The impact of population aging on SME digital transformation: Evidence from China.

Many societies around the world are rapidly aging and this has implications for social and economic development. We collect data on NEEQ-listed enterprises from 2010 to 2021 in China and empirically test the effect of population aging on the digital transformation of small and medium-sized enterprises (SMEs). The findings show that population aging has a significant positive impact on SME digital transformation, and private enterprises and enterprises in eastern regions of China tend to benefit more than other regions. The mechanism studies find that population aging positively impacts SME digital transformation by increasing labor costs, facilitating human capital accumulation, and raising savings rates. Furthermore, the threshold effect analyses find that the marginal promotion effect of population aging will weaken with greater aging and will strengthen with a higher level of marketization. Finally, we provide policy recommendations for promoting digital transformation in SMEs against the background of population aging.

Pyridine-Bridged Covalent Organic Frameworks with Adjustable Band Gaps as Intelligent Artificial Enzymes for Light-Augmented Biocatalytic Sensing.

One of the biggest challenges in biotechnology and medical diagnostics is finding extremely sensitive and adaptable biosensors. Since metal-based enzyme-mimetic biocatalysts may lead to biosafety concerns on accumulative toxicity, it is essential to synthesize metal-free enzyme-mimics with optimal biocatalytic activity and superior selectivity. Here, the pyridine-bridged covalent organic frameworks (COFs) with specific oxidase-like (OXD-like) activities as intelligent artificial enzymes for light-augmented biocatalytic sensing of biomarkers are disclosed. Because of the adjustable bandgaps of pyridine structures on the photocatalytic properties of the pristine COF structures, the pyridine-bridged COF exhibit efficient, selective, and light-responsive OXD-like biocatalytic activity. Moreover, the pyridine-bridged COF structures show tunable and light-augmented biocatalytic detection capabilities, which outperform the recently reported state-of-the-art OXD-mimics regarding biosensing efficiency. Notably, the pyridine-bridged COF exhibits efficient and multifaceted diagnostic activity, including the extremely low limit of detection (LOD), which enables visual assays for abundant reducibility biomarkers. It is believed that this design will offer unique metal-free biocatalysts for high-sensitive and low-cost colorimetric detection and also provide new insights to create highly efficient enzyme-like COF materials via linkage-modulation strategies for future biocatalytic applications.

Circular RNA circIL21R promotes cervical cancer cells proliferation and migration by sponging the miR-1205/PTBP1 axis.

Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.

A Comparison of PM2.5 Exposure Estimates from Different Estimation Methods and their Associations with Cognitive Testing and Brain MRI Outcomes.

BACKGROUND: Reported associations between particulate matter with aerodynamic diameter < 2.5µm (PM2.5) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity. OBJECTIVES: To assess agreement between PM2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM2.5 and cognitive or MRI outcomes. METHODS: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM2.5 exposure estimates with cognitive scores (n=4,678) and MRI outcomes (n=1,518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors. RESULTS: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM2.5-cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors. DISCUSSION: PM2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

The impact of smart manufacturing demonstration projects on green innovation of Chinese firms: Based on random forest methods.

Employing the data of Chinese A-share listed firms from 2010 to 2020 and random forest approaches, this paper investigates whether and how smart manufacturing demonstration projects influence green innovation of firms. The main results are as follows. First, smart manufacturing demonstration projects contribute to promoting firms' green innovation. Additionally, information processing capability improvement, innovation efficiency enhancement, public attention increasement, and signal effect are the main channels that improve firms' green innovation. Finally, the positive effect of smart manufacturing demonstration projects on firms' green innovation is pronounced for capital-intensive firms, and firms in western and eastern regions.

Exposure to low levels of heavy metals and chronic kidney disease in the US population: A cross sectional study.

