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1.
Heliyon ; 10(10): e31078, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803984

ABSTRACT

With the advent of positive psychology in the area of language education, more focus has been placed on the consequences of favorable teacher communication behaviors in language classes. Nonetheless, the function of language instructors' interpersonal behaviors in raising learners' engagement is somehow unknown. Furthermore, to the best of our knowledge, no research study has been carried out in Spanish language classes to explore the function of teacher communication behaviors in learners' engagement. To fill this lacuna, the current inquiry looked into the role of teachers' positive interpersonal factors in Chinese SFL learners' behavioral, cognitive, and emotional engagement. For this purpose, a random sample of 32 SFL learners was chosen to participate in our online interview sessions. The answers of SFL learners to the interview questions were thematically analyzed via MAXQDA software. The thematic analysis findings pointed to the value of teacher communication behaviors in improving SFL learners' engagement. The analysis outcomes also demonstrated the potential of 11 positive interpersonal behaviors (rapport, care, clarity, credibility, confirmation, immediacy, closeness, praise, feedback, respect, and stroke) in increasing Spanish language learners' academic engagement. The practical implications that may emerge from the present study's outcomes are finally discussed.

2.
Lancet Reg Health West Pac ; 47: 101086, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38774424

ABSTRACT

Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

3.
Prog Nucl Magn Reson Spectrosc ; 140-141: 1-41, 2024.
Article in English | MEDLINE | ID: mdl-38705634

ABSTRACT

Solid-state NMR spectroscopy (ssNMR) can provide details about the structure, host-guest/guest-guest interactions and dynamic behavior of materials at atomic length scales. A crucial use of ssNMR is for the characterization of zeolite catalysts that are extensively employed in industrial catalytic processes. This review aims to spotlight the recent advancements in ssNMR spectroscopy and its application to zeolite chemistry. We first review the current ssNMR methods and techniques that are relevant to characterize zeolite catalysts, including advanced multinuclear and multidimensional experiments, in situ NMR techniques and hyperpolarization methods. Of these, the methodology development on half-integer quadrupolar nuclei is emphasized, which represent about two-thirds of stable NMR-active nuclei and are widely present in catalytic materials. Subsequently, we introduce the recent progress in understanding zeolite chemistry with the aid of these ssNMR methods and techniques, with a specific focus on the investigation of zeolite framework structures, zeolite crystallization mechanisms, surface active/acidic sites, host-guest/guest-guest interactions, and catalytic reaction mechanisms.

4.
J Ethnopharmacol ; 332: 118376, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38782310

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. AIM OF THE STUDY: To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. MATERIAL AND METHODS: First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. RESULTS: zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. CONCLUSION: zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.

5.
Brain Commun ; 6(3): fcae144, 2024.
Article in English | MEDLINE | ID: mdl-38756537

ABSTRACT

The neuropathological mechanisms underlying the association between sleep duration and mild cognitive impairment remain poorly understood. This population-based study included 2032 dementia-free people (age ≥ 60 years; 55.1% women) derived from participants in the Multimodal Interventions to Delay Dementia and Disability in Rural China; of these, data were available in 841 participants for Alzheimer's plasma biomarkers (e.g. amyloid-ß, total tau and neurofilament light chain), 1044 for serum microvascular biomarkers (e.g. soluble adhesion molecules) and 834 for brain MRI biomarkers (e.g. whiter matter, grey matter, hippocampus, lacunes, enlarged perivascular spaces and white matter hyperintensity WMH). We used electrocardiogram-based cardiopulmonary coupling analysis to measure sleep duration, a neuropsychological test battery to assess cognitive function and the Petersen's criteria to define mild cognitive impairment. Data were analysed with multivariable logistic and general linear models. In the total sample (n = 2032), 510 participants were defined with mild cognitive impairment, including 438 with amnestic mild cognitive impairment and 72 with non-amnestic mild cognitive impairment. Long sleep duration (>8 versus 6-8 h) was significantly associated with increased likelihoods of mild cognitive impairment and non-amnestic mild cognitive impairment and lower scores in global cognition, verbal fluency, attention and executive function (Bonferroni-corrected P < 0.05). In the subsamples, long sleep duration was associated with higher plasma amyloid-ß40 and total tau, a lower amyloid-ß42/amyloid-ß40 ratio and smaller grey matter volume (Bonferroni-corrected P < 0.05). Sleep duration was not significantly associated with serum-soluble adhesion molecules, white matter hyperintensity volume, global enlarged perivascular spaces and lacunes (P > 0.05). Alzheimer's and neurodegenerative pathologies may represent common pathways linking long sleep duration with mild cognitive impairment and low cognition in older adults.

