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Baoyu Chen,1,* Qi Wang,1,* Chaobo Bai,1 Jing Chen,1 Danhua Zhao,1 Yuan Li,1 Junyi Chen,1 Xintong Guo,1 Jinjin Wang,1 Hongguang Chen,1 Xiaoxing Lai,2 Qiaoqin Wan,3 Zhiwen Wang,3 Nan Hu,4 Bing-Wei Zhang,4 Xuqiao Chen,5 Tao Ma,6 Junliang Yuan1 1Department of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, 100191, People’s Republic of China; 2Department of Health Care, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3School of Nursing, Peking University, Beijing, 100191, People’s Republic of China; 4Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 5Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; 6Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA*These authors contributed equally to this workCorrespondence: Junliang Yuan, Department of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), No. 51 hua Yuan Bei Road, Haidian District, Beijing, 100191, People’s Republic of China, Email junliangyuan@bjmu.edu.cnBackground: Behavioral and psychological symptoms of dementia (BPSD), as neuropsychiatric manifestations within dementia, constitute core features of dementia. However, there remains a gap in understanding the recognition of BPSD in China. Our current study was to explore the clinical awareness and treatment approaches for BPSD in China, focusing especially on the perspectives of neurologists and psychiatrists.Methods: A multicenter national survey was designed and a semi-structured questionnaire was distributed to healthcare professionals including doctors and nurses across all provinces of China. The questionnaire incorporated either closed (yes/no) and multiple-choice questions. The questions centered on the following areas: the perceived global frequency and relevance of BPSD; the assessment tools employed for evaluating BPSD; pharmacological approaches for addressing psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disorders; drug-related side effects; non-pharmacological treatment strategies. The anonymity of questionnaire responses was maintained to encourage participants to candidly express their viewpoints.Results: The majorities of respondents recognized the importance of BPSD. There were apparent differences in the perception of BPSD between neurologists and psychiatrists, encompassing variances in symptoms recognition, diagnostic approaches, and treatment strategies. A notable high percentage of neurology (27.8%) and psychiatry staff (23.6%) would not choose non-pharmacological interventions. Meanwhile, antipsychotics was overused in China. For aggression and agitation, more than half of neurologist and psychiatrist preferred antipsychotics. For psychosis, more than 80% of doctors chose antipsychotics. Nearly one-third of the medical staff expressed a preference for traditional Chinese medicine including ginkgo biloba extract.Conclusion: In summary, this study in China has shed light on the features related to perception, recognition, management, treatment options, and observed side effects associated with BPSD. Our findings have the potential to significantly enhance the understanding of BPSD characteristics among medical practitioners and offering valuable insights into improved management and treatment strategies of neuropsychic symptoms of dementia in China.Keywords: dementia, BPSD (behavioral and psychological symptoms of dementia), BPSD management, psychosis

Bai-Wen Zhang,1 Hao Dong,1 Zhe Wu,1 Xi Jiang,2 Wei Zou3 1Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 2Jinzhou Medical University, Jinzhou, 121001, People’s Republic of China; 3The Third Department of Acupuncture and Moxibustion, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of ChinaCorrespondence: Wei Zou, The Third Department of Acupuncture and Moxibustion, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China, Tel +86 0451-82161746, Email weizouzw@126.comAbstract: Neuralgia is a frequently occurring condition that causes chronic pain and burdens both patients and their families. Earlier research indicated that anti-inflammatory treatment, which was primarily utilized to address conditions like neuralgia, resulted in positive outcomes. However, recent years have witnessed the emergence of various novel mechanisms associated with pain-related disorders. This review provides a concise overview of the inflammatory mechanisms involved in neuralgia. It also examines recent advancements in research, exploring the influence of ion channels and synaptic proteins on neuralgia and its complications. Additionally, the interactions between these mechanisms are discussed with the aim of suggesting innovative therapeutic approaches and research directions for the management of neuralgia.Keywords: neuralgia, inflammatory mechanisms, innovative therapeutic approaches

Tao Sun,1– 4 Bo-Wen Zhang,1– 4 Rui Xiong,1– 4 Wen-Tian Zhou,1– 4 Jing-Jing Qiu5 1Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Jiangxi Clinical Research Center for Ophthalmic Disease, Nanchang City, Jiangxi Province, 330006, People’s Republic of China; 3Jiangxi Research Institute of Ophthalmology and Visual Science, Nanchang City, Jiangxi Province, 330006, People’s Republic of China; 4Jiangxi Provincial Key Laboratory for Ophthalmology, Nanchang City, Jiangxi Province, 330006, People’s Republic of China; 5Department of Ophthalmology of The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, People’s Republic of ChinaCorrespondence: Jing-Jing Qiu, Department of Ophthalmology of The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang City, Jiangxi Province, 330006, People’s Republic of China, Tel +86 15070001118, Email jingjingqiuoph@outlook.comObjective: To observe the efficacy and prognosis of low-temperature plasma ablation + drug therapy in the treatment of fungal corneal ulcers.Methods: The present paper presents a retrospective clinical study with a subject base of 34 eyes. Patients with a fungal corneal ulcer who visited the Affiliated Eye Hospital of Nanchang University between August 2019 and December 2021 were selected as the study participants. They were found to have highly reflective fungal hyphae in the corneal stroma layer via confocal microscope examination, which were revealed to be positive on etiology examination, with the ulcer and infiltration depths ≤ 1/2 of the corneal thickness. The efficacy and prognosis were observed after treatment with low-temperature plasma ablation + drug therapy.Results: A total of 34 cases (34 eyes) had clinical manifestations of corneal infiltration and corneal ulcer formation, with a corneal lesion diameter of 1.31– 8.64 mm (average = 4.79 ± 2.03 mm). The average healing time of corneal ulcers was 6.2 ± 1.7 days. Among a total of 34 cases (34 eyes) in patients with fungal keratitis, the infection was controlled and the ulcers gradually healed after treatment with low-temperature plasma system + drug therapy in a total of 30 cases (30 eyes, 88%). A total of three cases (3 eyes, 9%) exhibited no clear improvement after the treatment, and the patients underwent conjunctival flap covering surgery. One case (one eye, 3%) exhibited no clear improvement after further treatment, with the patient experiencing corneal perforation and ultimately undergoing penetrating keratoplasty.Conclusion: Low-temperature plasma ablation + drug therapy can effectively control the progression of fungal keratitis infection, as well as significantly shorten the ulcer healing time, and is, therefore, an effective method.Keywords: low-temperature plasma, keratitis, fungal infection, antimicrobial therapy, ophthalmic surgery

