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The identification of aging- and longevity-associated genes is important for promoting healthy aging. By analyzing a large cohort of Chinese centenarians, we previously found that single-nucleotide polymorphisms (SNPs) in the SLC39A11 gene (also known as ZIP11) are associated with longevity in males. However, the function of the SLC39A11 protein remains unclear. Here, we found that SLC39A11 expression is significantly reduced in patients with Hutchinson-Gilford progeria syndrome (HGPS). In addition, we found that zebrafish with a mutation in slc39a11 that significantly reduces its expression have an accelerated aging phenotype, including a shortened average lifespan, muscle atrophy and reduced swimming, impaired muscle regeneration, gut damage, and abnormal morphology in the reproductive system. Interestingly, these signs of premature aging were more pronounced in male zebrafish than in females. RNA-sequencing analysis revealed that cellular senescence may serve as a potential mechanism for driving this slc39a11 deficiency-induced phenotype in mutant zebrafish. Moreover, immunofluorescence showed significantly increased DNA damage and reactive oxygen species signaling in slc39a11 mutant zebrafish. Using inductively coupled plasma mass spectrometry (ICP-MS), we found that manganese significantly accumulates in slc39a11 mutant zebrafish, as well as in the serum of both global Slc39a11 knockout and hepatocyte-specific Slc39a11 knockout mice, suggesting that this metal transporter regulates systemic manganese levels. Finally, using cultured human fibroblasts, we found that both knocking down SLC39A11 and exposure to high extracellular manganese increased cellular senescence. These findings provide compelling evidence that SLC39A11 serves to protect against the aging process, at least in part by regulating cellular manganese homeostasis.
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PURPOSE: To investigate the inhibitory effect of sodium cantharidate (SCA) on human tongue squamous cell carcinoma CAL27 cells and its mechanism. METHODS: CAL27 cells were pretreated with different concentrations of SCA. Cell viability was analyzed by CCK-8 method. The migration and invasion of CAL27 cells were measured by scratch test and Transwell chamber, and the apoptosis rate was measured by flow cytometry. p53 protein and its phosphorylation sites Ser33, Ser37, Ser46, expression of BCL-2, BAX, and cleaved caspase 3 in CAL27 cells were detected by Western blot. Statistical analysis was performed with Graphpad Prism 9.0 software package. RESULTS: Compared with the blank control group, the proliferation, migration and invasion of CAL27 cells in sodium cantharidate group were significantly decreased, and the apoptosis rate was significantly increased(Pï¼0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). CONCLUSIONS: SCA can inhibit the proliferation, migration and invasion of human tongue squamous cell carcinoma CAL27 cells. It also down-regulates the ratio of BCL-2/BAX and up-regulates the expression of cleaved caspase 3 protein by regulating the phosphorylation of p53 protein, which induces apoptosis.
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Apoptose , Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Neoplasias da Língua , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2 , Humanos , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Neoplasias da Língua/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Fosforilação/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Invasividade NeoplásicaRESUMO
BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.
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Cardiotoxicidade , Doxorrubicina , Exossomos , Momordica charantia , Fator 2 Relacionado a NF-E2 , Animais , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Momordica charantia/química , Exossomos/metabolismo , Ratos , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismoRESUMO
Lipid droplets (LDs) are organelles specialized in the storage of neutral lipids, cholesterol esters and triglycerides, thereby protecting cells from the toxicity of excess lipids while allowing for the mobilization of lipids in times of nutrient deprivation. Defects in LD function are associated with many diseases. S-acylation mediated by zDHHC acyltransferases modifies thousands of proteins, yet the physiological impact of this post-translational modification on individual proteins is poorly understood. Here, we show that zDHHC11 regulates LD catabolism by modifying adipose triacylglyceride lipase (ATGL), the rate-limiting enzyme of lipolysis, both in hepatocyte cultures and in mice. zDHHC11 S-acylates ATGL at cysteine 15. Preventing the S-acylation of ATGL renders it catalytically inactive despite proper localization. Overexpression of zDHHC11 reduces LD size, whereas its elimination enlarges LDs. Mutating ATGL cysteine 15 phenocopies zDHHC11 loss, causing LD accumulation, defective lipolysis and lipophagy. Our results reveal S-acylation as a mode of regulation of ATGL function and LD homoeostasis. Modulating this pathway may offer therapeutic potential for treating diseases linked to defective lipolysis, such as fatty liver disease.
