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AIM: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. METHODS: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. RESULTS: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. CONCLUSIONS: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China.
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Análise Custo-Benefício , Diabetes Mellitus Tipo 2 , Custos de Medicamentos , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/economia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/economia , China , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Custos de Medicamentos/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Receptor do Peptídeo Semelhante ao Glucagon 2 , Polipeptídeo Inibidor GástricoRESUMO
BACKGROUND: Frailty becomes more pronounced with advancing age, tightly intertwined with adverse clinical outcomes. Across diverse medical disciplines, frailty is now universally recognized as not only a risk factor but also a predictive indicator for unfavorable clinical prognosis. METHODS: This study was a retrospective cohort study that included clinical data from patients (aged ≥ 65 years) with esophageal cancer treated surgically at the First Affiliated Hospital of Anhui Medical University in 2021. For each patient, we calculated their 11-index modified frailty index(mFI-11) scores and categorized the patients into a frailty group (mFI-11hign) and a non-frailty group (mFI-11low) based on the optimal grouping cutoff value of 0.27 from a previous study. The primary study index was the incidence of postoperative pulmonary infection, arrhythmia, anastomotic fistula, chylothorax, and electrolyte disturbance complications. Secondary study indicators included postoperative ICU stay, total hospitalization time, readmission rate within 30 days of discharge, and mortality within 30 days after surgery. We performed univariate and multivariate analyses to assess the association between mFI-11 and adverse outcomes as well as postoperative complications. RESULTS: Five hundred and fifteen patients were included, including 64.9% (334/515) in the non-frailty group and 35.1% (181/515) in the frailty group. Comparing postoperative complication rates between the two groups revealed lower incidences of postoperative anastomotic fistula (21.5% vs. 4.5%), chylothorax (16.0% vs. 2.1%), cardiac arrhythmia (61.9% vs. 9.9%), pulmonary infections (85.1% vs. 26.6%), and electrolyte disturbance (84.5% vs. 15.0%) in patients of the non-frailty group was lower than that in the frailty group (p < 0.05). mFI-11 showed better prognostic results in predicting postoperative complications. anastomotic fistula (area under the ROC curve AUROC = 0.707), chylothorax (area under the ROC curve AUROC = 0.744), pulmonary infection (area under the ROC curve AUROC = 0.767), arrhythmia (area under the ROC curve AUROC = 0.793), electrolyte disturbance (area under the ROC curve AUROC = 0.832), and admission to ICU (area under the ROC curve AUROC = 0.700). CONCLUSION: Preoperative frail elderly patients with esophageal cancer have a high rate of postoperative complications. mFI-11 can be used as an objective indicator for identifying elderly patients at risk for esophageal cancer.
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Neoplasias Esofágicas , Complicações Pós-Operatórias , Humanos , Neoplasias Esofágicas/cirurgia , Masculino , Feminino , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , China/epidemiologia , Fragilidade/epidemiologia , Fragilidade/diagnóstico , Idoso de 80 Anos ou mais , Esofagectomia/efeitos adversos , Fatores de Risco , Avaliação Geriátrica/métodos , Prognóstico , Idoso Fragilizado , População do Leste AsiáticoRESUMO
Polycystic ovary syndrome is a complicated hormonal and metabolic disorder. The exact pathogenesis of polycystic ovary syndrome is not clear thus far. Inflammation is involved in the progression of polycystic ovary syndrome. In addition, brown adipose tissue activity is impaired in polycystic ovary syndrome. Interestingly, glucagon-like peptide-1 receptor agonists have been reported to alleviate inflammation and promote browning of white adipose tissue. In this study, the effects of glucagon-like peptide-1 receptor agonists on polycystic ovary syndrome mice were explored. Mice were randomly assigned into four groups: control, dehydroepiandrosterone, dehydroepiandrosterone + liraglutide, and dehydroepiandrosterone + semaglutide. Relative indexes were measured after glucagon-like peptide-1 receptor agonist intervention. Glucose metabolism in polycystic ovary syndrome mice was ameliorated by glucagon-like peptide-1 receptor agonists, while the reproductive endocrine disorder of polycystic ovary syndrome mice was partially reversed. The messenger ribonucleic acid levels of steroidogenic enzymes and the expression of inflammatory mediators in serum and ovaries of polycystic ovary syndrome mice were improved. Furthermore, toll-like receptor 4 and phosphorylation of nuclear factor-kappa B protein levels were decreased by glucagon-like peptide-1 receptor agonists in ovary. Notably, after glucagon-like peptide-1 receptor agonist intervention, the expression of brown adipose tissue marker levels was considerably raised in the white adipose tissue of polycystic ovary syndrome mice. In conclusion, the hyperinsulinemia and hyperandrogenemia of polycystic ovary syndrome mice were alleviated by glucagon-like peptide-1 receptor agonist intervention, which was associated with mitigating inflammation and stimulating adipose tissue browning.
