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OBJECTIVE: The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown. METHODS: Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP). RESULTS: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4+ Th1 cells mediated tumor necrosis factor (TNF) pathway. INTERPRETATION: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488-507.
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Astrócitos , Exossomos , Neurônios GABAérgicos , Células-Tronco Neurais , Animais , Exossomos/transplante , Exossomos/metabolismo , Camundongos , Astrócitos/metabolismo , Humanos , Neurônios GABAérgicos/metabolismo , Células-Tronco Neurais/transplante , Células-Tronco Neurais/metabolismo , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Cognição/fisiologia , MasculinoRESUMO
The basal plane of transition metal dichalcogenides (TMDCs) is inert for the hydrogen evolution reaction (HER) due to its low-efficiency charge transfer kinetics. We propose a strategy of filling the van der Waals (vdW) layer with delocalized electrons to enable vertical penetration of electrons from the collector to the adsorption intermediate vertically. Guided by density functional theory, we achieve this concept by incorporating Cu atoms into the interlayers of tantalum disulfide (TaS2). The delocalized electrons of d-orbitals of the interlayered Cu can constitute the charge transfer pathways in the vertical direction, thus overcoming the hopping migration through vdW gaps. The vertical conductivity of TaS2 increased by 2 orders of magnitude. The TaS2 basal plane HER activity was extracted with an on-chip microcell. Modified by the delocalized electrons, the current density increased by 20 times, reaching an ultrahigh value of 800 mA cm-2 at -0.4 V without iR compensation.
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Although amino acid (AA) metabolism is linked to tumor progression and could serve as an attractive intervention target, its association with neuroblastoma (NB) is unknown. Based on AA metabolism-related genes, we established three NB subtypes associated with distinct prognoses and specific functions, with C1 and C2 having better outcomes. The C1 displayed enhanced metabolic activity and recruited metabolism-associated cells. The C2 exhibited an activated immune microenvironment and was more vulnerable to immunotherapy. The C3, characterized by cell cycle peculiarity, possessed a dismal prognosis and high frequency of gene mutations and was susceptible to chemotherapy. Furthermore, single-cell RNA sequencing analysis revealed that the C3-associated Scissor+ cell subpopulation was characterized by notorious functional states and orchestrated an immunosuppressive microenvironment. Additionally, we identified that ALK and BIRC5 contributed to the shorter lifespan of C3 and their corresponding inhibitors were potential interventions. In conclusion, we identified three distinct subtypes of NB, which help us foster individualized therapeutic strategies to improve the prognosis of NB.
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Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products (RAGE), activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 (timo A3) could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.
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Two-dimensional (2D) materials with spin polarization have great potential for achieving next-generation spintronic applications. However, spin polarization of 2D materials is usually produced at a cryogenic temperature because of thermal fluctuations, which severely hinder their further applications. Here, we report room-temperature intrinsic magnetic-induced circularly polarized photoluminescence (PL) in 2D Er2O2S flakes. The geff factor of 2D Er2O2S stays at around -6.3 from the liquid He temperature limit to room temperature, which is independent of temperature. This anomalous phenomenon in Er2O2S is totally different from previous materials, which all have a decreasing Zeeman splitting with increasing temperature resulting from thermal fluctuations. The anomalous temperature-dependent magnetic-induced circularly polarized PL originates from the weak electron-phonon coupling in 2D Er2O2S, which has been proven by both the temperature-dependent Raman and theoretical calculations. This work sheds light on the understanding and manipulation of 2D materials for practical spintronic applications.
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BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.
