Search

Abstract Efforts to develop disease-modifying treatments for Parkinson’s disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 µg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 µg) followed by 1, 7, and 14 days of recovery. This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology was used to map the time course of neuronal degeneration and the onset of neuroinflammation.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish ICI-AIN from other causes of AKI.The urine and plasma proteome contain actively secreted proteins that provide real-time insights into dynamic physiological processes. However, identification of effective biomarkers of disease using established technologies such as proximity ligation assays (PLA) and bead-based immunoassays is challenging due to their limited sensitivity and loss of precision in multiplex analysis.To address this, we employed cutting-edge NUcleic acid Linked Immuno-Sandwich Assay (NULISA) technology to measure protein expression in urine and plasma samples from AKI patients undergoing ICI therapy. NULISA offers 10,000-fold greater precision than PLA, enabling quantification of over 200 inflammatory proteins with unprecedented precision. Our analysis revealed that urine was more sensitive and specific than plasma in distinguishing ICI-AIN from non-AIN cases. Pathway analyses highlighted the involvement of JAK-STAT and tumor necrosis factor (TNF) signaling in ICI-AIN pathogenesis. We identified several novel urine biomarkers, including IL-5, Fas, TNFSF4, CD274, IL-20, TNFSF15, TSLP, TREM1 and CCL1 while confirming previously reported markers such as CXCL9 and TNF-α. Using statistical and machine learning methods, we constructed a novel urine biomarker signature—IL-5+Fas—that achieved an area under the curve of 0.94 for diagnosing ICI-AIN.By leveraging high-sensitivity proteomics, we developed a non-invasive strategy for diagnosing ICI-AIN. This approach will enable earlier intervention to mitigate immunotoxicity, preservation of antitumor efficacy of ICI therapy in non-AIN patients, and safe rechallenge of ICI therapy in patients previously treated for ICI-AIN.

The skeletal system comprises closely related yet functionally distinct bone and cartilage tissues, regulated by a complex network of transcriptional factors and signaling molecules. Among these, core-binding factor subunit beta (Cbfβ) emerges as a critical co-transcriptional factor that stabilizes Runx proteins, playing indispensable roles in skeletal development and homeostasis. Emerging evidence from genetic mouse models has highlighted the essential role of Cbfβ in directing the lineage commitment of mesenchymal stem cells (MSCs) and their differentiation into osteoblasts and chondrocytes. Notably, Cbfβ deficiency is strongly associated with severe skeletal dysplasia, affecting both endochondral and intramembranous ossification during embryonic and postnatal development. In this review, we synthesize recent advancements in understanding the structural and molecular functions of Cbfβ, with a particular focus on its interactions with key signaling pathways, including BMP/TGF-β, Wnt/β-catenin, Hippo/YAP, and IHH/PTHrP. These pathways converge on the Cbfβ/RUNX2 complex, which orchestrates a gene expression program essential for osteogenesis, bone formation, and cartilage development. The integration of these signaling networks ensures the precise regulation of skeletal development, remodeling, and repair. Furthermore, the successful local delivery of Cbfβ to address bone abnormalities underscores its potential as a novel therapeutic target for skeletal disorders such as cleidocranial dysplasia, osteoarthritis, and bone metastases. By elucidating the molecular mechanisms underlying Cbfβ function and its interactions with key signaling pathways, these insights not only advance our understanding of skeletal biology but also offer promising avenues for clinical intervention, ultimately improving outcomes for patients with skeletal disorders., (© 2025 Federation of American Societies for Experimental Biology.)

The skeletal system provides vital importance to support organ development and functions. The Notch signaling pathway possesses well-established functions in organ development and cellular homeostasis. The Notch signaling pathway comprises five typical ligands (JAG1, JAG2, DLL1, DLL3, and DLL4), four receptors (Notch1-4), and four intracellular domains (NICD1-4). Each component of the Notch signaling pathway has been demonstrated to be fundamental in osteoblast differentiation and bone formation. The dysregulation in the Notch signaling pathway is highly linked with skeletal disorders or diseases at the developmental and postnatal stages. Recent studies have highlighted the importance of the elements of the Notch signaling pathway in the skeletal system, as well as its interaction with signaling, such as Wnt/β-catenin, BMP, TGF-β, FGF, autophagy, and hedgehog (Hh) to construct a potential gene regulatory network to orchestrate osteogenesis and ossification. Our review has provided a comprehensive summary of the Notch signaling pathway in the skeletal system, as well as the insights targeting Notch signaling for innovative potential drug discovery targets or therapeutic interventions to treat bone disorders, such as osteoporosis and osteoarthritis. An in-depth molecular mechanistic strategy to modulate the Notch signaling pathway and its associated signaling pathway will be encouraged for consideration to trigger enhanced therapeutic approaches for bone disorders by defining Notch-regulating drugs for clinical use., (© 2025 Federation of American Societies for Experimental Biology.)

Objectives: The number of post-marketing studies assessing the vaccine effectiveness (VE) of the Lanzhou lamb rotavirus vaccine (LLR, licensed in 2000 exclusively in China) and the oral human attenuated pentavalent rotavirus vaccine (RotaTeq, licensed in China in 2018) in China is limited., Methods: A test-negative case-control study based on prospective surveillance was conducted among diarrhea patients aged 5 years and younger at five hospitals in Shanghai, China. Cases and controls were defined based on the results of real-time fluorescent quantitative reverse transcription polymerase chain reaction (rRT-PCR) of fecal samples for rotavirus. Both matched and unmatched case-control study designs were employed using logistic regression models, with adjustments for age at onset age and the rotavirus epidemic season., Results: In the LLR-specific analysis (247 cases, 2191 controls), the VE of partial LLR vaccination (2 doses) was 49.09 % (95 % CI: 1.69 % ∼ 73.64 %) in multivariate analyses. In the RotaTeq-specific analysis (42 cases and 523 controls), the VE of complete RotaTeq vaccination was 87.13 % (95 % CI: 45.87 % ∼ 96.94 %), 89.46 % (95 % CI: 55.03 % ∼ 97.53 %), and 85.69 % (95 % CI: 33.43 % ∼ 96.93 %) respectively in univariate, multivariate, and matched analyses, respectively. The vaccination coverage for any dose among 2893 patients with rotavirus-negative diarrhea born between 2011 and 2022 was 49.78 %. Following the licensure of RotaTeq in 2018, this coverage increased from 45.02 % to 61.77 %., Conclusions: RotaTeq demonstrates a robust protective effectiveness, while LLR provides a certain level of protection against mild to moderate rotavirus diarrhea in children in Shanghai. For privately purchased (non-NIP) vaccines, we estimate that the coverage for rotavirus vaccines among children in Shanghai is high. Complete rotavirus vaccination is recommended for age-eligible children. Further post-marketing research on rotavirus vaccines is necessary to inform decision-making regarding the introduction of rotavirus vaccination in China., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaohuan Gong reports financial support was provided by Shanghai Municipal Health Commission. Jian Chen reports financial support was provided by Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System. Huanyu Wu reports financial support was provided by Shanghai Municipal Science and Technology Major Project. Yaxu Zheng, Xiaohuan Gong reports financial support was provided by Shanghai Municipal Human Resources and Social Security Bureau. 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 © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Position-sensitive photodetectors (PSDs) have been widely used for seamless, high-resolution light tracking, but applications such as aerospace and prolonged field operations require stable performance in extreme environments. Conventional PSDs, typically based on the lateral photovoltaic effect of silicon or other semiconductor junctions, are prone to radiation damage and material degradation, limiting their reliability under harsh conditions. Silicon carbide (SiC), with its wide bandgap, high mobility, low defect density, and strong resistance to radiation damage, offers a promising alternative for developing robust detectors. In this work, we present a PSD based on undoped 4H-SiC, designed with a simple vertical structure that eliminates the need for complex multi-interface architectures. The device demonstrates excellent performance, including a light on-off ratio exceeding 10 3 under sub-milliwatt illumination, spatial resolution of ∼0.1 μm, and fast response times of ∼10 μs (rise) and ∼6.3 μs (fall). It also exhibits remarkable stability under γ-ray irradiation (300 krad) with minimal photocurrent variation, making it suitable for accurate position tracking in radiation-prone environments. This work highlights the potential of 4H-SiC-based PSDs for advanced sensing applications that demand both high performance and resilience in extreme environments.

