Genome-wide analysis of gustatory receptor genes and identification of the fructose gustatory receptor in Arma chinensis.

Gustatory receptors (GRs) allow insects to sense tastes in their external environment. Gustatory perception is crucial for distinguishing between beneficial and harmful or toxic compounds, affecting survival. This study is the first to identify and classify the GR genes and investigate their expression in the predatory Arma chinensis. Thirteen GR genes (ArmaGr1-ArmaGr13) were identified and classified into four families via phylogenetic analysis. In the predacious developmental stages, ArmaGr7 expression gradually increased from the 2nd to 5th instar stages and then to adults. However, ArmaGr7 was also highly expressed in the non-predation 1st instar nymph and egg stages. ArmaGr7 expression was localized in the antennae, scalpella, forelegs, wings, head, and midgut of male and female adults, with wings displaying the highest expression. Furthermore, ArmaGr7 expression was positively correlated with fructose solution intake; molecular docking results showed that fructose could effectively dock withArmaGr7. A protein structure comparison revealed that the ArmaGr7 structure was different from that of other GR43a-like proteins, which may be related to the gene splicing of the A. chinensis GR gene. These results elucidate the crucial role of ArmaGr7 in fructose recognition by A. chinensis and provide a foundation for further studies on gustatory perception.

Molecular Correlates of Diapause in Aphidoletes aphidimyza.

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.

Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.

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.

Effect of Guanylate Cyclase-22-like on Ovarian Development of Orius nagaii (Hemiptera: Anthocoridae).

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.

Venous blood parameters in determination of respiratory impairment in amyotrophic lateral sclerosis.

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.

miR-153-3p suppresses the differentiation and proliferation of neural stem cells via targeting GPR55.

Alzheimer's disease is the most frequent neurodegenerative disease and is characterized by progressive cognitive impairment and decline. NSCs (neural stem cells) serve as beneficial and promising adjuncts to treat Alzheimer's disease. This study aimed to determine the role of miR-153-3p expression in NSC differentiation and proliferation. We illustrated that miR-153-3p was decreased and GPR55 was upregulated during NSC differentiation. IL-1ß can induce miR-153-3p expression. Luciferase reporter analysis noted that elevated expression of miR-153-3p significantly inhibited the luciferase value of the WT reporter plasmid but did not change the luciferase value of the mut reporter plasmid. Ectopic miR-153-3p expression suppressed GPR55 expression in NSCs and identified GPR55 as a direct target gene of miR-153-3p. Ectopic expression of miR-153-3p inhibited NSC growth and differentiation into astrocytes and neurons. Elevated expression of miR-153-3p induced the release of proinflammatory cytokines, such as TNF-α, IL-1ß and IL-6, in NSCs. Furthermore, miR-153-3p inhibited NSC differentiation and proliferation by targeting GPR55 expression. These data suggested that miR-153-3p may act as a clinical target for the therapeutics of neurodegenerative diseases.

Model development and validation of noninvasive parameters based on coronary computed tomography angiography to predict culprit lesions in acute coronary syndromes within 3 years: value of plaque characteristics, hemodynamics and pericoronary adipose tissue.

Background: Machine learning (ML) is combined with noninvasive parameters from coronary computed tomography angiography (CTA) to construct predictive models to identify culprit lesions that may lead to acute coronary syndrome (ACS). Methods: We retrospectively analyzed 132 patients with ACS at the Fourth Affiliated Hospital of Harbin Medical University who had coronary CTA between 3 months and 3 years before the ACS event, with a total of 240 lesions. Lesions from 2020 (n=154) were included in the training set, and lesions from 2021 (n=86) were included in the test set for internal validation. We evaluated the role of plaque characteristics, hemodynamic parameters and pericoronary adipose tissue (PCAT) attenuation from CTA in identifying culprit ACS lesions. In the training set, logistic regression was used to screen CTA-derived parameters with P values <0.05 for the model construction. Logistic regression, random forest, Bayesian and K-nearest neighbor algorithms were used to build classification models, and their performance was assessed using the test set. The following models were established to evaluate the effectiveness of different combinations of models to identify culprit lesions: Model 1 was established for plaque characteristics; Model 2 was established for hemodynamic parameters; Model 3 was established for PCAT attenuation; Model 4 was established for plaque characteristics and hemodynamic parameters; and Model 5 was established for plaque characteristics, hemodynamic parameters and PCAT attenuation. Results: A total of ten high-risk factors were screened for the ML model construction, and the ML model based on the logistic regression algorithm had the best performance among the four algorithms (accuracy =0.721; sensitivity =0.892; specificity =0.592; positive prediction =0.623; and negative prediction =0.879). In this model, the minimum lumen area, positive remodeling and lesion-specific fat attenuation index (FAI) were the risk factors significantly associated with the culprit lesion. Analysis of the effect of different combinations of models to identify culprit lesions showed that Model 5 had the best predictive effect (AUC =0.819 and 95% CI: 0.722-0.916). Conclusions: ACS can be predicted using ML based on CTA parameters. Compared to other models, the model combining plaque characteristics, hemodynamic parameters and PCAT attenuation performed best in predicting the culprit lesion.

Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study.

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-ß (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 ß-cell function and TIR in these patients are important contributors to diabetes remission.

Identification of patients with acute coronary syndrome and representation of their degree of inflammation: application of pericoronary adipose tissue within different radial distances of the proximal coronary arteries.

Background: Pericoronary adipose tissue (PCAT) around the proximal right coronary artery (RCA) is considered a marker of coronary inflammation. We aimed to explore the segments of PCAT that represent coronary inflammation in patients with acute coronary syndrome (ACS) and to identify patients with ACS and stable coronary artery disease (CAD) prior to intervention. Methods: We retrospectively enrolled consecutive patients with ACS and stable CAD who underwent invasive coronary angiography (ICA) after coronary computed tomography angiography (CCTA) from November 2020 to October 2021 at the Fourth Affiliated Hospital of Harbin Medical University. The fat attenuation index (FAI) was obtained using PCAT quantitative measurement software, and the coronary Gensini score was also calculated to indicate the severity of CAD. The differences and correlations between FAI within different radial distances of proximal coronary arteries were evaluated, and the recognition ability of FAI for patients with ACS and stable CAD was evaluated by establishing receiver operator characteristic (ROC) curves. Results: A total of 267 patients were included in the cross-sectional study, including 173 patients with ACS. With the increase of radial distance from the outer wall of proximal coronary vessels, the FAI decreased (P<0.001). The FAI around the proximal left anterior descending artery (LAD) within the reference diameter from the outer wall of the vessel (LADref) had the highest correlation with the FAI around culprit lesions [r=0.587; 95% confidence interval (CI): 0.489-0.671; P<0.001]. The model based on clinical features, Gensini score, and LADref had the highest recognition performance for patients with ACS and stable CAD [area under the curve (AUC): 0.663; 95% CI: 0.540-0.785]. Conclusions: LADref is most correlated with FAI around culprit lesions in patients with ACS and has higher value in the preintervention differentiation of patients with ACS and stable CAD compared to the use of clinical features alone.

Pharmacokinetics, Pharmacodynamics and Safety of Janagliflozin in Chinese Type 2 Diabetes Mellitus Patients with Renal Impairment.

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.

Prion Protein Octarepeat Domain Forms Transient ß-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions.

Misfolding of the cellular prion protein (PrPC) is associated with the development of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Metal ions appear to play a crucial role in PrPC misfolding. PrPC is a combined Cu(II) and Zn(II) metal-binding protein, where the main metal-binding site is located in the octarepeat (OR) region. Thus, the biological function of PrPC may involve the transport of divalent metal ions across membranes or buffering concentrations of divalent metal ions in the synaptic cleft. Recent studies have shown that an excess of Cu(II) ions can result in PrPC instability, oligomerization, and/or neuroinflammation. Here, we have used biophysical methods to characterize Cu(II) and Zn(II) binding to the isolated OR region of PrPC. Circular dichroism (CD) spectroscopy data suggest that the OR domain binds up to four Cu(II) ions or two Zn(II) ions. Binding of the first metal ion results in a structural transition from the polyproline II helix to the ß-turn structure, while the binding of additional metal ions induces the formation of ß-sheet structures. Fluorescence spectroscopy data indicate that the OR region can bind both Cu(II) and Zn(II) ions at neutral pH, but under acidic conditions, it binds only Cu(II) ions. Molecular dynamics simulations suggest that binding of either metal ion to the OR region results in the formation of ß-hairpin structures. As the formation of ß-sheet structures can be a first step toward amyloid formation, we propose that high concentrations of either Cu(II) or Zn(II) ions may have a pro-amyloid effect in TSE diseases.

iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis.

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.

Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aß) peptides.

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-ß (Aß) peptides, and Aß 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 Aß peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods-mainly spectroscopy and imaging techniques-to characterize Aß/Ni(II) interactions in vitro, for different Aß variants: Aß(1-40), Aß(1-40)(H6A, H13A, H14A), Aß(4-40), and Aß(1-42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length Aß monomers. Equimolar amounts of Ni(II) ions retard Aß aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)·Aß 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 Aß dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in Aß monomers, while in a membrane-mimicking environment (SDS micelles) coil-coil helix interactions appear to be induced. For SDS-stabilized Aß 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 Aß aggregation processes that are involved in AD brain pathology.

