Gelatin-Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise-Induced Hearing Loss.

Nanoparticle-based drug delivery strategies have emerged as a crucial avenue for comprehensive sensorineural hearing loss treatment. Nevertheless, developing therapy vectors crossing both biological and cellular barriers has encountered significant challenges deriving from various external factors. Herein, the rational integration of gelatin nanoparticles (GNPs) with tetrahedral DNA nanostructures (TDNs) to engineer a distinct drug-delivery nanosystem (designed as TDN@GNP) efficiently enhances the biological permeability and cellular internalization, further resolving the dilemma of noise-induced hearing loss via loading epigallocatechin gallate (EGCG) with anti-lipid peroxidation property. Rationally engineering of TDN@GNP demonstrates dramatic alterations in the physicochemical key parameters of TDNs that are pivotal in cell-particle interactions and promote cellular uptake through multiple endocytic pathways. Furthermore, the EGCG-loaded nanosystem (TDN-EGCG@GNP) facilitates efficient inner ear drug delivery by superior permeability through the biological barrier (round window membrane), maintaining high drug concentration within the inner ear. The TDN-EGCG@GNP actively overcomes the cell membrane, exhibiting hearing protection from noise insults via reduced lipid peroxidation in outer hair cells and spiral ganglion neurons. This work exemplifies how integrating diverse vector functionalities can overcome biological and cellular barriers in the inner ear, offering promising applications for inner ear disorders.

Cyanidin-3-glucoside inhibits ferroptosis in renal tubular cells after ischemia/reperfusion injury via the AMPK pathway.

BACKGROUND: Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, is closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory and antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show that C3G exerts nephroprotective effects against I/R-AKI related ferroptosis by regulating the AMPK pathway. METHODS: Hypoxia/reoxygenation (H/R)-induced HK-2 cells and I/R-AKI mice were treated with C3G with or without inhibiting AMPK. The level of intracellular free iron, the expression of the ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and the levels of the lipid peroxidation markers 4-hydroxynonenal (4-HNE), lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were examined. RESULTS: We observed the inhibitory effect of C3G on ferroptosis in vitro and in vivo, which was characterized by the reversion of excessive intracellular free iron accumulation, a decrease in 4-HNE, lipid ROS, MDA levels and ACSL4 expression, and an increase in GPX4 expression and glutathione (GSH) levels. Notably, the inhibition of AMPK by CC significantly abrogated the nephroprotective effect of C3G on I/R-AKI models in vivo and in vitro. CONCLUSION: Our results provide new insight into the nephroprotective effect of C3G on acute I/R-AKI by inhibiting ferroptosis by activating the AMPK pathway.

Adenovirus-associated acute conjunctivitis in Beijing, China, 2011-2013.

BACKGROUND: Human adenovirus (HAdV)-associated acute conjunctivitis is a common infectious disease and causes significant morbidity among residents in Beijing, China. However, little is known about the epidemiology and type distribution of acute adenoviral conjunctivitis in Beijing. METHODS: Acute conjunctivitis surveillance was conducted in 18 hospitals in Beijing from July through October during 2011-2013. HAdVs were detected by PCR from eye swab and types were determined by partial hexon and fiber gene sequencing. Risk factors associated with adenoviral conjunctivitis were analyzed. RESULTS: Of 876 conjunctivitis cases, 349 (39.8%) were HAdV positive. HAdV detection was most common in conjunctivitis patients aged 18-40 years; patients with contact history with a conjunctivitis case; patients with specimen collected on days 4-6 post symptom onset and patients who worked in food service as catering attendants. Fifteen types were identified among adenoviral conjunctivitis cases. Five HAdV types (HAdV-4, - 37, - 53, - 64 and - 8) accounted for 81.1% of all adenoviral conjunctivitis cases. HAdV-37, - 4 and - 53 were the most common types associated with adenoviral conjunctivitis in 2011, 2012 and 2013, respectively. CONCLUSION: Multiple HAdV types were associated with acute conjunctivitis in Beijing. Predominant types associated with adenoviral conjunctivitis circulating in Beijing varied from year to year.

