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Succinate dehydrogenase inhibitors (SDHIs) are widely utilized fungicides that have been detected in various environments, raising significant concerns regarding their toxicity to aquatic organisms. A comprehensive analysis of SDHIs contamination and associated ecological risks has been challenging due to scattered data and varying scale. This study consolidated residue data from 194 aquatic environments across six regions, up to June 2024, providing an overview of SDHIs distribution and conducting a global-scale aquatic ecological risk assessment. We analyzed 20 SDHIs, with boscalid, fluopyram, flutolanil, fluxapyroxad, mepronil, and thifluzamide being the most frequently detected across Asia, Europe, North America, South America, Africa, and Australia. The concentrations and types of SDHIs varied significantly among continents, with data sourced from water, sediment and aquatic organisms. Utilizing a web-based Interspecies Correlation Estimation-Species Sensitivity Distribution (ICE-SSD) model, we identified substantial sensitivity differences among species, with benzovindiflupyr showing the lowest LC 50 of 3.5 μg/L, indicating a high risk when concentrations exceed 0.035 μg/L (Maximum Acceptable Concentration, MAC). Risk quotient (RQ) values revealed that flutolanil posed high risks to eight aquatic ecosystems and medium risks to five, while boscalid presented medium risk to one ecosystem. Our findings also demonstrated a significant correlation between the aquatic ecotoxicity of SDHIs and their characteristics (log Kow, solubility, and pKa). Collectively, we advocate for the restricted use of SDHIs and emphasize the necessity for further evaluation of their environmental behavior and integrated risks within the "One Health" framework., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objective: Transcranial sonography-based grading of Parkinson's Disease has gained increasing attention in recent years, and it is currently used for assistive differential diagnosis in some specialized centers. To this end, accurate midbrain segmentation is considered an important initial step. However, current practice is manual, time-consuming, and bias-prone due to the subjective nature. Relevant studies in the literature are scarce and lacks comprehensive model evaluations from application perspectives. Herein, we aimed to benchmark the best-performing U-Net model for objective, stable and robust midbrain auto-segmentation using transcranial sonography images., Methods: A total of 584 patients who were suspected of Parkinson's Disease were retrospectively enrolled from Beijing Tiantan Hospital. The dataset was divided into training (n = 416), validation (n = 104), and testing (n = 64) sets. Three state-of-the-art deep-learning networks (U-Net, U-Net+++, and nnU-Net) were utilized to develop segmentation models, under 5-fold cross-validation and three randomization seeds for safeguarding model validity and stability. Model evaluation was conducted in testing set in three key aspects: (i) segmentation agreement using DICE coefficients (DICE), Intersection over Union (IoU), and Hausdorff Distance (HD); (ii) model stability using standard deviations of segmentation agreement metrics; (iii) prediction time efficiency, and (iv) model robustness against various degrees of ultrasound imaging noise produced by the salt-and-pepper noise and Gaussian noise., Results: The nnU-Net achieved the best segmentation agreement (averaged DICE: 0.910, IoU: 0.836, HD: 2.793-mm) and time efficiency (1.456-s). Under mild noise corruption, the nnU-Net outperformed others with averaged scores of DICE (0.904), IoU (0.827), HD (2.941 mm) in the salt-and-pepper noise (signal-to-noise ratio, SNR = 0.95), and DICE (0.906), IoU (0.830), HD (2.967 mm) in the Gaussian noise (sigma value, σ = 0.1); by contrast, intriguingly, performance of the U-Net and U-Net+++ models were remarkably degraded. Under increasing levels of simulated noise corruption (SNR decreased from 0.95 to 0.75; σ increased from 0.1 to 0.5), the nnU-Net network exhibited marginal decline in segmentation agreement meanwhile yielding decent performance as if there were absence of noise corruption., Conclusions: The nnU-Net model was the best-performing midbrain segmentation model in terms of segmentation agreement, stability, time efficiency and robustness, providing the community with an objective, effective and automated alternative. Moving forward, a multi-center multi-vendor study is warranted when it comes to clinical implementation., Competing Interests: Declaration of competing interest All 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 B.V.)

As an important nonoil route for acquiring aromatics, the highly efficient conversion of methanol to aromatics over Zn/ZSM-5 zeolites remains an ongoing challenge. In this work, we developed a uniform loading approach of zinc and further combined it with a hollow capsule structure to design the high-performance Zn/ZSM-5 catalyst. The electrostatic assembly among EDTA 3- , n -butylamine + and negative silica-alumina gel gave rise to an "Inorganic-Organic Hybrid Sphere" in form of Na ( l + m + n +3 x )-( y + z ) ·{[(SiO) 4 Al - ] l /(SiO - ) m ( n -butylamine + ) y (EDTA 3- ) x ( n -butylamine + ) z (SiO - ) n , which further transformed into mesoporous aluminosilicates sphere (MASS) through calcination. The characteristic of abundant mesopore guaranteed MASS fantastic ability to evenly incorporate Zn ingredient inside, and the resultant Zn/MASS further served as a "hard template" for the direct synthesis of Hollow Zn/ZSM-5 capsules, rather than after impregnation. When tested in the methanol-to-aromatics (MTA) process, the direct synthesis method not only facilitated the homogeneous dispersion of the Zn ingredient, but also benefited for the generation of more (ZnOH) + sites and strengthened their synergism with zeolite acid for the superior aromatics selectivity (50.63%). Meanwhile, the hollow capsule structure increased the contact time of MTA intermediate products with the Zn/ZSM-5 shell, and it increased the coke-admitting capacity and suppressed the coke rate, which maintained quite an excellent stability (131 h). Therefore, the above combination of hollow capsule structure and uniform load of Zn ingredient brings forward a wide prospect to develop zeolite materials with excellent properties in catalysis.

Magnolia sieboldii , an important ornamental tree native to East Asia, comprises two subspecies in distinct regions, with wild populations facing suboptimal survival. This study aimed to understand the potential habitat distribution of these subspecies under future climate-change conditions to support climate-adaptive conservation. The maximum entropy (MaxEnt) model was used with occurrence and environmental data to simulate the current and future suitable habitats under various climate scenarios. Precipitation in the warmest quarter played a crucial role in shaping the potential habitats of both subspecies; however, they exhibited different sensitivities to temperature-related variables and altitude. Magnolia sieboldii subsp. sieboldii is more sensitive to temperature seasonality and annual mean temperature, whereas Magnolia sieboldii subsp. japonica is more affected by altitude, mean temperature in the driest quarter, and isothermality. Currently, the subsp. sieboldii is predicted to have larger, more contiguous suitable habitats across northeastern China, the Korean Peninsula, and Japan, whereas the subsp. japonica occupies smaller, more disjunct habitats scattered in central and western Japan and the southern Chinese mountains. These two subspecies will respond differently to future climate change. Potentially suitable habitats for subsp. sieboldii are expected to expand significantly northward over time, especially under the SSP585 scenario compared with the SSP126 scenario. In contrast, moderately and highly suitable habitats for the subsp. japonica are projected to contract southward significantly. Therefore, we recommend prioritizing the conservation of the subsp. japonica over that of the subsp. sieboldii . Strategies include in situ and ex situ protection, introduction and cultivation, regional hybridization, and international cooperation. Our study offers valuable insights for the development of targeted conservation strategies for both subspecies of M. sieboldii to counteract the effects of climate change.