Competing Interests: Competing interests: The authors declare no competing interests.

Naringenin (NAR), a natural flavonoid, exerts anti-inflammatory and antioxidant pharmacology. However, the pharmacological mechanisms through which NAR prevents and treats intervertebral disc degeneration (IDD) remain unclear. We utilized bioinformatics, machine learning, and network pharmacology to identify shared targets among NAR, senescence, and IDD. Subsequently, molecular docking was conducted to evaluate NAR's binding affinity to common target. Additionally, we used IL-1β to induce senescence and degeneration in nucleus pulposus cells (NPCs) and conducted a series of cellular assays, including immunoblotting, immunofluorescence, β-galactosidase staining, cell proliferation, cell cycle analysis, and measurement of reactive oxygen species levels, to investigate NAR's impact on IL-1β-induced senescence and degeneration of NPCs. Our study revealed that Insulin-like growth factor binding protein 3 (IGFBP3) was the only common target. IGFBP3 exhibited significant differences between the IDD and healthy groups and proved to be an effective diagnostic marker for IDD. Molecular docking confirmed the binding between NAR and IGFBP3. In vitro experiments, we observed that Igfbp3 expression increased in the senescence and degeneration groups. Igfbp3 knockdown and NAR attenuated IL-1β-induced senescence and degenerative phenotypes in NPCs. In contrast, the effect of NAR was attenuated by recombinant IGFBP3 protein. In conclusion, our findings suggest that NAR plays a preventive and therapeutic role in IDD, likely achieved through the inhibition of Igfbp3 expression., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: The animal studies involved in this study were approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University., (© 2025. The Author(s).)

The efficacy of bacteriophages in treating bacterial infections largely depends on the phages' vitality, which is impaired when they are naturally released from their hosts, as well as by culture media, manufacturing processes and other insults. Here, by wrapping phage-invaded bacteria individually with a polymeric nanoscale coating to preserve the microenvironment on phage-induced bacterial lysis, we show that, compared with naturally released phages, which have severely degraded proteins in their tail, the vitality of phages isolated from polymer-coated bacteria is maintained. Such latent phages could also be better amplified, and they more efficiently bound and lysed bacteria when clearing bacterial biofilms. In mice with bacterially induced enteritis and associated arthritis, latent phages released from orally administered bacteria coated with a polymer that dissolves at neutral pH had higher bioavailability and led to substantially better therapeutic outcomes than the administration of uncoated phages., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Sleep problems positively predict loneliness to a large extent, which would harm adolescent health. However, little is known about the underlying mechanism. This research investigates the potential mediating roles of rumination and resilience in the relation among adolescents and further examines the changing relationships. In Study 1, 1056 adolescents from two schools completed self-reported measures of sleep problems, loneliness, rumination, and resilience. We found that sleep problems were positively associated with loneliness, and that rumination and resilience mediated this relationship, both individually and sequentially. To examine the varying relationship between rumination, resilience, and loneliness, Study 2 adopted the cross-lagged design in a long-term longitudinal study of 131 students and found that rumination and resilience at T1 significantly predict loneliness at T2. To further directly explore the changing relationship between sleep problems and loneliness, we performed a short-term longitudinal study across 7 weeks of 242 adolescents in Study 3. The results replicated the findings of Study 2 and found sleep problems at T1 positively predicted loneliness at T2. These results underscore the significance of sleep problems in contributing to loneliness through mediating mechanisms and unveil the possible causal relationships, offering robust insights to alleviate adolescent loneliness., (© 2024 International Association of Applied Psychology.)

The activation of astrocytes in the injured lesion induces the progression of spinal cord injury (SCI). However, adverse side-effects during systemic administration have limited applications. Exosomes (Exos) are an emerging clinical treatment method that exerts anti-inflammatory effects by reducing pro-inflammatory factors and promoting functional recovery. Exosomes exhibit great potential as carriers of traditional Chinese medicine, attributed to their high delivery efficiency to internalized and targeted accumulation in inflammatory tissues. Herein, We synthesized resveratrol loaded microglia-derived exosomes (R-MDEs) for highly efficient accumulation and infiltration in the injured spinal cord. In vitro and in vivo experiments suggested that R-MDEs effectively accumulated in A1 astrocytes, inhibited reactive oxygen species (ROS) and glial scar formation by reprogramming the metabolic astrocytes. R-MDEs achieve a synergistic therapeutic effect of immunomodulation and neuroprotection, thereby shedding new light on the application of Exos and provides great potential for SCI., 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 © 2025 Elsevier B.V. All rights reserved.)

Background: Hepatic fibrosis, a chronic pathological condition, is associated with adverse outcomes in stroke patients. Cardioembolism (CE) is a common etiology of stroke, yet the association between hepatic fibrosis and CE remains understudied., Aim: This study aims to investigate the association between hepatic fibrosis and CE-induced stroke, as well as its impact on stroke patient prognosis., Methods: This retrospective study included 344 acute ischemic stroke (AIS) patients who underwent thrombolytic therapy. Hepatic fibrosis was assessed using the Fibrosis-4 (FIB-4) index and the Aspartate Aminotransferase-Platelet Ratio Index (APRI). Mediation analysis examined the role of CE in the association between hepatic fibrosis and 3-month functional outcomes., Results: Among 344 patients, 319 were classified using the Trial of Org 10172 in Acute Stroke Treatment criteria. Severe fibrosis (FIB-4 ≥ 2.01) was observed in 131 patients (38.08%), and CE was identified in 79 patients. FIB-4 was an independent predictor of CE (OR: 2.038, 95%CI: 1.507- 2.757, p < 0.001) and poor 3-month functional outcome (OR: 1.477, 95%CI: 1.103-1.978, p = 0.009) after adjusting for confounders. The effect of FIB-4 on poor 3-month functional outcomes was partially mediated by CE, with a mediation proportion of 30.63%., Conclusions: Hepatic fibrosis is a significant predictor of short-term functional outcomes in AIS, particularly cardioembolic stroke. The association between hepatic fibrosis and stroke outcomes is partially mediated through CE. These findings highlight the importance of assessing hepatic fibrosis in stroke patients, particularly those with CE etiology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Microalgae are rich sources of astaxanthin well recognized for their potent bioactivities such as antioxidant, anti-cancer, and anti-inflammatory activities. Recent interests focused on the bioactivities of microalgae-derived astaxanthin on treating or preventing cancers mediated by their antioxidant and anti-inflammatory properties. This is due to the special structural configuration of microalgae-derived astaxanthin in terms of unsaturation (conjugated double bonds), stereochemical isomerism (3 S ,3' S optical isomer) and esterification (monoester), which display more potent bioactivities, compared with those from the other natural sources such as yeasts and higher plants, as well as synthetic astaxanthin. This review focuses on the recent advances on the bioactivities of microalgae-derived astaxanthin in association with cancers and immune diseases, with emphasis on their potential applications as natural antioxidants. Various well-developed biotechnological approaches for inducing astaxanthin production from microalgal culture, along with the proven and emerging industrial technologies to commercialize astaxanthin products in a large-scale manner, are also critically reviewed. These would facilitate the manufacture of bioactive microalgae-derived astaxanthin products to be applied in the food and pharmaceutical industries as salutary nutraceuticals.