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Hiperandrogenismo , Hiperinsulinismo , Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Humanos , Camundongos , Animais , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hiperinsulinismo/tratamento farmacológico , Inflamação/tratamento farmacológico , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Desidroepiandrosterona/farmacologiaRESUMO
Increasing numbers of exopolysaccharides and their properties have been explored. However, the difficulty of extracting high-viscosity exopolysaccharides has hindered their further industrialization. In this research, we explored a strategy based on encapsulated structure control under different pH to efficiently extract Pantoea alhagi exopolysaccharides (PAPS). Results showed that at pH levels of 6, 12, and 13, the extraction efficiency of PAPS was elevated, and the yield did not decrease. The rheological properties of the pH-12-treated PAPS were better than those of PAPS treated at pH 7, while the pH-6-treated PAPS decreased. The effects of pH-12-treated PAPS on soil macroaggregates and soil's water evaporation rate were similar to those of PAPS treated at pH 7. In addition, we observed that treatment at pH 12 produced a significantly reduced encapsulated structure compared with treatment at pH 7. The proportion of unsaturated fatty acids after treatment at pH 12 was higher than after treatment at pH 7, which may result in reduced encapsulated structure in pH-12 conditions. These results enrich the understanding of the effect that alters pH conditions on the encapsulated structure to improve the extraction efficiency of exopolysaccharides and provide a theoretical basis for the extraction of exopolysaccharides with extreme viscosity.
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Pantoea , Viscosidade , Solo , Concentração de Íons de HidrogênioRESUMO
Prevalence of obesity becomes an important health issue worldwide, but the management of obesity remains unsatisfied. This study aimed to explore the mechanism of long non-coding RNA TUG/miR-204/SIRT1 axis, which was involved in the pathogenesis of obesity. Obesity mouse model was induced by high-fat diet and treated with taurine upregulated gene1 (TUG1) virus via tail intravenous injection. Then, body weight, serum glucose, insulin tolerance, testicular fat weight were detected, as well as the expression of TUG1, microRNA-204 (miR-204), sirtuin1 (SIRT1), and inflammation and fatty accumulation associated proteins and cytokines. Regulatory relationship between TUG1/SIRT1 and miR-204 was confirmed by dual-luciferase reporter activity assay. A high-glucose-induced 3T3-L1 cell model was also constructed to explore the regulatory mechanism of TUG/miR-204/SIRT1 axis in the pathogenesis of obesity at cell level after altering the expression of TUG1, miR-204, and SIRT1. Overexpression of TUG1 could significantly attenuate the weight, serum glucose, glucose, insulin tolerance, fatty accumulation, and inflammation in obesity mice, as well as the elevation of miR-204, but increase the expression of SIRT1, phosphorylated AKT (p-AKT), glucose transporter4 (GLUT4), and peroxisome proliferator activated receptorγ (PPARγ). Both TUG1 and SIRT1 were targets of miR-204 and could be negatively regulated by miR-204. Overexpression of TUG1 could suppress the inflammation in adipocytes via downregulating miR-204 and promote GLUT4/PPARγ/AKT pathway high-glucose-induced inflammation in 3T3-L1 cells. miR-204 inhibitors could also suppress high-glucose-induced inflammation in 3T3-L1 cells via promoting SIRT1/ GLUT4/PPARγ/AKT pathway. LncRNA TUG1 could negatively regulate miR-204 to alleviate inflammation and insulin tolerance via promoting SIRT1/GLUT4/PPARγ/AKT pathway.