Bo-Wen Zhang,1 Ni-Hong Pang,2 Ren-Ai Xu,1 Gao-Er Qu,3 Cong-Rong Tang1 1Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Pharmacy, The Third Affiliated Hospital of Shanghai University (Wenzhou People’s Hospital), Wenzhou, People’s Republic of China; 3Department of Pharmacy, Health Service Community of Yueqing Third People’s Hospital, Wenzhou, People’s Republic of ChinaCorrespondence: Cong-Rong Tang, Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 13867722688, Email 13867722688@163.comObjective: To evaluate the effect of axitinib on buspirone metabolism in vitro and in vivo.Methods: A microsome incubation assay was performed to study the effect and mechanism of axitinib on buspirone metabolizing. In vivo, buspirone was administered with or without axitinib to Sprague–Dawley rats. Plasma samples were collected and subjected to ultra-performance liquid chromatography–tandem mass spectrometry.Results: In both human liver microsomes (HLMs) and rat liver microsomes (RLMs), axitinib (100 μM) decreased buspirone hydroxylation and N-dealkylation by > 85%. Axitinib inhibited buspirone hydroxylation and N-dealkylation, with an IC50 of 15.76 and 9.74 for RLMs, and 10.63 and 9.902 for HLMs. Axitinib showed noncompetitive inhibition of both 6′-hydroxylation and N-dealkylation. Moreover, coadministration of axitinib and buspirone led to an increase in the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of buspirone by 4.3- and 5.3-fold, respectively, compared with the control group.Conclusion: Axitinib inhibited buspirone metabolism in vivo and in vitro, which increases the risk of the side effects of buspirone in the clinic. When coadministered with axitinib, a lower dosage of buspirone should be defined to avoid a toxic response. Axitinib is suspected to function as an inhibitor of CYP3A4.Keywords: buspirone, axitinib, drug-drug interactions, liver microsomes, noncompetitive inhibition

Predictions made in Albacete et al. [Int. J. Mod. Phys. E 22 (2013) 1330007] prior to the LHC p+Pb run at sNN = 5 TeV are compared to currently available data. Some predictions shown here have been updated by including the same experimental cuts as the data. Some additional predictions are also presented, especially for quarkonia, that were provided to the experiments before the data were made public but were too late for the original publication.

Heavy-ion collisions at very high colliding energies are expected to produce a quark-gluon plasma (QGP) at the highest temperature obtainable in a laboratory setting. Experimental studies of these reactions can provide an unprecedented range of information on properties of the QGP at high temperatures. We report theoretical investigations of the physics perspectives of heavy-ion collisions at a future high-energy collider. These include initial parton production, collective expansion of the dense medium, jet quenching, heavy-quark transport, dissociation and regeneration of quarkonia, photon and dilepton production. We illustrate the potential of future experimental studies of the initial particle production and formation of QGP at the highest temperature to provide constraints on properties of strongly interaction matter.

Hai-Yang Wang,1 Xiao-Xia Zhang,1 Cui-Ping Si,1 Yang Xu,1 Qian Liu,1 He-Tao Bian,1 Bing-Wei Zhang,2 Xue-Lin Li,3 Zhong-Rui Yan1 1Department of Neurology, Jining No 1 People’s Hospital, Jining, Shandong Province, China; 2Department of Neurology and Psychiatry, First Affiliate Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 3Department of Intensive Care Unit, Jining No 1 People’s Hospital, Jining, Shandong Province, China Objective: Impairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas.Methods: We performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta-regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified.Results: Compared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger’s tests further confirmed these findings. Conclusions: Impaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder. Keywords: anxiety disorder, emotion regulation, cognitive reappraisal, fMRI, prefrontoparietal network, signed differential mapping

Jiayang He,1 Ping Fang,2 Xiang Zheng,2 Chenchen Wang,2 Tenghui Liu,2 Bowen Zhang,2 Jian Wen,2 Ren-ai Xu3 1Department of Pharmacy, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China; 2Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Aim: The aim of this study was to study the effect of celecoxib on agomelatine metabolism in vitro and in vivo. Methods: Ten healthy male Sprague–Dawley rats were randomly divided into 2 groups: Group A (control group) and Group B (30 mg/kg celecoxib). Then a single dose of 20 mg/kg agomelatine was administered orally 30 min after administration of celecoxib. In an in vitro study, celecoxib with a series of concentrations was added to an incubation mixture containing recombinant human CYP2C9, human or rat liver microsomes to determine the half-maximal inhibitory concentration on the metabolism of agomelatine. Moreover, a mechanism study was performed to determine the inhibitory effect of celecoxib on CYP2C9. Results: The results showed that a single dose of 30 mg/kg celecoxib significantly increased the area under the concentration-time curve and maximum concentration of agomelatine. In addition, celecoxib inhibited the metabolism of agomelatine in the in vitro studies, which was determined to be by a competitive mechanism on CYP2C9. Those results indicated that celecoxib has an inhibitory effect on the metabolism of agomelatine both in vivo and in vitro. Conclusion: Thus, more attention should be paid when celecoxib is administered combined with agomelatine. Keywords: agomelatine, liver microsomes, pharmacokinetics, celecoxib, CYP2C9

Hai-Yang Wang,1 Bing-Wei Zhang,2 Xue-Lin Li31Department of Neurology, Jining No. 1 People’s Hospital, Jining, Shandong Province, People’s Republic of China; 2Department of Neurology and Psychiatry, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 3Department of Intensive Care Unit, Jining No. 1 People’s Hospital, Jining, Shandong Province, People’s Republic of China Following our recently published article1 in Neuropsychiatric Disease and Treatment, many readers have commented that the effects of comorbid depression cannot be ruled out as a factor in our results, since anxiety disorders and major depression are heterogeneous disorders. We would like to respond to the points made. View the original paper by Wang and colleagues