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COVID-19 , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , COVID-19/complicações , SARS-CoV-2 , Alta do Paciente , Estudos de Coortes , Seguimentos , Qualidade de Vida , FadigaRESUMO
BACKGROUND: Camellia nitidissima Chi is a popular ornamental plant because of its golden flowers, which contain flavonoids and carotenoids. To understand the regulatory mechanism of golden color formation, the metabolites of C. nitidissima petals at five different developmental stages were detected, a proteome map of petals was first constructed via tandem mass tag (TMT) analysis, and the accuracy of the sequencing data was validated via parallel reaction monitoring (PRM). RESULTS: Nineteen color components were detected, and most of these components were carotenoids that gradually accumulated, while some metabolites were flavonoids that were gradually depleted. A total of 97,647 spectra were obtained, and 6,789 quantifiable proteins were identified. Then, 1,319 differentially expressed proteins (DEPs) were found, 55 of which belong to the flavonoid and carotenoid pathways, as revealed by pairwise comparisons of protein expression levels across the five developmental stages. Notably, most DEPs involved in the synthesis of flavonoids, such as phenylalanine ammonium lyase and 4-coumarate-CoA ligase, were downregulated during petal development, whereas DEPs involved in carotenoid synthesis, such as phytoene synthase, 1-deoxy-D-xylulose-5-phosphate synthase, and ß-cyclase, tended to be upregulated. Furthermore, proteinâprotein interaction (PPI) network analysis revealed that these 55 DEPs formed two distinct PPI networks closely tied to the flavonoid and carotenoid synthesis pathways. Phytoene synthase and chalcone synthase exhibited extensive interactions with numerous other proteins and displayed high connectivity within the PPI networks, suggesting their pivotal biological functions in flavonoid and carotenoid biosynthesis. CONCLUSION: Proteomic data on the flavonoid and carotenoid biosynthesis pathways were obtained, and the regulatory roles of the DEPs were analyzed, which provided a theoretical basis for further understanding the golden color formation mechanism of C. nitidissima.
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Camellia , Carotenoides , Flavonoides , Flores , Proteínas de Plantas , Proteômica , Camellia/genética , Camellia/metabolismo , Camellia/crescimento & desenvolvimento , Flores/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Carotenoides/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Flavonoides/metabolismo , Vias Biossintéticas , Regulação da Expressão Gênica de Plantas , Proteoma/metabolismoRESUMO
Prostatitis represents a common disease of the male genitourinary system, significantly impacting the physical and mental health of male patients. While numerous studies have suggested a potential link between immune cell activity and prostatitis, the exact causal role of immune cells in prostatitis remains uncertain. This study aims to explore the causal relationship between immune cell characteristics and prostatitis using a bidirectional Mendelian randomization approach. This study utilizes data from the public GWAS database and employs bidirectional Mendelian randomization analysis to investigate the causal relationship between immune cells and prostatitis. The causal relationship between 731 immune cell features and prostatitis was primarily investigated through inverse variance weighting (IVW), complemented by MR-Egger regression, a simple model, the weighted median method, and a weighted model. Ultimately, the results underwent sensitivity analysis to assess the heterogeneity, horizontal pleiotropy, and stability of Single Nucleotide Polymorphisms (SNPs) in immune cells and prostatitis. MR analysis revealed 17 immune cells exhibiting significant causal effects on prostatitis. In contrast, findings from reverse MR indicated a significant causal relationship between prostatitis and 13 immune cells. Our study utilizes bidirectional Mendelian Randomization to establish causal relationships between specific immune cell phenotypes and prostatitis, highlighting the reciprocal influence between immune system behavior and the disease. Our findings suggest targeted therapeutic approaches and the importance of including diverse populations for broader validation and personalized treatment strategies.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Prostatite , Masculino , Humanos , Prostatite/genética , Prostatite/imunologia , Predisposição Genética para DoençaRESUMO
Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.