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Tecido Adiposo Branco/efeitos dos fármacos , Inflamação/metabolismo , Resistência à Insulina , MicroRNAs/metabolismo , Obesidade/metabolismo , RNA Longo não Codificante/metabolismo , Sirtuína 1/metabolismo , Células 3T3-L1 , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Proliferação de Células/fisiologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Hipoglicemiantes/farmacologia , Inflamação/etiologia , Inflamação/patologia , Insulina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , MicroRNAs/genética , Obesidade/genética , PPAR gama/metabolismo , RNA Longo não Codificante/genética , Sirtuína 1/genéticaRESUMO
Gestational diabetes mellitus (GDM) imparts a high risk of developing postpartum diabetes and is considered to be an early stage of type 2 diabetes mellitus (T2DM). In this study, a 75-g oral glucose tolerance test was performed on 472 women with GDM at 6-8 weeks after delivery. The clinical and metabolic characteristics were compared between the patients with normal glucose tolerance (NGT) and abnormal glucose metabolism (AGM). These data were then compared between pre-diabetic and diabetic patients. A total of 37.7% of the women with GDM continued to have abnormal glucose levels after delivery. Compared with the women who reverted to normal, HOMA-IR was significantly higher in AGM. A multiple stepwise regression analysis revealed that age, the postpartum body mass index (BMI), low density lipoprotein-cholesterol (LDL-C), 2 h glucose load plasma glucose (2 h PG), triglycerides (TG), hemoglobin A1c (HbA1c), 1 h glucose load plasma insulin (INS) level, and 2 h INS level were independent risk factors for the development of insulin resistance after delivery. This study has identified a high prevalence of AGM after GDM. Insulin resistance appears to be the major contributor. Any treatment to reduce the postpartum BMI and lipids level may be beneficial to decrease insulin resistance.
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Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Intolerância à Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Período Pós-Parto/metabolismo , Estado Pré-Diabético/metabolismo , Adulto , Povo Asiático , Glicemia/metabolismo , Índice de Massa Corporal , China/epidemiologia , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/epidemiologia , Feminino , Intolerância à Glucose/epidemiologia , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Estado Pré-Diabético/epidemiologia , Gravidez , Análise de Regressão , Fatores de Risco , Triglicerídeos/metabolismoRESUMO
Exosome is a kind of nanoscale-size extracellular vesicles secreted by the means of cell active stimulation with outer membrane structure of vacuoles corpuscle. It can carry and transfer a lot of biological molecules, such as DNA fragments, circular RNA (circRNA), messenger RNA (mRNA), microRNA (miRNA), functional proteins, transcription factors, etc., so as to achieve the goal of information transmission between cells. The relationship between exosomes and diabetes has received extensive attention in recent years. The exosomes play an important role in insulin sensitivity, glucose homeostasis and vascular endothelial function. This paper reviews the role of exosomes in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes as a target for diabetes treatment and its role in the diagnosis and treatment of diabetes.
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Diabetes Mellitus , Exossomos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Exossomos/metabolismo , Humanos , Resistência à Insulina/fisiologia , MicroRNAs/metabolismo , RNA Mensageiro/metabolismoRESUMO
Ultrafine ZnSnO3 nanoparticles, with an average diameter of 45 nm, homogeneously grown on reduced graphene oxide (rGO) have been successfully fabricated via methods of low temperature coprecipitation, colloid electrostatic self-assembly, and hydrothermal treatment. The uniformly distributed ZnSnO3 nanocrystals could inhibit the restacking of rGO sheets. In turn, the existence of rGO could hinder the growth and aggregation of ZnSnO3 nanoparticles in the synthesis process, increase the conductivity of the composite, and buffer the volume expansion of the ZnSnO3 nanocrystals upon lithium ion insertion and extraction. The obtained ZnSnO3/rGO exhibited superior cycling stability with a discharge/charge capacity of 718/696 mA h g-1 after 100 cycles at a current density of 0.1 A g-1.
