Impact of LDLR polymorphisms on lipid levels and atorvastatin's efficacy in a northern Chinese adult Han cohort with dyslipidemia.

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

An Intelligent Thermal Compensation System Using Edge Computing for Machine Tools.

This paper focuses on the use of smart manufacturing in lathe-cutting tool machines, which can experience thermal deformation during long-term processing, leading to displacement errors in the cutting head and damage to the final product. This study uses time-series thermal compensation to develop a predictive system for thermal displacement in machine tools, which is applicable in the industry using edge computing technology. Two experiments were carried out to optimize the temperature prediction models and predict the displacement of five axes at the temperature points. First, an examination is conducted to determine possible variances in time-series data. This analysis is based on the data obtained for the changes in time, speed, torque, and temperature at various locations of the machine tool. Using the viable machine-learning models determined, the study then examines various cutting settings, temperature points, and machine speeds to forecast the future five-axis displacement. Second, to verify the precision of the models created in the initial phase, other time-series models are examined and trained in the subsequent phase, and their effectiveness is compared to the models acquired in the first phase. This work also included training seven models of WNN, LSTNet, TPA-LSTM, XGBoost, BiLSTM, CNN, and GA-LSTM. The study found that the GA-LSTM model outperforms the other three best models of the LSTM, GRU, and XGBoost models with an average precision greater than 90%. Based on the analysis of training time and model precision, the study concluded that a system using LSTM, GRU, and XGBoost should be designed and applied for thermal compensation using edge devices such as the Raspberry Pi.

Luminescence properties and energy-transfer behavior of Y2-x-yBixEuyMgTiO6 phosphors.

In recent years, double perovskite has become a research hotspot of luminescent matrix materials due to its flexible structure, easy doping and good thermal stability. By using a high temperature solid-state technique, Bi3+ and Eu3+ co-doped Y2-x-yBixEuyMgTiO6 (0 ≤ x ≤ 0.1, 0 ≤ y ≤ 0.5) phosphors were made. X-ray diffraction (XRD) analysis shows that the crystal structure of all samples is monoclinic system, P21/n; Bi3+ and Eu3+ can be doped into the position of Y3+ in the substitution system of Y2MgTiO6. Both photoluminescence spectroscopy (PL) and X-ray excitation luminescence spectroscopy (XEL) were used to investigate the link between Bi3+ and Eu3+ doping concentrations and luminescence intensity. PL shows that: When 375 nm is used as the excitation wavelength, by varying the doping concentration of Eu3+ in the Y1.995-yBi0.005EuyMgTiO6 phosphor, it is possible to create the color-tunable emission from blue to red; The introduction of an appropriate amount of Bi3+ will increase the typical Eu3+ emission; The way that the system's Bi3+ and Eu3+ exchange energy can be observed by combining the fluorescence decay curve and photoluminescence. Fitting by concentration quenching model shows that the resonant dipole-dipole transition is the mechanism of energy transfer between Bi3+→Eu3+; X-rays may successfully stimulate the phosphor, and the spectral distribution of XEL and PL is basically the same; The introduction of an appropriate amount of Bi3+ is also beneficial to improving the sensitivity of XEL; Changes in temperature affect the sample's emission intensity; In addition, the samples remain stable for an extended period while being continuously exposed to X-rays at various environmental temperatures. The a forementioned findings suggest that the phosphor has potential use value in the lighting industry, X-ray imaging and temperature sensor.

Water consumption of electric power system in China: from electricity generation to consumption.

Understanding the water requirement of electricity generation is critical to the development of both electricity and water systems, while the water consumption of the whole electric power system remains unrevealed. Here, we examine the water consumption driven by electricity generation, transmission, and consumption in China, finding that 14 billion m3 of freshwater is consumed by electricity generation in 2019 and that 2.5 billion m3 of freshwater was virtually transferred via electricity transmission. Nationally, the freshwater consumption per unit of electricity generation was 1.9 m3/MWh. Based on the state-of-the-art electricity transmission data, we find that 59% of the transported electric power was from water-scarce provinces and 0.7 billion m3 of freshwater was lost due to the electricity loss in transmission lines in China. It is essential to link water resources with the whole electric power system (production, transmission, and consumption) rather than only part of the power system as in previous research.

