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Weikun Tang,1 Junpeng Fan,1 Yide He,1 Bihai Huang,2 Huihui Liu,1 Daiwen Pang,2 Zhixiong Xie11College of Life Sciences, 2College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSe-core QDs (MAA–QDs) were investigated. After incubation with different concentrations of MAA–QDs (0.043, 0.13, 0.4, 1.2, and 3.6 µmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA–QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium–mercaptoacetic acid complex (Cd–MAA) that is formed in the solution of MAA–QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd–MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles.Keywords: genotoxicity, MAA CdSe quantum dots, cadmium–MAA complex, transformation assay, DNA

Abstract Background Research suggests that an eight-week Mindfulness-Based Cognitive Therapy (MBCT) program may be effective in the treatment of generalized anxiety disorders. Our objective is to compare the clinical effectiveness of the MBCT program with a psycho-education programme and usual care in reducing anxiety symptoms in people suffering from generalized anxiety disorder. Methods A three armed randomized, controlled clinical trial including 9-month post-treatment follow-up is proposed. Participants screened positive using the Structure Clinical Interview for DSM-IV (SCID) for general anxiety disorder will be recruited from community-based clinics. 228 participants will be randomly allocated to the MBCT program plus usual care, psycho-education program plus usual care or the usual care group. Validated Chinese version of instruments measuring anxiety and worry symptoms, depression, quality of life and health service utilization will be used. Our primary end point is the change of anxiety and worry score (Beck Anxiety Inventory and Penn State Worry Scale) from baseline to the end of intervention. For primary analyses, treatment outcomes will be assessed by ANCOVA, with change in anxiety score as the baseline variable, while the baseline anxiety score and other baseline characteristics that significantly differ between groups will serve as covariates. Conclusions This is a first randomized controlled trial that compare the effectiveness of MBCT with an active control, findings will advance current knowledge in the management of GAD and the way that group intervention can be delivered and inform future research. Unique Trail Number (assigned by Centre for Clinical Trails, Clinical Trials registry, The Chinese University of Hong Kong): CUHK_CCT00267

OBJECTIVE: Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia. The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose, in contrast to a reduced dose. METHOD: In a multicenter open-label, randomized, controlled study, patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to a no-dose-reduction group (initial optimal therapeutic dose continued throughout the study), a 4-week group (initial optimal therapeutic dose continued for 4 weeks, followed by a 50% dose reduction that was maintained until the end of the study), or a 26-week group (initial optimal therapeutic dose continued for 26 weeks, followed by a 50% dose reduction until the end of the study). All patients continued until the last recruited patient completed the 1-year follow-up. RESULTS: Of the 404 patients who met the entry criteria and were randomly assigned, 374 completed the study. The estimated mean time from entry to relapse was 571 days in the 4-week group, 615 days in the 26-week group, and 683 days in the no-dose-reduction group, with estimated relapse rates of 30.5%, 19.5%, and 9.4%, respectively. Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms. CONCLUSIONS: Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period. There was negligible difference in side effects among the three groups. [ABSTRACT FROM AUTHOR]

Objective: Anxiety disorders (ANDI) commonly occur in patients with Parkinson's disease (PD) but their socio-demographic and clinical correlates have not yet been unequivocally determined. This study aimed to assess the frequency of ANDI and their correlates in Chinese PD patients. Methods: A cohort of 133 patients of PD were recruited from three neurology outpatient clinics. Participants' neurological, cognitive, and psychiatric status was assessed using standardized rating instruments. ANDI were diagnosed by qualified psychiatrists using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders--4th Edition (SCID-DSM IV). Results: Thirty-six patients (27.1%) were diagnosed with some types of ANDI; Generalized Anxiety Disorder, Agoraphobia, and Social Phobia were the commonest subtypes of ANDI in PD (n = 11, 8.3%, in each of the three subtypes). Nine patients had more than one subtype of ANDI. In multivariate logistic regression, younger age of onset of PD [odds ratio (OR) =2.654, 95% confident intervals (CI) = 1.120-6.289, p = 0.027), Geriatric Depression Scale score (OR = 1.179, 95% CI = 1.056-1.316, p = 0.003) and muscle cramps (>/= 1/week) (OR = 2.605, 95% CI = 1.098-6.184, p = 0.030) were independent correlates of ANDI. Conclusions: ANDI are common in Chinese PD patients. Younger age of onset of PD, severity of depressive symptoms, and muscle cramps may be independent correlates of ANDI suggesting that anxiety in PD has multifactorial origin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although confluent white matter lesion (WML) is associated with cognitive impairment, the mechanism explaining this association is controversial. We aimed to investigate comprehensively the MRI predictors of cognitive impairment in confluent WML. METHODS: Among 45 lacunar stroke patients who had confluent WML, we evaluated the association of executive function [Mattis Dementia Rating Scale - Initiation/Perseveration subscale (MDRS I/P)] and global cognition [Mini-Mental State Examination (MMSE)] with the volume of WML, measures of lacunes and microbleeds, and the volumes of 99 other specific brain regions. RESULTS: Regression analyses showed that WML volume predicted performance on the MDRS I/P (beta = -0.34, p = 0.016) independent of age. Volumes of cortical gray matter (cGM; beta = 0.41, p = 0.003), the lateral fronto-orbital gyrus (beta = 0.38, p = 0.01), superior frontal gyrus (beta = 0.29, p = 0.04), lateral ventricle (beta = -0.30, p = 0.04), and posterior limb of the internal capsule (beta = 0.43, p = 0.002) predicted MDRS I/P performance independent of WML volume. Volumes of cGM, and the lateral fronto-orbital gyrus predicted MMSE performance as well. CONCLUSION: Atrophy along the frontosubcortical pathways and cGM predict cognition in confluent WML independent of WML volume. [ABSTRACT FROM AUTHOR]

