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Background: Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to cardiovascular disease, and coronary artery disease (CAD) is their leading cause of death. We aimed to assess whether computed tomography (CT) based imaging parameters and radiomic features of pericoronary adipose tissue (PCAT) can improve the diagnostic efficacy of whether patients with T2DM have developed CAD. Methods: We retrospectively recruited 229 patients with T2DM but no CAD history (146 were diagnosed with CAD at this visit and 83 were not). We collected clinical information and extracted imaging manifestations from CT images and 93 radiomic features of PCAT from all patients. All patients were randomly divided into training and test groups at a ratio of 7:3. Four models were constructed, encapsulating clinical factors (Model 1), clinical factors and imaging indices (Model 2), clinical factors and Radscore (Model 3), and all together (Model 4), to identify patients with CAD. Receiver operating characteristic curves and decision curve analysis were plotted to evaluate the model performance and pairwise model comparisons were performed via the DeLong test to demonstrate the additive value of different factors. Results: In the test set, the areas under the curve (AUCs) of Model 2 and Model 4 were 0.930 and 0.929, respectively, with higher recognition effectiveness compared to the other two models (each p < 0.001). Of these models, Model 2 had higher diagnostic efficacy for CAD than Model 1 (p < 0.001, 95% CI [0.129–0.350]). However, Model 4 did not improve the effectiveness of the identification of CAD compared to Model 2 (p = 0.776); similarly, the AUC did not significantly differ between Model 3 (AUC = 0.693) and Model 1 (AUC = 0.691, p = 0.382). Overall, Model 2 was rated better for the diagnosis of CAD in patients with T2DM. Conclusions: A comprehensive diagnostic model combining patient clinical risk factors with CT-based imaging parameters has superior efficacy in diagnosing the occurrence of CAD in patients with T2DM. [ABSTRACT FROM AUTHOR]

Energy homeostasis is essential for organisms to maintain fluctuation in energy accumulation, mobilization. Lipids as the main energy reserve in insects, their metabolism is under the control of many physiological program. This study aimed to determine whether the adipokinetic hormone receptor (AKHR) was involved in the lipid mobilization in the Spodoptera litura. A full-length cDNA encoding AKHR was isolated from S. litura. The Sl AKHR protein has a conserved seven-transmembrane domain which is the character of a putative G protein receptor. Expression profile investigation revealed that SlAKHR mRNA was highly expressed in immatural stage and abundant in fat body in newly emerged female adults. Knockdown of SlAKHR expression was achieved through RNAi by injecting double-stranded RNA (dsRNA) into the 6th instar larvae. The content of triacylgycerol (TAG) in the fat body increased significantly after the SlAKHR gene was knockdown. And decrease of TAG releasing to hemolymph with increase of free fatty acid (FFA) in hemolymph were observed when the SlAKHR gene was knowned-down. In addition, lipid droplets increased in fat body was also found. These results suggested that SlAKHR is critical for insects to regulate lipids metabolism. [ABSTRACT FROM AUTHOR]

Aims: To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD). Materials and Methods: LixiLan‐O‐AP (NCT03798054) was a 24‐week multicentre study in adults (n = 878, mean age 56.0 years, mean body mass index 26.0 kg/m2) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%) and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open‐label once‐daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium‐glucose cotransporter‐2 inhibitors. The primary efficacy endpoint was change in HbA1c. Results: After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (−21 mmol/mol; −1.9%) compared with iGlar (−16 mmol/mol; −1.4%; P < 0.0001) and Lixi (−10 mmol/mol; −0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2‐hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference −1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant‐year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%). Conclusions: iGlarLixi achieved significant HbA1c reductions, to near‐normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well‐tolerated treatment option for Asian Pacific people with T2D. [ABSTRACT FROM AUTHOR]

Mutations in PINK1 and Parkin are a major cause of Parkinson's disease (PD) pathogenesis. In addition, PINK1 and Parkin are two mitochondrial proteins that jointly contribute to mitochondrial homeostasis via mitophagy. Mitochondrial dysfunction is the most significant mechanism underlying PD pathogenesis. Thus, understanding the regulatory mechanism of PINK1 and Parkin expression is beneficial to the treatment of PD. In this study, we found that miR-421 expression was upregulated in mice treated with MPTP, as well as in SH-SY5Y cells treated with methyl-4-phenylpyridine (MPP+). Inhibition of miR-421 alleviated neurodegeneration in MPTP-treated mice and promoted mitophagy in MPP+-treated SH-SY5Y cells. Bioinformatics software predicted that Pink1 is a downstream target protein of miR-421. In addition, miR-421-induced Pink1 and Parkin inhibition negatively modulates mitophagy in MPP+-treated SH-SY5Y cells. In addition, our study confirmed that Pink1/Parkin is responsible for miR-421-regulated cell mitophagy. Overall, this study revealed that miR-421 regulates nerve cell mitophagy through the Pink1/Parkin pathway. [ABSTRACT FROM AUTHOR]

Mutations in PINK1 and Parkin are a major cause of Parkinson's disease (PD) pathogenesis. In addition, PINK1 and Parkin are two mitochondrial proteins that jointly contribute to mitochondrial homeostasis via mitophagy. Mitochondrial dysfunction is the most significant mechanism underlying PD pathogenesis. Thus, understanding the regulatory mechanism of PINK1 and Parkin expression is beneficial to the treatment of PD. In this study, we found that miR-421 expression was upregulated in mice treated with MPTP, as well as in SH-SY5Y cells treated with methyl-4-phenylpyridine (MPP+). Inhibition of miR-421 alleviated neurodegeneration in MPTP-treated mice and promoted mitophagy in MPP+-treated SH-SY5Y cells. Bioinformatics software predicted that Pink1 is a downstream target protein of miR-421. In addition, miR-421-induced Pink1 and Parkin inhibition negatively modulates mitophagy in MPP+-treated SH-SY5Y cells. In addition, our study confirmed that Pink1/Parkin is responsible for miR-421-regulated cell mitophagy. Overall, this study revealed that miR-421 regulates nerve cell mitophagy through the Pink1/Parkin pathway. [ABSTRACT FROM AUTHOR]

Mutations in PINK1 and Parkin are a major cause of Parkinson's disease (PD) pathogenesis. In addition, PINK1 and Parkin are two mitochondrial proteins that jointly contribute to mitochondrial homeostasis via mitophagy. Mitochondrial dysfunction is the most significant mechanism underlying PD pathogenesis. Thus, understanding the regulatory mechanism of PINK1 and Parkin expression is beneficial to the treatment of PD. In this study, we found that miR-421 expression was upregulated in mice treated with MPTP, as well as in SH-SY5Y cells treated with methyl-4-phenylpyridine (MPP+). Inhibition of miR-421 alleviated neurodegeneration in MPTP-treated mice and promoted mitophagy in MPP+-treated SH-SY5Y cells. Bioinformatics software predicted that Pink1 is a downstream target protein of miR-421. In addition, miR-421-induced Pink1 and Parkin inhibition negatively modulates mitophagy in MPP+-treated SH-SY5Y cells. In addition, our study confirmed that Pink1/Parkin is responsible for miR-421-regulated cell mitophagy. Overall, this study revealed that miR-421 regulates nerve cell mitophagy through the Pink1/Parkin pathway. [ABSTRACT FROM AUTHOR]