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions., Methods: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance., Conclusion: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients., Competing Interests: Conflict of interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

Gender symmetry is a long-standing controversy in intimate partner violence (IPV) research. This study explored the gender directionality of IPV and differences in the quality of relationships between different dyadic patterns. IPV experiences and relationship quality of 371 heterosexual couples were examined. Results indicate that females reported more IPV perpetration than males. Generally, the male-only IPV and bidirectional IPV couples showed lower levels of relationship quality compared with female-only IPV and no-IPV couples. Future studies should realize that different dyadic types of IPV may have different mechanisms and consequences, and more attention should be paid to gender directionality., 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.

Background: Non-invasive measurement of liver stiffness (LS), traditionally performed in the supine position, has been established to assess liver fibrosis. However, fibrosis degree is not the sole determinant of LS, necessitating the identification of relevant confounders. One often-overlooked factor is body posture, and it remains unclear whether normal daily postures interfere with LS irrespective of fibrosis. A prospective two-group comparison study was conducted to investigate the relationship between posture and LS., Methods: Sixty-two adults participated, divided into two groups: patients with chronic liver disease and healthy controls. Both groups were assessed using transient elastography (TE) under the supine, seated, and standing postures. Randomization was applied to the order of the two upright postures. A two-way mixed ANOVA was conducted to assess the posture-dependence of LS and its variations between two groups., Results: Results showed that posture differentially affected LS depending on the presence of liver fibrosis. In 31 healthy individuals (baseline LS range: 3.5-6.8 kPa), a transition from the supine (5.0 ± 1.0 kPa) to seated (5.7 ± 1.4 kPa; p = 0.036) or standing (6.2 ± 1.7 kPa; p = 0.002) positions increased LS, indicating liver stiffening. Conversely, in 31 patients with varying fibrosis stages (baseline LS range: 8.8-38.2 kPa), posture decreased LS from the supine (15.9 ± 7.3 kPa) to seated (13.8 ± 6.2 kPa; p < 0.001) or standing (13.9 ± 6.2 kPa; p = 0.001) positions. No significant difference in LS was observed between the seated and standing positions in both groups (control group: 5.7 vs. 6.2 kPa, p = 0.305; patient group: 13.8 vs. 13.9 kPa, p = 1). Additionally, different postures did not elicit significant changes in the success rate (supine, 98.6 ± 4%; seated, 97.6 ± 6%; standing, 99.1 ± 3%; p = 0.258) and IQR/median value (supine, 25 ± 8%; seated, 29 ± 15%; standing, 29 ± 12%; p = 0.117), implying no impact on both measurement feasibility and reliability., Conclusions: We demonstrated, for the first time, the feasibility of utilizing upright postures as an alternative measurement protocol for TE. We further unravel a previously unrecognized role of transitioning between different postures to assist the diagnosis of cirrhosis. The findings suggested that daily physiological activity of postural changes suffices to alter LS. Therefore, body positioning should be standardized and carefully considered when interpreting LS., (© 2024. The Author(s).)

Type I interferon (IFN-I) and its downstream genes play a profound role in HIV infection. In this study, we found that an IFN-inducible gene, IFI27, was upregulated in HIV-1 infection, which in turn efficiently suppressed HIV-1 replication, specially degraded the viral gag protein, including p24 and p55 subunits. Notably, the anti-HIV-1 activity of IFI27 in Old World monkeys surpassed that in New World monkeys, and IFI27 has a higher potentially inhibitory effect on HIV-1 than simian immunodeficiency virus (SIV). Our initial observations showed that NPM-IFI27, the IFI27 variant in northern pig-tailed macaque ( Macaca leonina , NPM), exhibited a strong anti-HIV-1 activity. Further investigation demonstrated that NPM-IFI27 degraded p24 and p55 via the ubiquitin-proteasome pathway, with NPM-IFI27-37-115 interacting with the p24-N domain, and the NPM-IFI27-76-122 domain was closely associated with K48 ubiquitin recruitment. Additionally, Skp2 was identified as the probable E3 ubiquitin ligase responsible for the degradation of p24 and p55. Similarly, human IFI27 (Hu-IFI27) showed a mechanism similar to NPM-IFI27 in HIV-1 inhibition. These findings underscore the pivotal role of NPM-IFI27 in HIV-1 infection and provide a potential strategy for clinical anti-HIV-1 therapy.IMPORTANCEHIV-1 infection can trigger the production of IFN-I, which subsequently activates the expression of various IFN-stimulated genes (ISGs) to antagonize the virus. Therefore, discovering novel host antiviral agents for HIV-1 treatment is crucial. Our previous study revealed that IFI27 can influence HIV-1 replication. In this study, we observed that the NPM-IFI27 complex specifically inhibited HIV-1 by targeting its Gag protein. Further exploration demonstrated that IFI27 interacted with the HIV-1 p24 and p55 proteins, leading to their degradation through the ubiquitin-proteasome pathway. Notably, the NPM-IFI27-37-122 variant exhibited potent anti-HIV-1 activity, comparable to that of SAMHD1. These findings highlight the critical role and inhibitory mechanism of NPM-IFI27 in HIV-1 infection, providing a potential strategy for clinical antiviral therapy.

Objectives: To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL)., Methods: A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed., Results: Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23)., Conclusions: Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.

We demonstrate an on-chip photodetector by integrating a graphene and topological insulator Bi 2 Te 3 heterostructure on a thin-film lithium niobate waveguide. Lithium niobate on insulator (LNOI) waveguides are fabricated by the photolithography-assisted chemical mechanical etching method. The bismuth telluride (Bi 2 Te 3 ) and graphene heterostructure design provides enhanced photocurrent due to the effective photocarrier generation. The lithium niobate waveguide-integrated Bi 2 Te 3 /graphene heterojunction presents a high absorption coefficient of 2.1 dB/µm. The Bi 2 Te 3 /graphene heterojunction photodetector exhibits a responsivity of 2.54 mA/W without external bias at a 1.55 µm wavelength, which is enhancement of sevenfold as compared to the pure graphene-based photodetector. The photodetector has a 3 dB bandwidth of over 4.7 GHz. This work provides a potentially viable method for a self-powered, high responsivity, and fast response of the photodetector integrated with the LNOI photonic platform.

