Association between a high triglyceride-glucose index and chronic kidney disease in adult patients with latent autoimmune diabetes.

BACKGROUND: Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride-glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA). METHODS: This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed. RESULTS: A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all P < 0.05). The positive relationship between the TyG index and the urinary albumin/creatinine ratio was significant (r = 0.249, P = 0.010). There was also a significant correlation between the TyG index and the eGFR (r = - 0.211, P = 0.034) after adjusting for confounding factors. The area-under-the-curve value of the TyG index was 0.708 (95% confidence interval: 0.61-0.81, P < 0.001). CONCLUSIONS: The TyG index is significantly associated with the severity of CKD in patients with LADA. This conclusion supports the clinical application of the TyG index for the assessment of kidney disease in patients with LADA.

A privacy-preserving blockchain-based tracing model for virus-infected people in cloud.

The outbreak of COVID-19 has exposed the privacy of positive patients to the public, which will lead to violations of users' rights and even threaten their lives. A privacy-preserving scheme involving virus-infected positive patients is proposed by us. The traditional ciphertext policy attribute-based encryption (CP-ABE) has the features of enhanced plaintext security and fine-grained access control. However, the encryption process requires the high computational performance of the device, which puts a high strain on resource-limited devices. After semi-honest users successfully decrypt the data, they will get the real private data, which will cause serious privacy leakage problems. Traditional cloud-based data management architectures are extremely vulnerable in the face of various cyberattacks. To address the above challenges, a verifiable ABE scheme based on blockchain and local differential privacy is proposed, using LDP to perturb the original data locally to a certain extent to resist collusion attacks, outsourcing encryption and decryption to corresponding service providers to reduce the pressure on mobile terminals, and deploying smart contracts in combination with blockchain for fair execution by all parties to solve the problem of returning wrong search results in a semi-honest cloud server. Detailed security proofs are performed through the defined security goals, which shows that the proposed scheme is indeed privacy-protective. The experimental results show that the scheme is optimized in terms of data accuracy, computational overhead, storage performance, and fairness. In terms of efficiency, it greatly reduces the local load, enhances personal privacy protection, and has high practicality as well as reliability. As far as we know, it is the first case of applying the combination of LDP technology and blockchain to a tracing system, which not only mitigates poisoning attacks on user data, but also improves the accuracy of the data, thus making it easier to identify infected contacts and making a useful contribution to health prevention and control efforts.

Aptamer-based biosensing through the mapping of encoding upconversion nanoparticles for sensitive CEA detection.

A sensitive detection system based on aptamer-based biosensors for the detection of carcinoembryonic antigen (CEA) by mapping encoding upconversion nanoparticles (UCNPs) was constructed. In this sensor, oligonucleotides with CEA aptamer fragments immobilized on magnetic beads (MBs) were hybridized to complementary DNA modified on UCNPs (cDNA-UCNPs); thus, sandwich-structured probes were formed. In the presence of CEA, due to the stronger interaction between the aptamer and CEA than that of the aptamer and complementary DNA on UCNPs, the cDNA-UCNPs were isolated from the MBs, and the number of isolated UCNPs was directly related to the concentration of CEA. Using an inverted fluorescence microscope, the number of target-dependent UCNPs on a glass slide was counted, enabling the accurate determination of CEA in the solution. The dynamic range for CEA detection in PBS buffer was 0.02-6.0 ng mL-1 (0.1-30 pM) and a limit of detection (LOD) of 65 fM was achieved. We envisage that the system we developed can also have many promising applications in the sensitive detection of other biomarkers for early cancer diagnosis.

A Bridge-Linked Phosphorus-Containing Flame Retardant for Endowing Vinyl Ester Resin with Low Fire Hazard.