Aim: This study assessed the efficacy and safety of co‐administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. Methods: This multicentre, phase 3 trial consisted of a 24‐week, randomized, double‐blind, active‐controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once‐daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co‐administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. Results: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (−1.51%) and R100/H10 (−1.54%) groups compared with those receiving the corresponding doses of individual agents (−0.98% for R100, −0.86% for H5 and −0.95% for H10, respectively; p <.0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2‐h postprandial glucose were also more pronounced in the co‐administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. Conclusions: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co‐administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of once‐weekly subcutaneous semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes (T2D) in a multiregional clinical trial. Materials and Methods: In the 30‐week, randomized, double‐blind, double‐dummy, active comparator SUSTAIN China trial, 868 adults with T2D inadequately controlled on metformin (HbA1c 7.0%‐10.5%) were randomized to receive once‐weekly semaglutide 0.5 mg (n = 288), semaglutide 1.0 mg (n = 290) or once‐daily sitagliptin 100 mg (n = 290). The primary and confirmatory secondary endpoints were change from baseline to week 30 in HbA1c and body weight, respectively. Results: The trial enrolled ~70% (605/868) of the patients in China, and the remaining patients from four other countries, including the Republic of Korea. Both doses of semaglutide were superior to sitagliptin in reducing HbA1c and body weight after 30 weeks of treatment. The odds of achieving target HbA1c of less than 7.0% (53 mmol/mol), weight loss of 5% or higher, or 10% or higher, and the composite endpoint of HbA1c less than 7.0% (53 mmol/mol) without severe or blood glucose‐confirmed symptomatic hypoglycaemia no weight gain, were all significantly higher with both semaglutide doses compared with sitagliptin. The safety profile for semaglutide was consistent with the known class effects of GLP‐1 receptor agonists (RAs). Consistent efficacy and safety findings were seen in the Chinese subpopulation. Conclusions: Once‐weekly semaglutide was superior to sitagliptin in improving glycaemic control and reducing body weight in patients with T2D inadequately controlled on metformin. The safety and tolerability profiles were consistent with those of semaglutide and other GLP‐1 RAs. Semaglutide is an effective once‐weekly treatment option for the Chinese population. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. tRNA-derived fragments (tRFs) have been identified as potential biomarkers and cancer therapeutic targets. However, the influence of tRFs on GC remains unknown. The key tRFs were researched in vitro function and mechanism. Patients and Methods: Here, differentially expressed tRFs between GC and paracancerous tissues were identified by small RNA sequencing, and the role of key tRF was evaluated in vitro. Results: Eight tRFs were significantly differentially expressed between GC tissues and adjacent tissues: five were significantly upregulated and three were downregulated in GC tissues. The results of target gene prediction and functional enrichment analysis showed that tRFs with different expressions were mainly involved in cell adhesion and connection, cell migration, wingless-type (Wnt), mitogen-activated protein kinase (MAPK), and cancer signaling pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) indicated that the expression of tRF-24-V29K9UV3IU and its target genes (CCND2, FZD3, and VANGL1) in GC tissues and cells was decreased compared with those in the control group. Importantly, overexpression of tRF-24-V29K9UV3IU inhibited cell proliferation, migration and invasion, while promoted cell apoptosis of GC cells. Conclusion: This study suggests that tRF-24-V29K9UV3IU may hinder GC tumor progression by inhibiting cell proliferation, migration, invasion, while promoting cell apoptosis by regulating the Wnt signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract Dysregulation and aggregation of the peptide hormone IAPP (islet amyloid polypeptide, a.k.a. amylin) into soluble oligomers that appear to be cell-toxic is a known aspect of diabetes mellitus (DM) Type 2 pathology. IAPP aggregation is influenced by several factors including interactions with metal ions such as Cu(II). Because Cu(II) ions are redox-active they may contribute to metal-catalyzed formation of oxidative tyrosyl radicals, which can generate dityrosine cross-links. Here, we show that such a process, which involves Cu(II) ions bound to the IAPP peptide together with H 2 O 2 , can induce formation of large amounts of IAPP dimers connected by covalent dityrosine cross-links. This cross-linking is less pronounced at low pH and for murine IAPP, likely due to less efficient Cu(II) binding. Whether IAPP can carry out its hormonal function as a cross-linked dimer is unknown. As dityrosine concentrations are higher in blood plasma of DM Type 2 patients – arguably due to disease-related oxidative stress - and as dimer formation is the first step in protein aggregation, generation of dityrosine-linked dimers may be an important factor in IAPP aggregation and thus relevant for DM Type 2 progression. Highlights • Diabetes pathology includes elevated levels of reactive oxygen species (ROS). • Cu(II) ions bound to hIAPP generate dityrosine cross-links via ROS formation. • Less dityrosine forms at low pH and in mIAPP, likely due to weaker Cu(II) binding. • Dityrosine-linked IAPP dimers may be relevant in diabetes progression. [ABSTRACT FROM AUTHOR]

Abstract Aims The oncogenic role of lncRNA Hotair has been acknowledged in subset of malignancies, including gastric cancer (GC). However, the detailed molecular mechanisms that contribute to its oncogenic role of are largely elusive. This study was designed to explore the underlying mechanism that contributes the regulatory role of Hotair in GC pathogenesis and progression. Main methods Expression pattern of lncRNAs in GC tissues and adjacent normal tissues were identified by using microarray analysis. The cell proliferation of GC cells was examined by CCK-8 assay and colony formation assay, while migration and invasion capabilities of GC cells were examined by Transwell (with or without Matrigel) assay. Cell apoptosis was examined by Flow cytometer. qRT-PCR and western blotting were used to examine the expression of Hotair, miR-217, and other related genes. The potential target relationships were predicted by miRcode algorithm, and validated by dual luciferase reporter gene assay. Key findings We observed that Hotair was frequently up-regulated in GC tissues and cell lines, and high Hotair level was positively correlated with poor prognosis in GC patients. Knockdown of Hotair inhibited GC cells' viability, migration, invasion, Epithelial mesenchymal transition process. MiR-217 was decreased while GCP5 was increased in GC cells. Hotair negatively regulated the expression of miR-217 in GC while miR-217 targeted GCP5 to down-regulate its expression. Hotair promoted GC development by promoting GCP5 expression via sponging miR-217. Significance Hotair could serve as a potentially prognostic indicator and provide new light into its underlying biological-molecular mechanism in GC. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common malignancies worldwide. Emerging evidence has shown that aberrant expression of microRNAs (miRNAs) plays important roles in cancer progression. However, little is known about the potential role of miR-217 in GC. In this study, we investigated the role of miR-217 on GC cell proliferation and invasion. The expression of miR-217 was down-regulated in GC cells and human GC tissues. Enforced expression of miR-217 inhibited GC cells proliferation and invasion. Moreover, Glypican-5 (GPC5), a new ocncogene, was identified as the potential target of miR-217. In addition, overexpression of miR-217 impaired GPC5-induced promotion of proliferation and invasion in GC cells. In conclusion, these findings revealed that miR-217 functioned as a tumor suppressor and inhibited the proliferation and invasion of GC cells by targeting GPC5, which might consequently serve as a therapeutic target for GC patients. [ABSTRACT FROM AUTHOR]

