Long noncoding RNA lncPostn links TGF-ß and p53 signaling pathways to transcriptional regulation of cardiac fibrosis.

Cardiac fibroblasts are essential for the homeostasis of the extracellular matrix, whose remodeling in many cardiovascular diseases leads to fibrosis. Long noncoding RNAs (lncRNAs) are associated with cardiac pathologies, but their functions in cardiac fibroblasts and contributions to cardiac fibrosis remain unclear. Here, we aimed to identify fibroblast-enriched lncRNAs essential in myocardial infarction (MI)-induced fibrosis and explore the molecular mechanisms responsible for their functions. Global lncRNA profiling was performed in post-MI mouse heart ventricles and transforming growth factor-ß (TGF-ß)-treated primary cardiac fibroblasts and confirmed in published data sets. We identified the cardiac fibroblast-enriched lncPostn, whose expression is stimulated in cardiac fibrosis induced by MI and the extracellular growth factor TGF-ß. The promoter of lncPostn contains a functional TGF-ß response element, and lncPostn knockdown suppresses TGF-ß-stimulated cardiac fibroblast activation and improves cardiac functions post-MI. LncPostn stabilizes and recruits EP300 to the profibrotic periostin's promoter, representing a major mechanism for its transcriptional activation. Moreover, both MI and TGF-ß enhance lncPostn expression while suppressing the cellular growth gatekeeper p53. TGF-ß and p53 knockdown-induced profibrotic gene expression and fibrosis occur mainly through lncPostn and show additive effects. Finally, levels of serum lncPostn are significantly increased in patients' postacute MI and show a strong correlation with fibrosis markers, revealing a potential biomarker of cardiac fibrosis. Our findings identify the fibroblast-enriched lncPostn as a potent profibrotic factor, providing a transcriptional link between TGF-ß and p53 signaling pathways to regulate fibrosis in cardiac fibroblasts.NEW & NOTEWORTHY Cardiac fibroblasts are essential for the homeostasis of the extracellular matrix, whose remodeling in many cardiovascular diseases leads to fibrosis. Long noncoding RNAs are functional and contribute to the biological processes of cardiovascular development and disorders. Our findings identify the fibroblast-enriched lncPostn as a potent profibrotic factor and demonstrate that serum lncPostn level may serve as a potential biomarker of human cardiac fibrosis postacute myocardial infarction.

Enhanced Corrosion Inhibition of Q235 Steel by N,S Co-Doped Carbon Dots: A Sustainable Approach for Industrial Pickling Corrosion Inhibitors.

A high yield of environmentally friendly N,S-codoped (N,S-CDs) and N-doping carbon points (N-CDs) carbon dots was achieved through a biochemical oxidation reaction at room temperature in this study. Acetaldehyde, sodium hydroxide, benzotriazole (BTA), and 2-mercaptobenzimidazole (MB) with a similar structure were used as raw materials. The microstructure and properties of the corrosion inhibitor for Q235 steel were evaluated by various experiments. The results demonstrated enhanced corrosion inhibition rates of the N,S-CDs compared to the N-CDs using electrochemical tests (93.83% vs 77.65%) and weight loss experiments (96.35% vs 91.65%) at 50 mg/L, respectively, compared to the blank material, indicating that N,S codoping can significantly improve the corrosion inhibition effect of carbon dots. The significant improvements were attributed to the formation of dense adsorption films and the hydrophobic properties of N and S-CDs nanoparticles on the steel surface, leading to an effective barrier against corrosion. The findings from this study provide important experimental data for potential industrial applications and hold important practical value in the field of pickling corrosion inhibitors.

Evaluating the Efficacy of Wrist-Ankle Acupuncture Combined With Patient-Controlled Intravenous Analgesia for Managing Post Uvulopalatopharyngoplasty.

