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Objective: This study aimed to investigate the role of galectin-3 (Gal-3; coded by LGALS3 gene), as a biomarker for MCI in T2DM patients and to develop and validate a predictive nomogram integrating galectin-3 with clinical risk factors for MCI prediction. Additionally, microRNA regulation of LGALS3 was explored. Methods: The study employed a cross-sectional design. A total of 329 hospitalized T2DM patients were recruited and randomly allocated into a training cohort (n = 231) and a validation cohort (n = 98) using 7:3 ratio. Demographic data and neuropsychological assessments were recorded for all participants. Plasma levels of galectin-3 were measured using ELISA assay. We employed Spearman's correlation and multivariable linear regression to analyze the relationship between galectin-3 levels and cognitive performance. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for MCI in T2DM patients. Based on these analyses, a predictive nomogram incorporating galectin-3 and clinical predictors was developed. The model's performance was evaluated in terms of discrimination, calibration, and clinical utility. Regulatory miRNAs were identified using bioinformatics and their interactions with LGALS3 were confirmed through qRT-PCR and luciferase reporter assays. Results: Galectin-3 was identified as an independent risk factor for MCI, with significant correlations to cognitive decline in T2DM patients. The developed nomogram, incorporating Gal-3, age, and education levels, demonstrated excellent predictive performance with an AUC of 0.813 in the training cohort and 0.775 in the validation cohort. The model outperformed the baseline galectin-3 model and showed a higher net benefit in clinical decision-making. Hsa-miR-128-3p was significantly downregulated in MCI patients, correlating with increased Gal-3 levels, while Luciferase assays confirmed miR-128-3p's specific binding and influence on LGALS3. Conclusion: Our findings emphasize the utility of Gal-3 as a viable biomarker for early detection of MCI in T2DM patients. The validated nomogram offers a practical tool for clinical decision-making, facilitating early interventions to potentially delay the progression of cognitive impairment. Additionally, further research on miRNA128's regulation of Gal-3 levels is essential to substantiate our results.
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OBJECTIVE: Type 2 diabetes mellitus (T2DM) has beenis known as an important risk factor for cognitive impairment. Meanwhile, the liver plays a central role in the development of T2DM and insulin resistance. The present study attempted to identify and validate marker genes for mild cognitive impairment (MCI) in patients with T2DM. METHODS: In this study, insulin resistance-related differentially expressed genes were identified from the liver tissues of individuals with T2DM and those with normal glucose tolerance using the Gene Expression Omnibus database and MCI-associated genes were identified using the GeneCards database. Next, enrichment analysis was performed with overlapping T2DM and MCI genes, followed by the identification of specific genes using the LASSO logistic regression and SVM-RFE algorithms. An important experiment involved the implementation of clinical and in vitro validation using real-time quantitative polymerase chain reaction (RT-qPCR). Finally, multiple linear regression, binary logistic regression, and receiver operating characteristic curve analyses were performed to investigate the relationship between the key gene and cognitive function in these patients. RESULT: The present study identified 40 overlapping genes between MCI and T2DM, with subsequent enrichment analysis revealing their significant association with the roles of neuronal and glial projections. The marker gene complement receptor 1(CR1) was identified for both diseases using two regression algorithms. Based on RT-qPCR validation in 65 T2DM patients with MCI (MCI group) and 65 T2DM patients without MCI (NC group), a significant upregulation of CR1 mRNA in peripheral blood mononuclear cells was observed in the MCI group (P < 0.001). Furthermore, the CR1 gene level was significantly negatively associated with MoCA and MMSE scores, which reflect the overall cognitive function, and positively correlated with TMTB scores, which indicate the executive function. Finally, elevated CR1 mRNA levels were identified as an independent risk factor for MCI (OR = 1.481, P < 0.001). CONCLUSION: These findings suggest that CR1 is an important predictor of MCI in patients with T2DM. Thus, CR1 has potential clinical significance, which may offer new ideas and directions for the management and treatment of T2DM. The identification and clinical validation of dysregulated marker genes in both T2DM and MCI can offer valuable insights into the intrinsic association between these two conditions. The current study insights may inspire the development of novel strategies for addressing the complicated issues related to cognitive impairment associated with diabetes.