Mitochondrial complex I is the main source of reactive oxygen species (ROS) production, but the exact site of superoxide generation or their relative contribution is not clear. This study aims to determine the function of iron–sulfur clusters (ISCU) in the initiation of ROS generation. ISCU2 and ISCU8 were cloned from Spodoptera litura which shared the conserved amino acid sequence with other insects. The expressions of the two genes were ubiquitous throughout the whole development stages and tissues. Knockdown of ISCU2 and ISCU8 resulted in the decline of the ROS, whereas rotenone and azadirachtin treatment up-regulated ROS levels by increasing mRNA expression. Furthermore, antioxidant enzyme activity of SOD and POD were up-regulated by rotenone and azadirachtin treatment and then declined after ISCU was silenced. Our results suggest the possibility that the molecules of ISCU2 and ISCU8 in complex I may serve as potential sites in the initiation of ROS generation. [ABSTRACT FROM AUTHOR]

Background: Rhodojaponin III, as a botanical insecticide, affects a wide variety of biological processes in insects, including reduction of feeding, suspension of development, and oviposition deterring of adults in a dose-dependent manner. However, the mode of these actions remains obscure. Principal Findings: In this study, a comparative proteomic approach was adopted to examine the effect of rhodojaponin III on the Plutella xyllostella (L.). Following treating 48 hours, newly emergence moths were collected and protein samples were prepared. The proteins were separated by 2-DE, and total 31 proteins were significantly affected by rhodojaponin III compared to the control identified by MALDI-TOF/TOF-MS/MS. These differentially expressed proteins act in the nervous transduction, odorant degradation and metabolic change pathways. Further, gene expression patterns in treated and untreated moths were confirmed by qRT-PCR and western blot analysis. RNAi of the chemosensory protein (PxCSP) gene resulted in oviposition significantly increased on cabbage plants treated with rhodojaponin III. Conclusions: These rhodojaponin III-induced proteins and gene properties analysis would be essential for a better understanding of the potential molecular mechanism of the response to rhodojaponin III from moths of P. xylostella. [ABSTRACT FROM AUTHOR]

Abstract: Specific behaviors of insects are stimulated by the recognition of chemicals in the external environment by sensilla on chemoreceptive organs. Rhodojaponin III is a nonvolatile natural botanical insecticide, which has an intense effect of deterring oviposition activity against many insects. This study aimed to determine whether the Or83b protein is involved in the recognition of rhodojaponin III. The SlOr83b protein has a conserved seven-transmembrane domain and a putative receptor/receptor interaction loop. The Or83b mRNA is first transcribed in 1st larvae, and expressed in later larval stages. A high level of Or83b mRNA is expressed in pupal and adult stages. Knockdown of SlOr83b expression was achieved through RNAi by injecting double-stranded RNA (dsRNA) into the 8th day pupae, and oviposition significantly increased on rhodojaponin III treated cabbage leaves. These results suggest that Or83b is critical for insects to identify the nonvolatile the insecticide rhodojaponin III. [Copyright &y& Elsevier]

Objective To evaluate the predictive value of the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) for the presence of several cardiovascular risk conditions—hypertension, dyslipidaemia, metabolic syndrome (MS), and type 2 diabetes—in a Chinese population in Jinan, China. Methods Data for a representative, cross-sectional sample of 3006 adults (mean age; range 20–74 years) in Jinan from 2007 to 2008 were studied. The association of BMI, WC, and WHtR with cardiovascular risk conditions was assessed by use of receiver operating characteristic curve (ROC) analysis and by calculating the area under the ROC (AUC) and age adjusted odds ratios (ORs) for metabolic syndrome, dyslipidaemia, type 2 diabetes, and hypertension. Results AUC cut-off values showed that the association of WHtR and WC was higher than that for BMI for all risk conditions for both sexes, except for hypertension in men. The AUC values for WC showed a higher association with hypertension and metabolic syndrome for women than men (p<0.01 for hypertension, p<0.05 for metabolic syndrome). The ORs were highest for WHtR for metabolic syndrome, diabetes, and hypertension in women. The ORs were highest for BMI for hypertension in men. Conclusions Compared with BMI, measures of central obesity, particularly WHtR, show a better association with obesity related cardiovascular risk conditions for both sexes, except for hypertension in men, in Jinan, China. [ABSTRACT FROM PUBLISHER]

Simple Summary: Aphidoletes aphidimyza (Rondani) is an important predatory insect, primarily preying on aphids. The effective control of diapause in A. aphidimyza is a crucial practical issue in the field of biological pest control and large-scale artificial insect breeding. Previous research has shown that, in the European strain of A. aphidimyza, diapause occurs during the larval stage in the cocoon, it has a day-long response, and it enters diapause when the day length decreases. In this study, we evaluated the effects of photoperiod and temperature on the incidence of diapause in A. aphidimyza. We found that the diapause occurs in the cocooning larvae stage, and the highest diapause rate was recorded at under 15 °C and 10L:14D photoperiod conditions. Transcriptome sequencing analysis showed that differentially expressed genes were mainly enriched in the glucose metabolism pathway. The aphidophagous gall midge, Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae), a dominant natural enemy of aphids, has been used as a biological control agent in many countries to control aphids in greenhouses. To identify key factors that induce diapause in A. aphidimyza, we evaluated the effects of photoperiod and temperature on the incidence of diapause in A. aphidimyza under laboratory conditions. The results showed that temperature and photoperiod had significant impacts on development and diapause in A. aphidimyza. Low temperatures and a short photoperiod inhibited development, while high temperatures and a long photoperiod promoted development. Temperatures above 20 °C and a photoperiod greater than 14 h prevented diapause in A. aphidimyza. However, the highest diapause rate was recorded at under 15 °C and 10L:14D photoperiod conditions. At 15 °C, the first to third larvae were sensitive to a short photoperiod at any stage, and a short photoperiod had a cumulative effect on diapause induction. The longer the larvae received short light exposure, the higher the diapause rate appeared to be. Transcriptome sequencing analysis at different stages of diapause showed that differentially expressed genes were mainly enriched in the glucose metabolism pathway. Physiological and biochemical analyses showed that diapausing A. aphidimyza reduced water content; accumulated glycogen, trehalose, sorbitol, and triglycerides; and gradually reduced trehalose and triglyceride contents in the body with the extension of diapause time. Glycogen may be used as a source of energy, but sorbitol is usually used as a cryoprotectant. This study provided results on aspects of diapause in A. aphidimyza, providing data and theoretical support for promoting its commercial breeding and in-depth research on the molecular mechanisms underlying diapause regulation. [ABSTRACT FROM AUTHOR]