6.
Arch Gerontol Geriatr ; 125: 105479, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38768553

ABSTRACT

BACKGROUND: We sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. METHODS: This population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33(rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. RESULTS: A higher LIBRA index was associated with multivariable-adjusted ß-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33(rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: ß-coefficient=0.042; 95 %CI=0.008-0.077), the dominant (CA+AA vs. CC: 0.040; 0.007-0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009-0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (Pinteraction<0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). CONCLUSIONS: This population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association.

7.
Arch Virol ; 169(5): 88, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565755

ABSTRACT

Transcription of the covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is subject to dual regulation by host factors and viral proteins. MicroRNAs (miRNAs) can regulate the expression of target genes at the post-transcriptional level. Systematic investigation of miRNA expression in HBV infection and the interaction between HBV and miRNAs may deepen our understanding of the transcription mechanisms of HBV cccDNA, thereby providing opportunities for intervention. miRNA sequencing and real-time quantitative PCR (qRT-PCR) were used to analyze miRNA expression after HBV infection of cultured cells. Clinical samples were analyzed for miRNAs and HBV transcription-related indicators, using qRT-PCR, enzyme-linked immunoassay (ELISA), and Western blot. miRNA mimics or inhibitors were used to study their effects on the HBV life cycle. The target genes of miR-3188 and their roles in HBV cccDNA transcription were also identified. The expression of 10 miRNAs, including miR-3188, which was significantly decreased after HBV infection, was measured in clinical samples from patients with chronic HBV infection. Overexpression of miR-3188 inhibited HBV transcription, whereas inhibition of miR-3188 expression promoted HBV transcription. Further investigation confirmed that miR-3188 inhibited HBV transcription by targeting Bcl-2. miR-3188 is a key miRNA that regulates HBV transcription by targeting the host protein Bcl-2. This observation provides insights into the regulation of cccDNA transcription and suggests new targets for anti-HBV treatment.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , MicroRNAs , Humans , DNA, Circular/genetics , DNA, Viral/genetics , DNA, Viral/metabolism , Hepatitis B/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Viral Transcription , Virus Replication/genetics
8.
Front Pharmacol ; 15: 1288255, 2024.
Article in English | MEDLINE | ID: mdl-38645554

ABSTRACT

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

9.
Sci Bull (Beijing) ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38670853

ABSTRACT

Chronic hepatitis B virus (HBV) infection can lead to advanced liver pathology. Here, we establish a transgenic murine model expressing a basic core promoter (BCP)-mutated HBV genome. Unlike previous studies on the wild-type virus, the BCP-mutated HBV transgenic mice manifest chronic liver injury that culminates in cirrhosis and tumor development with age. Notably, agonistic anti-Fas treatment induces fulminant hepatitis in these mice even at a negligible dose. As the BCP mutant exhibits a striking increase in HBV core protein (HBc) expression, we posit that HBc is actively involved in hepatocellular injury. Accordingly, HBc interferes with Fis1-stimulated mitochondrial recruitment of Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15). HBc may also inhibit multiple Rab GTPase-activating proteins, including Rab7-specific TBC1D15 and TBC1D5, by binding to their conserved catalytic domain. In cells under mitochondrial stress, HBc thus perturbs mitochondrial dynamics and prevents the recycling of damaged mitochondria. Moreover, sustained HBc expression causes lysosomal consumption via Rab7 hyperactivation, which further hampers late-stage autophagy and substantially increases apoptotic cell death. Finally, we show that adenovirally expressed HBc in a mouse model is directly cytopathic and causes profound liver injury, independent of antigen-specific immune clearance. These findings reveal an unexpected cytopathic role of HBc, making it a pivotal target for HBV-associated liver disease treatment. The BCP-mutated HBV transgenic mice also provide a valuable model for understanding chronic hepatitis B progression and for the assessment of therapeutic strategies.