Efficacy of Allisartan Isoproxil in the Treatment of Mild-to-Moderate Essential Hypertension.

BACKGROUND: Allisartan isoproxil is a selective nonpeptide angiotensin II (AT1) receptor blocker developed by China, this study aimed to assess its clinical efficacy for essential hypertension (EH). METHODS: Patients with mild-to-moderate EH, selected at 44 sites in China from September 9, 2016, to December 7, 2018, were administered 240 mg allisartan isoproxil daily for 4 weeks. Patients with controlled blood pressure (BP) continued monotherapy for 8 weeks, others were randomly assigned (1:1) to A + D group (allisartan isoproxil 240 mg + indapamide 1.5 mg) or A + C group (allisartan isoproxil + amlodipine besylate 5 mg) for 8 weeks. BP were measured at week 4, 8 and 12. RESULTS: 2,126 patients were included in the analysis. After 12 weeks of treatment, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by 19.24 ± 12.02 and 10.63 ± 8.89 mm Hg, respectively, and the overall BP control rate was 78.56%. The sitting blood pressures (SBP/DBP) decreased by 19.12 ± 11.71/10.84 ± 8.73 mm Hg in patients with 12 weeks allisartan isoproxil monotherapy (both P < 0.0001). The BP reductions and control rates were comparable between A + D and A + C groups. 48 patients with monotherapy-controlled BP underwent ambulatory BP monitoring, with a mean decrease in ambulatory BP of 10.04 ± 10.87/5.50 ± 8.07 mm Hg after 12 weeks of treatment, and consistent reductions between day and night. SBP and DBP had trough-to-peak ratios of 64.64% and 62.63% and smoothness indices of 3.82 and 2.92, respectively. CONCLUSIONS: An allisartan isoproxil-based antihypertensive regimen can effectively control BP in patients with mild-to-moderate EH. PROJECT REGISTRATION NO: CTR20160138 (Registration and Information Disclosure Platform for China Drug Clinical Studies, http://www.chinadrugtrials.org.cn/index.html).

Electrochemical aptasensor based on gold nanoparticle decorated Ti3C2Tx nanocomposites for chloramphenicol detection.

Using gold (Au) nanoparticle decorated Ti3C2Tx (Ti3C2Tx-Au) nanocomposites, a highly sensitive electrochemical aptasensor for the effective detection of chloramphenicol has been developed. As a two-dimensional layered material, the prepared composite not only provides high surface area, good conductivity, and thermal stability but also substantial binding sites for aptamers with high sensitivity and selectivity for the accurate determination of chloramphenicol. Interestingly, the conductivity and active sites were enhanced by freeze-drying Ti3C2Tx and in situ formation of Ti3C2Tx-Au nanocomposite. The fabricated aptasensor exhibited a very low detection limit (S/N ≥ 3) of 13.18 fg mL-1 with a linear range of 1 ~ 700 pg mL-1 and correlation coefficient of 0.9992. The fabricated aptasensor demonstrated an excellent reproducibility, repeatability, long-term stability, and high selectivity toward chloramphenicol. Further, the aptasensor was applied to real milk samples, and the recoveries were ranged from 98.93 to 101.93%.

Dosimetric and spectroscopic study of LiMgPO4 doped with Tm3+ and Er3.

