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1.
Opt Lett ; 49(11): 3122-3125, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824343

ABSTRACT

Self-hybridizing structures based on transition metal dichalcogenides (TMDCs) are becoming promising candidates for the study of an intrinsic strong light-matter coupling because of the efficient mode overlap with much simplified geometries. However, realizing flexible tuning of intrinsic strong coupling in such TMDC-based structures is still challenging. Here, we propose a strategy for flexible tuning of the intrinsic strong light-matter coupling based on a bulk TMDC material. We report the first demonstration of the strong coupling of intrinsic excitons to whispering gallery modes (WGMs) supported by an all-TMDC nanocavity. Importantly, by simply controlling angles of incidence, a selective excitation of WGMs and an anapole can be realized, which enables a direct modulation of self-hybridized interactions from a bright WGM-exciton coupling to a dark anapole-exciton coupling. Our work is expected to provide unique opportunities for engineering a strong light-matter coupling and to open exciting avenues for highly integrated novel nanophotonic devices.

2.
JAMA Netw Open ; 7(6): e2415084, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38837156

ABSTRACT

Importance: Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited. Objectives: To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention. Design, Setting, and Participants: This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets. Main Outcomes and Measures: The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale. Results: The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment. Conclusions and Relevance: In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.


Subject(s)
Developmental Disabilities , Genetic Testing , Humans , Developmental Disabilities/genetics , Developmental Disabilities/diagnosis , Male , Female , Child, Preschool , Genetic Testing/methods , Genetic Testing/statistics & numerical data , Infant , Prospective Studies , Exome Sequencing/methods , China/epidemiology , DNA Copy Number Variations/genetics , Cognitive Dysfunction/genetics , Cognitive Dysfunction/diagnosis
3.
Article in English | MEDLINE | ID: mdl-38752993

ABSTRACT

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Pedobacter , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Soil Microbiology , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , Pedobacter/genetics , Pedobacter/classification , Pedobacter/isolation & purification , Fatty Acids/chemistry , China , DNA, Bacterial/genetics , Vitamin K 2/analogs & derivatives , Nucleic Acid Hybridization
4.
Gen Psychiatr ; 37(3): e101389, 2024.
Article in English | MEDLINE | ID: mdl-38808176

ABSTRACT

Background: Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN. Aims: The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN. Methods: In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline. Results: Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN. Conclusions: Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

5.
World J Gastrointest Oncol ; 16(3): 1059-1075, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38577469

ABSTRACT

BACKGROUND: Glycosylation, a commonly occurring post-translational modification, is highly expressed in several tumors, specifically in those of the digestive system, and plays a role in various cellular pathophysiological mechanisms. Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years, bibliometric analysis of this field remains scarce. The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors. AIM: To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors. METHODS: We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace (version 6.1.R6) to perform bibliometric analysis. RESULTS: A total of 2042 documents spanning from 1978 to the present were analyzed, with the research process divided into three phases: the period of obscurity (1978-1990), continuous development period (1991-2006), and the rapid outbreak period (2007-2023). These documents were authored by researchers from 66 countries or regions, with the United States and China leading in terms of publication output. Reis Celso A had the highest number of publications, while Pinho SS was the most cited author. Co-occurrence analysis revealed the most popular keywords in this field are glycosylation, expression, cancer, colorectal cancer, and pancreatic cancer. Furthermore, the Journal of Proteome Research was the most prolific journal in terms of publications, while the Journal of Biological Chemistry had the most citations. CONCLUSION: The bibliometric analysis shows current research focus is primarily on basic research in this field. However, future research should aim to utilize glycosylation as a target for treating tumor patients.

6.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 236-243, 2024 Mar 15.
Article in Chinese | MEDLINE | ID: mdl-38557374

ABSTRACT

OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.


Subject(s)
Gastrointestinal Microbiome , Milk Hypersensitivity , Infant , Child , Female , Animals , Cattle , Humans , Milk Hypersensitivity/diagnosis , Fatty Acids, Volatile , Bacteria/genetics , Butyric Acid , Milk Proteins
7.
BMC Med Genomics ; 17(1): 116, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684994

ABSTRACT

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.


