High-Performance Wearable Joule Heater Derived from Sea-Island Microfiber Nonwoven Fabric.

A three-dimensional (3D) hierarchical microfiber bundle-based scaffold integrated with silver nanowires (AgNWs) and porous polyurethane (PU) was designed for the Joule heater via a facile dip-coating method. The interconnected micrometer-sized voids and unique hierarchical structure benefit uniform AgNWs anchored and the formation of a high-efficiency 3D conductive network. As expected, this composite exhibits a superior electrical conductivity of 1586.4 S/m and the best electrothermal conversion performance of 118.6 °C at 2.0 V compared to reported wearable Joule heaters to date. Moreover, the durable microfiber bundle-PU network provides strong mechanical properties, allowing for the stable and durable electrothermal performance of such a composite to resist twisting, bending, abrasion, and washing. Application studies show that this kind of Joule heater is suitable for a wide range of applications, such as seat heating, a heating jacket, personal thermal management, etc.

Vaccine for digital images against steganography.

Digital image steganography serves as a technology facilitating covert communication through digital images by subtly incorporating secret data into a cover image. This practice poses a potential threat, as criminals exploit steganography to transmit illicit content, thereby jeopardizing information security. Consequently, it becomes imperative to implement defensive strategies against steganographic techniques. This paper proposes a novel defense mechanism termed "image vaccine" to safeguard digital images from steganography. The process of "vaccinating" an image renders it immune to steganographic manipulation. Notably, when criminals attempt to embed secret data into vaccinated images, the presence of such hidden information can be detected with a 100% probability, ensuring the consistent identification of stego images. This proactive approach enables the interception of stego image transmission, thereby neutralizing covert communication channels.

Starvation-induced phosphorylation activates gasdermin A to initiate pyroptosis.

Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B-E (GSDMB-GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress.

Rapid and direct detection of m6A methylation by DNAzyme-based and smartphone-assisted electrochemical biosensor.

m6A methylation detection is crucial for understanding RNA functions, revealing disease mechanisms, guiding drug development and advancing epigenetics research. Nevertheless, high-throughput sequencing and liquid chromatography-based traditional methods still face challenges to rapid and direct detection of m6A methylation. Here we report a DNAzyme-based and smartphone-assisted electrochemical biosensor for rapid detection of m6A. We initially identified m6A methylation-sensitive DNAzyme mutants through site mutation screening. These mutants were then combined with tetrahedral DNA to modify the electrodes, creating a 3D sensing interface. The detection of m6A was accomplished by using DNAzyme to capture and cleave the m6A sequence. The electrochemical biosensor detected the m6A sequence at nanomolar concentrations with a low detection limit of 0.69 nM and a wide detection range from 10 to 104 nM within 60 min. As a proof of concept, the 3'-UTR sequence of rice was selected as the m6A analyte. Combined with a smartphone, our biosensor shows good specificity, sensitivity, and easy-to-perform features, which indicates great prospects in the field of RNA modification detection and epigenetic analysis.

Simultaneous detection of multiple urinary biomarkers in patients with early-stage diabetic kidney disease using Luminex liquid suspension chip technology.

Background: Several urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously. Methods: The study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), ß2-microglobulin (ß2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, ß2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760. Conclusions: The urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

S-acylation of ATGL is required for lipid droplet homoeostasis in hepatocytes.

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.

Hypertension status and its risk factors in highlanders living in Ganzi Tibetan Plateau: a cross-sectional study.

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.

A Novel Role for the Longevity-Associated Protein SLC39A11 as a Manganese Transporter.

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.

Rescue of dead MnO2 for stable electrolytic Zn-Mn redox-flow battery: a metric of mediated and catalytic kinetics.

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.

Laser-induced stripping defect for highly selective electrochemical quantification of dopamine: Anti-interference from other catecholamine neurotransmitters.

Detecting dopamine (DA) is critical for early diagnosis of neurological and psychiatric disorders. However, the presence of other catecholamine neurotransmitters with structural similarities to DA causes significant interference in its detection. Herein, we introduce S stripping defects via laser-induced MoS2 to functionalize MoS2 electrodes and improve their selectivity for DA electrochemical detection. The sensing results show its excellent immunity to interference from other neurotransmitters, ensuring the preservation of the DA electrochemical signal even in the mixed neurotransmitters such as acetylcholine (ACh), γ-aminobutyric acid (GABA), epinephrine (EP), norepinephrine (NP), and serotonin (5-HT). DFT calculations further reveal that the negatively charged S-stripping defects enhance DA adsorption on the surface of the functionalized MoS2 electrode, contributing to its excellent performance. Moreover, this functionalized electrodes successfully monitor DA released from living PC12 cells in the presence of other interference, highlighting its potential applicability in intercellular signaling communication.

[Inhibitory effect and mechanism of sodium cantharidate on human tongue squamous cell carcinoma CAL27 cells].

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(P＜0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(P＜0.05 or P＜0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(P＜0.05 or P＜0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(P＜0.05 or P＜0.01). 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.

Prophylactic supplementation with Bifidobacterium infantis or its metabolite inosine attenuates cardiac ischemia/reperfusion injury.

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.

Urine microRNA-7977/G6PD level in DKD patients and its association with dysfunction of albumin-induced autophagy in proximal epithelial tubular cells.

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.

Placental Pathologic Features and Perinatal Outcomes in Pregnant Woman With Autoimmune Connective Tissue Disease.

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.

Momordica charantia L.-derived exosome-like nanovesicles stabilize p62 expression to ameliorate doxorubicin cardiotoxicity.

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.

CKIP-1 mediates CK2 translocation to regulate Nav1.5 and Kir2.1 channel complexes in cardiomyocytes.

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.

PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury.

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.

Inhibition of PKC-δ retards kidney fibrosis via inhibiting cGAS-STING signaling pathway in mice.

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.

Dynamic water migration and flavor analysis of sea cucumber in the process of Sichuan pepper seasoning soak.

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.

Different stages of flavor variations among canned Antarctic krill (Euphausia superba): Based on GC-IMS and PLS-DA.

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.