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Chronic hypoxia (CH) is commonly associated with various cardiovascular diseases, with cardiac hypertrophy being the most frequently observed alteration. Metabolic remodeling is another consequence seen in the hypoxic heart. However, the mechanistic linkage between metabolic remodeling and cardiac hypertrophy in the hypoxic heart remains clear. In this study, wild-type C57BL/6J mice were subjected to CH for four weeks. Echocardiography and morphological analysis were used to assess the cardiac effects. We found that four weeks of CH led to significant cardiac hypertrophy in the mice, while cardiac function remained unchanged compared to normoxic mice. Additionally, CH induced an elevation in cardiac alpha-ketoglutarate (α-KG) content. Promoting α-KG degradation in the CH hearts prevented CH-induced cardiac hypertrophy but led to noticeable cardiac dysfunction. Mechanistically, α-KG promoted the transcription of hypertrophy-related genes by regulating histone methylation. Silencing lysine-specific demethylase 5 (KDM5), a histone demethylation enzyme, blunted α-KG-induced transcription of hypertrophy-related genes. These data suggest that α-KG is required for CH-induced cardiac remodeling, thus establishing a connection between metabolic changes and cardiac remodeling in hypoxic hearts.
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Hyperglycemia-induced pathological microglial responses and subsequent neuronal damage are notable characteristics of diabetes-associated cognitive impairment (DACI). Cholesterol accumulation in the brain is a prevalent consequence of diabetes mellitus (DM), exacerbating pathological microglial responses. Regarding disordered glucose and lipid metabolism, the Sterol Regulatory Element-Binding Protein (SREBP) cleavage-activating protein (SCAP), a cholesterol sensor, exhibits increased expression and abnormal translocation from the endoplasmic reticulum to the Golgi, amplifying the inflammatory response. Therefore, we hypothesized that overexpression of microglia-SCAP and cholesterol accumulation in DM mice could induce pathological microglial responses associated with DACI. Our type 2 DM mice model presented an abnormal increase in microglial SCAP expression. The functional loss of microglia-specific SCAP in DM mice improved cognitive impairment, neuronal synaptic plasticity deficits, and abnormal microglial responses. Mechanistically, the accumulated SCAP directly bound to and enhanced the activation of the microglial-specific inflammatory amplifier, NLRP3 inflammasome, in Golgi, thereby increasing pathological microglial responses and promoting neuronal damage. These findings indicate an important regulatory axis of microglial responses from SCAP to the NLRP3 inflammasome pathway in microglia. These underscore the crosstalk between cholesterol disorders and pathological microglial responses, offering a promising avenue for pharmaceutical interventions in DACI.
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Disfunção Cognitiva , Inflamassomos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microglia/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Camundongos , Inflamassomos/metabolismo , Doenças Neuroinflamatórias/metabolismo , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Colesterol/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Plasticidade Neuronal , Neurônios/metabolismo , Encéfalo/metabolismoRESUMO
An effective method by high-speed countercurrent chromatography coordinated with silver nitrate for the preparative separation of sterones and triterpenoid saponins from Achyranthes bidentata Blume was developed. Methyl tert-butyl ether/n-butanol/acetonitrile/water (4:2:3:8, v/v/v/v) was selected for 20-hydroxyecdysone (compound 1), chikusetsusaponin IVa methyl ester (compound 4), 2'-glycan-11-keto-pigmented saponin V (compound 5), as well as a pair of isomers of 25S-inokosterone (compound 2) and 25R-inokosterone (compound 3), which were further purified by silver nitrate coordinated high-speed countercurrent chromatography. What is more, dichloromethane/methanol/isopropanol/water (6:6:1:4, v/v/v/v) was applied for calenduloside E (compound 6), 3ß-[(O-ß-d-glucuronopyranosyl)-oxy]-oleana-11,13-dien-28-oic acid (compound 7), zingibroside R1 (compound 8) and chikusetsusaponin IVa (compound 9). Adding Ag+ to the solvent system resulted in unique selectivity for 25R/25S isomers of inokosterone, which increased the complexing capability and stability of Ag+ coordinated 25S-inokosterone, as well as the α value between them. These results were further confirmed by the computational calculation of geometry optimization and frontier molecular orbitals assay. Comprehensive mass spectrometry and nuclear magnetic resonance analysis demonstrated the structures of the obtained compounds.