Objective: The objective of this study is to assess the therapeutic efficacy of low-temperature plasma ablation (LTP) combined with drug treatment in the treatment of fungal keratitis (FK) caused by various pathogens, thereby establishing a clinical foundation for the use of LTP in treating FK., Methods: A retrospective study was performed, including 76 patients (76 eyes) with FK diagnosed at the Affiliated Eye Hospital of Nanchang University. The patients were categorized into the Fusarium group, Alternaria group, Aspergillus group, and other genus groups based on positive results from biological cultures. Key clinical parameters, including best-corrected visual acuity (BCVA), maximum ulcer lesion diameter, and healing grades, were assessed and compared at baseline (pre-treatment), on postoperative day 3, and at postoperative week 3., Results: The study demonstrated that the BCVA (LogMAR) of all patients revealed no significant differences at postoperative day 3 (F = 2.54, p = 0.063) and week 3 (F = 1.86, p = 0.143). Although BCVA improved to varying degrees compared to preoperative levels, the changes were not statistically significant (p > 0.05). After treatment with LTP combined with pharmacotherapy across all four groups, an average of 53 patients (69.74%) achieved grade I healing, with the group effect being nonsignificant (F = 2.85, p = 0.071), while the effect of time post-treatment was significant (F = 67.85, p < 0.001). Additionally, the corneal scar diameter at postoperative week 3 was significantly smaller compared to the preoperative lesion diameter (p < 0.05). Multiple comparisons revealed significant differences in scar diameter among patients with grade I healing at postoperative week 3 (F = 3.48, p = 0.023), with notable differences observed between the Alternaria and Fusarium groups (p = 0.017). The average rate of grade III healing, defined by the occurrence of corneal perforation and/or the need for therapeutic penetrating keratoplasty, was 7.89%., Conclusion: Low-temperature plasma ablation demonstrates effective therapeutic outcomes for FK caused by various pathogens that are unresponsive to pharmacological treatments, with no significant complications., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: This study was conducted with approval from the Ethics Committee of The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University (No.YLP201810003). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants. Informed consent for publication: All participants signed a document of informed consent., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Anthocyanin accumulation in leaves or flowers mitigates photooxidation damage from Reactive Oxygen Species (ROS) and functions in plant/animal interactions. Among the most conspicuously anthocyanin-accumulating tissues are stigmas, especially in wind-pollinated trees. In the walnut genus (Juglans), yellow stigmas are ancestral, but a few species have dark red stigmas. We have used a natural F1 hybrid resulting from crosses between yellow-stigma and red-stigma species to investigate the genetic basis of the red stigmas. We found that a Copia transposable element (TE) insertion in the ubiquitin-protein ligase gene MIEL1 suppresses its expression in stigmas through RNA-directed DNA methylation and has gone to fixation in red-stigma species. A younger Gypsy TE insertion fully inhibits MIEL1 expression, but is not fixed, explaining the color segregation in hybrid populations. Based on reference genomes and whole-genome sequencing data representing 20 of the 22 species of Juglans, we traced the evolution of MIEL1, finding the insertions in all consistently-red-stigma species. Red stigmas had lower levels of ROS than yellow stigmas, and population-genetic data reveal strong positive selection on the TE-bearing MIEL1 allele. In combination, these results suggest that anthocyanin-accumulating stigma tissues support pollen germination and growth by protecting cells from ROS., (© The Author(s) 2025. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Metal halide perovskites emerge as promising semiconductors for optoelectronic devices due to ease of fabrication, attractive photophysical properties, their low cost, highly tunable material properties, and high performance. High-quality thin films of metal halide perovskites are the basis of most of these applications including solar cells, light-emitting diodes, photodetectors, and electronic memristors. A typical fabrication method for perovskite thin films is the solution method, which has several limitations in device reproducibility, adverse environmental impact, and utilization of raw materials. Thermal evaporation holds great promise in addressing these bottlenecks in fabricating high-quality halide perovskite thin films. It also has high compatibility with mass-production platforms that are well-established in industries. This review first introduces the basics of the thermal evaporation method with a particular focus on the critical parameters influencing the thin film deposition. The research progress of the fabrication of metal halide perovskite thin films is further summarized by different thermal evaporation approaches and their applications in solar cells and other optoelectronic devices. Finally, research challenges and future opportunities for both fundamental research and commercialization are discussed., (© 2024 The Authors. Small Methods published by Wiley‐VCH GmbH.)

Ethnopharmacological Relevance: Cattle bile Arisaema (CBA) and Pig bile Arisaema (PBA) are both processed products fermented from Arisaema erubescens (Wall.) Schott and animal bile, which are recorded in China Pharmacopoeia. Traditionally, bile Arisaema was often used for clearing heat and eliminating phlegm, calming wind and calming panic. Modern pharmacological researches suggest that both two drugs exert an antipyretic effect, while there is lack of the systematical and comparative evidence on underlying mechanism., Aim of the Study: To comprehensively clarify the differences and underlying mechanisms of antipyretic effect of the two drugs., Methods: In this study, an accurate and reliable detection method based on ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ MS) for comparing the content difference of bile acids from the two drugs was successfully established and applied. Besides, a dry yeast-induced fever rat model was established, and rectal temperature and content of pyrogenic cytokines were conducted to evaluate the antipyretic effect of CBA and PBA. Serum and hypothalamus untargeted metabolomics analysis based on ultra-performance liquid chromatography coupled with quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS/MS) technology were performed for elucidating the changes of metabolic profile., Results: The results indicated that CBA and PBA both exerted a significantly antipyretic effect, but CBA showed the characteristic of quicker onset and longer duration than that of PBA. The ELISA and western blotting analysis exhibited that the underlying antipyretic mechanism of the two drugs was closely associated with inhibiting inflammation through regulating TLR4/NF-κB signaling pathway. Moreover, the metabolism pathway analysis revealed that lipid metabolism and amino acid metabolism were greatly disturbed, which showed a certain correlation with antipyretic effect of two drugs., Conclusion: Collectively, our results delineate a potential mechanism of two different bile Arisaemas against febrile via regulating metabolic disorders and targeting inhibition of inflammation for the improvement of fever symptom of the body. Notably, our current study suggested that CBA might be a better choice for suppressing fever clinically., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As the name implies, structure-based drug design requires confidence in the holo complex structure. The ability to clarify which protein conformation to use when ambiguity arises would be incredibly useful. We present a large scale validation of the computational method Protein Reorganization Free Energy Perturbation (PReorg-FEP) and demonstrate its quantitative accuracy in selecting the correct protein conformation among candidate models in apo or ligand induced states for 14 different systems. These candidate conformations are pulled from various drug discovery related campaigns: cryptic conformations induced by novel hits in lead identification, binding site rearrangement during lead optimization, and conflicting structural biology models. We also show an example of a pH-dependent conformational change, relevant to protein design.

