Research on Hydrogen-Induced Induced Cracking Sensitivity of X80 Pipeline Steel under Different Heat Treatments.

X80 pipeline steel has played a vital role in oil and gas transportation in recent years. However, hydrogen-related issues frequently lead to pipeline failures during service, resulting in significant losses of properties and lives. Three heat treatment processes (furnace cooling (FC), air cooling (AC), and water cooling (WC)) were carried out to investigate the effect of different microstructures on hydrogen-induced cracking (HIC) susceptibility of X80 pipeline steel. The WC sample demonstrated the highest hydrogen embrittlement index, registering at 21.9%, while the AC and FC samples exhibited progressively lower values of 15.45% and 10.98%, respectively. Under equivalent hydrogen charging durations, crack dimensions with a maximum length exceeding 30 µm in the WC sample generally exceed those in the FC sample and AC sample. The variation is attributed to the difference in microstructures of the samples, predominantly lath bainite (LB) in water-cooled samples, granular bainite (GB) in air-cooled samples, and ferrite/pearlite (F/P) in FC samples. The research results demonstrate that the sensitivity of lath bainite (LB) to HIC is significantly higher than that of pearlite, ferrite, and granular bainite (GB). The presence of a large amount of martensite/austenite (M/A) constituents within bainite results in a multitude of hydrogen trap sites. HIC cracks in bainite generally propagate along the profiles of M/A constituents, showing both intergranular and transgranular cracking modes.

Structural identification and anti-neuroinflammatory effect of a heteropolysaccharide ATP50-3 from Acorus tatarinowii rhizome.

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1ß, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-ß-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-ß-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 â†’ residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.

Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1→ and →4)-ß-D-Glcp-(1→ residues substituted at the 4-position to the →4)-α-D-GalAp-(1→ residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

Structural clarification of mannoglucan GSBP-2 from Ganoderma sinense and its effects on triple-negative breast cancer migration and invasion.

Ganoderma sinense, known as Lingzhi in China, is a medicinal fungus with anti-tumor properties. Herein, crude polysaccharides (GSB) extracted from G. sinense fruiting bodies were used to selectively inhibit triple-negative breast cancer (TNBC) cells. GSBP-2 was purified from GSB, with a molecular weight of 11.5 kDa and a composition of α-l-Fucp-(1→, ß-d-Glcp-(1→, ß-d-GlcpA-(1→, →3)-ß-d-Glcp-(1→, →3)-ß-d-GlcpA-(1→, →4)-α-d-Galp-(1→,→6)-ß-d-Manp-(1→, and →3,6)-ß-d-Glcp-(1→ at a ratio of 1.0:6.3:1.7:5.5:1.5:4.3:8.0:7.9. The anti-MDA-MB-231 cell activity of GSBP-2 was determined by methyl thiazolyl tetrazolium, colony formation, scratch wound healing, and transwell migration assays. The results showed that GSBP-2 could selectively inhibit the proliferation, migration, and invasion of MDA-MB-231 cells through the regulation of genes targeting epithelial-mesenchymal transition (i.e., Snail1, ZEB1, VIM, CDH1, CDH2, and MMP9) in the MDA-MB-231 cells. Furthermore, Western blotting results indicated that GSBP-2 could restrict epithelial-mesenchymal transition by increasing E-cadherin and decreasing N-cadherin expression through the PI3K/Akt pathway. GSBP-2 also suppressed the angiogenesis of human umbilical vein endothelial cells. In conclusion, GSBP-2 could inhibit the proliferation, migration, and invasion of MDA-MB-231 cells and showed significant anti-angiogenic ability. These findings indicate that GSBP-2 is a promising therapeutic adjuvant for TNBC.

Structural characterization of a galactoglucomannan with anti-neuroinflammatory activity from Ganoderma lucidum.