Background: Due to the high prevalence of posterior horseshoe anal fistula and causing numerous complications, this study aimed to investigate the clinical effect of radial incision combined with tunnel floating line drainage (RCTD) and arc incision internal drainage in the treatment of the disease and the influence on perianal flora., Methods: Ninety-six subjects treated with high posterior horseshoe anal fistula were stochastically assigned to a joint group (RCTD), and control group (arc incision internal drainage). The operation-related conditions, complication rate, anal function, and recurrence rate of 6 months after operation were compared, and perianal secretions were collected before operation and 1 day after operation to detect the changes of microbial flora., Results: After operation, it was corroborated notable difference between joint group and control group in operation time, intraoperative blood loss, wound healing time, visual analogue scale score 6 hours after operation and phase I cure rate. Chi square test analysis showed notable difference between control group (27.08%) and joint group (10.40%) in incidence of complications, in terms of number of pathogens detected around anus, significantly smaller of the incremental change for the joint subgroup versus the control subgroup 1 day after operation., Conclusion: RCTD can be the best choice for patients with high posterior horseshoe anal fistula. This operation method has the advantages of short operation time, less trauma, fewer complications, fast recovery of anal function, and can also reduce perianal pathogenic bacteria infection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Antidepressants are among the most extensively prescribed psychotropic drugs worldwide. Discontinuation induced withdrawal symptoms have been reported for almost all antidepressants. The incidence of antidepressant withdrawal syndrome (AWS) and other characteristics remain unknown. We searched the PubMed, Embase, PsycINFO, MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases from inception to December 31, 2023. Randomized double-blinded trials, longitudinal or cross-sectional studies that reported the incidence and other characteristics of antidepressant withdrawal symptoms were included. The pooled incidence of AWS was calculated by a random effects model. We included 35 studies, of which 2 studies just provided incidence of specific withdrawal symptoms, and 4 studies only described other characteristics. The pooled incidence of AWS from all available studies was 42.9%, from 11 RCTs was 44.4%, in studies in which the treatment duration was mostly 8-12 weeks, which usually appear within 2 weeks, and were generally measured for <4 weeks. The incidence in selective serotonin-norepinephrine reuptake inhibitors was the lowest (29.7%), followed by selective serotonin reuptake inhibitors (45.6%) and tricyclic antidepressants (59.7%), without significant differences (p = 0.221). Treatment duration showed a dose-response to the incidence of AWS (6-12 W: 35.1%, 12-24 W: 42.7%, >24 W: 51.4%). The half-life did not show such a simple dose-dependent relationship. The pooled estimate was robust regardless whether withdrawal symptoms were measured in RCTs or observational studies (including face-to-face and online survey studies). Tapering the dose reduced the incidence of AWS compared with abrupt stoppage (34.5% vs 42.5%), without a significant difference (p = 0.484). Risk factors for withdrawal symptoms included being female, younger, experiencing adverse effects early in treatment, taking higher doses or longer duration of medication, abrupt cessation of drugs, and those with a lower clearance of drugs or with serotonin 1A receptor gene variation. The findings suggest the incidence of AWS are common and some clinical characteristics and risk factors which can help clinicians identify who is at greater risk of experiencing AWS. Discontinuation studies on long-term antidepressant users with long follow-up periods are required in the future., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

To explore the effects of microplastic input and straw addition on nitrogen and phosphorus leaching in orange orchard soil, indoor soil column leaching simulation experiments were conducted on orange orchard soil in Dangyang City, Hubei Province. The experiment analyzed the effects of different treatments on the leaching characteristics of soil nitrogen and phosphorus. The results showed that： ① The increase in microplastic input increased the leaching capacity of the soil （TN, NO 3 - -N, NH 4 + -N, and TP） when only microplastic input was added. ② Under the addition of straw, the input of microplastics increased, which reduced the leaching amount of TN and NO 3 - -N in the soil, and increased the leaching amount of NH 4 + -N and TP in the soil. ③ Under the input of microplastics, the key influencing factors of soil nitrogen and phosphorus leaching were soil bulk density and water content. Under straw addition, it was mainly affected by soil carbon and nitrogen content. Among them, microplastic input and straw addition significantly increased soil pH, but their path coefficients for nitrogen and phosphorus leaching were not significantly correlated. The results showed that the effects of polypropylene microplastic input and straw addition on soil nitrogen and phosphorus leaching were related to the amount of microplastics input and whether straw was added. The results showed that the input of microplastics would increase the amount of soil nitrogen and phosphorus leaching. Although nitrogen leaching loss caused by microplastic input could be reduced under straw addition, soil phosphorus leaching loss was significantly increased.

Human immunodeficiency virus-1 (HIV-1) infection disrupts the homeostatic equilibrium between the host and commensal microbes. However, the dynamic changes of plasma commensal viruses and their role in HIV/simian immunodeficiency virus (SIV) pathogenesis are rarely reported. Here, we investigated the longitudinal changes of plasma virome, inflammation levels, and disease markers using an SIV-infected Macaca leonina model. Large expansions of plasma Anelloviridae , Parvoviridae , Circoviridae and other commensal viruses, and elevated levels of inflammation and D-dimer were observed since the chronic phase of SIV infection. Anelloviridae abundance appears to correlate positively with the CD4 + T cell count but negatively with SIV load especially at the acute phase, whereas other commensal viruses' abundances show opposite correlations with the two disease markers. Antiretroviral therapy slightly reduces but does not substantially reverse the expansion of commensal viruses. Furthermore, 1387 primate anellovirus open reading frame 1 sequences of more than 1500 nucleotides were annotated. The data reveal different roles of commensal viruses in SIV pathogenesis.

