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The efficacy of single chemotherapy drugs in cancer treatment is often limited. Combining administration targeting multiple targets has emerged as an effective strategy to improve cancer treatment. Ursolic acid, a triterpenoid compound in various natural foods, was identified as a novel inhibitor of lung cancer specific target TMEM16A. The IC50 of ursolic acid on the whole-cell current of TMEM16A was 13.85 ± 1.64 µM. Molecular dynamics simulations and site-directed mutagenesis experiments indicated the binding sites of ursolic acid on TMEM16A as L381, R535, E623, and C625. Ursolic acid significantly inhibited the proliferation and migration of LA795 cells, while promoting cancer cell apoptosis. Mechanistic studies revealed that ursolic acid inhibited lung cancer through the MAPK and EMT pathways, and induced DNA and membrane damage. Next, a degradable and self-repairing hydrogel drug-loading system was designed to enhance the targeting effect of the ursolic acid and cisplatin drug combination. In vivo experiments showed that the hydrogel-loaded ursolic acid and cisplatin enhanced the antitumor activity and reduced the toxicity. This study presents a novel approach of multi-target combination therapy using ursolic acid and cisplatin, combined with the targeted delivery capability of the hydrogel system, which significantly improves the therapeutic efficacy in lung cancer.
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Glycoproteins are difficult to be detected by imprinting strategy due to their low natural abundance, high flexible conformation and large size. Herein, a high-density boric acid modified metal-organic framework (MOF) surface molecularly imprinted polymer (SMIP) resonant light scattering sensor was constructed for the high-sensitivity detection of target glycoproteins. A MOF with large specific surface area was selected as the substrate material to support the boric acid group with high loading density (4.66 %). The introduction of the boric acid group in the SMIP provided a high-affinity binding site for the recognition and binding of glycoproteins. Shallow surface cavities with rapid mass transfer (equilibrium time 20 min) were thus formed by surface imprinting. Furthermore, high sensitivity (limit of detection 15 pM) was achieved at physiological pH (7.4), which was conducive to the detection of glycoproteins with low natural abundance in complex biological samples and maintaining physiological activity.
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Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06-5.28), colloid-type (HR 1.95, 95% CI: 1.03-3.67), and necrosis-type (HR 2.21, 95% CI: 1.13-4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.
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Few reports exist on one-step enzymatic methods for the simultaneous production of biodiesel and eicosapentaenoic acid ethyl ester (EPA-EE), a high-value pharmaceutical compound. This study aimed to efficiently express Rhizomucor miehei lipase (pRML) in Pichia pastoris X-33 via propeptide mutation and high-copy strain screening. The mutated enzyme was then used to simultaneously catalyze the production of both biodiesel and EPA-EE. The P46N mutation in the propeptide (P46N-pRML) significantly boosted its production, with the four-copy strain increasing enzyme yield by 3.7-fold, reaching 3425 U/mL. Meanwhile, its optimal temperature increased to 45-50 °C, pH expanded to 7.0-8.0, specific activity doubled, Km reduced to one-third, and kcat/Km increased 7-fold. Notably, P46N-pRML efficiently converts Nannochloropsis gaditana oil's eicosapentaenoic acid (EPA). Under optimal conditions, it achieves up to 93% biodiesel and 92% EPA-EE yields in 9 h. Our study introduces a novel, efficient one-step green method to produce both biodiesel and EPA-EE using this advanced enzyme.