According to traditional Chinese medicine theory, Ganoderma lucidum (G. lucidum) presents certain effects for nourishing nerves and calming the mind. G. lucidum polysaccharides (GLPs) have various biological activities; however, the structural characterization and the structure-activity relationship in anti-neuroinflammation of GLPs needs to be further investigated. In this work, the crude polysaccharide GL70 exhibited a remarkable impact on enhancing the spatial learning and memory function, as well as reducing the anxiety symptoms of the lipopolysaccharide (LPS)-induced rat model of Alzheimer's disease (AD). A galactoglucomannan (GLP70-1-2) was isolated from GL70, and characterized by monosaccharide composition, partial acid hydrolysis, methylation, and NMR analysis. The backbone of GLP70-1-2 was →6)-α-D-glcp-(1 â†’ 6)-ß-D-galp-(1 â†’ [6)-ß-D-manp-(1]3 â†’ 4)-α-D-Glcp-(1 â†’ 6)-α-D-glcp-(1 â†’ 2)-ß-D-galp-(1 â†’ [4)-α-D-glcp-(1 â†’ 6)-ß-D-manp-(1 â†’ 2)-ß-D-galp-(1]2 â†’ 6)-ß-D-glcp-(1 â†’ 6)-ß-D-glcp-(1→ with two side chains attached to O-4 of →6)-ß-D-galp-(1→ and O-3 of →6)-ß-D-glcp-(1→, respectively. In addition, GLP70-1-2 exhibited remarkable efficacy in decreasing the level of pro-inflammatory factors in LPS-activated BV2 cells through the TLR4/MyD88/NF-κB pathway. Collectively, GLP70-1-2 exhibited significant anti-neuroinflammatory activity and may have the potential for developing as a drug for AD.

The role and application of vesicles in triple-negative breast cancer: Opportunities and challenges.

Extracellular vesicles (EVs) carry DNA, RNA, protein, and other substances involved in intercellular crosstalk and can be used for the targeted delivery of drugs. Triple-negative breast cancer (TNBC) is rich in recurrent and metastatic disease and lacks therapeutic targets. Studies have proved the role of EVs in the different stages of the genesis and development of TNBC. Cancer cells actively secrete various biomolecules, which play a significant part establishing the tumor microenvironment via EVs. In this article, we describe the roles of EVs in the tumor immune microenvironment, metabolic microenvironment, and vascular remodeling, and summarize the application of EVs for objective delivery of chemotherapeutic drugs, immune antigens, and cancer vaccine adjuvants. EVs-based therapy may represent the next-generation tool for targeted drug delivery for the cure of a variety of diseases lacking effective drug treatment.

Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

Objective: The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM. Results: Twenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI. Conclusion: Current evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.

Two polysaccharides from Rehmannia glutinosa: isolation, structural characterization, and hypoglycemic activities.

Rehmannia glutinosa (RG) as a Chinese herbal medicine can be used both in medicine and food. As the main component of RG, the polysaccharides have a hypoglycemic effect, however, the hypoglycemic activity of RG homopolysaccharides remains unknown. We isolated and purified two polysaccharides, RGP70-1-1 and RGP70-1-2 (4.9 kDa and 2.8 kDa) from RG. The structural characteristics, including monosaccharide composition, linkage, and configuration were analyzed by FT-IR, HPLC, GC-MS, NMR spectroscopy, Congo test, and SEM. RGP70-1-1 and RGP70-1-2 consist of four monosaccharides (glucose, mannose, arabinose, and galactose). RGP70-1-1 contains 14 connection modes, with the linkages including l-Araf-(1→, →3)-l-Araf-(1→, →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →2,5)-l-Araf-(1→, d-Manp-(1→, →2)-d-Manp-(1→, →4)-d-Manp-(1→, d-Galp-(1→, →4)-d-Galp-(1→, →4,6)-d-Galp-(1→, →6)-d-Glcp-(1→, →4,6)-d-Glcp-(1→, →3,6)-d-Glcp-(1→. The linkages of RGP70-1-2 is including →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →4)-d-Manp-(1→, →3,6)-d-Manp-(1→, d-Galp-(1→, →6)-d-Galp-(1→, d-Glcp-(1→, →6)-d-Glcp-(1→, →4,6)-d-Glcp-(1→. Furthermore, RGP70-1-1 and RGP70-1-2 can inhibit α-glucosidase and α-amylase. RGP70-1-1 stimulated GLP-1 secretion in STC-1 cells and was related to the up-regulation of PI3K and p-AKT protein expression. The findings revealed a natural product with potential hypoglycemic activity, which may be used as a GLP-1 secretagogue and a beneficial functional food ingredient for T2D.

Breaking the mold: Overcoming resistance to immune checkpoint inhibitors.

