA, the ME.red module was identified as positively correlated. Moreover, 10 genes, A-ARR (CQW23_24856), CHIb (CQW23_04881), ERF1b (CQW23_08898), PP2C (CQW23_15893), ABI5 (CQW23_29948), P450 (CQW23_16085), Aldedh1 (CQW23_06433), GDA (CQW23_12764), Aldedh2 (CQW23_14182), and Aldedh3 (CQW23_11481), were validated by qRT-PCR. This study provides valuable insights into the genetic mechanisms underlying salt stress tolerance in pepper. It offers potential targets for future breeding efforts to enhance salt stress resilience in this crop.

For advanced synthetic intermediates or natural products with multiple unactivated and energetically similar C(sp3)-H bonds, controlling regioselectivity for the C-H activation is particularly challenging. The use of cytochrome P450 enzymes (CYPs) is a promising solution to the 'regioelectivity' challenge in remote C-H activation. Notably, CYPs and organic catalysts share a fundamental principle: they strive to control the distance and geometry between the metal reaction center and the target C-H site. Most structural analyses of the regioselectivity of CYPs are limited to the active pocket, particularly when explaining why regioselectivity could be altered by enzyme engineering through mutagenesis. However, the substructures responsible for forming the active pocket in CYPs are well known to display complex dynamic changes and substrate-induced plasticity. In this context, we highlight a comparative study of the recently reported paralogous CYPs, IkaD and CftA, which achieve different regioselectivity towards the same substrate ikarugamycin by distinct substructure conformations. We propose that substructural conformation-controlled regioselectivity might also be present in CYPs of other natural product biosynthesis pathways, which should be considered when engineering CYPs for regioselective modifications., (© 2024 Wiley‐VCH GmbH.)

Porcine deltacoronavirus (PDCoV) is an important enteric coronavirus that has caused enormous economic losses in the pig industry worldwide. However, no commercial vaccine is currently available. Therefore, developing a safe and efficacious live-attenuated vaccine candidate is urgently needed. In this study, the PDCoV strain CH/XJYN/2016 was continuously passaged in LLC-PK cells until passage 240, and the virus growth kinetics in cell culture, pathogenicity in neonatal piglets, transcriptome differences after LLC-PK infection, changes in the functional characteristics of the spike (S) protein in the high- and low-passage strains, genetic variation of the virus genome, resistance to pepsin and acid, and protective effects of this strain when used as a live-attenuated vaccine were examined. The results of animal experiments demonstrated that the virulent PDCoV strain CH/XJYN/2016 was completely attenuated and not pathogenic in piglets following serial cell passage. Genome sequence analysis showed that amino acid mutations in nonstructural proteins were mainly concentrated in Nsp3, structural protein mutations were mainly concentrated in the S protein, and the N, M, and E genes were conserved. Transcriptome comparison revealed that compared with negative control cells, P10-infected LLC-PK cells had the most differentially expressed genes (DEGs), while P0 and P240 had the least number of DEGs. Analysis of trypsin dependence and related structural differences revealed that the P10 S protein interacted more strongly with trypsin and that the P120 S protein interacted more strongly with the APN receptor. Moreover, the infectivity of P240 was not affected by pepsin but was significantly decreased after exposure to low pH. Furthermore, the P240-based live-attenuated vaccine provided complete protection to piglets against the challenge of virulent PDCoV. In conclusion, we showed that a PDCoV strain was completely attenuated through serial passaging in vitro . These results provide insights into the potential molecular mechanisms of PDCoV attenuation and the development of a promising live-attenuated PDCoV vaccine.IMPORTANCEPorcine deltacoronavirus (PDCoV) is one of the most important enteropathogenic pathogens that cause diarrhea in pigs of various ages, especially in suckling piglets, and causes enormous economic losses in the global commercial pork industry. There are currently no effective measures to prevent and control PDCoV. As reported in previous porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus studies, inactivated vaccines usually elicit less robust protective immune responses than live-attenuated vaccines in native sows. Therefore, identifying potential attenuation mechanisms, gene evolution, pathogenicity differences during PDCoV passaging, and immunogenicity as live-attenuated vaccines is important for elucidating the mechanism of attenuation and developing safe and effective vaccines for virulent PDCoV strains. In this study, we demonstrated that the virulence of the PDCoV strain CH/XJYN/2016 was completely attenuated following serial cell passaging in vitro , and changes in the biological characteristics and protection efficacy of the strain were evaluated. Our results help elucidate the mechanism of PDCoV attenuation and support the development of appropriate designs for the study of live PDCoV vaccines., Competing Interests: The authors declare no conflict of interest.

Background: The impact of weather on human health has been proven, but the impact of extreme weather events on cardiometabolic multimorbidity (CMM) needs to be urgently explored., Objectives: Investigating the impact of extreme temperature, relative humidity (RH), and laboratory testing parameters at admission on adverse events in CMM hospitalizations., Designs: Time-stratified case-crossover design., Methods: A distributional lag nonlinear model with a time-stratified case-crossover design was used to explore the nonlinear lagged association between environmental factors and CMM. Subsequently, unbalanced data were processed by 1:2 propensity score matching (PSM) and conditional logistic regression was employed to analyze the association between laboratory indicators and unplanned readmissions for CMM. Finally, the previously identified environmental factors and relevant laboratory indicators were incorporated into different machine learning models to predict the risk of unplanned readmission for CMM., Results: There are nonlinear associations and hysteresis effects between temperature, RH and hospital admissions for a variety of CMM. In addition, the risk of admission is higher under low temperature and high RH conditions with the addition of particulate matter (PM, PM 2.5 and PM 10 ) and O 3 _8h. The risk is greater for females and adults aged 65 and older. Compared with first quartile (Q1), the fourth quartile (Q4) had a higher association between serum calcium (HR = 1.3632, 95% CI: 1.0732 ~ 1.7334), serum creatinine (HR = 1.7987, 95% CI: 1.3528 ~ 2.3958), fasting plasma glucose (HR = 1.2579, 95% CI: 1.0839 ~ 1.4770), aspartate aminotransferase/ alanine aminotransferase ratio (HR = 2.3131, 95% CI: 1.9844 ~ 2.6418), alanine aminotransferase (HR = 1.7687, 95% CI: 1.2388 ~ 2.2986), and gamma-glutamyltransferase (HR = 1.4951, 95% CI: 1.2551 ~ 1.7351) were independently and positively associated with unplanned readmission for CMM. However, serum total bilirubin and High-Density Lipoprotein (HDL) showed negative correlations. After incorporating environmental factors and their lagged terms, eXtreme Gradient Boosting (XGBoost) demonstrated a more prominent predictive performance for unplanned readmission of CMM patients, with an average area under the receiver operating characteristic curve (AUC) of 0.767 (95% CI:0.7486 ~ 0.7854)., Conclusions: Extreme cold or wet weather is linked to worsened adverse health effects in female patients with CMM and in individuals aged 65 years and older. Moreover, meteorologic factors and environmental pollutants may elevate the likelihood of unplanned readmissions for CMM., (© 2024. The Author(s).)