Identification of immune signatures in Parkinson's disease based on co-expression networks.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and there is less research on the relationship between immunity and PD. In this study, the protein-protein interaction networks (PPI) data, 2747 human immune-related genes (HIRGs), 2078 PD-related genes (PDRGs), and PD-related datasets (GSE49036 and GSE20292) were downloaded from the Human Protein Reference Database (HPRD), Amigo 2, DisGeNET, and Gene Expression Omnibus (GEO) databases, respectively. An immune- or PD-directed neighbor co-expressed network construction (IOPDNC) was drawn based on the GSE49036 dataset and HPRD database. Furthermore, a PD-directed neighbor co-expressed network was constructed. Modular clustering analysis was performed on the genes of the gene interaction network obtained in the first step to obtain the central core genes using the GraphWeb online website. The modules with the top 5 functional scores and the number of core genes greater than six were selected as PD-related gene modules. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of different module genes were performed. The single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to calculate the immune cell infiltration of the PD and the normal samples. The quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was performed to investigate the expression of module genes. An IOPDNC and PD-directed neighbor co-expressed network (PDNC network) were constructed. Furthermore, a total of 5 immune-PD modules were identified which could distinguish between PD and normal samples, and these module genes were strongly related to PD in protein interaction level or gene expression level. In addition, functional analysis indicated that module genes were involved in various neurodegenerative diseases, such as Alzheimer disease, Huntington disease, Parkinson disease, and Long-term depression. In addition, the genes of the 6 modules were significantly associated with these 4 differential immune cells (aDC cells, eosinophils, neutrophils, and Th2 cells). Finally, the result of qRT-PCR manifested that the expression of 6 module genes was significantly higher in normal samples than in PD samples. In our study, the immune-related genes were found to be strongly related to PD and might play key roles in PD.

Diagnosis of coronary artery disease in patients with type 2 diabetes mellitus based on computed tomography and pericoronary adipose tissue radiomics: a retrospective cross-sectional study.

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.

Evaluating the Effects of Cu2+ on the Development and Reproduction of Spodoptera litura (Lepidoptera: Noctuidae) Based on the Age-Stage, Two-Sex Life Table.

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.

Effect of Insulin Receptor on Juvenile Hormone Signal and Fecundity in Spodoptera litura (F.).

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.

Comparison of Efficacy and Safety of TACE Combined with Microwave Ablation and TACE Combined with Cryoablation in the Treatment of Large Hepatocellular Carcinoma.

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.

Inhibition of miR-421 Preserves Mitochondrial Function and Protects against Parkinson's Disease Pathogenesis via Pink1/Parkin-Dependent Mitophagy.

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.

Effect of 320-row CT reconstruction technology on fractional flow reserve derived from coronary CT angiography based on machine learning: single- versus multiple-cardiac periodic images.

Background: Fractional flow reserve derived from computed tomography (CT-FFR) can be used to noninvasively evaluate the functions of coronary arteries and has been widely welcomed in the field of cardiovascular research. However, whether different image reconstruction schemes have an effect on CT-FFR analysis through single- and multiple-cardiac periodic images in the same patient has not been investigated. Methods: This study retrospectively enrolled 122 patients who underwent 320-row computed tomography (CT) examination with both single- and multiple-cardiac periodic reconstruction schemes; a total of 366 coronary arteries were analyzed. The lowest CT-FFR values of each vessel and the poststenosis CT-FFR values of the lesion-specific coronary artery were measured using the two reconstruction techniques. The Wilcoxon signed-rank test was used to compare differences in CT-FFR values between the two reconstruction techniques. Spearman correlation analysis was performed to determine the relationship between CT-FFR values derived using the two methods. Bland-Altman and intraclass correlation coefficient (ICC) analyses were performed to evaluate the consistency of CT-FFR values. Results: In all blood vessels, the lowest CT-FFR values showed no significant differences between the two reconstruction techniques in the left anterior descending artery (LAD; P=0.65), left circumflex artery (LCx; P=0.46), or right coronary artery (RCA; P=0.22). In blood vessels with atherosclerotic plaques, the poststenosis CT-FFR values (2 cm distal to the maximum stenosis) exhibited no significant differences between the two reconstruction techniques in the LAD (P=0.78), LCx (P=1.00), or RCA (P=1.00). The mean CT-FFR values of single- and multiple-cardiac periodic images showed excellent correlation and minimal bias in all groups. Conclusions: CT-FFR analysis based on an artificial intelligence deep learning neural network is stable and not affected by the type of 320-row CT reconstruction technology.