Investigating spatial patterns and determinants of tourist attractions utilizing POI data: A case study of Hubei Province, China.

Exploring the spatial distribution characteristics of tourist attractions and the influencing factors is of significant importance for destination development, yet little relevant research has been conducted. This study explores the spatial patterns and determinants of tourist attractions using Hubei Province of China as a case based on the POI (Points of Interest) data, combined with standard deviation ellipse, GeoDetector method and so on. The results show that: (1) The distribution of tourist attractions in Hubei Province is concentrated in Wuhan and Huanggang. (2) The overall spatial patterns of tourist attractions in Hubei Province show a trend of "overall dispersion, partial concentration", with the direction of northwest-southeast. (3) The permanent population, passenger traffic volume, per capita GDP, and the added value of the tertiary industry are the primary factors influencing the spatial distribution of tourist attractions in Hubei Province. Additionally, topography and river systems factors also impact their distribution. This study provides critical information for theory and practice in terms of tourism resources optimization.

A biomass phosphonamide enables biodegradable polylactide with favorable flame retardancy and rapid crystallization.

PLA is widely known as biodegradable plastics whose further application in fields such as automotive and architectural is still constrained by its flammability and unsatisfactory crystallization properties. To address the aforementioned concerns, a novel biomass phosphonamide PDPA was synthesized with chemical structure confirmed by FTIR, NMR and elemental analysis tests. Immediately thereafter, PLA/PDPA composites were prepared by melting blending, with a focus on flame retardancy, crystallization properties and flame-retardant mechanism. As expected, PDPA efficiently enhanced both the flame retardancy and crystallization properties of PLA. Specifically, the PLA/4.0PDPA obtained UL-94 V-0 grade and the LOI value increased to 28.6 % with only 4 wt% PDPA added, which comes down to the superior free radical capture and dilution effect of PDPA in the vapor phase and the melting droplet effect. More appealingly, the crystallinity of PLA/4.0PDPA was significantly enhanced to 43.4 % from 2.5 % of PLA, and the shortest t1/2 was 4 mins in the isothermal crystallization process due to the excellent heterogeneous nucleation of PDPA. Moreover, PLA/PDPA composites maintain almost the same mechanical performance as pure PLA. In brief, this work provides a green strategy for the preparation of PLA composites with excellent comprehensive performance and shows great potential in engineering materials.

Fresnel lens three-dimensionally printed on the facet of a single mode fiber for trapping, manipulation, and spectrum.

Fiber optical tweezers (FOTs) provide a functionality for micro-/nanoparticle manipulation with a slim and flexible optical fiber setup. An added in situ spectroscopic functionality can achieve characterization of the trapped particle, potentially useful for endoscopic, in-vivo studies in an inherently heterogeneous environment if the applicator end is all-fiber-built. Here, we demonstrate all-fiber optical tweezers (a-FOTs) for the trapping and in situ spectral measurement of a single, cell-sized microparticle. The key to ensure the simultaneous bifunctionality is a high numerical aperture (NA) Fresnel lens fabricated by two-photon direct laser writing (DLW) corrected by grid-correction methods. We demonstrate trapping and time-resolved, in situ spectroscopy of a single upconversion particle (UCP), a common fluorescent biomarker in biophotonics. The system achieves a 0.5-s time resolution in the in situ spectral measurement of a trapped UCP. The all-fiber designed system preserves the advantages of flexibility and robustness of the fiber, potentially useful for in-vivo biomedical studies such as cell-to-cell interactions, pH and temperature detection, and nucleic acids detection.

Effects of Selenium and Cadmium on Human Liver and Kidney Functions in Exposed Black Shale Areas.

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long-term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B-Se) and urine selenium (U-Se) levels were detected in these areas, measuring 416.977 µg/L and 352.690 µg/L and 104.527 µg/L and 51.820 µg/L, respectively. Additionally, the median blood Cd (B-Cd) and urine Cd (U-Cd) levels were markedly elevated at 4.821 µg/L and 3.848 µg/L and at 7.750 µg/L and 7.050 µg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 µmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 µmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.

RoMAT: Role-based multi-agent transformer for generalizable heterogeneous cooperation.