The functionalization of aliphatic C-H bonds is a crucial step in the synthesis and transformation of complex molecules relevant to medicinal, agricultural and materials chemistry. As such, there is substantial interest in the development of general synthetic platforms that enable the efficient diversification of aliphatic C-H bonds. Here we report a hypervalent iodine reagent that releases a potent hydrogen atom abstractor for C-H activation under mild photochemical conditions. Using this reagent, we demonstrate selective (N-phenyltetrazole)thiolation of aliphatic C-H bonds for a broad scope of substrates. The synthetic utility of the thiolated products is showcased through various derivatizations. Simply by altering the radical trapping agent, our method can directly transform C-H bonds into diverse functionalities, including C-S, C-Cl, C-Br, C-I, C-O, C-N, C-C and C=C bonds., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Telemedicine has been increasingly utilized by plastic surgeons since the start of the COVID-19 pandemic as it minimizes visit time, costs, and viral exposures. However, patient comfort level and preference for telemedicine visits in the aesthetic surgery perioperative period remains unknown. The purpose of this study was to evaluate patient comfort and preferences regarding perioperative telemedicine visits for aesthetic surgery., Methods: An IRB-approved cross-sectional survey was conducted in January 2022 on Amazon's Mechanical Turk (MTurk) platform to assess respondents' comfort and preferences regarding periprocedural telemedicine visits. Survey responses were compared using descriptive and multivariate analyses., Results: A total of 505 participants (54% male, 46% female; mean age 37.7±11.5 years) completed the survey. The majority of respondents reported feeling either very or somewhat comfortable having their initial consult via telemedicine for both aesthetic surgery (72%) and non-surgical aesthetic procedures (74%). Respondents were most comfortable having an initial telemedicine consult for head and neck procedures, and least comfortable having telemedicine consults for sensitive areas, including the breast and buttocks. Respondents were significantly more comfortable scheduling non-surgical procedures than surgical procedures after a telemedicine consult alone (65% vs 58%; p < 0.001)., Conclusions: Our data suggests that the majority of aesthetic surgery patients are comfortable with having initial consultations via telemedicine. Particularly in young patients seeking non-surgical aesthetic procedures, telemedicine consults alone may be substituted for in-office visits prior to procedural scheduling. However, for operations and procedures requiring physical examination of sensitive areas, including the breasts and gluteal regions, in-person visits remain the preferred modality., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., Competing Interests: Declarations. Conflict of interest: None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (© 2025. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Saccharomyces cerevisiae predominantly ferments sugar to ethanol, irrespective of the presence of oxygen, which is known as the Crabtree-effect. Traditional methods rely on static controls of glycolytic flux to make S. cerevisiae Crabtree-negative, which are not favorable for future biomanufacturing applications. Considering native metabolic pathways typically harness dynamic regulatory networks, we therefore aim to develop an alternative strategy using dynamic regulation of the yeast central metabolism to generate Crabtree-negative S. cerevisiae. We reported that manipulating a single step at sugar phosphorylation can alter the mode of yeast metabolism with attenuated Crabtree-effect. By implementing catabolite-regulated sugar phosphorylation, the diauxic shift in budding yeast was effectively reduced. The Crabtree-attenuated metabolism in the engineered yeast was confirmed by multidimensional characterizations such as cell morphology, the measurement of sugar utilization rate and ethanol production, and transcriptomics. In addition, we demonstrated that the Crabtree-attenuated metabolism could substantially improve the mitochondrial synthesis of short branched-chain fatty acids from amino acid catabolism, and allow the synthesis and accumulation of retinaldehyde. Taken together, we present for the first time that manipulation of sugar phosphorylation can alter the mode of yeast metabolism, and the synthetic Crabtree-attenuated yeast factory established here might serve as a non-fermentative biomanufacturing chassis., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2025. Published by Elsevier Inc.)