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Carcinoma de Células de Transição , MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Invasividade Neoplásica/genética , Proliferação de Células/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
BACKGROUND: Premature ovarian insufficiency (POI) is a condition characterized by a substantial decline or loss of ovarian function in women before the age of 40. However, the pathogenesis of POI remains to be further elucidated, and specific targeted drugs which could delay or reverse ovarian reserve decline are urgently needed. Abnormal DNA damage repair (DDR) and cell senescence in granulosa cells are pathogenic mechanisms of POI. Ubiquitin-specific protease 14 (USP14) is a key enzyme that regulates the deubiquitylation of DDR-related proteins, but whether USP14 participates in the pathogenesis of POI remains unclear. METHODS: We measured USP14 mRNA expression in granulosa cells from biochemical POI (bPOI) patients. In KGN cells, we used IU1 and siRNA-USP14 to specifically inhibit USP14 and constructed a cell line stably overexpressing USP14 to examine its effects on DDR function and cellular senescence in granulosa cells. Next, we explored the therapeutic potential of IU1 in POI mouse models induced by D-galactose. RESULTS: USP14 expression in the granulosa cells of bPOI patients was significantly upregulated. In KGN cells, IU1 treatment and siUSP14 transfection decreased etoposide-induced DNA damage levels, promoted DDR function, and inhibited cell senescence. USP14 overexpression increased DNA damage, impaired DDR function, and promoted cell senescence. Moreover, IU1 treatment and siUSP14 transfection increased nonhomologous end joining (NHEJ), upregulated RNF168, Ku70, and DDB1, and increased ubiquitinated DDB1 levels in KGN cells. Conversely, USP14 overexpression had the opposite effects. Intraperitoneal IU1 injection alleviated etoposide-induced DNA damage in granulosa cells, ameliorated the D-galactose-induced POI phenotype, promoted DDR, and inhibited cell senescence in ovarian granulosa cells in vivo. CONCLUSIONS: Upregulated USP14 in ovarian granulosa cells may play a role in POI pathogenesis, and targeting USP14 may be a potential POI treatment strategy. Our study provides new insights into the pathogenesis of POI and a novel POI treatment strategy.
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Senescência Celular , Dano ao DNA , Reparo do DNA , Células da Granulosa , Insuficiência Ovariana Primária , Ubiquitina Tiolesterase , Feminino , Insuficiência Ovariana Primária/patologia , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/genética , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia , Senescência Celular/efeitos dos fármacos , Animais , Humanos , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Reparo do DNA/efeitos dos fármacos , Camundongos , Adulto , Camundongos Endogâmicos C57BL , Linhagem CelularRESUMO
Mode-pairing quantum key distribution (MP-QKD) holds great promise for the practical implementation of QKD in the near future. It combines the security advantages of measurement device independence while still being capable of breaking the Pirandola-Laurenza-Ottaviani-Banchi bound without the need for highly demanding phase-locking and phase-tracking technologies for deployment. In this work, we explore optimization strategies for MP-QKD in a wavelength-division multiplexing scenario. The simulation results reveal that incorporation of multiple wavelengths not only leads to a direct increase in key rate but also enhances the pairing efficiency by employing our novel pairing strategies among different wavelengths. As a result, our work provides a new avenue for the future application and development of MP-QKD.
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BACKGROUND: Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. METHODS: Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. RESULTS: Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. CONCLUSIONS: Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.
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Biomarcadores , Glicemia , Bases de Dados Factuais , Infarto do Miocárdio , Valor Preditivo dos Testes , Choque Cardiogênico , Triglicerídeos , Humanos , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/sangue , Choque Cardiogênico/epidemiologia , Feminino , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Glicemia/metabolismo , Prognóstico , Biomarcadores/sangue , Medição de Risco , Triglicerídeos/sangue , Incidência , Fatores de Risco , China/epidemiologia , Fatores de Tempo , Mortalidade Hospitalar , Idoso de 80 Anos ou maisRESUMO
Lightweight and robust aerogels with multifunctionality are highly desirable to meet the technological demands of current society. Herein, we designed lightweight, elastic, and superhydrophobic multifunctional organic-inorganic fibrous hybrid aerogels which were assembled with organic aramid nanofibers and inorganic hierarchical porous carbon fibers. Thanks to the organic-inorganic fiber hybridization strategy, the optimal aerogels possessed remarkable compressibility and elasticity. Benefiting from the microscopic hierarchical porous structure of carbon fibers and the macroscopic macroporous lamellar structure of aerogels, the optimal aerogels exhibited superb lightweight property, conspicuous electromagnetic microwave absorption ability, and outstanding oily wastewater purification capacity. As for electromagnetic microwave absorption, it achieved a strong reflection loss of -41.8 dB, and the effective absorption bandwidth reached 6.86 GHz. Besides, the oil adsorption capacity for trichloromethane reached as high as 93.167 g g-1 with a capacity retention of 95.6% after 5 cycles. Meanwhile, it could act as a gravity-driven separation membrane to continuously separate trichloromethane from a trichloromethane-water mixture with a high flux of 7867.37 L·m-2·h-1, even for surfactant-stabilized water-in-n-heptane emulsions of 3794.94 L·m-2·h-1. Such a strategy might shed some light on the construction of multifunctional aerogels toward broader applications.