This study presents an investigation into the propagation characteristics of a symmetric Pearcey-Pearcey space-time (SPPST) wave packet in a dispersive medium for the first time, to the best of our knowledge, in an optical system based on the fractional Schrödinger equation. Subsequently, the influence of the dispersion (normal and abnormal dispersion) on the SPPST packet is analyzed comprehensively. By manipulating the parameters of the SPPST wave packet including the parameters of the symmetric Pearcey beam, the value of the chirp, and the dispersion in the medium, it is possible to control its shape, orientation, and propagation dynamics. Simultaneously, the study delves into the effects of the combination of the dispersion and the second-order chirp on the evolution of SPPST wave packets and the associated intensity with these wave packets. Studying self-focusing wave packets with spatiotemporal symmetry provides new theoretical support for the development of quantum optics and optical communication.

Spatially resolved photoluminescence (PL) and electroluminescence (EL) imaging technologies play a crucial role in evaluating the performance and stability of photovoltaic devices. However, their application in perovskite devices presents unique challenges. In this study, we report a discrepancy between the electrical performance of perovskite solar modules (PSMs) and the EL images. Following the application of a reverse bias voltage, we observed an increase in EL brightness associated with prolonged carrier lifetime and transport length. Furthermore, cross-sectional Kelvin probe force microscopy identified a significant potential increase primarily at the electron-transport layer (ETL) side after reverse bias, suggesting the presence of defective ETL/perovskite interfaces with filled hole traps. To address this EL mismatch, we proposed a mild reverse current recovery method aimed at aligning EL images with the cell performance without compromising device efficiency. This approach effectively mitigates discrepancies, ensuring alignment between the device performance and EL imaging. Our study underscores that caution is required when utilizing EL imaging to monitor spatial homogeneity in PSMs for future industrial production.

Ovarian cancer (OC) is the deadliest malignancy of the female reproductive system. The standard first-line therapy for OC involves cytoreductive surgical debulking followed by chemotherapy based on platinum and paclitaxel. Despite these treatments, there remains a high rate of tumor recurrence and resistance to platinum. Recent studies have highlighted the potential anti-tumor properties of metformin (met), a traditional diabetes drug. In our study, we investigated the impact of met on the anticancer activities of cisplatin (cDDP) both in vitro and in vivo. Our findings revealed that combining met with cisplatin significantly reduced apoptosis in OC cells, decreased DNA damage, and induced resistance to cDDP. Furthermore, our mechanistic study indicated that the resistance induced by met is primarily driven by the inhibition of the ATM/CHK2 pathway and the upregulation of the Rad51 protein. Using an ATM inhibitor, KU55933, effectively reversed the cisplatin resistance phenotype. In conclusion, our results suggest that met can antagonize the effects of cDDP in specific types of OC cells, leading to a reduction in the chemotherapeutic efficacy of cDDP., Competing Interests: Declaration of competing interest We declare the manuscript is an original work which has not been previously published in whole or in part and is not under consideration for publication in any other journals. Its publication has been approved by all co-authors. All authors have contributed to this work and state no existing competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Central Nervous System (CNS) infections caused by Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a major clinical challenge and are associated with high mortality rates. Polymyxin is used as a salvage treatment for CRKP CNS infection; however, heteroresistance to polymyxin may impact clinical outcomes. In this study, we report a rare case of polymyxin-resistant Klebsiella intracranial infection, which was successfully treated with intravenous and intraventricular antibiotic injections., Case Presentation: A 46-year-old woman with a 1-day history of post-traumatic disturbance of consciousness and cerebrospinal fluid (CSF) rhinorrhea was referred to our hospital. She underwent external ventricular drainage and decompressive craniectomy, and had a persistent fever. A CSF test confirmed intracranial infection. The minimum inhibitory concentration of polymyxin in this patient was 16 μg/mL. She was diagnosed with polymyxin-resistant pan drug-resistant (PDR) Klebsiella pneumoniae (PDR-Kp) intracranial infection. We successfully treated the infection using intravenous ceftazidime/avibactam (CAZ/AVI) and polymyxin B, combined with an intraventricular injection of polymyxin B according to the CSF microbiological culture results., Conclusion: CAZ/AVI combined with polymyxin B may be an effective salvage treatment for CNS infections caused by polymyxin-resistant PDR-KP., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

Aims: This study explored the relationships between family resilience, dyadic coping and psychological adjustment among adolescents with chronic illnesses and their parents. The actor-partner interdependence mediation model was used to validate the mediating role of dyadic coping in the relationship between family resilience and psychological adjustment., Design: This is a cross-sectional study., Methods: A total of 318 parent-adolescents dyads were recruited from three paediatric hospitals in Wenzhou, Hangzhou, Shanghai city, China, between June 2022 and August 2023. The parents had a mean age of 41.62 years, and the adolescents had a mean age of 12.66 years. Participants independently completed a self-report questionnaire assessed family resilience, dyadic coping and psychological adjustment. Data analysis was conducted using the actor-partner interdependence mediation model., Results: The findings suggest that in the actor effects, family resilience directly influenced psychological adjustment, and family resilience is related to psychological adjustment through positive dyadic coping. In the partner effect, parents' family resilience influenced adolescents' psychological adjustment through the parents' positive dyadic coping. Similarly, adolescents' family resilience influenced parents' psychological adjustment through both parents' positive dyadic coping and adolescents' negative dyadic coping. Additionally, there was a partner effect between parents' family resilience and adolescents' psychological adjustment., Conclusion: This study demonstrated the importance of developing effective dyadic interventions based on family resilience or positive dyadic coping strategies to improve the mental health of adolescents with chronic illnesses and their parents., Impact: The mediating role of dyadic coping in the relationship between family resilience and psychological adjustment among adolescents with chronic illnesses and their parents was demonstrated. Future psychosocial interventions should focus on increasing parents' positive dyadic coping strategies and improving adolescents' negative dyadic coping strategies., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