Subject(s)
Histone-Lysine N-Methyltransferase , Sotos Syndrome , Humans , Histone-Lysine N-Methyltransferase/genetics , Sotos Syndrome/genetics , Male , Female , Child, Preschool , Child , Infant , Intracellular Signaling Peptides and Proteins/genetics , Exome Sequencing , Mutation , Karyotyping , Histone Methyltransferases/genetics , Nuclear Proteins/genetics
8.
Alzheimers Dement ; 2024 Apr 27.
Article in Italian | MEDLINE | ID: mdl-38676366

ABSTRACT

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

9.
Asian J Psychiatr ; 95: 104007, 2024 May.
Article in English | MEDLINE | ID: mdl-38520944

ABSTRACT

OBJECTIVES: To examine different trajectories of cognitive changes in elderly adults and explore the mediating role of depressive symptoms. DESIGN: A 7-year, community-based, prospective cohort study. SETTING: The downtown neighborhood of Shanghai, China. PARTICIPANTS: A cohort of 394 older adults, with an average age of 71.8 years, was recruited in 2015 and has been reassessed every two years until 2021. METHODS: Latent Class Growth Analysis was used to model aging trajectories and Linear Mixed-Effect Models for Repeated Measures were used to estimate the least squares mean changes of cognition between subjects with depression (DEP+) and without (DEP-) across all visits. RESULTS: Three cognitive trajectories were identified: the "successful aging" (SA) trajectory had the best and most consistent performance (n=229, 55.9%); the "normal aging" (NA) trajectory showed lower but stable cognition (n=141, 37.3%); while the "cognitive decline" (CD) trajectory displayed poor and declining cognition (n=24, 6.8%). Depressive symptoms were found to be influential across all trajectories. In the CD trajectory, the MoCA scores of the DEP+ group increased in within-group comparisons and were significantly higher than those of the DEP- group at visits 1 and 3 in between-group comparisons. A similar trend was observed in the NA trajectory, though it did not reach statistical significance. CONCLUSIONS: Our research suggests that mild and decreasing depressive symptoms can be a reversible factor that might slow down the irreversible cognitive decline in the elderly. Therefore, we suggest that even mild depressive symptoms in the elderly should be monitored and detected.


Subject(s)
Cognitive Dysfunction , Depression , Humans , Aged , Male , Female , Depression/epidemiology , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/epidemiology , Follow-Up Studies , China/epidemiology , Aging/physiology , Aged, 80 and over , Prospective Studies , Middle Aged
10.
ACS Nano ; 18(13): 9636-9644, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38497667

ABSTRACT

A two-dimensional (2D) ferroelectric semiconductor, which is coupled with photosensitivity and room-temperature ferroelectricity, provides the possibility of coordinated conductance modulation by both electric field and light illumination and is promising for triggering the revolution of optoelectronics for monolithic multifunctional integration. Here, we report that semiconducting Sn2P2S6 crystals can be achieved in a 2D morphology using a chemical vapor transport approach with the assistant of space confinement and experimentally demonstrate the robust ferroelectricity in atomic-thin Sn2P2S6 nanosheet at room temperature. The intercorrelated programming of ferroelectric order along out-of-plane (OOP) and in-plane (IP) directions enables a tunable bulk photovoltaic (BPV) effect through multidirectional electrical control. By combining the capability of anisotropic in-plane optical absorption, a highly integrated Sn2P2S6 optoelectronic device vertically sandwiched with graphene electrodes yields the polarization-dependent open-circuit photovoltage with a dichroic ratio of 2.0 under 405 nm light illumination. The reintroduction of ferroelectric Sn2P2S6 to the 2D asymmetric semiconductor family provides possibilities to hardware implement of the self-powered polarization-sensitive photodetection and spotlights the promising applications for next-generation photovoltaic devices.