Introduction : The homeostasis of intestinal epithelial cells (IECs) is disrupted in diabetes, leading to functional changes of the gastrointestinal tract and increasing the risk of diabetic enteropathy. Methods: The aim of this study is to explore the effect of autophagy on the expression of inflammatory factors under high glucose in vitro. The effect of glucose at different concentrations (5, 10, 30 and 50 Mm) on IEC-6 cells was analyzed. Dorsomorphin (AMPK antagonist) and GSK621 (AMPK agonist) were used to examine the relationship between the autophagy and the AMPK/ULK1 signaling pathway in IEC-6 cells. Results: Our results showed that the high glucose significantly inhibited the growth of IECs, and induced more shrinkage and necrosis of cells. Autophagy was inhibited by high glucose. Furthermore, the levels of cytokines, including IL-22, INF-γ, NOS2, and TNF-α, were significantly increased, which were positively correlated with glucose concentration. Additionally, we confirmed that Dorsomorphin down-regulated the expression of p-AMPK and autophagy protein compared with GSK621. Similar, cellular immunofluorescence also detected low autophagy expression. However, GSK621 and Rapamycin increased the level of autophagy and down-regulated the secretion of pro-inflammatory factors compared with Dorsomorphin. Conclusion: Therefore, our results demonstrate that AMPK mediated autophagy may regulate levels of inflammation in IECs and improve cell survival under high glucose. [ABSTRACT FROM AUTHOR]

The Chinese citrus fruit fly, Bactrocera minax (Enderlein), is an economically important pest of citrus. The fly has an obligatory pupal diapause in soil from November to March. However, techniques for predicting or determining the emergence of the adult have, thus far, not been well documented. In this study, we investigated the effects of different pre-diapause temperatures (8, 12, 16, and 20°C) and pupal body weight (five groups according to pupal weight: G-58, 55.0–61.0 mg; G-68, 65–71 mg; G-78, 75–81 mg; G-88, 85–91 mg; G-95, 92–98 mg) on pupal period (the indicator of diapause intensity). The pupal period of B. minax larvae pupated at 8°C was 193.41 d, which was significantly shorter than that of larvae incubated at higher temperatures, suggesting that there was a lower diapause intensity for larvae pupated at lower pre-diapause temperatures. There were also significant differences in the pupal periods at different pupal body weights. The pupal period of G-58 was significantly shorter than that of the heavier groups (G-88 and G-95), and the pupal period increased with increasing pupal body weight in the five groups. Moreover, the pupal period of B. minax significantly and positively correlated to pupal body weight. These findings demonstrate that the pre-diapause temperature and pupal body weight are suitable indicators for predicting the pupal period of overwintering individuals, and the results of this study will contribute to the development of new and effective strategies for predicting the occurrence and population dynamics of B. minax adult. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, the effect of the targeted silencing of OnGCY on the reproduction of the pirate bug Orius nagaii was evaluated. OnGCY silencing significantly inhibited ovarian development and egg production and significantly reduced the expression of the gene encoding the vitellogenin (Vg) gene. These data provide insights into the function of OnGCY in insect reproduction, which could guide research for the mass rearing of natural enemies for the biological control of insect pests. This study identified and characterized the gene encoding recep tor-type guanylate cyclase-22-like (GCY-22; OnGCY) from the pirate bug Orius nagaii, an important biological control agent. The full-length cDNA of the GCY of O. nagaii was obtained by rapid amplification of cDNA ends (RACE); it had a total length of 4888 base pairs (bp), of which the open reading frame (ORF) was 3750 bp, encoding a polypeptide of 1249 amino acid residues. The physicochemical properties of OnGCY were predicted and analyzed by using relevant ExPASy software, revealing a molecular formula of C6502H10122N1698O1869S57, molecular weight of ~143,811.57 kDa, isoelectric point of 6.55, and fat index of 90.04. The resulting protein was also shown to have a signal peptide, two transmembrane regions, and a conserved tyrosine kinase (tyrkc). Silencing OnGCY by RNA interference significantly inhibited ovarian development and decreased fertility in female O. nagaii in the treated versus the control group. Additionally, OnGCY silencing significantly decreased the expression levels of other GCY and Vg genes. Thus, these results clarify the structure and biological function of OnGCY, which has an important role in insect fecundity. The results also provide a reference for agricultural pest control and future large-scale breeding of biological control agents. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of Gla‐300 versus Gla‐100 in insulin‐naïve people with type 2 diabetes in Asia Pacific. Materials and Methods: In this open‐label, randomized, active‐controlled, 26‐week study, insulin‐naïve participants with type 2 diabetes inadequately controlled with non‐insulin antihyperglycaemic drugs were randomized (2:1) to Gla‐300 or Gla‐100. The initial daily dose of basal insulin was 0.2 U/kg and was adjusted at least weekly for 8–12 weeks to a target fasting self‐monitored plasma glucose (SMPG) of 4.4–5.6 mmol/L. Results: Of the 604 participants randomized, 570 (Gla‐300, n = 375; Gla‐100, n = 195) completed the study. Non‐inferiority of Gla‐300 versus Gla‐100 in HbA1c reduction from baseline to week 26 was confirmed. In the Gla‐300 and Gla‐100 groups, 51.1% and 52.2% of participants achieved the HbA1c target of <7.0% (rate ratio [95% CI]: 0.98 [0.84 to 1.14]) and 19.1% and 21.9% achieved the target without hypoglycaemia during the last 12 weeks of treatment (rate ratio [95% CI]: 0.87 [0.63 to 1.20]). Changes in fasting plasma glucose and 24‐hour average eight‐point SMPG were comparable between groups. Incidence of hypoglycaemia at any time of day was similar between treatment groups at week 26, but incidence of any nocturnal hypoglycaemia was numerically lower with Gla‐300 than Gla‐100 over the initial 12‐week titration period and 26‐week on‐treatment period. Rates of adverse events were similar between groups and low for serious adverse events. Conclusions: Glycaemic control of Gla‐300 is non‐inferior to Gla‐100 with a similar or lower incidence and proportion of hypoglycaemia in people with type 2 diabetes in Asia Pacific, reinforcing the results in the global EDITION programme. [ABSTRACT FROM AUTHOR]

Aim: To investigate the post‐treatment effect of dorzagliatin in drug‐naïve patients with type 2 diabetes (T2D) regarding the achievement of stable glycaemic control and drug‐free diabetes remission. Materials and Methods: Patients who completed dorzagliatin treatment in the SEED trial and achieved stable glycaemic control were enrolled in this 52‐week study without any antidiabetic medication. The primary endpoint was the diabetes remission probability at week 52 using the Kaplan–Meier method. The potential factors that contribute to stable glycaemic control and diabetes remission based on the characteristics of patients before and after treatment with dorzagliatin were analysed. A post hoc sensitivity analysis of diabetes remission probability using the American Diabetes Association (ADA) definition was conducted. Results: The Kaplan–Meier remission probability was 65.2% (95% CI: 52.0%, 75.6%) at week 52. Based on the ADA definition, the remission probability was 52.0% (95% CI: 31.2%, 69.2%) at week 12. The significant improvements in the insulin secretion index ΔC30/ΔG30 (41.46 ± 77.68, P =.0238), disposition index (1.22 ± 1.65, P =.0030), and steady‐state variables of HOMA2‐β (11.49 ± 14.58, P <.0001) and HOMA2‐IR (−0.16 ± 0.36, P =.0130) during the SEED trial were important factors in achieving drug‐free remission. A significant improvement in time in range (TIR), a measure of glucose homeostasis, in the SEED trial from 60% to more than 80% (estimated treatment difference, 23.8%; 95% CI: 7.3%, 40.2%; P =.0084) was observed. Conclusions: In drug‐naïve patients with T2D, dorzagliatin treatment leads to stable glycaemic control and drug‐free diabetes remission. Improvements in β‐cell function and TIR in these patients are important contributors to diabetes remission. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters. [ABSTRACT FROM AUTHOR]

