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.

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.

Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promotes Thyroid Cancer Cell Proliferation and Migration via Ubiquitin-Dependent Degradation of Kisspeptin-1.

BACKGROUND/AIMS: Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism. METHODS: The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively. RESULTS: Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis. CONCLUSION: Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.

Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: A mechanism for hepatoprotective effect against alcoholic liver disease.

Alcohol exposure induces adipose hyperlipolysis and causes excess fatty acid influx into the liver, leading to alcoholic steatosis. The impacts of omega-3 polyunsaturated fatty acids (n-3 PUFA) on ethanol-induced fatty liver are well documented. However, the role of n-3 PUFA in ethanol-induced adipose lipolysis has not been sufficiently addressed. In this study, the fat-1 transgenic mice that synthesizes endogenous n-3 from n-6 PUFA and their wild type littermates with an exogenous n-3 PUFA enriched diet were subjected to a chronic ethanol feeding plus a single binge as model to induce liver injury with adipose lipolysis. Additionally, the differentiated adipocytes from 3T3-L1 cells were treated with docosahexaenoic acid or eicosapentaenoic acid for mechanism studies. Our results demonstrated that endogenous and exogenous n-3 PUFA enrichment ameliorates ethanol-stimulated adipose lipolysis by increasing PDE3B activity and reducing cAMP accumulation in adipocyte, which was associated with activation of GPR120 and regulation of Ca2+/CaMKKß/AMPK signaling, resultantly blocking fatty acid trafficking from adipose tissue to the liver, which contributing to ameliorating ethanol-induced adipose dysfunction and liver injury. Our findings identify that endogenous and exogenous n-3 PUFA enrichment ameliorated alcoholic liver injury by activation of GPR120 to suppress ethanol-stimulated adipose lipolysis, which provides the new insight to the hepatoprotective effect of n-3 PUFA against alcoholic liver disease.

Biotransformation of isofraxetin-6-O-ß-d-glucopyranoside by Angelica sinensis (Oliv.) Diels callus.

Isofraxetin-6-O-ß-d-glucopyranoside, identified from traditional medicinal herbal Xanthoceras sorbifolia Bunge, has been demonstrated to be a natural neuroinflammatory inhibitor. In order to obtain more derivatives with potential anti-neuroinflammatory effects, biotransformation was carried out. According to the characteristics of coumarin skeleton, suspension cultures of Angelica sinensis (Oliv.) Diels callus (A. sinensis callus) were employed because of the presence of diverse phenylpropanoids biosynthetic enzymes. As a result, 15 products were yielded from the suspension cultures, including a new coumarin: 8'-dehydroxymethyl cleomiscosin A (1), together with 14 known compounds. Their structures were elucidated by extensive spectroscopic analysis. Furthermore, the biotransformed pathways were discussed. Among them, compound 13 was transformed from isofraxetin-6-O-ß-d-glucopyranoside, while compounds 1-6, 10-12, 14-15 were derived from the culture medium stimulated by the substrate. The biotransformation processes include hydroxylation, oxidation and esterification. Furthermore, their inhibitory effects on lipopolysaccharide (LPS)-activated nitric oxide (NO) production were evaluated in BV2 microglial cells. It is worth noting that, 1, 1'-methanediylbis(4-methoxybenzene) (3), obtucarbamates A (5), 2-nonyl-4-hydroxyquinoline N-oxide (10) and 1H-indole-3-carbaldehyde (11) exhibited significant inhibitory effect against neuroinflammation with IC50 values at 1.22, 10.57, 1.02 and 0.76µM respectively, much stronger than that of the positive control minocycline (IC50 35.82µM).

Acute hypervolemic hemodilution effect on oxygen metabolism and blood pharmacokinetics in patients undergoing acute laparotomy during induction of general anesthesia.