Background: Elevated blood pressure (BP) in childhood is associated with adult hypertension and arterial stiffness. However, the effect of long-term time in target range (TTR) for BP since childhood on the risk of arterial stiffness in midlife remains unclear., Objectives: The purpose of this study was to determine the independent association of TTR for systolic blood pressure (SBP) from childhood to midlife with arterial stiffness in adulthood., Methods: This study used data from the ongoing cohort of the Hanzhong Adolescent Hypertension Study. SBP-TTR was assessed over 36 years, with the target ranges of SBP defined as the 90th to 95th percentile of SBP for age, sex, and height in childhood, and 110 to 130 mm Hg in adulthood. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1,400 cm/s., Results: Of the total 1,959 participants, 55.5% (1,088 of 1,959) were men, and the mean age was 49 years. The risk of arterial stiffness exhibited a gradual decrease with increasing SBP-TTR over the 36-year follow-up. Compared with the participants in the lowest quartile of SBP-TTR from childhood to midlife, those in the highest quartile showed significantly reduced arterial stiffness risk in midlife. This association persisted even after adjusting for mean SBP and SBP variability. Furthermore, men in the highest quartile of SBP-TTR demonstrated a markedly lower arterial stiffness risk than those in the lowest quartile, whereas this effect was not observed in women., Conclusions: Higher long-term SBP-TTR from childhood to midlife is associated with a reduced risk of arterial stiffness in midlife, regardless of the mean SBP or SBP variability., Competing Interests: This work was financially supported by the Science and Technology Innovation 2030-“Cancer, Cardiovascular and Cerebrovascular, Respiratory and Metabolic Diseases Prevention and Treatment Research” Major Project (2023ZD0503900, 2023ZD0503901); National Natural Science Foundation of China No. 82470457 (to Dr Yang Wang), 82070437 (to Dr Mu), and 82070549 (to Dr Li); the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AFCRF-2022-002, XJTU1AF-CRF-2023-004, and XJTU1AF-CRF-2024-003); Xi'an Science and Technology Program Project (24YXYJ0141); Fundamental Research Funds for the Central Universities (No. xzy012023113); the Key R&D Projects in Shaanxi Province (No. 2023-ZDLSF-50); and the International Joint Research Center for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Purpose: As a globally popular physical activity, swimming also presents challenges due to its inherent aquatic risks. Therefore, the cultivation of swimming competence emerges as a crucial strategy in preventing drowning incidents. This study aimed to develop and validate the Swimming Competence Assessment Scale in College Students (SCAS) to address the gap in structured swimming proficiency evaluation, essential for drowning prevention and water safety education., Methods: The research involved 160 full-time second-year college students, including 92 males (age: 20.48 ± 0.51 ) and 68 females (age: 20.65 ± 0.70 ), who underwent two swimming ability assessments. The evaluation covered fundamental swimming skills, including entry, submersion, rotation, prone and supine swimming, floating, and exiting the water., Results: Exploratory Factor Analysis revealed goodness-of-fit for a two-factor model swimming coherent motion and swimming stable posture, which supported the construct validity. The inter-factor construct reliability (CR = 0.866, CR = 0.835) and the square root of Average Variance Extracted ( A V E 1  = 0.754, A V E 1  = 0.848) exceeded the standards for supporting convergent and discriminant validity. The inter-rater reliability (IRR = 0.542) and Cronbach's alpha ( α  = 0.840, α = 0.827) coefficient results have demonstrated the internal reliability of the SACS. Positive correlation between SCAS scores at pre-test and post-test provided evidence for SCAS's test-retest reliability (TRR = 0.825, TRR = 0.758)., Conclusion: SCAS is a valid and reliable assessment scale. It assesses college students' swimming competence through two aspects: Swimming Coherent Motion and Swimming Stable Posture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Chen, Ning, Zhang and Shen.)

Background: Emotional dysregulation, particularly unconscious catastrophic cognitions, plays a pivotal role in the genesis of panic disorder (PD). However, no studies have yet applied the percentage of amplitude fluctuation (PerAF) metric in resting-state functional magnetic resonance imaging to examine spontaneous neural functioning and its relation to catastrophic cognitions in PD., Objectives: To explore the interplay between resting-state neural activity, functional connectivity (FC), and unconscious emotion regulation in individuals with PD., Design: Cross-sectional study., Methods: The study encompassed 51 participants, including 26 PD patients and 25 healthy individuals. The PerAF algorithm was employed to explore the local spontaneous neural activity in PD. Regions exhibiting aberrant spontaneous neural activity were used as seed points for whole-brain FC analysis. Correlations were utilized to examine associations between local neural activity patterns and neurocognitive assessments in PD., Results: The study revealed that compared to healthy individuals, PD patients exhibited elevated PerAF values in key emotion-regulation-related brain regions, including the ventromedial prefrontal cortex (vmPFC), striatum, amygdala, dorsomedial prefrontal cortex (dmPFC), and cerebellum. In addition, the resting-state FC between vmPFC and precuneus, as well as between the cerebellum and precuneus, was weakened in PD patients. Furthermore, positive associations were noted between PerAF measurements of vmPFC and amygdala and catastrophizing scores., Conclusion: PD involves regional and network-level alterations in resting-state brain activity. The fronto-striatal-limbic circuits play a critical role in catastrophic-style emotion regulation in PD patients. Reduced FC within the default mode network and cerebellum-default mode network may signify a coordination anomaly in introspection and cognitive activities in PD. These findings complement the model of implicit emotion regulation in PD and suggest potential intervention targets., (© The Author(s), 2024.)

Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured&#95;bacterium&#95;o&#95;Mollicutes&#95;RF39, Rikenellaceae&#95;RC9&#95;gut&#95;group, and negatively correlated with Bacillus , Marvinbryantia , Roseburia , Angelakisella , Enterorhabdus , Bacteroides , Muribaculum , and genera of uncultured&#95;bacterium&#95;f&#95;Eggerthellaceae, uncultured&#95;bacterium&#95;f&#95;Xanthobacteraceae, Prevotellaceae&#95;UCG-001, uncultured&#95;bacterium&#95;f&#95;Erysipelotrichaceae, uncul-tured&#95;bacterium&#95;f&#95;Lachnospiraceae, uncultured&#95;bacterium&#95;f&#95;Ruminococcaceae, Eubacterium&#95;coprostanoligenes&#95;group, Ruminococcaceae&#95;UCG-005, and uncultured&#95;bacterium&#95;f&#95;Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Zhang, Zeng, Ma, Wang, Yuan, Xu, Geng, Fan, Gao, Arshad, Gao, Zhao, Liu and Mu.)

The heat shock transcription factor (HSF) family is one of the most widely studied transcription factor families in plants; HSFs can participate in the response to various stressors, such as heat stress, high salt, and drought stress. Based on garlic transcriptome data, we screened and identified 22 garlic HSFs. The HSF proteins of garlic and Arabidopsis can be divided into three (A, B, C) subfamilies. The phylogenetic relationship, chromosome localization, sequence characteristics, conserved motifs, and promoter analysis of the HSF family were analyzed through bioinformatics methods. RT-qPCR analysis showed that the nine selected genes had different degrees of response to heat stress. In addition, we isolated and identified a class B HSF gene, AsHSFB1, from garlic variety 'Xusuan No.6'. Subsequently, the AsHSFB1 gene was overexpressed in Arabidopsis thaliana. Under heat stress, the germination rate and growth of wild-type plants were better than that of transgenic plants. Moreover, after heat treatment, the contents of peroxidase, catalase, and chlorophyll a and b of transgenic plants were lower, but the contents of malondialdehyde (MDA) and leaf conductivity were higher. Nitroblue tetrazolium (NBT) staining showed that the stained area of transgenic plant leaves was larger than that of the wild type. Further studies showed that AsHSFB1 overexpression inhibited the expression of related reverse resistance genes. These results indicate that AsHSFB1 might play a negative regulatory role in garlic resistance under high stress. Altogether, these findings provide valuable data for revealing the function of HSF genes and lay a foundation for the subsequent selection of heat-resistant garlic varieties., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. The sampling of plant material was performed in compliance with institutional guidelines. The research conducted in this study required neither approval from an ethics committee, nor did it involve any human or animal subjects. The use of the garlic cultivar ‘Xusuan NO.6’ plants in this experiment was authorized by the Jiangsu Provincial Department of Agriculture and Rural Affairs. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In recent years, nanomaterials have been widely used in the biomedical field. The biphenylene network is a highly promising planar carbon nanomaterial. To better explore its biomedical applications, we need to understand the biological effects of the biphenylene network. To investigate the biological effects of the novel nanomaterial biphenylene network, we used molecular dynamics simulations to study the interactions of the novel planar carbon nanomaterial biphenylene network with α-helical and β-sheet proteins. We found that both types of proteins adsorb flatly on the surface of the biphenylene network; the strong van der Waals interaction is the main adsorption force, while π-π stacking also provides an auxiliary force for the adsorption. When the HP35 protein whose secondary structure is an α-helix was adsorbed on biphenylene network, the entire structure of α-helix 2 was disrupted and α-helix 3 partly recovered its helical structure after being disrupted. In contrast to the β-sheet YAP65 protein, only part of the structure of β-sheet 1 was disrupted. Therefore, the biocompatibility of the biphenylene network with the β-sheet YAP65 protein is better than that of the α-helical HP35 protein, which may be due to the different surface curvature of the protein's secondary structure. Our research promotes the application of the biphenylene network in biomedicine and provides a theoretical basis and experimental direction for practical experiments.