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Humanin (MT-RNR2) is an endogenous polypeptide that is involved in many diseases, including T2DM. Gestational diabetes mellitus (GDM) is defined as hyperglycemia during pregnancy. The aim of this study was to evaluate serum humanin levels in women with or without GDM and to elucidate possible correlations with anthropometric parameters, metabolic parameters and the incidence of GDM. Eighty-four women with GDM and 73 control women were enrolled in this study. The clinical and biochemical parameters of all subjects were determined. Serum humanin levels were measured by an ELISA. Serum humanin levels were significantly lower in women with GDM than in control women. Moreover, humanin levels were significantly negatively correlated with the presence of GDM, body weight, BMI at 24 weeks of gestation, TG, FPG, 1 hPG, 2 hPG, FINS, and HOMA-IR. In contrast, humanin levels were significantly positively correlated with FT3 and FT4. A binary logistic analysis showed that humanin levels were associated with the incidence of GDM. Additional follow-up studies are needed to highlight whether and how decreased humanin levels play an important role in GDM.
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Diabetes Gestacional/sangue , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , GravidezRESUMO
The study is aimed to investigate the pathogenesis underlying the increased prevalence of thyroid nodule (TN) in different levels of metabolic syndrome (MetS) components and analyze the relationships between TN and MetS components. A total of 6,798 subjects, including 2201 patients with TN, were enrolled in this study. Anthropometric, biochemical, thyroid ultrasonographic, and other metabolic parameters were all measured. There was obviously sexual difference in the prevalence of TN (males 26.0%, females 38.5%, resp.). The prevalence of TN in hyperuricemia (45.7% versus 37.4%, P = 0.001), NAFLD (41.2% versus 36.4%, P < 0.05), and MetS (41.4% versus 35.4%, P < 0.001) groups was significantly increased only in females. Insulin resistance [OR = 1.31 (1.15, 1.49)], MetS [OR = 1.18 (1.03, 1.35)], and diabetes [OR = 1.25 (1.06, 1.48)] were all independent risk factors for TN in total subjects, whereas, after stratified analysis of gender, MetS [OR = 1.29, (1.09, 1.53)] and diabetes [OR = 1.47, (1.17, 1.84)] are still strongly and independently associated with the higher risks of TN in female subjects, but not in males. Our results suggest that the components of MetS might associate with the higher risks of TN in women than in men, but further cohort study of this gender disparity in the association between TN and MetS is required.
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Síndrome Metabólica/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/patologia , Fatores de Risco , Fatores Sexuais , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologiaRESUMO
Gestational diabetes mellitus (GDM) is considered as an early stage of type 2 diabetes mellitus. In this study, we compared demographic and clinical data between six GDM subjects and six normal glucose tolerance (NGT; healthy controls) subjects and found that homeostasis model of assessment for insulin resistance index (HOMA-IR) increased in GDM. Many previous studies demonstrated that omental adipose tissue dysfunction could induce insulin resistance. Thus, to investigate the cause of insulin resistance in GDM, we used label-free proteomics to identify differentially expressed proteins in omental adipose tissues from GDM and NGT subjects (data are available via ProteomeXchange with identifier PXD003095). A total of 3528 proteins were identified, including 66 significantly changed proteins. Adipocyte plasma membrane-associated protein (APMAP, a.k.a. C20orf3), one of the differentially expressed proteins, was down-regulated in GDM omental adipose tissues. Furthermore, mature 3T3-L1 adipocytes were used to simulate omental adipocytes. The inhibition of APMAP expression by RNAi impaired insulin signaling and activated NFκB signaling in these adipocytes. Our study revealed that the down-regulation of APMAP in omental adipose tissue may play an important role in insulin resistance in the pathophysiology of GDM.
