Combined gut microbiome and metabolomics to reveal the mechanism of proanthocyanidins from the roots of Ephedra sinica Stapf on the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that primarily affects mucosa and submucosa of colon and rectum. Although the exact etiology of UC remains elusive, increasing evidence has demonstrated that the gut microbiome and its interaction with host metabolism plays an important role in UC development. The objective of this study was to investigate the therapeutic potential and mechanism of dimeric proanthocyanidins (PAC) enriched from ethyl acetate extract of Ephedra roots on UC from the perspective of gut microbiota and metabolic regulation. In this study, a bio-guided strategy integrating LC-MS analysis, DMAC assay, antioxidant screening, and antiinflammation activity screening was used to enrich dimeric PAC from Ephedra roots, then untargeted metabolomics combined with gut microbiota analysis was performed to investigate the therapeutic mechanism of PRE on UC. This is the first study that combines a bio-guided strategy to enrich dimeric PAC from Ephedra roots and a comprehensive analysis of their effects on gut microbiota and host metabolism. Oral administration of PRE was found to significantly relieve dextran sodium sulfate (DSS)-induced ulcerative colitis symptoms in mice, characterized by the reduced disease activity index (DAI), increased colon length and improved colon pathological damage, together with the down-regulation of colonic inflammatory and oxidative stress levels. In addition, 16 S rRNA sequencing combined with untargeted metabolomics was conducted to reveal the effects of PRE on gut microbiota composition and serum metabolites. PRE improved gut microbiota dysbiosis through increasing the relative abundance of beneficial bacteria Lachnospiraceae_NK4A136_group and decreasing the level of potentially pathogenic bacteria such as Escherichia-Shigella. Serum metabolomics showed that the disturbed tryptophan and glycerophospholipid metabolism in UC mice was restored after PRE treatment. Collectively, PRE was proved to be a promising anti-UC candidate, which deserves further investigation in future research.

LoC-SERS platform for rapid and sensitive detection of colorectal cancer protein biomarkers.

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection.

FLPP: A Federated-Learning-Based Scheme for Privacy Protection in Mobile Edge Computing.

Data sharing and analyzing among different devices in mobile edge computing is valuable for social innovation and development. The limitation to the achievement of this goal is the data privacy risk. Therefore, existing studies mainly focus on enhancing the data privacy-protection capability. On the one hand, direct data leakage is avoided through federated learning by converting raw data into model parameters for transmission. On the other hand, the security of federated learning is further strengthened by privacy-protection techniques to defend against inference attack. However, privacy-protection techniques may reduce the training accuracy of the data while improving the security. Particularly, trading off data security and accuracy is a major challenge in dynamic mobile edge computing scenarios. To address this issue, we propose a federated-learning-based privacy-protection scheme, FLPP. Then, we build a layered adaptive differential privacy model to dynamically adjust the privacy-protection level in different situations. Finally, we design a differential evolutionary algorithm to derive the most suitable privacy-protection policy for achieving the optimal overall performance. The simulation results show that FLPP has an advantage of 8∼34% in overall performance. This demonstrates that our scheme can enable data to be shared securely and accurately.

Ultrasensitive detection of gastric cancer biomarkers via a frequency shift-based SERS microfluidic chip.

Highly sensitive protein biomarker detection is critical for the diagnosis of gastric cancer (GC), however the accurate and sensitive detection of low-abundance proteins in early-stage GC is still a challenge. Herein, a surface-enhanced Raman scattering frequency shift assay was performed on a developed microfluidic chip for the detection of GC protein biomarkers carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The chip is made up of three groups of parallel channels and each parallel channel consists of two reaction regions, enabling the simultaneous analysis of multiple biomarkers in multiple samples. The presence of CEA and VEGF in the sample can be captured by the 4-mercaptobenzoic acid (4-MBA)-conjugated antibody functionalized gold nano-sheet (GNS-) substrate, resulting in the Raman frequency shift. As a result, a typical Raman frequency shift of 4-MBA presented a linear relationship with the concentration of CEA and VEGF. The limit of detection (LOD) of the proposed SERS microfluidic chip reaches as low as 0.38 pg mL-1 for CEA and 0.82 pg mL-1 for VEGF. During the detection process, only one step of sample addition is involved, which eliminates the multiple reaction step-induced nonspecific adsorption and significantly increases the convenience and specificity. In addition, serum samples from GC patients and healthy subjects were tested and the results were in good agreement with the current gold-standard method ELISA, suggesting the potential application of the SERS microfluidic chip in clinical settings for early diagnosis and prognosis of GC.

Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer.

Gastric cancer is one of the top causes of cancer-related death globally. Although novel treatment strategies have been developed, attempts to eradicate gastric cancer have been proven insufficient. Oxidative stress is continually produced and continually present in the human body. Increasing evidences show that oxidative stress contributes significantly to the development of gastric cancer, either through initiation, promotion, and progression of cancer cells or causing cell death. As a result, the purpose of this article is to review the role of oxidative stress response and the subsequent signaling pathways as well as potential oxidative stress-related therapeutic targets in gastric cancer. Understanding the pathophysiology of gastric cancer and developing new therapies for gastric cancer depends on more researches focusing on the potential contributors to oxidative stress and gastric carcinogenesis.