Multi-task multi-agent systems (MASs) are challenging to model because they involve heterogeneous agents with different behavior patterns that need to cooperate across various tasks. Existing networks for single-agent policies are not suitable for this setting, as they cannot share policies among agents without losing task-specific performance. We propose a novel framework called Role-based Multi-Agent Transformer (RoMAT), which uses a sequence modeling technique and a role-based actor to enable agents to adapt to different tasks and roles in MASs. RoMAT has a modular model architecture, where backbone networks are shared by all agents, but a small part of the parameters (role-based actor) is independent, depending on the agents' exclusive structures. We evaluate RoMAT on several benchmark tasks and show that it can capture the behavior patterns of heterogeneous agents and achieve better performance and generalization than other methods in both single and multi-task settings.

Regulation of plant resistance to salt stress by the SnRK1-dependent splicing factor SRRM1L.

Most splicing factors are extensively phosphorylated but their physiological functions in plant salt resistance are still elusive. We found that phosphorylation by SnRK1 kinase is essential for SRRM1L nuclear speckle formation and its splicing factor activity in plant cells. In Arabidopsis, loss-of-function of SRRM1L leads to the occurrence of alternative pre-mRNA splicing events and compromises plant resistance to salt stress. In Arabidopsis srrm1l mutant line, we identified an intron-retention Nuclear factor Y subunit A 10 (NFYA10) mRNA variant by RNA-Seq and found phosphorylation-dependent RNA-binding of SRRM1L is indispensable for its alternative splicing activity. In the wild-type Arabidopsis, salt stress can activate SnRK1 to phosphorylate SRRM1L, triggering enrichment of functional NFYA10.1 variant to enhance plant salt resistance. By contrast, the Arabidopsis srrm1l mutant accumulates nonfunctional NFYA10.3 variant, sensitizing plants to salt stress. In summary, this work deciphered the molecular mechanisms and physiological functions of SnRK1-SRRM1L-NFYA10 module, shedding light on a regulatory pathway to fine-tune plant adaptation to abiotic stress at the post-transcriptional and post-translational levels.

Elliptical spiral zone plate fabrication using direct laser writing for generating an elliptical perfect vortex beam.

We report and fabricate a novel, to our knowledge, vortex beam generator called elliptical spiral zone plate (ESZP) using direct laser writing (DLW), which can generate the elliptical perfect vortex beam (EPVB). It is shown that the radius of the EPVB can be adjusted by tuning the control parameters of the ESZP. It is verified through the interference experiment and the Hermitian-Gaussian light field that the topological charge of the EPVB is consistent with the design. In addition, we integrate the ESZP at the tip of the single-mode fiber. Our work may set the scene for applications in fiber optical tweezers, optical communications, and integrated optics.

Synthesis of renewable furan-based phosphate and the superior flame retardancy in biodegradable polylactide.

Currently, it has long been considered a challenge to provide sustainable additives for polylactide (PLA) in green way to endow it excellent comprehensive properties. Given the flammability and unsatisfactory crystallization performance of PLA, a furan-based phosphate furfurylamine trimethylphosphate (FATMP) was synthesized from 2-furfurylamine and amino trimethylphosphonic acid by a simple hydration reaction, and the PLA/FATMP composites were prepared by melting blending process. The tensile performance, crystallization behaviors, flame retardancy, and flame-retardant mechanism received special attention. Results showed that the incorporation of only 3 wt% FATMP could indeed increase the LOI value of PLA from 19.8 to 27.3 %, and simultaneously acquired V-0 rating in the vertical burning test owing to the favorable synergistic effect between the vapor phase and the condensed phase. Additionally, the half-crystallization time of PLA was decreased from 12.4 to 5.1 mins with the addition of FATMP, which acted as a nucleating agent. More appealingly, the tensile performance of PLA/FATMP composites was also well maintained. In general, the PLA/FATMP composites we proposed could be promising candidates in application fields where favorable flame retardancy and crystallization ability are required.

Three-dimensional printing of a beam expander to enable the combination of hundred-micron optical elements and a single-mode fiber.

We use a flexible two-photon photopolymerization direct laser writing to fabricate an integrated diffractive lens system on a fiber tip to expand the output beam of the fiber. The results show that the micro-integrated beam expander based on double lenses (axial size of about 100 µm) has a magnification of 5.9 and a loss of 0.062 dB. Subsequently, we demonstrate the fabrication of a spiral phase plate (diffractive optical elements) and micro-lens arrays (refractive optical elements) on an integrated beam expander, and their optical properties are measured and analyzed, respectively. This Letter is an exploration of the future integrated micro-optical systems on an optical fiber tip.