BACKGROUND/AIMS: To investigate acute hypervolemic hemodilution effect on oxygen metabolism and blood pharmacokinetics in patients undergoing acute laparotomy during Induction of general anesthesia. METHODOLOGY: Forty ASA I-II patients undergoing acute laparotomy were randomly divided into 2 groups (n=20 each): Patients of group A received Voluven 7 ml/kg in 20 mins before induction and 8 ml/kg after induction. Patients of group B received 6 ml/kg/h Plasmalyte A. Hemodynamic parameters MAP, HR and CVP were collected at 6 set points during the surgery: T1: before AHH; T2: before anesthesia induction; T3: right intubation; T4: 10 min after intubation; T5: 20 min after intubation; T6: skin incision. Arterial and venous blood samples were taken for blood gas analysis and determination of lactic acid, Hb and Hct: T1: before AHH, T2: right after AHH, T3: 0.5 h after AHH, T4: l h after AHH. Arterial Oxygen Content (Ca02), Central Venous Oxygen Content (Ccv02) and Oxygen Extraction Ratio (ER02) were calculated. RESULTS: The hemodynamic parameters were maintained within normal limits during operation in group A (P <0.05). CaO2, CcvO2, ERO2 and Lac between the two groups were no significant difference (P> 0.05). Compared with T1, CaO2/CcvO2 atT 2~4 reduced in both groups (P <0.05). Compared with group A, Hb and Hct in group B increased at T2~4 (P <0.05). CONCLUSIONS: Acute hypervolemic hemodilution in patients undergoing acute laparotomy during Induction of general anesthesia have some preventive hypotension effect, more conducive to the smooth blood pharmacokinetics; Voluven induced expansion of applications is safe and effective, and has no effect on the body's metabolic rate of oxygen.

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.

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 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 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.

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.

[Optimal culture conditions of transgenic Polygonium multiflorum hairy root and the effect of elicitor on its growth].

OBJECTIVE: To optimize the culture medium of transgenic Polygonium multiflorum hairy root and the effect of different elicitors on its growth. METHODS: Measured the growth curve of hairy root in four media, including MS, 1/2 MS, B5 and White and estimated the effects of elicitors on the hairy root biomass. RESULTS: MS medium was the most suitable of the four media for hairy root growth. The different concentrations of elicitors, salicylic acid and methyl jasmonate, inhibited the biomass accumulation of hairy root. CONCLUSION: MS is the optimum medium for transgenic Polygonium multiflorum hairy root. Two usual plant elicitors, salicylic acid and methyl jasmonate, can inhibit the growth of transgenic hairy root.

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.

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.

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.

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.

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.

A bioluminescence assay for DNA methyltransferase activity based on methylation-resistant cleavage.

DNA methyltransferase (MTase) is a kind of important regulatory factor in various biological processes. Current methods to investigate DNA MTase activity are still limited in the sensitivity and/or generality. Therefore, developing methods with high sensitivity and improved generality is needed. Here, we develop a new bioluminescence strategy based on methylation-resistant cleavage and protein expression in vitro to detect DNA MTase activity. In the strategy, Dam MTase was used as a model enzyme and MboI as the methylation-resistant endonuclease, and luciferase reporter DNA (LR-DNA) was used as their action target. Because the completely methylated LR-DNA could be expressed as detectable luciferase, Dam MTase activity was quantified by measuring the luminescence intensity of the expressed luciferase. The assay provides a very low detection limit (0.08 U/ml) as well as a wide linear range (0.2-100 U/ml). Besides, the analysis mode has improved generality and could be extended to the detection of other DNA MTases and the corresponding inhibitor screening.

Effect of selective inflow occlusion on hemodynamic conditions during laparoscopic left hemihepatectomy effect of selective inflow occlusion on hemodynamic conditions during laparoscopic left hemihepatectomy.

BACKGROUND/AIMS: Selective inflow occlusion instead of portal triad clamping was used during laparoscopic left hemihepatectomy in our institution. This study observed its hemodynamic effects during operation. METHODOLOGY: Hemodynamic parameters including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were collected at 6 time points: after induction, after insufflation with CO2, after patient in reverse Trendelenburg position, after left branch of hepatic artery was occluded, after left branch of portal vein was occluded and after desufflation with patient supine. RESULTS: No severe perioperative cardiopulmonary complications were observed. Occlusion of left branch of hepatic artery brought no significant hemodynamic change. Occlusion of left branch of portal vein increased CVP and CI and decreased SVR. CO2 inflation caused HR, MAP and SVR to increase. The change to reverse Trendelenburg position caused CVP and PAP to decrease. When placed in the supine position with deflation, MAP, CVP, PAP, PCWP and CI went to a higher than base level. HR and SVR returned to base level. CONCLUSIONS: Using selective inflow occlusion in laparoscopic left hemihepatectomy caused few hemodynamic changes before and after occlusion in patients without cardiopulmonary diseases. However, the change of position and inflation or deflation caused significant changes.