OBJECTIVE: The aim of this study is to investigate the impact of combining wrist-ankle acupuncture with patient-controlled intravenous analgesia (PCIA) on active pain and food intake in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) after undergoing uvulopalatopharyngoplasty (UPPP). METHODS: Sixty patients with OSAHS who underwent UPPP at our hospital's Department of Otorhinolaryngology from January 2020 to October 2023 were selected and randomly divided into 2 groups of 30 each: an observation group and a control group. The control group received general anesthesia administered by an anesthesiologist and used a PCIA pump. In addition to this treatment, the observation group received the combined intervention of wrist-ankle acupuncture. Active pain levels were monitored at 0, 6, 12, 24, 36, and 48 hours after UPPP, and food intake was observed at 24, 36, and 48 hours postoperation. The results were compared and recorded for both groups. RESULTS: The analgesic effect on active pain in the observation group was significantly greater than in the control group at 6, 12, 24, 36, and 48 hours postoperation, and the differences were statistically significant (P<0.05). In addition, when comparing food intake scores at 24, 36, and 48 hours postoperation, the observation group had significantly higher food intake than the control group, and the differences were statistically significant (P<0.05). CONCLUSIONS: The combined intervention of wrist-ankle acupuncture and PCIA provides effective pain relief for OSAHS patients after UPPP, enhances their food intake, improves their quality of life, and supports early recovery.

Controlling internal nutrients loading at low temperature using oxygen-loading zeolite and submerged macrophytes enhances environmental resilience to subsequent high temperature.

Nutrients releasing from anoxic sediment can be enhanced in summer because the dissolved oxygen (DO) consumption, nitrogen (N) and phosphorus (P) migration are susceptible to temperature. Herein, we proposed a method to hinder the aquatic environmental deterioration in warm seasons through consecutive application of oxygen- and lanthanum-modified zeolite (LOZ) and submerged macrophytes (V. natans) at low temperature scenario (5 °C, with depleted DO in water), and the effect was examined with drastic increasing the ambient temperature to 30 °C. The investigation was conducted in a microcosm scale including sediment cores (with a diameter of 11 cm, height of 10 cm) and overlying water (with depth of 35 cm). During the 60 days experiment, application of LOZ at 5 °C facilitated slower releasing and diffusion of oxygen from LOZ and the growth of V. natans. Thereby, when the temperature was increased to 30 °C and maintained for 35 days, the DO reached 10.01 mg/L, and the release of P and N from the sediment was reduced by 86% and 92%, respectively. This was achieved from the joint efforts of adsorption, biological conversion, chemical inactivation, and assimilation. Also, the LOZ inhibited 80% N2O, 75% CH4, and 70% CO2 emissions primary by promoting V. natans growth and reshaping microbiota. Meanwhile, the colonization of V. natans benefited the sustainable improvement in the water quality. Our results addressed the time that the remediation of anoxic sediment can be applied.

Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations.

The triglyceride-glucose (TyG) index has been identified as a reliable alternative biomarker of insulin resistance (IR). Recently, a considerable number of studies have provided robust statistical evidence suggesting that the TyG index is associated with the development and prognosis of cardiovascular disease (CVD). Nevertheless, the application of the TyG index as a marker of CVD has not systemically been evaluated, and even less information exists regarding the underlying mechanisms associated with CVD. To this end, in this review, we summarize the history of the use of the TyG index as a surrogate marker for IR. We aimed to highlight the application value of the TyG index for a variety of CVD types and to explore the potential limitations of using this index as a predictor for cardiovascular events to improve its application value for CVD and provide more extensive and precise supporting evidence.

FAM83A promotes proliferation and metastasis via Wnt/ß-catenin signaling in head neck squamous cell carcinoma.

This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/ß-catenin signaling pathway. Rescue experiment demonstrated the inhibition of ß-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt-ß-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/ß-catenin signaling pathway in HNSCC.

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

OBJECTIVE: To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. METHODS: GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. RESULTS: Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05). CONCLUSION: Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

Fusion machine learning model predicts CAD-CAM ceramic colors and the corresponding minimal thicknesses over various clinical backgrounds.