Quantitative Phosphoproteomic Analysis Provides Insights into the Sodium Bicarbonate Responsiveness of Glycine max.

Sodium bicarbonate stress caused by NaHCO3 is one of the most severe abiotic stresses affecting agricultural production worldwide. However, little attention has been given to the molecular mechanisms underlying plant responses to sodium bicarbonate stress. To understand phosphorylation events in signaling pathways triggered by sodium bicarbonate stress, TMT-labeling-based quantitative phosphoproteomic analyses were performed on soybean leaf and root tissues under 50 mM NaHCO3 treatment. In the present study, a total of 7856 phosphopeptides were identified from cultivated soybeans (Glycine max L. Merr.), representing 3468 phosphoprotein groups, in which 2427 phosphoprotein groups were newly identified. These phosphoprotein groups contained 6326 unique high-probability phosphosites (UHPs), of which 77.2% were newly identified, increasing the current soybean phosphosite database size by 43.4%. Among the phosphopeptides found in this study, we determined 67 phosphopeptides (representing 63 phosphoprotein groups) from leaf tissue and 554 phosphopeptides (representing 487 phosphoprotein groups) from root tissue that showed significant changes in phosphorylation levels under sodium bicarbonate stress (fold change >1.2 or <0.83, respectively; p < 0.05). Localization prediction showed that most phosphoproteins localized in the nucleus for both leaf and root tissues. GO and KEGG enrichment analyses showed quite different enriched functional terms between leaf and root tissues, and more pathways were enriched in the root tissue than in the leaf tissue. Moreover, a total of 53 different protein kinases and 7 protein phosphatases were identified from the differentially expressed phosphoproteins (DEPs). A protein kinase/phosphatase interactor analysis showed that the interacting proteins were mainly involved in/with transporters/membrane trafficking, transcriptional level regulation, protein level regulation, signaling/stress response, and miscellaneous functions. The results presented in this study reveal insights into the function of post-translational modification in plant responses to sodium bicarbonate stress.

Novel heterozygous mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome: A care-compliant case report.

RATIONALE: The diagnosis of Gentleman syndrome (GS) is usually delayed because the clinical symptoms are easily mistaken. PATIENT CONCERNS: A 19-year-old male patient was referred to endocrinology due to intermittent twitch of extremities for approximately 7 years. DIAGNOSES: The diagnosis of GS was made based on the laboratory and gene detection results. We identified 2 new variants in the SLC12A3 gene [c.857 A > C (exon7) and c.2089_2095del (exon17)] in his Asian family. INTERVENTIONS: The patient received the treatment of potassium chloride sustained release tablets, potassium magnesium aspartate and spironolactone. After given potassium supplement through enema, his serum potassium level was corrected to normal. OUTCOMES: The electrolyte imbalance including hypokalemia and hypomagnesemia were improved with a remission of the clinical manifestations. But the patient's condition still could not remain stable for his irregular oral potassium supplementation during the follow-up of nearly 3 months. LESSONS: Our finding broadens the variant spectrum of SLC12A3 and contributes to a more quickly genetic counseling. As a result, when a patient presents with persistent, unspecified, and inadequately treated hypokalemia, tests for GS should indeed be considered. For suspected cases of GS, genetic testing should always be considered in the diagnosis.

A crosslinked network polypyrrole coated cobalt doped Fe2O3@carbon cloth flexible anode material for quasi-solid asymmetric supercapacitors.

Iron(III) oxide (Fe2O3) exhibits a substantial theoretical specific capacitance and a broad operational voltage window, making it a prospective anode material. The crystal structure of Fe2O3 was altered through cobalt doping, and its electronic conductivity was improved by supporting it with carbon cloth (Co-Fe2O3@CC). Subsequently, a crosslinked network of polypyrrole (PPy) was synthesized onto Co-Fe2O3@CC via an ice-water bath, resulting in the formation of PPy/Co-Fe2O3@CC. This PPy nano-crosslinked network not only established three-dimensional electron transport pathways on the Fe2O3 surface but also amplified the composite material's specific surface area to 45.229 m2 g-1, thereby promoting its electrochemical performance. At a current density of 2 mA cm-2, PPy/Co-Fe2O3@CC displayed an area specific capacitance of 704 mF cm-2, a value 2.2 times higher than that of Co-Fe2O3@CC. The assembled PPy/Co-Fe2O3@CC//Ni-MnO2@CC asymmetric supercapacitor demonstrated an energy density of 1.41 mW h cm-3 at a power density of 54 mW cm-3, making the synthesized electrode material a promising candidate for flexible supercapacitors.