Objectives: GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that inhibits HBV replication by interfering with assembly and disassembly of the virus nucleocapsid, this prospective, open-label, comparative, phase 2b trial evaluated the antiviral activity and safety of GLS4/ritonavir (RTV) combined with entecavir in hepatitis B e antigen-positive patients., Methods: 250 CHB patients were enrolled, including treatment-naïve patients and those interrupted anti-HBV drugs for ≥ 6 months (Part A, n=125), and patients who had taken ETV for ≥1 year and had achieved viral suppression (Part B, n=125). Patients were randomly allocated to receive 120mg GLS4/100mg RTV plus 0.5mg ETV or 0.5mg ETV monotherapy for 96 weeks., Results: In the mid-term, in Part A (n=122), greater least-squares mean (LSM) changes from baseline were observed in the GLS4/RTV plus ETV cohort than in ETV monotherapy cohort in HBV DNA (-6.28 vs -5.72 log10 IU/ml, p=0.0005), HBsAg (-0.87 vs -0.65 log10 IU/ml, p=0.0653), HBV pgRNA (-3.83 vs -1.91 log10 copies/ml, p<0.0001); The proportions of both HBV DNA and pgRNA negative patients were 17.3% (13/75, GLS4/RTV plus ETV) and 0% (0/30, ETV monotherapy). In Part B (n=123), greater mean LSM reductions in HBsAg (-0.17 vs -0.06 log10 IU/ml, p=0.0013), HBV pgRNA (-1.61 vs -0.28 log10 copies/ml, p<0.0001) were also observed in the GLS4/RTV+ETV cohort. the proportions of both HBV DNA and pgRNA-negative patients were 71.6% (48/67, GLS4/RTV plus ETV) and 18.9% (7/37, ETV monotherapy), respectively. No patients achieved HBsAg loss at week 48. GLS4/RTV + ETV were well tolerated, the most common adverse events were elevated alanine aminotransferase levels and hypertriglyceridemia, which were reversed by temporary GLS4/RTV discontinuation., Conclusions: The primary analysis at week 48 showed that the antiviral efficacy of GLS4/RTV with ETV was clearly superior to that of ETV monotherapy. GLS4/RTV with ETV was well tolerated; further studies evaluating its safety and efficacy are ongoing. (clinical trial identifier: NCT04147208)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Robert G. Gish, MD, declares the following financial disclosures: Consulting Fees:Abacus Aligos, Altimunne, Antios, Dynavax, Enyo, Gilead Sciences, GlaxoSmithKline, Janssen, Precision BioSciences, Tune Therapeutics, Venatorx, and Virion. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Gilead Sciences Inc. and VBI Vaccines. Meeting and Travel Support: See consulting and speaker board entities Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Hepatitis B Foundation, NVHR (National Viral Hepatitis Roundtable), APHF (Asian Pacific Health Foundation), and CEVHAP (Coalition to Eliminate Viral Hepatitis Among Populations at Highest Risk). Stock and Stock Options: He holds stock or stock options from Abacus and Virion. All the other 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 © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiovascular disease is a leading cause of death, with ischemic heart disease being a significant contributor. While percutaneous coronary intervention (PCI) effectively reduces mortality in myocardial infarction patients, its efficacy for unstable angina (UA) patients is controversial. Complications associated with PCI further limit application in UA. RIC is hypothesized to be an effective co-intervention that reduces PCI-related complications and may potentially enhance the efficacy of the PCI procedure itself., Methods: This is a pragmatic, prospective, dual-center, double-blind, randomized controlled clinical trial assessing the effect of remote ischemic conditioning (RIC) during percutaneous coronary intervention (PCI) on injury in unstable angina patients aged ≥ 18 years undergoing coronary angiography. Participants will be randomized to receive either RIC or Sham RIC, in addition to standard pharmacotherapy. Primary outcome includes periprocedural myocardial injury measured by hs-cTnT levels, while secondary outcomes encompass major adverse cardiovascular events, coronary artery lesions Gensini Score, arrhythmia, angina incidence, SAQ scores, ECG changes, and cardiac function assessed by two-dimensional echocardiography. The trial aims to recruit 574 participants and is scheduled to be initiated on 15 January 2024. We will conduct the primary statistical analysis using the intention-to-treat principle. Results from the trial will be presented as comparative summary statistics following the Consolidated Standards of Reporting Trials (CONSORT) guidelines., Trial Registration: ChiCTR2400079855, 15 January 2024., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board of the First Affiliated Hospital of Nanjing Medical University has sanctioned the trial protocol (Reference No. 2023-SR-161). Any substantive modifications pertaining to the study protocol, be it eligibility criteria, intervention methodologies, outcome measures, or analytical approaches, will be executed under the vigilant oversight and endorsement of the respective review board. All endeavors undertaken in this trial with human participants shall align scrupulously with the rigorous ethical tenets set forth by both the institutional/national research committees and the 1964 Helsinki Declaration, inclusive of subsequent amendments or analogous ethical benchmarks. Prior to their enrolment and allocation, explicit written consents shall be procured from all participating individuals. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Spinal Muscular Atrophy (SMA, MIM#253300) is an autosomal recessive neuromuscular disorder caused by defects in the Survival Motor Neuron (SMN) gene. The SMN1 gene, recognized as the primary pathogenic gene for SMA, exhibits a high degree of sequence homology with SMN2 gene. Individuals with the SMN1 2 + 0 genotype represent a unique type of SMA carrier, characterized by two SMN1 copies on one chromosome and zero copies on the other. Accurate identification of this type of carrier is crucial for genetic counseling in families. This study included 28 samples from five SMA families, each with an affected patient carrying a homozygous deletion of the SMN1 gene and a parent suspected to be a SMN1 2 + 0 carrier. Comprehensive Analysis of SMA (CASMA), based on third-generation sequencing technology, was used to detect the SMN1 and SMN2 copy numbers in the samples, and SMN1 2 + 0 carriers were identified through SMN1 haplotypes in parent-child trios (CASMA-trio). The results were compared with those obtained using Multiplex Ligation-dependent Probe Amplification (MLPA) combined with Short Tandem Repeat (STR) linkage analysis. The SMN1 and SMN2 copy numbers detected by MLPA and CASMA were concordant across 25 peripheral blood samples, whereas CASMA failed to accurately determine the copy numbers in the remaining 3 amniotic fluid samples. CASMA-trio identified 5 members from 4 families as SMN1 2 + 0 carriers, which were consistent with the results from STR linkage analysis. However, the two methods yielded inconsistent results for the proband's father in one family. These findings suggest that CASMA has the potential to detect SMN1 and SMN2 copy numbers. Compared to STR linkage analysis, CASMA-trio only requires a parent-child trio to analyze SMN1 2 + 0 carriers, demonstrating a broader application prospect. Implementing CASMA-trio can facilitate comprehensive screening for SMA carriers., Competing Interests: Declarations. Competing interests : The authors declare no competing interests.  Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University (Ethics Approval [2021] No. 254). All patients provided their voluntary informed consent prior to the procedure being performed., (© 2025. The Author(s).)

Bacteria-based vaccines have received increasing attention given the ability to induce strong systemic immune responses. However, the application of bacteria as therapeutic agents inevitably suffers from infection-associated side effects due to the living characteristics. Here, the use of bacteria-derived flagella is described to construct self-adjuvated nanofiber vaccines. With the help of charge-reversal mediated by decoration with cationic polymers, the flagella can be coated with negatively charged antigens through electrostatic interaction. By virtue of the large aspect ratio, the resulting nanofiber vaccines show prolonged retention at the injection site and increased uptake by dendritic cells and macrophages. Thanks to the innate immunogenicity, self-adjuvated flagella robustly promote dendritic cell maturation and macrophage polarization, resulting in the elicitation of antigen-specific T-cell and B-cell immune responses. In ovalbumin-overexpressing melanoma-bearing mice, immunization with ovalbumin-carried vaccines not only exhibits a favorable tolerance, but also displays superior inhibition efficacies on tumor growth and metastasis separately under the therapeutic and prophylactic settings. The flexibility of this approach is further demonstrated for vaccine fabrication by coating with the SARS-CoV-2 Spike protein S1 subunit. Bacterial flagella-based self-adjuvated nanofiber platform proposes a versatile strategy to develop various vaccines for disease prevention and treatment., (© 2025 Wiley‐VCH GmbH.)

The non-proteinogenic tris -amino acid labionin was discovered in 2010 and since has been described in many natural products, defining an entire family of lanthipeptides. The unusual amino acid is biosynthetically produced by the sequential condensation of a cysteine onto two dehydroalanines. An attempt in 2011 to synthesize the amino acid monomeric unit was unsuccessful yet served as a valuable foundation and guide to the present work. A recently disclosed methodology for the selective opening of aziridines by mercaptan nucleophiles was applied to another methodology for contrasteric aziridination, thus enabling a short synthesis of challenging and elusive labionin.