Objectives: To examine the point prevalence of depressive disorders and their clinical correlates in Chinese patients with Parkinson's disease.Patients and Methods: Chinese people with Parkinson's disease attending 2 general neurology outpatient clinics were recruited consecutively and a convenience sample was taken from among those attending a Parkinson's disease clinic. The Chinese-Bilingual Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) was used to identify patients who suffered from different kinds of depressive disorder. The demographic and clinical variables of those with depression were compared with those participants who did not have depression.Results: The point prevalence of any type of depressive disorder was 26.3%. Major depressive episodes were diagnosed in 19 (14.3%) patients, 7 of whom had concurrent dysthymia. Three percent had minor depression and 9% had dysthymia. A history of depression, the age of onset of Parkinson's disease, and global disability were found to be the clinical correlates of depression in Parkinson's disease.Conclusion: This study indicates that depression is frequent among Chinese people with Parkinson's disease attending neurology clinics in Hong Kong. The clinical correlates of Parkinson's disease found in this study concurred with those found in other studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: To our knowledge, there are no previous data on drinking problems in patients with pneumoconiosis. The aim of this study was to examine drinking patterns and the impact of drinking on lung function and health-related quality of life (HRQOL) in Chinese patients with pneumoconiosis. METHODS: Three hundred patients with pneumoconiosis were recruited from a community-based case registry. The HRQOL was measured with the St. George's Respiratory Questionnaire (SGRQ). Pulmonary function, comorbidity, and psychosocial variables were also assessed. The alcohol use of the patients was evaluated with the Alcohol Use Disorders Identification questionnaire. RESULTS: Of the 300 patients, 72.3% (217) reported that they had not consumed any alcohol during the past year, whereas 83 patients (27.7%) did report drinking alcohol. In the drinking group, 88.0% (73) consumed <7 standard drinks per week, and none of them exceeded the safety limit of 21 standard drinks per week. The drinking group (n = 83) was younger, had less concurrent medical diseases, and lower (i.e., better) unadjusted SGRQ symptom, activity, impact, and total scores than the nondrinking group (n = 217). The SGRQ scores, which were adjusted for age, duration of occupation, concurrent medical diseases, smoking status, and forced expiratory volume in 1 sec predicted tests (FEV1%), remained significantly lower for the drinking group. Although the drinking group had a higher unadjusted FEV1% predicted, the difference between the FEV1% of the two groups, after adjustment for covariates, was of borderline significance only. CONCLUSIONS: Most Chinese patients with pneumoconiosis in this study did not consume alcohol, and among those who did, the level of alcohol consumption was low. This low level of alcohol consumption was associated with a better HRQOL and possibly with better lung function. [ABSTRACT FROM AUTHOR]

Objective: To determine which screening instrument is most suitable for detecting depression in Chinese stroke patients. Method: A random sample of 60 Chinese subjects recruited from consecutively admitted patients with first-ever stroke to a rehabilitation facility were assessed using the Visual Analogue Mood Scale (VAMS), the Hospital Anxiety and Depression Scale (HADS), and the Geriatric Depression Scale (GDS). Psychiatric diagnoses, which served as a benchmark for the comparison of screening instruments, were made using the SCID-DSM-III-R. Rating instruments were compared with respect to response rate, sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves. Results: The VAMS was not useful in screening for depression in Chinese stroke patients while both the HADS and the GDS demonstrated satisfactory accuracy in detecting depression in Chinese stroke patients. Conclusions: Screening instruments for poststroke depression are culture-specific and even scales well established in other cultures should be tested before being used in clinical practice and research. [ABSTRACT FROM AUTHOR]

Objectives: Chronic obstructive pulmonary disease is associated with physical and psychological burdens. Although there is research about health-related quality of life (HRQOL) of such patients, less is known about the psychosocial condition of their family caregivers. The objectives of this study were to examine the HRQOL and the burden of chronic obstructive pulmonary disease patient caregivers, and to identify associated relevant factors. Methods: A total of 81 eligible caregivers completed a caregiver survey on HRQOL (Short Form-36 Questionnaire), caregiving burden (Cumulative Illness Rating Scale, CIRS) and other biopsychosocial factors. Descriptive statistics, correlations, and multiple linear regression models were used to analyse data. Results: The caregiver's Mental Component Summary measure of the Short Form-36 was associated with each caregiver's total CIRS scores, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Lubben Social Network Scale. The caregiver's Physical Component Summary measure was associated with the patient's disability allowance, the caregiver's total CIRS score, and the Barthel Index score. Caregivers' Caregiving Burden Scale scores were associated with their Geriatric Depression Scale total score and the need to take care of other family members. Conclusions: This study demonstrates that depressive and anxiety symptoms are associated with caregivers' burden and HRQOL. Further studies on evaluating interventions on caregivers' HRQOL and burden should take mood symptoms into consideration. [ABSTRACT FROM AUTHOR]