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An ingenious microstructure of electromagnetic microwave absorption materials is crucial to achieve strong absorption and a broad bandwidth. Herein, one-dimensional (1D) carbon fibers with implantation of zero-dimensional (0D) ZIF-8-derived carbon frameworks and construction of a three-dimensional (3D) microcosmic multichannel porous structure are fabricated by electro-blown spinning, solvent-thermal reaction, and high-temperature pyrolysis techniques. The 1D carbon fiber skeleton with a multichannel structure provides a direct axial conductive pathway for charge transport, which plays an important role in dielectric loss. The 0D surface carbon frameworks offer plenty of heterogeneous interfaces to trigger intensive interfacial polarization loss and act as dihedral angles for microwave scattering. The 3D microcosmic multichannel pores can not only generate multiple reflections as much as possible to dissipate electromagnetic microwave energy but also supply huge interior cavities to improve impedance matching. Thanks to the synergistic effect of a strong electrically conductive pathway for enhancing the conductive loss, a plenteous heterogeneous interface for triggering intensive interfacial polarization loss, microcosmic multichannel pores for generating multiple reflections and improving impedance matching, and N and O atom doping for inducing dipole polarization, the optimal sample with an ingenious microstructure delivers an excellent absorption performance of a minimum reflection loss of -35.5 dB at a thickness of 5.0 mm and an effective absorption bandwidth of 6.72 GHz (10.96-17.68 GHz) at a thickness of 2.0 mm. Such a well-designed multichannel porous carbon fiber may pave the way for the exploitation of high-performance microwave absorbing materials.
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AIMS: To elucidate the clinical determinants of the coefficient of variation (CV) of glucose by analysing the pancreatic ß-cell function of subjects with type 2 diabetes mellitus (T2DM). METHODS: A total of 716 Chinese subjects with T2DM were included. Continuous glucose monitoring (CGM) was used to assess blood glucose, and the CV was calculated. C-peptide concentration at 0, 0.5, 1, 2 and 3 hours (Cp0h, Cp0.5h, Cp1h, Cp2h and Cp3h, respectively) was measured after a standard 100-g steamed bun meal test to assess pancreatic ß-cell function. The determinants of glucose variability defined by the CV of CGM values were explored from two perspectives: the CV of qualitative variables and the CV of quantitative variables. RESULTS: Our data revealed that C-peptide concentration (Cp0h, Cp0.5h, Cp1h, Cp2h, Cp3h), area under the curve for C-peptide concentration at 0.5 and 3 hours (AUC-Cp0.5h and AUC-Cp3h) decreased with increasing CV quartile (P < 0.05). The CV was negatively correlated with homeostatic model assessment of ß-cell function index, C-peptide concentration at all timepoints, and AUC-Cp0.5h and AUC-Cp3h (P < 0.001). Quantile regression analysis showed that AUC-Cp0.5h had an overall negative effect on the CV in the 0.05 to 0.95 quartiles, and AUC-Cp3h tended to have a negative effect on the CV in the 0.2 to 0.65 quartiles. After adjusting for confounders, multinomial logistic regression showed that each 1-unit increase in AUC-Cp0.5h was associated with a 31.7% reduction in the risk of unstable glucose homeostasis (CV > 36%; P = 0.036; odds ratio 0.683; 95% confidence interval 0.478-0.976). We also identified the AUC-Cp0.5h (0.735 ng/mL) and AUC-Cp3h (13.355 ng/mL) cut-off values for predicting unstable glucose homeostasis (CV >36%) in T2DM subjects. CONCLUSION: Our study suggests that impaired pancreatic ß-cell function may be a clinical determining factor of CV of glucose in people with T2DM.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Glicemia/análise , Glucose , Automonitorização da Glicemia , Peptídeo C , Monitoramento Contínuo da Glicose , China/epidemiologiaRESUMO
The decellularized tilapia skin (dTS) has gained significant attention as a promising material for tissue regeneration due to its ability to provide unique structural and functional components that support cell growth, adhesion, and proliferation. However, the clinical application of dTS is limited by its low mechanical strength and rapid biodegradability. Herein, we prepare a novel RGD (arginine-glycine-aspartic acid) functionalized dTS scaffold (dTS/RGD) by using transglutaminase (TGase) crosslinking. The developed dTS/RGD scaffold possesses excellent properties, including a medium porosity of â¼59.2%, a suitable degradation rate of approximately 80% over a period of two weeks, and appropriate mechanical strength with a maximum tensile stress of â¼46.36 MPa which is much higher than that of dTS (â¼32.23 MPa). These properties make the dTS/RGD scaffold ideal for promoting cell adhesion and proliferation, thereby accelerating skin wound healing in a full-thickness skin defect model. Such an enzymatic cross-linking strategy provides a favorable microenvironment for wound healing and holds great potential for application in skin regeneration engineering.
