Advancements in research on the association between the biological CLOCK and type 2 diabetes.

Due to the Earth's rotation, the natural environment exhibits a light-dark diurnal cycle close to 24 hours. To adapt to this energy intake pattern, organisms have developed a 24-hour rhythmic diurnal cycle over long periods, known as the circadian rhythm, or biological clock. With the gradual advancement of research on the biological clock, it has become increasingly evident that disruptions in the circadian rhythm are closely associated with the occurrence of type 2 diabetes (T2D). To further understand the progress of research on T2D and the biological clock, this paper reviews the correlation between the biological clock and glucose metabolism and analyzes its potential mechanisms. Based on this, we discuss the potential factors contributing to circadian rhythm disruption and their impact on the risk of developing T2D, aiming to explore new possible intervention measures for the prevention and treatment of T2D in the future. Under the light-dark circadian rhythm, in order to adapt to this change, the human body forms an internal biological clock involving a variety of genes, proteins and other molecules. The main mechanism is the transcription-translation feedback loop centered on the CLOCK/BMAL1 heterodimer. The expression of important circadian clock genes that constitute this loop can regulate T2DM-related blood glucose traits such as glucose uptake, fat metabolism, insulin secretion/glucagon secretion and sensitivity in various peripheral tissues and organs. In addition, sleep, light, and dietary factors under circadian rhythms also affect the occurrence of T2DM.

Comparison of different treatment strategies for T3N1-3 stage gastric cancer based on the SEER database.

Treatment options for T3N1 stage gastric cancer exhibit regional variation, with optimal approach remaining unclear. We derived our data from the SEER database, using Cox proportional risk regression models for univariate and multivariate analyses of 5-years overall survival (5yOS) and 5-years cancer-specific survival (5yCSS). The results showed that younger age, female, non-white race, highly differentiated histologic grade, non-Signet ring cell adenocarcinoma, low N stage, lesser curvature of the stomach, OP followed by adjuvant C/T with or without RT, partial gastrectomy, C/T and others, Radiation therapy, and Chemotherapy were significantly associated with better 5yOS and 5yCSS. For patients with stage T3N1-3 gastric cancer, multimodal treatment regimens demonstrate superior survival outcomes compared to surgery or radiotherapy alone. Among them, OP followed by adjuvant C/T with or without RT emerges as particularly efficacious, potentially offering enhanced benefits for non-Asian populations.

Development of simultaneous quantitation method for 20 free advanced glycation end products using UPLC-MS/MS and clinical application in kidney injury.

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N6-carboxyethyl-L-arginine (CEA), N6-carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N6-formyl-lysine, N6-carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease.

Tanshinone IIA modulates cancer cell morphology and movement via Rho GTPases-mediated actin cytoskeleton remodeling.

Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.

Effects of moisture content and landfill age on the shear strength properties of municipal solid waste in Xi'an, China.

With the continued expansion of waste landfills, accidents may occur if the landfills are not properly stabilized. In this study, samples of municipal solid waste (MSW) from a waste landfill in Xi'an, China were collected through on-site drilling. Considering the effects of nine landfill ages (1, 2, 3, 11, 12, 13, 21, 22, and 23 y) and six moisture contents (natural, 20, 40, 60, 80, and 100%), 324 groups of MSW were tested in the laboratory using a direct shear test apparatus. The results indicate the following: (1) with an increase in horizontal shear displacement, the shear stress of MSW gradually increases without a peak stress phenomenon, which is a displacement hardening curve; (2) with an increase in landfill age, the shear strength of MSW increases; (3) with an increase in moisture content, the shear strength of MSW increases; (4) with an increase in landfill age, the cohesion (c) decreases and the internal friction angle (φ) increases; and (5) with an increase in moisture content, the c and φ of MSW increases. The c range found in this study was 6.04-18.69 kPa, while the φ was 10.78-18.26°. The results of this study can provide a reference for stability calculations for MSW landfills.

Efficacy and safety of Gegen Qinlian decoction in the treatment of type II diabetes mellitus: a systematic review and meta-analysis of randomized clinical trials.