Objective: To date, few studies have investigated depot antipsychotic medication in Chinese patients with schizophrenia in general and outpatients with schizophrenia in particular. This study examined the frequency, and sociodemographic and clinical correlates of depot anti-psychotic medication in Hong Kong.Patients and Methods: 267 clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong using standardised assessment instruments. Data on prescription patterns of all psychotropic drugs were collected at the time of the diagnostic interview. Results: Depot antipsychotic treatment was employed in 36.7% (n = 98) of the sample. Patients on depot antipsychotics were older, had longer duration of illness and more psychiatric hospitalisations and better scores on the social domain of quality of life. They were more likely to receive antipsychotic polypharmacy and anticholinergic drugs and to be on priority follow-up status and on conditional discharge, and less likely to receive clozapine. In multiple logistic regression analysis, the use of antipsychotic polyphannacy, history of suicide attempts, educational level and being on conditional discharge all significantly predicted the use of depot antipsychotics.Conclusion: The use of depot antipsychotics appeared to be independent of the severity of psychotic symptoms. It is a cause for concern that depot antipsychotic therapy was associated with antipsychotic polypharmacy because the very advantage of depot antipsychotics is lost in clinically stable outpatients. It seems that clinicians are more reluctant to prescribe depot anti-psychotic for younger patients than older ones. Regular surveys of prescribing practices with the aim of more rational use of depot antipsychotics are warranted. [ABSTRACT FROM AUTHOR]

CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either P. falciparum or P. vivax CelTOS, and with transmission reducing activity against P. falciparum. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat P. falciparum and P. vivax malaria., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Structural and functional abnormalities in the cortical-striatal network (CSN) are hypothesised to play a key role in the pathogenesis of neurological disease-associated fatigue. Some small-scale functional MRI (fMRI) studies have suggested that poststroke fatigue (PSF) is related to focal functional connectivity (FC) changes. To date, there has been no published large-scale fMRI study on PSF. This planned study will examine the role of the CSN FC on PSF., Methods and Analysis: The planned study will be a prospective cohort study conducted at the Neurology Unit of the Prince of Wales Hospital. We will recruit 738 participants. The project duration will be 36 months. A psychiatrist will administer the Fatigue Severity Scale (FSS) at 3 months (P1) following the index stroke. PSF is defined as an FSS Score≥4.0. PSF severity will be defined by the FSS total score at P1. Participants with PSF at P1 will undergo two follow-up assessments at 9 (P2) and 15 (P3) months post stroke. PSF remission at P2 or P3 will be defined as a 50% reduction in FSS. Participants will undergo MRI examinations within 2 weeks of the 3-month poststroke assessment. Structural MRI, resting-state fMRI and diffusion tensor imaging will be performed. FC, structural connectivity, infarcts, cerebral microbleeds and white matter hyperintensities will be analysed. For the primary analysis, the effect of PSF on the FC, structural connectivity and diffusion metrics of CSN of stroke survivors, voxel-wise two-sample t-tests will be performed with FDR correction for multiple comparison and significance level set at p<0.05., Ethics and Dissemination: Ethical approval was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster clinical research ethics committee. The study findings will be shared through peer-reviewed journal publications, national and international conferences and social media platforms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Apathy is a frequent and debilitating condition among subarachnoid hemorrhage (SAH) survivors. Few studies have evaluated apathy in SAH, and none have examined the course of the condition, predictors of persistent apathy, or its impact on functional outcomes. The proposed study will examine, for the first time, the 12-month course of apathy and its impact on functional outcomes in the largest cohort of SAH survivors to date., Methods and Analysis: The current study is designed as a prospective cohort study with a duration of 36 months. We will recruit 240 participants. A trained research assistant will assess apathy using the Apathy Evaluation Scale 3 months after SAH. Patients' level of functioning, comorbidity, global cognitive functioning, and depressive symptoms will be assessed. All SAH patients will participate in follow-up assessments of apathy and functioning at 9 (T2) and 15 months (T3) post-SAH or at 6 and 12 months after the first assessment. Predictors of persistent apathy and the impact of apathy on functional outcomes will be examined., Discussion: This will be the first large-scale 1-year follow-up study of apathy in SAH survivors. The findings will provide valuable data to advance our understanding of the clinical course of apathy in this population. Moreover, the results will have clinical relevance by providing essential information to patients, caregivers, and clinicians; promoting the evaluation of apathy; and facilitating the development of prevention strategies, rehabilitation programs, and therapeutic options., Ethics and Dissemination: Ethical approval for this study was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2023.339) on 3 October 2023. The findings of this study will be shared through publication in a peer-reviewed journal, presentations at relevant conferences, and dissemination through social media platforms., 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 Tang and Wong.)