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INTRODUCTION: We aimed to investigate the association between perinatal outcomes and placental pathological features in pregnant women with ACTD, including systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and undifferentiated connective tissue disease (UCTD). MATERIALS AND METHODS: Placental tissue from SLE (n = 44), APS (n = 45), and UCTD (n = 45) were included, and contemporaneous deliveries of placenta were served as a control group (n = 46) between September 2015 and March 2021. The placental histopathology was evaluated using the Manual of Human Placental Pathology and classified according to the Amsterdam consensus framework. RESULTS: SLE pregnant women have a higher rate of cesarean section (61.40%), premature birth (24.56%), and SGA (26.32%) when compared to control group (p = 0.008, p = 0.005, and p = 0.000, respectively). The rate of vascular malperfusion, inflammatory-immune lesions, and other placental lesions in the SLE group was 47.73%, 56.82%, and 63.64%, which were higher than the control group (p = 0.000, p = 0.000, and p = 0.006, respectively). In the meantime, the incidence of inflammatory-immune lesions in the APS group (42.22%, p = 0.004) and vascular malperfusion in the UCTD group (37.78%, p = 0.007) were increased when compared to the control group. CONCLUSIONS: SLE appeared to confer increased risk for a wide range of adverse perinatal outcomes. We determined elevated placental histopathology risk for most women with ACTD, including vascular maldevelopment, vascular malperfusion, and inflammatory-immune lesions.
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Lúpus Eritematoso Sistêmico , Placenta , Complicações na Gravidez , Resultado da Gravidez , Humanos , Feminino , Gravidez , Placenta/patologia , Placenta/imunologia , Adulto , Complicações na Gravidez/imunologia , Lúpus Eritematoso Sistêmico/patologia , Síndrome Antifosfolipídica/patologia , Síndrome Antifosfolipídica/imunologia , Recém-Nascido , Doenças do Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/imunologia , Nascimento Prematuro , Doenças do Tecido Conjuntivo Indiferenciado/imunologia , Doenças do Tecido Conjuntivo Indiferenciado/patologia , CesáreaRESUMO
Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia-reperfusion (I/R) injury, we found that the prophylactic administration of a well-known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R-induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro-inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen-glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R-induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.
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Studies have shown that decreased expression of glucose-6-phosphate dehydrogenase (G6PD) play an important role in DKD. However, the upstream and downstream pathways of G6PD downregulation leading to DKD have not been elucidated.We conducted a series of studies including clinical study, animal studies, and in vitro studies to explore this. Firstly, a total of 90 subjects were evaluated. The urinary G6PD activity and its association with the clinical markers were analyzed. Then, urine differentially microRNAs that can bind and degrade G6PD were screened and verified in DKD patients. After that, high glucose (HG)-cultured Human kidney cells (HK-2) and Zucker diabetic fatty (ZDF) rats were used to test the roles of miR-7977/G6PD/albumin-induced autophagy in DKD. The plasma and urinary G6PD activity were decreased significantly in patients with DKD, accompanied by increased urinary mir-7977 level. The fasting plasma glucose (FPG), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and urinary albumin excretion were independent predictors of urinary G6PD activity by multiple linear regression analysis.The increased expression of miR-7977 and decreased expression of G6PD were also found in the kidney of ZDF rats with early renal tubular damage.In HK-2 cells cultured with normal situation, low level of albumin could induce autophagy along with the stimulation of G6PD although this was impaired under high glucose. Overexpression of G6PD reversed albumin-induced autophagy in HK2 cells under high glucose.Inhibition mir-7977 expression led to significantly increased expression of G6PD and reversed the effects of high glucose on albumin induced autophagy.Our study supports a new mechanism of G6PD downregulation in DKD.