Objective: To analyze the clinical characteristics and prognosis of children with hypodiploid B-cell precursor acute lymphoblastic leukemia (BCP-ALL)., Methods: The clinical data of 1 287 children with BCP-ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. According to the results of chromosome karyotype, all the patients were grouped into hypodiploid subgroup and non-hypodiploid subgroup. The clinical characteristics, early treatment response ［minimal residual disease (MRD) on middle stage of induction chemotherapy and end of induction chemotherapy］ and long-term efficacy ［overall survival (OS) and event-free survival (EFS)］ were compared. The prognostic factors of hypodiploid BCP-ALL were further explored., Results: Among 1 287 BCP-ALL patients， 28 patients (2.2%) were hypodiploid BCP-ALL. The proportion of patients with white blood cell count （WBC）≥50×10 9 /L in the hypodiploid subgroup was significantly higher than that in the non-hypodiploid subgroup ( P =0.004), while there was no statistically significant difference in gender ratio, age group at initial diagnosis, and early treatment response between the two groups (all P >0.05). The 5-year EFS and OS rate of the hypodiploid subgroup were 75.0%(95% CI ：66.8%-83.2%) and 77.8%(95% CI ：69.8%-85.8%), respectively, which were lower than those of non-hypodiploid subgroup ［EFS: 79.6%(95% CI ：78.4%-80.8%); OS: 86.4%(95% CI ：85.4%-87.5%)］, but the difference was not statistically significant (all P >0.05). Further subgroup analysis by risk stratification showed that the 5-year EFS and OS rates of the hypodiploid subgroup were significantly lower than those in the low-risk (LR) group ［LR group EFS: 91.4% (95% CI ：88.4%-93.6% ), P < 0.001; OS: 94.7% (95% CI ：92.1%-96.4%), P < 0.001］ ; it was similar to that of BCP-ALL children stratified into intermediate-risk (IR) excluding hypodiploid ［IR group EFS: 79.4%(95% CI ：74.9%-83.2%), P =0.343; OS: 87.3%(95% CI ：83.6%-90.2%), P =0.111］; while was higher than that of EFS in HR group, but the difference was not statistically significant ［HR group EFS: 58.7%(95% CI ：52.6%-64.8%), P =0.178. OS: 69.9%(95% CI ：63.5%-75.4%), P =0.417］. Univariate analysis showed that gender, age, white blood cell count, and MRD on middle stage of induction chemotherapy had no significant impact on OS and EFS; chromosome count< 40 was a risk factor for lower OS ( P =0.026), but has no significant effect on EFS; MRD≥0.01% after induction therapy was a risk factor for lower OS and EFS ( P =0.002, and 0.001, respectively)., Conclusion: Children with hypodiploid BCP-ALL have an intermediate prognosis, and MRD ≥0.01% after induction chemotherapy may be a risk factors for poor prognosis.

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Malignant gliomas are an exceptionally lethal form of cancer with limited treatment options. Dihydroartemisinin (DHA), a sesquiterpene lactone antimalarial compound, has demonstrated therapeutic effects in various solid tumors. In our study, we aimed to investigate the mechanisms underlying the anticancer effects of DHA in gliomas. To explore the therapeutic and molecular mechanisms of DHA, we employed various assays, including cell viability, flow cytometry, mitochondrial membrane potential, glucose uptake and glioma xenograft models. Our data demonstrated that DHA significantly inhibited glioma cell proliferation in both temozolomide-resistant cells and glioma stem-like cells. We found that DHA-induced apoptosis occurred via the mitochondria-mediated pathway by initiating mitochondrial dysfunction before promoting apoptosis. Moreover, we discovered that DHA treatment substantially reduced the expression of the mitochondrial biogenesis-related gene, ERRα, in glioma cells. And the ERRα pathway is a critical target in treating glioma with DHA. Our results also demonstrated that the combination of DHA and temozolomide synergistically inhibited the proliferation of glioma cells. In vivo, DHA treatment remarkably extended survival time in mice bearing orthotopic glioblastoma xenografts. Thus, our findings suggest that DHA has a novel role in modulating cancer cell metabolism and suppressing glioma progression by activating the ERRα-regulated mitochondrial apoptosis pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Multiple sclerosis is a common inflammatory neurological disease among young adults and is the tenth leading cause of the global burden of disease. Existing common treatments such as pharmacological and palliative therapies do not control the neurodegenerative process or cure multiple sclerosis. Numerous epidemiological surveys, randomised controlled trials, and systematic reviews with meta-analyses support the effects of physical activity on health-related outcomes among patients with multiple sclerosis. Moreover, bibliometric analysis can provide a broad evidence synthesis beyond systematic reviews and meta-analyses, allowing researchers and other stakeholders to obtain a one-stop overview of this research field. Therefore, this bibliometric analysis aims to provide insight into the knowledge structure of the field of physical activity for multiple sclerosis over the past three decades, and to predict emerging research trends., Methods: This study strictly complied with step-by-step guidelines of bibliometric analysis, combining performance analysis and science mapping. Four indexes from the Web of Science Core Collection were selected as data sources, and articles and review articles in the field of physical activity for multiple sclerosis from 1994 to 2023 were included in this analysis. Mircrosoft Excel, RStudio, VOSviewer 1.6.20, and CiteSpace 6.3.R1 (64-bit) Advanced were used to perform performance analysis and science mapping., Results: Over the past three decades, this field published a total of 1,271 documents, with the scientific output showing a rapid upward trend over the past two decades. Robbert W Motl was the most prolific author in this field, with a total of 300 publications. The USA contributed nearly half of the publications in this field (549 documents), and the University of Illinois System was the institution with the highest number of publications (222 documents). Multiple Sclerosis and Related Disorders was the journal that published the highest number of documents in this field (117 documents), while more than a third of this field's publications were included in the category: Clinical Neurology (438 documents). The Reference co-citation analysis identified three main research trends, including shifts in research methodology, changes in health outcomes in randomised controlled trials, and shifts in different types of physical activity interventions. Combining the results from reference co-citation analysis and citation burst analysis, the combination of behaviour change technique and telerehabilitation may be the emerging research trend., Conclusion: This bibliometric analysis identifies rapid growth in the field of physical activity for multiple sclerosis over the past two decades. Moreover, the combination of performance analysis and science mapping provides insight into knowledge structure in this field and informed future research trends for researchers and the relevant stakeholders., 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 B.V.)

Pornography has become increasingly prevalent worldwide with the development of the Internet, and considerable research on the effects of pornography use has emerged. Based on existing research and the Pornography Problems Due to Moral Incongruence (PPMI) model, we examined problematic pornography use (PPU) as a mediator and moral disapproval of pornography use as a moderator in the links between pornography use frequency and mental health problems in a Chinese sample ( N = 833). Our results support the completely mediated effect of PPU ( ab  = 0.16) and the moderated effect of moral disapproval of pornography use on the association between pornography use frequency and PPU. Pornography use frequency was strongly associated with PPU when participants experienced high moral incongruence (MI), and the indirect effect of PPU was weaker ( ab  = 0.13) at the lower level of moderator (-1 SD ), and stronger ( ab  = 0.23) at the higher level of moderator (+1 SD ). However, the direct effect of MI on mental health problems was not supported. This study advances our understanding of the internal mechanism between pornography use and mental health and extends the PPMI model to the Chinese cultural context (characterized as low religiosity and sexually conservative). The findings confirm the cross-cultural consistency of the PPMI model in China and highlight another important source of MI besides religiosity: cultural characteristics.