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Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Diabetes Gestacional/metabolismo , Proteínas de Membrana/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Células 3T3-L1 , Tecido Adiposo/fisiopatologia , Adulto , Animais , Western Blotting , Cromatografia Líquida , Diabetes Gestacional/genética , Diabetes Gestacional/fisiopatologia , Feminino , Humanos , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Proteínas de Membrana/genética , Camundongos , NF-kappa B/metabolismo , Omento/metabolismo , Gravidez , Proteoma/genética , Interferência de RNA , Transdução de Sinais , Espectrometria de Massas em TandemRESUMO
Obesity-induced endoplasmic reticulum (ER) stress and inflammation lead to adipocytes dysfunction. Autophagy helps to adapt to cellular stress and involves in regulating innate inflammatory response. In present study, we examined the activity of rapamycin, a mTOR kinase inhibitor, against endoplasmic reticulum stress and inflammation in adipocytes. An in vitro model was used in which 3T3-L1 adipocytes were preloaded with palmitate (PA) to generate artificial hypertrophy mature adipocytes. Elevated autophagy flux and increased number of autophagosomes were observed in response to PA and rapamycin treatment. Rapamycin attenuated PA-induced PERK and IRE1-associated UPR pathways, evidenced by decreased protein levels of eIF2α phosphorylation, ATF4, CHOP, and JNK phosphorylation. Inhibiting autophagy with chloroquine (CQ) exacerbated these ER stress markers, indicating the role of autophagy in ameliorating ER stress. In addition, cotreatment of CQ abolished the anti-ER stress effects of rapamycin, which confirms the effect of rapamycin on ERs is autophagy-dependent. Furthermore, rapamycin decreased PA-induced nuclear translocation of NFκB P65 subunit, thereby NFκB-dependent inflammatory cytokines MCP-1 and IL-6 expression and secretion. In conclusion, rapamycin attenuated PA-induced ER stress/NFκB pathways to counterbalance adipocytes stress and inflammation. The beneficial of rapamycin in this context partly depends on autophagy. Stimulating autophagy may become a way to attenuate adipocytes dysfunction.
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Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Palmitatos/farmacologia , Sirolimo/farmacologia , Células 3T3-L1 , Adipócitos/ultraestrutura , Animais , Western Blotting , Quimiocina CCL2/metabolismo , Cloroquina/farmacologia , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Interleucina-6/metabolismo , Camundongos , Microscopia Eletrônica , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Objectives: Vaccination and the emergence of the highly transmissible Omicron variant changed the fate of the COVID-19 pandemic. It is very challenging to estimate the number of lives saved by vaccination given the multiple doses of vaccination, the time-varying nature of transmissibility, the waning of immunity, and the presence of immune evasion. Methods: We established a S-SV-E-I-T-D-R model to simulate the number of lives saved by vaccination in six states in the United States (U.S.) from March 5, 2020, to March 23, 2023. The cumulative number of deaths were estimated under three vaccination scenarios based on two assumptions. Additionally, immune evasion by the Omicron and loss of protection afforded by vaccination or infection were considered. Results: The number of deaths averted by COVID-19 vaccinations (including three doses) ranged from 0.154-0.295% of the total population across six states. The number of deaths averted by the third dose ranged from 0.008-0.017% of the total population. Conclusions: Our estimate of death averted by COVID-19 vaccination in the U.S. was largely in line with an official estimate (at a level of 0.15-0.20% of the total population). We found that the additional contribution of the third dose was small but significant.