BACKGROUND: Exposure to heavy metals (cadmium, mercury, and lead) has been linked with adverse health outcomes, especially their nephrotoxic effects at high levels of exposure. We conducted a replication study to examine the association of low-level heavy metal exposure and chronic kidney disease (CKD) using a larger NHANES data set compared to previous studies. METHODS: The large cross-sectional study comprised 5,175 CKD cases out of 55677 participants aged 20-85 years from the 1999-2020 National Health and Nutrition Examination Survey [NHANES]. Logistic regression analysis was applied to estimate the associations between CKD and heavy metals [Cd, Pb, Hg] measured as categorical variables after adjusting with age, race, gender, socioeconomic status, hypertension, diabetes mellitus and blood cotinine level as smoking status. RESULTS: Compared to the lowest quartile of blood Cd, exposures to the 2nd, 3rd and 4th quartiles of blood Cd were statistically significantly associated with higher odds of CKD after adjustment for blood Pb and Hg, with OR = 1.79, [95% CI; 1.55-2.07, p<0.0001], OR = 2.17, [95% CI; 1.88-2.51, p<0.0001] and OR = 1.52, [95% CI; 1.30-1.76, p<0.0001] respectively. The 2nd, 3rd and 4th quartiles of blood Cd remained statistically significantly associated with higher odds of CKD after adjustment for blood cotinine level, with OR = 2.06, [95% CI; 1.80-2.36, p<0.0001], OR = 3.18, [95% CI; 2.79-3.63, p<0.0001] and OR = 5.54, [95% CI; 4.82-6.37, p<0.0001] respectively. Exposure to blood Pb was statistically significantly associated with higher odds of CKD in the 2nd, 3rd and 4th quartile groups, after adjustment for all co-variates (ag, gender, race, socio-economic status, hypertension, diabetes mellitus, blood cadmium, mercury, and cotinine levels) in all the four models. Blood Hg level was statistically significantly associated with lower odds of CKD in the 2nd quartile group in model 2, 3rd quartile group in model 1, 2 and 3, and the 4th quartile group in all the four models. CONCLUSIONS: Our findings showed that low blood levels of Cd and Pb were associated with higher odds of CKD while low blood levels of Hg were associated with lower odds of CKD in the US adult population. However, temporal association cannot be determined as it is a cross sectional study.

[Research Progress in the Roles of MRE11-RAD50-NBS1 Complex and Human Diseases].

DNA is susceptible to various factors in vitro and in vivo and experience different forms of damage,among which double-strand break(DSB)is a deleterious form.To maintain the stability of genetic information,organisms have developed multiple mechanisms to repair DNA damage.Among these mechanisms,homologous recombination(HR)is praised for the high accuracy.The MRE11-RAD50-NBS1(MRN)complex plays an important role in HR and is conserved across different species.The knowledge on the MRN complex mainly came from the previous studies in Saccharomyces cerevisiae and Caenorhabditis elegans,while studies in the last decades have revealed the role of mammalian MRN complex in DNA repair of higher animals.In this review,we first introduces the MRN complex regarding the composition,structure,and roles in HR.In addition,we discuss the human diseases such as ataxia-telangiectasia-like disorder,Nijmegen breakage syndrome,and Nijmegen breakage syndrome-like disorder that are caused by dysfunctions in the MRN complex.Furthermore,we summarize the mouse models established to study the clinical phenotypes of the above diseases.

A wafer scale thin film of ultra-small Sc2O3 nanocrystals on a 2D COF with high rigidity.

Scandium oxide (Sc2O3) has a wide range of applications in metallurgy, chemical industry, electronics and many other high-tech fields. However, most Sc2O3 materials exist in the powder or bulk form, while nanostructured Sc2O3 has rarely been reported as there is a lack of a common method to control its dimensionality, hindering the understanding of new properties and potential applications of nano-Sc2O3 materials. In this paper, we establish a procedure to synthesize a two-dimensional (2D) Sc2O3-covalent organic framework (COF) composite film where the crystal size of Sc2O3 domains is as small as ∼3 nm. The composite film is prepared by a Schiff base condensation reaction at the sharp n-pentane/water interface using a combination of surfactant-monolayer-assisted interfacial synthesis and laminar assembly polymerization methods. Then the conditions of nucleation and uniform film formation of the 2D Sc2O3/COF are explored further. Meanwhile, an atomic force microscopy indentation test shows that the material has a high Young's modulus of 89.1 ± 3.8 GPa, which is much higher than those of the majority of reported 2D polymer materials. We further extended this synthesis method to the preparation of Yb2O3 (ytterbium oxide) and/or Er2O3 (erbium oxide)-incorporated 2D COF composite films, verifying the universality of this strategy. This work provides an opportunity to vary the dimensionality of many kinds of metal oxides and explore the potential applications of low-dimensional Sc2O3 materials.