Aim: The study aims to systematically assess the efficacy and safety of Gegen Qinlian decoction in the treatment of type 2 diabetes mellitus. Methods: We systematically searched a total of nine databases from the time of creation to 20 March 2023. The quality of the literature was assessed using the risk of bias assessment tool in the Cochrane Handbook. RevMan 5. 3 and Stata 14.0 were applied to conduct meta-analysis. Results: A total of 17 studies, encompassing 1,476 patients, were included in the study. Gegen Qinlian decoction combined with conventional treatment was found to significantly reduce FBG (MD = -0.69 mmol/L, 95% CI -0.84 to -0.55, p < 0.01; I2 = 67%, p<0.01), 2hPG (MD = -0.97 mmol/L, 95% CI -1.13 to -0.81, p < 0.01; I2 = 37%, p=0.09), HbA1c (MD = -0.65%, 95% CI -0.78 to -0.53, p < 0.01; I2 = 71%, p<0.01), TC (MD = -0.51 mmol/L, 95% CI -0.62 to -0.41, p < 0.01; I2 = 45%, p=0.09), TG (MD = -0.17mmol/L, 95% CI -0.29 to -0.05, p < 0.01; I2 = 78%, p<0.01), LDL-C (MD = -0.38mmol/L, 95% CI -0.53 to -0.23, p < 0.01; I2 = 87%, p<0.01), HOMA-IR (SMD = -1.43, 95% CI -2.32 to -0.54, p < 0.01; I2 = 94%, p<0.01), and improved HDL-C (MD = 0.13 mmol/L, 95% CI 0.09-0.17, p < 0.01; I2 = 30%, p=0.24). Only three studies explored the differences in efficacy between GQD alone and conventional treatment in improving glucose-lipid metabolism and insulin resistance, and some of the outcome indicators, such as 2hPG and HDL-C, were examined in only one study. Therefore, the effect of GQD alone on glucose-lipid metabolism and insulin resistance cannot be fully determined, and more high-quality studies are needed to verify it. Publication bias analysis revealed no bias in the included studies. Conclusion: Gegen Qinlian Decoction has certain efficacy and safety in enhancing glycolipid metabolism and alleviating insulin resistance, potentially serving as a complementary therapy for type 2 diabetes mellitus. Rigorous, large-sample, multicenter RCTs are needed to verify this. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023413758, PROSPERO CRD42023413758.

Strength characteristics of geosynthetic reinforced mechanically biologically treated waste by triaxial test.

The reinforcement strength characteristics of mechanically biologically treated (MBT) waste were studied by conducting consolidated undrained triaxial tests with MBT waste collected from the Hangzhou Tianziling landfill pilot project. In the tests, the effects of the reinforcement material used (geomembrane, geotextile, and geogrid) and the number of reinforcement layers used (one, two, and three layers) were assessed. The results showed the following: (1) even through the axial strain increases up to 25%, the deviator stress of MBT waste could not reach a well-defined peak; (2) the reinforcement effect is related to the type of reinforcement material, with geogrid exhibiting the best reinforcement effect and geomembrane the worst; (3) the strength ratio of reinforced MBT waste is related to the confining pressure and the number of reinforcement layers, with a greater strength ratio in the MBT waste attained with a lower confining pressure in a logarithmic relationship and a greater strength ratio in the MBT waste attained with a greater number of reinforcement layers in a linear relationship; (4) the reinforced MBT waste shear strength parameter variation ranges for the cohesion (c), internal friction angle (φ), effective cohesion (c'), and effective internal friction angle (φ') are 3.92-13.69 kPa, 19°-29°, 10.10-27.94 kPa, and 24°-45°, respectively; and (5) the deviations in the test values from the apparent cohesion method and the semi-empirical formula method are less than 15%, indicating that these two theories of reinforced sand can also be applied to MBT waste. The results of this study are useful as a baseline reference for the stability assessment of MBT waste landfills.

Effects of the reinforcement content and reinforcement scale on the shear strength characteristics of mechanically biologically treated waste.

Mechanical and biological treatment (MBT), which can be used for waste reduction and for the burning of methane from biological treatments to generate electricity and heating, has become a popular research topic in environmental geotechnical engineering. This study investigated the mechanical behaviour of MBT waste and the effects of different reinforcement contents and reinforcement scales on its shear strength characteristics, and 68 groups of MBT waste samples from the Hangzhou Tianziling landfill were tested in the laboratory with a direct shear test apparatus. The samples exhibited displacement hardening behaviour in their mechanical response. The results show that the content and scale of the reinforced materials in MBT waste play an important role in the strength characteristics of MBT waste, and graphs showing the variation of the MBT waste shear strength and shear strength parameters with different reinforcement contents and reinforcement scales are shown. The range of cohesion c is 6.0-12.0 kPa, and the internal friction angle φ is 15.6-26.6°, respectively. The results of this study provide a reference for the assessment of slope stability at MBT landfills.