OBJECTIVES: This study has developed and optimized a machine learning model to accurately predict the final colors of CAD-CAM ceramics and determine their required minimum thicknesses to cover different clinical backgrounds. METHODS: A total of 120 ceramic specimens (2 mm, 1 mm and 0.5 mm thickness; n = 10) of four CAD-CAM ceramics - IPS e.max, IPS ZirCAD, Upcera Li CAD and Upcera TT CAD - were studied. The CIELab coordinates (L*, a* and b*) of each specimen were obtained over seven different clinical backgrounds (A1, A2, A3.5, ND2, ND7, cobalt-chromium alloy (CC) and medium precious alloy (MPA)) using a digital spectrophotometer. The color difference (ΔE) and lightness difference (ΔL) results were submitted to 39 different models. The prediction results from the top-performing models were used to develop a fusion model via the Stacking integrated learning method for best-fitting prediction. The SHapley Additive exPlanation (SHAP) was performed to interpret the feature importance. RESULTS: The fusion model, which combined the ExtraTreesRegressor (ET) and XGBRegressor (XGB) models, demonstrated minimal prediction errors (R2 = 0.9) in the external testing sets. Among the investigated variables, thickness and background colors (CC and MPA) majorly influenced the final color of restoration. To achieve perfect aesthetic restoration (ΔE<2.6), at least 1.9 mm IPS ZirCAD or 1.6 mm Upcera TT CAD were required to cover the CC background, while two tested glass-ceramics did not meet the requirements even with thicknesses over 2 mm. SIGNIFICANCE: The fusion model provided a promising tool for automate decision-making in material selection with minimal thickness over various clinical background.

Electrostatic generator enhancements for powering IoT nodes via efficient energy management.

Electrostatic generators show great potential for powering widely distributed electronic devices in Internet of Things (IoT) applications. However, a critical issue limiting such generators is their high impedance mismatch when coupled to electronics, which results in very low energy utilization efficiency. Here, we present a high-performance energy management unit (EMU) based on a spark-switch tube and a buck converter with an RF inductor. By optimizing the elements and parameters of the EMU, a maximum direct current output power of 79.2 mW m-2 rps-1 was reached for a rotary electret generator with the EMU, achieving 1.2 times greater power output than without the EMU. Furthermore, the maximum power of the contact-separated triboelectric nanogenerator with an EMU is 1.5 times that without the EMU. This excellent performance is attributed to the various optimizations, including utilizing an ultralow-loss spark-switch tube with a proper breakdown voltage, adding a matched input capacitor to enhance available charge, and incorporating an RF inductor to facilitate the high-speed energy transfer process. Based on this extremely efficient EMU, a compact self-powered wireless temperature sensor node was demonstrated to acquire and transmit data every 3.5 s under a slight wind speed of 0.5 m/s. This work greatly promotes the utilization of electrostatic nanogenerators in practical applications, particularly in IoT nodes.

Study on the regulation of ε-CL-20 by an external electric field.

CONTEXT: To explore the influence of the external electric field (EEF) on ε-CL-20. The molecular structure, frontier molecular orbitals (FMOs), global reactivity parameters (GRP), surface electrostatic potential, nitro charge, and UV-Vis spectra of ε-CL-20 under EEF were studied using density functional theory (DFT). The calculation results show that the electric field applied along N16-N24 has a significant effect on the structure of ε-CL-20. With an increase in the positive EEF, the bond length of the initiating bond decreases, and the bond order and bond dissociation energy increase, which increases the thermal stability of ε-CL-20 to a certain extent. In addition, with an increase in the positive EEF intensity, the LUMO migrates from both sides of the positive electric field to one side of the nitro group, and the HOMO migrates from the skeleton to the nitro group. It is worth noting that in the negative EEF, when the electric field strength changed from 0 to 0.016 a.u., the negative charge of the total nitro group gradually decreased. When the electric field strength becomes 0.02 a.u., the negative charge of the total nitro group suddenly increases, and ε-CL-20 is significantly polarized. When the electric field strength is sufficiently strong, the occupied and unoccupied orbitals of the ε-CL-20 molecule change, resulting in a change in the energy level difference between the occupied and unoccupied orbitals, which further excites the corresponding excited state, resulting in a new UV-Vis absorption peak. METHODS: Based on the density functional theory (DFT), the structural optimization and energy calculation were carried out by using B3LYP/6-311 + G(d, p) and B3LYP/def2-TZVPP methods, respectively. After optimization convergence, vibration analysis was performed without imaginary frequencies to obtain stable configurations. Then the molecular structure, frontier molecular orbitals (FMOs), global reactivity parameters (GRP), surface electrostatic potential, nitro charge, and UV-Vis spectra were analyzed.