Lipotoxicity: The missing link between diabetes and periodontitis?

Lipotoxicity refers to the accumulation of lipids in tissues other than adipose tissue (body fat). It is one of the major pathophysiological mechanisms responsible for the progression of diabetes complications such as non-alcoholic fatty liver disease and diabetic nephropathy. Accumulating evidence indicates that lipotoxicity also contributes significantly to the toxic effects of diabetes on periodontitis. Therefore, we reviewed the current in vivo, in vitro, and clinical evidence of the detrimental effects of lipotoxicity on periodontitis, focusing on its molecular mechanisms, especially oxidative and endoplasmic reticulum stress, inflammation, ceramides, adipokines, and programmed cell death pathways. By elucidating potential therapeutic strategies targeting lipotoxicity and describing their associated mechanisms and clinical outcomes, including metformin, statins, liraglutide, adiponectin, and omega-3 PUFA, this review seeks to provide a more comprehensive and effective treatment framework against diabetes-associated periodontitis. Furthermore, the challenges and future research directions are proposed, aiming to contribute to a more profound understanding of the impact of lipotoxicity on periodontitis.

Erratum: Thioredoxin 1 supports colorectal cancer cell survival and promotes migration and invasion under glucose deprivation through interaction with G6PD: Erratum.

[This corrects the article DOI: 10.7150/ijbs.71809.].

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

TRIM25 promotes glioblastoma cell growth and invasion via regulation of the PRMT1/c-MYC pathway by targeting the splicing factor NONO.

BACKGROUND: Ubiquitination plays an important role in proliferating and invasive characteristic of glioblastoma (GBM), similar to many other cancers. Tripartite motif 25 (TRIM25) is a member of the TRIM family of proteins, which are involved in tumorigenesis through substrate ubiquitination. METHODS: Difference in TRIM25 expression levels between nonneoplastic brain tissue samples and primary glioma samples was demonstrated using publicly available glioblastoma database, immunohistochemistry, and western blotting. TRIM25 knockdown GBM cell lines (LN229 and U251) and patient derived GBM stem-like cells (GSCs) GBM#021 were used to investigate the function of TRIM25 in vivo and in vitro. Co-immunoprecipitation (Co-IP) and mass spectrometry analysis were performed to identify NONO as a protein that interacts with TRIM25. The molecular mechanisms underlying the promotion of GBM development by TRIM25 through NONO were investigated by RNA-seq and validated by qRT-PCR and western blotting. RESULTS: We observed upregulation of TRIM25 in GBM, correlating with enhanced glioblastoma cell growth and invasion, both in vitro and in vivo. Subsequently, we screened a panel of proteins interacting with TRIM25; mass spectrometry and co-immunoprecipitation revealed that NONO was a potential substrate of TRIM25. TRIM25 knockdown reduced the K63-linked ubiquitination of NONO, thereby suppressing the splicing function of NONO. Dysfunctional NONO resulted in the retention of the second intron in the pre-mRNA of PRMT1, inhibiting the activation of the PRMT1/c-MYC pathway. CONCLUSIONS: Our study demonstrates that TRIM25 promotes glioblastoma cell growth and invasion by regulating the PRMT1/c-MYC pathway through mediation of the splicing factor NONO. Targeting the E3 ligase activity of TRIM25 or the complex interactions between TRIM25 and NONO may prove beneficial in the treatment of GBM.

Improving impact of heparan sulfate on the endothelial glycocalyx abnormalities in atherosclerosis as revealed by glycan-protein interactome.