Achieving both high efficiency and high stability in blue thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs) is challenging for practical displays and lighting. Here, we have successfully developed a series of sky-blue to pure-blue emitting donor-acceptor (D-A) type TADF materials featuring a four-coordinated boron with 2,2'-(pyridine-2,6-diyl)diphenolate (dppy) ligands, i.e. 1-8. Synergistic engineering of substituents on the phenyl bridge as well as the electronic properties and the attached positions of heteroatom N-donors not only enables fine-tuning of the emission colors, but also modulates the nature and energies of their triplet excited states that are important for the reverse intersystem crossing (RISC). Particularly for the compound with two methyl substituents on the phenyl bridge (compound 8), RISC is significantly facilitated through the vibronic coupling of the energetically close-lying triplet charge transfer ( 3 CT) and the triplet local excited ( 3 LE) states, when compared to analogue 7. Efficient sky-blue to pure-blue OLEDs with electroluminescence peaks ( λ EL ) at 460-492 nm have been obtained, in which ca . five-fold higher external quantum efficiencies (EQEs) of 18.9% have been demonstrated by 8 than that by 7. Moreover, ca . thirty times longer device operational half-lifetimes (LT 50 ) of 9113 hours for 8 than that for 7 as well as satisfactory LT 50 reaching 26 643 hours for 6 at an initial luminance of 100 cd m -2 have also been demonstrated. To the best of our knowledge, these results represent one of the best high-performance blue OLEDs based on tetracoordinated boron TADF emitters. Moreover, the design strategy presented here has provided an attractive strategy for enhancing the device performance of blue TADF-OLEDs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The human AAA-ATPase Bcs1L translocates the fully assembled Rieske iron-sulfur protein (ISP) precursor across the mitochondrial inner membrane, enabling respiratory Complex III assembly. Exactly how the folded substrate is bound to and released from Bcs1L has been unclear, and there has been ongoing debate as to whether subunits of Bcs1L act in sequence or in unison hydrolyzing ATP when moving the protein cargo. Here, we captured Bcs1L conformations by cryo-EM during active ATP hydrolysis in the presence or absence of ISP substrate. In contrast to the threading mechanism widely employed by AAA proteins in substrate translocation, subunits of Bcs1L alternate uniformly between ATP and ADP conformations without detectable intermediates that have different, co-existing nucleotide states, indicating that the subunits act in concert. We further show that the ISP can be trapped by Bcs1 when its subunits are all in the ADP-bound state, which we propose to be released in the apo form., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function. Using the HMM-based approach we screened 50 high-scoring candidate sequences in Escherichia coli, leading to the discovery of 13 new TDases. The X-ray crystal structures of two new enzymes from Legionella species were determined, and the ability of anhydrotetracycline to inhibit their tetracycline-inactivating activity was confirmed. Using the MSA-based approach we identified 31 amino acid positions 100% conserved across all known TDase sequences. The roles of these positions were analyzed by alanine-scanning mutagenesis in two TDases, to study the impact on cell and in vitro activity, structure, and stability. These results expand the diversity of TDase sequences and provide valuable insights into the roles of important residues in TDases, and flavin monooxygenases more broadly., (© 2024. The Author(s).)

Background: Post-stroke behavioral disinhibition (PSBD) is common in stroke survivors and often presents as impulsive, tactless or vulgar behavior. However, it often remains undiagnosed and thus untreated, even though it can lead to a longer length of stay in a rehabilitation facility. The proposed study will aim to evaluate the clinical, neuropsychological and magnetic resonance imaging (MRI) correlates of PSBD in a cohort of stroke survivors and describe its 12-month course., Methods: This prospective cohort study will recruit 237 patients and will be conducted at the Neurology Unit of the Prince of Wales Hospital. The project duration will be 24 months. The patients will be examined by multiple MRI methods, including diffusion-weighted imaging, within 1 week after stroke onset. The patients and their caregivers will receive a detailed assessment at a research clinic at 3, 9 and 15 months after stroke onset (T1, T2 and T3, respectively). The disinhibition subscale of the Frontal Systems Behavior Scale (FrSBe) will be completed by each subject and caregiver, and scores ≥65 will be considered to indicate PSBD.A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest (ROIs), together with other significant variables identified in the univariate analyses. For patients with PSBD at T 1 , the FrSBe disinhibition scores will be compared between the groups of patients with and without ROI infarcts, using covariance analysis. The demographic, clinical and MRI variables of remitters and non-remitters will be examined again at T 2 and T 3 by logistic regression., Discussion: This project will be the first MRI study on PSBD in stroke survivors. The results will shed light on the associations of lesions in the orbitofrontal cortex, anterior temporal lobe and subcortical brain structures with the risk of PSBD. The obtained data will advance our understanding of the pathogenesis and clinical course of PSBD in stroke, as well as other neurological conditions. The findings are thus likely to be applicable to the large population of patients with neurological disorders at risk of PSBD and are expected to stimulate further research in this field., 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 Tang, Hui and Leung.)

Nine new alkaloids, eugeniinalines A-H ( 1 - 8 ) and (+)-eburnamenine N -oxide ( 9 ), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia . The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A ( 1 ) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G ( 7 ) and its seco -derivative, eugeniinaline H ( 8 ), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine ( 10 ) and melokhanine A ( 11 ) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7 R , 20 R , 21 S ). Eugeniinalines A and G ( 1 and 7 ) showed cytotoxic activity against the HT-29 cancer cell line with IC 50 values of 7.1 and 7.2 μM, respectively.