11.
Angew Chem Int Ed Engl ; 63(18): e202401950, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38453651

ABSTRACT

A mononuclear valence tautomeric (VT) complex, [Co(pycz)2(Sq)(Cat)] (1-trans), where pycz = 9-(pyridin-4-yl)-9H-carbazole, Sq⋅- = 3,5-di-tert-butyl-semiquinonato, and Cat2- = 3,5-di-tert-butyl-catecholato, is synthesized in the trans configuration, which undergoes one-step valence tautomeric transition above room temperature. Remarkably, 1-trans can transform into its isomeric structure, [Co(pycz)2(Sq)(Sq)] (1-cis), at temperature above 350 K in a single-crystal-to-single-crystal way by in situ molecular twist, and the resulting 1-cis exhibits a pronounced two-step VT transition during magnetic measurements that is rare for mononuclear VT complexes. Such drastic solid-state structural transformation is reported in VT compounds for the first time, which is actuated by a crystal surface's melting-recrystallization induced phase transition process. DFT calculations offer an underlying mechanism suggesting a concerted bond rotation during the structural transformation. The results demonstrate an unconventional approach that realizes structural transformation of VT complexes and the control of VT performance.

12.
BMC Pharmacol Toxicol ; 25(1): 26, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38504370

ABSTRACT

Browning of white adipose tissue (WAT) is become an appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Dapagliflozin is widely used in the treatment of type 2 diabetes, and it is also found that the drug exhibits regulate systemic metabolism such as obesity, insulin resistance and hepatic steatosis. However, the precise role of dapagliflozin on WAT remodeling remains to be elucidated. The current study aimed to explore the role of dapagliflozin on WAT browning in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice (n = 6 per group) were used to establish obesity model by following feeding with HFD for 6 weeks. The mice were randomly treated with or without dapagliflozin for the experimental observation. The volume and fat fraction of WAT were quantified, H&E, UCP-1 staining and immunohistochemistry were conducted to investigate the white-to-brown fat conversion and angiogenesis in WAT respectively. Quantitative real-time polymerase chain reaction (qPCR) was employed to explore the mRNA expression levels of genes related to fat browning and angiogenesis in WAT. Subsequently, 3T3-L1 cells were used to explore the effect of dapagliflozin on preadipocytes differentiation in vitro. Our results demonstrated that dapagliflozin could reduce body weight gain and promote WAT browning in HFD induced obese mice via regulating lipogenesis and angiogenesis in WAT. Furthermore, dapagliflozin reduce cells differentiation, up-regulate the expression of WAT browning and angiogenesis genes in 3T3-L1 adipocytes in vitro. In conclusion, dapagliflozin can potentially promote WAT browning in HFD induced obese mice via improving lipogenesis and angiogenesis in WAT.


Subject(s)
Angiogenesis , Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Male , Mice , Animals , Mice, Obese , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Mice, Inbred C57BL , Obesity/drug therapy , Obesity/metabolism , Adipose Tissue, White/metabolism , Diet, High-Fat/adverse effects
13.
Article in English | MEDLINE | ID: mdl-38462585