Endothelial dysfunction induced by oxidative stress is an early predictor of atherosclerosis, which can cause various cardiovascular diseases. The glycocalyx layer on the endothelial cell surface acts as a barrier to maintain endothelial biological function, and it can be impaired by oxidative stress. However, the mechanism of glycocalyx damage during the development of atherosclerosis remains largely unclear. Herein, we established a novel strategy to address these issues from the glycomic perspective that has long been neglected. Using countercharged fluorescence protein staining and quantitative mass spectrometry, we found that heparan sulfate, a major component of the glycocalyx, was structurally altered by oxidative stress. Comparative proteomics and protein microarray analysis revealed several new heparan sulfate-binding proteins, among which alpha-2-Heremans-Schmid glycoprotein (AHSG) was identified as a critical protein. The molecular mechanism of AHSG with heparin was characterized through several methods. A heparan analog could relieve atherosclerosis by protecting heparan sulfate from degradation during oxidative stress and by reducing the accumulation of AHSG at lesion sites. In the present study, the molecular mechanism of anti-atherosclerotic effect of heparin through interaction with AHSG was revealed. These findings provide new insights into understanding of glycocalyx damage in atherosclerosis and lead to the development of corresponding therapeutics.

Delocalization Engineering of Heme-Mimetic Artificial Enzymes for Augmented Reactive Oxygen Catalysis.

Developing artificial enzymes based on organic molecules or polymers for reactive oxygen species (ROS)-related catalysis has broad applicability. Herein, inspired by porphyrin-based heme mimics, we report the synthesis of polyphthalocyanine-based conjugated polymers (Fe-PPc-AE) as a new porphyrin-evolving structure to serve as efficient and versatile artificial enzymes for augmented reactive oxygen catalysis. Owing to the structural advantages, such as enhanced π-conjugation networks and π-electron delocalization, promoted electron transfer, and unique Fe-N coordination centers, Fe-PPc-AE showed more efficient ROS-production activity in terms of Vmax and turnover numbers as compared with porphyrin-based conjugated polymers (Fe-PPor-AE), which also surpassed reported state-of-the-art artificial enzymes in their activity. More interestingly, by changing the reaction medium and substrates, Fe-PPc-AE also revealed significantly improved activity and environmental adaptivity in many other ROS-related biocatalytic processes, validating the potential of Fe-PPc-AE to replace conventional (poly)porphyrin-based heme mimics for ROS-related catalysis, biosensors, or biotherapeutics. It is suggested that this study will offer essential guidance for designing artificial enzymes based on organic molecules or polymers.

Radiotherapy-Induced Astrocyte Senescence Promotes an Immunosuppressive Microenvironment in Glioblastoma to Facilitate Tumor Regrowth.

Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to the recurrence of glioma. However, the mechanisms by which such radiation-induced changes are involved in tumor regrowth have not yet been fully investigated. In the present study, how cranial irradiation-induced senescence in non-neoplastic brain cells contributes to glioma progression is explored. It is observed that senescent brain cells facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. Further, it is identified that astrocytes are one of the most susceptible senescent populations and that they promoted chemokine secretion in glioma cells via the senescence-associated secretory phenotype. By using senolytic agents after radiotherapy to eliminate these senescent cells substantially prolonged survival time in preclinical models. The findings suggest the tumor-promoting role of senescent astrocytes in the irradiated glioma microenvironment and emphasize the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas.

Alterations in mitochondrial structure and function in response to environmental temperature changes in Apostichopus japonicus.

Global temperatures have risen as a result of climate change, and the resulting warmer seawater will exert physiological stresses on many aquatic animals, including Apostichopus japonicus. It has been suggested that the sensitivity of aquatic poikilothermal animals to climate change is closely related to mitochondrial function. Therefore, understanding the interaction between elevated temperature and mitochondrial functioning is key to characterizing organisms' responses to heat stress. However, little is known about the mitochondrial response to heat stress in A. japonicus. In this work, we investigated the morphological and functional changes of A. japonicus mitochondria under three representative temperatures, control temperature (18 °C), aestivation temperature (25 °C) and heat stress temperature (32 °C) temperatures using transmission electron microscopy (TEM) observation of mitochondrial morphology combined with proteomics and metabolomics techniques. The results showed that the mitochondrial morphology of A. japonicus was altered, with decreases in the number of mitochondrial cristae at 25 °C and mitochondrial lysis, fracture, and vacuolization at 32 °C. Proteomic and metabolomic analyses revealed 103 differentially expressed proteins and 161 differential metabolites at 25 °C. At 32 °C, the levels of 214 proteins and 172 metabolites were significantly altered. These proteins and metabolites were involved in the tricarboxylic acid (TCA) cycle, substance transport, membrane potential homeostasis, anti-stress processes, mitochondrial autophagy, and apoptosis. Furthermore, a hypothetical network of proteins and metabolites in A. japonicus mitochondria in response to temperature changes was constructed based on proteomic and metabolomic data. These results suggest that the dynamic regulation of mitochondrial energy metabolism, resistance to oxidative stress, autophagy, apoptosis, and mitochondrial morphology in A. japonicus may play important roles in the response to elevated temperatures. In summary, this study describes the response of A. japonicus mitochondria to temperature changes from the perspectives of morphology, proteins, and metabolites, which provided a better understanding the mechanisms of mitochondrial regulation under environment stress in marine echinoderms.