Olivine-type phosphate LiMgPO4 doped with rare earth elements is considered a novel dosimetric material with excellent performance that is suitable for thermoluminescence (TL) and optically stimulated luminescence (OSL) measurements. Novel LiMgPO4:Tm,Er samples were synthesized by a high-temperature solid-state reaction method. A detailed study of the TL and OSL of the samples was performed using ß-ray irradiation and X-ray-excited optical luminescence (XEOL) spectroscopy. Density functional theory (DFT) calculations were performed to predict the preferential positions of thulium and erbium, and photoluminescence (PL) spectra and TL 3D spectra were analyzed. The DFT calculation results show that Mg is preferentially replaced by Tm/Er in the LiMgPO4 system. The PL/TL3D/XEOL spectra of the samples are dominated by the characteristic luminescence of Tm3+, and the OSL decay curve of photoluminescence has fast and slow decay components with decay constants of 5 s and 42 s, respectively. The TL and XEOL results show that LiMgPO4:Tm,Er has strong emission signals under different types of radiation rays. The PL/TL3D/XEOL spectral results show that Er3+ has no radiative excitation, but Tm3+ has strong luminescence, such that the sample still emits strong TL and PL signals. Two TL emission peaks occur at approximately 120 °C and 300 °C, where the high-temperature peak is significantly more intense than the low-temperature peak, promoting the stability of the TL and OSL signals of the samples. The TL curve consists of 6 general TL dynamic peaks. The nonlinear parameters of the TL dose response are R = 0.08 and D 0 = 479 Gy, and the OSL dose response is linear in the range of 0.2-1000 Gy. The TL and OSL signals of the LiMgPO4:Tm,Er phosphor have good repeatability. Therefore, the LiMgPO4:Tm,Er phosphor can be used for radiation dose measurement.

Synthesis of Triblock Polycarboxylate Superplasticizers with Well-Defined Structure and Its Dispersing Performance in ß-Hemihydrate Gypsum.

In this work, a novel AaBAb-type triblock polycarboxylate superplasticizers (PCEs) with well defined molecular structures were designed and synthesized, firstly, by reversible addition-fragmentation chain transfer (RAFT) polymerization, to explore the structure-property relationship PCEs in the ß-hemihydrate gypsum (ß-HH) system. Three PCEs with the same molecular weight and different structure were obtained by changing the feed ratio of the RAFT agent, initiator, and monomer. The effect of the chemical structure of PCEs on their dispersing property and water reduction capacity were assessed in gypsum by measuring the flowability of pastes and the adsorption ability of PCEs on gypsum. Results showed that among three PCEs, when the monomer ratio is 5:1 and a:b = 1:1, PCE-1 exhibited a higher working efficiency, verifying the contribution of regulating structural parameters to the improvement in performances of gypsum paste, because PCE-1 showed the strongest binding capacity with calcium ions due to the relatively equal amount of carboxyl groups at both ends. The AaBAb-type PCEs provide a special advantage over the conventional comb polymer to understand the relation between the structure and property of PCEs, and a direction for further development of PCEs of high performance.

High-sensitive ferrocene labeled aptasensor for the detection of Mucin 1 by tuning the sequence constitution of complementary probe.

A strand displacement-based "signal-off" electrochemical aptasensor is reported for the detection of Mucin 1 (MUC 1) based on a high original signal. Different from the conventional "signal-off" electrochemical biosensors where electrochemical substances are dispersed in electrolyte solution, here the current signal was generated by the complementary probe (CP) associated with ferrocene (Fc) labeled aptamer (Apt.-Fc). Because Apt.-Fc and MUC 1 have a higher affinity, Apt.-Fc dissociates from CP in the presence of MUC 1, resulting in a reduction of detection current signal generated by oxidation of labeled Fc. In this system, high detection signal is necessary to improve the sensor's performance. For this aim, a strategy is proposed for changing the modalities of electron transport and the quantity of Apt.-Fc introduced by simply tuning the sequence constitution of CP. As expected, a high detection current signal was obtained after selecting CP(Apt.-Fc)-TTT as the optimal CP. The aptasensor was then employed to detect MUC 1, and satisfactory detection results with a low detection limit (LOD) of 0.087 pM (S/N = 3), good specificity, good stability, and feasibility of detection of MUC 1 in artificial serum (recovery of 92-101%, RSD of 1.36-5.23%) were obtained.

Accuracy Evaluation of Carotid-Femoral Pulse Wave Velocity Estimated by Smart Terminal Watch.