Periodic DFT study of structural transformations of cocrystal CL-20/MMI under high pressure.

CONTEXT: The crystal and molecular structure, electronic properties, optical parameters, and elastic properties of a 1:2 hexanitrohexaazaisowurtzitane (CL-20)/2-mercapto-1-methylimidazole (MMI) cocrystal under 0 ~ 100 GPa hydrostatic pressure were calculated. The results show that the cocrystal CL-20/MMI undergoes three structural transitions at 72 GPa, 95 GPa, and 97 GPa, respectively, and the structural transition occurs in the part of the MMI compound. Structural mutations formed new bonds S1-S2, C2-C7, and N1C5 at 72GPa, 95 GPa, and 97 GPa, respectively. Similarly, the formation of new bonds is confirmed on the basis of an analysis of the changes in lattice constants, cell volumes, and partial densities of states (PDOS) for S1, S2, C2, C7, N1, and C3 at the corresponding pressures. The optical parameters show that the pressure makes the peaks of various optical parameters of CL-20/MMI larger, and the optical activity is enhanced. The optical parameters also confirm the structural mutation of CL-20/MMI under the corresponding pressure. METHOD: CL-20/MMI was calculated by using the first-principles norm-conservative pseudopotential based on density functional theory (DFT) in the CASTEP software package. For the optimization results, the Broyden-Fletcher-Goldfarb-Shanno (BFGS) method is selected to optimize the geometry of the cocrystal in the range of 0-100 GPa. GGA/PBE (Perdew-Burke-Ernzerhof) was selected to relax the cocrystal CL-20/MMI fully without constraints at atmospheric pressure. The sampling scheme in the Brillouin zone [10] is the Monkhorst-Pack scheme, and the number of k-point grids was 2 × 2 × 2. By contrast, this study will use the LDA method to calculate.

Theoretical study on different substituent-modified derivatives of 6-dinitrophenyl-5,6,7,8-tetrahydro-4-imidazo [4,5-e]furazano[3,4-b] pyrazine.

CONTEXT: The compounds of the "565" parent ring structure have received much attention from researchers because of their excellent detonation performance. In the present study, 81 derivatives were designed by introducing different substituents based on 6-dinitrophenyl-5,6,7,8-tetrahydro-4-imidazo[4,5-e]furazano[3,4-b] pyrazine (DIOP), which is a compound of the parent ring structure of 565, and the performance of these derivatives, such as the electronic structure, energy gap, heat of formation, and detonation performance, were investigated. Among these energy-containing derivatives, the density ranges from 1.70 to 2.17 g/cm3, the detonation velocity ranges from 8.01 to 10.26 km/s, and the detonation pressure ranges from 27.99 to 49.88 GPa. Through comprehensive analysis of several properties of DIOP derivatives, it was found that the oxygen balance of derivatives with the -ONO2 group was greater than zero and close to zero, while the oxygen balance of derivatives with other groups was almost all less than zero. Among them, G8 (D = 10.1 km/s, P = 47.72 GPa), H8 (D = 10.11 km/s, P = 47.92 GPa), and I8 (D = 10.26 km/s, P = 49.88 GPa) had higher detonation velocity and pressure among all derivatives, and their impact sensitivity was better than RDX. Therefore, three potential high-energy and less sensitive energy-containing derivatives, G8, H8, and I8, were screened out. The intramolecular interactions of the three derivatives were further analyzed, and it was found that there were intensive van der Waals interactions and significant spatial steric effects within the molecules, which had a positive effect on reducing the shock sensitivity of the compounds. Moreover, the three derivatives have a large degree of stacking, which leads to a high density. METHODS: All calculations in this paper are performed using Gaussian16 based on density functional theory. Firstly, the structures of the derivatives were optimized at the level of B3LYP-D3/6-311G**, and then single-site energy calculations were carried out at the level of M06-2X-D3/def2-TZVPP, to reveal the effects of single substituents versus multiple substituents and isomerism on the properties of the DIOP-based energetic derivatives. Multiwfn was used to plot the density of states (DOS) of the derivatives and to calculate the molecular surface electrostatic potential at 0.001 e/Bohr3 electron density, 0.25 Bohr lattice spacing surface.