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Purpose: Polycystic ovary syndrome (PCOS) is a frequent cause of infertility in reproductive-age women. Our work aims to evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on gut microbiota, with metabolic parameters including body weight and the hormone profile in PCOS. Patients and Methods: Dehydroepiandrosterone (DHEA)-induced PCOS mice were established and then treated with two GLP-1RAs: liraglutide and novel form semaglutide for four weeks. Changes in body weight and metabolic parameters were measured. Fecal samples were collected and analyzed using metagenomic sequencing. Results: Liraglutide and semaglutide modulated both alpha and beta diversity of the gut microbiota in PCOS. Liraglutide increased the Bacillota-to-Bacteroidota ratio through up-regulating the abundance of butyrate-producing members of Bacillota like Lachnospiraceae. Moreover, liraglutide showed the ability to reverse the altered microbial composition and the disrupted microbiota functions caused by PCOS. Semaglutide increased the abundance of Helicobacter in PCOS mice (p < 0.01) which was the only bacteria found negatively correlated with body weight. Moreover, pathways involving porphyrin and flavonoids were increased after semaglutide intervention. Conclusion: Liraglutide and semaglutide improved reproductive and metabolic disorders by modulating the whole structure of gut microbiota in PCOS. The greater efficacy in weight loss compared with liraglutide observed after semaglutide intervention was positively related with Helicobacter. The study may provide new ideas in the treatment and the underlying mechanisms of GLP-1RAs to improve PCOS.
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The intrinsic physical and mechanical properties of red blood cells (RBCs), including their geometric and rheological characteristics, can undergo changes in various circulatory and metabolic diseases. However, clinical diagnosis using RBC biophysical phenotypes remains impractical due to the unique biconcave shape, remarkable deformability, and high heterogeneity within different subpopulations. Here, we combine the hydrodynamic mechanisms of fluid-cell interactions in micro circular tubes with a machine learning method to develop a relatively high-throughput microfluidic technology that can accurately measure the shear modulus of the membrane, viscosity, surface area, and volume of individual RBCs. The present method can detect the subtle changes of mechanical properties in various RBC components at continuum scales in response to different doses of cytoskeletal drugs. We also investigate the correlation between glycosylated hemoglobin and RBC mechanical properties. Our study develops a methodology that combines microfluidic technology and machine learning to explore the material properties of cells based on fluid-cell interactions. This approach holds promise in offering novel label-free single-cell-assay-based biophysical markers for RBCs, thereby enhancing the potential for more robust disease diagnosis.
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Deformação Eritrocítica , Eritrócitos , Viscosidade , Reologia , Microfluídica/métodosRESUMO
With distinctive advantages spanning excellent flexibility, rich physical properties, strong electrostatic tunability, dangling-bond-free surface, and ease of integration, 2D layered materials (2DLMs) have demonstrated tremendous potential for photodetection. However, to date, most of the research enthusiasm has been merely focused on developing novel prototype devices. In the past few years, researchers have also been devoted to developing various downstream applications based on 2DLM photodetectors to contribute to promoting them from fundamental research to practical commercialization, and extensive accomplishments have been realized. In spite of the remarkable advancements, these fascinating research findings are relatively scattered. To date, there is still a lack of a systematic and profound summarization regarding this fast-evolving domain. This is not beneficial to researchers, especially researchers just entering this research field, who want to have a quick, timely, and comprehensive inspection of this fascinating domain. To address this issue, in this review, the emerging downstream applications of 2DLM photodetectors in extensive fields, including imaging, health monitoring, target tracking, optoelectronic logic operation, ultraviolet monitoring, optical communications, automatic driving, and acoustic signal detection, have been systematically summarized, with the focus on the underlying working mechanisms. At the end, the ongoing challenges of this rapidly progressing domain are identified, and the potential schemes to address them are envisioned, which aim at navigating the future exploration as well as fully exerting the pivotal roles of 2DLMs towards the practical optoelectronic industry.