The high flammability of vinyl ester resin (VE) significantly limits its widespread application in the fields of electronics and aerospace. A new phosphorus-based flame retardant 6,6'-(1-phenylethane-1,2 diyl) bis (dibenzo[c,e][1,2]oxaphosphinine 6-oxide) (PBDOO), was synthesized using 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and acetophenone. The synthesized PBDOO was further incorporated with VE to form the VE/PBDOO composites, which displayed an improved flame retardancy with higher thermal stability. The structure of PBDOO was investigated using Fourier transformed infrared spectrometry (FTIR) and nuclear magnetic resonances (NMR). The thermal stability and flame retardancy of VE/PBDOO composites were investigated by thermogravimetric analysis (TGA), vertical burn test (UL-94), limiting oxygen index (LOI), and cone calorimetry. The impacts of PBDOO weight percentage (wt%) on the flame-retardant properties of the formed VE/PBDOO composites were also examined. When applying 15 wt% PBDOO, the formed VE composites can meet the UL-94 V-0 rating with a high LOI value of 31.5%. The peak heat release rate (PHRR) and the total heat release (THR) of VE loaded 15 wt% of PBDOO decreased by 76.71% and 40.63%, respectively, compared with that of untreated VE. In addition, the flame-retardant mechanism of PBDOO was proposed by analyzing pyrolysis behavior and residual carbon of VE/PBDOO composites. This work is expected to provide an efficient method to enhance the fire safety of VE.

Hyperglycemia and Correlated High Levels of Inflammation Have a Positive Relationship with the Severity of Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. METHODS: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). RESULTS: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. CONCLUSION: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.

Retinal Organoid Technology: Where Are We Now?

It is difficult to regenerate mammalian retinal cells once the adult retina is damaged, and current clinical approaches to retinal damages are very limited. The introduction of the retinal organoid technique empowers researchers to study the molecular mechanisms controlling retinal development, explore the pathogenesis of retinal diseases, develop novel treatment options, and pursue cell/tissue transplantation under a certain genetic background. Here, we revisit the historical background of retinal organoid technology, categorize current methods of organoid induction, and outline the obstacles and potential solutions to next-generation retinal organoids. Meanwhile, we recapitulate recent research progress in cell/tissue transplantation to treat retinal diseases, and discuss the pros and cons of transplanting single-cell suspension versus retinal organoid sheet for cell therapies.

Association of plasma ß-amyloid 40 and 42 concentration with type 2 diabetes among Chinese adults.

AIMS/HYPOTHESIS: There is evidence for a bidirectional association between type 2 diabetes and Alzheimer's disease. Plasma ß-amyloid (Aß) is a potential biomarker for Alzheimer's disease. We aimed to investigate the association of plasma Aß40 and Aß42 with risk of type 2 diabetes. METHODS: We performed a case-control study and a nested case-control study within a prospective cohort study. In the case-control study, we included 1063 newly diagnosed individuals with type 2 diabetes and 1063 control participants matched by age (±3 years) and sex. In the nested case-control study, we included 121 individuals with incident type 2 diabetes and 242 matched control individuals. Plasma Aß40 and Aß42 concentrations were simultaneously measured with electrochemiluminescence immunoassay. Conditional logistic regression was used to evaluate the association of plasma Aß40 and Aß42 concentrations with the likelihood of type 2 diabetes. RESULTS: In the case-control study, the multivariable-adjusted ORs for type 2 diabetes, comparing the highest with the lowest quartile of plasma Aß concentrations, were 1.97 (95% CI 1.46, 2.66) for plasma Aß40 and 2.01 (95% CI 1.50, 2.69) for plasma Aß42. Each 30 ng/l increment of plasma Aß40 was associated with 28% (95% CI 15%, 43%) higher odds of type 2 diabetes, and each 5 ng/l increment of plasma Aß42 was associated with 37% (95% CI 21%, 55%) higher odds of type 2 diabetes. Individuals in the highest tertile for both plasma Aß40 and Aß42 concentrations had 2.96-fold greater odds of type 2 diabetes compared with those in the lowest tertile for both plasma Aß40 and Aß42 concentrations. In the nested case-control study, the multivariable-adjusted ORs for type 2 diabetes for the highest vs the lowest quartile were 3.79 (95% CI 1.81, 7.94) for plasma Aß40 and 2.88 (95% CI 1.44, 5.75) for plasma Aß42. The multivariable-adjusted ORs for type 2 diabetes associated with each 30 ng/l increment in plasma Aß40 and each 5 ng/l increment in plasma Aß42 were 1.44 (95% CI 1.18, 1.74) and 1.47 (95% CI 1.15, 1.88), respectively. CONCLUSIONS/INTERPRETATION: Our findings suggest positive associations of plasma Aß40 and Aß42 concentration with risk of type 2 diabetes. Further studies are warranted to elucidate the underlying mechanisms and explore the potential roles of plasma Aß in linking type 2 diabetes and Alzheimer's disease.