Background: Janagliflozin is a novel sodium–glucose cotransport-2 inhibitor. Despite its remarkable effect in glycemic control, no systematic research has evaluated the effect of renal impairment (RI) on its pharmacokinetics and pharmacodynamics. Methods: Here, patients with T2DM (n = 30) were divided into normal renal function (eGFR ≥ 90 mL/min/1.73 m2), mild RI (eGFR between 60 and 89 mL/min/1.73 m2), moderate RI-I (eGFR between 45 and 59 mL/min/1.73 m2), and moderate RI-II (eGFR between 30 and 44 mL/min/1.73 m2) groups. They were administered 50 mg janagliflozin orally, and plasma and urine samples were collected for the determination of janagliflozin concentration. Results: Following oral administration, janagliflozin was rapidly absorbed, with the time to Cmax of 2–6 h for janagliflozin and 3–6 h for its metabolite XZP-5185. Plasma exposure levels were similar for janagliflozin in T2DM patients with or without RI but decreased for the metabolite XZP-5185 in T2DM patients with eGFR between 45 and 89 mL/min/1.73 m2. Janagliflozin significantly promoted the excretion of urinary glucose, even in patients with reduced eGFR. Janagliflozin was well tolerated in patients with T2DM with or without RI, and no serious adverse events (SAEs) occurred during this trial. Conclusions: The exposure levels of janagliflozin in T2DM patients were slightly increased with worsening of RI (i.e., 11% increase in the AUC in patients with moderate RI compared with the normal renal function group). Despite worsening of renal function, janagliflozin exerted a significant pharmacologic effect and was well tolerated, even in patients with moderate RI, implying a promising role in the treatment of patients with in T2DM. Registration: China Drug Trial register (http://www.chinadrugtrials.org.cn/I) identifier no.: CTR20192721. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time‐in‐ranges calculated from seven‐point self‐measured blood glucose. Methods: Two phase III trials were analysed. LixiLan‐O‐AP was performed in insulin‐naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan‐L‐CN was performed in insulin‐treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time‐in‐ranges from baseline to end‐of‐treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time‐in‐range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time‐below‐the‐range [dTBR] and < 25% derived time‐above‐the‐range [dTAR]) were calculated. Results: The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1: 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD2: 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan‐O‐AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan‐L‐CN. In LixiLan‐O‐AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan‐L‐CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. Conclusion: iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin‐naïve and insulin‐experienced AP people with T2D. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD brains display deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-β (Aβ) peptides, and Aβ oligomers are likely a toxic species in AD pathology. AD patients display altered metal homeostasis, and AD plaques show elevated concentrations of metals such as Cu, Fe, and Zn. Yet, the metal chemistry in AD pathology remains unclear. Ni(II) ions are known to interact with Aβ peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods—mainly spectroscopy and imaging techniques—to characterize Aβ/Ni(II) interactions in vitro, for different Aβ variants: Aβ(1–40), Aβ(1–40)(H6A, H13A, H14A), Aβ(4–40), and Aβ(1–42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length Aβ monomers. Equimolar amounts of Ni(II) ions retard Aβ aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)·Aβ binding affinity is in the low µM range. The redox-active Ni(II) ions induce formation of dityrosine cross-links via redox chemistry, thereby creating covalent Aβ dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in Aβ monomers, while in a membrane-mimicking environment (SDS micelles) coil–coil helix interactions appear to be induced. For SDS-stabilized Aβ oligomers, Ni(II) ions direct the oligomers towards larger sizes and more diverse (heterogeneous) populations. All of these structural rearrangements may be relevant for the Aβ aggregation processes that are involved in AD brain pathology. [ABSTRACT FROM AUTHOR]

Copper (Cu2+) is a micronutrient that promotes the development and reproduction of organisms. However, with the rapid expansion of modern industry and agriculture, Cu2+ concentrations are increasing, which might have negative impacts on biological and ecological safety. Spodoptera litura is not only an intermittent outbreak pest but also can be used as a model organism to assess environmental and ecological risks. Therefore, the effects of the life history and population parameters of S. litura fed on artificial diets with different Cu2+ concentrations were analyzed using the age-stage, two-sex life table. Our results showed that not only the preadult survival rate but also the intrinsic rate of increase (r) and the finite rate of increase (λ) were significantly increased under exposure to low Cu2+ concentrations (2, 4, and 8 mg/kg). In addition, the population growth of S. litura was significantly faster, indicating that S. litura can adapt well to low concentrations and is likely to undergo outbreaks of damage. Whereas, in addition to a significant reduction in preadult survival rate, population growth rate, pupal weight, pupal length, adult body weight, and oviposition were also significantly reduced under exposure to high Cu2+ concentration (32 mg/kg). And when the concentration reached 64 mg/kg, the survival rate of adults was extremely low, suggesting a decrease in the adaptation of S. litura. These results can help to understand the population dynamics of S. litura and predict potential ecological risks. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. Materials and methods: LixiLan‐L‐CN (NCT03798080) was a 30‐week randomized, active‐controlled, open‐label, parallel‐group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. Results: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2, corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: −0.7 (95% confidence interval: −0.9, −0.6)%; p <.0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p <.0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: −0.9 (95% confidence interval: −1.4, −0.5) kg; p =.0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar. Conclusions: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long‐standing T2D advancing therapy from basal insulin. [ABSTRACT FROM AUTHOR]

