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Diabetic kidney disease (DKD) is one of the most common chronic complications of type 2 diabetes mellitus (T2DM), and it is particularly important to identify a high-quality method for evaluating disease progression. Urinary exosomes contain microRNA that might promise early diagnostic and monitoring markers of DKD. The present study aimed to identify novel exosome-related markers associated with inflammation and fibrosis to assess the progression of DKD. Exosomes were extracted from the urine of 83 participants to determine the expression levels of miRNA-615-3p and miRNA-3147 in 20 healthy people, 21 patients with T2DM and 42 patients with DKD, as determined by RT-qPCR. The circulating expression level of TGF-β1 was detected by ELISA. Serum Cystatin C was measured by a latex-enhanced immunoturbidimetric method. The correlation analyses were performed for all clinical and laboratory parameters. The expression level of urinary exosomal miRNA-615-3p in DKD patients was significantly higher than that in the control group and the T2DM group by RT-qPCR. The expression of miRNA-3147 showed an upward trend in the three groups of subjects, but it was not statistically significant. The urinary exosomal miRNA-615-3p was positively correlated with serum Cystatin C, plasma TGF-β1, creatinine, BUN, PCR and 24-h urine protein, and negatively correlated with eGFR and albumin. The diagnostic efficacy of urinary exosomal miRNA-615-3p combined with the ACR was higher than that of ACR alone. Urinary exosomal miRNA-615-3p may be used as a novel biomarker for evaluating the progression of DKD, and may be involved in the process of inflammation and fibrosis in DKD. The combined diagnosis of urinary exosomal miRNA-615-3p and ACR may be used as more stable and sensitive diagnostic criteria for DKD. [ABSTRACT FROM AUTHOR]

Different microbial aggregates show substantial differences in morphology, and extracellular polymer substances have been confirmed to play a key role in the formation of aggregates. In this study, three different microbial aggregates and their exopolysaccharides were compared. The results show that the granular sludge was largest in size and the most compact in shape. Biofilms with a certain thickness had the next greatest density, and flocculent sludge, with the smallest particle size, was the loosest. The extended Derjaguin-Landau-Verwey-Overbeek analysis shows that hydrogen bonding, hydrophobic and electrostatic interactions affect the aggregation of microorganisms. A comparison of exopolysaccharides shows that granular sludge exopolysaccharides show the highest hydrophobicity (38.08%) and lowest surface charge (−20.5 mV), followed by biofilm exopolysaccharides (27.9% and −24.8 mV respectively). The results of Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy show that the contents of hydrophilic and hydrophobic functional groups and charged functional groups of exopolysaccharides affect the above properties of exopolysaccharides, thereby affecting microbial aggregation. In addition, the hydrogen bond content of exopolysaccharides in granular sludge (19.3%), biofilm (19.2%) and activated sludge (18.9%) decreased sequentially. This also affects the cross-linking of microbial exopolysaccharides to form hydrogels. Finally, the results of confocal laser scanning microscopy showed that, different from the other two aggregates, the extracellular α-polysaccharides of granular sludge are mainly distributed in the nucleus, which is more conducive to aggregation. The research results of this thesis provide a new understanding of the differences in the aggregation morphology of different aggregates from the perspective of exopolysaccharides. [ABSTRACT FROM AUTHOR]

Cu-Ni-Al–Fe-Mn alloy billets were prepared by heating–cooling combined mould (HCCM) continuous casting at different casting speeds. Then, the cold deformation behaviour of billets was studied by multi-pass cold rolling, and the effects of HCCM continuous casting on cold deformability were discussed by comparing with the mould casting (MC) alloy. The results show that HCCM continuous casting significantly improves the cold deformability of Cu-Ni-Al–Fe-Mn alloy billets. When the rolling reduction is 94%, HCCM continuous casting samples have good edge quality without obvious crack, while the MC sample has severe edge cracks. With the rolling reduction increasing from 40% to 94%, the elongation of the MC samples decreases from 6% to 2%, while that of HCCM continuous casting samples maintains in 6%∼9%, showing good continuous deformability. The HCCM continuous casting samples with lower casting speeds have [001] oriented columnar grains along the casting direction, which make the deformation mechanism change from nano-crystallization to parallel stacking faults. In the meanwhile, HCCM continuous casting improves deformation coordination of as-cast grains and restrains intergranular cracking, which is reflected in the influence on misorientation between as-cast grains and distribution of coarse NiAl phases. In addition, nano-twins found in the rolled MC sample promote the initiation and propagation of cracks. [ABSTRACT FROM AUTHOR]