SIRT1 attenuates renal fibrosis by repressing HIF-2α.

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase belonging to class III histone deacetylases. Previous studies have shown that SIRT1 is involved in kidney physiology regulation and protects the kidney from various pathological factors. However, the underlying mechanisms behind its function have yet to be fully elucidated. In our study, we found that ablation of Sirt1 in renal interstitial cells resulted in more severe renal damage and fibrosis in unilateral ureteral obstruction (UUO) model mice. We also observed that hypoxia-inducible factor (HIF)-2α expression was increased in Sirt1 conditional knockout mice, suggesting that HIF-2α might be a substrate of SIRT1, mediating its renoprotective roles. Therefore, we bred Hif2a deficient mice and subjected them to renal trauma through UUO surgery, ultimately finding that Hif2a ablation attenuated renal fibrogenesis induced by UUO injury. Moreover, in cultured NRK-49F cells, activation of SIRT1 decreased HIF-2α and fibrotic gene expressions, and inhibition of SIRT1 stimulated HIF-2α and fibrotic gene expressions. Co-immunoprecipitation analysis revealed that SIRT1 directly interacted with and deacetylated HIF-2α. Together, our data indicate that SIRT1 plays a protective role in renal damage and fibrosis, which is likely due to inhibition of HIF-2α.

Salidroside ameliorates Adriamycin nephropathy in mice by inhibiting ß-catenin activity.

Salidroside is a major phenylethanoid glycoside in Rhodiola rosea L., a traditional Chinese medicine, with multiple biological activities. It has been shown that salidroside possesses protective effects for alleviating diabetic renal dysfunction, contrast-induced-nephropathy and other kidney diseases. However, the involved molecular mechanism was still not understood well. Herein, we examined the protective effects of salidroside in mice with Adriamycin (ADR)-induced nephropathy and the underlying molecular mechanism. The results showed that salidroside treatment ameliorates proteinuria; improves expressions of nephrin and podocin; and reduces kidney fibrosis and glomerulosclerosis induced by ADR. Mechanistically, ADR induces a robust accumulation of ß-catenin in the nucleus and stimulates its downstream target gene expression. The application of salidroside largely abolishes the nuclear translocation of ß-catenin and thus inhibits its activity. Furthermore, the activation of ß-catenin almost completely counteracts the protective roles of salidroside in ADR-injured podocytes. Taken together, our data indicate that salidroside ameliorates proteinuria, renal fibrosis and podocyte injury in ADR nephropathy, which may rely on inhibition of ß-catenin signalling pathway.

Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice.

BACKGROUND: Salidroside, an active component from Traditional Chinese Medicine Rhodiola rosea L., has various pharmacological functions including anti-inflammatory, anti-cancer and anti-oxidative properties. However, whether salidroside plays a beneficial role in diabetic nephropathy is still unclear. PURPOSE: The objective of this work was to investigate the potential roles of salidroside against diabetic nephropathy and the underlying molecular mechanisms. METHODS: Streptozocin was given to obese mice to generate diabetic nephropathy animal model. Salidroside was administered to these mice and proteinuria, podocyte integrity, renal morphology and fibrosis, mitochondrial biogenesis were examined. RESULTS: Our results showed that salidroside treatment greatly attenuates diabetic nephropathy as evidenced by decreased urinary albumin, blood urea nitrogen and serum creatinine. Morphological analysis indicated that salidroside improves renal structures in diabetic nephropathy. The decreases in nephrin and podocin expression were markedly reversed by salidroside. Moreover, kidney fibrosis in diabetic nephropathy mice was largely prevented by salidroside. Mechanistically, in salidroside-treated mice, the mitochondrial DNA copy and electron transport chain proteins were significantly enhanced. Meanwhile, the reduced Sirt1 and PGC-1α expression in diabetic nephropathy was almost completely counteracted in the presence of salidroside. CONCLUSIONS: Our data showed that salidroside plays a beneficial role against diabetic nephropathy in mice, which probably via Sirt1/PGC-1α mediated mitochondrial biogenesis.

The effect of proton irradiation on the properties of a graphene oxide paper.

A graphene oxide paper (GOP) was irradiated with 500 keV proton for total fluence of 2 × 1013 cm-2 to 2 × 1015 cm-2 in a ground-based irradiation simulator. The spacing of layer, surface chemical composition, structural defects, thermal conductivity and electrical property of the GOP before and after irradiation was measured. The results indicated that the spacing of layer decreased after irradiation. The ratio of total carbon atom and total oxygen atom increased from 2.40 to 4.31 as well as the sp2 hybridized carbons obviously increased after 2 × 1015 cm-2 irradiation. The XPS analysis suggested the occurrence of reduction, and the Raman spectra indicated that the defects were produced after proton irradiation. Furthermore, the thermal conductivity of GOP decreased, and then increased smoothly as the irradiation fluences were increased, and the electrical property showed the similar trend. The change in the thermal and electrical properties for GOP could be attributed to the defects and the removal of oxygen-containing functional groups, which lead to the phonon conduct path and scattering centers changed under proton irradiation. This study could promote the application of GOP in future space expeditions.