Selenium hyperaccumulator plant Cardamine enshiensis: from discovery to application.

Selenium (Se) is an essential trace element for animals and humans. Se biofortification and Se functional agriculture are emerging strategies to satisfy the needs of people who are deficient in Se. With 200 km2 of Se-excess area, Enshi is known as the "world capital of Se." Cardamine enshiensis (C. enshiensis) is a Se hyperaccumulation plant discovered in the Se mine drainage area of Enshi. It is edible and has been approved by National Health Commission of the People's Republic of China as a new source of food, and the annual output value of the Se-rich industry in Enshi City exceeds 60 billion RMB. This review will mainly focus on the discovery and mechanism underlying Se tolerance and Se hyperaccumulation in C. enshiensis and highlight its potential utilization in Se biofortification agriculture, graziery, and human health.

Do high soil geochemical backgrounds of selenium and associated heavy metals affect human hepatic and renal health? Evidence from Enshi County, China.

It is unclear whether the United States Environmental Protection Agency (US EPA) method can accurately assess heavy metal risks in high-Se areas. Herein, a black shale outcropping in Enshi County, China, was taken as the study area, and a carbonate outcropping in Lichuan County was the control area. Selenium and associated heavy metal concentrations in rock, soil, rice, human blood and urine samples and human sensitive hepatic and renal biomarkers were measured. The results showed that the contents of selenium, cadmium, molybdenum and copper in the study area were 3.68 ± 2.72 µg/g, 2.65 ± 1.42 µg/g, 16.3 ± 15.5 µg/g, and 57.3 ± 17.6 µg/g, respectively, in soil (n = 47) and 1.072 ± 0.924 µg/g, 0.252 ± 0.310 µg/g, 2.800 ± 2.167 µg/g, and 10.91 ± 27.42 µg/g, respectively, in rice (n = 47). The daily adult intake levels of selenium, cadmium and molybdenum from rice consumption in the study area (exposure group) exceed the recommended tolerance values in China. According to the US EPA method, these environmental media pose a significant risk to human health. However, in the exposure group (n = 111), the median levels of the sensitive hepatic biomarkers alanine aminotransferase (18 U/L), aspartate aminotransferase (28 U/L) and total bilirubin (10.9 µmol/L) and the sensitive renal biomarkers serum creatinine (70.1 µmol/L), urinary nitrogen (5.73 mmol/L) and uric acid (303.80 µmol/L) were within reference ranges and had values equivalent to those of the control group (P > 0.05). The elements tended to differentiate during migration from one medium to another. Due to the complex interaction between selenium and heavy metals, a survey of human health indicators is indispensable when the US EPA method is used to assess the heavy metal risks in high-Se areas. The recommended molybdenum tolerable intake in the U.S. (2000 µg/d) is reasonable based on a comparison.

The Role of GmSnRK1-GmNodH Module in Regulating Soybean Nodulation Capacity.

SnRK1 protein kinase plays hub roles in plant carbon and nitrogen metabolism. However, the function of SnRK1 in legume nodulation and symbiotic nitrogen fixation is still elusive. In this study, we identified GmNodH, a putative sulfotransferase, as an interacting protein of GmSnRK1 by yeast two-hybrid screen. The qRT-PCR assays indicate that GmNodH gene is highly expressed in soybean roots and could be induced by rhizobial infection and nitrate stress. Fluorescence microscopic analyses showed that GmNodH was colocalized with GsSnRK1 on plasma membrane. The physical interaction between GmNodH and GmSnRK1 was further verified by using split-luciferase complementary assay and pull-down approaches. In vitro phosphorylation assay showed that GmSnRK1 could phosphorylate GmNodH at Ser193. To dissect the function and genetic relationship of GmSnRK1 and GmNodH in soybean, we co-expressed the wild-type and mutated GmSnRK1 and GmNodH genes in soybean hairy roots and found that co-expression of GmSnRK1/GmNodH genes significantly promoted soybean nodulation rates and the expression levels of nodulation-related GmNF5α and GmNSP1 genes. Taken together, this study provides the first biological evidence that GmSnRK1 may interact with and phosphorylate GmNodH to synergistically regulate soybean nodulation.