The study aimed to explore the effect and mechanism of resistance exercise (RE) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) mice. Six 8-week-old male m/m mice were used as control (Con) group, and db/db mice of the matched age were randomly divided into model control (db/db) group and db+RE group, with 6 mice in each group. The db+RE group was given 8 weeks of resistance climbing ladder exercise intervention. The fasting blood glucose and body weight of the mice were measured weekly. After the intervention, the spatial learning and memory of the mice were detected by Morris water maze, and the neuronal damage in the hippocampus of the mice was detected by Nissl staining. The protein expression levels of PSD93, PSD95, BDNF, CREB, p-CREB, IL-6, IL-1β, TNF-α, Iba-1, iNOS, CD206, Arg1, triggering receptor expressed on myeloid cells 2 (TREM2), NF-κB, p-STAT3, and STAT3 were detected by Western blot. The mRNA expression levels of inflammatory factors and TREM2 in hippocampus were evaluated by qRT-PCR, and the expression and localization of Iba-1, CD206, CD86, and TREM2 were determined by immunofluorescence staining. The results showed that the spatial learning and memory of the db/db group were significantly declined, the neurons in the hippocampus were damaged, the protein levels of PSD93, PSD95, BDNF, CD206, Arg1, TREM2 and the ratio of p-CREB/CREB were significantly down-regulated, the mRNA and protein expression levels of IL-6, IL-1β and TNF-α were significantly up-regulated, and the protein levels of iNOS, Iba-1, NF-κB and the ratio of p-STAT3/STAT3 were significantly increased compared with the Con group. However, the 8-week RE improved the spatial learning and memory of db/db mice, alleviated the damage of hippocampal neurons, promoted the polarization of M2 microglia, and inhibited the neuroinflammation. The above results suggest that RE can improve cognitive dysfunction in T2DM mice, and its mechanism may be related to regulating microglia polarization via TREM2/NF-κB/STAT3 signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-β1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/β-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Material design is essential for the development and preparation of new materials. In this paper, a new two-dimensional heterostructure material (B@Si) consisting of boronene and silicene is designed and used as an anode material for lithium-ion batteries in order to improve the performance of lithium-ion batteries, and the structural properties, stability, electronic properties, and performance as an anode material for lithium-ion batteries are systematically investigated by first-principle calculations of the B@Si heterostructure. The results show that the B@Si heterostructure is energetically, thermodynamically and dynamically stable, and although the Dirac cone in the energy band structure of silicene disappears after the formation of the heterojunction, the overall electrical conductivity of the material improves considerably and the electron transport rate is faster. Due to the synergistic effect, Li has more stable adsorption sites and lower diffusion barriers than boronene and silicene in the B@Si heterostructure, higher theoretical specific capacity (1208 mAhg -1 ), and stronger mechanical properties (C 11  = 296.6 N/m, C 22  = 142.8 N/m). The volume expansion in the fully lithiated state is also only 8 %. These advantages indicate that B@Si heterostructures are good potential anode materials for high-performance Li-ion batteries., Competing Interests: All authors declare no conflict of interest in this manuscript., (© 2024 The Authors.)

Embryonic stem cells (ESCs), with abilities of infinite proliferation (self-renewal) and to differentiate into distinct cell types (pluripotency), show attenuated inflammatory response against cytokines or pathogens, which is recognized as a unique characteristic of ESCs compared with somatic cells. However, the underlying molecular mechanisms remain unclear, and whether the attenuated inflammatory state is involved in ESC differentiation is completely unknown. Our recent study demonstrated that macroautophagy/autophagy-related protein ATG5 inhibits the inflammatory response of mouse ESCs (MmESCs) by promoting the degradation of BTRC/β-TrCP1 and further the downregulation of NFKB/NF-κB signaling. In addition, maintenance of an attenuated inflammation status in MmESCs is required for their differentiation. In conclusion, ATG5 is a key regulator for the regulation of inflammatory response and differentiation of MmESCs.

In pursuing cheap and effective oxygen reduction catalysts, the Fe/N/C system emerges as a promising candidate. Nevertheless, the structural transformations of starting materials into Fe- and N-doped carbon catalysts remains poorly characterized under pyrolytic conditions. Here, we explore the evolution of Fe species and track the formation of Fe-N 4 site development by employing diverse in-situ diagnostic techniques. In-situ heating microscopy reveals the initial formation of FeO x nanoparticles and subsequent internal migration within the carbon matrix, which stops once FeO x is fully reduced. The migration and decomposition of nanoparticles then leads to carbon layer reconstruction. Experimental and theoretical analysis reveals size-dependent behavior of FeO x where nanoparticles below 7 nm readily release Fe atoms to form Fe-N 4 while nanoparticles with sizes >10 nm tend to coalesce and impede Fe-N 4 site formation. The work visualizes the pyrolysis process of Fe/N/C materials, providing theoretical guidance for the rational design of catalysts., (© 2024. The Author(s).)

The SBP-box gene significantly influences plant growth, development, and stress responses, yet its function in pepper plants during drought stress remains unexplored. Using virus-induced gene silencing and overexpression strategies, we examined the role of CaSBP13 during drought stress in plants. The results revealed that the expression of CaSBP13 can be induced by drought stress. Silencing of CaSBP13 in pepper notably boosted drought resistance, as evident by decreased active oxygen levels. Furthermore, the water loss rate, relative electrical conductivity, malondialdehyde content, and stomatal density were reduced in CaSBP13-silenced plants compared to controls. In contrast, CaSBP13 overexpression in Nicotiana benthamiana decreased drought tolerance with elevated reactive oxygen levels and stomatal density. Additionally, ABA signaling pathway genes ( CaPP2C , CaAREB ) exhibited reduced expression levels in CaSBP13-silenced plants post drought stress, as compared to control plants. On the contrary, CaPYL9 and CaSNRK2.4 showed heightened expression in CaSBP13-sienced plants under the same conditions. However, a converse trend for NbAREB , NbSNRK2.4 , and NbPYL9 was observed post-four day drought in CaSBP13-overexpression plants. These findings suggest that CaSBP13 negatively regulates drought tolerance in pepper, potentially via ROS and ABA signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang and Zhang.)