Background: Chronic ketamine use has been associated with cognitive impairments, while depressive symptoms are commonly observed in individuals using ketamine. However, the influence of depressive symptoms on cognitive impairments in chronic ketamine users remains unclear. This study aimed to examine the impact of depressive symptoms on cognitive function in this population., Methods: A cross-sectional study was conducted with a sample of chronic ketamine users. Participants underwent comprehensive cognitive assessments, including measures of attention, executive function, working memory, verbal and visual memory. Depressive symptoms were assessed using Beck Depression Inventory (BDI) scores. Multivariate analyses were utilized to compare the cognitive performance of individuals who use ketamine, both with and without depressive symptoms, as well as a control group, while controlling for relevant covariates., Results: The results revealed a significant negative impact of depressive symptoms on cognitive impairments, particularly in the domains of memory and executive function, among chronic ketamine users. The analysis of partial correlations revealed that among individuals who use ketamine and have depressive symptoms, those with higher levels of depressive symptoms demonstrated poorer cognitive performance compared to individuals with lower levels of depressive symptoms, controlling for potential confounding factors., Conclusions: The findings suggest that depressive symptoms contribute to cognitive impairments, specifically in memory and executive function, in chronic ketamine users. Therefore, it is crucial to evaluate depressive symptoms when considering cognitive enhancement treatment for this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Post-stroke fatigue (PSF) is a frequent problem in stroke survivors and often hinders their rehabilitation. PSF is difficult to treat, and pharmacological therapy is often ineffective. Transcranial direct current stimulation (tDCS) can modulate motor, sensory, cognitive and behavioral responses, as it alters neuronal activity by delivering a small amount of current via the scalp to the cortex, resulting in prolonged alterations to brain function. tDCS has been studied for the treatment of fatigue associated with other neurological diseases, namely, multiple sclerosis, Parkinson's disease and post-polio syndrome., Aims: This proposed project will examine the effect of tDCS on PSF., Sample Size Estimates: We will recruit 156 participants aged 18 to 80 with chronic stroke and allocate them equally to two groups (i.e., n  = 78 per group)., Methods and Design: This proposed project will be a double-blind randomized control trial. The participants will be randomly divided into two groups. The control group will receive sham tDCS, and the treatment group will receive active tDCS. The latter treatment will involve application of a constant 2-mA current via one 5 × 5-cm anodal electrode positioned on the scalp over the C3 or C4 positions (motor cortex) of the lesioned hemisphere and one cathodal electrode positioned at the ipsilateral shoulder in two 20-min sessions per day for 5 days. The period of follow-up will be 4 weeks., Study Outcomes: The primary outcome measure will be a change in fatigue severity, as measured using the modified fatigue impact scale (MFIS). The participants' scores on the MFIS (total score and physical, cognitive and psychosocial subscores) will be collected before treatment (T0), after 10 treatment sessions, i.e., 1 day after the fifth treatment day (T1), and 1 week (T2), 2 weeks (T3) and 4 weeks (T4) thereafter. Both per-protocol analysis and intention-to-treat analysis will be performed., Discussion: This proposed project will provide proof-of-concept, i.e., demonstrate the benefits of tDCS for the treatment of PSF. The beneficiaries are the subjects participated in the study. This will stimulate further research to optimize tDCS parameters for the treatment of PSF., Clinical Trial Registration: www.Chictr.org.cn, identifier: ChiCTR2100052515., 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 Tang, Lu, Leung, Kim and Fong.)

Patients with rheumatoid arthritis (RA) often experience depression and poor sleep. Depression and poor sleep may, in turn, worsen RA disease activity. This cross-sectional study aimed to investigate the relationship between RA disease activity as measured using the Disease Activity Score-28 (DAS28-ESR), depression measured using the Beck's Depression Inventory-II (BDI-II), and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI). Anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). A total of 164 consecutive patients with RA were recruited from the Rheumatology Specialist Clinic of a regional hospital in Hong Kong. They were asked to complete questionnaires that included demographic information, the Health Assessment Questionnaire (HAQ), BDI-II, HADS-A, and PSQI. The DAS28-ESR was assessed by the attending rheumatologists. Clinical information was retrieved from the electronic medical records. The mean DAS28-ESR score was 3.35 ± 1.24 (SD). The mean BDI-II was 10.97 ± 9.15 (SD). The mean HADS-A score was 5.57 ± 3.77 (SD). The mean PSQI score was 7.55 ± 4.16 (SD). The BDI-II score was statistically correlated with the DAS28-ESR and PSQI scores. Multiple regression analysis revealed that the association of BDI-II with DAS28-ESR and PSQI was confounded by the HAQ. The association of DAS28-ESR with BDI-II but not with PSQI is in accordance with the results of previous studies. The association between the HAQ and BDI-II has also been demonstrated in previous studies. Clinicians should be aware of mood and sleep problems in patients with RA and adopt a multidisciplinary approach to their management. Future studies should provide information on causality in a more representative sample of patients with RA., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The conventional medium chain chlorinated paraffin (MCCP) and zinc dialkyl dithiophosphate (ZDDP) additives have greatly enhanced the extreme pressure (EP) and anti-wear (AW) performance of the metalworking fluids. However, chlorine- and zinc-containing additives are restricted in use due to eco-toxicity issue. Herein, ashless and non-corrosive dimercaptobenzothiadiazole derivatives, namely bis-2,5-benzylsulfanyl-[1,3,4]thiadiazole (BBST) and bis-2,5-octylsulfanyl-[1,3,4]thiadiazole (BOST) consist of three sulfur atoms have been synthesized and evaluated. The performance of BBST shows a weld load ( P D ) of 3089 N and AW value of 5 mm 2 , which represents an improvement of 3.1 and 7.4 folds over naphthenic base oil (NBO). In addition, BBST also outperformed BOST, MCCP, and ZDDP in terms of its weld load and AW properties. Based on XPS analysis and molecular electrostatic potential maps (MEPS), BBST exhibits superior tribology performance due to the interaction between the sulfur (S), nitrogen (N), and π-electrons of the benzene ring with the metal surface. The formation of FeS, Fe 2 O 3 and Fe⋯N coordinate bonds contributes to the creation of an excellent tribofilm., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The realization of operationally stable blue organic light-emitting diodes is a challenging issue across the field. While device optimization has been a focus to effectively prolong device lifetime, strategies based on molecular engineering of chemical structures, particularly at the subatomic level, remains little. Herein, we explore the effect of targeted deuteration on donor and/or acceptor units of thermally activated delayed fluorescence emitters and investigate the structure-property relationship between intrinsic molecular stability, based on isotopic effect, and device operational stability. We show that the deuteration of the acceptor unit is critical to enhance the photostability of thermally activated delayed fluorescence compounds and hence device lifetime in addition to that of the donor units, which is commonly neglected due to the limited availability and synthetic complexity of deuterated acceptors. Based on these isotopic analogues, we observe a gradual increase in the device operational stability and achieve the long-lifetime time to 90% of the initial luminance of 23.4 h at the luminance of 1000 cd m -2 for thermally activated delayed fluorescence-sensitized organic light-emitting diodes. We anticipate our strategic deuteration approach provides insights and demonstrates the importance on structural modification materials at a subatomic level towards prolonging the device operational stability., (© 2023. Springer Nature Limited.)