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The virtues of electrolytic MnO2 aqueous batteries are high theoretical energy density, affordability and safety. However, the continuous dead MnO2 and unstable Mn2+/MnO2 electrolysis pose challenges to the practical output energy and lifespan. Herein, we demonstrate bifunctional cationic redox mediation and catalysis kinetics metrics to rescue dead MnO2 and construct a stable and fast electrolytic Zn-Mn redox-flow battery (eZMRFB). Spectroscopic characterizations and electrochemical evaluation reveal the superior mediation kinetics of a cationic Fe2+ redox mediator compared with the anionic ones (e.g. I- and Br-), thus eliminating dead MnO2 effectively. With intensified oxygen vacancies, density functional theory simulations of the reaction pathways further verify the concomitant Fe-catalysed Mn2+/MnO2 electrolysis kinetics via charge delocalization and activated O 2p electron states, boosting its rate capability. As a result, the elaborated eZMRFB achieves a coulombic efficiency of nearly 100%, ultra-high areal capacity of 80 mAh cm-2, rate capability of 20 C and a long lifespan of 2500 cycles. This work may advance high-energy aqueous batteries to next-generation scalable energy storage.
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BACKGROUND: The updated status of hypertension and its risk factors are poorly evaluated in Tibetan highland areas. We initiated a large-scale cross-sectional survey to provide updated status of hypertension and its risk factors (especially salt intake) in the Ganzi Tibetan Plateau, China. METHODS: Stratified multistage random sampling was performed to obtain a representative sample of 4,036 adult residents from 4 counties in the Ganzi Tibetan area. The whole survey population was used to present the epidemiology and risk factors of hypertension. The participants with blood and urine biochemistry data were used to analyze the relationship between salt intake parameters and hypertension. RESULTS: Stratified multistage random sampling was performed to obtain a representative sample of 4,036 adult residents. The overall prevalence rate of hypertension was 33.5% (the age-adjusted prevalence rate was 28.9%). A total of 50.9% of the hypertensive patients knew their conditions; 30.1% of them received antihypertensive treatment; and 11.2% of them had their blood pressure controlled. Age, male sex, living altitude ≥ 3500 m, overweight and abdominal obesity were positively correlated with hypertension. In addition, the adjusted odds ratio (OR) for hypertension was 1.33 (95% CI: 1.01-1.74) for drinking tea with salt, and 1.51 (95% CI: 1.32-1.72) for per SD increase in the estimation of 24-hour urinary sodium excretion (e24hUSE). Furthermore, per 100mmol/day increase in e24hUSE was associated with elevation of blood pressure (+ 10.16, 95% CI: 8.45-11.87 mmHg for SBP; +3.83, 95% CI: 2.74-4.93 mmHg for DBP) in this population. CONCLUSIONS: Our survey suggests a heavy disease burden of hypertension in the Ganzi Tibetan Plateau. Age, male sex, altitude of residence ≥ 3500 m, overweight, abdominal obesity, and excessive salt intake (shown as drinking tea with adding salt and a higher level of e24hUSE) all increased the risk of hypertension in this highland area.
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Altitude , Pressão Sanguínea , Hipertensão , Cloreto de Sódio na Dieta , Humanos , Estudos Transversais , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Adulto , Prevalência , Tibet/epidemiologia , Cloreto de Sódio na Dieta/efeitos adversos , Adulto Jovem , Medição de Risco , Idoso , Chá , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/fisiopatologia , Inquéritos Epidemiológicos , Fatores Sexuais , Fatores Etários , Adolescente , Anti-Hipertensivos/uso terapêutico , Sobrepeso/epidemiologia , Sobrepeso/diagnóstico , Nível de SaúdeRESUMO
The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called "quasiparticle poisoning". Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events.