10.
Interv Neuroradiol ; : 15910199241250081, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38665125

ABSTRACT

PURPOSE: Endovascular treatment (EVT) of acute ischemic stroke caused by large-vessel occlusion (AIS-LVO) over 24 h of onset remains controversial. This study was to explore the safety and efficacy of EVT for patients with AIS-LVO between 24 and 72 h of symptom onset after rigorous imaging evaluation. METHODS: Patients with AIS-LVO treated with EVT were retrospectively enrolled and divided into two groups according to the time from symptom onset to groin puncture: 64 in the over-time group (>24 h) and 257 in the within-time group (≤24 h). Outcomes included 3-month modified Rankin Scale (mRS) score, functional independence (defined as mRS 0-2), successful cerebral reperfusion, symptomatic intracranial hemorrhage (sICH), and 3-month mortality. RESULTS: Patients in the over-time group had no significant differences in the functional independence (40.6% vs 42.5%, odds ratio or OR 0.91, 95% confidence interval or CI 0.52-1.60, p = 0.753), successful reperfusion (96.7% vs 95.8%, OR 0.76, 95% CI 0.36-1.59, p = 0.467), sICH (8.3% vs 6.7%, OR 1.20, 95% CI 0.42-3.38, p = 0.735), 3-month mortality (13.3% vs 10.8%, OR 1.17, 95% CI 0.51-2.70, p = 0.716) compared with patients in the within-time group. After matching adjustment, the results did not change significantly. CONCLUSIONS: The safety and effectiveness of EVT treatment for selected AIS-LVO patients with symptom onset of 24-72 h are not inferior to those treated within 6-24 h of onset, especially in a short term based on the pre-treatment advanced neuroimaging computed tomography perfusion even though further investigations are necessary to prove this finding.

11.
Front Bioeng Biotechnol ; 12: 1303035, 2024.
Article in English | MEDLINE | ID: mdl-38456008

ABSTRACT

Walking is an indispensable mode of transportation for human survival. Gait is a characteristic of walking. In the clinic, patients with different diseases exhibit different gait characteristics. Gait analysis describes the specific situation of human gait abnormalities by observing and studying the kinematics and dynamics of limbs and joints during human walking and depicting the corresponding geometric curves and values. In foot and ankle diseases, gait analysis can evaluate the degree and nature of gait abnormalities in patients and provide an important basis for the diagnosis of patients' diseases, the correction of abnormal gait and related treatment methods. This article reviews the relevant literature, expounds on the clinical consensus on gait, and summarizes the gait characteristics of patients with common ankle and foot diseases. Starting from the gait characteristics of individuals with different diseases, we hope to provide support and reference for the diagnosis, treatment and rehabilitation of clinically related diseases.

12.
Adv Sci (Weinh) ; 11(18): e2310065, 2024 May.
Article in English | MEDLINE | ID: mdl-38447147

ABSTRACT

According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell-mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA-mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA-ERK1/2-ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA-treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.


Subject(s)
Autophagy-Related Protein-1 Homolog , CD8-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Animals , Mice , Humans , Autophagy-Related Protein-1 Homolog/metabolism , Autophagy-Related Protein-1 Homolog/genetics , MAP Kinase Signaling System/immunology , Coumarins/pharmacology , Coumarins/metabolism , Disease Models, Animal , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/metabolism , Mice, Inbred C57BL , Autophagy/immunology
13.
Brain Behav Immun ; 119: 36-50, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38555991

ABSTRACT

This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.

14.
Stroke ; 55(5): 1288-1298, 2024 May.
Article in English | MEDLINE | ID: mdl-38511349

ABSTRACT

BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

15.
Zhongguo Zhong Yao Za Zhi ; 49(2): 389-402, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403315

ABSTRACT

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.


Subject(s)
Drugs, Chinese Herbal , Oral Ulcer , Rats , Male , Animals , Drugs, Chinese Herbal/pharmacology , Oral Ulcer/drug therapy , Interleukin-6 , Hot Temperature , Tumor Necrosis Factor-alpha , Rats, Sprague-Dawley , Metabolomics/methods , Chromatography, High Pressure Liquid , Superoxide Dismutase , Biomarkers
16.
Sleep Breath ; 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38374476