To evaluate the accuracy of the smartwatch in estimating carotid-femoral pulse wave velocity (cfPWV). A cohort of gender-matched volunteers aged 18-80 years were recruited. At the sitting and supine positions, cfPWV was measured alternately by smartwatch and CompliorAnalyse, for each participant, and nine sets of data were collected from each participant with a 60 s interval between measurements. The accuracy of cfPWV measurement for smartwatches was assessed using mean error (ME) and mean absolute error (MAE), while the consistency of the two methods was assessed using the Bland-Altman analysis and concordance class correlation. A total of 347 participants were enrolled. The mean cfPWV was 9.01 ± 2.29 m/s measured by CompliorAnalyse and 9.06 ± 1.94 m/s by smartwatch. The consistency correlation coefficient (CCC) was 0.9045 (95% CI 0.8853-0.9206), the ME was 0.046 ± 0.92, and the MAE was 0.66 (95% CI 0.59-0.73). Bland-Altman analysis showed that the error of 95% samples was in the range between -1.77 m/s and 1.86 m/s. The Kappa value of cfPWV greater than 10 m/s was 0.79, the area under the ROC curve was 0.97 (P < 0.001), sensitivity was 0.90, specificity was 0.93, positive predictive value was 0.83 and negative predictive value was 0.96. Smartwatch can accurately estimate cfPWV to evaluate arterial stiffness. This method is simple and feasible and is suitable for people to actively and early monitor vascular elasticity.

Influence of Lanthanum-Doped Tungsten Wire Drawing Process on Microstructure and Properties.

A reasonable preparation processing of Lanthanum-doped tungsten wire plays a decisive role in the final properties of the wire. This paper gives the optimum drawing process parameters of lanthanum-doped tungsten wire with φ1.00 mm-φ0.50 mm and explains the phenomenon of coarsening of fiber-like grains in the preparation processing of tungsten wire. The final optimum process parameters of lanthanum-doped tungsten wire are given: the temperature is 950 °C (the first pass temperature is 950 °C, and the temperature decreases by about 20 °C for each pass), the compression ratio is 15%, mold temperature is 550 °C, because of the limitation of equipment conditions, the wire drawing speed is fixed at 0.19 m/s. It is found that the fiber-like grains of the tungsten wire coarsen when the temperature is too high, and it is prone to breakage when the temperature is too low during the drawing process. When the compression ratio is too high (for example, 22%), there is a negative impact on the surface quality and the straightness of the tungsten wire. When the compression ratio is too low, the processing die time is increased, and the production cost is increased.

Insights into the combined effects of environmental concentration of difenoconazole and tebuconazole on zebrafish early life stage.

Limited literature had focused on the combined effect of triazole fungicides on aquatic organisms at environmental concentrations. In this research, difenoconazole (DIF) and tebuconazole (TEB) mixture exhibited additive effect on the acute toxicity to zebrafish embryos. The transcriptomics and metabolomics demonstrated DIF and TEB mixtures at aquatic life benchmark and environmental concentration simultaneously influenced the lipid metabolism, arachidonic acid metabolism, steroid hormone biosynthesis and tryptophan metabolism, but showed diverse response patterns mediating the combined effects on zebrafish embryos after 120 h exposure. The DIF and TEB mixture at aquatic life benchmark caused combined effect on yolk sac resorption and metabolites, was less than the additive effect of individual DIF and TEB. It was found environmental concentration of DIF and TEB caused much lower levels of IFN and IL6, induced higher levels of PGE2, l-kynurenine and formylanthranilate in zebrafish larvae, and their binary mixture caused synergistic effect on the accumulation of metabolites in metabolic pathways, which might cause more negative effect and risk on growth in zebrafish later life stages. Results further demonstrated that adding arachidonic acid (AA) increased the transcripts of Pla2, Ptgs1, Cyp19a and Cxcl8b, allayed the accumulation of PLA2 and 17ß-E2, and induced more PGF2α, IFN and IL6 levels in zebrafish larvae, indicated AA metabolism might play important regulatory roles on hormone synthesis and immune response caused by DIF and TEB mixtures. Current results indicated the risk assessment of mixtures based on single concentration may not precisely estimate the environmental risk and health effect, it is crucially important to consider the multi-concentration combinations, and more attention should be paid to the environmental concentration.

Efficient depolymerization of lignin through microwave-assisted Ru/C catalyst cooperated with metal chloride in methanol/formic acid media.