Functional characterization of wild soybean (Glycine soja) GsSnRK1.1 protein kinase in plant resistance to abiotic stresses.

Protein kinases play crucial roles in the regulation of plant resistance to various stresses. In this work, we determined that GsSnRK1.1 was actively responsive to saline-alkali, drought, and abscisic acid (ABA) stresses by histochemical staining and qRT-PCR analyses. The wild-type GsSnRK1.1 but not the kinase-dead mutant, GsSnRK1.1(K49M), demonstrated in vitro kinase activity by phosphorylating GsABF2. Intriguingly, we found that GsSnRK1.1 could complement the loss of SNF1 kinase in yeast Msy1193 (-snf1) mutant, rescue growth defects of yeast cells on medium with glycerol as a carbon resource, and promote yeast resistance to NaCl or NaHCO3. To further elucidate GsSnRK1.1 function in planta, we knocked out SnRK1.1 gene from the Arabidopsis genome by the CRISPR/Cas9 approach, and then expressed GsSnRK1.1 and a series of mutants into snrk1.1-null lines. The transgenic Arabidopsis lines were subjected to various abiotic stress treatments. The results showed that GsSnRK1.1(T176E) mutant with enhanced protein kinase activity significantly promoted, but GsSnRK1.1(K49M) and GsSnRK1.1(T176A) mutants with disrupted protein kinase activity abrogated, plant stomatal closure and tolerance to abiotic stresses. In conclusion, this study provides the molecular clues to fully understand the physiological functions of plant SnRK1 protein kinases.

Myocarditis or Pericarditis Following the COVID-19 Vaccination in Adolescents: A Systematic Review.

Background: By 16 May 2022, 12,186,798,032 people had been vaccinated with COVID-19 vaccines. Our study found that myocarditis/pericarditis may occur in adolescents after COVID-19 vaccination. Methods: In this regard, we conducted a meta-analysis of seven groups of adolescents aged 12-19 years to compare the incidence of myocarditis/pericarditis after vaccination and compare the relative risk incidence after the first and second doses of a COVID-19 vaccine, and between males and females for risk incidence. Results: We analyzed 22,020,997 subjects from seven studies, including 130 cases of confirmed myocarditis/pericarditis. The overall mean incidence rate was 1.69 cases per 100,000 person-years. Of these, 19 of the 12,122,244 people who received a first dose of a COVID-19 vaccine had myocarditis/pericarditis, an incidence rate of 0.0022% (95% CI 0.0001-0.0034), and 111 of the 1,008,753 people who received a second dose had myocarditis/pericarditis, an incidence rate of 0.0107% (95% CI 0.0059-0.0155). The prevalence relative ratio (RR) after the first and second doses was RR = 5.53 (95% CI: 3.01-10.16), with a higher prevalence after the second dose than after the first dose of a COVID-19 vaccine. After a second dose of a COVID-19 vaccine, the RR for males relative to females was RR = 13.91 (95% CI: 4.30-44.95), with a more pronounced risk of disease in males than in females. Conclusions: Our study showed that myocarditis/pericarditis occurred after vaccination with the BNT162b2 or Comirnaty vaccine, especially after the second vaccination in male adolescents, but the incidence of myocarditis/pericarditis after vaccination with the above vaccines was very rare (0.0022%). Therefore, it is recommended that adolescents should be vaccinated with the COVID-19 universal vaccine as soon as possible and closely monitored for subsequent adverse reactions, which can be treated promptly.

Epigenetic Regulation of Plant Tolerance to Salt Stress by Histone Acetyltransferase GsMYST1 From Wild Soybean.