Objective: To determine whether radiomics analysis of pericoronary adipose tissue (PCAT) captured by coronary computed tomography angiography (CCTA) could discriminate acute myocardial infarction (MI) from unstable angina (UA). Methods: In a single-center retrospective case-control study, patients with acute MI (n = 105) were matched to patients with UA (n = 105) and all patients were randomly divided into training and validation cohorts with a ratio of 7:3. Fat attenuation index (FAI) and PCAT radiomics features selected by Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) around the proximal three major epicardial coronary vessels (LAD [left anterior descending artery], LCx [left circumflex artery], and RCA [right coronary artery]) were used to build logistic regression models. Finally, a FAI model, three radiomics models of PCAT (LAD, LCx, and RCA), and a combined model that used the scores of these independent models were constructed. The performance of the models was evaluated by identification, calibration, and clinical application. Results: In training and validation cohorts, compared with the FAI model (AUC = 0.53, 0.50), the combined model achieved superior performance (AUC = 0.97, 0.95) while there was a significant difference of AUC between two models (p < 0.05). The calibration curves of the combined model demonstrated the smallest Brier score loss. Decision curve analysis suggested that the combined model provided higher clinical benefit than the FAI model. Conclusions: The CCTA–based radiomics phenotype of PCAT outperforms the FAI model in discriminating acute MI from UA. The combination of PCAT radiomics and FAI could further enhance the performance of acute MI identification. Key Points: • Fat attenuation index based on CCTA can detect inflammation-induced changes in the ratio of lipid to aqueous phase in pericoronary adipose tissue. • Fat attenuation index cannot distinguish acute MI patients from UA patients, suggesting that the two groups have the same degree of ratio of lipid to aqueous phase in pericoronary adipose tissue. • Radiomics features of PCAT have the potential to distinguish acute MI patients from UA patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The tobacco cutworm, Spodoptera litura (F.), exemplifies strong reproductive capacities and damages many agricultural crops. The insulin signaling pathway is known as a key determinant of female reproduction in insects. However, the detailed molecular mechanisms in these processes are poorly studied. Here, we injected bovine insulin into the newly emerged moth, resulting in gene expression changes in the insulin pathway, while knockdown of SlInR caused an inverse gene expression change involved in the insulin pathway. Further studies indicated that the content of JH-III, Vg, total proteins and triacylgycerol could be suppressed by SlInR dsRNA injection. Furthermore, stunted ovaries and lower fecundity were observed by RNAi. Our studies indicated that SlInR plays a key role in JH-III synthesis and the ovarian development in S. litura. Insulin signaling can regulate various physiological functions, such as energy metabolism and reproduction and so on, in many insects, including mosquito and locust. However, the molecular mechanism of this physiological process remains elusive. The tobacco cutworm, Spodoptera litura, is one of the most important pests of agricultural crops around the world. In this study, phosphoinositide 3-kinase (SlPI3K), protein kinase B (SlAKT), target of rapamycin (SlTOR), ribosomal protein S6 kinase (SlS6K) and transcription factor cAMP-response element binding protein (SlCREB) genes, except transcription factor forkhead box class O (SlFoxO), can be activated by bovine insulin injection. Then, we studied the influence of the insulin receptor gene (SlInR) on the reproduction of S. litura using RNA interference technology. qRT-PCR analysis revealed that SlInR was most abundant in the head. The SlPI3K, SlAKT, SlTOR, SlS6K and SlCREB genes were decreased, except SlFoxO, after the SlInR gene knockdown. Further studies revealed that the expression of vitellogenin mRNA and protein, Methoprene-tolerant gene (SlMet), could be down-regulated by the injection of dsRNA of SlInR significantly. Furthermore, a depletion in the insulin receptor by RNAi significantly decreased the content of juvenile hormone III (JH-III), total proteins and triacylgycerol. These changes indicated that a lack of SlInR could impair ovarian development and decrease fecundity in S. litura. Our studies contribute to a comprehensive insight into reproduction, regulated by insulin and the juvenile hormone signaling pathway through nutrition, and a provide theoretical basis for the reproduction process in pest insects. [ABSTRACT FROM AUTHOR]

A reasonable assessment of microgrid power quality (MGPQ) is essential for ensuring the safe and stable operation of the system. However, due to the complex and variable operating conditions of microgrid (MG), the results of power quality (PQ) assessments are often discrete. Therefore, further research is needed to determine how to accurately estimate the overall PQ of a MG based on these discrete evaluation results. To address this issue, a model for evaluating MGPQ based on confidence estimation using Chebyshev inequality is proposed in this paper. Firstly, Chebyshev inequality is utilized to describe the discreteness of PQ evaluation results in MG. Secondly, the multi-scale adaptive phase number selection CRITIC method and probabilistic statistics method are employed to evaluate the PQ index of the MG under multiple working conditions. Furthermore, sample standard deviation (SD) is used to quantify the dispersion of evaluation results, and a 90% confidence level is used to estimate the confidence interval of multiple evaluation results. Finally, the example presented in this paper demonstrates that at least 90% probability exists for an evaluation result to fall within ±3.16 SDs from its mean. Compared with traditional methods, this paper comprehensively reflects the overall PQ status of MG from three aspects by considering index data characteristics, different time scales, and confidence intervals—providing clear and practical guidance for MG users and managers to ensure safe and stable operation of the MG. [ABSTRACT FROM AUTHOR]

Purpose. To retrospectively evaluate the efficacy and safety of TACE combined with microwave ablation (MWA) and TACE combined with cryoablation (CRA) in the treatment of large hepatocellular carcinoma. Methods. A retrospective analysis was performed on 81 patients with large hepatocellular carcinoma (tumor diameter 5～8 cm cm) who received TACE combined with ablation in our hospital from February 2015 to February 2019. The study patients were divided into TACE combined with MWA group (T-MWA, n = 41) and TACE combined with CRA group (T-CRA, n = 40) according to the treatment plan. Overall survival (OS) and progress free survival (PFS) were compared between the two groups, and complications were observed. Survival curves for OS and PFS were constructed by the Kaplan–Meier method. Differences in overall survival were compared using the log-rank test. Results. There was no statistical difference in general conditions between the two groups of patients. The results showed that 30 (73.2%) patients in T-MWA group achieved objective response (OR) and 39 (95.1%) patients achieved disease control (DC), compared with 24 (60.0%) patients in T-CRA group who achieved objective response (OR) and 37 (92.5%) patients who achieved disease control (DC). The median OS was 19.2 months in the T-MWA group and 18.6 months in the T-CRA group (P = 0.64). The median PFS was 9.3 months in the T-MWA group and 12.3 months in the T-CRA group (P = 0.6). Univariate and multivariate analysis showed that portal vein tumor thrombus (PVTT), intrahepatic tumor diameter, and the number of tumor lesions were common prognostic factors for OS and PFS. In terms of surgery-related complications and adverse reactions, abdominal pain and gastrointestinal reactions were observed in 13 (31.7%) and 11(26.8%) cases in the T-MWA group, while we observed 4 (10.0%) and 2 (5.0%) cases in the T-CRA group, respectively. The difference between the two was statistically significant (P < 0.05). Conclusion. TACE combined with MWA and TACE combined with CRA were equally effective in the treatment of large hepatocellular carcinoma. TACE-CRA can effectively reduce the incidence of abdominal pain and gastrointestinal reactions in patients. However, compared with TACE-MWA, TACE-CRA is more likely to cause thrombocytopenia. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (degludec) in Chinese people with type 2 diabetes (T2D) treated with basal insulin. Materials and Methods: In DUAL II China, a randomized, double‐blinded, multicentre, treat‐to‐target trial, Chinese adults with T2D and HbA1c of 7.5% or more on basal insulin and metformin, with or without other oral antidiabetic drugs (OADs), were randomized 2:1 to 26 weeks of treatment with either IDegLira (max. dose 50 U degludec/1.8 mg liraglutide) or degludec (max. 50 U/day), respectively, combined with metformin. At 26 weeks, superiority of IDegLira over degludec was assessed for change in HbA1c (primary endpoint), and body weight and number of severe or blood glucose (BG)‐confirmed hypoglycaemic episodes (confirmatory secondary endpoints). Results: Overall, 453 participants were randomized to IDegLira (n = 302) or degludec (n = 151). Superiority was confirmed for IDegLira over degludec in HbA1c change (−1.9% vs. −1.0%, respectively, estimated treatment difference [ETD] [95% confidence interval]: −0.92% [−1.09; −0.75], P <.0001), body weight change (−0.7 vs. +0.4 kg, respectively, ETD [95% CI]: −1.08 kg [−1.63; −0.52], P =.0002) and severe or BG‐confirmed hypoglycaemia (estimated rate ratio [95% CI]: 0.53 [0.30; 0.94], P =.0297). The odds of achieving HbA1c less than 7.0% without hypoglycaemia and/or weight gain were greater with IDegLira than degludec (P <.0001 for all). Daily insulin dose at 26 weeks was lower for IDegLira (34.3 U) than degludec (37.4 U) (P =.0014). No unexpected safety signals were observed. Conclusions: IDegLira may be an efficacious and well‐tolerated treatment intensification option for Chinese people with T2D uncontrolled on basal insulin and OADs. [ABSTRACT FROM AUTHOR]