Objective: To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children., Methods: A retrospective analysis was performed on 23 children with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation (arthrography with elastic nail group) from January 2019 to December 2022, including 12 males and 11 females, aged from 2 to 12 years old with an average of (7.36±1.89) years old;According to Judet fracture types, 14 children were type Ⅲ and 9 children were type Ⅳ. In addition, 23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation (elastic nail group), including 11 males and 12 females, aged from 2 to 14 years old with an average of (7.50±1.91) years old;Judet classification included 15 children were type Ⅲ and 8 children were type Ⅳ. Operative time and intraoperative fluoroscopy times were compared between two groups. Metaizeau evaluation criteria was used to evaluate fracture reduction, and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups., Results: Both groups were followed up for 12 to 24 months with an average of (16.56±6.34) months. Operative time and intraoperative fluoroscopy times of elastic nail group were (56.64±19.27) min and (21.13±7.87) times, while those of joint angiography with elastic nail group were (40.33±11.50) min and (12.10±3.52) times;there were difference between two groups ( P <0.05). According to Metaizeau evaluation, 11 patients got excellent result, 9 good and 3 fair in joint angiography with elastic nail group, while in elastic nail group, 5 excellent, 13 good, 4 acceptable, and 1 poor;the difference between two groups was statistically significant ( P <0.05). According to Tibone-Stoltz criteria, 14 patients got excellent result, 8 good, and 1 fair in joint arthrography with elastic nail group;while in elastic nail group, 12 patients got excellent result, 9 good, 1 fair and 1 poor;there was no significant difference between two groups ( P >0.05)., Conclusion: Compared to percutaneous elastic intramedullary nail fixation, closed reduction assisted by arthrography has advantages of reduced operation time, decreased intraoperative fluoroscopy frequency, and improved fracture reduction. Arthrography enables clear visualization of the anatomical structures of radius, head, neck, bone, and cartilage in children, facilitating comprehensive display of fracture reduction and brachioradial joint alignment. This technique more precisely guides the depth of elastic intramedullary nail implantation in radius neck, thereby enhancing surgical efficiency and success rate.

Background: Good gastric preparation is indispensable for Magnetic-controlled Capsule Endoscopy (MCE) examination, but there is no consensus yet. We aim to explore the clinical application value of positioning exercises in improving the quality of MCE examination., Methods: Clinical data of 326 patients who underwent MCE examination from January 2020 to December 2023 were collected. The included patients were divided into two groups: the conventional medication preparation group (CMP group, accepted mucosal cleansing medication only) and the positioning exercises group (PE group, accepted mucosal cleansing medication plus positioning exercises). A comparison was made between the two groups in terms of gastric cavity cleanliness score, visibility score, and detection rate of positive lesions., Results: The examination time was (21.29 ± 5.82) minutes in the PE group and (30.54 ± 6.37) minutes in the CMP group, showing a significant difference between the two groups (P < 0.001). The total cleanliness score and visibility score in the CMP group were 15.89 ± 2.82 and 10.93 ± 2.12, respectively. In contrast, the total cleanliness score and visibility score in the PE group were 19.52 ± 2.26 and 15.09 ± 2.31, respectively. The PE group showed significantly better cleanliness scores and visibility scores in all six anatomical regions compared to the CMP group (All P < 0.001). However, there was no significant difference in the detection rate of positive lesions between the two groups (All P > 0.05)., Conclusion: Positioning exercises before MCE examination can improve the quality of gastric mucosal images and reduce the duration of the examination for patients., (© 2024. The Author(s).)

Currently, the relationship between axial rotation of the vertebrae and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) remains controversial. The aim of this study is to quantitatively assess the effect of vertebral rotation on volumetric bone mineral density (v-BMD) and areal bone mineral density (a-BMD), further to propose the corrected strategies. To achieve this, a phantom, which was rotated from 0° to 25° in 5° increments, was utilized. Bone mineral content (BMC), a-BMD, v-BMD, and projected area (p-AREA) were measured. The Kruskal-Wallis non-parametric test or one-way ANOVA was used to examine the differences in variables between the different groups. The Pearson and Spearman correlation was used to test the relationships between quantitative parameters and rotated angles. Linear regression analysis was used to evaluate the relationship between angles and quantitative parameters. The findings indicate that, as the angle increased, a-BMD and v-BMD decreased (P < 0.001) , and the p-AREA increased (P < 0.001), but the BMC stays constant. The rotated angle was negative correlated (r = - 0.925, P < 0.001) with a-BMD and v-BMD (r = - 0.880, P < 0.001), positive (r = 0.930, P =  < 0.001) correlated with p-AREA. The linear regression analysis showed that a-BMD = 0.808-0.01 × Angle and v-BMD = 151.808-1.588 × Angle. This study showed that, axial rotation might lead to a lower measured for a-BMD and v-BMD, it should be modified. This gives clinicians some insights into how to deal with osteoporosis in scoliosis patients. It's essential for clinicians to incorporate these findings into their diagnostic processes to prevent potential misdiagnosis and over-treatment of osteoporosis., (© 2024. The Author(s).)

The human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future., (© 2024 Wiley-VCH GmbH.)

Background: Trop-2 is closely related to the development and progression of a variety of tumours and poor prognosis. This study aimed to construct an iodine-124 ( 124 I)-labelled antibody-drug conjugate (ADC) positron emission tomography (PET) probe which could noninvasively image Trop-2 in vivo, providing an important method for the diagnosis of tumours with high Trop-2 expression in clinical practice and monitoring their treatment., Methods: In this study, a novel Trop-2-targeting molecular probe, 124 I-IMMU-132, was constructed to better reveal the expression of Trop-2. The targeting and binding abilities of the probe to Trop-2-positive tumours were investigated in Capan-1/MDA-MB-468/Mcf-7 cells and their animal models., Results: The constructed 124 I-IMMU-132 probe maintained both reliable radiochemical characteristics and binding affinity (K d = 2.200 nmol/L). The uptake of the probe by Trop-2-positive Capan-1/MDA-MB-468 cells increased in a time-dependent manner. The probe bound specifically to Capan-1/MDA-MB-468 tumours in vivo. The SUVmax Tumour/muscle ratio gradually increased with time, from 4.30 ± 0.55-10.78 ± 1.80 (p < 0.01) in the Capan-1 model and from 8.84 ± 0.95-32.20 ± 2.9 (p < 0.001) in the MDA-MB-468 model. The biodistribution and pharmacokinetics of 124 I-IMMU-132 in a mouse model were consistent with the imaging results, and the dosimetry estimation in humans was acceptable., Conclusions: 124 I-IMMU-132 PET is a promising imaging technique for delineating Trop-2-positive tumours. It has great potential in early diagnosis and targeted selection of patients that could benefit from its application., Competing Interests: Declaration of Competing Interest We declare that none of our authors have financial or other conflicts of interest that might be construed as influencing the results or interpretation of our study. This study has not been presented anywhere else., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hypothesis: Metal-organic frameworks (MOFs) are highly suitable precursors for supercapacitor electrode materials owing to their high porosity and stable backbone structures that offer several advantages for redox reactions and rapid ion transport., Experiments: In this study, a carbon-coated Ni 9 S 8 composite (Ni 9 S 8 @C-5) was prepared via sulfuration at 500 ℃ using a spherical Ni-MOF as the sacrificial template., Finding: The stable carbon skeleton derived from Ni-MOF and positive structure-activity relationship due to the multinuclear Ni 9 S 8 components resulted in a specific capacity of 278.06 mAh·g -1 at 1 A·g -1 . Additionally, the hybrid supercapacitor (HSC) constructed using Ni 9 S 8 @C-5 as the positive electrode and the laboratory-prepared coal pitch-based activated carbon (CTP-AC) as the negative electrode achieved an energy density of 69.32 Wh·kg -1 at a power density of 800.06 W·kg -1 , and capacity retention of 83.06 % after 5000 cycles of charging and discharging at 5 A·g -1 . The Ni-MOF sacrificial template method proposed in this study effectively addresses the challenges associated with structural collapse and agglomeration of Ni 9 S 8 during electrochemical reactions, thus improving its electrochemical performance. Hence, a simple preparation method is demonstrated, with broad application prospects in supercapacitor electrodes., 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.)