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Achyranthes , Colestenos , Ácido Oleanólico/análogos & derivados , Saponinas , Distribuição Contracorrente , Achyranthes/química , Nitrato de Prata , Extratos Vegetais/química , Água/química , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The chemical composition of the aqueous part of the extract from Lindera aggregata was studied, which was separated and purified by the macroporous resin column chromatography, MCI medium pressure column chromatography, semi-preparative high-performance liquid phase and other methods. The structures of the compounds were identified according to physical and chemical properties and spectroscopic data. Thirteen compounds were isolated and identified from the aqueous extracts, which were identified as(1S,3R,5R,6R,8S,10S)-epi-lindenanolide H(1), tachioside(2), lindenanolide H(3), leonuriside A(4), 3,4-dihydroxyphenyl ethyl ß-D-glucopyranoside(5), 3,4,5-trimethoxyphenol-1-O-6-α-L-rhamnose-(1â6)-O-ß-D-glucoside(6), 5-hydroxymethylfurfural(7),(+)-lyoniresin-4-yl-ß-D-glucopyranoside(8), lyoniside(9), norboldine(10), norisopordine(11), boldine(12), reticuline(13). Among them, compound 1 was a new one, and compounds 2, 5, 6, 8, 9 were obtained from L. aggregata for the first time. The inflammatory model was induced by lipopolysaccharide(LPS) in the RAW264.7 cells. The results showed that compounds 1, 8, 10 and 12 had significant anti-inflammatory activity.
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Lindera , Sesquiterpenos , Lindera/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , GlucosídeosRESUMO
Cathodic protection is widely used to protect structural steel from corrosion in marine environments. However, an inappropriate cathodic potential may lead to hydrogen embrittlement (HE). Therefore, this study investigates the relationship between cathodic protection potential, structure and composition of calcareous deposits, and hydrogen embrittlement susceptibility of Q460 steel. The slow strain rate test results and fracture analysis reveal that Q460 steel had the smallest HE susceptibility when covered with the calcareous deposits formed under -1.1 VSCE. The deposits have a relatively thin calcium-rich inner layer and a condensed magnesium-rich outer layer, which can significantly inhibit hydrogen entry. A sustained deposition reaction during slow strain rate testing (SSRT) in artificial seawater can also decrease the HE susceptibility of Q460 steel.
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BACKGROUND: Iridoschisis is a rare condition that primarily affects individuals aged 60-70 years. The predominant characteristics of iridoschisis involve the tissue splitting and separation of the iris stromal layers, often resulting in two distinct layers and the presence of floating fibers in the anterior chamber. This article reports the case of a 48-year-old male with iridoschisis with partial lens dislocation in both eyes. CASE PRESENTATION: Trauma is the leading factor in the development of iridoschisis. However, there is no documented case of ocular trauma in the patient's medical history. Visible white atrophic fibers were observed bilaterally in the anterior iris stroma of both eyes of the individual, accompanied by a small quantity of iris tissue within the anterior chamber. In this instance, the magnitude of the iridoschisis corresponded with the degree of lens dislocation. We were apprised that the patient had regularly used a cervical massager for a prolonged period of time, positioning it upon the ocular region. Frequent stimulation of both eyes with excessive force resulted in the development of iridoschisis and the partial dislocation of the lens.During the initial surgical procedure, phacoemulsification (Phaco) was carried out on the left eye without the placement of an intraocular lens (IOL). Following a two-month interval, we proceeded with the IOL suspension. Subsequently, the right eye underwent Phaco, accompanied by the implantation of an IOL. After closely monitoring the patient's progress for two months, it was evident that their vision had significantly improved, substantiating the success of the surgical interventions. CONCLUSIONS: This finding posits that the recurrent friction applied to both eyes may induce iridoschisis and various ocular complications. In the event of ocular intricacies manifesting, expeditious medical intervention becomes imperative.