This study introduces a novel image reconstruction technique based on a diffusion model that is conditioned on the native data domain. Our method is applied to multi-coil MRI and quantitative MRI (qMRI) reconstruction, leveraging the domain-conditioned diffusion model within the frequency and parameter domains. The prior MRI physics are used as embeddings in the diffusion model, enforcing data consistency to guide the training and sampling process, characterizing MRI k-space encoding in MRI reconstruction, and leveraging MR signal modeling for qMRI reconstruction. Furthermore, a gradient descent optimization is incorporated into the diffusion steps, enhancing feature learning and improving denoising. The proposed method demonstrates a significant promise, particularly for reconstructing images at high acceleration factors. Notably, it maintains great reconstruction accuracy for static and quantitative MRI reconstruction across diverse anatomical structures. Beyond its immediate applications, this method provides potential generalization capability, making it adaptable to inverse problems across various domains.

Glycoproteins are abundant within the human reproductive system and alterations in glycosylation lead to reproductive disorders, suggesting that glycans play an important role in reproductive function. In this study, we used the Drosophila reproductive system as a model to investigate the biological functions of O-glycosylation. We found that O-glycosylation in the male accessory glands, an organ responsible for secreting seminal fluid proteins, plays important roles in female postmating behavior. The loss of one O-glycosyltransferase, PGANT9, in the male reproductive system resulted in decreased egg production in mated females. We identified one substrate of PGANT9, lectin-46Ca (CG1656), which is known to affect female postmating responses. We further show that the loss of lectin-46Ca O-glycosylation affects its ability to associate with sperm tails, resulting in reduced transfer within the female reproductive system. Our results provide the first example that O-glycosylation of a seminal fluid protein affects its ability to associate with sperm in vivo. These studies may shed light on the biological function of O-glycans in mammalian reproduction., (Published by Oxford University Press on behalf of National Academy of Sciences 2024.)

Volitional modulation of neural activity is not confined to the cortex but extends to various brain regions. Yet, it remains unclear whether neurons in the basal ganglia structure, the external globus pallidus (GPe), can be volitionally controlled. Here, we employed a volitional conditioning task to compare the volitional modulation of GPe and primary motor cortex (M1) neurons as well as the underlying circuits and control mechanisms. The results revealed that the volitional modulation of GPe neuronal activity engaged both M1 and substantia nigra pars reticulata (SNr) neurons, indicating the involvement of the cortex-GPe-SNr loop. In contrast, the volitional modulation of M1 neurons primarily occurred through the engagement of M1 local circuitry. Furthermore, lesioning M1 neurons did not affect the volitional learning or volitional control signal in GPe, whereas lesioning of GPe neurons impaired the learning process for the volitional modulation of M1 neuronal activity at the intermediate stage. Additionally, lesion of GPe neurons enhanced M1 neuronal activity when performing the volitional control task without reward delivery and a random reward test. Taken together, our findings demonstrated that GPe neurons could be volitionally controlled by engagement of the cortical-basal ganglia circuit and inhibit learning process for the volitional modulation of M1 neuronal activity by regulating M1 neuronal activity. Thus, GPe neurons can be effectively harnessed for independent volitional modulation for neurorehabilitation in patients with cortical damage. KEY POINTS: The cortical-basal ganglia circuit contributes to the volitional modulation of GPe neurons. Volitional modulation of M1 neuronal activity mainly engages M1 local circuitry. Bilateral GPe lesioning impedes volitional learning at the intermediate stages. Lesioning of GPe neurons inhibits volitional learning process by regulating M1 neuronal activity., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Background: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms., Methods: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences., Results: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, p FDR  < 0.05) and the rolandic operculum (t = -4.57, p FDR  < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log10 8 ) and "modulation of chemical synaptic transmission" (p < -log10 8 ) in both cells., Conclusions: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623., Competing Interests: Declaration of competing interest All authors declare that No conflict of interest exists., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Cancer patients not only experience a variety of problems associated with the treatment of their disease but also a range of psychological problems such as anxiety and depression, which may lead to reduced adherence to treatment and a lower quality of life for cancer patients. Telehealth interventions are widely used for cancer patients, and their effectiveness in improving anxiety and depression in cancer patients is variable and still contradictory., Methods: Embase, Pubmed, Web of Science, PsycINFO, CINAHL Complete, and the Cochrane Central Register of Controlled Trials were searched from inception to 19 April 2022. Data synthesis was conducted using STATA 15.0, and scores for anxiety and depression were calculated using standardized mean differences and 95% confidence intervals., Results: A total of 13125 cancer patients from 68 randomized controlled trials were included in the systematic evaluation. The meta-analysis showed that the telehealth intervention had a significant effect on anxiety (standardized mean differences = -0.40, 95% confidence intervals: -0.6 to 0.2, p  < 0.001) and depression (standardized mean differences = -0.48, 95% confidence intervals: -0.67 to 0.28, p  < 0.001) in patients with cancer., Discussion: Telehealth interventions significantly improved anxiety and depression levels in cancer patients compared to traditional care interventions. Breast cancer patients most often received telehealth interventions; electronic device-based and application-based telehealth interventions were more effective than online interventions; short-term interventions were more effective than medium-term and long-term interventions, and different outcome measurement tools led to different intervention outcomes. More high-quality research is needed to explore the effects of telehealth interventions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Porcine deltacoronavirus (PDCoV), an enteropathogenic coronavirus, causes severe watery diarrhoea, dehydration and high mortality in piglets, which has the potential for cross-species transmission in recent years. Growth factor receptor-bound protein 2 (Grb2) is a bridging protein that can couple cell surface receptors with intracellular signal transduction events. Here, we investigated the reciprocal regulation between Grb2 and PDCoV. It is found that Grb2 regulates PDCoV infection and promotes IFN-β production through activating Raf/MEK/ERK/STAT3 pathway signalling in PDCoV-infected swine testis cells to suppress viral replication. PDCoV N is capable of interacting with Grb2. The proline-rich motifs in the N- or C-terminal region of PDCoV N were critical for the interaction between PDCoV-N and Grb2. Except for Deltacoronavirus PDCoV N, the Alphacoronavirus PEDV N protein could interact with Grb2 and affect the regulation of PEDV replication, while the N protein of Betacoronavirus PHEV and Gammacoronavirus AIBV could not interact with Grb2. PDCoV N promotes Grb2 degradation by K48- and K63-linked ubiquitin-proteasome pathways. Overexpression of PDCoV N impaired the Grb2-mediated activated effect on the Raf/MEK/ERK/STAT3 signal pathway. Thus, our study reveals a novel mechanism of how host protein Grb2 protein regulates viral replication and how PDCoV N escaped natural immunity by interacting with Grb2.