An outbreak of Coxsackievirus A6-associated hand, foot, and mouth disease in a kindergarten in Beijing in 2015.

BACKGROUND: Coxsackievirus A6 (CVA6) is one of the major agents to cause hand, foot and mouth disease (HFMD) outbreaks globally. The objective of this study is to investigate the epidemiologic and clinical manifestations of CVA6 outbreak, and thus guide the diagnosis and treatment of the disease, as well as disease prevention. METHODS: An HFMD outbreak in a kindergarten was reported to Shijingshan District Center for Disease Control and Prevention (SCDC) on November 2, 2015 in Beijing, China. Epidemiological investigation was conducted. We performed a nine-week follow-up study to collect and analyze the clinical manifestations of HFMD cases. RESULTS: The outbreak yield 56 (15.7%) clinical diagnosed HFMD cases out of 357 registered children in the kindergarten with the mean age of 3.5 years old. This outbreak lasted for three days and ceased after initiating infectious disease controlling procedures, including periodical suspension of the kindergarten activities, environmental disinfection, and family health education. Fifty-one cases were followed for nine weeks. The positive rate of clinical manifestations of rash, fever, desquamation, pigmentation and onychomadesis were 100.0%, 84.3%, 68.6%, 17.6% and 43.1%, respectively. Children developed desquamation within the first 4 weeks after disease onset and developed onychomadesis between the 3th and 8th week after disease onset. Children with desquamation had 9.3 (95%CI: 1.836-47.437) times higher odds of developing onychomadesis compared to those without this manifestation. Ten out of 14 collected samples were CVA6 positive, and five positive samples shared a high degree of similarity in the VP1 nucleotide and amino acid sequences (99.9-100.0% and 100%). CONCLUSION: This HFMD outbreak was caused by CVA6, featured with delayed symptoms. Emerging CVA6-associated HFMD and its delayed symptoms should be paid more attention to reduce outbreaks and provide more information to doctors and parents.

Increased norovirus activity was associated with a novel norovirus GII.17 variant in Beijing, China during winter 2014-2015.

BACKGROUND: Norovirus (NoV) is a leading cause of sporadic cases and outbreaks of acute gastroenteritis (AGE). Increased NoV activity was observed in Beijing, China during winter 2014-2015; therefore, we examined the epidemiological patterns and genetic characteristics of NoV in the sporadic cases and outbreaks. METHODS: The weekly number of infectious diarrhea cases reported by all hospitals in Beijing was analyzed through the China information system for disease control and prevention. Fecal specimens were collected from the outbreaks and outpatients with AGE, and GI and GII NoVs were detected using real time reverse transcription polymerase chain reaction. The partial capsid genes and RNA-dependent RNA polymerase (RdRp) genes of NoV were both amplified and sequenced, and genotyping and phylogenetic analyses were performed. RESULTS: Between December 2014 and March 2015, the number of infectious diarrhea cases in Beijing (10,626 cases) increased by 35.6% over that of the previous year (7835 cases), and the detection rate of NoV (29.8%, 191/640) among outpatients with AGE was significantly higher than in the previous year (12.9%, 79/613) (χ(2) = 53.252, P < 0.001). Between November 2014 and March 2015, 35 outbreaks of AGE were reported in Beijing, and NoVs were detected in 33 outbreaks, all of which belonged to the GII genogroup. NoVs were sequenced and genotyped in 22 outbreaks, among which 20 were caused by a novel GII.17 strain. Among outpatients with AGE, this novel GII.17 strain was first detected in an outpatient in August 2014, and it replaced GII.4 Sydney_2012 as the predominant variant between December 2014 and March 2015. A phylogenetic analysis of the capsid genes and RdRp genes revealed that this novel GII.17 strain was distinct from previously identified GII variants, and it was recently designated as GII.P17_GII.17. This variant was further clustered into two sub-groups, named GII.17_2012 and GII.17_2014. During winter 2014-2015, GII.17_2014 caused the majority of AGE outbreaks in China and Japan. CONCLUSIONS: During winter 2014-2015, a novel NoV GII.17 variant replaced the GII.4 variant Sydney 2012 as the predominant strain in Beijing, China and caused increased NoV activity.