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Biocombustibles , Ácido Eicosapentaenoico , Proteínas Fúngicas , Lipasa , Rhizomucor , Estramenopilos , Rhizomucor/enzimología , Rhizomucor/genética , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/análogos & derivados , Lipasa/metabolismo , Lipasa/genética , Lipasa/química , Biocombustibles/análisis , Estramenopilos/genética , Estramenopilos/enzimología , Estramenopilos/metabolismo , Estramenopilos/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Expresión Génica , Estabilidad de Enzimas , Cinética , Temperatura , Concentración de Iones de Hidrógeno , Saccharomycetales/genética , Saccharomycetales/metabolismo , Saccharomycetales/enzimologíaRESUMEN
Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising approach for MM treatment. This review will delve into the outstanding performance of antibody-drug conjugates, peptide-drug conjugates, aptamer-drug conjugates, and nanocarrier drug delivery systems in preclinical studies or clinical trials for MM and monitor their adverse reactions during treatment.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in women of reproductive age. It is difficult for patients with PCOS to achieve weight loss with conventional treatment. The aim of this study was to investigate weight loss and changes in hypothalamic-pituitary axis hormone levels in patients with PCOS combined with obesity after sleeve gastrectomy. METHODS: A retrospective analysis of 12 patients without PCOS and 24 patients with PCOS who underwent bariatric surgery at Beijing Luhe hospital from 2020 to 2022 was performed. The study assessed the changes in body weight and hormonal indexes of the hypothalamic-pituitary axis before and six months after the surgery. RESULTS: Patients with PCOS experienced greater weight loss compared to those without the condition. Following surgery, individuals with PCOS showed lower levels of postoperative testosterone, prolactin, and free testosterone indices compared to preoperative levels. Additionally, postoperative LH and FSH levels were higher than preoperative levels. Analysis of thyroid axis hormone levels revealed that FT3 and TSH levels were notably reduced in patients with PCOS postoperatively. Furthermore, growth hormone levels were found to be elevated in patients with PCOS following surgery. CONCLUSION: Bariatric surgery enhances hormone levels in the hypothalamic-pituitary axis in women with PCOS, leading to greater improvements in patients with PCOS compared to those with simple obesity.
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Sistema Hipotálamo-Hipofisario , Síndrome del Ovario Poliquístico , Pérdida de Peso , Humanos , Femenino , Síndrome del Ovario Poliquístico/cirugía , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Estudios Retrospectivos , Adulto , Sistema Hipotálamo-Hipofisario/metabolismo , Pérdida de Peso/fisiología , Testosterona/sangre , Obesidad Mórbida/cirugía , Obesidad Mórbida/sangre , Obesidad Mórbida/complicaciones , Gastrectomía/métodos , Cirugía Bariátrica , Adulto Joven , Peso Corporal , Resultado del TratamientoRESUMEN
The traditional Chinese medicine (TCM) industry in China exhibits significant regional disparities in health service utilization, the underlying reasons for which are yet to be fully explored. This study employs Geodetector models to analyze the factors affecting TCM service utilization, providing the first examination of spatial distribution patterns and influencing factors for both TCM outpatient (TCMOSU) and inpatient services (TCMISU). The findings of this study reveal spatial disparities across China's provinces, showing a prevalence of TCMOSU in the east and TCMISU decreasing from southwest to northeast. Global Moran's I autocorrelation analysis revealed a positive spatial correlation between TCMOSU and TCMISU across Chinese provinces, suggesting spatial clustering and the potential for interregional collaboration in the development of TCM services. Local Moran's I autocorrelation analysis revealed clusters of TCMOSU in wealthier eastern provinces, such as Jiangsu and Tianjin, and clusters of TCMISU in the southwest. Factor detector analysis revealed that disposable income per capita was the most significant factor linking higher incomes with increased TCMOSU. In contrast, TCMISU was primarily influenced by demographic factors, such as the illiteracy rate and population urbanization rate, emphasizing traditional practices in lower education regions. Interaction detector analysis revealed the joint effects of these factors, demonstrating how regional economic status, health status, and healthcare resource indicators interact with other factors for TCMOSU and how demographic factors significantly influence the prevalence of TCMISU. This study highlights the importance of considering health status together with regional economic, demographic, and healthcare resources when formulating TCM healthcare policies and allocating such resources in China. Promoting the balanced and coordinated regional development of TCM services across the country requires the development of strategies that account for these varied regional characteristics.
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Medicina Tradicional China , Factores Socioeconómicos , Análisis Espacial , Humanos , China/epidemiología , Medicina Tradicional China/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
Environmental accumulation of nano- and microplastics pose serious risks to human health. Polystyrene (PS) is a polymer commonly used in the production of plastics. However, PS can adsorb cadmium (Cd), thereby influencing bioavailability and toxicity in vivo. Moreover, PS and Cd can accumulate in the mammalian kidney. Therefore, the aim of the present study was to assess the effects of combined exposure to PS and Cd in the kidney. Kidney damage was evaluated in male mice gavaged with PS (diameter, 100â¯nm and/or 1 µm) and Cd for 25 days.The results showed that PS at 100â¯nm caused more severe oxidative damage and cell apoptosis than PS at 1 µm. Combined exposure to PS at both 100â¯nm and 1 µm caused more severe kidney damage than the single administration groups. The extent of kidney toxicity caused by Cd differed with the combination of PS particles at 100â¯nm vs. 1 µm. The degree of damage to kidney function, pathological changes, and cell apoptosis induced by Cd+100â¯nm PS+1µm PS was the most severe. An increase in the Bax/Bcl2 ratio and overexpression of p53 and caspase-3 revealed that renal cell apoptosis might be induced via the mitochondrial pathway. Collectively, these findings demonstrate that the size of PS particles dictates the combined effects of PS and Cd in kidney tissues. Kidney damage caused by the combination of different sizes of PS particle and Cd is more complicated under actual environmental conditions.