Pfs25 is a leading antigen for a malaria transmission-blocking vaccine and shows moderate transmission-blocking activity and induction of rapidly decreasing antibody titers in clinical trials. A comprehensive definition of all transmission-reducing epitopes of Pfs25 will inform structure-guided design to enhance Pfs25-based vaccines, leading to potent transmission-blocking activity. Here, we compiled a detailed human antibody epitope map comprising epitope binning data and structures of multiple human monoclonal antibodies, including three new crystal structures of Pfs25 in complex with transmission-reducing antibodies from Malian volunteers immunized with Pfs25 conjugated to EPA and adjuvanted with AS01. These structures revealed additional epitopes in Pfs25 capable of reducing transmission and expanded this characterization to malaria-exposed humans. This work informs immunogen design to focus the antibody response to transmission-reducing epitopes of Pfs25, enabling development of more potent transmission-blocking vaccines for malaria., (© 2023. Springer Nature Limited.)

Objective: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar., Methods: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection., Results: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication., Conclusions: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in reporting this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes., Methods: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage., Results: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (β = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (β = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004)., Discussion: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

A new class of thermally activated delayed fluorescence (TADF) tetradentate C ∧ C ∧ N ∧ N ligand-containing gold(III) complexes containing acridinyl moieties has been designed and synthesized. These complexes exhibit orange-red to deep-red emission with photoluminescence quantum yields (PLQYs) of up to 0.76 in solid-state thin films. Short excited-state lifetimes of ≤2.0 μs and large radiative decay rate constants ( k r ) in the order of 10 5 s -1 have also been found in the complexes. High-performance solution-processed and vacuum-deposited organic light-emitting devices (OLEDs) based on these complexes have been fabricated, demonstrating high maximum external quantum efficiencies (EQEs) of 12.2 and 12.7%, respectively, which are among the best values ever reported for red-emitting gold(III)-based OLEDs. In addition, satisfactory operational half-lifetime (LT 50 ) values of up to 34,058 h have been attained in these red-emitting devices. It is found that the operational stability is strongly dependent on the choice of functional groups on the acridinyl moieties, of which the incorporation of -O- and -S- linkers can effectively prolong the LT 50 value by an order of magnitude. The TADF properties of the complexes are substantiated by the hypsochromic shift in emission energies and the remarkable enhancement in the emission intensity upon increasing temperature. The TADF properties have also been supported by temperature-dependent ultrafast transient absorption studies, with the direct observation of reverse intersystem crossing (RISC) and the determination of the activation parameters for the very first time, together with their excited-state dynamics.

The precise location of an ion or electron, whether it is internally solvated or residing on the surface of a water cluster, remains an intriguing question. Subtle differences in the hydrogen bonding network may lead to a preference for one or the other. Here we discuss spectroscopic probes of the structure of gas-phase hydrated ions in combination with quantum chemistry, as well as H/D exchange as a means of structure elucidation. With the help of nanocalorimetry, we look for thermochemical signatures of surface vs internal solvation. Examples of strongly size-dependent reactivity are reviewed which illustrate the influence of surface vs internal solvation on unimolecular rearrangements of the cluster, as well as on the rate and product distribution of ion-molecule reactions.

Pfs230 domain 1 (Pfs230D1) is an advanced malaria transmission-blocking vaccine antigen demonstrating high functional activity in clinical trials. However, the structural and functional correlates of transmission-blocking activity are not defined. Here, we characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccinees immunized with Pfs230D1. These hmAbs exhibited diverse transmission-reducing activity, yet all bound to Pfs230D1 with nanomolar affinity. We compiled epitope-binning data for seventeen hmAbs and structures of nine hmAbs complexes to construct a high-resolution epitope map and revealed that potent transmission-reducing hmAbs bound to one face of Pfs230D1, while non-potent hmAbs bound to the opposing side. The structure of Pfs230D1D2 revealed that non-potent transmission-reducing epitopes were occluded by the second domain. The hmAb epitope map delineated binary hmAb combinations that synergized for extremely high-potency, transmission-reducing activity. This work provides a high-resolution guide for structure-based design of enhanced immunogens and informs diagnostics that measure the transmission-reducing response., Competing Interests: Declaration of interests N.H.T., W.K.T., P.E.D., C.H.C., I.S., S.A.H., C.A.L., and K.M. are listed as inventors on a provisional patent application related to this work., (Published by Elsevier Inc.)