In vivo and in vitro evidence of the sex-dependent pharmacokinetics and disposition of G004, a potential hypoglycemic agent, in rats.

G004 is a novel sulfonylurea hypoglycemic drug which aimed at reducing macro- and micro-vascular complications as well as controlling glucose excursion in type 2 diabetes mellitus. The pharmacokinetics of G004 in rats was sex- and dose-dependent over the dose range of 1-10 mg kg(-1). The mean AUC values in the female rats were fivefold higher than those in males. Drug blood and tissue levels in female rats were higher than the most counterparts of males. Compared with male rats, G004 was eliminated slowly from female rats in the bile, urine and feces. Consistent with the in vivo observations, marked sex-related difference of the metabolizing activity between the male and female liver microsomes (RLM) was observed. The intrinsic clearance (V max/K m) of G004 was 3.1-fold larger in the RLM from male than female rats. Seventeen oxidative metabolites were identified in rat liver microsomes. The amount of three metabolites of G004 showed relatively sex-related difference in RLM incubations. CYP2C11 was demonstrated mainly contributing to the sex-related differences in the pharmacokinetics and disposition of G004 in rats.

Environmental enrichment attenuates depressive-like behavior in maternal rats by inhibiting neuroinflammation and apoptosis and promoting neuroplasticity.

Gestational stress can exacerbate postpartum depression (PPD), for which treatment options remain limited. Environmental enrichment (EE) may be a therapeutic intervention for neuropsychiatric disorders, including depression, but the specific mechanisms by which EE might impact PPD remain unknown. Here we examined the behavioral, molecular, and cellular impact of EE in a stable PPD model in rats developed through maternal separation (MS). Maternal rats subjected to MS developed depression-like behavior and cognitive dysfunction together with evidence of significant neuroinflammation including microglia activation, neuronal apoptosis, and impaired synaptic plasticity. Expanding the duration of EE to throughout pregnancy and lactation, we observed an EE-associated reversal of MS-induced depressive phenotypes, inhibition of neuroinflammation and neuronal apoptosis, and improvement in synaptic plasticity in maternal rats. Thus, EE effectively alleviates neuroinflammation, neuronal apoptosis, damage to synaptic plasticity, and consequent depression-like behavior in mother rats experiencing MS-induced PPD, paving the way for new preventive and therapeutic strategies for PPD.

Resting-state EEG as a potential indicator to predict sleep quality in depressive patients.

OBJECTIVES: To investigate the changes in sleep quality, heart rate variability (HRV) and resting-state electroencephalogram (rsEEG) in patients with major depressive disorder (MDD), and to explore whether HRV and rsEEG may be served as more convenient tools to assess sleep quality in MDD patients. METHOD: We included a total of 91 subjects (46 healthy controls and 45 MDD patients) and compared their sleep quality, HRV and power spectra of rsEEG. Correlation analyses were conducted to discuss the relationship between HRV and seven factors of PSQI. Multiple linear regression model was used to examine whether absolute band power could predict sleep quality in MDD patients. RESULTS: We found higher PSQI scores and lower levels of HRV in depressive individuals compared with healthy controls. In MDD patients, sleep latency was negatively correlated with RMSSD and HF. Delta, theta, and alpha band power of rsEEG were higher in MDD patients. Regression analyses showed delta band power of TP8, as well as theta, alpha band power of AF3 predicts PSQI score of MDD patients. CONCLUSIONS: The findings of our study show that some aspects of sleep problems had negative correlations with parasympathetic activity and the regression model supports that the band power of rsEEG may be used as a potential indicator to evaluate the sleep quality in MDD patients. SIGNIFICANCE: Cortical hyperarousal may be one of the reasons leading to poor sleep quality of MDD patients. And resting-state EEG can be used as a potential indicator for clinical assessment of MDD patients' sleep quality.