The novel glycyrrhetinic acid-tetramethylpyrazine conjugate TOGA induces anti-hepatocarcinogenesis by inhibiting the effects of tumor-associated macrophages on tumor cells.

Hepatocellular carcinoma (HCC), with its high recurrence and metastasis rates, is a leading cause of cancer-related mortality, and available treatments include surgical resection and liver transplantation. TOGA is a novel conjugate combining 18ß-glycyrrhetinic acid (GA), an active component of licorice, and tetramethylpyrazine, an effective component of Chuanxiong, with a small-molecule amino acid. This study examined the anti-hepatoma effects of TOGA and its specific mechanisms of action. We found that TOGA significantly prevented tumor growth in both nude mice carrying liver cancer xenograftsand mice carrying orthotopic tumors with little toxicity. NanoString analysis screening illustrated that TOGA may exert its anti-tumor effects by targeting interleukin (IL)-1R receptor 1 (IL-1R1). Further, TOGA significantly prevented the invasion and migration of HepG2 cells induced by tumor-associated macrophages (TAMs) or IL-1ß, as confirmed by the reduced expression of the epithelial-mesenchymal transition (EMT)-related proteins Snail and Vimentin. Furthermore, IL-1ß-induced activation of the IL-1R1/IκB/IKK/NF-κB signaling pathway in HepG2 cells was proved to be inhibited by TOGA. Taken together, TOGA effectively prevents the support of TAMs from fueling tumorigenesis through a mechanism related to the NF-κB pathway, and it may be a promising GA-modified drug for the treatment of HCC.

Mibefradil Alleviates High-Glucose-induced Cardiac Hypertrophy by Inhibiting PI3K/Akt/mTOR-mediated Autophagy.

Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus. Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high-glucose-induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in a high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated through immunofluorescence, and mRNA expression of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and ß-myosin heavy chain) was assessed by using quantitative real-time polymerase chain reaction. Changes in the expression of p-PI3K, p-Akt, and p-mTOR were evaluated using Western blotting, and autophagosome formation was detected using transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and ß-myosin heavy chain, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil on high-glucose-induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose-induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study shows that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with diabetes mellitus.

Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 improves diabetic retinopathy.

Diabetes induced a serious of complications including diabetic retinopathy. Our study aimed to investigate the role of Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in diabetic retinopathy. A mice model of diabetic retinopathy was established, and expression of SDF-1 and CXCR4 in retina was examined by Real-time quantitative PCR (qRT-PCR). Cells of human retinal pigment epithelial cell line ARPE-19 were treated with CXCR4 siRNAs and expression vector, and cell viability was detected by MTT assay. We found that expression of SDF-1 and CXCR4 in retina was significantly downregulated in mice with diabetic retinopathy than in normal healthy mice. High glucose treatment downregulated the expression of SDF-1 and CXCR4 in ARPE-19 cells at both mRNA and protein levels. Transfection with CXCR4 siRNAs decreased, while transfection with CXCR4 expression vector increased cell viability under high glucose treatment. We concluded that SDF-1/CXCR4 pathway improved diabetic retinopathy possibly by increasing cell viability. Abbreviations: SDF-1: Stromal cell-derived factor 1; CXCL12: C-X-C motif chemokine 12; qRT-PCR: Real-time quantitative PCR.

[Huaier aqueous extract inhibits proliferation of human hepatoma SK-HEP-1 cells through up-regulation of autophagy].

The purpose of this study was to investigate the effect of Huaier on autophagy of human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the proliferation of SK-HEP-1 cells under different concentrations and different times. Acridine orange staining was used to measure the effect of Huaier on the autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to examine the effect of Huaier on the expression and distribution of autophagy marker LC3 in SK-HEP-1 cells. In addition， LC3 expression was also checked by immunoblot analysis in the presence of Huaier. At last， the effects of Huaier in combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK-HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous extract significantly inhibited the proliferation of human hepatoma SK-HEP-1 cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically promoted the formation of autolysosome in SK-HEP-1 cells. Moreover， Huaier markedly increased the number and intensity of intracellular LC3 fluorescent puncta and up-regulated LC3-Ⅱ expression. These data indicated that Huaier evidently activated autophagy of SK-HEP-1 cells. Additionally， autophagy inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier treatment. Therefore， autophagy activation is involved in the inhibitory effects of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.

Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common form of neurodegenerative disorder that leads to a decline in cognitive function. In AD, aggregates of amyloid ß peptide precede the accumulation of neurofibrillary tangles, both of which are hallmarks of the disease. The great majority (>90 %) of the AD cases are not originated from genetic defects, therefore supporting the central roles of epigenetic modifications that are acquired progressively during the life span. Strong evidences have indicated the implication of epigenetic modifications, including histone modification and DNA methylation, in AD. Recent studies revealed that 5-hydroxymethylcytosine (5hmC) is dynamically regulated during neurodevelopment and aging. RESULTS: We show that amyloid peptide 1-42 (Aß1-42) could significantly reduce the overall level of 5hmC in vitro. We found that the level of 5hmC displayed differential response to the pathogenesis in different brain regions, including the cortex, cerebellum, and hippocampus of APP-PSEN1 double transgenic (DTg) mice. We observed a significant decrease of overall 5hmC in hippocampus, but not in cortex and cerebellum, as the DTg mice aged. Genome-wide profiling identified differential hydroxymethylation regions (DhMRs) in DTg mice, which are highly enriched in introns, exons and intergenic regions. Gene ontology analyses indicated that DhMR-associated genes are highly enriched in multiple signaling pathways involving neuronal development/differentiation and neuronal function/survival. CONCLUSIONS: 5hmC-mediated epigenetic regulation could potentially be involved in the pathogenesis of AD.

Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share phenotypic and pathologic overlap. Recently, an expansion of GGGGCC repeats in the first intron of C9orf72 was found to be a common cause of both illnesses; however, the molecular pathogenesis of this expanded repeat is unknown. Here we developed both Drosophila and mammalian models of this expanded hexanucleotide repeat and showed that expression of the expanded GGGGCC repeat RNA (rGGGGCC) is sufficient to cause neurodegeneration. We further identified Pur α as the RNA-binding protein of rGGGGCC repeats and discovered that Pur α and rGGGGCC repeats interact in vitro and in vivo in a sequence-specific fashion that is conserved between mammals and Drosophila. Furthermore, overexpression of Pur α in mouse neuronal cells and Drosophila mitigates rGGGGCC repeat-mediated neurodegeneration, and Pur α forms inclusions in the fly eye expressing expanded rGGGGCC repeats, as well as in cerebellum of human carriers of expanded GGGGCC repeats. These data suggest that expanded rGGGGCC repeats could sequester specific RNA-binding protein from their normal functions, ultimately leading to cell death. Taken together, these findings suggest that the expanded rGGGGCC repeats could cause neurodegeneration, and that Pur α may play a role in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia.

Rapid and efficient generation of a transplantable population of functional retinal ganglion cells from fibroblasts.

Glaucoma and other optic neuropathies lead to progressive and irreversible vision loss by damaging retinal ganglion cells (RGCs) and their axons. Cell replacement therapy is a potential promising treatment. However, current methods to obtain RGCs have inherent limitations, including time-consuming procedures, inefficient yields and complex protocols, which hinder their practical application. Here, we have developed a straightforward, rapid and efficient approach for directly inducing RGCs from mouse embryonic fibroblasts (MEFs) using a combination of triple transcription factors (TFs): ASCL1, BRN3B and PAX6 (ABP). We showed that on the 6th day following ABP induction, neurons with molecular characteristics of RGCs were observed, and more than 60% of induced neurons became iRGCs (induced retinal ganglion cells) in the end. Transplanted iRGCs had the ability to survive and appropriately integrate into the RGC layer of mouse retinal explants and N-methyl-D-aspartic acid (NMDA)-damaged retinas. Moreover, they exhibited electrophysiological properties typical of RGCs, and were able to regrow dendrites and axons and form synaptic connections with host retinal cells. Together, we have established a rapid and efficient approach to acquire functional RGCs for potential cell replacement therapy to treat glaucoma and other optic neuropathies.

DNA Adjuvant Hydrogel-Optimized Enzymatic Cascade Reaction for Tumor Chemodynamic-Immunotherapy.