Purpose: High densities of tumor infiltrating CD3 and CD8 T-cells are associated with superior prognosis in colorectal cancer (CRC). Their value as predictors of benefit from adjuvant chemotherapy is uncertain., Patients and Methods: Tumor tissue from 868 patients in the QUASAR trial (adjuvant fluorouracil/folinic acid v observation in stage II/III CRC) was analyzed by CD3 and CD8 immunohistochemistry. Pathologists, assisted by artificial intelligence, calculated CD3 and CD8 cell densities (cells/mm 2 ) in the core tumor (CT) and invasive margin (IM). Participants were randomly partitioned into training and validation sets. The primary outcome was recurrence-free interval (RFI), 2-year RFI for assessment of biomarker-treatment interactions. Maximum-likelihood methods identified optimal high-risk/low-risk group cutpoints in the training set. Prognostic analyses were repeated in the validation set., Results: In the training set, the recurrence rate in the high-risk group was twice that in the low-risk group for all measures (CD3-CT: rate ratio [RR], 2.00, P = .0008; CD3-IM: 2.38, P < .00001; CD8-CT: 2.17, P = .0001; CD8-IM: 2.13, P = .0001). This was closely replicated in the validation set (RR, 1.96, 1.79, 1.72, 1.72, respectively). In multivariate analyses, prognostic effects were similar in colon and rectal cancers, and in stage II and III disease. Proportional reductions in recurrence with adjuvant chemotherapy were of similar magnitude in the high- and low-recurrence risk groups. Combining information from CD3-IM and CD3-CT (CD3 Score) generated high-, intermediate-, and low-risk groups with numbers needed to treat (NNTs) to prevent one disease recurrence being 11, 21, and 36, respectively., Conclusion: Recurrence rates in the high-risk CD3/CD8 groups are twice those in the low-risk groups. Proportional reductions with chemotherapy are similar, allowing NNTs derived in QUASAR to be updated using contemporary, nonrandomized data sets.

Background: Photo-thermo-sensitive male sterility (PTMS), which refers to the male sterility triggered by variations in photoperiod and temperature, is a crucial element in the wheat two-line hybrid system. The development of safe production and efficient propagation for male sterile lines holds utmost importance in two-line hybrid wheat. Under the stable photoperiod condition, PTMS is mainly induced by high or low temperatures in wheat, but the effect of daily temperature difference (DTD) on the fertility conversion of PTMS lines has not been reported. Here, three BS type PTMS lines including BS108, BS138, and BS366, as well as a control wheat variety J411 were used to analyze the correlation between fertility and DTD using differentially sowing tests, photo-thermo-control experiments, and transcriptome sequencing., Results: The differentially sowing tests suggested that the optimal sowing time for safe seed production of the three PTMS lines was from October 5th to 25th in Dengzhou, China. Under the condition of 12 h 12 °C, the PTMS lines were greatly affected by DTD and exhibited complete male sterility at a temperature difference of 15 °C. Furthermore, under different temperature difference conditions, a total of 20,677 differentially expressed genes (DEGs) were obtained using RNA sequencing. Moreover, through weighted gene co-expression network analysis (WGCNA) and KEGG enrichment analysis, the identified DEGs had a close association with "starch and sucrose metabolism", "phenylpropanoid biosynthesis", "MAPK signaling pathway-plant", "flavonoid biosynthesis", and "cutin, and suberine and wax biosynthesis". qRT-PCR analysis showed the expression levels of core genes related to KEGG pathways significantly decreased at a temperature difference of 15 ° C. Finally, we constructed a transcriptome mediated network of temperature difference affecting male sterility., Conclusions: The findings provide important theoretical insights into the correlation between temperature difference and male sterility, providing guidance for the identification and selection of more secure and effective PTMS lines., (© 2024. The Author(s).)

Heavy metal accumulation in agricultural products has become a major concern. Previous studies have focused on the transport of heavy metals from the soil and their accumulation in crops. However, recent studies revealed that wheat leaves, ears, and awns can also transport and accumulate heavy metals. Wheat grains can be influenced by two sources of heavy metals: soil contamination and atmospheric deposition. To comprehend the transport characteristics of heavy metals in soil, atmospheric deposition, and wheat, 37 samples each for wheat rhizosphere soil, wheat roots, stems, leaves, and grains were collected. Fifteen samples of atmospheric dry deposition and atmospheric wet deposition were collected from Linshu County (northern area), China. Based on the test data, the characteristics of heavy metals and their distribution in the study area were analyzed. Migration patterns of heavy metals in crops from different sources were investigated using Pearson correlation and redundancy analysis. Finally, a predictive model for heavy metals in wheat grains was developed using multiple linear regression analysis. Significant disparities in the distribution of heavy metals existed among wheat roots, stems, leaves, and grains. The coefficient of variation of heavy metals in atmospheric deposition was relatively high, indicating discernible spatial patterns influenced by human activities. Notably, a positive correlation was observed between the concentration of heavy metals in wheat grains and atmospheric deposition of Hg, Cd, and Pb. Conversely, Zn and Ni levels in wheat grains were significantly negatively associated with soil Zn, Ni, pH, and OM content. The contribution of heavy metal elements from different sources varied in their impact on the grain's heavy metal content. Specifically, atmospheric deposition was the primary source of Hg and Pb in wheat grains, while Cd, Ni, Cu, and Zn were predominantly derived from soil. Using a multiple linear regression model, we could accurately predict Hg, Pb, Cd, Ni, Zn, and As concentrations in crop grains. This model can facilitate quantitative evaluation of ecological risk of heavy metals accumulation in crops in the study area., (© 2024. The Author(s).)