ABSTRACT

BACKGROUND: Several studies have suggested that smoking may impair cognitive function and worsen psychiatric symptoms in people with schizophrenia, but the results have not been consistent. There have been few studies to date that have examined the effects of smoking in older men with chronic schizophrenia. METHODS: The participants in our study consisted of 167 order Chinese males with chronic schizophrenia and 359 normal control subjects. We split them into smoking and non-smoking groups based on whether or not they smoked. Second, we compared their differences in terms of general demographic characteristics (such as age, education, body mass index, age of illness onset, and course of disease), disease information (such as hypertension, diabetes, and hyperlipidemia), lifestyle factors (such as physical exercise and lunch break), blood biochemical indicators (such as albumin, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and fasting blood glucose), and medication usage (such as clozapine, olanzapine, risperidone, and chlorpromazine). Lastly, a neuropsychological test battery was used to assess their psychiatric and cognitive symptoms, for example, the Montreal Cognitive Assessment (MoCA) was used to assess their overall cognitive functioning. Their depressive symptoms were assessed by the geriatric depression scale (GDS). Activities of daily living (ADL) were used to assess their ability to lead a daily life, while the positive and negative syndrome scales (PANSS) were used to assess their psychiatric symptoms. RESULTS: Smokers who develop schizophrenia at older ages had a higher body mass index than non-smokers. We also found that plasma albumin, triglycerides, low-density lipoprotein, and fasting blood glucose concentrations were significantly higher in smokers. In contrast, smokers with schizophrenia also had lower PANSS total scores, negative symptom scores, and general psychopathology scores. A forward stepwise binary logistics regression analysis demonstrated a significant association between negative symptom scores and smoking status (B = 0.112, p < 0.001, OR = 1.119, 95% confidence interval: 1.059-1.181). Correlation analysis was carried out and it was found that the amount of cigarette consumption per day had a negative correlation with plasma albumin level(r = - 0.290, p = 0.004). However, no such association was found in normal controls. CONCLUSIONS: Elderly Chinese men with schizophrenia have a higher percentage of smokers, and although smoking can reduce their plasma albumin levels, it does contribute to the prevention of negative symptoms.

14.
Br J Pharmacol ; 181(13): 1897-1915, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38413375

ABSTRACT

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.


Subject(s)
A Kinase Anchor Proteins , Basolateral Nuclear Complex , Depression , Lipoylation , Mice, Inbred C57BL , Animals , A Kinase Anchor Proteins/metabolism , Male , Mice , Depression/metabolism , Depression/psychology , Basolateral Nuclear Complex/metabolism , Stress, Psychological/metabolism , Behavior, Animal
15.
BMC Public Health ; 24(1): 475, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38360567

ABSTRACT

BACKGROUND: To evaluate the current prevalence of prediabetes in northeast China, and further determine the association between prediabetes alone or coexistent with hypertension and cardiovascular disease (CVD) mortality. METHODS: In the prospective study, 15,557 participants without diabetes among aged ≥40 years in northeast China, were followed for a median of 5.5 years. Following the American Diabetes Association, prediabetes was defined as fasting plasma glucose (FPG) range of 5.6-6.9 mmol/L or glycated hemoglobin (HbA1c) range of 5.7-6.4% in people without diabetes. RESULTS: The prevalence of prediabetes was 44.3% among population aged ≥40 years in northeast China. Prediabetes alone did not promote risk of CVD mortality. However, when the subgroups were stratified by hypertension, the CVD mortality risk in prediabetes plus hypertension subjects increased significantly compared with population without prediabetes and hypertension. Multivariate-adjusted hazard ratios for CVD mortality in prediabetes subgroups plus hypertension were 2.28 (95% CI: 1.50, 3.47) for those diagnosed by FPG < 5.6 mmol/L & HbA1c 5.7-6.4%, 2.18 (95% CI: 1.53, 3.10) for those diagnosed by FPG 5.6-6.0 mmol/L & HbA1c < 6.5% and 2.35 (95% CI: 1.65, 3.35) for those diagnosed by FPG 6.1-6.9 & HbA1c < 6.5% compared with the reference group. Moreover, the percentage of hypertension in prediabetes subjects was high (60.4%), but the awareness, treatment and control rates were far from satisfactory (45.3, 35.1 and 4.8%, respectively). CONCLUSIONS: The prevalence of prediabetes remains high in northeast China, and the CVD mortality was elevated significantly in prediabetes coexistent with hypertension. Considering the high percentage and low control rate of hypertension in prediabetes, strategies focused on HbA1c screening, FPG lowering and blood pressure management should be emphasized in northeast China.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Hypertension , Prediabetic State , Humans , Prediabetic State/diagnosis , Glycated Hemoglobin , Blood Glucose , Cohort Studies , Prospective Studies , Prevalence , Risk Factors , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Hypertension/complications
16.
Arch Clin Neuropsychol ; 39(4): 409-417, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38180808