Background: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them., Methods: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases., Results: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis., Conclusions: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Furin primarily localizes to the trans-Golgi network (TGN), where it cleaves and activates a broad range of immature proproteins that play critical roles in cellular homeostasis, disease progression, and infection. Furin is retrieved from endosomes to the TGN after being phosphorylated, but it is still unclear how furin exits the TGN to initiate the post-Golgi trafficking and how its activity is regulated in the TGN. Here three membrane-associated RING-CH finger (MARCHF) proteins (2, 8, 9) are identified as furin E3 ubiquitin ligases, which catalyze furin K33-polyubiquitination. Polyubiquitination prevents furin from maturation by blocking its ectodomain cleavage inside cells but promotes its egress from the TGN and shedding. Further ubiquitin-specific protease 32 (USP32) is identified as the furin deubiquitinase in the TGN that counteracts the MARCHF inhibitory activity on furin. Thus, the furin post-Golgi trafficking is regulated by an interplay between polyubiquitination and phosphorylation. Polyubiquitination is required for furin anterograde transport but inhibits its proprotein convertase activity, and phosphorylation is required for furin retrograde transport to produce fully active furin inside cells., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.

Myeloid-derived growth factor (MYDGF) is a cytokine that exhibits a variety of biological functions. This study focused on utilizing BL21(DE3) strain engineering and fermentation strategies to achieve high-level expression of soluble human MYDGF (hMYDGF) in Escherichia coli. Initially, the E. coli expressing strain BL21(DE3) was engineered by deleting the IpxM gene and inserting the GROEL/S and Trigger factor genes. The engineered E. coli strain BL21(TG)/pT-MYDGF accumulated 3557.3 ± 185.6 μg/g and 45.7 ± 6.7 mg/L of soluble hMYDGF in shake flask fermentation, representing a 15.6-fold increase compared to the control strain BL21(DE3)/pT-MYDGF. Furthermore, the yield of hMYDGF was significantly enhanced by optimizing the fermentation conditions. Under optimized conditions, the 5L bioreactor yielded up to 2665.8 ± 164.3 μg/g and 407.6 ± 42.9 mg/L of soluble hMYDGF. The results indicate that the implementation of these optimization strategies could enhance the ratio and yield of soluble proteins expressed by E.coli, thereby meeting the demands of industrial production. This study employed sophisticated strategies to lay a solid foundation for the industrial application of hMYDGF., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transcranial sonography (TCS) has been introduced to assess hyper-echogenicity in the substantia nigra of the midbrain for Parkinson's disease (PD); however, its subjective and resource-demanding nature has impeded its widespread application. An AI-empowered TCS-based PD classification tool is greatly demanding, yet relevant research is severely scarce. Therefore, we proposed a novel dual-channel CNXV2-DANet for TCS-based PD classification using a large cohort. A total of 1176 TCS images from 588 subjects were retrospectively enrolled from Beijing Tiantan Hospital, encompassing both the left and right side of the midbrain for each subject. The entire dataset was divided into a training/validation/testing set at a ratio of 70%/15%/15%. Development of the proposed CNXV2-DANet was performed on the training set with comparisons between the single-channel and dual-channel input settings; model evaluation was conducted on the independent testing set. The proposed dual-channel CNXV2-DANet was compared against three state-of-the-art networks (ConvNeXtV2, ConvNeXt, Swin Transformer). The results demonstrated that both CNXV2-DANet and ConvNeXt V2 performed more superiorly under dual-channel inputs than the single-channel input. The dual-channel CNXV2-DANet outperformed the single-channel, achieving superior average metrics for accuracy (0.839 ± 0.028), precision (0.849 ± 0.014), recall (0.845 ± 0.043), F 1-score (0.820 ± 0.038), and AUC (0.906 ± 0.013) compared with the single channel metrics for accuracy (0.784 ± 0.037), precision (0.817 ± 0.090), recall (0.748 ± 0.093), F 1-score (0.773 ± 0.037), and AUC (0.861 ± 0.047). Furthermore, the dual-channel CNXV2-DANet outperformed all other networks (all p -values < 0.001). These findings suggest that the proposed dual-channel CNXV2-DANet may provide the community with an AI-empowered TCS-based tool for PD assessment.

Given the increasing trend of aging population in the world, neurodegenerative diseases (NDDs), a common type of diseases that mostly occur in the elderly, have attracted much more attention. It has been shown that tumor necrosis factor receptor-associated factor 6 (TRAF6) is involved in the regulation of neuroinflammation, an important pathological feature of NDDs, and affects the occurrence and development of NDDs. Most importantly, the regulatory effect of TRAF6 is related to its ubiquitination. Therefore, in the present paper, the molecular structure, biological function, and ubiquitination mechanism of TRAF6, and its relationship with some common NDDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, were analyzed and summarized. The possible molecular mechanisms by which TRAF6 regulates the occurrence of NDDs were also elucidated, providing a theoretical basis for exploring the etiology and treatment of NDDs.