Puerarin alleviates diabetic nephropathy by inhibiting Caspase-1-mediated pyroptosis.

BACKGROUND AND PURPOSE: Diabetic nephropathy (DN) is an important cause of end-stage renal disease, with podocyte injury as the main feature. Pyroptosis plays a non-negligible role in the process of diabetic nephropathy. Puerarin (PR) treatment of diabetic nephropathy has great potential, but the mechanism is not very clear. This article aims to study the protective effect and mechanism of puerarin on DN. METHODS: Streptozotocin (STZ)-induced C57 BL/6J mouse model of DN was given PR, Necrosulfomide (NSA), Nigericin for 12 weeks; A 60 mM high glucose(HG) induced MPC5 cell injury model was administered to PR, NSA, and Nigericin interventions for 24 h. RESULTS: After 12 weeks of administration, PR reduced fasting blood glucose levels in DN mice, alleviated glomerular lesions, reduced podocyte damage, and protected renal function. Meanwhile, PR also inhibits the expression of pyroptosis-related proteins. In addition, PR alleviated the release of Interleukin 18 (IL-18), Interleukin 1beta (IL-1ß), and lactate dehydrogenase (LDH) in MPC5 cells under HG conditions, downregulated the expression of pyrozozois-related proteins, and improved Caspase-1-mediated pyroptosis in MPC5 cells. CONCLUSION: Our study suggests that the beneficial effects of PR in diabetic nephropathy may be associated with inhibition of Caspase-1-mediated pyroptosis.

Combination of gold nanoclusters and silicon quantum dots for ratiometric fluorometry: One system, two mechanisms.

A ratiometric fluorometry based on silicon quantum dots (SiQDs) and gold nanoclusters (AuNCs) is constructed for detecting activity of butyrylcholinesterase (BChE) in human serum. By using thiobutyrylcholine iodide (BTCh) as the substrate of BChE-catalyzed hydrolysis reaction, variation of fluorescence emission from AuNCs is employed as an indicator of BChE activity since one of the hydrolysis products, thiocholine (TCh), would influence the aggregation state of AuNCs and consequently led to the change of fluorescence quantum efficiency of AuNCs. It is interesting that there are two mechanisms working for the fluorescence emission of aggregated AuNCs: aggregation-induced emission enhancement (AIEE) and aggregation-caused quenching (ACQ) with the presence of TCh at very low and higher concentration levels, respectively. Although both of these mechanisms can be utilized for sensing BChE, their opposite influence on the fluorescence emission of aggregated AuNCs should be worthy of attention, especially in the process of developing fluorescence methods for detecting trace targets by using AuNCs. In order to eliminate the fluctuation of fluorophotometer, SiQDs is chosen as the fluorophore to develop by ratiometric fluorescence methods in this work. Additionally, obvious aggregation of AuNCs induces significant decrease of inner filter effect (IFE) on the fluorescence emitted from SiQDs, while mild aggregation of AuNCs demonstrates little IFE. The linear ranges for detecting activity of BChE are 0.004 - 0.05 U/L and 0.5 - 20 U/L by ratiometric fluorometry based on the AIEE and ACQ, respectively. The very different responses originated from AIEE and ACQ of AuNCs would respectively make their own contributions to the determination of BChE activities at very low or high levels, which facilitate the developments of enhanced or quenched fluorescence methods. However, the detection of BChE activities at medium levels might suffer from the combination of AIEE and ACQ with ambiguous fractions. Therefore, it must be careful during the processes of developing and applying fluorescence methods based on the AIEE and ACQ of AuNCs, as well as the process of evaluating their analytical performance.