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Apoptosis , Cadmio , Riñón , Tamaño de la Partícula , Poliestirenos , Animales , Poliestirenos/toxicidad , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Ratones , Apoptosis/efectos de los fármacos , Cadmio/toxicidad , Caspasa 3/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Contaminantes Ambientales/toxicidadRESUMEN
Tyrosinase is a biological macromolecule closely related to browning of fruit and vegetables, melanin production, and tyrosinase inhibitors are usually used to prevent browning and pigmentation. In this study, longan shell tannins (LSTs) were screened as tyrosinase inhibitors and their structures were proved to be mixtures of procyanidins (condensed tannins) and ellagitannins (hydrolyzed tannins). Enzymatic experiments verified that LSTs were efficient inhibitors, and the IC50 values for monophenolase and bisphenolase were 176.04 ± 10 and 59.94 ± 5 µg mL-1, respectively. Fluorescence detections and molecular docking revealed that the combination of LSTs to tyrosinase was mainly driven by hydrogen bonding, hydrophobic interaction, as well as van der Waals force, which changed the microenvironment of tyrosine and tryptophan residues as well as enzyme conformation. Circular dichroism and molecular dynamics simulation showed that LSTs affected secondary structures of tyrosinase, resulting in structural stretching and conformational modification of the enzyme. In addition, preservation studies demonstrated that LSTs owned the ability to delay the browning of fresh-cut apples by inhibiting phenolic metabolism, strengthening the antioxidant system, and reducing lipid peroxidation. This paper testified that LSTs are exteaordinary tyrosinase inhibitors, and offered a scientific foundation for the application of LSTs in food industry and medicine.
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Inhibidores Enzimáticos , Malus , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Taninos , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/química , Malus/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Taninos/química , Taninos/farmacología , Simulación de Dinámica Molecular , Frutas/química , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
BACKGROUND: Fine particulate matter (PM2.5) has been implicated in various health concerns. However, a comprehensive understanding of the specific PM2.5 components affecting depression remains limited. METHODS: This study conducted a Cox proportional-hazards model to assess the effect of PM2.5 components on the incidence of depression based on the China Health and Retirement Longitudinal Study (CHARLS). Participants with 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) score of 10 or higher were classified as exhibiting depression. RESULTS: Our findings demonstrated a significant positive correlation between long-term exposure to black carbon (BC), sulfate (SO42-), and organic matter (OM) components of PM2.5 and the prevalence of depression. Per 1 Interquartile Range (IQR) increment in 3-year average concentrations of BC, OM, and SO42- were associated with the hazard ratio (HR) of 1.54 (95 % confidence intervals (CI): 1.44, 1.64), 1.24 (95%CI: 1.16, 1.34) and 1.25 (95%CI: 1.16, 1.35). Notably, females, younger individuals, those with lower educational levels, urban residents, individuals who were single, widowed, or divorced, and those living in multi-story houses exhibited heightened vulnerability to the adverse effects of PM2.5 components on depression. LIMITATIONS: Firstly, pollutant data is confined to subjects' fixed addresses, overlooking travel and international residence history. Secondly, the analysis only incorporates five fine particulate components, leaving room for further investigation into the remaining fine particulate components in future studies. CONCLUSIONS: This study provides robust evidence supporting the detrimental impact of PM2.5 components on depression. The identification of specific vulnerable populations contributes to a deeper understanding of the underlying mechanisms involved in the relationship between PM2.5 components and depression.
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Depresión , Material Particulado , Modelos de Riesgos Proporcionales , Humanos , Material Particulado/efectos adversos , Femenino , China/epidemiología , Masculino , Persona de Mediana Edad , Anciano , Depresión/epidemiología , Estudios Longitudinales , Exposición a Riesgos Ambientales/efectos adversos , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Incidencia , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Estudios de Cohortes , Prevalencia , Hollín/efectos adversosRESUMEN
Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7 % via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251â mV at 10â mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz 2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.