The regulation of high-energy insensitive compound 2,6-diamino-3,5-dinitropyrazine-1-oxide by external electric field.

CONTEXT: The influence of external electric fields (EEFs) on chemical substances has always been a hot topic in the field of theoretical chemistry research. 2,6-Diamino-3,5-dinitropyrazine-1-oxide (LLM-105) is an energetic material with excellent comprehensive properties and enormous potential for application. This article explores the molecular structure, electronic structure, energy change, frontier molecular orbitals (FMOs) and density of states (DOS), UV-Vis spectra, and infrared spectra of LLM-105 under various electric field conditions. The results indicate that negative EEF can improve the stability of LLM-105, reflected in the initiation of changes in bond length and HOMO-LOMO gap. EEF has a significant impact on the electronic structure of LLM-105. The polarization of the electronic structure brings about a change in total energy, which is reflected in the analysis of energy changes. In addition, the external electric field will cause the frequency of the infrared spectra and the UV-Vis spectra to have different degrees of blue shift. The results of the analysis are helpful to understand the changes of energetic materials under the applied electric field. METHODS: Based on the density functional theory (DFT), the structural optimization and energy calculation were carried out by using B3LYP/6-311G(d, p) and B3LYP/def2-TZVPP methods, respectively. After optimization convergence, vibration analysis was performed without imaginary frequencies to obtain stable configurations. Then, the molecular structure, electronic structure, energy changes, molecular orbital and density of states, UV-Vis spectra, and infrared spectra were analyzed.

[Spatial and Temporal Scale Effects of Landscape Pattern on Riverine Nitrogen and Phosphorus Nutrients in the Qingshan Lake Watershed].

The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen （N） and phosphorus （P） concentrations. The results showed that： ① The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. ② At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ③ The contribution rate of landscape configuration to riverine N and P concentration variations （20.1%-36.5%） was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.

Nutrition support and clinical outcomes following allogeneic stem cell transplantation.

Nutrition support is frequently required post allogeneic stem cell transplantation (SCT) and while there is some evidence on the benefits of enteral nutrition (EN), parenteral nutrition (PN) is widely used in practice. The study aimed to examine the impact of EN versus PN on early outcomes following SCT. All patients who underwent allogeneic SCT over 2.5 years were included in the analysis. Data was retrospectively collected on mode of nutrition support with clinical outcome data obtained from an existing database. Clinical outcomes were compared between groups by logistic, poisson and negative binomial regression, with adjustment for baseline confounders as appropriate. Patients who received EN then changed to PN had a longer length of hospital stay compared to those who received EN only (IR 1.24, 95% CI: 1.11-1.38, p < 0.001). Compared to those who received EN only, patients who received EN that changed to PN or PN only had a longer time to neutrophil engraftment (IR 1.11, 95% CI: 1.02-1.20, p = 0.016 and IR 1.16, 95% CI: 1.03-1.30, p = 0.017) and platelet engraftment (IR 1.20, 95% CI 1.08-1.33, p < 0.001 and IR 1.24, 95% CI 1.08-1.42, p = 0.002). Enteral nutrition should be first line nutritional support for patients undergoing allogeneic SCT.

Theoretical insight into different energetic groups on the performance of energetic materials 2,5,7,9-tetranitro-2,5,7,9-tetraazabicyclo[4,3,0]nonane-8-one.