ABSTRACT

OBJECTIVE: This study aimed to determine the predictive values of informant-reported memory decline (IMD) among subjective cognitive decline (SCD) older adults from a 7-year community-based cohort study. METHOD: Ninety SCD participants were included. Demographic data and neuropsychological test scores at both baseline and 7-year follow-up were collected. Differences between SCD with IMD (+IMD) and SCD without IMD (-IMD) were compared. Logistic regression models were used to determine whether baseline IMD could predict diagnostic outcomes at 7-year follow-up. RESULTS: Forty-one percent of SCD adults had IMD. At baseline, the +IMD group showed more depressive symptoms (p = 0.016) than the -IMD group. Furthermore, the Beijing-version Montreal Cognitive Assessment (MoCA), Digit Span Test-Forward, Visual Matching and Reasoning, and Wechsler Adult Intelligence Scale-RC Picture Completion (WAIS-PC) scores in the +IMD group were significantly lower than those in the -IMD group. Fifty-four percent of +IMD participants converted to mild cognitive impairment (MCI) or dementia at follow-up, and 22.6% of the -IMD participants converted to MCI. Follow-up Mini-Mental State Examination, MoCA, and Verbal Fluency Test scores of the +IMD group were significantly lower than those in the -IMD group. The +IMD group was more likely to progress to cognitive impairment at 7-year follow-up (OR = 3.361, p = 0.028). CONCLUSIONS: SCD participants with +IMD may have poorer cognition and are more likely to convert to cognitive impairment over time. Our long-term follow-up study confirmed the importance of informants' perceptions of SCD, which can help clinicians identify individuals at risk of cognitive decline.


Subject(s)
Cognitive Dysfunction , Neuropsychological Tests , Humans , Female , Male , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Aged , Longitudinal Studies , Middle Aged , Neuropsychological Tests/statistics & numerical data , Disease Progression , Diagnostic Self Evaluation , Mental Status and Dementia Tests , Aged, 80 and over , Depression/diagnosis , Memory Disorders/diagnosis , Memory Disorders/etiology
17.
BMJ Open Diabetes Res Care ; 12(1)2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38216296

ABSTRACT

INTRODUCTION: Diabetic foot ulcer (DFU) is a disabling complication of diabetes mellitus. Here, we attempted to assess whether long-term intrafemoral artery infusion of low-dose urokinase therapy improved DFUs and decreased cardiovascular events in patients with DFUs. RESEARCH DESIGN AND METHODS: This trial was a single-center, randomized, parallel study. A total of 195 patients with DFU were randomized to continuous intrafemoral thrombolysis or conventional therapy groups. The continuous intrafemoral thrombolysis group received continuous intrafemoral urokinase injection for 7 days, and conventional therapy just received wound debridement and dressing change. Then, a follow-up of average 6.5 years was performed. RESULTS: Compared with conventional therapy, at the first 1 month of intervention stage, the ulcers achieved a significant improvement in continuous intrafemoral thrombolysis group including a complete closure (72.4% vs 17.5%), an improved ulcer (27.6% vs 25.8%), unchanged or impaired ulcer (0% vs 56.7%). During the 6.5-year follow-up, for the primary outcome of ulcer closure rate, continuous intrafemoral thrombolysis therapy obtained a better complete healing rate (HR 3.42 (95% CI 2.35 to 4.98, p<0.0001)). For the secondary outcome of cardiovascular disease events, continuous intrafemoral thrombolysis therapy had a lower incidence of cardiovascular events (HR 0.50 (95% CI 0.34 to 0.74, p<0.0001)). Importantly, intrafemoral thrombolysis therapy decreased the incidence of cardiovascular death (HR 0.42 (95%CI 0.20 to 0.89, p=0.0241)). Additionally, continuous intrafemoral thrombolysis therapy improved local skin oxygenation and peripheral neuropathy as well as glycolipid metabolic profiles when compared with conventional therapy group (p<0.05). CONCLUSIONS: Continuous intrafemoral thrombolysis therapy has a better therapeutic efficacy to improve DFUs and decrease cardiovascular events. TRIAL REGISTRATION NUMBER: NCT01108120.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Humans , Diabetic Foot/drug therapy , Follow-Up Studies , Urokinase-Type Plasminogen Activator/therapeutic use , Wound Healing , Arteries
18.
Prev Med ; 180: 107859, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38228252