Background: Destruxins (dtxs) are the mycotoxin produced by certain entomopathogenic fungi, such as Metarhizium anisopliae, Aschersonia sp, Alternaria brassicae and Ophiosphaerella herpotrichae. It can affect a wide variety of biological processes in insects, including innate immune, Ca2+ channel in cells, and apoptosis in a dose-dependent manner. Dtxs have been used as biological control agent for a long time, however, their molecular mechanism of action is still unknown. Principal Findings: In this study, both digital gene expression (DGE) and two-dimensional electrophoresis (2-DE) approaches were adopted to examine the effects of dtx A on Plutella xyllostella (L.) larvae. By using DGE and 2-DE analyses, 1584 genes and 42 protein points were identified as being up- or down regulated at least 2-fold in response to dtx A. Firstly, injection of dtx A to larvae accelerated the increase of peptidoglycan recognition protein (PGRP), which could activate the Toll signal pathway inducing production of antibacterial substances such as cecropin and gloverin. Dtx A also stimulated prophenoloxidase (proPO) system which plays an important role in innate immunity and leads to melanization of external organisms. Secondly, dtx A suppressed the expression of genes related to the Toll pathway, and induced expression of serine proteinase inhibitors (serpins), especially the serpin 2 that blocked process of the proPO system. Finally, other physiological process like xenobiotics detoxification, apoptosis, calcium signaling pathway and insect hormone biosynthesis, were also mediated in response to dtx A toxicity. Conclusions: Transcript and protein profiling analyses will provide an insight into the potential molecular mechanism of action in P. xylostella larvae in response to dtx A. [ABSTRACT FROM AUTHOR]

The Inside front cover image is based on the Original Article I Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study i by Jiao'e Zeng MD et al., https://doi.org/10.1111/dom.15179. [Extracted from the article]

The characteristic of an ideal bacteria-detection method should have high sensitivity and specificity, be easy to operate, and not have a time-consuming culture process. In this study, we report a new bacteria-detection strategy that can recognize bacteria quickly and directly by surface-enhanced Raman scattering (SERS) with the formation of well-defined bacteria-aptamer@AgNPs. SERS signals generated by bacteria-aptamer@AgNPs exhibited a linear dependence on bacteria (R2 = 0.9671) concentration ranging from 101 to 107 cfu/mL. The detection limit is sensitive down to 1.5 cfu/mL. Meanwhile, the bacteria SERS signal was dramatically enhanced by its specifically recognized aptamer, and the bacteria could be identified directly and visually through the SERS spectrum. This strategy eliminates the puzzling data analysis of previous studies and offers significant advantages over existing approaches, getting a critical step toward the creation of SERS-based biochips for rapid in situ bacteria detection in mixture samples. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to develop a plasmid-based lux bio-reporter for use to obtain in vivo images of Brucella suis vaccine strain 2 (B.suis S2) infection with high resolution and good definition.Procedures: The pBBR-lux (pBBR1MCS-2-lxCDABE) plasmid that carries the luxCDABE operon was introduced into B. suis S2 by electroporation yielding B. suis S2-lux. The spatial and temporal transit of B. suis S2 in mice and guinea pigs was monitored by bioluminescence imaging.Results: The plasmid pBBR-lux is stable in vivo and does not appear to impact the virulence or growth of bacteria. This sensitive luciferase reporter could represent B. suis S2 survival in real time. B. suis S2 mainly colonized the lungs, liver, spleen, and uterus in mice and guinea pigs as demonstrated by bioluminescence imaging.Conclusion: The plasmid-based lux bioreporter strategy can be used to obtain high resolution in vivo images of B. suis S2 infection in mice and guinea pigs. [ABSTRACT FROM AUTHOR]

Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens , has been found to exhibit various anti-tumor effects. In this work, to investigate its pharmacological effects on human colorectal carcinoma HCT-116 and LoVo cells, cell proliferation and apoptosis were respectively evaluated by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, annexin V-FITC, and propidium iodide (PI) staining. Western blotting was used to detect the expression levels of Bim, Bax, Bcl-2, cytosolic cytochrome c , procaspase-9, cleaved caspase-9, procaspase-3, and caspase-3 proteins. Caspase-Glo-9 and Caspase-Glo-3 assays were applied to determine caspase-9 and caspase-3 activity. MicroRNA-32 (miR-32) expression level was detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The in vivo anti-tumor effects of oridonin were evaluated using cell lines HCT-116 and LoVo xenograft model. The results indicated that oridonin effectively inhibited cell proliferation and induced apoptosis in HCT-116 and LoVo cells in a concentration-dependent manner. Oridonin treatment upregulated the expression levels of Bim, Bax, cytosolic cytochrome c , cleaved caspase-9 and cleaved caspase-3 proteins, downregulated the expression levels of Bcl-2, procaspase-9 and procaspase-3 proteins, and meanwhile obviously activated caspase-9 and caspase-3 in a dose-dependent manner in HCT-116 and LoVo cells. The results of qRT-PCR demonstrated that oridonin treatment significantly decreased miR-32 expression, and furthermore, suppression of miR-32 expression by miR-32 inhibitors augmented oridonin-mediated inhibitory and apoptotic effects in HCT-116 and LoVo cells. In vivo results indicated that oridonin administration through intraperitoneal injection suppressed tumor growth in nude mice. Therefore, these findings suggest that oridonin maybe is a potential candidate for colorectal cancer treatment. [ABSTRACT FROM AUTHOR]