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Extração de Catarata , Doenças da Íris , Subluxação do Cristalino , Lentes Intraoculares , Facoemulsificação , Masculino , Humanos , Pessoa de Meia-Idade , Doenças da Íris/diagnóstico , Doenças da Íris/cirurgia , Iris/cirurgia , Facoemulsificação/métodos , Subluxação do Cristalino/diagnóstico , Subluxação do Cristalino/etiologia , Subluxação do Cristalino/cirurgiaRESUMO
In the present study, twelve compounds from Dioscorea spongiosa were successfully purified by an efficient technique combined bioassay-guided fractionation macroporous resin column chromatography (MRCC) pretreatment and high-speed counter-current chromatography (HSCCC) separation for the first time. Then, D101 MRCC was used to fractionate the crude extract into five parts, which further applied the bioassay-guided fractionation strategy to screen the active fractions of 2 and 4. As for the separation, 200 mg Fr.2 was purified by HSCCC using EtOAc/n-BuOH/H2 O (2:2:3, v/v), leading to annulatomarin (1), dioscoresides C (2), diosniponol C (3), methyl protodioscin (4), pseudoprotodioscin (5), protogracillin (6), as well as 200 mg Fr.4 yielding montroumarin (7), dioscorone A (8), diosniponol D (9), protodioscin (10), gracillin (11), and dioscin (12) using CH2 Cl2 /MeOH/H2 O (3:3:2, v/v) with the purities over 95.0%. Finally, the isolates were assayed for their anti-inflammatory, urico-lowering, and anti-diabetic activities in vitro, which indicated that the steroidal saponins of 5, 6, and 11 showed all these three activities.
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Distribuição Contracorrente , Dioscorea , Distribuição Contracorrente/métodos , Dioscorea/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Bioensaio , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Zinc-air batteries (ZABs) have attracted considerable attention for their high energy density, safety, low noise, and eco-friendliness. However, the capacity of mechanically rechargeable ZABs was limited by the cumbersome procedure for replacing the zinc anode, while electrically rechargeable ZABs suffer from issues including low depth of discharge, zinc dendrite and dead zinc formation, and sluggish oxygen evolution reaction, etc. To address these issues, we report a hybrid redox-mediated zinc-air fuel cell (HRM-ZAFC) utilizing 7,8-dihydroxyphenazine-2-sulfonic acid (DHPS) as the anolyte redox mediator, which shifts the zinc oxidation reaction from the electrode surface to a separate fuel tank. This approach decouples fuel feeding and electricity generation, providing greater operation flexibility and scalability for large-scale power generation applications. The DHPS-mediated ZAFC exhibited a superior peak power density of 0.51â W/cm2 and a continuous discharge capacity of 48.82â Ah with ZnO as the discharge product in the tank, highlighting its potential for power generation.
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One new phenolic cyclobutantetraol ester united chromone glycoside (1), one new amide (2), and three new phenyl ethanol glycosides (3-5) were obtained from the water extract of Scindapsus officinalis (Roxb.) Schott, in which compound 1 was the first reported structure incorporating the phenolic cyclobutantetraol ester and chromone via the glucose phenolic metabolites in nature. Structures of the isolated compounds, including absolute configurations, were elucidated according to the analysis of HRESIMS, NMR, ECD and BLYP/6-31G* geometry optimization calculations of 13C NMR data. All isolates (1-5) were evaluated for the antidiabetic activity by the insulin resistance (IR) model and anti-inflammatory activity against NO production in vitro. Compounds 1-3 showed strong antidiabetic activities, greatly promoting the glucose consumption in the insulin resistance HepG2 cells compared with the model group, however, 1-5 showed weak anti-inflammatory activities.