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ABSTRACT: Data were obtained from the Global Burden of Disease study 2019. Joinpoint regression model was used to analyze the temporal trends from 1990 to 2019 of neck pain burden, focusing on age-standardized incidence rates, age-standardized prevalence rates, and age-standardized years lived with disability (YLDs) rates at the global, regional, and national levels. The age-period-cohort analysis was used to estimate the effects of age (5-99 years), period (1990-2019), and cohort (1893-2012) at the global, regional, and national levels. Future projections for the global burden of neck pain from 2020 to 2044 were estimated using the nordpred age-period-cohort model. From 1990 to 2019, the global incidence, prevalence cases, and YLDs counts of neck pain have increased by 71.89%, 98.21%, and 78.17%, respectively. The joinpoint analysis indicated significant shifts in the global trends of age-standardized neck pain burden, which varied across regions and nations. The age-period-cohort model indicated that the neck pain burden was predominantly concentrated in middle-aged and older age, with period and cohort effects showing minimal variation from 1990 to 2019. Compared with 2019, the incident cases, prevalent cases, and YLDs counts of neck pain were projected to increase by 134%, 142%, and 140% by 2044. The global burden of neck pain has persisted at a relatively elevated level from 1990 to 2019, with projections indicating a continuing upward trend. Future research is urgently needed to better understand the predictors and clinical course of neck pain and to enhance prevention and management strategies.
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Diabetes is closely associated with K+ disturbances during disease progression and treatment. However, it remains unclear whether K+ imbalance occurs in diabetes with normal kidney function. In this study, we examined the effects of dietary K+ intake on systemic K+ balance and renal K+ handling in streptozotocin (STZ)-induced diabetic mice. The control and STZ mice were fed low or high K+ diet for 7 days to investigate the role of dietary K+ intake in renal K+ excretion and K+ homeostasis and to explore the underlying mechanism by evaluating K+ secretion-related transport proteins in distal nephrons. K+-deficient diet caused excessive urinary K+ loss, decreased daily K+ balance, and led to severe hypokalemia in STZ mice compared with control mice. In contrast, STZ mice showed an increased daily K+ balance and elevated plasma K+ level under K+-loading conditions. Dysregulation of the NaCl cotransporter (NCC), epithelial Na+ channel (ENaC), and renal outer medullary K+ channel (ROMK) was observed in diabetic mice fed either low or high K+ diet. Moreover, amiloride treatment reduced urinary K+ excretion and corrected hypokalemia in K+-restricted STZ mice. On the other hand, inhibition of SGLT2 by dapagliflozin promoted urinary K+ excretion and normalized plasma K+ levels in K+-supplemented STZ mice, at least partly by increasing ENaC activity. We conclude that STZ mice exhibited abnormal K+ balance and impaired renal K+ handling under either low or high K+ diet, which could be primarily attributed to the dysfunction of ENaC-dependent renal K+ excretion pathway, despite the possible role of NCC.NEW & NOTEWORTHY Neither low dietary K+ intake nor high dietary K+ intake effectively modulates renal K+ excretion and K+ homeostasis in STZ mice, which is closely related to the abnormality of ENaC expression and activity. SGLT2 inhibitor increases urinary K+ excretion and reduces plasma K+ level in STZ mice under high dietary K+ intake, an effect that may be partly due to the upregulation of ENaC activity.
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Diabetes Mellitus Experimental , Canales Epiteliales de Sodio , Potasio en la Dieta , Potasio , Animales , Diabetes Mellitus Experimental/metabolismo , Potasio/metabolismo , Potasio/orina , Masculino , Potasio en la Dieta/metabolismo , Canales Epiteliales de Sodio/metabolismo , Ratones Endogámicos C57BL , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Canales de Potasio de Rectificación Interna/metabolismo , Canales de Potasio de Rectificación Interna/genética , Ratones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Riñón/metabolismo , Riñón/efectos de los fármacos , Riñón/fisiopatología , Hipopotasemia/metabolismo , Amilorida/farmacología , Eliminación Renal/efectos de los fármacos , Homeostasis , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Glucósidos/farmacología , Estreptozocina , Compuestos de Bencidrilo , Transportador 2 de Sodio-GlucosaRESUMEN
BACKGROUND: Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors. METHODS: We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay. RESULTS: In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024-2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548-32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236-0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216-0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207-0.679), moderate stroke (OR: 0.644, 95% CI: 0.462-0.901), and severe stroke (OR: 0.506, 95% CI: 0.285-0.908). CONCLUSIONS: Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.