Effects of Early Adverse Life Events on Depression and Cognitive Performance from the Perspective of the Heart-Brain Axis.

Early adverse life events (EALs) increase susceptibility to depression and impair cognitive performance, but the physiological mechanisms are still unclear. The target of this article is to clarify the impact of adverse childhood experiences on emotional and cognitive performance from the perspective of the heart-brain axis. We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test cognitive function and the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Heart rate variability (HRV) and electroencephalograms (EEG) were acquired at rest. We observed that subjects with depression had experienced more traumatic events during their childhood. Furthermore, they exhibited lower heart rate variability and higher power in the delta, theta, and alpha frequency bands. Moreover, heart rate variability partially mediated the association between childhood trauma exposure and depressive symptoms. Our findings suggested that adverse life events in childhood could influence the development of depression in adulthood, which might be linked to cardiac autonomic dysfunction and altered brain function.

Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with non-alcoholic fatty liver disease (NAFLD) by bioinformatics analysis and machine learning.

Background: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are closely related to immune and inflammatory pathways. This study aimed to explore the diagnostic markers for CKD patients with NAFLD. Methods: CKD and NAFLD microarray data sets were screened from the GEO database and analyzed the differentially expressed genes (DEGs) in GSE10495 of CKD date set. Weighted Gene Co-Expression Network Analysis (WGCNA) method was used to construct gene coexpression networks and identify functional modules of NAFLD in GSE89632 date set. Then obtaining NAFLD-related share genes by intersecting DEGs of CKD and modular genes of NAFLD. Then functional enrichment analysis of NAFLD-related share genes was performed. The NAFLD-related hub genes come from intersection of cytoscape software and machine learning. ROC curves were used to examine the diagnostic value of NAFLD related hub genes in the CKD data sets and GSE89632 date set of NAFLD. CIBERSORTx was also used to explore the immune landscape in GSE104954, and the correlation between immune infiltration and hub genes expression was investigated. Results: A total of 45 NAFLD-related share genes were obtained, and 4 were NAFLD-related hub genes. Enrichment analysis showed that the NAFLD-related share genes were significantly enriched in immune-related pathways, programmed cell death, and inflammatory response. ROC curve confirmed 4 NAFLD-related hub genes in CKD training set GSE104954 and other validation sets. Then they were used as diagnostic markers for CKD. Interestingly, these 4 diagnostic markers of CKD also showed good diagnostic value in the NAFLD date set GSE89632, so these genes may be important targets of NAFLD in the development of CKD. The expression levels of the 4 diagnostic markers for CKD were significantly correlated with the infiltration of immune cells. Conclusion: 4 NAFLD-related genes (DUSP1, NR4A1, FOSB, ZFP36) were identified as diagnostic markers in CKD patients with NAFLD. Our study may provide diagnostic markers and therapeutic targets for CKD patients with NAFLD.

Monolithic 3D Integration of Analog RRAM-Based Computing-in-Memory and Sensor for Energy-Efficient Near-Sensor Computing.

In the era of the Internet of Things, vast amounts of data generated at sensory nodes impose critical challenges on the data-transfer bandwidth and energy efficiency of computing hardware. A near-sensor computing (NSC) architecture places the processing units closer to the sensors such that the generated data can be processed almost in situ with high efficiency. This study demonstrates the monolithic three-dimensional (M3D) integration of a photosensor array, analog computing-in-memory (CIM), and Si complementary metal-oxide-semiconductor (CMOS) logic circuits, named M3D-SAIL. This approach exploits the high-bandwidth on-chip data transfer and massively parallel CIM cores to realize an energy-efficient NSC architecture. The 1st layer of the Si CMOS circuits serves as the control logic and peripheral circuits. The 2nd layer comprises a 1 k-bit one-transistor-one-resistor (1T1R) array with InGaZnOx field-effect transistor (IGZO-FET) and resistive random-access memory (RRAM) for analog CIM. The 3rd layer comprises multiple IGZO-FET-based photosensor arrays for wavelength-dependent optical sensing. The structural integrity and function of each layer are comprehensively verified. Furthermore, NSC is implemented using the M3D-SAIL architecture for a typical video keyframe-extraction task, achieving a high classification accuracy of 96.7% as well as a 31.5× lower energy consumption and 1.91× faster computing speed compared to its 2D counterpart.