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Diabetic kidney disease (DKD) is often featured with redox dyshomeostatis. Pyruvate dehydrogenase kinase 4 (PDK4) is the hub for DKD development. However, the mechanism by which PDK4 mediates DKD is poorly understood. The current work aimed to elucidate the relationship between PDK4 and DKD from the perspective of redox manipulation. Oxidative stress was observed in the human proximal tubular cell line (HK-2 cells) treated with a high concentration of glucose and palmitic acid (HGL). The mechanistic study showed that PDK4 could upregulate Kelch-like ECH-associated protein 1 (Keap1) in HGL-treated HK-2 cells through the suppression of autophagy, resulting in the depletion of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of redox homeostasis. At the cellular level, pharmacological inhibition or genetic knockdown of PDK4 could boost Nrf2, followed by the increase of a plethora of antioxidant enzymes and ferroptosis-suppression enzymes. Meanwhile, the inhibition or knockdown of PDK4 remodeled iron metabolism, further mitigating oxidative stress and lipid peroxidation. The same trend was observed in the DKD mice model. The current work highlighted the role of PDK4 in the development of DKD and suggested that PDK4 might be a promising target for the management of DKD.
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Nefropatias Diabéticas , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Humanos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Masculino , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Linhagem Celular , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologiaRESUMO
The aim of the present study was to explore changes in the profile of volatile compounds (VCs) in canned Antarctic krill (Euphausia superba) at different processing stages using partial least squares discriminant analysis (PLS-DA) and gas chromatography-mass spectrometry (GC-IMS). A total of 43 VCs were detected using GC-IMS in all krill meat samples, which included mainly alcohols, aldehydes, ketones, esters, and furans. Considering the different processing stages, the highest variation in VCs and the highest VC content were observed in krill meat which underwent both blanching and salt addition. PLS-DA further revealed flavor differences in canned Antarctic krill meat at different processing stages, with octanal, 2-hexanol, 2-octane, 2,3,5-trimethyl pyrazine, and cis-3-hexanol as the main contributors to observed differences in VC profiles. These findings contribute to the production of high-quality canned krill meat, enhancing its flavor quality and providing a feasible theoretical basis for future krill meat pretreatment and industry development.
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Euphausiacea , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos Voláteis , Animais , Euphausiacea/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Paladar , Análise Discriminante , Análise dos Mínimos Quadrados , Alimentos em Conserva/análiseRESUMO
Soaking in seasoning solution is the main process of sea cucumber seasoning. This study analyzed the dynamic changes in water migration and flavor substances in sea cucumbers during soaking in a Sichuan pepper solution. It was found that the sea cucumber experienced a process of water absorption followed by water loss during the 0-48 h soaking process. During this period, the flavor compounds in sea cucumbers showed different dynamic trends. A total of 46 volatiles were identified, of which 29 were key flavor compounds. Its flavor profiles tended to stabilize as soaking time increased. m-Xylene, d-Limonene, Eucalyptol, p-Xylene, Sabinene, Beta-Myrcene, and Beta-Phellandrene were the main characteristic substances contributing to the differences in sea cucumber flavor. Correlation analysis predicted the relationship between water migration and the dynamic shifts in flavor compounds. This study provides a crucial reference for future studies on the processing and flavor modulation of sea cucumber products.