Rhodojaponin-III is a nonvolatile botanical grayanoid diterpene compound, which has antifeedant and oviposition deterrence effects against many kinds of insects. However, the molecular mechanism of the chemoreception process remains unknown. In this study, the important role of BdorCSP2 in the recognition of Rhodojaponin-III was identified. The full length cDNA encoding BdorCSP2 was cloned from legs of Bactrocera dorsalis. The results of expression pattern revealed that BdorCSP2 was abundantly expressed in the legs of adult B. dorsalis. Moreover, the expression of BdorCSP2 could be up-regulated by Rhodojaponin-III. In order to gain comprehensive understanding of the recognition process, the binding affinity between BdorCSP2 and Rhodojaponin-III was measured by fluorescence binding assay. Silencing the expression of BdorCSP2 through the ingestion of dsRNA could weaken the effect of oviposition deterrence and antifeedant of Rhodojaponin-III. These results suggested that BdorCSP2 of B. dorsalis could be involved in chemoreception of Rhodojaponin-III and played a critical role in antifeedant and oviposition behaviors induced by Rhodojaponin-III. [ABSTRACT FROM AUTHOR]

Background: The diamondback moth Plutella xyllostella has developed a high level of resistance to the latest insecticide chlorantraniliprole. A better understanding of P. xylostella’s resistance mechanism to chlorantraniliprole is needed to develop effective approaches for insecticide resistance management. Principal Findings: To provide a comprehensive insight into the resistance mechanisms of P. xylostella to chlorantraniliprole, transcriptome assembly and tag-based digital gene expression (DGE) system were performed using Illumina HiSeq™ 2000. The transcriptome analysis of the susceptible strain (SS) provided 45,231 unigenes (with the size ranging from 200 bp to 13,799 bp), which would be efficient for analyzing the differences in different chlorantraniliprole-resistant P. xylostella stains. DGE analysis indicated that a total of 1215 genes (189 up-regulated and 1026 down-regulated) were gradient differentially expressed among the susceptible strain (SS) and different chlorantraniliprole-resistant P. xylostella strains, including low-level resistance (GXA), moderate resistance (LZA) and high resistance strains (HZA). A detailed analysis of gradient differentially expressed genes elucidated the existence of a phase-dependent divergence of biological investment at the molecular level. The genes related to insecticide resistance, such as P450, GST, the ryanodine receptor, and connectin, had different expression profiles in the different chlorantraniliprole-resistant DGE libraries, suggesting that the genes related to insecticide resistance are involved in P. xylostella resistance development against chlorantraniliprole. To confirm the results from the DGE, the expressional profiles of 4 genes related to insecticide resistance were further validated by qRT-PCR analysis. Conclusions: The obtained transcriptome information provides large gene resources available for further studying the resistance development of P. xylostella to pesticides. The DGE data provide comprehensive insights into the gene expression profiles of the different chlorantraniliprole-resistant stains. These genes are specifically related to insecticide resistance, with different expressional profiles facilitating the study of the role of each gene in chlorantraniliprole resistance development. [ABSTRACT FROM AUTHOR]

Deregulated reactive oxygen species (ROS) production can lead to the disruption of structural and functional integrity of cells as a consequence of reactive interaction between ROS and various biological components. Catalase (CAT) is a common enzyme existing in nearly all organisms exposed to oxygen, which decomposes harmful hydrogen peroxide, into water and oxygen. In this study, the full length sequence that encodes CAT-like protein from Spodoptera litura named siltCAT (GenBank accession number: JQ_663444) was cloned and characterized. Amino acid sequence alignment showed siltCAT shared relatively high conservation with other insect, especially the conserved residues which defined heme and NADPH orientation. Expression pattern analysis showed that siltCAT mRNA was mainly expressed in the fat body, midgut, cuticle and malpighian tube, and as well as over last instar larvae, pupa and adult stages. RNA interference was used to silence CAT gene in SL-1 cells and the fourth-instar stage of S. litura larvae respectively. Our results provided evidence that CAT knockdown induced ROS generation, cell cycle arrest and apoptosis in SL-1 cells. It also confirmed the decrease in survival rate because of increased ROS production in experimental groups injected with double-stranded RNA of CAT (dsCAT). This study implied that ROS scavenging by CAT is important for S. litura survival. [ABSTRACT FROM AUTHOR]

Abstract: Hybrid fiber amplifier chains employing polarization-maintaining (PM)/non-polarization-maintaining (non-PM) Yb-doped fibers (YDF) were proposed and the polarization extinction ratio (PER) degradation in the amplifier chains was studied experimentally. It was found that the PER increased if the PM YDF was pumped, while the PER decreased gradually if the non-PM YDF was pumped. In addition, it was shown that the hybrid high power fiber amplifier was also coherently combinable experimentally, and it was found that the contrast of pattern captured while using the PM/non-PM hybrid amplifier chains just decreased by 17% compared with only using PM amplifier, which confirmed the feasibility and potential application of the hybrid fiber amplifier chains in the coherent beam combination (CBC) of fiber lasers. [Copyright &y& Elsevier]

Abstract: Seeding high power fiber amplifier employing multi-tone fiber laser is an effective approach to suppress stimulated Brillouin scattering (SBS). In this paper, a two-stage 1064nm high power fiber amplification system was set up. Single-, two- and three-tone fiber lasers were employed. SBS threshold powers and maximum output powers of the multi-tone cases are enhanced compared with the single-tone case. The multi-tone amplifiers also show comparable optical-to-optical efficiency to the single-tone amplifier. To demonstrate and validate coherence property of the two multi-tone fiber amplifiers, the output laser beams of the amplifiers were self-interfered in our self-made coherent beam combining system. The laser beams of the multi-tone cases showed good coherence property comparable to the single-tone case, which implied that the high power output laser light of the multi-tone fiber amplifiers could be used for coherent beam combining. [Copyright &y& Elsevier]

Simple Summary: Worldwide, pest control involves extensive use of insecticides, which results in serious environmental pollution problems. On the other hand, insecticides can be recognized by proteins named CSPs in insects, which allow them to accurately respond to these environmental chemical signals for their survival, but the mechanism is poorly studied. Here, we report the crystal structure of the CSP8 protein from the tobacco cutworm Spodoptera litura, a major plant pest in Asia. We also studied its binding properties to compounds like rhodojaponin III, a non-volatile plant metabolite. Our studies showed that the protein binds to these molecules with different affinities and provided important insight into the molecular recognition mechanism of the sensory protein SlCSP8 and the CSP protein family in general. Spodoptera litura F. is a generalist herbivore and one of the most important economic pests feeding on about 300 host plants in many Asian countries. Specific insect behaviors can be stimulated after recognizing chemicals in the external environment through conserved chemosensory proteins (CSPs) in chemoreceptive organs, which are critical components of the olfactory systems. To explore its structural basis for ligand-recognizing capability, we solved the 2.3 Å crystal structure of the apoprotein of S. litura CSP8 (SlCSP8). The SlCSP8 protein displays a conserved spherical shape with a negatively charged surface. Our binding assays showed that SlCSP8 bound several candidate ligands with differential affinities, with rhodojaponin III being the most tightly bound ligand. Our crystallographic and biochemical studies provide important insight into the molecular recognition mechanism of the sensory protein SlCSP8 and the CSP family in general, and they suggest that CSP8 is critical for insects to identify rhodojaponin III, which may aid in the CSP-based rational drug design in the future. [ABSTRACT FROM AUTHOR]