Florfenicol resistance genes (FRGs) are widely present in livestock farms. The aim of this study was to evaluate the removal efficiencies of FRGs as well as the relationships between FRGs, mobile genetic elements (MGEs) and bacterial communities during the natural drying (ND) and anaerobic digestion (AD) processes of manure treatment in swine farms by combining bacterial isolation, quantitative PCR and metagenomic approaches. Solid manure showed a higher abundance of FRGs than fresh manure and was the main contamination source of fexA and fexB in ND farms, whilst biogas slurry displayed a lower abundance of FRGs than the wastewater in AD farms. Moreover, fresh manure and wastewater showed a high abundance of optrA, and wastewater was the main contamination source of cfr in both ND and AD farms. Both optrA/fexA-positive enterococci and cfr/fexA-positive staphylococci were mainly isolated along the farms' treatment processes. The cfr-positive staphylococci were highly prevalent in wastewater (57.14 % - 100 %) and may be associated with nasal-derived cfr-positive porcine staphylococci. An increased abundance of Enterococcus, Jeotgalibaca and Vagococcus in the bacterial community structures may account for the high optrA abundance in wastewater and Jeotgalibaca may be another potential host of optrA. Furthermore, the abundance of FRG-related MGEs increased by 22.63 % after the ND process and decreased by 66.96 % in AD farms. A significant correlation was observed between cfr and ISEnfa4, whereas no significance was found between optrA and IS1216E, although IS1216E is the predominant insertion sequence involved in the transfer of optrA. In conclusion, manure and wastewater represented independent pollution sources of FRGs in swine farms. Associated MGEs might play a key role in the transfer and persistence of FRGs. The AD process was more efficient in the removal of FRGs than the ND method, nevertheless a longer storage of slurry may be required for a complete removal., 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 B.V.)

Activated receptor tyrosine kinases (RTKs) rely on the assembly of signaling proteins into high-dimensional protein complexes for signal transduction. Shc1, a prototypical scaffold protein, plays a pivotal role in directing phosphotyrosine (pY)-dependent protein complex formation for numerous RTKs typically through its two pY-binding domains. The three conserved pY sites within its CH1 region (Shc1 CH1 ) hold particular significance due to their substantial contribution to its functions. However, how Shc1 differentially utilizes these sites to precisely coordinate protein complex assembly remains unclear. Here, we employed multiple peptide ligation techniques to synthesize an array of long protein fragments (107 amino acids) covering a significant portion of the Shc1 CH1 region with varying phosphorylation states at residues Y239, 240, 313, and S335. By combining these phospho-Shc1 CH1 fragments with integrated proteomics sample preparation and quantitative proteomic analysis, we were able to comprehensively resolve the site-specific interactomes of Shc1 with single amino acid resolution. By applying this approach to different cancer cell lines, we demonstrated that these phospho-Shc1 CH1 fragments can be effectively used as a diagnostic tool to assess cell type-specific RTK signaling networks. Collectively, these biochemical conclusions help to better understand the sophisticated organization of pY-dependent Shc1 adaptor protein complexes and their functional roles in cancer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Previous findings have revealed that disorders of lipid metabolism may be a risk factor for pulmonary function damage; however, the combined effect of dyslipidemia and central obesity on pulmonary function is unclear. The cardiometabolic index (CMI) is a composite of serum lipids (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)) and visceral fat parameters (waist-to-height ratio (WHtR)). This research aimed to investigate the link between CMI and pulmonary function, employing large-scale demographic data sourced from the National Health and Nutrition Examination Survey (NHANES) database., Methods: This cross-sectional study used data involving 4125 adults aged 20 and above collected by NHANES between 2007 and 2012. We defined CMI as the exposure variable and measured outcomes using forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC to evaluate pulmonary function. Weighted multiple linear regression models and subgroup analyses were employed to investigate separate relationships between CMI and pulmonary function. In addition, to investigate variations across different strata and evaluate the robustness of the findings, interaction tests and sensitivity analyses were conducted., Results: Results from the weighted multiple linear regression analysis indicated a unit increase in log2-CMI was associated with a reduction of 82.63 mL in FEV1 and 112.92 mL in FVC. The negative association remained significant after transforming log2-CMI by quartile (Q). When the log2-CMI level reached Q4, β coefficients (β) were -128.49 (95% CI: -205.85, -51.13), -169.01 (95% CI: -266.72, -71.30), respectively. According to the interaction test findings, the negative association linking log2-CMI with FEV1 and FVC persists regardless of confounding factors including age, gender, BMI, physical activity (PA), and smoking status. A subsequent sensitivity analysis provided additional confirmation of the stability and reliability of the results. For females, the inflection points for the nonlinear relationships between log2-CMI and FEV1, as well as log2-CMI and FVC, were identified at 2.33 and 2.11, respectively. While in males, a consistent negative association was observed., Conclusions: Our findings suggest that higher CMI is associated with lower FEV1 and FVC. CMI may serve as a complementary consideration to the assessment and management of pulmonary function in clinical practice., (© 2024. The Author(s).)

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less., Competing Interests: Declaration of competing interest The authors do not have any conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle., (© 2024. The Author(s).)

Exciplex emitters naturally have thermally activated delayed fluorescence characteristics due to their spatially separated molecular orbitals. However, the intermolecular charge transfer potentially induces diverse non-radiative decay channels, severely hindering the construction of efficient red exciplexes. Thus, a thorough comprehension of this energy loss is of paramount importance. Herein, different factors, including molecular rigidity, donor-acceptor interactions and donor-donor/acceptor-acceptor interactions, that impact the non-radiative decay were systematically investigated using contrasting exciplex emitters. The exciplex with rigid components and intermolecular hydrogen bonds showed a photoluminescence quantum yield of 84.1% and a singlet non-radiative decay rate of 1.98 × 10 6 s -1 at an optimized mixing ratio, respectively, achieving a 3.3-fold increase and a 70% decrease compared to the comparison group. In the electroluminescent device, a maximum external quantum efficiency of 23.8% was achieved with an emission peak of 608 nm, which represents the state-of-the-art organic light-emitting diodes using exciplex emitters. Accordingly, a new strategy is finally proposed, exploiting system rigidification to construct efficient red exciplex emitters that suppress non-radiative decay., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML)., Methods: A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology, Affiliated Hospital of Jinggangshan University from January 2020 to December 2022. Among them, 26 patients received venetoclax combined with azacitidine chemotherapy (observation group), and 22 patients received daunorubicin plus cytarabine chemotherapy (control group). The differences in complete response (CR) rate, objective response rate (ORR), progressionfree survival (PFS), overall survival(OS) and adverse reactions (AR) were compared between the two groups., Results: There was no significant difference in age, sex ratio, absolute value of trilineage cell and proportion of bone marrow primordial cells between the two groups before treatment (all P >0.05). The CR rate and the ORR rate of the observation group was significantly higher than that of the control group ( P < 0.05). After treatment, there were no significant difference in the adverse reactions such as myelosuppression, granulocytosis, secondary infection, mucosal damage, liver and kidney damage, cardiotoxicity and gastrointestinal toxicity between the two groups ( P >0.05). The median PFS and the median OS of the observation group were significantly better than those of the control group ( P < 0.05)., Conclusion: The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia. Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC 50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV., Competing Interests: Declaration of competing interest None., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

We report on an experimental simulation of the spin-1 Heisenberg model with composite bosons in a one-dimensional chain based on the two-component Bose-Hubbard model. Exploiting our site- and spin-resolved quantum gas microscope, we observed faster superexchange dynamics of the spin-1 system compared to its spin-1/2 counterpart, which is attributed to the enhancement effect of multi-bosons. We further probed the nonequilibrium spin dynamics driven by the superexchange and single-ion anisotropy terms, unveiling the linear expansion of the spin-spin correlations, which is limited by the Lieb-Robinson bound. Based on the superexchange process, we prepared and verified the entangled qutrits pairs with these composite spin-1 bosons, potentially being applied in qutrit-based quantum information processing.