ABSTRACT

OBJECTIVE: To investigate the prevalence and associated factors of excessive daytime sleepiness (EDS) among rural-dwelling Chinese older adults. METHODS: We collected data on demographic, epidemiological, and clinical factors via in-person interviews and clinical examinations following a structured questionnaire. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, the Berlin questionnaire (BQ) to assess obstructive sleep apnea (OSA) risk; and the Epworth Sleepiness Scale (ESS) to assess sleep characteristics. EDS was defined as the total ESS score > 10. RESULTS: This population-based study engaged 4845 participants (age ≥ 65 years, 57.3% female) in the 2018 examination of the Multimodal Interventions to Delay Dementia and Disability in Rural China. The prevalence of EDS was 9.3% in the total sample, 8.3% in females, and 10.6% in males, and the prevalence decreased with advanced age. Logistic regression analysis revealed that EDS was significantly associated with age (multivariable-adjusted odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.95-0.99), female sex (0.53; 0.36-0.77), hypertension (0.68; 0.54-0.85), depressive symptoms (2.68; 2.07-3.46), high OSA risk (2.11; 1.69-2.63), and poor sleep quality (2.12; 1.60-2.82). CONCLUSION: EDS affects nearly one-tenth of rural older adults in China. Older age, female sex, and hypertension were associated with a decreased likelihood of EDS, while depressive symptoms, high OSA risk, and poor sleep quality were correlated with an elevated likelihood of EDS.

17.
Kidney Int Rep ; 9(2): 401-409, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38344711

ABSTRACT

Introduction: Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown. Methods: A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed. Results: Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection. Conclusion: Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.

18.
BMJ Open ; 14(2): e079006, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38320838

ABSTRACT

OBJECTIVES: To quantitatively assess and compare retinal macular structures of rural-dwelling older adults in China using two different optical coherence tomography (OCT) scanners and to examine their associations with demographic, lifestyle, clinical and ocular factors. DESIGN, SETTING AND PARTICIPANTS: This population-based, cross-sectional study included 971 participants (age ≥60 years) derived from the Multimodal Interventions to Delay Dementia and Disability in Rural China study. We collected data on demographics, lifestyle factors, clinical conditions (eg, cardiovascular disease (CVD)) and ocular factors (eg, visual acuity and spherical equivalent). We used two models of spectral-domain OCT to measure macular parameters in nine Early Treatment Diabetic Retinopathy Study subfields. Data were analysed using the multiple general linear models. RESULTS: Spectralis OCT demonstrated higher macular thickness but a lower macular volume than Primus 200 OCT (p<0.05). Nasal quadrant of the inner and outer subfields was the thickest, followed by superior quadrant. Adjusting for multiple potential confounding variables, older age was significantly correlated with lower average inner and outer macular thicknesses and overall macular volume. Men had higher macular parameters than women. The presence of CVD was correlated with lower central macular thickness (ß=-6.83; 95% CI: -13.08 to -0.58; p=0.032). Middle school or above was associated with higher average inner macular thickness (ß=7.85; 95% CI: 1.14 to 14.55; p=0.022) and higher spherical equivalent was correlated with lower average inner macular thickness (ß=-1.78; 95% CI: -3.50 to -0.07; p=0.042). CONCLUSIONS: Macular thickness and volume assessed by Spectralis and Primus 200 OCT scanners differ. Older age and female sex are associated with lower macular thickness and volume. Macular parameters are associated with education, CVD and spherical equivalent. TRIAL REGISTERATION NUMBER: MIND-China study (ChiCTR1800017758).


Subject(s)
Diabetic Retinopathy , Tomography, Optical Coherence , Male , Humans , Female , Aged , Middle Aged , Cross-Sectional Studies , Tomography, Optical Coherence/methods , Retina/diagnostic imaging , Refraction, Ocular
19.
Plant Cell ; 36(5): 1892-1912, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38262703

ABSTRACT

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.


Subject(s)
Endosperm , Gene Expression Regulation, Plant , Oryza , Plant Proteins , Starch , Oryza/genetics , Oryza/metabolism , Oryza/growth & development , Endosperm/metabolism , Endosperm/genetics , Starch/metabolism , Starch/biosynthesis , Plant Proteins/metabolism , Plant Proteins/genetics , Amylopectin/metabolism , Mutation , Plants, Genetically Modified
20.
J Endocrinol ; 261(2)2024 May 01.
Article in English | MEDLINE | ID: mdl-38265817

ABSTRACT

The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.


Subject(s)
Microbiota , Osteoarthritis , Osteoporosis , Female , Mice , Animals , Humans , Tumor Necrosis Factor-alpha , Anti-Bacterial Agents/pharmacology , Dysbiosis , Lipopolysaccharides , Cartilage/metabolism , Osteoarthritis/metabolism , Osteoarthritis/pathology , Ovariectomy
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