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Hipoglicemiantes , Resistência à Insulina , Humanos , Hipoglicemiantes/farmacologia , Estrutura Molecular , Glicosídeos/química , Cromonas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Fenóis , Ésteres , GlucoseRESUMO
Structural MRI and PET imaging play an important role in the diagnosis of Alzheimer's disease (AD), showing the morphological changes and glucose metabolism changes in the brain respectively. The manifestations in the brain image of some cognitive impairment patients are relatively inconspicuous, for example, it still has difficulties in achieving accurate diagnosis through sMRI in clinical practice. With the emergence of deep learning, convolutional neural network (CNN) has become a valuable method in AD-aided diagnosis, but some CNN methods cannot effectively learn the features of brain image, making the diagnosis of AD still presents some challenges. In this work, we propose an end-to-end 3D CNN framework for AD diagnosis based on ResNet, which integrates multi-layer features obtained under the effect of the attention mechanism to better capture subtle differences in brain images. The attention maps showed our model can focus on key brain regions related to the disease diagnosis. Our method was verified in ablation experiments with two modality images on 792 subjects from the ADNI database, where AD diagnostic accuracies of 89.71% and 91.18% were achieved based on sMRI and PET respectively, and also outperformed some state-of-the-art methods.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Redes Neurais de Computação , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Encéfalo/diagnóstico por imagemRESUMO
The recombinant genotypes that can be produced when closely related species mate improve the genetic diversity of the population. Among closely related species, the link between interspecific reproduction behaviors and genetic diversity has barely been studied. Reticulitermes chinensis and R. flaviceps, which live close to each other, were used as research subjects in our study to find out how preferring conspecifics affects reproductive behavior between species. We discovered that neither R. chinensis nor R. flaviceps displayed preference behavior for conspecifics. Males of R. chinensis and R. flaviceps chased and groomed not only intraspecific females but also interspecific females. In a brief period of time, 2 mating behaviors, intra- and interspecific mating, were also observed. There were no significant differences in the duration of each behavior (tandem, grooming, and mating) between interspecies and intraspecies partners. Moreover, genetic analysis showed both interspecific mating and intraspecific mating can produce living offspring when the 2 types of mating occur in a colony. Our findings showed that there was no obvious intraspecific preference between the 2 species of termite Reticulitermes when it came to tandem, grooming, and mating, which not only makes it easier for interspecific hybridization to occur but also sheds light on the genetic diversity.
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Isópteros , Masculino , Feminino , Animais , Isópteros/genética , Reprodução , Simpatria , Hibridização Genética , Variação GenéticaRESUMO
AIMS: Insulin resistance (IR) is a pivotal factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Nevertheless, the impact of IR on cognitive dysfunction in T2DM patients with NAFLD remains inadequately understood. We aim to investigate the effect of IR on mild cognitive impairment (MCI) in T2DM individuals with NAFLD. MATERIALS AND METHODS: 143 T2DM individuals were categorized into Non-MCI and MCI groups, as well as Non-NAFLD and NAFLD groups. Clinical parameters and cognitive preference test outcomes were compared. Correlation and regression analyses were executed to explore the interconnections between IR and cognitive details across all T2DM patients, as well as within the subgroup of individuals with NAFLD. RESULTS: In comparison to the Non-MCI group, the MCI group displayed elevated HOMA-IR levels. Similarly, the NAFLD group exhibited higher HOMA-IR levels compared to the Non-NAFLD group. Additionally, a higher prevalence of MCI was observed in the NAFLD group as opposed to the Non-NAFLD group. Notably, HOMA-IR levels were correlated with Verbal Fluency Test (VFT) and Trail Making Test-B (TMTB) scores, both related to executive functions. Elevated HOMA-IR emerged as a risk factor for MCI in the all patients. Intriguingly, increased HOMA-IR not only correlated with TMTB scores but also demonstrated an influence on TMTA scores, reflecting information processing speed function in patients with NAFLD. CONCLUSION: IR emerges as a contributory factor to cognitive dysfunction in T2DM patients. Furthermore, it appears to underlie impaired executive function and information processing speed function in T2DM individuals with NAFLD.
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BACKGROUND: Interleukin (IL)-10 plays a notable role in the inflammatory-associated mild cognitive impairment (MCI). We aimed to investigate whether IL-10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test-B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test-A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL-10, miR-let-7c-5p and cognitive function. RESULTS: Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL-10 in plasma and higher miR-let-7c-5p levels in exosomes from plasma. The IL-10 level was negatively associated with MoCA. Likewise, miR-let-7c-5p levels were negatively correlated with IL-10 levels and MoCA. Elevated miR-let-7c-5p levels and decreased IL-10 levels are risk factors for MCI in T2DM patients. Increased miR-let-7c-5p and downregulated IL-10 may influence VFT and TMTB, respectively, associated with executive function. CONCLUSIONS: We demonstrated that IL-10 is correlated to the executive function of T2DM patients. Decreased IL-10 may result from the regulation of miR-let-7c-5p in exosomes.