Immune checkpoint blockade-based therapies are effective against a sorts of cancers. However, drug resistance is a problem that cannot be ignored. This review intends to elucidate the mechanisms underlying drug tolerance induced by PD-1/PD-L1 inhibitors, as well as to outline proposed mechanism-based combination therapies and small molecule drugs that target intrinsic immunity and immune checkpoints. According to the differences of patients and types of cancer, the optimization of individualized combination therapy will help to enhance PD-1/PD-L1-mediated immunoregulation, reduce chemotherapy resistance, and provide new ideas for chemotherapy-resistant cancer.

Curculigo orchioides polysaccharide COP70-1 stimulates osteogenic differentiation of MC3T3-E1 cells by activating the BMP and Wnt signaling pathways.

The crude polysaccharide CO70 isolated from Curculigo orchioides could alleviate ovariectomy-induced osteoporosis in rats. To clarify the bioactive components, a new heteropolysaccharide (COP70-1) was purified from CO70 in this study, which was consisted of ß-D-Manp-(1→, →4)-α-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →3,4)-ß-D-Manp-(1→, →4,6)-ß-D-Manp-(1→, and →4,6)-α-D-Galp-(1→. COP70-1 significantly promoted the osteoblastic differentiation of MC3T3-E1 cells through improving alkaline phosphatase activity, the deposition of calcium as well as up-regulating the expression of osteogenic markers (RUNX2, OSX, BSP, OCN, and OPN). Furthermore, COP70-1 stimulated the expression of critical transcription factors of the BMP and Wnt pathways, including BMP2, p-SMAD1, active-ß-catenin, p-GSK-3ß, and LEF-1. In addition, LDN (BMP pathway inhibitor) and DKK-1 (Wnt pathway inhibitor) suppressed the COP70-1-induced osteogenic differentiation of MC3T3-E1 cells. Therefore, COP70-1 was one of the bioactive constituents of C. orchioides for targeting osteoblasts to treat osteoporosis by triggering BMP/Smad and Wnt/ß-catenin pathways.

Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities.

Breast cancer is the leading cause of cancer-related deaths in females worldwide, and the liver is one of the most common sites of distant metastases in breast cancer patients. Patients with breast cancer liver metastases face limited treatment options, and drug resistance is highly prevalent, leading to a poor prognosis and a short survival. Liver metastases respond extremely poorly to immunotherapy and have shown resistance to treatments such as chemotherapy and targeted therapies. Therefore, to develop and to optimize treatment strategies as well as to explore potential therapeutic approaches, it is crucial to understand the mechanisms of drug resistance in breast cancer liver metastases patients. In this review, we summarize recent advances in the research of drug resistance mechanisms in breast cancer liver metastases and discuss their therapeutic potential for improving patient prognoses and outcomes.

General self-efficacy and frailty in hospitalized older patients: The mediating effect of loneliness.

This study aimed to explore the relationship between general self-efficacy and frailty in hospitalized older adults with chronic diseases, and to examine the mediating role of loneliness. A total of 327 hospitalized older patients aged 60 years or above with chronic diseases were recruited. Cross-sectional data on the patients' general self-efficacy, frailty and loneliness were collected using questionnaires. The PROCESS macro of the bias correction bootstrapping method was used to test the mediation model. The results showed that the significant mediating role of loneliness between general self-efficacy and frailty (B = -0.735, 95% CI [-0.923, -0.564]) explained 42.4% of the total effect of general self-efficacy on frailty. These findings highlighted the importance of loneliness in older patients with chronic diseases in hospital, especially those with low general self-efficacy.

Discrete Missing Data Imputation Using Multilayer Perceptron and Momentum Gradient Descent.

Data are a strategic resource for industrial production, and an efficient data-mining process will increase productivity. However, there exist many missing values in data collected in real life due to various problems. Because the missing data may reduce productivity, missing value imputation is an important research topic in data mining. At present, most studies mainly focus on imputation methods for continuous missing data, while a few concentrate on discrete missing data. In this paper, a discrete missing value imputation method based on a multilayer perceptron (MLP) is proposed, which employs a momentum gradient descent algorithm, and some prefilling strategies are utilized to improve the convergence speed of the MLP. To verify the effectiveness of the method, experiments are conducted to compare the classification accuracy with eight common imputation methods, such as the mode, random, hot-deck, KNN, autoencoder, and MLP, under different missing mechanisms and missing proportions. Experimental results verify that the improved MLP model (IMLP) can effectively impute discrete missing values in most situations under three missing patterns.

Structural elucidation and anti-neuroinflammatory activity of Polygala tenuifolia polysaccharide.