Monolithic three-dimensional integration of RRAM-based hybrid memory architecture for one-shot learning.

In this work, we report the monolithic three-dimensional integration (M3D) of hybrid memory architecture based on resistive random-access memory (RRAM), named M3D-LIME. The chip featured three key functional layers: the first was Si complementary metal-oxide-semiconductor (CMOS) for control logic; the second was computing-in-memory (CIM) layer with HfAlOx-based analog RRAM array to implement neural networks for feature extractions; the third was on-chip buffer and ternary content-addressable memory (TCAM) array for template storing and matching, based on Ta2O5-based binary RRAM and carbon nanotube field-effect transistor (CNTFET). Extensive structural analysis along with array-level electrical measurements and functional demonstrations on the CIM and TCAM arrays was performed. The M3D-LIME chip was further used to implement one-shot learning, where ~96% accuracy was achieved on the Omniglot dataset while exhibiting 18.3× higher energy efficiency than graphics processing unit (GPU). This work demonstrates the tremendous potential of M3D-LIME with RRAM-based hybrid memory architecture for future data-centric applications.

Macrophage migration inhibitory factor in acute kidneyinjury.

Acute kidney injury (AKI) is a complex clinical syndrome with multiple etiologies and pathogenesis, which lacks early biomarkers and targeted therapy. Recently, macrophage migration inhibitory factor (MIF) family protein have received increasing attention owing to its pleiotropic protein molecule character in acute kidney injury, where it performed a dual role in the pathological process. macrophage migration inhibitory factor and macrophage migration inhibitory factor-2 are released into the peripheral circulation when Acute kidney injury occurs and interact with various cellular pathways. On the one hand, macrophage migration inhibitory factor exerts a protective effect in anti-oxidation and macrophage migration inhibitory factor-2 promotes cell proliferation and ameliorates renal fibrosis. On the other hand, macrophage migration inhibitory factor aggravates renal injury as an upstream inflammation factor. Herein, we provide an overview on the biological role and possible mechanisms of macrophage migration inhibitory factor and macrophage migration inhibitory factor-2 in the process of Acute kidney injury and the clinical application prospects of macrophage migration inhibitory factor family proteins as a potential therapeutic target.

Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia.

Xanthine oxidase (XO) utilizes molecular oxygen as a substrate to convert purine substrates into uric acid, superoxide, and hydrogen peroxide, which is one of the main enzyme pathways to produce reactive oxygen species (ROS) during septic inflammation and oxidative stress. However, it is not clear whether XO inhibition can improve sepsis-induced renal hypoxia in sepsis-induced acute kidney injury (SI-AKI) mice. In this study, pretreatment with febuxostat, an XO-specific inhibitor, or kidney knockdown of XO by shRNA in vivo significantly improved the prognosis of SI-AKI, not only by reducing the levels of blood urea nitrogen, serum creatinine, tumor necrosis factor-α, interleukin-6, and interleukin-1ß in peripheral blood but also by improving histological damage and apoptosis, reducing the production of ROS, and infiltrating neutrophils and macrophages in the kidney. More importantly, we found that pharmacological and genetic inhibition of XO significantly improved renal hypoxia in SI-AKI mice by a hypoxia probe via fluorescence staining. This effect was further confirmed by the decrease in hypoxia-inducible factor-1α expression in the kidneys of mice with pharmacological and genetic inhibition of XO. In vitro, the change in XO activity induced by lipopolysaccharide was related to the change in hypoxia in HK-2 cells. Febuxostat and XO siRNA significantly relieved the hypoxia of HK-2 cells cultured in 2% oxygen and reversed the decrease in cell viability induced by lipopolysaccharide. Our results provide novel insights into the nephroprotection of XO inhibition in SI-AKI, improving cell hypoxia by inhibiting XO activity and reducing apoptosis, inflammation, and oxidative stress.

Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation.

The activation of Yes-associated protein (YAP) pathway is mutually causal with the increase of extracellular matrix (ECM) stiffness. Polydatin (PD) has been proved to have anti-fibrosis effect in diabetic kidney disease (DKD), but it is still a mystery whether PD participates in YAP-related mechano-transduction. Therefore, this study intends to solve the following two problems: 1) To construct an in vitro system of polyacrylamide hydrogels (PA gels) based on the true stiffness of kidneys in healthy and DKD rats, and observe the effect of PD on pathological matrix stiffness-induced YAP expression in renal fibroblasts; 2) Compared with verteporfin (VP), a pharmacological inhibitor of YAP, to explore whether the therapeutic effect of PD on DKD in vivo model is related to the regulation of YAP. In this study, the in vitro system of PA gels with 3 kPa, 12 kPa and 30 kPa stiffness was constructed and determined for the first time to simulate the kidney stiffness of healthy rats, rats with DKD for 8 weeks and 16 weeks, respectively. Compared with the PA gels with 3 kPa stiffness, the PA gels with 12 kPa and 30 kPa stiffness significantly increased the expression of YAP, α-smooth muscle actin (α-SMA) and collagen I, and the production of reactive oxygen species (ROS) in renal fibroblasts, and the PA gels with 30 kPa stiffness were the highest. PD significantly inhibited the above-mentioned changes of fibroblasts induced by pathological matrix stiffness, suggesting that the inhibition of PD on fibroblast-to-myofibroblast transformation and ECM production was at least partially associated with regulating YAP-related mechano-transduction pathway. Importantly, the inhibitory effect of PD on YAP expression and nuclear translocation in kidneys of DKD rats is similar to that of VP, but PD is superior to VP in reducing urinary protein, blood glucose, blood urea nitrogen and serum creatinine, as well as decreasing the expression of α-SMA and collagen I, ROS overproduction and renal fibrosis. Our results prove for the first time from the biomechanical point of view that PD is a potential therapeutic strategy for delaying the progression of renal fibrosis by inhibiting YAP expression and nuclear translocation.

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms.

Backgrounds: The neural circuit mechanisms underlying depression remain unclear. Recently optogenetics has gradually gained recognition as a novel technique to regulate the activity of neurons with light stimulation. Scientists are now transferring their focus to the function of brain regions and neural circuits in the pathogenic progress of depression. Deciphering the circuitry mechanism of depressive-like behaviors may help us better understand the symptomatology of depression. However, few studies have summarized current progress on optogenetic researches into the neural circuit mechanisms of depressive-like behaviors. Aims: This review aimed to introduce fundamental characteristics and methodologies of optogenetics, as well as how this technique achieves specific neuronal control with spatial and temporal accuracy. We mainly summarized recent progress in neural circuit discoveries in depressive-like behaviors using optogenetics and exhibited the potential of optogenetics as a tool to investigate the mechanism and possible optimization underlying antidepressant treatment such as ketamine and deep brain stimulation. Methods: A systematic review of the literature published in English mainly from 2010 to the present in databases was performed. The selected literature is then categorized and summarized according to their neural circuits and depressive-like behaviors. Conclusions: Many important discoveries have been made utilizing optogenetics. These findings support optogenetics as a powerful and potential tool for studying depression. And our comprehension to the etiology of depression and other psychiatric disorders will also be more thorough with this rapidly developing technique in the near future.

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury via SIRT6-Mediated Autophagy Activation.