Background: We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV)., Methods: The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022., Results: In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively)., Conclusions: In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aims to develop an effective bivalent subunit vaccine that is promising to prevent both porcine deltacoronavirus (PDCoV) and porcine epidemic diarrhea virus (PEDV). The receptor-binding domains (RBDs) of PDCoV and PEDV were fused and cloned into the eukaryotic expression vector pCDNA3.1(+). The fusion protein PDCoV-RBD-PEDV-RBD (pdRBD-peRBD) was expressed by the ExpiCHO TM expression system and purified. Mice were immunized with the fusion protein at three different doses (10, 20, and 30 μg). The humoral immune response and cellular immune response induced by the fusion protein were evaluated by ELISA and flow cytometry. The neutralization titers of the serum of immunized mice against PDCoV and PEDV were determined by the microneutralization test. The results showed that high levels of IgG antibodies were induced in the three different dose groups after booster immunization, and there was no significant difference in the antibody level between different dose groups, indicating that the immunization dose of 10 μg could achieve the fine immune effect. The results of flow cytometry showed that the immunization groups demonstrated increased proportion of CD 3 + CD 4 + T cells and decreased proportion of CD 3 + CD 8 + T cells, which was consistent with the expectation about the humoral immune response induced by the subunit vaccine. At the same time, the levels of interleukin (IL)-2, IL-4, and interferon (IFN)-γ in the serum were determined. The results showed that the fusion protein induced both humoral immune effect and cellular immune response. The results of the neutralization test showed that the antibody induced by 10 μg fusion protein neutralized both PDCoV and PEDV in vitro , with the titers of 1:179.25 and 1:141.21, respectively. The above results suggested that the pdRBD-peRBD could induce a high level of humoral immune response at a dose of 10 μg, and the induced antibody could neutralize both PDCoV and PEDV. Therefore, the fusion protein pdRBD-peRBD is expected to be an effective subunit vaccine that can simultaneously prevent PDCoV and PEDV.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute the only medication class that consistently prevents or attenuates human heart failure (HF) independent of ejection fraction. We have suggested earlier that the protective mechanisms of the SGLT2i Empagliflozin (EMPA) are mediated through reductions in the sodium hydrogen exchanger 1 (NHE1)-nitric oxide (NO) pathway, independent of SGLT2. Here, we examined the role of SGLT2, NHE1 and NO in a murine TAC/DOCA model of HF. SGLT2 knockout mice only showed attenuated systolic dysfunction without having an effect on other signs of HF. EMPA protected against systolic and diastolic dysfunction, hypertrophy, fibrosis, increased Nppa/Nppb mRNA expression and lung/liver edema. In addition, EMPA prevented increases in oxidative stress, sodium calcium exchanger expression and calcium/calmodulin-dependent protein kinase II activation to an equal degree in WT and SGLT2 KO animals. In particular, while NHE1 activity was increased in isolated cardiomyocytes from untreated HF, EMPA treatment prevented this. Since SGLT2 is not required for the protective effects of EMPA, the pathway between NHE1 and NO was further explored in SGLT2 KO animals. In vivo treatment with the specific NHE1-inhibitor Cariporide mimicked the protection by EMPA, without additional protection by EMPA. On the other hand, in vivo inhibition of NOS with L-NAME deteriorated HF and prevented protection by EMPA. In conclusion, the data support that the beneficial effects of EMPA are mediated through the NHE1-NO pathway in TAC/DOCA-induced heart failure and not through SGLT2 inhibition., (© 2024. The Author(s).)

Objective: To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU)., Methods: This retrospective cohort study was conducted at a large children's hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission., Results: A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN., Conclusion: This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes., (© 2024. The Author(s).)

Introduction: Chronic inflammation is the major pathological feature of Atherosclerosis(As). Inflammation may accelerate plaque to develop, which is a key factor resulting in the thinning of the fibrous cap and the vulnerable rupture of plaque. Presently, clinical treatments are still lacking. It is necessary to find a safe and effective treatment for As inflammation. Simiaoyongan Decoction (SMYA) has potential anti-inflammatory and plaque protection effects. This protocol aims to evaluate the efficacy, safety, and mechanism of SMYA for patients with carotid atherosclerotic plaque., Methods/design: The assessment of SMYA clinical trial is designed as a randomized, double-blind, placebo-controlled study. The sample size is 86 cases in total, with 43 participants in the intervention group and the control group respectively. The intervention group takes SMYA, while the control group takes SMYA placebo. The medication lasts for 14 days every 10 weeks, with a total of 50 weeks. We will use carotid artery high resolution magnetic resonance imaging (HR-MRI) to measure plaque. The plaque minimum fiber cap thickness (PMFCT) is adopted as the primary outcome. The secondary outcomes include plaque fiber cap volume, volume percentage of fiber cap, lipid-rich necrotic core (LRNC) volume, volume percentage of LRNC, internal bleeding volume of plaque, internal bleeding volume percentage of plaque, plaque calcification volume, volume percentage of plaque calcification, lumen stenosis rate, average and a maximum of vessel wall thickness, vessel wall volume, total vessel wall load, carotid atherosclerosis score, hs-CRP, IL-1β and IL-6, the level of lipid profiles and blood glucose, blood pressure, and body weight., Discussion: We anticipate that patients with As plaque will be improved from SMYA by inhibiting inflammation to enhance plaque stability. This study analyzes plaque by using HR-MRI to evaluate the clinical efficacy and safety of SMYA. Moreover, we conduct transcriptome analysis, proteomic analysis, and metagenomic analysis of blood and stool of participants to study the mechanism of SMYA against As plaque. This is the first prospective TCM trial to observe and treat As plaque by inhibiting inflammatory reaction directly. If successful, the finding will be valuable in the treatment of As plaque and drug development, especially in the "statin era"., Trial Registration Number: This trial is registered on Chinese Clinical Trials.gov with number ChiCTR2000039062 on October 15, 2020 ( http://www.chictr.org.cn )., (© 2024. The Author(s).)

Milvexian, an oral activated Factor XI (FXIa) inhibitor, is in clinical studies where it may be combined with antiplatelet agents, including aspirin and/or clopidogrel, to prevent thromboembolic diseases. This phase I trial assessed safety, pharmacokinetics, and pharmacodynamics of milvexian coadministration with aspirin and/or clopidogrel in healthy participants through 3 drug-drug interaction studies using a 3-period, 3-treatment, crossover design. A total of 113 participants were randomized to receive milvexian (200 mg; twice daily for 5 days) or matched placebo coadministered with once-daily aspirin (325 mg for 5 days) and/or clopidogrel (Day 1: 300 mg; Days 2-5: 75 mg). Milvexian was safe and well tolerated, with and without aspirin and/or clopidogrel. Eight mild bleeding adverse events (AEs) were reported in 5 of 113 participants across various treatment arms. Peak and total exposures of milvexian were similar with or without clopidogrel and/or aspirin. Exposure-dependent prolongation of activated partial thromboplastin time and reduction of FXI clotting activity by milvexian were similar with coadministration of aspirin and/or clopidogrel. Milvexian, with or without coadministration of aspirin and/or clopidogrel, did not affect bleeding time or platelet aggregation. Administration of milvexian alone or with aspirin and/or clopidogrel was safe and well tolerated without increased incidence of AEs, including bleeding. Pharmacokinetic and pharmacodynamic effects of milvexian, including bleeding time, were similar with or without aspirin and/or clopidogrel.ClinicalTrials.gov Identifier: NCT03698513., (© 2024. The Author(s).)