Lignin, an abundant aromatic biopolymer, has the potential to produce various biofuels and chemicals through biorefinery activities and is expected to benefit the future circular economy. Microwave-assisted efficient degradation of lignin in methanol/formic acid over Ru/C catalyst cooperated with metal chloride was investigated, concerning the effect of type and dosage of metal chloride, dosage of Ru/C, reaction temperature, and reaction time on depolymerized product yield and distribution. Results showed that 91.1 wt% yield of bio-oil including 13.4 wt% monomers was obtained under the optimum condition. Yields of guaiacol-type compounds and 2,3-dihydrobenzofuran were promoted in the presence of ZnCl2. Formic acid played two roles: (1) acid-catalyzed cleavage of linkages; (2) acted as an in situ hydrogen donor for hydrodeoxygenation in the presence of Ru/C. A possible mechanism for lignin degradation was proposed. This work will provide a beneficial approach for efficient depolymerization of lignin and controllable product distribution.

Health risks of sulfentrazone exposure during zebrafish embryo-larvae development at environmental concentration.

Knowledge about the negative effects and mechanism of sulfentrazone (SUL) on aquatic early life stages is still limited. Here we investigated the lethal and sub-lethal effects of SUL during zebrafish embryo-larvae development. Results demonstrated that the 96 h and 120 h-LC50 of SUL to embryonic zebrafish was 2.02 mg/L, and the 30 d-LC50 was 0.899 mg/L after embryos exposed to SUL for 30 d. High concentrations of SUL delayed yolk sac absorption, disordered the hatching and heart rate during zebrafish embryonic stage, while 0.0100-0.100 mg/L SUL had no phenotypic changes on embryonic development, but decreased the body weight of larvae after 30 d exposure. RNA-seq identified 321, 394 and 727 differentially expressed genes in larvae after embryos exposed to 0.0100 mg/L, 0.0400 mg/L and 0.400 mg/L SUL for 30 d, found that the transcriptional profiles involved in heart development and endocrine disruption were simultaneously influenced by different concentrations of SUL, such as adrenergic signaling in cardiomyocytes, cardiac muscle contraction, cell adhesion molecules and steroid biosynthesis. Biochemical analysis showed that SUL increased the levels of E2, T3 and TSH, induced the activities of mitochondrial complex IV, cytochrome c oxidase, Ca2+-ATPase, total Na+K+-ATPase and Ca2+Mg2+-ATPase, and decreased ATP formation after embryos exposed to SUL for 5 d and 30 d. Further comprehensive analysis demonstrated that SUL caused more significantly alteration on the transcript, level or activity of the key elements involved in heart development and endocrine disruption after 30 d exposure, indicated long-term SUL exposure might cause more negative effects on zebrafish at doses below the presumed no-observed-adverse-effect level during early life development. The results inferred the environmental concentration of SUL might cause potential cardiac and endocrine health risk in zebrafish later life stages, also facilitated a better understanding of the sub-lethal effects and molecular mechanism of SUL on aquatic organism.

Research on household emergency supplies storage from the theory of planned behavior and intention-behavior gap in the context of COVID-19.

Introduction: In the context of COVID-19 epidemic, household-level emergency supplies are becoming a critical link in the national emergency response mechanism for public health emergencies. The main goal of this study is to analyze the forming process of household emergency supplies storage intention and behavior based on the theory of planned behavior. Methods: A total of 486 valid questionnaires were obtained from China and analyzed using structural equation modeling. Results: The study found that subjective norms and perceived behavioral control had a positive impact on residents' intention to store emergency supplies, while attitudes did not play a significant role. Community institutional trust and community network play significant moderating roles in the transformation from intentions to behaviors. Discussion: This study explored the influencing factors of residents' household emergency supplies storage, and introduced community institutional trust and community network as moderating variables to analyze the process of transformation of residents' household emergency supplies storage intentions to behaviors from the perspective of community situation, and initially constructed a two-stage integration model including intention formation and behavior transformation. By analyzing the forming process of household emergency supplies behavior, this paper revealed the effective paths for the formation of household emergency supplies storage intention, and put forward policy suggestions from the government and community levels.

Association Between Heart Rate and Major Adverse Cardiovascular Events Among 9,991 Hypertentive Patients: A Multicenter Retrospective Follow-Up Study.