In the treatment of malignant tumors, the effectiveness of cisplatin (CP) is limited by its nephrotoxicity, leading to cisplatin-induced acute kidney injury (CP-AKI). Polydatin (PD) has been demonstrated to regulate autophagy in tumors, sepsis, and diabetes. We have recently confirmed that PD attenuated CP-AKI by inhibiting ferroptosis, but it is not clear whether PD can regulate autophagy to protect from CP-AKI. The purpose of this study was to investigate the effect of PD on autophagy in CP-treated HK-2 cells and CP-AKI mouse models, exploring the role of sirtuin 6 (SIRT6) upregulated by PD. In this study, the blocking of autophagy flux was observed in both CP-treated HK-2 cells in vitro and CP-AKI mouse models in vivo, whereas this blocking was reversed by PD, which was characterized by the increase of autophagy microtubule-associated protein light chain 3 II expression and autophagolysosome/autophagosome ratio and the decrease of p62 expression. Furthermore, PD also significantly increased the expression of SIRT6 in vivo and in vitro. The protective effect of PD manifested by the stimulating of autophagy flux, with the reducing of inflammatory response and oxidative stress, which included downregulation of tumor necrosis factor-α and interleukin-1ß, decreased activity of myeloperoxidase and content of malondialdehyde, and increased activity of superoxide dismutase and level of glutathione, both in vivo and in vitro, was reversed by either inhibition of autophagy flux by chloroquine or downregulation of SIRT6 by OSS-128167. Taken together, the present findings provide the first evidence demonstrating that PD exhibited nephroprotective effects on CP-AKI by restoring SIRT6-mediated autophagy flux mechanisms.

Machine learning algorithm-based identification and verification of characteristic genes in acute kidney injury.

Background: Acute kidney injury is a common renal disease with high incidence and mortality. Early identification of high-risk acute renal injury patients following renal transplant could improve their prognosis, however, no biomarker exists for early detection. Methods: The GSE139061 dataset was used to identify hub genes in 86 DEGs between acute kidney injury and control samples using three machine learning algorithms (LASSO, random forest, and support vector machine-recursive feature elimination). We used GSEA to identify the related signal pathways of six hub genes. Finally, we validated these potential biomarkers in an in vitro hypoxia/reoxygenation injury cell model using RT-qPCR. Results: Six hub genes (MDFI, EHBP1L1, FBXW4, MDM4, RALYL, and ESM1) were identified as potentially predictive of an acute kidney injury. The expression of ESM1 and RALYL were markedly increased in control samples, while EHBP1L1, FBXW4, MDFI, and MDM4 were markedly increased in acute kidney injury samples. Conclusion: We screened six hub genes related to acute kidney injury using three machine learning algorithms and identified genes with potential diagnostic utility. The hub genes identified in this study might play a significant role in the pathophysiology and progression of AKI. As such, they might be useful for the early diagnosis of AKI and provide the possibility of improving the prognosis of AKI patients.

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis.

Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 µM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc- inhibitor erastin (10 µM), and the effect of the 40 µM dose of PD was more obvious than that of ferrostatin-1 (1 µM) and deferoxamine (DFO, 100 µM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc--GSH-GPx4 axis and iron metabolism.

Experimental study on the magnetic characteristics of coal fly ash at different combustion temperatures.

Two different coals containing iron minerals were combusted in a drop tube furnace at different temperatures. The ash samples collected were analyzed in detail to investigate the transformation behaviors of iron-bearing minerals and the magnetic characteristics of coal fly ash (FA). The vibrating sample magnetometer (VSM) was used to analyze the magnetic characteristics of the ash samples and Mössbauer spectroscopy was used to analyze the iron-bearing components in FA. The results indicate that combustion temperature does not significantly affect the crystals phases formed in FA, but does change the relative content of crystals. With an increase in temperature, the relative content of maghemite (γ-Fe2O3) and magnetite (Fe3O4) decreases, while the relative content of hematite (α-Fe2O3) increases. The rising combustion temperature also results in a decreasing trend on saturation magnetization of FA. Furthermore, there is a significant positive correlation between the equivalent content of iron-bearing minerals and the saturation magnetization of FA, which can be applied to remove the particulates from flue gas more efficiently.