A tetranuclear copper(I) complex, [Cu 4 {μ-(Ph 2 P) 2 NH} 4 (μ 4 -S)](PF 6 ) 2 ( 1 ), was synthesized. It was found to display intense and long-lived phosphorescence in the solid and solution states. The lowest-energy excited state was assigned as ligand-to-metal charge transfer (LMCT) [S 2- → Cu 4 ] mixed with some metal-centered (ds/dp) character. In addition, the phosphorescent state of this complex was found to be quenched by pyridinium acceptors via an oxidative electron-transfer quenching process. An excited-state reduction potential of -1.74 V versus saturated salt calomel electrode was estimated through oxidative quenching studies with a series of structurally related pyridinium acceptors, indicative of its strong reducing power in the excited state. From the transient absorption difference spectrum of the tetranuclear copper(I) sulfido complex and 4-(methoxycarbonyl)- N -methylpyridinium hexafluorophosphate, in addition to the characteristic absorption of the pyridinyl radical at ca. 395 nm, two absorption bands at ca. 500 and 660 nm were also observed. The former was assigned as an LMCT absorption [S 2- → Cu 4 ] and the latter as an intervalence charge-transfer transition, associated with the mixed-valence species Cu I /Cu I /Cu I /Cu II .

The tumor-associated antigen mesothelin is expressed at high levels on the cell surface of many human cancers, while its expression in normal tissues is limited. The binding of mesothelin to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. Immunotherapeutic strategies targeting mesothelin are being intensively investigated. Here, we report the crystal structures of mesothelin that reveal a compact, right-handed solenoid consisting of 24 short helices and connecting loops. These helices form a nine-layered spiral coil that resembles ARM/HEAT family proteins. Glycan attachments have been identified in the structure for all three predicted N-glycosylation sites and confirmed with samples from cell culture and patient ascites. The structures of full-length mesothelin and its complex with the Fab of MORAb-009 reveal the interaction of the antibody with the complete epitope, which has not been reported previously. The N-terminal half of mesothelin is conformationally rigid, suitable for eliciting specific antibodies, whereas its C-terminal portion is more flexible. The structure of the C-terminal shedding-resistant fragment of mesothelin complexed with a mAb 15B6 displays an extended linear epitope and helps explain the protection afforded by the antibody for the shedding sites., Significance: The structures of full-length mesothelin and its complexes with antibodies reported here are the first to be determined experimentally, providing atomic models for structural organization of this protein and its interactions with antibodies. It offers insights into the function of mesothelin and guidance for further development of therapeutic antibodies., Competing Interests: I. Pastan reports a patent to WO 2014031476 pending. No disclosures were reported by the other authors., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: Post-traumatic stress disorder (PTSD) frequently follows neurological disorders such as non-traumatic subarachnoid hemorrhage (SAH) and has debilitating consequences., Objective: The aim of this systematic review was the critical appraisal of the literature on the frequency, severity, and temporal progression of PTSD in patients with SAH, the etiology of PTSD, and its effect on patients' quality of life (QoL)., Material and Methods: Studies were obtained from three databases: PubMed EMBASE, PsycINFO, and Ovid Nursing. The inclusion criteria were English-language studies on adults (defined as at least 18 years of age) in which ≥10 of the participants received a diagnosis of PTSD following SAH. Applying these criteria, 17 studies (N = 1,381) were included., Results: Between 1% and 74% of the participants in each study had PTSD, with a weighted average of 36.6% across all studies. Post-SAH PTSD showed significant correlations with premorbid psychiatric disorders, neuroticism, and maladaptive coping styles. The risk of PTSD was also higher in participants with comorbid depression and anxiety. Stress related to post-ictal events and fear of recurrence were associated with PTSD. However, the risk of PTSD was lower in participants with effective social support networks. The participants' QoL was negatively affected by PTSD., Conclusions: This review highlights the high occurrence of PTSD in SAH patients. The temporal progression and chronicity of post-SAH PTSD warrant further research, as do its neuroanatomical and neurochemical correlates. We call for more randomized controlled trials investigating these aspects., Competing Interests: None

Pfs28 is a Plasmodium falciparum malaria transmission-blocking vaccine candidate that is anchored to the parasite surface through a C-terminal glycosylphosphatidylinositol (GPI) moiety, and plays a role in parasite survival in the mosquito midgut. Pfs28 contains epidermal growth factor (EGF)-like domains and is part of a family of sexual stage malaria proteins that includes the related vaccine antigen Pfs25. The lack of structural definition of Pfs28 and the immune response to this candidate has limited further malaria vaccine development for this antigen. Here, we present the crystal structure of Pfs28, examine its conservation with P. vivax Pvs28, and evaluate the cross-reactivity of Pfs28 to antibodies that recognize Pfs25. Pfs28 is comprised of four EGF-like domains stabilized by ten disulfide bridges with an overall architecture that highly resembles Pfs25. Despite the high sequence and structural similarity between these antigens, no cross reactivity of Pfs28 to anti-Pfs25 monoclonal antibodies could be demonstrated., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Decanuclear and pentanuclear gold(I) sulfido complexes of phenanthrene- and dibenzothiophene-based diphosphine ligands were synthesized and characterized. Unprecedented stimuli-induced reversible transformation between decanuclear and pentanuclear gold(I) sulfido complexes was observed, which could be readily monitored by NMR and UV-vis absorption spectroscopy in solution. Remarkably, the decanuclear gold(I) sulfido complex ( Au 10 -L Ph ) was found to show a highly reversible transformation process, which is stable for over 10 successive cycles in solution. The stimuli-induced reversible transformation behavior of the gold(I) sulfido complexes was found to depend on the P-P bite distance of the bidentate phosphine ligands.