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COVID-19 , Accidente Cerebrovascular Isquémico , Tiempo de Tratamiento , Humanos , COVID-19/epidemiología , Femenino , Masculino , China/epidemiología , Estudios Prospectivos , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/terapia , Anciano , Persona de Mediana Edad , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Riesgo , SARS-CoV-2 , Anciano de 80 o más Años , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Temporomandibular disorders (TMD) is the leading cause of pain and disability among frequently occurring facial pain and the second leading cause of musculoskeletal conditions. AIM: We examined whether acupuncture could alleviate pain intensity in patients with temporomandibular disorders (TMD). DESIGN AND METHODS: Sixty participants with TMD were randomly assigned (ratio 1:1) to receive three acupuncture or sham acupuncture sessions weekly for 4 weeks. The primary outcome was the change in the mean weekly pain intensity from baseline to week 4. Secondary and exploratory outcomes included proportion of participants with ≥30% or ≥ 50% reduction in pain intensity, change in jaw opening and movement, graded chronic pain scale, jaw functional limitations scale-20-item, Depression, Anxiety and Stress Scales-21, Pittsburgh sleep quality index at week 4 and 8, and the pressure pain threshold and surface electromyography at week 4. RESULTS AND CONCLUSION: The acupuncture group showed significantly reduced pain intensity compared to the sham group at week 4 (-1.49, 95% confidence interval [CI]: -2.32 to -0.65; P < 0.001) and week 8 (-1.23, 95% CI: -2.11 to -0.54; P = 0.001). Acupuncture's effectiveness surpassed sham's at 4 weeks and lasted 8 weeks. Participants in the acupuncture group experienced significantly greater improvements in the 30% and 50% response rate, jaw opening and movement, GCPS, JFLS-20, DASS-21 and PSQI than those in the sham acupuncture group. There were no significant between-group differences in PPT and sEMG. In summary, acupuncture provided marked pain relief and improvement in physical and emotional function for patients with TMD compared with sham acupuncture.
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Plant senescence is a highly regulated developmental program crucial for nutrient reallocation and stress adaptation in response to developmental and environmental cues. Stress-induced and age-dependent natural senescence share both overlapping and distinct molecular responses and regulatory schemes. Previously, we have utilized a carbon-deprivation (C-deprivation) senescence assay using Arabidopsis (Arabidopsis thaliana) seedlings to investigate senescence regulation. Here we conducted a comprehensive time-resolved transcriptomic analysis of Arabidopsis wild type seedlings subjected to C-deprivation treatment at multiple time points, unveiling substantial temporal changes and distinct gene expression patterns. Moreover, we identified ALTERED MERISTEM PROGRAM 1 (AMP1), encoding an endoplasmic reticulum protein, as a potential regulator of senescence based on its expression profile. By characterizing loss-of-function alleles and overexpression lines of AMP1, we confirmed its role as a negative regulator of plant senescence. Genetic analyses further revealed a synergistic interaction between AMP1 and the autophagy pathway in regulating senescence. Additionally, we discovered a functional association between AMP1 and the endosome-localized ABNORMAL SHOOT3 (ABS3)-mediated senescence pathway and positioned key senescence-promoting transcription factors downstream of AMP1. Overall, our findings shed light on the molecular intricacies of transcriptome reprogramming during C-deprivation-induced senescence and the functional interplay among endomembrane compartments in controlling plant senescence.
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Atypical sustained attention is a symptom in a number of neurological and psychological conditions. Investigations into its neural underpinnings are required for improved management and treatment. Rodents are useful in investigating the neurobiology underlying atypical sustained attention and several rodent tasks have been developed for use in touchscreen testing platforms that mimic methodology used in human clinical attention assessment. This systematic review was conducted to assess how translatable these rodent tasks are to equivalent clinical human tasks. Studies using the rodent Continuous Performance Task (rCPT), Sustained Attention Task (SAT), and 5-choice CPT (5C-CPT) were sought and screened. Included in the review were 138 studies, using the rCPT (n = 21), SAT (n = 90), and 5C-CPT (n = 27). Translatability between rodent and human studies was assessed based on (1) methodological similarity, (2) performance similarity, and (3) replication of results. The 5C-CPT was found to be the most translatable cross-species paradigm with good utility, while the rCPT and SAT require adaptation and further development to meet these translatability benchmarks. With greater replication and more consistent results, greater confidence in the translation of sustained attention results between species will be engendered.