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Aromatizantes , Pepinos-do-Mar , Paladar , Compostos Orgânicos Voláteis , Água , Animais , Pepinos-do-Mar/química , Água/análise , Água/química , Aromatizantes/química , Aromatizantes/análise , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Capsicum/química , Manipulação de AlimentosRESUMO
Kidney fibrosis is considered to be the ultimate aggregation pathway of chronic kidney disease (CKD), but its underlying mechanism remains elusive. Protein kinase C-delta (PKC-δ) plays critical roles in the control of growth, differentiation, and apoptosis. In this study, we found that PKC-δ was highly upregulated in human biopsy samples and mouse kidneys with fibrosis. Rottlerin, a PKC-δ inhibitor, alleviated unilateral ureteral ligation (UUO)-induced kidney fibrosis, inflammation, VDAC1 expression, and cGAS-STING signaling pathway activation. Adeno-associated virus 9 (AAV9)-mediated VDAC1 silencing or VBIT-12, a VDAC1 inhibitor, attenuated renal injury, inflammation, and activation of cGAS-STING signaling pathway in UUO mouse model. Genetic and pharmacologic inhibition of STING relieved renal fibrosis and inflammation in UUO mice. In vitro, hypoxia resulted in PKC-δ phosphorylation, VDAC1 oligomerization, and activation of cGAS-STING signaling pathway in HK-2 cells. Inhibition of PKC-δ, VDAC1 or STING alleviated hypoxia-induced fibrotic and inflammatory responses in HK-2 cells, respectively. Mechanistically, PKC-δ activation induced mitochondrial membrane VDAC1 oligomerization via direct binding VDAC1, followed by the mitochondrial DNA (mtDNA) release into the cytoplasm, and subsequent activated cGAS-STING signaling pathway, which contributed to the inflammation leading to fibrosis. In conclusion, this study has indicated for the first time that PKC-δ is an important regulator in kidney fibrosis by promoting cGAS-STING signaling pathway which mediated by VDAC1. PKC-δ may be useful for treating renal fibrosis and subsequent CKD.
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Sodium and potassium channels, especially Nav1.5 and Kir2.1, play key roles in the formation of action potentials in cardiomyocytes. These channels interact with, and are regulated by, synapse-associated protein 97 (SAP97). However, the regulatory role of SAP97 in myocyte remains incompletely understood. Here, we investigate the function of SAP97 phosphorylation in the regulation of Nav1.5 and Kir2.1 channel complexes and the upstream regulation of SAP97. We found that SAP97 is phosphorylated by casein kinase II (CK2) in vitro. In addition, transfection of casein kinase 2 interacting protein-1 (CKIP-1) into cardiomyocytes to drive CK2 from the nucleus to the cytoplasm, increased SAP97 phosphorylation and Nav1.5 and Kir2.1 current activity. These findings demonstrated that CKIP-1 modulates the subcellular translocation of CK2, which regulates Nav1.5 and Kir2.1 channel complex formation and activity in cardiomyocytes.
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Caseína Quinase II , Miócitos Cardíacos , Canal de Sódio Disparado por Voltagem NAV1.5 , Canais de Potássio Corretores do Fluxo de Internalização , Miócitos Cardíacos/metabolismo , Caseína Quinase II/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Animais , Ratos , Fosforilação , Transporte Proteico , Humanos , Proteínas de Transporte/metabolismo , Ratos Sprague-DawleyRESUMO
Changes in microcirculation lead to the progression of organ pathology in diabetes. Although neuroimmune interactions contribute to a variety of conditions, it is still unclear whether abnormal neural activities affect microcirculation related to diabetes. Using laser speckle contrast imaging, we examined the skin of patients with type 2 diabetes and found that their microvascular perfusion was significantly compromised. This phenomenon was recapitulated in a high-fat-diet-driven murine model of type 2 diabetes-like disease. In this setting, although both macrophages and mast cells were enriched in the skin, only mast cells and associated degranulation were critically required for the microvascular impairment. Sensory neurons exhibited enhanced TRPV1 activities, which triggered mast cells to degranulate and compromise skin microcirculation. Chemical and genetic ablation of TRPV1+ nociceptors robustly improve skin microcirculation status. Substance P (SP) is a neuropeptide and was elevated in the skin and sensory neurons in the context of type 2 diabetes. Exogenous administration of SP resulted in impaired skin microcirculation, whereas neuronal knockdown of SP dramatically prevented mast cell degranulation and consequently improved skin microcirculation. Overall, our findings indicate a neural-mast cell axis underlying skin microcirculation disturbance in diabetes and shed light on neuroimmune therapeutics for diabetes-related complications.