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori , which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori -infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti- H. pylori functional foods.

The aging process is linked to numerous cellular changes, among which are modifications in the functionality of dermal fibroblasts. These fibroblasts play a crucial role in sustaining the healing of skin wounds. Reduced cell proliferation is a hallmark feature of aged dermal fibroblasts. Long intergenic non-coding RNA (lincRNAs), such as LincRNA-EPS (Erythroid ProSurvival), has been implicated in various cellular processes. However, its role in aged dermal fibroblasts and its impact on the cell cycle and its regulator, Cyclin D1 (CCND1), remains unclear. Primary dermal fibroblasts were isolated from the skin of 17-week-old (young) and 88-week-old (aged) mice. Overexpression of LincRNA-EPS was achieved through plasmid transfection. Cell proliferation was detected using the MTT assay. Real-time PCR was used to quantify relative gene expressions. Our findings indicate a noteworthy decline in the expression of LincRNA-EPS in aged dermal fibroblasts, accompanied by reduced levels of CCND1 and diminished cell proliferation in these aging cells. Significantly, the overexpression of LincRNA-EPS in aged dermal fibroblasts resulted in an upregulation of CCND1 expression and a substantial increase in cell proliferation. Mechanistically, LincRNA-EPS induces CCND1 expression by sequestering miR-34a, which was dysregulated in aged dermal fibroblasts, and directly targeting CCND1. These outcomes underscore the crucial role of LincRNA-EPS in regulating CCND1 and promoting cell proliferation in aged dermal fibroblasts. Our study provides novel insights into the molecular mechanisms underlying age-related changes in dermal fibroblasts and their implications for skin wound healing. The significant reduction in LincRNA-EPS expression in aged dermal fibroblasts and its ability to induce CCND1 expression and enhance cell proliferation highlight its potential as a therapeutic target for addressing age-related skin wound healing.

Accurate identification and precise classification of freshwater mussel species that are among the most threatened freshwater taxa in the world, play a crucial role in informing conservation and management efforts for these organisms. However, due to the variability in shell morphology, relying solely on shell characteristics for species taxonomy poses significant challenges, thereby impeding effective conservation planning and management. The freshwater mussel genus Ptychorhynchus Simpson, 1900 is one such group in need of study. We integrate molecular phylogeny, shell morphology and soft-body anatomy to examine the classification of Ptychorhynchus denserugata (Haas, 1910) and Ptychorhynchus resupinatus (von Martens, 1902). The COI barcoding data support the clustering of P. denserugata and Nodularia douglasiae within a single clade, and P. denserugata shares the diagnostic feature of the genus Nodularia , i.e. knobs or bumps on the inner mantle surface in the excurrent aperture. Therefore, by integrating molecular data and anatomical characteristics, we confirm that the nominal species P. denserugata syn. nov. is a new synonym for N. douglasiae . The multi-locus (COI + ND1 + 16S rRNA + 18S rRNA + 28S rRNA ) phylogeny and mitochondrial phylogenomics support the transfer of P. resupinatus from Ptychorhynchus to the newly elevated genus Cosmopseudodon stat. rev., as Cosmopseudodon resupinatus stat. rev. that is still considered the designated type species. We also describe a new species based on integrative taxonomy, i.e. Cosmopseudodon wenshanensis sp. nov. The comprehensive understanding of the taxonomy and diversity of the revised Cosmopseudodon species, and shell heteromorphism of N. douglasiae (=P. denserugata syn. nov.), will serve as a crucial foundation for further scientific assessment and conservation strategies pertaining to these taxa. ZooBank: urn:lsid:zoobank.org:pub:E48968B1-DF0F-42AD-8F31-B8C95F23CE57.