Chemodynamic therapy (CDT) shows immense potential in cancer treatment as it not only directly kills tumor cells but also induces anti-tumor immune responses. However, the efficacy of CDT is hampered by challenges in targeting CDT catalysts specifically to tumors using nanomaterials, along with the limitations of low H2 O2 levels and short catalyst duration within the tumor microenvironment. In this study, DNA adjuvant hydrogel to arrange a glucose oxidase-ferrocene cascade for continuously generating reactive oxygen species (ROS) from glucose in situ for tumor CDT combined with immunotherapy is employed. By precisely tuning the catalyst spacing with DNA double helix, ROS production efficiency is elevated by up to nine times compared to free catalysts, resulting in stronger immunogenetic cell death. Upon intratumoral injection, the DNA hydrogel system elicited potent anti-tumor immune responses, thereby effectively inhibiting established tumors and rejecting re-challenged tumors. This work offers a novel platform for integrated CDT and immunotherapy in cancer treatment.

Body temperature responsive capsules templated from Pickering emulsion for thermally triggered release of ß-carotene.

In recent years, functional foods with lipophilic nutraceutical ingredients are gaining more and more attention because of its potential healthy and commercial value, and developing of various bioderived food-grade particles for use in fabrication of Pickering emulsion has attracted great attentions. Herein, the bio-originated sodium caseinate-lysozyme (Cas-Lyz) complex particles were firstly designed to be used as a novel interfacial emulsifier for Pickering emulsions. Pickering emulsions of various food oils were all successfully stabilized by the Cas-Lyz particles without addition of any synthetic surfactants, while the fluorescence microscopy and SEM characterizations clearly evidenced Cas-Lyz particles were attached on the surface of emulsion droplets. Additionally, the Cas-Lyz particles stabilized emulsion can also be used to encapsulate the ß-carotene-loaded soybean oil, suggestion a potential method to carry lipophilic bioactive ingredients in an aqueous formulation for food, cosmetic and medical industry. At last, we present a Pickering emulsion strategy that utilizes biocompatible, edible and body temperature-responsive lard oil as the core material in microcapsules, which can achieve hermetic sealing and physiological temperature-triggered release of model nutraceutical ingredient (ß-carotene).

Peripheral amyloid-ß clearance mediates cognitive impairment in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent risk factor for cognitive impairment. Cerebral amyloid-ß (Aß) accumulation, as an important pathology of cognitive impairment, can be caused by impaired Aß clearance in the periphery. The liver is the primary organ for peripheral Aß clearance, but the role of peripheral Aß clearance in NAFLD-induced cognitive impairment remains unclear. METHODS: We examined correlations between NAFLD severity, Aß accumulation, and cognitive performance in female Sprague-Dawley rats. The impact of NAFLD on hepatic Aß clearance and the involvement of low-density lipoprotein receptor-related protein 1 (LRP-1) were assessed in rat livers and cultured hepatocytes. Additionally, a case-control study, including 549 NAFLD cases and 549 controls (782 males, 316 females), investigated the interaction between NAFLD and LRP-1 rs1799986 polymorphism on plasma Aß levels. FINDINGS: The severity of hepatic steatosis and dysfunction closely correlated with plasma and cerebral Aß accumulations and cognitive deficits in rats. The rats with NAFLD manifested diminished levels of LRP-1 and Aß in liver tissue, with these reductions inversely proportional to plasma and cerebral Aß concentrations and cognitive performance. In vitro, exposure of HepG2 cells to palmitic acid inhibited LRP-1 expression and Aß uptake, which was subsequently reversed by a peroxisome proliferator-activated receptor α (PPARα) agonist. The case-control study revealed NAFLD to be associated with an increment of 8.24% and 10.51% in plasma Aß40 and Aß42 levels, respectively (both P < 0.0001). Moreover, the positive associations between NAFLD and plasma Aß40 and Aß42 levels were modified by the LRP-1 rs1799986 polymorphism (P for interaction = 0.0017 and 0.0015, respectively). INTERPRETATION: LRP-1 mediates the adverse effect of NAFLD on peripheral Aß clearance, thereby contributing to cerebral Aß accumulation and cognitive impairment in NAFLD. FUNDING: Major International (Regional) Joint Research Project, National Key Research and Development Program of China, National Natural Science Foundation of China, and the Angel Nutrition Research Fund.