Polygala tenuifolia is extensively used to treat amnesia in traditional Chinese medicine, and pharmacological studies have reported the beneficial effects of P. tenuifolia on intelligence and cognition. In the present study, the crude polysaccharide alkali-extracted from P. tenuifolia roots (PTB) inhibited lipopolysaccharide-induced microglia/astrocyte activation and significantly improved the learning and memory ability of Alzheimer's disease (AD) rats. To determine its bioactive components, a heteropolysaccharide (PTBP-1-3) was isolated from PTB. Structural analysis showed that PTBP-1-3 was composed of α-L-Araf-(1→, â†’3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, ß-D-Xylp-(1→, →2,3,4)-ß-D-Xylp-(1→, α-L-Rhap-(1→, ß-D-Galp-(1→, →4)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →6)-α-D-Glcp-(1→, →3,6)-α-D-Glcp-(1→, →6)-α-D-Manp-(1→, and →2,4)-ß-D-Manp-(1→ residues. PTBP-1-3 decreased the production of NO, TNF-α, and IL-1ß in lipopolysaccharide-activated BV2 microglia cells in a manner similar to that of minocycline. In conclusion, PTBP-1-3 exhibited a potent inhibitory effect on neuroinflammation, and could be one of the bioactive ingredients in PTB for anti-neuroinflammation. PTB and PTBP-1-3 may be potential therapeutic agents for the treatment of AD.

Structural characterization and anti-osteoporosis activity of two polysaccharides extracted from the rhizome of Curculigo orchioides.

Curculigo orchioides is widely used to treat osteoporosis in China. In this study, we identified the active substances in the crude polysaccharide (CO50) from C. orchioides that had anti-osteoporosis activity in vivo. Two polysaccharides, COP50-1 and COP50-4, were purified from CO50. Based on structural analysis, COP50-1 was composed of α-D-Glcp-(1→, ß-D-Galp-(1→, →4)-α-D-Glcp-(1→, →3,4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →4,6)-ß-D-Manp-(1→, whereas COP50-4 was composed of α-L-Araf-(1→, →2)-α-L-Rhap-(1→, ß-D-Manp-(1→, α-D-Galp-(1→, →2,4)-α-L-Rhap-(1→, →2)-ß-D-Manp-(1→, →4)-α-D-GlcAp-(1→, →3)-α-D-GalAp-(1→, →4,6)-α-D-Galp-(1→, →2,3,6)-ß-D-Manp-(1→, →2,3,5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→ and →3)-α-D-Galp-(1→. Pharmacological assessment revealed that COP50-1 had no obvious osteogenic activity. However, COP50-4 (0.5 µM) significantly enhanced the differentiation and mineralization of osteoblasts in vitro. Moreover, the effect of COP50-4 was greater than that of 17ß-estradiol. Therefore, COP50-4 may be an effective component of CO50 that has great potential for development as an alternative drug for the treatment of osteoporosis.

An L-theanine derivative targets against SARS-CoV-2 and its Delta and Omicron variants.

Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2 in addition to its activity against lung cancer. TBrC showed extracellular inhibition of SARS-CoV-2 Mpro/3CL and the host cell receptor ACE2 while interacting with the viral spike glycoproteins (wild-type, Delta, and Omicron mutants). Moreover, TBrC and L-theanine significantly suppressed growth and TNFα-induced nuclear transcriptional activation of NF-κB in human lung cancer cells without affecting the viability of normal lung cells, suggesting a potential protection of TBrC and L-theanine from pulmonary damages in SARS-CoV-2 infected patients, especially for lung cancer patients with SARS-CoV-2 infection.

Red yeast rice ameliorates non-alcoholic fatty liver disease through inhibiting lipid synthesis and NF-κB/NLRP3 inflammasome-mediated hepatic inflammation in mice.