Background: Myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder with significant morbidity and mortality. Traditional Chinese medicine (TCM) offers an alternative approach to standard pharmacological and surgical interventions, which are often associated with adverse side effects. This case report details the clinical remission of a 50-year-old male with moderate generalized MG following exclusive treatment with a modified Buzhong Yiqi decoction (BYD), a TCM formula, without the use of immunosuppressive agents., Case Summary: The patient presented with diplopia, bilateral ptosis, weakness in chewing, limb weakness, and other symptoms indicative of spleen and stomach qi deficiency. Modified BYD was prescribed, focusing on strengthening the spleen, nourishing qi and blood, and enhancing immune response. The treatment included ingredients such as Radix Astragali, Angelica sinensis, Atractylodes macrocephala, and others, aiming to restore balance and improve the patient's condition. After two weeks of TCM treatment, the patient showed significant improvement in symptoms of myasthenia. By the second month, all clinical symptoms had disappeared. The patient continued to receive the TCM regimen until the thirtieth month of treatment. At the time of writing this report, the patient has no clinical symptoms and has experienced no relapse. Notably, no obvious adverse effects were reported throughout the treatment., Conclusion: The success of this case suggests that TCM may serve as an independent treatment option for moderate MG, offering a steroid-free alternative, which would be particularly valuable for patients who are intolerant of or refuse steroid therapy, potentially with significant clinical implications. However it needs a randomized clinical trial comparing TCM to conventional Western medicine treatment to validate it., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O 2 in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia. Filopodia-derived small EVs (sEVs) were enriched with the sphingolipid ceramide, consistent with increased ceramide in the plasma membrane of filopodia. Ceramide was colocalized with neutral sphingomyelinase 2 (nSMase2) and acid sphingomyelinase (ASM), two sphingomyelinases generating ceramide at the plasma membrane. Inhibition of nSMase2 and ASM prevented oxidative stress-induced sEV shedding but only nSMase2 inhibition prevented filopodia formation. nSMase2 was S-palmitoylated and interacted with ASM in filopodia to generate ceramide for sEV shedding. sEVs contained nSMase2 and ASM and decreased the level of these two enzymes in oxidatively stressed Hela cells. A novel metabolic labeling technique for EVs showed that oxidative stress induced secretion of fluorescent sEVs labeled with NBD-ceramide. NBD-ceramide-labeled sEVs transported ceramide to mitochondria, ultimately inducing cell death in a proportion of neuronal (N2a) cells. In conclusion, using Hela cells we provide evidence that oxidative stress induces interaction of nSMase2 and ASM at filopodia, which leads to shedding of ceramide-rich sEVs that target mitochondria and propagate cell death., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Aqueous zinc-ion batteries (AZIBs) based on vanadium oxides or sulfides are promising candidates for large-scale rechargeable energy storage due to their ease of fabrication, low cost, and high safety. However, the commercial application of vanadium-based electrode materials has been hindered by challenging problems such as poor cyclability and low-rate performance. To this regard, sophisticated nanostructure engineering technology is used to adeptly incorporate VS 2 nanosheets into the MXene interlayers to create a stable 2D heterogeneous layered structure. The MXene nanosheets exhibit stable interactions with VS 2 nanosheets, while intercalation between nanosheets effectively increases the interlayer spacing, further enhancing their stability in AZIBs. Benefiting from the heterogeneous layered structure with high conductivity, excellent electron/ion transport, and abundant reactive sites, the free-standing VS 2 /Ti 3 C 2 T z composite film can be used as both the cathode and the anode of AZIBs. Specifically, the VS 2 /Ti 3 C 2 T z cathode presents a high specific capacity of 285 mAh g -1 at 0.2 A g -1 . Furthermore, the flexible Zn-metal free in-plane VS 2 /Ti 3 C 2 T z //MnO 2 /CNT AZIBs deliver high operation voltage (2.0 V) and impressive long-term cycling stability (with a capacity retention of 97% after 5000 cycles) which outperforms almost all reported Vanadium-based electrodes for AZIBs. The effective modulation of the material structure through nanocomposite engineering effectively enhances the stability of VS 2 , which shows great potential in Zn 2+ storage. This work will hasten and stimulate further development of such composite material in the direction of energy storage., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Purpose: This study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE)., Methods: This study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified., Results: Analysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC., Conclusion: The manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Establishing effective charge transfer channels between two semiconductors is key to improving photocatalytic activity. However, controlling hetero-structures in situ and designing binding modes pose significant challenges. Herein, hydrolytic SnCl 2 ·2H 2 O is selected as the metal source and loaded in situ onto a layered carbon nitriden supramolecular precursor. A composite photocatalyst, S 4 -Sn-N 2 , with electron pathways of SnS 2 and tubular carbon nitriden (TCN) is prepared through pyrolysis and vulcanization processes. The contact interface of SnS 2 -TCN is increased significantly, promoting the formation of S 4 -Sn-N 2 micro-structure in a Z-scheme charge transfer channel. This structure accelerates the separation and transport of photogenerated carriers, maintains the stronger redox ability, and improves the stability of SnS 2 in this series of heterojunctions. Therefore, the catalyst demonstrated exceptional photocatalytic hydrogen production efficiency, achieving a reaction rate of 86.4 µmol h -1 , which is 3.15 times greater than that of bare TCN., (© 2024 Wiley‐VCH GmbH.)

The drugs extending healthspan in clinic have always been searched. Nitazoxanide is an FDA-approved clinical antiprotozoal drug. Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo . Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK, oral nitazoxanide protects against experimental hyperlipidemia, hepatic steatosis, and atherosclerosis. Here, we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway. Additionally, both nitazoxanide and tizoxanide improve high glucose-induced shortening of C. elegans lifespan. Nitazoxanide has been a clinical drug with a good safety profile, we suggest that it is a novel anti-aging drug., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

The Yangtze River Delta (YRD) experienced record-breaking heat in the summer of 2022. However, the urban heat pattern and the role of urban expansion over the last two decades in this hot summer have not been explored. Using the advanced mesoscale Weather Research and Forecasting (WRF) model, we reproduced the fine spatial features and investigated the urban heat island (UHI) and dry island (UDI) effects during the two identified heatwaves in 2022. We further replace the current (2020) land use with the historical (2001) land use in WRF to evaluate the impacts of urban expansion from 2001 to 2020 on air temperature and moisture. Our finding revealed that the conversion of land use resulted in near-surface warming and drying, with pronounced diurnal variations, especially during the July heatwave. The analysis of surface energy balance demonstrated that the substantial decrease in evapotranspiration (ET) was the primary driver of daytime warming, elevating temperatures by 7 °C (July heatwave) and 2 °C (August heatwave). This ET reduction also led to the strong daytime coupling of warming and drying effects over new urban areas. At night, the release of stored heat resulted in the temperature increase of 2 °C (1 °C) during July (August) heatwave, highlighting the nighttime as a critical period for heightened thermal risk. Additionally, urban expansion at the periphery contributed modestly to the warming of urban cores, exacerbating conditions in an already hot environment. This study enhances understanding of the impacts of urban expansion on air temperature and humidity during extreme heatwaves, thereby supporting targeted adaptation and mitigation for extreme events within large cities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Liping Zhang reports financial support was provided by National Natural Science Foundation of China. Liping Zhang reports financial support was provided by China Yangtze Power Co., Ltd. If there are other authors, they 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.)

Organic matter (OM) accumulation in lake sediments has doubled owing to human activities over the past 100 years, which has negatively affected the restoration of submerged vegetation and ecological security. Changes in the pollution structure of sediments caused by plant recovery and rhizosphere chemical processes under different sediment OM levels are the theoretical basis for the rational application of plant rehabilitation technology in lake management. This study explored how Vallisneria natans mediates changes in sediment N and P through rhizospheric metabolites and microbial community and function under low (4.94 %) and high (17.35 %) sediment OM levels. V. natans promoted the accumulation of NH 4 -N in the high-OM sediment and the transformation of Fe/Al-P to Ca-P in the low-OM sediment. By analyzing 63 rhizospheric metabolites and the sediment microbial metagenome, the metabolites lactic acid and 3-hydroxybutyric acid and the genus Anammoximicrobium were found to mediate NH 4 -N accumulation in the high-OM sediment. Additionally, 3-hydroxy-decanoic acid, adipic acid, and the genus Bdellovibrionaceae mediated the transformation of Fe/Al-P to Ca-P in the low-OM sediment. The growth of V. natans enriched the abundance of functional genes mediating each step from nitrate to ammonia and the genes encoding urease in the high-OM sediment, and it up-regulated three genes related to microbial phosphorus uptake in the low-OM sediment. This study revealed the necessity of controlling endogenous pollution by recovering submerged macrophytes under high- and low-OM conditions from the perspective of the transformation of inorganic nitrogen and phosphorus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qiaohong Zhou has patent A device for in-situ collection of submerged plant root exudates and an application method licensed to 201810346832. 7. If there are other authors, they 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 B.V.)