CONTEXT: Energetic materials are a class of materials containing explosive groups or containing oxidants and combustibles. The optimization of energetic materials has a significant impact on the development of industry and national defense. For high-energy density compounds (HEDC) that have not been synthesized or are dangerous to experimental operation, it is of guiding significance to predict its energy level, physicochemical properties, and safety through molecular design and theoretical calculation. Cyclic urea nitramine series compounds are a type of energetic compounds with high density and excellent detonation performance. In this study, 2,5,7,9-tetranitro-2,5,7,9-tetraazabicyclo[4,3,0]nonane-8-one (K-56) was used as the parent structure, and 36 energetic derivatives were designed. The effects of introducing single and multiple substituents on the electronic structure, energy gap, heat of formation, detonation performance, thermal stability, thermodynamic parameters, and surface electrostatic potential of K-56 and its derivatives were discussed in detail. The results exhibit the following: (1) the single substitution of -C(NO2)3 (A6) can reduce the detonation velocity of K-56 by 11.9 % and the detonation pressure by 19.8 %, while the double substitution of -C(NO2)3 (B6) can increase the density of K-56 by 11.6 %, the detonation velocity by 10.9 %, and the detonation pressure by 31 %. (2) The heat of formation of K-56 (-110.0 kJ mol-1) increased by 324.18 % and 628.81 %, respectively, proving that -N3 is an extremely effective group to improve HOF. (3) The thermal stability of the derivatives generated by the monosubstitution of the target group on the six-membered ring is better than that of the parent compound. METHODS: Gaussian16 and Multiwfn 3.8 packages are the software for calculation. In this study, the parent structure K-56 and its derivatives were optimized at the B3LYP/6-311G (d,p) level to obtain the zero point energy and thermal correction data of all compounds. Then the vibration analysis of the optimized structure is carried out to confirm that its configuration is stable. Then the M06-2X-D3/def2-TZVPP basis set is used to calculate the single point energy.

Triglyceride-glucose index for the detection of subclinical heart failure with preserved ejection fraction in patients with type 2 diabetes.

Objectives: The triglyceride-glucose (TyG) index has been identified as a reliable and simple surrogate of insulin resistance. In this study, we sought to determine the association between TyG index and cardiac function among asymptomatic individuals with type 2 diabetes (T2DM) without history of any cardiovascular disease. Materials and methods: The cross-sectional study enrolled 180 T2DM patients without cardiac symptoms. Heart failure with preserved ejection fraction (HFpEF) was defined as Heart Failure Association (HFA)-PEFF score ≥ 5 points. Results: A total of 38 (21.1%) diabetic patients were identified with HFpEF. Compared with the low-TyG group (TyG index <9.47), patients in high-TyG group (TyG index ≥9.47) showed increased risk of metabolic syndrome and diastolic dysfunction (p < 0.05 for each). Furthermore, after adjustment of confounding variables, the TyG index showed positive correlation with risk factors of metabolic syndrome (including BMI, waist circumference, blood pressure, HbA1c, TG, TC, non-HDL-C, and fasting blood glucose, p < 0.05 for each) and parameters of diastolic dysfunction (E/e' ratio, p < 0.0001) in patients with T2DM. Moreover, Receiver Operating Characteristic curve analysis showed that the TyG index could be better to predict the risk of suspected HFpEF than other indicators (AUC: 0.706, 95% CI: 0.612-0.801). According, on multiple regression analysis, TyG index was independently correlated with the incidence of HFpEF (odds ratio: 0.786, p = 0.0019), indicating that TyG index could be a reliable biomarker to predict the risk of HFpEF. Conclusion: The TyG index showed a positive correlation with the risk of subclinical HFpEF in patients with T2DM, providing a new marker to predict and treat HFpEF in diabetes.

Molecular design and theoretical study of oxadiazole-bifurazan derivatives.