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms., (© 2024. The Author(s).)

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M ( 1 ) and N ( 2 ), along with three known ones ( 3 - 5 ). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1 - 4 showed middle cytotoxicity against MCF-7 cells with IC 50 values range of 68.1 ∼ 87.32 μM. Compounds 1 - 5 displayed obvious antioxidant activity with the IC 50 values range of 0.86 ∼ 5.78 mg/mL.

Co-immunoprecipitation (coIP) is an experimental technique to study protein-protein interactions (PPIs). However, single-step coIP can only be used to identify the interaction between two proteins and does not solve the interaction testing of ternary complexes. Here, we present a protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step coIP approach. We describe steps for cell culture and transfection, elution of target proteins, and two-step coIP including western blot analyses. For complete details on the use and execution of this protocol, please refer to Li et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes., Methods and Results: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets., Conclusions: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals., (© 2024. The Author(s).)

Background: Emotion regulation deficits, particularly in cognitive reappraisal, are crucial in depression and anxiety. However, research on the neural mechanisms of implicit emotion regulation is lacking, and it remains unclear whether these mechanisms are shared or distinct between the two disorders., Methods: We investigated the neural mechanisms of implicit cognitive reappraisal in 28 individuals with major depressive disorder (MDD), 25 with generalized anxiety disorder (GAD), and 30 healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). Participants completed an implicit cognitive reappraisal task and underwent neuropsychological and clinical assessments., Results: We found that MDD patients reported higher levels of rumination and lower utilization of cognitive reappraisal, while GAD patients reported reduced use of perspective-taking. Notably, both MDD and GAD patients exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared to HC participants during implicit cognitive reappraisal. Specifically, inadequate OFC activation was observed in MDD patients, while GAD patients demonstrated OFC deactivation during the task. Furthermore, DLPFC activation showed a negative correlation with depression severity in MDD patients, while OFC activation was positively correlated with perspective-taking in GAD patients., Limitations: fNIRS has limited depth and spatial resolution., Conclusion: Our fNIRS study is the first to reveal shared and distinct neurobiological profiles of depression and anxiety in implicit emotion regulation. These findings underscore the significance of reduced DLPFC/OFC activation in emotion regulation impairment and highlight unique OFC activation patterns in these disorders. These insights have potential implications for developing cognitive-behavioral therapy and transcranial magnetic stimulation as treatment approaches., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To explore the clinical effects of early rehabilitation treatment after repair surgery of skin and soft tissue defects accompanied by extensor tendon injury on the back of hand. Methods: This study was a retrospective non-randomized controlled study. From February 2015 to February 2023, 24 patients (15 males and 9 females, aged 12-55 years) with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand, who met the inclusion criteria and were repaired with flap transplantation and tendon grafting or tendon anastomosis, were admitted to the First Affiliated Hospital of Air Force Medical University. According to different intervention time for postoperative rehabilitation treatment of patients, the patients were divided into conventional rehabilitation group and early rehabilitation group, with 12 cases in each group. Patients in early rehabilitation group received rehabilitation treatment immediately after surgery under the rehabilitation guidance of specialized rehabilitation physicians based on the characteristics of different postoperative periods. Patients in conventional rehabilitation group began rehabilitation treatment from the third week after surgery, and their rehabilitation treatment was the same as that of patients in early rehabilitation group from the second week after surgery. The patients in 2 groups were treated in the hospital until the sixth week after surgery. The occurrence of flap vascular crisis and tendon rupture were observed within 6 weeks after surgery. After 6 weeks of surgery, the manual muscle test was used to measure the pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, and grip force of the affected hand; the total action motion method was used to evaluate the finger joint range of motion of the affected hand, and the excellent and good ratio was calculated; the Carroll upper extremity function test was used to score and rate the function of the affected hand. Results: Within 6 weeks after surgery, only 1 patient in conventional rehabilitation group suffered from venous crisis, and the flap survived after the second surgical exploration and anastomosis of blood vessels; there was no occurrence of tendon rupture in patients of 2 groups. After 6 weeks of surgery, there were no statistically significant differences in pinching force between the index finger and thumb, lateral pinching force, three-point pinching force, or grip force of the affected hand between the two groups of patients ( P >0.05); the excellent and good ratio of the finger joint range of motion of the affected hand of patients in early rehabilitation group was 11/12, which was higher than 7/12 in conventional rehabilitation group, but there was no statistically significant difference ( P >0.05); the affected hand function score of patients in early rehabilitation group was 90±6, which was significantly higher than 83±8 in conventional rehabilitation group ( t =2.41, P <0.05); the function rating of the affected hand of patients in early rehabilitation group was obviously better than that in conventional rehabilitation group ( Z =2.04, P <0.05). Conclusions: Early rehabilitation treatment for patients with skin and soft tissue defects accompanied by extensor tendon injury on the back of hand after repair surgery can improve hand function, but it would not increase surgery related complications, which is worthy of clinical promotion and application.

Single-walled carbon nanotube (SWCNT) films exhibit exceptional optical and electrical properties, making them highly promising for scalable integrated devices. Previously, we employed SWCNT films as templates for the chemical vapor deposition (CVD) synthesis of one-dimensional heterostructure films where boron nitride nanotubes (BNNTs) and molybdenum disulfide nanotubes (MoS 2 NTs) were coaxially nested over the SWCNT networks. In this work, we have further refined the synthesis method to achieve precise control over the BNNT coating in SWCNT@BNNT heterostructure films. The resulting structure of the SWCNT@BNNT films was thoroughly characterized using a combination of electron microscopy, UV-vis-NIR spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and Raman spectroscopy. Specifically, we investigated the pressure effect induced by BNNT wrapping on the SWCNTs in the SWCNT@BNNT heterostructure film and demonstrated that the shifts of the SWCNT's G and 2D ( G ') modes in Raman spectra can be used as a probe of the efficiency of BNNT coating. In addition, we studied the impact of vacuum annealing on the removal of the initial doping in SWCNTs, arising from exposure to ambient atmosphere, and examined the effect of MoO 3 doping in SWCNT films by using UV-vis-NIR spectroscopy and Raman spectroscopy. We show that through correlation analysis of the G and 2D ( G ') modes in Raman spectra, it is possible to discern distinct types of doping effects as well as the influence of applied pressure on the SWCNTs within SWCNT@BNNT heterostructure films. This work contributes to a deeper understanding of the strain and doping effect in both SWCNTs and SWCNT@BNNTs, thereby providing valuable insights for future applications of carbon-nanotube-based one-dimensional heterostructures.