ABSTRACT

BACKGROUND AND AIMS: This study aimed to assess the potential of neck circumference (NC) and neck-to-height ratio (NHR) as predictors of future cardiovascular disease (CVD) mortality in a general population from Northeastern China. METHODS: A multi-center prospective study was conducted in Northeastern China, involving 18, 796 participants. The associations between NC or NHR and the incidence of overall CVD mortality, stroke mortality, and coronary heart disease (CHD) mortality were examined using multivariate Cox regression models. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. Reclassification analyses were conducted to determine the incremental predictive value of NC or NHR. RESULTS: NC was significantly associated with the risk of CVD mortality, independent of other anthropometric measurements for obesity. Individuals in the highest quartile of NC had a 1.83-fold (95% CI 1.29 to 2.61) and a 2.40-fold (95% CI 1.45 to 4.00) higher risk of overall CVD mortality and CHD mortality, respectively. Larger NC was significantly related to a heightened risk of ischemic stroke mortality, although no such association was observed with hemorrhagic stroke mortality. Furthermore, the risk of overall CVD mortality, stroke mortality, and CHD mortality increased by approximately 1.21 to 1.25 times per 1-SD change in NC. Similar findings were observed for NHR. The percentages of correct classification of overall CVD mortality improved by 12.1% and 16.3% after the addition of NC or NHR into established models, respectively. CONCLUSIONS: NC and NHR might be promising predictors of CVD mortality, with higher values indicating greater risk.


Subject(s)
Cardiovascular Diseases , Coronary Disease , Stroke , Humans , Cardiovascular Diseases/epidemiology , Prospective Studies , Risk Factors
19.
Sleep Med ; 113: 232-237, 2024 01.
Article in English | MEDLINE | ID: mdl-38064794

ABSTRACT

BACKGROUND: The relationship between afternoon napping and cognitive function in the elderly is very complex and the mechanism is unknown. METHODS: In the current study, 194 community elders with normal cognitive functions were included. All subjects completed baseline clinical assessment, baseline neuropsychological test as well as baseline structural MRI. Based on their napping status, these 194 participants were divided into the napping group (n = 88) and the non-napping group (n = 106). We then compared the differences in cognitive performance and structural magnetic resonance between the two groups. RESULTS: In the intergroup analysis, we found that the nappers showed poorer cognitive performance on both overall cognitive function and domain specific cognitive function; while on the whole sample, we found a significant negative association (F = 20.27, p<0.001) between afternoon napping and left amygdala volume. However, we did not find any effect of night sleep length or napping frequency on cognitive performance or left amygdala volume. CONCLUSIONS: In community elders with normal cognitive functions, afternoon napping is associated with cognitive performance, and left amygdala may play an important role in this process.


Subject(s)
Cognition , Sleep , Humans , Aged , Neuropsychological Tests
20.
J Am Chem Soc ; 146(1): 39-44, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38117532

ABSTRACT

Herein, we reported the isolation of 2π-aromatic disiladiboretenes (L2Si2B2Ph2) [L = ArC(NtBu)2, Ar = Ph (1), Mes (2)], which have been synthesized from the straightforward reduction of silylene-borane adducts (LSiX → BX2Ph) [X = Cl, Br] with potassium graphite (KC8). X-ray diffraction analysis of 1 and 2 revealed that the Si2B2 units are completely planar, and DFT calculations suggested delocalization of 2π-electrons over the Si2B2 rings. Moreover, their photophysical properties and reactivity toward sulfur were also investigated in detail.

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