Toll-like receptors (TLRs) are important pattern recognition receptors that can recognize pathogen-associated molecular patterns (PAMPs), which in turn activate immune cells in vivo to perform immune functions. In this study, two TLR1 subfamily members (TLR2 and TLR14), one TLR5 subfamily member (TLR5S) and one TLR11 subfamily member (TLR22) genes were first identified in Mastacembelus armatus. In MaTLR2, MaTLR14 and MaTLR22, three main domains were identified, including leucine-rich repeat (LRR) domain, a transmembrane domain (TM) and an intracellular Toll/IL-1 receptor (TIR) domain as in most TLRs with no TM domain and TIR domain in MaTLR5S. The tissue expression of MaTLR2, MaTLR5S, MaTLR14 and MaTLR22 showed that they were ubiquitously expressed in all tested tissues. After infection with Aeromonas veronii, expression of MaTLR2, MaTLR14 and MaTLR22 was all downregulated in spleen and liver, but upregulated in kidney. By contrast, MaTLR5S showed upregulation in all three organs after bacterial infection. The amino acid sequence identity of MaTLR2 with other teleosts varied from 64.7% to 76.8%, while MaTLR5S exhibited a range of 70.9%-75.9%. MaTLR14 demonstrated a higher degree of similarity, with sequence identities ranging from 74% to 83.3%. In contrast, MaTLR22 showed the most variability, with sequence identities spanning from 42.5% to 74.6%. Phylogenetic analysis of TLR genes of M. aramatus clustered with Perciformes fishes, which aligned with traditional taxonomic classifications. The site model of PAML was used to detect the robust positively selected sites in extant teleost fishes. In total, 20, 12, 19 and 6 sites in the subsets of teleost TLR2, TLR5S, TLR14 and TLR22 were separately identified, indicating that the teleost TLR2, TLR5S, TLR14 and TLR22 had been subject to positive selection pressures. Our results will lay a good function for better understanding the potential function of TLRs in antibacterial process and their co-evolution with pathogens., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Myocardial infarction (MI) remains a leading cause of global health burden, and adverse cardiac remodeling after MI seriously affects patient recovery. Macrophages play an important role in the cardiac remodeling post-MI. Quercitrin (Que), a bioflavonoid commonly found in fruits, vegetables, and various Chinese medicines, possesses a therapeutic effect in MI, but whether it has a role in the prevention of MI is unclear. This study investigated the potential preventive value and mechanism of Que against MI. In this study, we treated adult male C57BL/6 mice with Que for 2 weeks and then constructed the MI model. We found that pre-treatment with Que improved cardiac fractional shortening and ejection fraction, and elevated the survival of mice after MI. In addition, pre-administration of Que attenuated cardiac hypertrophy and diminished the infarct size of the heart post-MI. Picrosirius red staining of heart sections and detection of fibrosis markers' levels by real-time polymerase chain reaction and western blot analyses revealed that Que repressed cardiac fibrosis after MI. Que pre-administration inhibited the levels of inflammatory factors and the infiltration of inflammatory cells, and increased the proportion of M2-like macrophages in the infarcted area of the heart. Furthermore, we found that Que pre-treatment polarized macrophage from M1-like to M2-like, which promoted the proliferation, migration, and activation of cardiac fibroblasts in vitro. Collectively, these data demonstrated that pre-administration Que promoted survival and reduced adverse ventricular remodeling after MI partially through modifying macrophage polarization. This provides an experimental basis for the future application of Que in cardiovascular diseases including MI., 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 © 2025 Elsevier B.V. All rights reserved.)

Acanthocephala are known as thorny-headed worms and are common parasites in animals, but acanthocephaliasis in humans is rare, with limited medical literature available. Infections are acquired via direct ingestion of arthropod intermediate hosts. In this case report, a female toddler is evaluated for passage of a pseudosegmented worm in the stool, which was later identified as Moniliformis moniliformis She is treated with pyrantel pamoate with a resolution of worms in stool. This case report aims to expand knowledge surrounding infections by the Acanthocephala phylum and the nuances of identification and treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Achieving ultrathin polymersomes (UTPSs) with controllable light-responsive kinetics poses a prospective strategy to address the growing demands of intelligent and miniature systems, but it remains challenging. Herein, we reported the self-assembly of numerous side-chain-type amphiphilic alternating azocopolymers (AAACs) into a series of UTPSs with diameters spanning 210-270 nm and ultrathin vesicular thickness spanning 1.91-2.14 nm. The light-triggered reversible size transitions for these UTPSs are rendered by the photo-isomerization of azobenzene moiety upon alternating irradiation with UV and visible light. The systematical isomerization kinetic study proved that the light-responsive rate of distinct UTPSs was highly dependent on the electronic effect of para-substituents of azobenzenes within AAACs. Notably, the rate constant of electron-withdrawn nitro-modified UTPSs was 6.7 times greater than that of electron-donated hydroxyl-modified UTPSs. The proof-of-concept cargo release activity for different UTPSs was evaluated using a hydrophilic model drug of methylene blue (MB), with a light-controllable releasing performance that highly depended on the para-substituent-induced light-responsive kinetics. Our work offers an innovative strategy to fabricate stimuli-responsive UTPSs with a controllable responsive performance for the targeted applications in bionanotechnology., (© 2025 Wiley‐VCH GmbH.)

Maize is one of the most important crops for human food, animal feed, and industrial raw materials. Ear shank length (ESL) and ear shank node number (ESNN) are crucial selection criteria in maize breeding, impacting grain yield and dehydration rate during mechanical harvesting. To unravel the genetic basis of ESL and ESNN in maize, an association panel consisting of 379 multi-parent doubled-haploid (DH) lines was developed for genome-wide association studies (GWAS) and genomic selection (GS). The heritabilities of ESL and ESNN were 0.68 and 0.55, respectively, which were controlled by genetic factors and genotype-environment interaction factors. Using five different models for GWAS, 11 significant single nucleotide polymorphisms (SNPs) located on chromosomes 1, 2, and 4 were identified for ESL, with the phenotypic variation explained (PVE) value of each single SNP ranging from 4.91% to 21.35%, and 11 significant SNPs located on chromosomes 1, 2, 4, and 5 were identified for ESNN, with the PVE value of each SNP ranging from 1.22% to 18.42%. Genetic regions in bins 1.06, 2.06, and 2.08 were significantly enriched in SNPs associated with ear shank-related traits. The GS prediction accuracy using all markers by the five-fold cross-validation method for ESL and ESNN was 0.39 and 0.37, respectively, which was significantly improved by using only 500-1000 significant SNPs with the lowest P-values. The optimal training population size (TPS) and marker density (MD) for ear shank-related traits were 50%-60% and 3000, respectively. Our results provide new insights into the GS of ear shank-related traits., 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.)

Liquid biopsies are expected to advance cancer management, and particularly physical cues are gaining attention for indicating tumorigenesis and metastasis. Atomic force microscopy (AFM) has become a standard and important tool for detecting the mechanical properties of single living cells, but studies of developing AFM-based methods to efficiently measure the mechanical properties of circulating tumor cells (CTCs) in liquid biopsy for clinical utility are still scarce. Herein, we present a proof-of-concept study based on the complementary combination of AFM and microfluidics, which allows label-free sorting of individual CTCs and subsequent automated AFM measurements of the mechanical properties of CTCs. With the use of a microfluidic system containing contraction-expansion microchannels, specific cancer cell types were separated and harvested in a marker-independent manner. Subsequently, automated AFM indentation and force spectroscopy experiments were performed on the enriched cells under the precise guidance of the label-free identification of cells using a deep learning optical image recognition model. The effectiveness of the presented method was verified on three experimental sample systems, including mixed microspheres with different sizes, a mixture of different types of cancer cells, and a mixture of cancer cells and blood cells. The study illustrates a feasible framework based on the integration of AFM and microfluidics for non-destructive and efficient nanomechanical phenotyping of CTCs in bodily fluids, which offers additional possibilities for the clinical applications of AFM-based nanomechanical analysis and will also benefit the field of mechanobiology as well as cancer liquid biopsy.