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Cognição , Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Interleucina-10 , MicroRNAs/genéticaRESUMO
To verify the effect of sleep ambient music intervention (SAMI) on sleep quality and mental status of college students, and to further explore the minimum effective duration of SAMI, this study was designed as a pre-and post-intervention self-controlled exploratory study. Participants were subjected to a one-week no-intervention test, then 4 weeks of music intervention followed. Subjective sleep quality data were collected using the Pittsburgh Sleep Quality Index (PSQI); objective sleep quality data were collected with Actigraphy; and mental status data were collected using the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II). Data were analyzed and processed using mixed-effects models and repeated measures. The results showed that compared with the no-intervention week, college students' subjective sleep quality, objective sleep onset latency (SOL), trait anxiety, and depression symptom were reduced at week 1; week 2; week 3; week 4 under SAMI; state anxiety of college students at week 3 and week 4 under SAMI were also reduced. And there were differences in sleep quality among college students of different genders too. Compared with females, males had worse sleep efficiency (SE), shorter total sleep time (TST), and more awaking times (AT). In addition, 3 days was the minimum effective length for SAMI to shorten objective SOL, and 2 days was the minimum effective length to shorten the subjective SOL of college students. The findings of this study suggest that SAMI can improve subjective sleep quality, shorten objective SOL, and reduce anxiety and depression in college students. Interventions for more than 3 days had a significant effect on shortening SOL and long-term effects seemed to emerge after 3 weeks.
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BACKGROUND: Increased levels of low-density lipoprotein cholesterol (LDL-C) have been identified as one potential risk factor for diabetic peripheral neuropathy (DPN) in patients. The current study seeks to clarify the link between LDL-C, hyperglycemia, and DPN in patients with type 2 diabetes mellitus (T2DM). METHODS: Here, a total of 120 T2DM individuals were recruited. These volunteers with T2DM were divided into 2 groups, based on the presence or absence of peripheral neuropathy. Additionally, their baseline characteristics were compared. Association among LDL-C and glycosylated hemoglobin (HbA1c) levels and DPN, particularly with respect to specific nerve conduction velocity were analyzed. To identify factors influencing DPN, regression was performed. Furthermore, mediation analysis was employed to evaluate the indirect, direct and total effects of LDL-C on specific nerve conduction velocity, with HbA1c serving as a mediator. RESULTS: Compared to 55 patients without DPN, 65 patients with DPN demonstrated elevated levels of LDL-C and HbA1c. Both LDL-C and HbA1c have been found to be associated with reduced the motor fiber conduction velocities of Ulnar (or the Common peroneal) nerve in diabetic patients. HbA1c is one of the known risk factors for DPN in individuals with T2DM. Further mediation analysis revealed that the effect of LDL-C on the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities are fully mediated by HbA1c in patients with T2DM. CONCLUSIONS: The impact of elevated LDL-C levels upon the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities in patients with T2DM was found to be entirely mediated by increased HbA1c levels.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas , Neuropatias Diabéticas/etiologia , LDL-Colesterol , Fatores de RiscoRESUMO
BACKGROUND: Male factors-caused decline in total fertility has raised significant concern worldwide. LncRNAs have been identified to play various roles in biological systems, including spermatogenesis. This study aimed to explore the role of lncRNA5251 in mouse spermatogenesis. METHODS: The expression of lncRNA5251 was modulated in mouse testes in vivo or spermatogonial stem cells (C18-4 cells) in vitro by shRNA. RESULTS: The sperm motility in two generations mice after modulation of lncRNA5251 (muF0 and muF1) was decreased significantly after overexpression of lncRNA5251. GO enrichment analysis found that knockdown lncRNA5251 increased the expression of genes related to cell junctions, and genes important for spermatogenesis in mouse testes. Meanwhile, overexpressing lncRNA5251 decreased the gene and/or protein expression of important genes for spermatogenesis and immune pathways in mouse testes. In vitro, knockdown lncRNA5251 increased the expression of genes for cell junction, and the protein levels of some cell junction proteins such as CX37, OCLN, JAM1, VCAM1 and CADM2 in C18-4 cells. LncRNA5251 is involved in spermatogenesis by modulation of cell junctions. CONCLUSION: This will provide a theoretical basis for improving male reproductive ability via lncRNA.