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children's cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child's cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one's adverse genetic background jointly contribute to an increased risk of CDD in children., Competing Interests: Declaration of competing interest The authors have no competing financial interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heavy rainfall and flooding disasters are increasing due to global warming. A clear understanding of the mechanism of heavy rain and floods is the basic premise of disaster risk management. However, most previous studies emphasized more on the single anomalous signal from the average state in the whole season, which may neglect the combined influence of multiple signals in the ocean-atmosphere and differential characteristics of anomalous signals at different periods. Here, our study aimed to reveal the possible influence mechanism of heavy rain and floods in the middle and lower reaches of the Yangtze River Basin (MLRYRB) by systematically analyzing the monthly-scale and daily-scale ocean-atmosphere anomaly patterns in the preceding periods of heavy rainfall and flooding events. The results showed that heavy rainfall and flooding events were highly likely to occur in the region one month after El Niño decayed, with the flooding intensity in June having the negative correlation with the sea ice concentration anomaly in the Arctic with a lag of about 5 months (150 days). Besides, North Atlantic Oscillation, Western Pacific subtropical high, blocking, East Asian subtropical westerly jet, and the water vapor fluxes from the Arabian Sea and western Pacific Ocean could be used as the anomalous signals inducing heavy rain and floods. The daily-scale conceptual model inducing heavy rainfall and flooding events was built based on the patterns of all anomalous signals, which detailed the possible impact mechanism of heavy rain and floods in the region. By making targeted forecasts of anomalous signals and using this information in water resources planning and management based on climate mechanisms, it will have a significant impact on water management in the country., 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.)

The monitoring and evaluation of fluoride pollution are essentially important to make sure that concentrations do not exceed threshold limit, especially for surrounding atmosphere and soil, which are located close to the emission source. This study aimed to describe the atmospheric HF and edaphic fluoride distribution from an electrolytic aluminum plant located in Yunnan province, on which the effects of meteorological conditions, time, and topography were explored. Meanwhile, six types of solid waste genereted from different electrolytic aluminum process nodes were characterized to analyze the fluoride content and formation characteristics. The results showed that fluoride in solid waste mainly existed in the form of Na 3 AlF 6 , AlF 3 , CaF 2 , and SiF 4 . Spent electrolytes, carbon residue, and workshop dust are critical contributors to fluoride emissions in the primary aluminum production process, and the fluorine content is 17.14 %, 33.30 %, and 31.34 %, respectively. Unorganized emissions from electrolytic aluminum plants and solid waste generation are the primary sources of fluoride in the environment, among which the edaphic fluoride content increases most at the sampling sites S1 and S7. In addition, the atmospheric HF concentration showed significant correlations with wind speed, varying wildly from March to September, with daily average and hourly maximum HF concentrations of 4.32 μg/m 3 and 9.0 μg/m 3 , respectively. The results of the study are crucial for mitigating fluorine pollution in the electrolytic aluminum industry., 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.)

Getah virus (GETV) is a re-emerging mosquito-borne RNA virus that induces fever, hind limb edema, swollen submandibular lymph nodes, and urticaria in horses. In pigs, the virus often results in stillbirths among pregnant sows, and neurological symptoms leading to death in piglets. Currently, there are no specific treatments or drugs available for GETV infection. The use of reporter viruses to monitor viral replication and spread in real-time within infected cells and animals provides a powerful tool for targeting antiviral drugs throughout the viral life cycle. Their fluorescence-tracked characteristics greatly facilitate virus neutralization tests (VNTs). In this study, we engineered two recombinant viruses by inserting different reporter protein genes at the 3' end of the structural protein gene, an unreported location that can accommodate exogenous genes. The rGEEiLOV and rGEEGFP viruses demonstrated genetic stability for at least five passages and replicated at a rate similar to that of the parental virus in BHK-21 cells. The rGEEGFP virus facilitated viral neutralization testing. Additionally, we used the reporter virus rGEEGFP to confirm ivermectin, a broad-spectrum antiparasitic agent, as a potential inhibitor of GETV in vitro. Ivermectin appears to inhibit the early replication stages of the virus and can block cell-to-cell viral transmission. In conclusion, rGEEGFP holds significant potential for antiviral screening to identify specific inhibitors against GETV and for use in viral neutralization tests., Competing Interests: Declaration of competing interest The research was conducted in the absence of any commercial or financial relationships., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to analyze the clinical significance of cerebrospinal fluid (CSF) cytokines in hemophagocytic lymphohistiocytosis associated with central nervous system (CNS-HLH)., Methods: CSF cytokine levels, including interferon (IFN)-γ, soluble CD25 (sCD25), interleukin (IL)-6, IL-10, IL-18, and CXCL9 were measured at disease onset and during the treatment. Five newly diagnosed patients with demyelination disease were enrolled for comparison., Results: Sixty-five samples from 36 patients (13 in the CNS group and 23 in the non-CNS group) were detected. Levels of CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 in the CNS group were higher than those in the non-CNS group ( P =0.038, <0.001, <0.001, 0.005, and <0.001), and levels of CSF sCD25, IL-10, IL-18, and CXCL9 in the CNS group were higher than those in the demyelination group ( P =0.001, 0.008, 0.004, and 0.003). There was no significant difference in IL-6 levels among the 3 groups ( P =0.339). CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 could assist in diagnosing CNS-HLH. The diagnostic efficiency of CSF sCD25, IL-10, and CXCL9 was better, with a cutoff value of 154.64, 1.655, and 19.54 pg/mL, respectively. The area under the curve was >0.9, with sensitivity and specificity >80%. Correlation analysis suggested that in the CNS group, IFN-γ levels in CSF and serum correlated positively ( R =0.459, P =0.007), while there was no correlation between CSF CXCL9 and serum IFN-γ ( P =0.915)., Conclusions: CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 levels were significantly higher in HLH patients with CNS involvement than those without and could predict HLH patients with CNS involvement. CSF CXCL9 might be a more sensitive biomarker to CNS-HLH than IFN-γ, while CSF IL-6 does not seem to play a vital role., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)