Natural Compounds with Aldose Reductase (AR) Inhibition: A Class of Medicative Agents for Fatty Liver Disease.

Fatty liver disease (FLD), which includes both non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), is a worldwide health concern. The etiology of ALD is long-term alcohol consumption, while NAFLD is defined as an abnormal amount of lipid present in liver cells, which is not caused by alcohol intake and has recently been identified as a hepatic manifestation of metabolic syndrome (such as type 2 diabetes, obesity, hypertension, and obesity). Inflammation, oxidative stress, and lipid metabolic dysregulation are all known to play a role in FLD progression. Alternative and natural therapies are desperately needed to treat this disease since existing pharmaceuticals are mostly ineffective. The aldose reductase (AR)/polyol pathway has recently been shown to play a role in developing FLD by contributing to inflammation, oxidative stress, apoptosis, and fat accumulation. Herein, we review the effects of plantderived compounds capable of inhibiting AR in FLD models. Natural AR inhibitors have been found to improve FLD in part by suppressing inflammation, oxidative stress, and steatosis via the regulation of several critical pathways, including the peroxisome proliferator-activated receptor (PPAR) pathway, cytochrome P450 2E1 (CYP2E1) pathway, AMP-activated protein kinase (AMPK) pathway, etc. This review revealed that natural compounds with AR inhibitory effects are a promising class of therapeutic agents for FLD.

Dynamic pruning group equivariant network for motor imagery EEG recognition.

Introduction: The decoding of the motor imaging electroencephalogram (MI-EEG) is the most critical part of the brain-computer interface (BCI) system. However, the inherent complexity of EEG signals makes it challenging to analyze and model them. Methods: In order to effectively extract and classify the features of EEG signals, a classification algorithm of motor imagery EEG signals based on dynamic pruning equal-variant group convolutional network is proposed. Group convolutional networks can learn powerful representations based on symmetric patterns, but they lack clear methods to learn meaningful relationships between them. The dynamic pruning equivariant group convolution proposed in this paper is used to enhance meaningful symmetric combinations and suppress unreasonable and misleading symmetric combinations. At the same time, a new dynamic pruning method is proposed to dynamically evaluate the importance of parameters, which can restore the pruned connections. Results and Discussion: The experimental results show that the pruning group equivariant convolution network is superior to the traditional benchmark method in the benchmark motor imagery EEG data set. This research can also be transferred to other research areas.

Construction of a Competitive Endogenous RNA Network Related to Exosomes in Diabetic Retinopathy.

BACKGROUND: The competing endogenous RNA (ceRNA) network plays an important role in the occurrence and development of a variety of diseases. This study aimed to construct a ceRNA network related to exosomes in diabetic retinopathy (DR). METHODS: We explored the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of samples to obtain differentially expressed lncRNAs (DELs), miRNAs (DEMs) and mRNAs (DEGs) alongside the progress of DR. Next, Gene Set Enrichment Analysis (GSEA) analysis of DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of up-DEGs were performed. In addition, a ceRNA network related to exosomes in DR was constructed on the base of DELs, DEMs and DEGs. Finally, the function of the ceRNA network was explored by GO and KEGG enrichment analysis. RESULTS: Through our analysis, 267 DELs (93 up and 174 down), 114 DEMs (64 up and 50 down) and 2368 DEGs (1252 up and 1116 down) were screened. The GSEA analysis results show that these genes were mainly related to cytokine-cytokine receptor interaction, hippo signaling pathway and JAK-STAT signaling pathway. The GO and KEGG results show that these up-DEGs were mainly enriched in viral gene expression, components of ribosomes, mineral absorption, Wntprotein binding, and TGF-ß signaling pathway. Besides, a ceRNA network, including 15 lncRNAs (e.g., C1orf145, FGF14-IT1, and PRNT), 3 miRNAs (miR-10a-5p, miR-1297 and miR-507) and 11 mRNAs (NCOR2, CHAC1 and LIX1L, etc.) was constructed. Those 5 lncRNAs were up-regulated, 1 miRNA was down-regulated and 5 mRNAs were up-regulated in DR, while 10 lncRNAs were downregulated, 2 miRNAs were up-regulated and 6 mRNAs were down-regulated in DR. CONCLUSION: The novel ceRNA network that we constructed will provide new insights into the underlying molecular mechanisms of exosomes in DR.