Disposable plasmonic metasurfaces with high biosensing performance are urgently sought for clinical label-free detection. Low-cost aluminum (Al) and titanium nitride (TiN) offer promising alternatives to noble metals for constructing these metasurfaces. However, Al suffers from limited chemical stability, and TiN exhibits weak plasmonic effects, both of which hinder their application in meta-biosensing. Here we integrate their complementary advantages and propose the TiN/Al meta-biosensors. They not only empower the unique near-field enhancement for sensing by TiN/Al hybrid plasmonic modes, but also construct a robust TiN armor against external wear, heat, moisture and corrosion during the bio-detection process. Compared to traditional gold-based counterparts, our meta-biosensors offer superior optical sensitivity at a much lower cost and with fewer pretreatment steps. The excellent biosensing performance facilitates the development of a high-throughput detection system for serum small extracellular vesicles (sEVs), aiding in the diagnosis and follow-up of prostate cancer. The sEVs meta-biosensing demonstrates a diagnostic sensitivity of 100% for significantly distinguishing early cancer, breaking through the conventional testing limitation. Moreover, it doubles the prediction accuracy of cancer recurrence risk following surgery. Our research highlights the potential for large-scale development of powerful meta-biosensors based on non-noble materials, opening up significant opportunities in cancer diagnosis and prognosis., 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 © 2025 Elsevier B.V. All rights reserved.)

The concurrent targeting of Fms-like tyrosine kinase 3 (FLT3)/VEGFR2/Histone deacetylase (HDAC) represents a novel and promising therapeutic strategy for acute myeloid leukemia. In this work, we hybridized essential pharmacophores from sorafenib and SAHA (vorinostat) and then conducted structure-activity relationship studies to identify two lead compounds 26 and 32 that potently inhibit FLT3, VEGFR2, and HDAC in a nanomolar range. In cell evaluation, compounds 26 and 32 exhibited potent proliferative activities against a panel of leukemia cells including MV4-11 and MOLM-13. Western blotting analysis also showed that compounds 26 and 32 suppressed the phosphorylation of FLT3, STAT3, and ERK1/2 and increased histone H3 acetylation in a dose-dependent manner, indicating the effective inhibition of FLT3, VEGFR2, and HDAC. Supported by its pharmacokinetic properties, compound 26 showed remarkable anticancer efficacy in a MV4-11 xenograft model. Additionally, it demonstrated superior efficacy compared to midostaurin and gilteritinib in the Ba/F3-FLT3-ITD-N701K xenograft model.

Lyssavirus glycoprotein plays a crucial role in mediating virus entry and serves as the major target for neutralizing antibodies. During membrane fusion, the lyssavirus glycoprotein undergoes a series of low-pH-induced conformational transitions. Here, we report the structures of Ikoma lyssavirus and Mokola lyssavirus glycoproteins, with which we believe that we have trapped the proteins in pre-fusion and post-fusion states respectively. By analyzing the available lyssaviral glycoprotein structures, we present a sequential conformation-transition model, in which two structural elements in the glycoprotein undergo fine-modulated secondary structural transitions, changing the glycoprotein from a bended hairpin conformation to an extended linear conformation. In addition, such conformational change is further facilitated, as observed in our surface plasmon resonance assay, by the pH-regulated interactions between the membrane-proximal region and the pleckstrin homology and the fusion domains. The structural features elucidated in this study will facilitate the design of vaccines and anti-viral drugs against lyssaviruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gaining mechanistic insights into the structure-performance relationship connecting the donor and acceptor is essential to the rational design of high performance nonlinear optics (NLO) materials. Here, intramolecular boron/nitrogen (B/N)-locking strategies in combination with various electron-withdrawing groups, R (R = TXO, DPzS, TTR, DPyS, DTC, DSCZ, DMPS and TXO2), are proposed to address this issue. With the decreasing of torsion angles (θ 1 and θ 2 ) between donor (TPA) and acceptor (Py-Ph) units, the first hyperpolarizability (β) values are increased 45-65% and 4-27% by intramolecular B/N-locking strategies, respectively. Intriguingly, we also found some good linear correlations between θ 1 , θ 2 , and lgβ (where the determination coefficient R 2 ranges from 0.84 to 1.00). Meanwhile, between θ 1 , θ 2 , and the excited energy (Δ E ) of the crucial excited state there have also good correlations, namely, the R 2 ranges from 0.80 to 1.00. As a result, given the fact of finding results, one can draw some meaningful insights, namely, intramolecular B/N-locking strategies hold good application perspective for enhancing β, and θ 1 and θ 2 can serve as effective descriptors in designing high-performance NLO materials based on the D-A architecture system.

Excessive accumulations of reactive oxygen species (ROS) and M1 macrophages are closely associated with the complex pathogenesis of spinal cord injury (SCI). Thus, therapeutics that synergistically exert the elimination of ROS and repolarization of pro-inflammation macrophages are gaining increasing notice. We developed a prussian blue-based nanoflower (KPBF) with near-infrared (NIR) photothermal and antioxidant properties. The KPBF's biofunctions were similar to those of other antioxidant enzymes, such as catalase and superoxide dismutase, which are capable of reducing ROS. With NIR irradiation, KPBF efficiently heated the injured spinal cord lesion. By modifying the CKLVFFAED peptide, KPBF remarkably penetrated through the blood-spinal cord barrier (BSCB) into the local lesion. Moreover, KPBF repolarized M1 macrophages and alleviated neuroinflammation in SCI mice. Overall, KPBF presented a universal nanotherapeutic system with immunoregulation and antioxidant activities for acute SCI recovery.

Ocean warming due to climate change endangers coral reefs, and regional nitrogen overloading exacerbates the vulnerability of reef-building corals as the dual stress disrupts coral-Symbiodiniaceae mutualism. Different forms of nitrogen may create different interactive effects with thermal stress, but the underlying mechanisms remain elusive. To address the gap, we measured and compared the physiological and transcriptional responses of the Symbiodiniaceae Cladocopium goreaui to heat stress (31°C) when supplied with different types of nitrogen (nitrate, ammonium, or urea). Under heat stress (HS), cell proliferation and photosynthesis of C. goreaui declined, while cell size, lipid storage, and total antioxidant capacity increased, both to varied extents depending on the nitrogen type. Nitrate-cultured cells exhibited the most robust acclimation to HS, as evidenced by the fewest differentially expressed genes (DEGs) and less ROS accumulation, possibly due to activated nitrate reduction and enhanced ascorbate biogenesis. Ammonium-grown cultures exhibited higher algal proliferation and ROS scavenging capacity due to enhanced carotenoid and ascorbate quenching, but potentially reduced host recognizability due to the downregulation of N-glycan biosynthesis genes. Urea utilization led to the greatest ROS accumulation as genes involved in photorespiration, plant respiratory burst oxidase (RBOH), and protein refolding were markedly upregulated, but the greatest cutdown in photosynthate potentially available to corals as evidenced by photoinhibition and selfish lipid storage, indicating detrimental effects of urea overloading. The differential warming nitrogen-type interactive effects documented here has significant implication in coral-Symbiodiniaceae mutualism, which requires further research.IMPORTANCERegional nitrogen pollution exacerbates coral vulnerability to globally rising sea-surface temperature, with different nitrogen types exerting different interactive effects. How this occurs is poorly understood and understudied. This study explored the underlying mechanism by comparing physiological and transcriptional responses of a coral symbiont to heat stress under different nitrogen supplies (nitrate, ammonium, and urea). The results showed some common, significant responses to heat stress as well as some unique, N-source dependent responses. These findings underscore that nitrogen eutrophication is not all the same, the form of nitrogen pollution should be considered in coral conservation, and special attention should be given to urea pollution., Competing Interests: The authors declare no conflict of interest.