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RNA Longo não Codificante , Motilidade dos Espermatozoides , Masculino , Animais , Camundongos , Junções Intercelulares , Fertilidade , RNA Longo não Codificante/genética , Espermatogênese/genéticaRESUMO
Studies have identified that mating induces a series of physiological changes in animals. In this period, males tending to invest more energy, immune peptides, and other substances to reduce the cost of living for females. This results in lower survival rates in later life than females. Meanwhile, both males and females shorten lifespans due to reproduction. However, the reasons why termites' queens and kings are both extremely long-lived and highly fecund are unclear. Therefore, this study aimed to examine the effects of mating on the expression of immune and DNA repair genes for lifespan extension in termite queens and kings. Here, we reported that mated queens show relatively higher expression of immune genes (phenoloxidase, denfensin, termicin, transferrin), antioxidant genes (CAT, SOD), detoxification genes (GST, CYP450) than virgin queens in the Reticulitermes chinensis. In addition, mated kings also highly expressed these genes, except for termicin, transferrin, GST, and CYP450. After mating, both queens and kings significantly upregulated the expression of DNA repair genes (MLH1, BRCA1, XRCC3, RAD54-like). Mismatch repair genes (MMR) MSH2, MSH4, MSH6 were considerably increased in mated queens, while MSH4, MSH5, MSH6 were upregulated in mated kings. Our results suggest that mating increases the expression of immune and DNA repair genes in the termite queens and kings, and thus possibly improving their survival during reproductive span due to the omnipresent pathogens.
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Isópteros , Animais , Feminino , Masculino , Isópteros/genética , Isópteros/metabolismo , Reprodução/genética , Fertilidade , Reparo do DNA , Transferrinas/genética , Transferrinas/metabolismoRESUMO
Background: Cephalosporins are used as first-line antimicrobial prophylaxis for orthopedics surgeries. However, alternative antibiotics are usually used in the presence of penicillin allergy (PA), which might increase the risk of surgical site infection (SSI). This study aimed to analyze the relationship between SSI after orthopedic surgeries and PA among surgical candidates and related alternative antibiotic use. Methods: In this single-center retrospective cohort study, we compared inpatients with and without PA from January 2015 to December 2021. The primary outcome was SSI, and the secondary outcomes were SSI sites and perioperative antibiotic use. Moreover, pathogen characteristics of all SSIs were also compared between the two cohorts. Results: Among the 20,022 inpatient records, 1704 (8.51%) were identified with PA, and a total of 111 (0.55%) SSI incidents were reported. Compared to patients without PA, patients with PA had higher postoperative SSI risk (1.06%, 18/1704 vs. 0.51%, 93/18318), shown both in multivariable regression analysis (odds ratio [OR] 2.11; 95% confidence interval [CI], 1.26-3.50; p= 0.004) and propensity score matching (OR 1.84; 95% CI, 1.05-3.23; p= 0.034). PA was related to elevated deep SSI risk (OR 2.79; 95% CI, 1.47-5.30; p= 0.002) and had no significant impact on superficial SSI (OR 1.39; 95% CI, 0.59-3.29; p= 0.449). The PA group used significantly more alternative antibiotics. Complete mediation effect of alternative antibiotics on SSI among these patients was found in mediation analysis. Pathogen analysis revealed gram-positive cocci as the most common pathogen for SSI in our study cohort, while patients with PA had higher infection rate from gram-positive rods and gram-negative rods than non-PA group. Conclusion: Compared to patients without PA, patients with PA developed more SSI after orthopedic surgeries, especially deep SSI. The elevated infection rate could be secondary to the use of alternative prophylactic antibiotics.