CONTEXT: The design and synthesis of new high energy density materials is an important part of the research in the field of high energy materials. However, the synthesis of high-energy materials is very difficult and dangerous. Therefore, it is necessary to design the compounds in advance and evaluate the performance of the designed compounds, so as to screen the high-energy candidate compounds with excellent performance and provide reference for future synthesis and application. 1,2,5-oxadiazole (furazan) and 1,2,4-oxadiazole are five-membered nitrogen-oxygen heterocycles. Because their structures contain high-energy N-O, C=N bonds, they can effectively improve the energy density and oxygen balance of compounds, which has attracted widespread attention. In this paper, 42 kinds of oxadiazole-bifurazan energetic derivatives were designed by inserting different functional groups and changing the parent bridging groups with 1,2,4-oxadiazole and furazan as the basic structural units. Their electronic structures, aromaticity, heats of formation (HOFs), detonation properties, thermodynamic properties and electrostatic potential were systematically studied by density functional than theory (DFT). The results show that -C (NO2)3 has the greatest improvement effect on HOFs among all the substituent groups. The detonation performance of -N=N- bridged oxadiazole-bifurazan derivatives is better than that of -NH-NH- bridged derivatives. And -C(NO2)3 is the most effective group to improve the detonation performance and density of compounds. Compared with the parent compounds, when a -C(NO2)3 was introduced, the density increased by about 5.5%. A6 (D = 10.30 km·s-1, P = 48.86 GPa) and D6 (D = 9.57 km·s-1, P = 42.31 GPa) are the compounds with the best D and P among the designed compounds, which are higher than RDX and HMX, and are potential candidates for new high-energy materials. METHODS: With the help of Gaussian16 software and Multiwfn 3.8 package, the B3LYP method in density functional theory was selected. The 6-311G (d, p) basis set was used to optimize the structure of the 42 derivatives, and the high-precision def2-TZVPP basis set was used to calculate the energy.

Insight into the role of PCSK9 in glucose metabolism.

Diabetes mellitus (DM) is strongly associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) was recently identified as an important regulator of circulating low-density lipoprotein-cholesterol (LDL-C) levels via degradation of the LDL receptor, proving to be a valid target to improve lipoprotein profiles and cardiovascular outcomes in patients with ASCVD. Beyond LDL receptor processing and cholesterol homeostasis, the PCSK9 protein has recently been verified to be associated with glucose metabolism. Importantly, clinical trials suggest that treatment with PCSK9 inhibitors for patients with DM is more effective. Hence, in this review, we summarize the current findings derived from experimental, preclinical, and clinical studies regarding the association between PCSK9 and glucose metabolism, including the relationship of PCSK9 genetic mutations to glucose metabolism and diabetes, the link between plasma PCSK9 concentrations and glucose metabolic parameters, the effects of glucose-lowering drugs on plasma PCSK9 levels and the impacts of PCSK9 inhibitors on cardiovascular outcomes of patients with DM. Clinically, exploring this field may improve our understanding regarding the roles of PCSK9 in glucose metabolism and may offer an in-depth interpretation of how PCSK9 inhibitors exert effects on the treatment of patients with DM.

Effect of Lactobacillus plantarum and flavourzyme on physicochemical and safety properties of grass carp during fermentation.

The present study aimed to investigate the change in physicochemical and safety properties of grass carp during fermentation with flavourzyme and Lactobacillus plantarum (FLF). The natural fermentation (NF) and fermentation with Lactobacillus plantarum (LF) samples were used as control. The results showed that with increasing fermentation time, the pH and water activity (Aw) in each fermented grass carp sample gradually decreased, while the a-amino nitrogen (ANN), thiobarbituric acid reactive substance (TBARS), total volatile base nitrogen (TVB-N), biogenic amines (BAs), and harmful microbial gradually increased. Besides, compared with NF samples at each fermentation time, significantly lower pH, Aw, TBARS, TVB-N, BAs, and harmful microbial presented in LF and FLF samples. However, FLF samples have a higher AAN content than that of NF and LF samples during fermentation. Overall, the fermentation with Lactobacillus plantarum and flavourzyme could contribute to fermented grass carp products with better physicochemical and safety properties.