The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of great importance in maintaining the survival and function of cells and could be a potential therapeutic target for human diseases. Organelle-specific autophagy is one of the major subtypes of autophagy, selectively targeting different organelles for quality control. This type of autophagy includes mitophagy, pexophagy, reticulophagy (endoplasmic reticulum), ribophagy, lysophagy, and nucleophagy. These kinds of organelle-specific autophagy are reported to be beneficial for inflammatory disorders by eliminating damaged organelles and maintaining homeostasis. In this review, we summarized the recent findings and mechanisms covering different kinds of organelle-specific autophagy, as well as their involvement in various diseases, aiming to arouse concern about the significance of the quality control of multiple organelles in the treatment of inflammatory diseases. Abbreviations: ABCD3: ATP binding cassette subfamily D member 3; AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATF: activating transcription factor; ATG: autophagy related; ATM: ATM serine/threonine kinase; BCL2: BCL2 apoptosis regulator; BCL2L11/BIM: BCL2 like 11; BCL2L13: BCL2 like 13; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CANX: calnexin; CAT: catalase; CCPG1: cell cycle progression 1; CHDH: choline dehydrogenase; COPD: chronic obstructive pulmonary disease; CSE: cigarette smoke exposure; CTSD: cathepsin D; DDIT3/CHOP: DNA-damage inducible transcript 3; DISC1: DISC1 scaffold protein; DNM1L/DRP1: dynamin 1 like; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 alpha kinase 3; EMD: emerin; EPAS1/HIF-2α: endothelial PAS domain protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBXO27: F-box protein 27; FKBP8: FKBP prolyl isomerase 8; FTD: frontotemporal dementia; FUNDC1: FUN14 domain containing 1; G3BP1: G3BP stress granule assembly factor 1; GBA: glucocerebrosidase beta; HIF1A/HIF1: hypoxia inducible factor 1 subunit alpha; IMM: inner mitochondrial membrane; LCLAT1/ALCAT1: lysocardiolipin acyltransferase 1; LGALS3/Gal3: galectin 3; LIR: LC3-interacting region; LMNA: lamin A/C; LMNB1: lamin B1; LPS: lipopolysaccharide; MAPK8/JNK: mitogen-activated protein kinase 8; MAMs: mitochondria-associated membranes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MOD: multiple organelles dysfunction; MTPAP: mitochondrial poly(A) polymerase; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; NLRP3: NLR family pyrin domain containing 3; NUFIP1: nuclear FMR1 interacting protein 1; OMM: outer mitochondrial membrane; OPTN: optineurin; PD: Parkinson disease; PARL: presenilin associated rhomboid like; PEX3: peroxisomal biogenesis factor 3; PGAM5: PGAM family member 5; PHB2: prohibitin 2; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RHOT1/MIRO1: ras homolog family member T1; RIPK3/RIP3: receptor interacting serine/threonine kinase 3; ROS: reactive oxygen species; RTN3: reticulon 3; SEC62: SEC62 homolog, preprotein translocation factor; SESN2: sestrin2; SIAH1: siah E3 ubiquitin protein ligase 1; SNCA: synuclein alpha; SNCAIP: synuclein alpha interacting protein; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TICAM1/TRIF: toll-like receptor adaptor molecule 1; TIMM23: translocase of inner mitochondrial membrane 23; TNKS: tankyrase; TOMM: translocase of the outer mitochondrial membrane; TRIM: tripartite motif containing; UCP2: uncoupling protein 2; ULK1: unc-51 like autophagy activating kinase; UPR: unfolded protein response; USP10: ubiquitin specific peptidase 10; VCP/p97: valosin containing protein; VDAC: voltage dependent anion channels; XIAP: X-linked inhibitor of apoptosis; ZNHIT3: zinc finger HIT-type containing 3. [ABSTRACT FROM AUTHOR]

There are more than 18,500 grotto statues in Anyue County, Sichuan Province, China. These grotto statues painted with diverse colors were first sculpted in the Sui Dynasty (581–618 AD) and play a significant role in the history of grotto art development in China. However, due to natural weathering and human factors, the grotto paintings are suffering from many problems, such as flaking and powdering. To study the composition, structure, and destructive factors at work in the paint layers, a set of effective detection methods were integrated, including Raman spectroscopy, scanning electron microscopy–energy dispersive spectroscopy, enzyme-linked immunosorbent assay, immunofluorescence microscopy, and others. The pigments, layer structures, binding materials, and elemental migrations of 22 polychrome samples from the Anyue grottoes are detected. The results show that the Anyue grottoes were painted with more than ten pigments. Casein, egg white, mammalian glue, and plant glue were also detected in samples as binding materials. The accumulation of sulfur and calcium on the surface of several samples was found, which was the main reason for the flaking of the pigments. This study provides not only a reference method but also basic information for the subsequent restoration design. [ABSTRACT FROM AUTHOR]

Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated. Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6–12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure. Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension. [ABSTRACT FROM AUTHOR]

Background: We have previously reported that the long-term exposure of organophosphorus induces vascular dementia (VD) in rats. As a coenzyme, vitamin B6 is mainly involved in the regulation of metabolisms. Whether vitamin B6 improves VD remains unknown.Methods: The model of VD was induced by feeding rats with isocarbophos (0.5 mg/kg per two day, 12 weeks). The blood flow of the posterior cerebral artery (PCA) in rat was assessed by transcranial Doppler (TCD). The learning and memory were evaluated by the Morris Water Maze (MWM) test.Results: Administration of vitamin B6 increased the blood flow in the right and left posterior cerebral arteries and improved the functions of learning and memory in isocarbophos-treated rats. Vitamin B6 increased the protein levels of N-methyl-D-aspartate receptor (NMDAR) 2B, postsynaptic densities (PSDs) protein 95, and calmodulin-dependent protein kinase II (CaMK-II) in the hippocampus, which were decreased by isocarbophos in rats. Morphological analysis by light microscope and electronic microscope indicated disruptions of the hippocampus caused by isocarbophos were normalized by vitamin B6. Importantly, the antagonist of NMDAR signaling by eliprodil abolished these beneficial effects produced by vitamin B6 on PCA blood flow, learning, memory, and hippocampus structure in rats, as well as the protein expression of NMDAR 2B, PSDs protein 95, and CaMK-II in the hippocampus.Conclusion: Vitamin B6 activates NMDAR signaling to prevent isocarbophos-induced VD in rats. [ABSTRACT FROM AUTHOR]

The objective of this study is to develop playability heuristics based on a lexical analysis of nouns and adjectives frequently used in online game reviews. Built on a previous lexical analysis of adjectives in online game reviews, it is argued that nouns together with adjectives will likely provide more contextual information than adjectives alone, and therefore the patterns among these words can be used to develop playability heuristics. A revised lexical approach is adopted to analyze nouns and adjectives from 821,122 online reviews. Ninety seven factors emerge from this analysis. Based on the nouns and adjectives highly loaded on these factors, a new process is introduced and 90 playability heuristics are derived. This study significantly expands the current pool of playability heuristics that facilitate the computer game design process. The lexical method adopted in this study demonstrates its effectiveness in developing interface design guidelines based on a large number of online reviews on a system or product. It can be extended to other fields that are human-behavior centered. [ABSTRACT FROM PUBLISHER]

The peptide transporter 1 (PEPT1) in the apical membrane of enterocytes is the central mechanism for regulating the absorption of di- and tripeptides. Dietary proteins may affect PEPT1 abundance and peptide absorption. The present study aimed to characterize changes in PEPT1 mRNA and PEPT1 protein levels in the duodenum and jejunum of young rats after 7-day diet intervention with casein (reference), soy, beef, pork, chicken and fish proteins and further evaluate the impact on the epithelial absorption capacity. RT-PCR and western blot analyses showed that: (1) PEPT1 protein level in duodenum was higher (p < 0.05) for soy protein group than that for casein group. However, no difference was observed in jejunal PEPT1 protein level between any two diet groups (p > 0.05). The soy protein group had lower crypt depth and higher V/C ratio in the jejunum (p < 0.05). (2) PEPT1 mRNA levels were lower (p < 0.05) in rat duodenum and jejunum in pork, chicken and fish protein groups, whose trend was contrary to the results of jejunual histological observation with lower crypt depth, greater villus height and higher V/C ratio. In conclusion, different meat proteins alter distinct PEPT1 expression level and absorption capacity as reflected by gut morphology in small intestine. [ABSTRACT FROM PUBLISHER]

An electrochemical sensor for L-tryptophan based on a molecularly imprinted polymer was developed. The sensing film was prepared by the co-electropolymerization of o-phenylenediamine and hydroquinone on a gold electrode in the presence of L-tryptophan as the template. The performance of the L-tryptophan sensor was characterized by cyclic voltammetry, differential pulse voltammetry, and alternating current impedance. Under the optimal experimental conditions, the relative current change was linear to the concentration of L-tryptophan in the range of 1.0 × 10−8to 1.0 × 10−6 mol/L and a detection limit of 0.50 × 10−8 mol/L was obtained. The sensor showed high sensitivity and selectivity for L-tryptophan. The imprinting factor was 3.58 and selectivity factors of L-tryptophan compared to analogs were larger than 2. The sensor also demonstrated good resistance to acidic, basic, and organic environments. [ABSTRACT FROM AUTHOR]