BACKGROUND: Red yeast rice (RYR), a nutraceutical with a profound cholesterol-lowering effect, was found to attenuate non-alcoholic fatty liver disease (NAFLD) in mice. Despite monacolin K in RYR being a specific inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMCGR), the mechanisms underlying the protective effects of RYR against NAFLD are not fully elucidated. METHODS: Using a mouse model of high-fat diet (HFD) feeding and a cellular model of HepG2 cells challenged by lipopolysaccharide (LPS) and palmitic acid (PA), the possible molecular mechanisms were exploited in the aspects of NF-κB/NLRP3 inflammasome and mTORC1-SREBPs signaling pathways by examining the relevant gene/protein expressions. Subsequently, the correlation between these two signals was also verified using cellular experiments. RESULTS: RYR ameliorated lipid accumulation and hepatic inflammation in vivo and in vitro. RYR improved lipid metabolism through modulating mTORC1-SREBPs and their target genes related to triglyceride and cholesterol synthesis. Furthermore, RYR suppressed hepatic inflammation by inhibiting the NF-κB/NLRP3 inflammasome signaling. Interestingly, the treatment with RYR or MCC950, a specific NLRP3 inhibitor, resulted in the reduced lipid accumulation in HepG2 cells challenged by LPS plus PA, suggesting that the inhibitory effects of RYR on NLRP3 inflammasome-mediated hepatic inflammation may partially, in turn, contribute to the lipid-lowering effect of RYR. CONCLUSIONS: The modulation of NF-κB/NLRP3 inflammasome and lipid synthesis may contribute to the ameliorative effects of RYR against HFD-induced NAFLD.

PTP70-2, a novel polysaccharide from Polygala tenuifolia, prevents neuroinflammation and protects neurons by suppressing the TLR4-mediated MyD88/NF-κB signaling pathway.

PTP70-2, a novel polysaccharide isolated from Polygala tenuifolia in our previous publication, exhibits potential anti-inflammatory effects. Here, we investigate the mechanisms underlying these effects and the neuroprotective activity of PTP70-2 in lipopolysaccharide (LPS)-damaged BV2 microglial cells and neuroinflammation-injured primary cortical neurons. The results suggest that PTP70-2 dramatically reduces the LPS-stimulated inflammatory cytokines overexpression, as well as down-regulates the levels of TLR4-, MyD88-, and NF-κB-related proteins. The effect of PTP70-2 in down-regulation of proinflammatory cytokines and downstream proteins implicated in MyD88 and NF-κB signaling is related to the TLR4 pathway. Furthermore, this effect is enhanced by the co-incubation of BV2 cells with PTP70-2 and TAK242, a TLR4 inhibitor, before exposure to LPS. Importantly, PTP70-2 prevents neuroinflammation-induced neurotoxicity by mitigating ROS overproduction and MMP dissipation. Overall, the PTP70-2's anti-neuroinflammation and neuroprotection are involved to the modulation of the TLR4-mediated MyD88/NF-κB signaling pathway.

In vitro and in silico anti-osteoporosis activities and underlying mechanisms of a fructan, ABW90-1, from Achyranthes bidentate.

Achyranthes bidentata is a traditional Chinese medicine used to treat osteoporosis. AB90, a crude saccharide from A. bidentata, showed excellent osteoprotective effects in ovariectomized rats, and ABW90-1, an oligosaccharide purified from AB90, stimulated significant differentiation of osteoblasts. However, the osteogenic effects and underlying mechanisms of ABW90-1 have remained unknown. In the present study, we found that ABW90-1 significantly promoted ALP activity, mineralization, and the expression of osteogenic markers in MC3T3-E1 cells. ABW90-1 showed strong binding with the WNT signaling complex and BMP2 based on number of interactions, hydrogen bond length, and binding energy in silico. ABW90-1 significantly increased the expression of active-ß-catenin, p-GSK-3ß, LEF-1, BMP2, and p-SMAD1. Importantly, the osteogenic effects of ABW90-1 were partially suppressed by DKK-1 and Noggin, which are specific inhibitors of the WNT and BMP signaling pathways, respectively. Collectively, these findings suggest that ABW90-1 has osteogenic effects through crosstalk between WNT/ß-catenin and BMP2/SMAD1 signaling pathways.

Research Progress on Circular RNA in Glioma.

The discovery of circular RNA (circRNA) greatly complements the traditional gene expression theory. CircRNA is a class of non-coding RNA with a stable cyclic structure. They are highly expressed, spatiotemporal-specific and conservative across species. Importantly, circRNA participates in the occurrence of many kinds of tumors and regulates the tumor development. Glioma is featured by limited therapy and grim prognosis. Cancer-associated circRNA compromises original function or creates new effects in glioma, thus contributing to oncogenesis. Therefore, this article reviews the biogenesis, metabolism, functions and properties of circRNA as a novel potential biomarker for gliomas. We elaborate the expression characteristics, interaction between circRNA and other molecules, aiming to identify new targets for early diagnosis and treatment of gliomas.