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Oligopeptídeos , Regeneração , Pele , Tilápia , Alicerces Teciduais , Transglutaminases , Animais , Alicerces Teciduais/química , Tilápia/metabolismo , Transglutaminases/metabolismo , Transglutaminases/química , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Cicatrização , Proliferação de Células , Engenharia Tecidual , Porosidade , Camundongos , Adesão Celular , HumanosRESUMO
PURPOSE: Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. METHODS: A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group (N = 45) received conventional psychological care and treatment, and the experimental group (N = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). RESULTS: Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences (P < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients (P < 0.05), and there was an interaction with intervention factors (P < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention (P < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. CONCLUSIONS: The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).
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Neoplasias , Grupo Associado , Angústia Psicológica , Apoio Social , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Adulto , Neoplasias/psicologia , Neoplasias/terapia , Depressão/terapia , Depressão/etiologia , Depressão/psicologia , Ansiedade/etiologia , Ansiedade/terapia , Estresse Psicológico/etiologia , Estresse Psicológico/terapia , Intervenção Baseada em InternetRESUMO
A Gram-stain-negative, motile (by single polar flagellum) and rod-shaped bacterium, designated W1-6T, was isolated from a sediment of drainage ditch in winery in Guiyang, south-western China. Strain W1-6T showed the highest 16S rRNA gene sequence similarities with the type strain of Acidovorax wautersii (98.1%) and Simplicispira lacusdiani (97.9%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain W1-6T was placed adjacent to the members of the genus Simplicispira and formed a separat subclade. Cells showed oxidase and catalase negative reactions. The only respiratory quinone detected was ubiquinone-8 (Q-8). Summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) were predominant cellular fatty acids (> 10%) of strain W1-6T. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and five unidentified phospholipids were found in the polar lipid extraction. The genomic DNA G + C content was 65.6%. Strain W1-6T shared the highest digital DNA-DNA hybridization [dDDH, (27.6%)] and average nucleotide identity [ANI (84.3%)] values with the type strain of S. lacusdiani. The dDDH and ANI values were below the cutoff level (dDDH 70%; ANI 95-96%) for species delineation. The polyphasic characteristics indicated that the strain W1-6T represents a novel species of the genus Simplicispira, for which the name Simplicispira sedimenti sp. nov. is proposed. The type strain is W1-6T (= CGMCC 1.16274T = NBRC 115624T).
Assuntos
Ácidos Graxos , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , China , Ubiquinona , DNA , Drenagem , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genéticaRESUMO
Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor-α (TNF-α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF-α promoter region are considered to influence its transcription and are associated with the TNF-α level. Therefore, it is worth detecting the association of the variants in the TNF-α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF-α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (p = .002, OR = 1.563; 95% CI: 1.18-2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log-additive mode (p = .002, OR = 1.56; 95% CI: 1.17-2.07). The haplotypes analysis identified that the rs1799724-rs1800629CA was associated with high risk of the development of T2DM (p = .002, OR = 1.559, 95% CI: 1.173-2.072). Conversely, the rs1799724-rs1800629CG was a protective haplotype of T2DM (p = .001, OR = 0.732, 95% CI: 0.607-0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (p = .017). Our results revealed that the rs1800629 in the TNF-α gene promoter region was associated with T2DM in a Chinese Han population.
RESUMO
INTRODUCTION: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. METHODS: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. CONCLUSION: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.