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An effective strategy to improve the proton conductivity of metal-organic frameworks (MOFs) is to regulate the pore size of composite materials. In this work, composite materials of MOF-808@MOG-808-X (X is the mass ratios of MOF-808 to MOG-808) was successfully prepared by grinding and blending. MOF-808@MOG-808-1:2 was optimal for its suitable pore structure, which facilitates the practical construction of hydrogen bonding networks, promotes rapid and stable proton conduction, and enables the proton conductivity, achieving a 1 + 1 > 2 effect. At 353 K and 93% relative humidity (RH), the maximum proton conductivity of MOF-808@MOG-808-1:2 reaches 1.08 × 10-1 S·cm-1. Next, MOF-808@MOG-808-1:2 was blended with chitosan (CS) to obtain composite proton exchange membranes (PEMs), namely, CS@MOF-808@MOG-808-1:2-Y (Y = 5%, 10%, or 15%) with the maximum proton conductivity reaching 1.19 × 10-2 S·cm-1 at 353 K and 93% RH for CS@MOF-808@MOG-808-1:2-10% with additional stability. The conductive mechanisms of the composite materials were revealed by activation energy calculation. This investigation not only proposes a simple grinding-blending method for the development of MOF-doped composite materials for proton conductivity but also provides a producting material basis for future applications of MOFs in proton exchange membrane fuel cells (PEMFCs).
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The natural flavor of sea cucumber is generally not easily accepted by consumers. In this study, the effect of different cooking conditions on the adsorption of the characteristic flavor of Sichuan pepper by sea cucumber was investigated by response surface methodology, and the optimal cooking conditions were identified. A total of 45 volatiles were identified based on gas chromatography-mass spectrometry, of which 27 were key flavor actives. Low-field nuclear magnetic resonance and textural analysis showed that the addition of Sichuan pepper during the cooking process affected the water migration and the textural properties of sea cucumbers. It was shown that the addition of Sichuan pepper could significantly improve the flavor and other quality characteristics of sea cucumber. This study has important practical guiding significance for the flavor improvement and product innovation of sea cucumber food.
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Culinária , Cromatografia Gasosa-Espectrometria de Massas , Pepinos-do-Mar , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Animais , Pepinos-do-Mar/química , Adsorção , Paladar , Aromatizantes/químicaRESUMO
Heat shuttling phenomenon is characterized by the presence of a non-zero heat flow between two bodies without net thermal bias on average. It was initially predicted in the context of nonlinear heat conduction within atomic lattices coupled to two time-oscillating thermostats. Recent theoretical works revealed an analog of this effect for heat exchanges mediated by thermal photons between two solids having a temperature dependent emissivity. In this paper, we present the experimental proof of this effect using systems made with composite materials based on phase change materials. By periodically modulating the temperature of one of two solids we report that the system akin to heat pumping with a controllable heat flow direction. Additionally, we demonstrate the effectiveness of a simultaneous modulation of two temperatures to control both the strength and direction of heat shuttling by exploiting the phase delay between these temperatures. These results show that this effect is promising for an active thermal management of solid-state technology, to cool down solids, to insulate them from their background or to amplify heat exchanges.
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BACKGROUND: The public health service capability of primary healthcare personnel directly affects the utilization and delivery of health services, and is influenced by various factors. This study aimed to examine the status, factors, and urban-rural differences of public health service capability among primary healthcare personnel, and provided suggestions for improvement. METHODS: We used cluster sampling to survey 11,925 primary healthcare personnel in 18 regions of Henan Province from 20th to March 31, 2023. Data encompassing demographics and public health service capabilities, including health lifestyle guidance, chronic disease management, health management of special populations, and vaccination services. Multivariable regression analysis was employed to investigate influencing factors. Propensity Score Matching (PSM) quantified urban-rural differences. RESULTS: The total score of public health service capability was 80.17 points. Chronic disease management capability scored the lowest, only 19.60. Gender, education level, average monthly salary, professional title, health status, employment form, work unit type, category of practicing (assistant) physician significantly influenced the public health service capability (all P < 0.05). PSM analysis revealed rural primary healthcare personnel had higher public health service capability scores than urban ones. CONCLUSIONS: The public health service capability of primary healthcare personnel in Henan Province was relatively high, but chronic disease management required improvement. Additionally, implementing effective training methods for different subgroups, and improving the service capability of primary medical and health institutions were positive measures.