Attenuated inflammatory response is a property of embryonic stem cells (ESCs). However, the underlying mechanisms are unclear. Moreover, whether the attenuated inflammatory status is involved in ESC differentiation is also unknown. Here, we found that autophagy-related protein ATG5 is essential for both attenuated inflammatory response and differentiation of mouse ESCs and that attenuation of inflammatory signaling is required for mouse ESC differentiation. Mechanistically, ATG5 recruits FBXW7 to promote ubiquitination and proteasome-mediated degradation of β-TrCP1, resulting in the inhibition of nuclear factor κB (NF-κB) signaling and inflammatory response. Moreover, differentiation defects observed in ATG5-depleted mouse ESCs are due to β-TrCP1 accumulation and hyperactivation of NF-κB signaling, as loss of β-TrCP1 and inhibition of NF-κB signaling rescued the differentiation defects. Therefore, this study reveals a previously uncharacterized mechanism maintaining the attenuated inflammatory response in mouse ESCs and further expands the understanding of the biological roles of ATG5., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transforming growth factor β 1 (TGF-β1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-β1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-β1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain ( COL1A1 ). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo . Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-β1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-β1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Purpose: The inhibitory effect of Apatinib on cytochrome P450 (CYP450) enzymes has been studied. However, it is unknown whether the inhibition is related to the major metabolites, M1-1, M1-2 and M1-6., Methods: A 5-in-1 cocktail system composed of CYP2B6/Cyp2b1, CYP2C9/Cyp2c11, CYP2E1/Cyp2e1, CYP2D6/Cyp2d1 and CYP3A/Cyp3a2 was used in this study. Firstly, the effects of APA and its main metabolites on the activities of HLMs, RLMs and recombinant isoforms were examined. The reaction mixture included HLMs, RLMs or recombinant isoforms (CYP3A4.1, CYP2D6.1, CYP2D6.10 or CYP2C9.1), analyte (APA, M1-1, M1-2 or M1-6), probe substrates. The reactions were pre-incubated for 5 min at 37 °C, followed by the addition of NAPDH to initiate the reactions, which continued for 40 min. Secondly, IC 50 experiments were conducted to determine if the inhibitions were reversible. The reaction mixture of the "+ NADPH Group" included HLMs or RLMs, 0 to 100 of μM M1-1 or M1-2, probe substrates. The reactions were pre-incubated for 5 min at 37 °C, and then NAPDH was added to initiate reactions, which proceeded for 40 min. The reaction mixture of the "- NADPH Group" included HLMs or RLMs, probe substrates, NAPDH. The reactions were pre-incubated for 30 min at 37 °C, and then 0 to 100 μM of M1-1 or M1-2 was added to initiate the reactions, which proceeded for 40 min. Finally, the reversible inhibition of M1-1 and M1-2 on isozymes was determined. The reaction mixture included HLMs or RLMs, 0 to 10 μM of M1-1 or M1-2, probe substrates with concentrations ranging from 0.25K m to 2K m ., Results: Under the influence of M1-6, the activity of CYP2B6, 2C9, 2E1 and 3A4/5 was increased to 193.92%, 210.82%, 235.67% and 380.12% respectively; the activity of CYP2D6 was reduced to 92.61%. The inhibitory effects of M1-1 on CYP3A4/5 in HLMs and on Cyp2d1 in RLMs, as well as the effect of M1-2 on CYP3A in HLMs, were determined to be noncompetitive inhibition, with the K i values equal to 1.340 μM, 1.151 μM and 1.829 μM, respectively. The inhibitory effect of M1-1 on CYP2B6 and CYP2D6 in HLMs, as well as the effect of M1-2 on CYP2C9 and CYP2D6 in HLMs, were determined to be competitive inhibition, with the K i values equal to 12.280 μM, 2.046 μM, 0.560 μM and 4.377 μM, respectively. The inhibitory effects of M1-1 on CYP2C9 in HLMs and M1-2 on Cyp2d1 in RLMs were determined to be mixed-type, with the K i values equal to 0.998 μM and 0.884 μM. The parameters could not be obtained due to the atypical kinetics of CYP2E1 in HLMs under the impact of M1-2., Conclusions: M1-1 and M1-2 exhibited inhibition for several CYP450 isozymes, especially CYP2B6, 2C9, 2D6 and 3A4/5. This observation may uncover potential drug-drug interactions and provide valuable insights for the clinical application of APA., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hu reports article publishing charges, equipment, drugs, or supplies, and writing assistance were provided by Guo-Xin., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Panic disorder (PD) involves emotion dysregulation, but its underlying mechanisms remain poorly understood. Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance. However, there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators., Aim: To study the neural mechanisms of implicit emotion regulation in PD with event-related potentials (ERP)., Methods: A total of 25 PD patients and 20 healthy controls (HC) underwent clinical eva-luations. The study utilized a case-control design with random sampling, selecting participants for the case group from March to December 2018. Participants performed an affect labeling task, using affect labeling as the experimental condition and gender labeling as the control condition. ERP and behavioral data were recorded to compare the late positive potential (LPP) within and between the groups., Results: Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling. In the HC group, late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease. Importantly, a significant group × condition interaction effect was observed. Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group. Furthermore, among PD patients under the affect labeling, the late LPP was negatively correlated with disease severity, symptom frequency, and intensity., Conclusion: PD patients demonstrate abnormalities in implicit emotion regulation, hampering their ability to mobilize cognitive resources for downregulating negative emotions. The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity., 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.)

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dong, Wen, Zhang, Wu and Zou.)

The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood-brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve., (Copyright © 2023 IBRO. Published by Elsevier Inc. All rights reserved.)