Defining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria vaccine antigen and antibodies to MSP-1 are associated with protection from disease. However, MSP-1-based vaccines performed poorly in clinical trials in part due to a limited understanding of the protective antibody response to MSP-1 and of immune evasion by antigenic diversion. Antigenic diversion was identified as a mechanism wherein parasite neutralization by a MSP-1-specific rodent antibody was disrupted by MSP-1-specific non-inhibitory blocking/interfering antibodies. Here, we investigated a panel of MSP-1-specific naturally acquired human monoclonal antibodies (hmAbs). Structures of multiple hmAbs with diverse neutralizing potential in complex with MSP-1 revealed the epitope of a potent strain-transcending hmAb. This neutralizing epitope overlaps with the epitopes of high-affinity non-neutralizing hmAbs. Strikingly, the non-neutralizing hmAbs outcompete the neutralizing hmAb enabling parasite survival. These findings demonstrate the structural and mechanistic basis for a generalizable pathogen immune evasion mechanism through neutralizing and interfering human antibodies elicited by antigenic diversion, and provides insights required to develop potent and durable malaria interventions., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The receptor binding domain (RBD) of the SARS-CoV-2 spike protein is the primary target of neutralizing antibodies and is a component of almost all current vaccines. Here, RBD immunogens were created with stabilizing amino acid changes that improve the neutralizing antibody response, as well as characteristics for production, storage, and distribution. A computational design and in vitro screening platform identified three improved immunogens, each with approximately nine amino acid changes relative to the native RBD sequence, and four key changes conserved between immunogens. The changes are adaptable to all vaccine platforms and compatible with mutations in emerging variants of concern. The immunogens elicit higher levels of neutralizing antibodies than native RBD, focus the immune response to structured neutralizing epitopes, and have increased production yields and thermostability. Incorporating these variant-independent amino acid changes in next-generation COVID vaccines may enhance the neutralizing antibody response and lead to longer duration and broader protection.

Objective: To explore the effect of three interventions including caloric restriction, rope-skipping exercise and caloric restriction combined with rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students. Methods: This study was a pilot randomized controlled trial. Overweight or obese students who met the inclusion criteria were recruited at Sun Yat-sen University in September 2019 and were randomly divided into four groups: caloric restriction group (CR), rope-skipping group (RS), combined group (CR-RS) and control group (CT). The intervention in each group lasted 8 weeks, specifically: the daily energy intake of CR was 100% to 110% of the basal metabolic energy; RS was instructed to rope three times a week, and CR-RS combined caloric restriction with rope-skipping. At the baseline and end of 8-week intervention, basic information, anthropometric indicators and fasting vein blood of students were collected. Paired t test and Wilcoxon paired-samples signed rank test were used for comparison before and after intervention, and analysis of covariance was used for comparison between groups after intervention. Results: A total of 29 students completed the trial and were included in the final analysis (7, 9, 7 and 6 students in CR, RS, CR-RS and CT, respectively). The mean age of students were (19.00±1.00) years, including 11 males and 18 females. The baseline characteristics of four groups were comparable. After 8 weeks of intervention, compared with CT, there was an increase in the body fat percentage and fat mass index in CR and CR-RS ( P <0.05). Insulin level decreased in CR-RS ( P <0.05). Systolic blood pressure in CR and diastolic blood pressure in CR-RS were higher ( P <0.05). Compared with baseline, fat mass index decreased in CR ( P <0.05), while body weight, BMI, and fat mass index decreased in CR-RS ( P <0.05). Conclusion: It is suggested that the caloric restriction alone and calorie restriction combined with rope-skipping exercise can benefit overweight or obese college students with cardiometabolic risk factors.

Background: Post-traumatic stress disorder (PTSD) is a common and debilitating illness that accompanies many neurological disorders, including stroke., Objective: The aim of this systematic review was to identify and critically appraise all published studies that have reported the frequency, severity, and time course of PTSD after stroke, the factors associated with its development, and its impact on patients' lives., Material and Methods: The PubMed EMBASE, PsycINFO, and Ovid Nursing databases were searched for studies published in English that had recruited at least 10 patients (>18 years old) after stroke and who were also diagnosed with PTSD., Results: Twenty studies covering a total of 1785 patients met the study inclusion criteria. The frequency of PTSD ranged from 3% to 31%, with a weighted proportion of 16.5%. PTSD runs a chronic course. PTSD after stroke was associated with premorbid neuroticism, negative affect, and maladaptive coping styles. Comorbid depression and anxiety also increased the risk of PTSD. Psychological factors such as negative appraisal and perceived high risk of recurrence and distress were associated with PTSD. Good social support reduced the risk of PTSD. PTSD reduced patients' quality of life, physical functioning, and medication compliance., Conclusions: PTSD is common after stroke. Further research is needed to clarify its time course and identify the neurochemical factors and brain circuits associated with the development of post-stroke PTSD. Randomized controlled treatment trials targeting PTSD in stroke are warranted., Competing Interests: None