Objective: To assess the effect of heart rate at baseline on major adverse cardiovascular events (MACEs) among hypertensive patients in China. Methods: A multicenter retrospective study was conducted with a 24 month follow-up period. A total of 10,031 hypertensive patients treated with standard antihypertensive drugs were grouped according to their heart rate before treatment: <65 beats per min (bpm), 65-69 bpm, 70-74 bpm, 75-79 bpm, and ≥80 bpm. The occurrence of any of MACEs was as the endpoint event during the 24 month follow-up period. The effect of heart rate at baseline on MACEs was analyzed using univate and multivariable Cox proportional regression analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs). The restricted cubic spline (RCS) model was used to fit the Cox proportional harzard model with 5 knots at the 5th, 25th, 50th, 75th, and 95th percentiles of heart rate. Results: Totally 9,991 patients were finally enrolled with the mean systolic pressure (SBP)/diastolic pressure (DBP) of 130.59 ± 7.13/77.66 ± 5.99 mmHg at 24 month follow-up. The incidence of MACEs was 4.80% (n = 480). After adjustment for age, gender, baseline blood pressure, alcohol drinking, smoking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease and antihypertensive drug use, patients with heart rate <65 bpm (HR = 1.450, 95% CI: 1.098-1.915) and ≥80 bpm (HR = 1.391, 95% CI: 1.056-11.832) showed 0.45 fold and 0.391 fold increases of MACE risks, compared with patients with heart rate of 70-74 bpm. Furthermore, MACE risks were increased by 86.0% and 65.4% in men, and 59.3% and 69.0% in elderly patients aged ≥65 years at heart rate <65 bpm or ≥80 bpm, respectively. We also found a non-liner U-shaped correlation between heart rate and the occurrence of MACEs. Conclusions: Heart rate might be an independent risk factor for MACEs in hypertensive patients. An appropriate range of heart rate control may offer guidance to hypertension treatment.

Effectiveness of an impedance cardiography guided treatment strategy to improve blood pressure control in a real-world setting: results from a pragmatic clinical trial.

OBJECTIVE: To test the effectiveness of an impedance cardiography (ICG) guided treatment strategy on improving blood pressure (BP) control in real-world clinical practice. DESIGN: A single-centre, pragmatic randomised trial. SETTING: A hypertension clinic of the Peking University People's Hospital in Beijing, China. PARTICIPANTS: Adults who sought outpatient care for hypertension in the hypertension clinic at the Peking University People's Hospital between June and December 2019. INTERVENTIONS: A computerised clinical decision support of recommending treatment choices to providers based on patients' haemodynamic profiles measured by ICG. MAIN OUTCOME MEASURES: Changes in systolic BP (SBP) and diastolic BP (DBP) levels at the follow-up visit 4-12 weeks after baseline. Secondary outcomes included achievement of BP goal of <140/90 mm Hg and the changes in BP by baseline BP, age, sex and body mass index (BMI). RESULTS: A total of 102 adults (mean age was 54±14 years; 41% were women) completed the study. The mean baseline SBP was 150.9 (SD of 11.5) mm Hg and mean baseline DBP was 91.1 (11.3) mm Hg. At the follow-up visit, the mean SBP and DBP decreased by 19.9 and 11.3 mm Hg in the haemodynamic group, as compared with 12.0 and 4.9 mm Hg in the standard care group (p value for difference between groups <0.001). The proportion of patients achieving BP goal of <140/90 mm Hg in the haemodynamic group was 67%, as compared with 41% in the standard care group (p=0.017). The haemodynamic group had a larger effect on BP reduction consistently across subgroups by age, sex, BMI and baseline BP. CONCLUSIONS: An ICG-guided treatment strategy led to greater reductions in BP levels than were observed with standard care in a real-world population of outpatients with hypertension. There is a need for further validation of this strategy for improving blood pressure treatment selection. TRIAL REGISTRATION NUMBER: NCT04715698.

Histology and multi-omic profiling reveal the mixture toxicity of tebuconazole and difenoconazole in adult zebrafish.