Background: Cronkhite-Canada syndrome (CCS) is a rare disease, that causes gastrointestinal polyps, ectodermal abnormalities, and gastrointestinal symptoms. CCS is prone to thromboembolism, but clinical workers have not yet established a clinical consciousness of preventing thromboembolism. The present case illustrates pulmonary embolism (PE) complicated by CCS., Case Summary: A 46-year-old male patient presented with mucus, purulent, and bloody stool. Ectodermal changes included skin pigmentation, alopecia, and nail dystrophy. Colonoscopy revealed the presence of multiple polyps. After a comprehensive evaluation, the patient was diagnosed with CCS. During the disease, he was also diagnosed with pulmonary embolism, Riehl's melanosis, and intestinal flora imbalance. After symptomatic treatment with omeprazole, mesalazine, rivaroxaban, nutritional support, and regulation of intestinal flora, the patient's symptoms were significantly relieved., Conclusion: CCS complicated with PE was reported for the first time in China in this study. Despite the fact that CCS is extremely rare, patients with CCS should be classified as a high-risk venous thromboembolism (VTE) population, and emphasis should be placed on venous thromboembolism risk assessment and stratification, deep venous thromboembolism screening, prevention of VTE, and careful long-term follow-up., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this work, we have found that a prenotched double-network (DN) hydrogel, when subjected to tensile loading in a pure-shear geometry, exhibits intriguing stick-slip crack dynamics. These dynamics synchronize with the oscillation of the damage (yielding) zone at the crack tip. Through manipulation of the loading rate and the predamage level of the brittle network in DN gels, we have clarified that this phenomenon stems from the significant amount of energy dissipation required to form the damage zone at the crack tip, as well as a kinetic contrast between the rapid crack extension through the yielding zone (slip process) and the slow formation of a new yielding zone controlled by the external loading rate (stick process)., Competing Interests: Competing interests statement:The authors declare no competing interest.

The tree shrew ( Tupaia belangeri ) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.

Objective: To study the expression of the Homeobox C6 (HOXC6) gene in the homeobox family in PCa, its effect on the biological behavior of PCa cells and its action mechanism., Methods: Based on the studies of HOXC6 retrieved from the database of Gene Expression Profiling Interactive Analysis (GEPIA), we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients. We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot, stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prostatic epithelial RWPE-1 cells using the siRNA plasmid, and determined the effects of HOXC6 on the proliferation, migration and invasiveness of PCa cells by CCK8, plate cloning and scratch healing and Transwell invasion assays. Using the GEPIA database, we analyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1 (SFRP1) gene with HOXC6, and detected the expressions of HOXC6, SFRP1, Wnt and β-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot., Results: The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue (P< 0.01), and in the PCa cells than in the normal prostatic epithelial cells (P< 0.01). Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression (P = 0.011). The relative expression of the HOXC6 protein, absorbance value, number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls (P< 0.05). According to the GEPIA database, highly expressed SFRP1 was associated with a good prognosis of PCa, and the protein expressions of Wnt and β-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line (P< 0.05). The expressions of the Wnt and β-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group compared with those in the siRNA negative control and PCa PC-3 groups (P< 0.05)., Conclusion: HOXC6 is highly expressed in PCa tissues and related to the proliferation, migration and invasiveness of PCa cells. HOXC6 promotes the growth of DU145 and PC-3 cells in PCa by inhibiting the SFRP1/Wnt/β-catenin signaling pathway, and may be a potential target for clinical treatment of PCa.

In medical image analysis, anatomical landmarks usually contain strong prior knowledge of their structural information. In this paper, we propose to promote medical landmark localization by modeling the underlying landmark distribution via normalizing flows. Specifically, we introduce the flow-based landmark distribution prior as a learnable objective function into a regression-based landmark localization framework. Moreover, we employ an integral operation to make the mapping from heatmaps to coordinates differentiable to further enhance heatmap-based localization with the learned distribution prior. Our proposed Normalizing Flow-based Distribution Prior (NFDP) employs a straightforward backbone and non-problem-tailored architecture (i.e., ResNet18), which delivers high-fidelity outputs across three X-ray-based landmark localization datasets. Remarkably, the proposed NFDP can do the job with minimal additional computational burden as the normalizing flows module is detached from the framework on inferencing. As compared to existing techniques, our proposed NFDP provides a superior balance between prediction accuracy and inference speed, making it a highly efficient and effective approach. The source code of this paper is available at https://github.com/jacksonhzx95/NFDP.

Background: Stroke is the second leading cause of death across the globe. Early screening and risk detection could provide early intervention and possibly prevent its incidence. Imaging modalities, including 1D-Transcranial Doppler Ultrasound (1D-TCD) or Transcranial Color-code sonography (TCCS), could only provide low spatial resolution or 2D image information, respectively. Notably, 3D imaging modalities including CT have high radiation exposure, whereas MRI is expensive and cannot be adopted in patients with implanted devices. This study proposes an alternative imaging solution for reconstructing 3D Doppler ultrasound geared towards providing a screening tool for the 3D vessel structure of the brain., Methods: The system comprises an ultrasound phased array attached to a servo motor, which can rotate 180˚ at a speed of 2˚/s. We extracted the color Doppler ROI from the image before reconstructing it into a 3D view using a customized pixel-based algorithm. Different vascular diameters, flow velocity, and depth were tested using a vascular phantom with a pumped flow to confirm the system for imaging blood flow. These variables were set to mimic the vessel diameter, flow speed, and depth of the Circle of Willis (CoW) during a transcranial screening., Results and Conclusions: The lower values of absolute error and ratio were found in the larger vascular channels, and vessel diameter overrepresentation was observed. Under different flow velocities, such diameter overrepresentation in the reconstructed flow did not change much; however, it did change with different depths. Meanwhile, the setting of the velocity scale and the color gain affected the dimension of reconstructed objectives. Moreover, we presented a 3D image of CoW from a subject to demonstrate its potential. The findings of this work can provide a good reference for further studies on the reconstruction of the CoW or other blood vessels using Doppler imaging., 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 B.V. All rights reserved.)