Vascular dementia (VaD), attributed to cerebrovascular pathology, is a leading cause of cognitive decline, characterized by memory loss, bradyphrenia, and affective lability, with memory deficits being particularly pronounced. The potential of enriched environment (EE) to ameliorate cognitive impairments by enhancing hippocampal synaptic plasticity, neurogenesis, and white matter remodeling has garnered considerable interest. In this study, we used a rat model for VaD through the procedure of bilateral common carotid artery ligation (BCCAO). We randomly assigned male Sprague-Dawley (SD) rats to three groups: the control sham-operated group (Sham group), the surgery-induced dementia group (BCCAO group), and the surgery-induced dementia group with enriched environment (EE group). The Sham and BCCAO groups were kept under standard lab conditions, whereas the EE group was housed in an enriched setting. Employing a behavioral assay battery, we observed that EE intervention significantly improved the spatial learning and memory performance in the Morris water maze. Subsequent neuromorphological assessments utilizing transmission electron microscopy disclosed an increase in synaptic density and postsynaptic density (PSD) thickness within the hippocampal CA1 region, indicative of structural synaptic modulation. Further probing into the molecular underpinnings revealed that EE upregulated the expression of PSD95, corroborating its role in enhancing cognitive faculties. Additionally, our investigation into the PGC-1α/FNDC5/BDNF pathway demonstrated that EE intervention elevated the expression of these neurotrophic factors, suggesting a mechanistic link to synaptic and cognitive restoration. In summation, our findings elucidate the neurorestorative potential of EE in a preclinical VaD model, presenting a non-pharmacological intervention that modulates synaptic architecture and activates neuroprotective pathways. The observed correlations between synaptic remodeling and cognitive enhancement underscore the therapeutic relevance of EE in VaD, warranting further investigation for clinical applications., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sleep monitoring devices present potential improvements to address the challenges of sleep disorders. However, systematic evaluations are lacking. This study investigates the functional characteristics of existing sleep monitoring devices in the Chinese market and delves into population preferences., Objective: We aim to summarize the characteristics of mobile health devices with sleep monitoring function in China, analyzing product features and market prices, and collect population preferences for mobile health devices, providing a concrete basis for the ongoing development of mobile health technologies., Methods: Data on 203 sleep devices were gathered from four major mobile shopping platforms (Tmall, JD.com, Pinduoduo, and Suning) using relevant keywords. A two-level variance model was employed to analyzed the link between device features and sales. Additionally, a structured questionnaire assessed public usage and attitudes towards these devices, with 167 responses collected via social networks., Results: Our study found that smart bracelets, which make up 82.6% of sleep monitoring devices, effectively track heart rate, physical activity blood oxygen saturation, sleep duration, and assess sleep quality. Most devices cost under 500 RMB, influencing sales (β   = -1.111 to -3.490, p  < 0.001-.002). Features such as sleep quality assessment (β=0.520, p  = 0.03), measuring physical activity (β=0.464, p  = 0.03) and blood oxygen saturation (β=0.465, p  = 0.02) are significantly associated with higher sales volumes. Usage peaks during and after exercise (41.0%) and during sleep (21.3%), with 60.4% preferring to spend under 500 RMB., Conclusions: The study confirms a strong preference for smart bracelets with health tracking features, particularly for sleep monitoring, at a price point below 500 RMB. These findings highlight the potential of affordable, multifunctional devices to shape the future of smart healthcare, especially through cloud-based enhancements that improve doctor-patient communication., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Background: Stroke is a prevalent neurological disorder globally, often resulting in post-stroke depression (PSD). The cardiometabolic index (CMI) is a novel marker for assessing cardiovascular and metabolic health, but its association with PSD has not been adequately investigated. This study aims to explore the relationship between CMI and PSD, providing a basis for clinical prevention and treatment., Methods: We utilized data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) in this cross-sectional analysis. Multivariable logistic regression and restricted cubic spline (RCS) models were applied to assess the independent and linear relationships between CMI and PSD. To minimize confounding, propensity score matching (PSM) was employed. Subgroup analyses and interaction tests were also conducted to further explore potential effect modifications., Results: A total of 1082 participants were included, with 18.67% diagnosed with PSD. Higher CMI levels were positively associated with PSD in stroke patients. In the fully adjusted model, the association between CMI and PSD remained significant (OR = 1.06; 95% CI 1.01-1.12). RCS analysis indicated a linear relationship between CMI and PSD (nonlinearity P = 0.334). Subgroup analyses showed that this association persisted across different groups (all P for trend > 0.05). After covariate balance through PSM, the positive association between CMI and PSD was further supported., Conclusion: This study demonstrates a positive association between CMI and PSD. CMI may serve as a useful tool for evaluating the risk of depressive symptom in stroke patients, potentially aiding in targeted clinical interventions., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Abstract: Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed., (Copyright © 2025 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Food allergy has become a global food safety issue, and inducing tolerance of the immune system to allergens is seen as an effective way to address this problem. In this study, shrimp ( Penaeus vannamei ) was covalently modified with fucoidan to explore its potential as an oral tolerance inducer. The results showed that this strategy not only had no adverse effect on the growth of mice but also achieved significant immune tolerance induction effects. Specifically, it significantly reduced specific antibody levels, improved vascular permeability and intestinal barrier function, and inhibited mast cell degranulation. Further studies showed that these positive results were related to tolerogenic peptides (SLLKANIQL, GLTEFQAV, GDFPGAFKVF, ALNLNPTLALI, and AALDIDSKPF) produced in shrimp allergens. Moreover, this strategy mainly down-regulated gene expression in exogenous substance metabolic and immune-related signaling pathways, thereby reducing immune response to antigens. Overall, fucoidan-mediated covalent modification promises to be an efficient method for producing oral tolerance inducers.

The multi-petal "Hutou" jasmine (Jasminum sambac var. Trifoliatum) is highly valued for bonsai cultivation and landscape design, however, the aroma profile and mechanisms underlying floral scent formation remain elusive. In this study, we generate a nearly complete telomere-to-telomere (T2T) genome assembly of "Hutou" jasmine (487.45 Mb with contig N50 of 38.93 Mb). Metabolomic profiling unveils that 16 significantly differential volatiles (SDVs) may play a crucial role in the formation of flower aroma. Among them, five scented SDVs, particularly α-farnesene and pentanoic acid 1-ethenyl-1,5-dimethyl-4-hexenyl ester, contribute to the characteristic aroma profile of "Hutou" jasmine flowers. Weighted gene co-expression network analysis (WGCNA) identifies HTWRKY41, HTWRKY53, and HTHSP90 as the hub genes potentially regulating the production of these 16 metabolites. The expression of selected genes and duplication events drive the increased relative content of major sesquiterpenoids in terpenoid biosynthetic pathway. Four structural genes (BEAT3, BSMT1, BPBT2, and BPBT3) are potentially implicated in the emission of downstream key volatile esters (benzyl acetate, methyl benzoate, and benzyl benzoate) in the phenylpropanoids synthesis. Our integrated dataset of genomics, transcriptomics, and metabolomics present here provides a theoretical basis for the practical utilization of fragrance and genetic improvement in horticultural applications of "Hutou" jasmine., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