The combination effects of triazole fungicides on aquatic organisms remain largely unknown. In current study, an integrated histological, transcriptome, metabonomics and microbiology was applied to investigate the mixture effects and risk of tebuconazole (TEB) and difenoconazole (DIF) co-exposure on zebrafish liver and gonad at aquatic life benchmark. TEB and DIF mixture showed additive effect on the acute toxicity to adult zebrafish, the combined toxicity on liver was less than the additive effect of individual TEB and DIF, and TEB and DIF mixture also reduced the toxic effects on gonad and intestinal microflora. Transcriptomics and metabolomics further showed TEB and DIF mixture could induce more differentially expressed genes (DEGs) to regulate the metabolic pathways involved in energy metabolism, steroid hormone biosynthesis, retinol metabolism and microbial metabolism, to balance the energy metabolism and supplies, and maintain the steroid hormone and RA level, further reduced the toxic effect on liver and gonad caused by TEB and DIF. Our results showed the different responses and patterns on transcriptional and metabolic profiles mediated in the diverse toxicity and combination effects of TEB and DIF. The present results provided a deep mechanistic understanding of the combined effects and mode of action of DIF and TEB mixture on aquatic organisms, suggesting the concept of additive effects might sufficiently protective when evaluated the combination effects and ecological risk of TEB and DIF at aquatic life benchmarks.

A sensitive electrochemical DNA sensor for detecting Helicobacter pylori based on accordion-like Ti3C2Tx: a simple strategy.

A novel electrochemical DNA sensor was designed to detect Helicobacter pylori based on accordion-like Ti3C2Tx. Here the multilayer Ti3C2Tx obtained by DMSO delamination was used to modify the glass carbon electrode, with a large specific surface area and excellent conductivity. Au nanoparticles were supported on the modified electrode and worked as an effective carrier to fix the capture probe (cpDNA) with sulfhydryl group through the firm binding of Au-S bond. Such an accordion-like Ti3C2Tx structure provides an ultrahigh electroactive surface area and ample binding sites for accommodating Au nanoparticles, which is advantageous for the signal amplification during the detection. And further, the sandwich structure formed by hybridizing cpDNA with target DNA sequence (tDNA) and rpDNA (rpDNA is a strand of DNA that can be base-paired with the tested tDNA) increases greatly the current signal and enhances the sensitivity of the electrochemical DNA sensor. Under optimal conditions, the developed electrochemical DNA sensor showed a wide linear range from 10-11 to 10-14 M and a low detection limit of 1.6 × 10-16 M and exhibited good sensitivity, reproducibility, and stability. A novel electrochemical DNA sensor with simple sandwich structure was designed to detect H. pylori based on accordion-like Ti3C2Tx.

Factors associated with acute cardiac injury and their effects on mortality in patients with COVID-19.

To determine the incidence of acute cardiac injury (ACI), the factors associated with ACI and the in-hospital mortality in patients with COVID-19, especially in severe patients. All consecutive in-patients with laboratory-confirmed COVID-19 from Tongji Hospital in Wuhan during February 1 and March 29, 2020 were included. The demographic, clinical characteristics, laboratory, radiological and treatment data were collected. Univariate and Firth logistic regression analyses were used to identify factors associated with ACI and in-hospital mortality, and Kaplan-Meier method was used to estimate cumulative in-hospital mortality. Among 1031 patients included, 215 (20.7%) had ACI and 501 (48.6%) were severe cases. Overall, 165 patients died; all were from the severe group, and 131 (79.39%) had ACI. ACI (OR = 2.34, P = 0.009), male gender (OR = 2.58, P = 0.001), oximeter oxygen saturation (OR = 0.90, P < 0.001), lactate dehydrogenase (OR = 3.26, P < 0.001), interleukin-6 (IL-6) (OR = 8.59, P < 0.001), high sensitivity C-reactive protein (hs-CRP) (OR = 3.29, P = 0.016), N-terminal pro brain natriuretic peptide (NT-proBNP) (OR = 2.94, P = 0.001) were independent risk factors for the in-hospital mortality in severe patients. The mortality was significantly increased among severe patients with elevated hs-CRP, IL-6, hs-cTnI, and/or NT-proBNP. Moreover, the mortality was significantly higher in patients with elevation of both hs-cTnI and NT proBNP than in those with elevation of either of them. ACI develops in a substantial proportion of patients with COVID-19, and is associated with the disease severity and in-hospital mortality. A combination of hs-cTnI and NT-proBNP is valuable in predicting the mortality.