Cognitive reappraisal is an effective emotion regulation strategy involving prefrontal cortex (PFC) control of the amygdala. Its aberrant functioning is closely associated with panic disorder (PD). However, the resting-state functional connectivity (rsFC) between the PFC, implicated in cognitive reappraisal, and the amygdala in PD has not been studied. Thus, this study aims to investigate the rsFC patterns and their association with cognitive reappraisal and PD. This study involved 51 participants, including 26 untreated patients with PD and 25 healthy controls (HC). We evaluated the habit of cognitive reappraisal assessment and the severity of PD using neuropsychological and clinical measures. Resting-state fMRI was utilized to evaluate the rsFC pattern between the PFC, engaged in cognitive reappraisal, and the amygdala. Mediation analysis was performed to explore the role of this rsFC in the relationship between cognitive reappraisal and PD severity. PD patients showed reduced rsFC between the PFC and the amygdala compared to HC. This weakened rsFC was associated with the severity of PD symptoms. Moreover, cognitive reappraisal was negatively correlated with PD severity, and mediation analysis indicated that the rsFC of the PFC-amygdala played a mediating role in this association. Abnormal PFC-amygdala rsFC may play a pivotal role in PD development and/or manifestation and mediate the association between cognitive reappraisal and PD severity, potentially serving as a clinical indicator for monitoring and intervention., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To explore the effect of exercise prescription based on a progressive mode in treating elderly patients with lower limb dysfunction after deep burns. Methods: A randomized controlled trial was conducted. From January 2021 to January 2023, 60 elderly patients with lower limb dysfunction after deep burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University. The patients were divided into conventional rehabilitation group (30 cases, 17 males and 13 females, aged (65±3) years) and combined rehabilitation group (30 cases, 16 males and 14 females, aged (64±3) years) according to the random number table. For patients in both groups, the red-light treatment was started after the lower limb wounds healed or when the total area of scattered residual wounds was less than 1% of the total body surface area. After 2 weeks of red-light treatment, the patients in conventional rehabilitation group were given conventional rehabilitation treatments, including joint stretching, resistance, and balance training; in addition to conventional rehabilitation treatments, the patients in combined rehabilitation group were given exercise prescription training based on a progressive mode three times a week, mainly including dumbbell press, Bobath ball horizontal support, and high-level pulldown trainings. The training time for patients in both groups was 12 weeks. Before training (after 2 weeks of red-light treatment) and after 12 weeks of training, the upper limb and lower limb motor functions of the patients were evaluated using the simple Fugl-Meyer scale, the physical fitness of patients was evaluated using the simple physical fitness scale, and the patient's risk of falling was evaluated by the time consumed for the timed up and go test. The adverse events of patients that occurred during training were recorded. After 12 weeks of training, a self-designed satisfaction survey was conducted to investigate patients' satisfaction with the training effect. Data were statistically analyzed with independent sample t test, paired sample t test, Mann-Whitney U test, Wilcoxon signed rank test, and chi-square test. Results: Before training, the scores of upper limb and lower limb motor functions of patients between the two groups were similar ( P >0.05). After 12 weeks of training, the scores of upper limb motor function of patients in conventional rehabilitation group and combined rehabilitation group were significantly higher than those before training (with t values of -11.42 and -13.67, respectively, P <0.05), but there was no statistically significant difference between the two groups ( P >0.05). The score of lower limb motor function of patients in combined rehabilitation group was 28.9±2.6, which was significantly higher than 26.3±2.6 in conventional rehabilitation group ( t =-3.90, P <0.05), and the scores of lower limb motor function of patients in conventional rehabilitation group and combined rehabilitation group were significantly higher than those before training (with t values of -4.14 and -6.94, respectively, P <0.05). Before training, the individual and total scores of physical fitness of patients between the two groups were similar ( P >0.05). After 12 weeks of training, the balance ability score, walking speed score, chair sitting score, and total score of physical fitness of patients in conventional rehabilitation group and combined rehabilitation group were significantly increased compared with those before training (with Z values of -4.38, -3.55, -3.88, -4.65, -4.58, -4.68, -4.42, and -4.48, respectively, P <0.05), and the balance ability score, walking speed score, chair sitting score, and total score of physical fitness of patients in combined rehabilitation group were significantly increased compared with those in conventional rehabilitation group (with Z values of -3.93, -3.41, -3.19, and -5.33, P <0.05). Before training, the time consumed for the timed up and go test for patient's risk of falling in the two groups was close ( P >0.05). After 12 weeks of training, the time consumed for the timed up and go test for patient's risk of falling in combined rehabilitation group was (28.0±2.1) s, which was significantly shorter than (30.5±1.8) s in conventional rehabilitation group ( t =4.94, P <0.05). Moreover, the time consumed for the timed up and go test for patient's risk of falling in both conventional rehabilitation group and combined rehabilitation group was significantly shorter than that before training (with t values of 14.80 and 15.86, respectively, P <0.05). During the training period, no adverse events such as muscle tissue strain, edema, or falling occurred in any patient. After 12 weeks of training, the satisfaction score of patients with the training effect in combined rehabilitation group was 13.5±1.2, which was significantly higher than 8.5±1.4 in conventional rehabilitation group ( t =21.78, P <0.05). Conclusions: The exercise prescription training based on a progressive mode can significantly promote the recovery of lower limb motor function and physical fitness of elderly patients with lower limb dysfunction after deep burns, and effectively reduce the patient's risk of falling without causing adverse events during the training period, resulting in patient's high satisfaction with the training effect.

Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni 0.85 Se/MoSe 2 heterostructural electrocatalyst, Mo x -Ni 0.85 Se/MoSe 2 , was successfully prepared by simultaneously doping Mo cations into the Ni 0.85 Se lattice (Mo x -Ni 0.85 Se) and growing atomic MoSe 2 nanosheets epitaxially at the edge of the Mo x -Ni 0.85 Se. Such an Mo x -Ni 0.85 Se/MoSe 2 catalyst requires only 110 mV to drive current densities of 10 mA cm -2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm -2 . The experimental results, combined with the density functional theory calculations, reveal that the Mo x -Ni 0.85 Se/MoSe 2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni 0.85 Se can regulate the local electronic configuration of the Mo x -Ni 0.85 Se/MoSe 2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mo x -Ni 0.85 Se/MoSe 2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

For an effective drug, strong binding to the target protein is a prerequisite, but it is not enough. To produce a particular functional response, drugs need to either block the proteins' functions or modulate their activities by changing their conformational equilibrium. The binding free energy of a compound to its target is routinely calculated, but the timescales for the protein conformational changes are prohibitively long to be efficiently modeled via physics-based simulations. Thermodynamic principles suggest that the binding free energies of the ligands with different receptor conformations may infer their efficacy. However, this hypothesis has not been thoroughly validated. We present an actionable protocol and a comprehensive study to show that binding thermodynamics provides a strong predictor of the efficacy of a ligand. We apply the absolute binding free energy perturbation method to ligands bound to active and inactive states of eight G protein-coupled receptors and a nuclear receptor and then compare the resulting binding free energies. We find that carefully designed restraints are often necessary to efficiently model the corresponding conformational ensembles for each state. Our method achieves unprecedented performance in classifying ligands as agonists or antagonists across the various investigated receptors, all of which are important drug targets.

Objective: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation., Methods: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9., Results: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry., Conclusion: Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

The electrochemical reduction of oxygen via the 2e pathway is an environmentally friendly approach to the electrosynthesis of H 2 O 2 . Nevertheless, its sluggish kinetics and limited selectivity hinder its practical application. Herein, single Fe atoms anchored on graphene oxide (SA Fe/GO) with Fe-O 4 -C sites are developed as an efficient electrocatalyst for the electro-synthesis of H 2 O 2 . These Fe-O 4 -C site active centres could efficiently enhance the activity and selectivity towards 2e electrochemical oxygen reduction in an alkaline environment. The newly-developed SA Fe/GO electrocatalyst demonstrates exceptional electrochemical performance, exhibiting impressive activity with an onset potential of 0.90 and H 2 O 2 production of 0.60 mg cm -2 h -1 at 0.4 V. Remarkably, it achieves a remarkable H 2 O 2 selectivity of over 95.5%.