To describe cervical bone mineral density (BMD) in children and adolescents using Cone-beam Computed Tomography (CBCT) combined with K2HPO4 liquid phantoms. Children and adolescents aged 7-19 years who underwent CBCT for orthodontic treatment in our imaging department between January 2023 and June 2023 were selected. The CT values of the second (C2) and third (C3) cervical vertebrae were measured using the software supplied with the CBCT. K2HPO4 liquid phantoms were prepared according to standard protocols and scanned monthly. Regression equations were established between BMD values and CT values. The BMD values of C2 and C3 were then calculated and subsequently analyzed. A total of 455 children and adolescents participated in the study. The BMD values for females were found to be significantly higher than those for males across all age groups (P < 0.05). When comparing the BMD values between C2 and C3, a statistically significant difference was observed (P < 0.05). Furthermore, there were notable variations in the BMD values of C3 among females across different age groups (P < 0.05). However, no significant differences were detected in the BMD values of C2 overall or in the BMD values of C3 among males across no significant differences were detected across different age groups (P > 0.05). The results of this study provide reference values for BMD of C2 and C3 using CBCT combined with liquid phantoms. These reference values, obtained from healthy individuals, enable the assessment of BMD for systemic bone metabolism, orthodontics, implants, and tooth extraction, providing significant economic and social benefits., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Jinan Stomatological Hospital, Shandong, China. All procedures were explained to patients, the written informed consent was signed by the patients or their parents. And in this study all methods were carried out in accordance with relevant guidelines and regulations., (© 2025. The Author(s).)

Background: Recent studies have highlighted bidirectional signalling between tumours and neurons; however, the interactions between tumours and neurons in response to radio-/chemotherapy remain obscure, which hampers the tumour treatment., Methods: Glioblastoma organoids (GBOs) and primary neuron coculture, targeted metabonomics, RNA pulldown, mass spectrum, co-immunoprecipitation, RNA-sequencing, transcript/protein validations and multi-electrode arrays were performed to analyse neuron-tumour interaction in response to therapy. In vivo validations were conducted in orthotopic mouse models. Diagnostic and prognostic values were evaluated in serum, tissue-microarray as well as TCGA., Results: GBOs recruited and induced pro-tumour-survival senescent neurons upon radiation/chemotherapeutic treatment. Targeted metabonomics revealed that significantly increased tumour-derived prostaglandin E2 (PGE2) induced neuronal senescence phenotype. Screening of enzymes involved in PGE2 synthesis identified prostaglandin E synthase 3 (PTGES3) as the key enzyme responsible for PGE2 upregulation. Biochemical studies revealed that irradiation or chemotherapeutic drug-triggered asparagine endopeptidase (AEP) specifically cleaved eIF4A1 to produce teIF4A1-C, which dissociated from DDX6 and recruited eIF4A3 and PABPN1 to promote the mRNA stability of PTGES3. Elevated PGE2 reciprocally enhanced AEP expression. Inhibiting PGE2 or AEP reduced neuronal senescence and delayed tumour progression. Strikingly, single-cell analysis further showed that expressions of AEP/PTGES3/EIF4A1 in tumour cells were consistent with senescent neuronal CDKN1A in high-neuronal-connectivity glioblastoma. The serum PGE2 concentration was elevated after radiation and higher in resistant glioblastoma patients. High expression of PTGES3 was associated with a poor prognosis., Conclusions: Our study revealed that the AEP/PGE2 feedback loop modulates tumour-induced neuronal senescence upon radio-/chemotherapy and highlight the therapeutic value to improve tumour therapy., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

We developed a unique water droplet templating method to fabricate polymer films with three-dimensionally ordered porous structures. This technique is based on a polymer/solvent/H 2 O ternary system, and the key is to choose a volatile and hydrophobic solvent that is slightly miscible with H 2 O. With the fast evaporation of the solvent, water droplets separate from the casting solution and condense from the air to act as pore templates inside the film and on the surface, respectively. According to this law, nitrocellulose (NC) films were produced from the NC/methyl acetate (MA)/H 2 O system in which the solubility of H 2 O in MA is 8.1 wt %. By modulating the solution concentration (density) from 3% to 9% NC, the distribution of separated water droplets (pores) in the solution can be flexibly controlled from sinking to floating. On the other hand, substantial ordered honeycomb pores, originated from condensed water droplets, distribute uniformly on the surface of NC films. This water droplet templating technique can be extensively applied in various polymer films, providing an effective pathway to designing polymer films with a desirable porous structure and diverse functionalities.

With 0.3 M KCl replacing NaCl, the effect of L-Arg on beef myosin's gel, structure, and aggregation was investigated. L-Arg could enhance hydrogen and ionic bonds, increasing myosin solubility and reducing turbidity. The content of regular secondary structures (β-sheet) increased, and the content of random coil structures decreased significantly ( p < 0.05). The results of dynamic light scattering (DLS) and atomic force microscope (AFM) further demonstrated that L-Arg could improve the uniformity and dispersion of myosin aggregate size and inhibit the aggregation of myosin between the head and the tail. Moreover, as the hydrophobic interaction and disulfide bonds were the main forces, a thermal gel dominated by myosin oligomers and filaments was formed. In the 0.3 M KCl, 0.1 M NaCl, and 0.2 M L-Arg system, the hardness, elasticity, and water holding capacity (WHC) of beef myosin gel were effectively improved, providing a salt reduction reference for beef products.

Vibration characteristics are important reference indicators for reflecting the overall performance of RV reducers. At present, there is no factory testing standard for vibration characteristics applicable to production enterprises in the industry. This study conducted vibration characteristic tests on RV40E reducers at different speed ratios. Through a large number of sample comparisons, suitable vibration characteristic factory testing standards for production enterprises were provided. Detailed on-site inspection standards have been developed based on research and analysis results for defective products such as eccentricity, gear defects, and detection errors. This standard can cover 90% of defect types within the factory. The samples are specific and executable. This study solves the problem of the lack of clear vibration detection standards in the industry. For the first time, such a detailed sample set of internal data within a company has been provided. It has extremely practical engineering application value and provides data reference for the development of RV reducer industry., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The four-drug regimen for heart failure with reduced ejection fraction (HFrEF) significantly reduces the risks of hospitalization and mortality. To identify key adverse drug events (ADEs) warranting attention with this regimen, we conducted a real-world pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) events., Research Design and Methods: We collected ADE reports of the four-drug regimen from FAERS that matched this regimen over a 10-year period. Disproportionality analysis and subgroup analysis were performed using four algorithms. Time-to-onset (TTO) analysis was used to assess the temporal risk patterns of ADE occurrence. Lastly, logistic regression was applied to investigate the relationship-value between patient characteristics and ADEs., Results: A total of 1,237 cases with 6,580 ADE reports were collected. Disproportionality analysis identified the most frequent ADEs as hypotension, acute kidney injury (AKI), and hyperkalemia. TTO analysis revealed a median TTO of 39 days for all important medical events, and the median TTO for AKI was 28 days, both fitting an early failure curve., Conclusion: In the comprehensive management of HFrEF with the four-drug regimen, in addition to routine monitoring of ADEs such as hypotension and hyperalemia, early-onset AKI should be a particular focus.