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BACKGROUND: The intricate pathophysiological mechanisms of major depressive disorder (MDD) necessitate the development of comprehensive early indicators that reflect the complex interplay of emotional, physical, and cognitive factors. Despite its potential to fulfill these criteria, interoception remains underexplored in MDD. This study aimed to evaluate the potential of interoception in transforming MDD's clinical practices by examining interoception deficits across various MDD stages and analyzing their complex associations with the spectrum of depressive symptoms. METHODS: This study included 431 healthy individuals, 206 subclinical depression individuals, and 483 MDD patients. Depressive symptoms and interoception function were assessed using the PHQ-9 and MAIA-2, respectively. RESULTS: Interoception dysfunction occurred in the preclinical phase of MDD and further impaired in the clinical stage. Antidepressant therapies showed limited efficacy in improving interoception and might damage some dimensions. Interoceptive dimensions might predict depressive symptoms, primarily enhancing negative thinking patterns. The predictive model based on interoception was built with random split verification and demonstrated good discrimination and predictive performance in identifying MDD. CONCLUSIONS: Early alterations in the preclinical stage, multivariate associations with depressive symptoms, and good discrimination and predictive performance highlight the importance of interoception in MDD management, pointing to a paradigm shift in diagnostic and therapeutic approaches.
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Transtorno Depressivo Maior , Interocepção , Humanos , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/tratamento farmacológico , Interocepção/fisiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (Pâ <â .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.
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Artroplastia do Joelho , Prótese do Joelho , Tantálio , Tíbia , Artroplastia do Joelho/métodos , Artroplastia do Joelho/instrumentação , Humanos , Tíbia/cirurgia , Cimentos Ósseos , Porosidade , Desenho de Prótese , Resultado do Tratamento , Reoperação/estatística & dados numéricos , Articulação do Joelho/cirurgiaRESUMO
Liquid fermentation could revolutionize mushroom polysaccharide production, but the low temperature constraint hampers the process. This study implemented adaptive laboratory evolution (ALE) to enhance the thermotolerance of Naematelia aurantialba strains and increase expolysaccharide production. After 75 ALE cycles at 30 °C, the adaptive strain surpassed the wild-type strain by 5 °C. In a 7.5 L fermentor at 30 °C, the ALE strain yielded 17 % more exopolysaccharide than the wild type strain at 25 °C. Although the exopolysaccharide synthesized by both strains shares a consistent monosaccharide composition, infrared spectrum, and glycosidic bond composition, the ALE strain's exopolysaccharide has a larger molecular weight. Furthermore, the ALE strain's exopolysaccharide exhibits superior cryoprotection performance compared to that produced by the original strain. The adapted strain demonstrated lower ROS levels and increased activity of antioxidant enzymes, indicating improved performance. Fatty acid profiling and transcriptomics revealed reconfiguration of carbohydrate metabolism, amino acid metabolism, and membrane lipid synthesis in thermophilic strains, maintaining cellular homeostasis and productivity. This study provides efficient strains and fermentation methods for high-temperature mushroom polysaccharide production, reducing energy consumption and costs.
Assuntos
Basidiomycota , Reatores Biológicos , Polissacarídeos , Temperatura , FermentaçãoRESUMO
Mushroom polysaccharides exhibit numerous health-enhancing attributes that are intricately linked to the breakdown, assimilation, and exploitation of polysaccharides within the organism. Naematelia aurantialba polysaccharides (NAPS-A), highly prized polysaccharides derived from mushrooms, remain shrouded in uncertainty regarding their characteristics pertaining to gastrointestinal digestion and gut microbial fermentation. The study aimed to understand the digestion and fecal fermentation patterns of NAPS-A. After simulated digestion, NAPS-A's physicochemical properties remained unchanged. However, during in vitro fecal fermentation, indigestible NAPS-A underwent significant changes in various properties, such as reducing sugar, chemical composition, constituent monosaccharides, Molecular weight, apparent viscosity, FT-IR spectra, and microscopic morphology. Notably, NAPS-A was effectively utilized by the gut microbiota, with unchanged properties after digestion but altered after fermentation. It influenced gut microbe composition by increasing beneficial bacteria (Lactobacillus, Faecalibacterium, and Roseburia), lowering pH, and producing short-chain fatty acids. NAPS-A fermentation enriches carbohydrate, fatty acid, and amino acid metabolic pathways through PICRUSt prediction analysis. Overall, these findings emphasize NAPS-A's role in regulating gut bacteria and their metabolic functions, despite its challenging digestibility.