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BACKGROUND: Recovery strategies are used to enhance performance and reduce injury risk in athletes. In previous systematic reviews, individual recovery strategies were investigated to clarify their effectiveness for mixed groups of athletes. However, the current evidence is ambiguous, and a clear overview of (training) recovery for endurance athletes is still lacking. METHODS: We conducted an umbrella review based on a literature search in PubMed, Cochrane Database of Systematic Reviews, and Web of Science. Reviews published in English and before December 2022 were included. Systematic reviews and meta-analyses were eligible if they investigated the effectiveness of one or more recovery strategies compared with a placebo or control group after a training session in endurance athletes. RESULTS: Twenty-two reviews (nine systematic reviews, three meta-analyses, and ten systematic reviews with meta-analyses included) met the inclusion criteria. In total, sixty-three studies with 1100 endurance athletes were included in our umbrella review. Out of the sixty-three studies, eight provided information on training recovery time frame for data synthesis. Among them, cryotherapy and compression garments showed positive effects, while applying massage showed no effect. In general, none of the included recovery strategies showed consistent benefits for endurance athletes. CONCLUSION: There is no particular recovery strategy that can be advised to enhance recovery between training sessions or competitions in endurance athletes. However, individual studies suggest that compression garments and cryotherapy are effective training recovery strategies. Further research should improve methodology and focus on the different time courses of the recovery process. REGISTRATION: The review protocol was registered with the International Prospective Register of Systematic Reviews with the number CRD42021260509.
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BACKGROUND: Assembling framework nucleic acid (FNA) nanoarchitectures and tuning luminescent quantum dots (QDs) for fluorescence assays represent a versatile strategy in analytical territory. Rationally, FNA constructs could offer a preferential orientation to efficiently recognize the target and improve detection sensitivity, meanwhile, regulating size-dependent multicolor emissions of QDs in one analytical setting for ratiometric fluorescence assay would greatly simplify operation procedures. Nonetheless, such FNA/QDs-based ratiometric fluorescence nanoprobes remain rarely explored. RESULTS: We designed a sensitive and signal amplification-free fluorescence aptasensor for lead ions (Pb2+) that potentially cause extensive contamination to environment, cosmetic, food and pharmaceuticals. Red and green emission CdTe quantum dots (rQDs and gQDs) were facilely prepared. Moreover, silica nanosphere encapsulating rQDs served as quantitative internal reference and scaffold to anchor a predesigned FNA and DNA sandwich containing Pb2+ binding aptamer and gQD modified DNA signal reporter. On binding of Pb2+, the gQD-DNA signal reporter was set free, resulting in fluorescence quenching at graphene oxide (GO) interface. Owing to the rigid structure of FNA, the fluorescence signal reporter orderly arranged at the silica nanosphere could sensitively respond to Pb2+ stimulation. The dose-dependent fluorescence signal-off mode enabled ratiometric analysis of Pb2+ without cumbersome signal amplification. Linear relationship was established between fluorescence intensity ratio (I555/I720) and Pb2+ concentration from 10 nM to 2 µM, with detection limit of 1.7 nM (0.43 ppb), well addressing the need for Pb2+ routine monitoring. The designed nanoprobe was applied to detection of Pb2+ in soil, cosmetic, milk, drug, and serum samples, with the sensitivity comparable to conventional ICP-MS technique. SIGNIFICANCE: Given the programmable design of FNA and efficient recognition of target, flexible tuning of QDs emission, and signal amplification-free strategy, the present fluorescence nanoprobe could be a technical criterion for other heavy metal ions detection in a straightforward manner.
Asunto(s)
ADN , Grafito , Plomo , Nanosferas , Puntos Cuánticos , Dióxido de Silicio , Espectrometría de Fluorescencia , Puntos Cuánticos/química , Plomo/análisis , Plomo/química , Grafito/química , Dióxido de Silicio/química , Nanosferas/química , ADN/química , Compuestos de Cadmio/química , Límite de Detección , Telurio/química , Aptámeros de Nucleótidos/química , Fluorescencia , Técnicas Biosensibles/métodosRESUMEN
Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.