Salt stress is one of the most devastating environmental factors threatening soybean growth and yield. However, the molecular link between salt stress and epigenetics has not been well-elucidated in soybean. In this study, from the wild soybean cDNA library, we isolated a GsSnRK1 kinase interacting protein (GsMSTY1) which is phylogenetically homologous with histone acetyltransferase MYST family with unknown function. GsMSTY1 gene is dominantly expressed in wild soybean roots and is highly responsive to abiotic stresses. GsMYST1 was able to be phosphorylated at the Ser44 site by GsSnRK1 and demonstrated in vivo acetyltransferase activity in transgenic soybean roots revealed by an anti-H4ace antibody. A transcription factor protein GsNAC83 was identified to interact with both GsMYST1 and GsSnRK1, and GsNAC83 could recruit the GsMYST1-GsSnRK1 module to COR15B gene promoter determined by ChIP-qPCR assay. To dissect the molecular functions of this ternary complex, we treated the transgenic soybean roots with salt stress and found that the stress could activate GsSnRK1, and the activated GsSnRK1 subsequently phosphorylated GsMYST1 to enhance its acetyltransferase activity which may epigenetically promote the target gene expression. To explore the physiological functions, we coexpressed GsSnRK1 and GsMYST1 genes in soybean hairy roots and found that only GsSnRK1(wt)/GsMYST1(wt) but not the mutant genes could promote soybean resistance to salt stress, implicating that phosphorylation of GsMYST1 is required for it to acetylate histone H4 on the target genes to upregulate expression of the stress-related genes. Our data shed new light on the functions of the GsSnRK1-GsMYST1-GsNAC83 module and its regulatory mechanism on plant tolerance to abiotic stresses.

The Association Between Pancreatic Steatosis and Metabolic Syndrome: A 5-Year Follow-up Study Among a General Chinese Population.

OBJECTIVES: To date, the complete natural history of pancreatic steatosis is unknown. This study aimed to investigate the association of fatty pancreas (FP) in the incidence of metabolic syndrome and its components among Chinese patients with a 5-year follow-up. METHODS: Three independent cross-sectional surveys were carried out in 2013, 2015, and 2018. Fatty pancreas was diagnosed via transabdominal sonography. Logistic regression analysis was used to estimate the correlation between FP and metabolic syndrome. New cases of metabolic syndrome and its components were estimated by Cox proportional hazards models. RESULTS: At baseline, 12,551 individuals classified into FP (n = 1010) and non-FP (n = 11,541) groups were finally enrolled. In cross-sectional analyses, odds ratio of FP was 2.378 (95% confidence interval [CI], 2.085-2.713; P < 0.001). In longitudinal analyses, FP was associated with the occurrence of metabolic syndrome (hazard ratio [HR], 3.179; 95% CI, 2.197-4.6; P < 0.001), type 2 diabetes mellitus (HR, 13.99; 95% CI, 7.865-24.883; P < 0.001), nonalcoholic fatty liver disease (HR, 31.843; 95% CI, 7.73-131.171; P < 0.001), and hypertension (HR, 12.801; 95% CI, 7.323-22.38; P < 0.001). CONCLUSIONS: Pancreatic steatosis is strongly associated with the occurrence of metabolic syndrome and its components such as hypertension and diabetes.

microRNA-15b-5p shuttled by mesenchymal stem cell-derived extracellular vesicles protects podocytes from diabetic nephropathy via downregulation of VEGF/PDK4 axis.

Diabetic nephropathy (DN) is a severe complication of diabetes lethal for end-stage renal disease, with less treatment methodologies and uncertain pathogenesis. In the current study, we determined the role of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) containing microRNA (miR)-15b-5p in DN. After extraction and identification of MSC-derived EVs, mouse podocyte line MPC5 was selected to establish an in vitro high-glucose (HG) cell model, where expression of miR-15b-5p, pyruvate dehydrogenase kinase 4 (PDK4) and VEGFA expression in tissues and cells were determined. The loss- and gain- function assays were conducted to determine the roles of miR-15b-5p, PDK4 and VEGFA. MPC5 cells were then co-cultured with MSC-derived EVs and their biological behaviors were detected by Western blot, CCK-8 assay, and flow cytometry. The binding relationship between miR-15b-5p and PDK43 by dual luciferase reporter gene assay. The expression of miR-15b-5p was downregulated in podocytes under HG environment, but highly expressed in mouse MSCs-derived EVs. EVs-derived miR-15b-5p could protect MPC5 cell apoptosis and inflammation. miR-15b-5p inhibited the expression of PDK4 by directly bound to the 3'UTR region of PDK4 gene. miR-15b-5p inhibits VEGF expression by binding to PDK4. Inhibition of PDK4 decreased VEGFA expression and reduced apoptosis and inflammation. Collectively, miR-15b-5p shuttled by MSC-derived EV can play protective roles in HG-induced mouse podocyte injury, possibly by targeting PDK4 and decreasing the VEGFA expression.