Search

Aims: As the impact of inclisiran in stroke prevention in atherosclerotic cardiovascular disease (ASCVD) patients or those at high risk of ASCVD is still unclear, we conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to quantify the effectiveness of inclisiran in stroke prevention in these patients.Methods: Literature research was conducted in four electronic databases (PubMed, EMBASE, Web of Science, CENTRAL) and two clinical trials registers (ClinicalTrials.gov, WHO ICTRP) from the inception of the study to 17 October 2022, and was updated by the end of the study on 5 January 2023. Two authors independently screened the studies, extracted the data, and assessed the bias. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). The intervention effect was estimated by calculating risk ratio (RR), weighted mean difference (WMD), and 95% confidence interval (CI) with R 4.0.5. Sensitivity analysis by changing meta-analysis model was also performed to test the robustness of the pooled results. If this was not possible, a descriptive analysis was conducted.Results: Four RCTs (n = 3,713 patients) were rated as high-risk bias. Meta-analysis of three RCTs (ORION-9, ORION-10, and ORION-11) showed that inclisiran reduced myocardial infarction (MI) risk by 32% (RR = 0.68, 95%CI = 0.48–0.96) but did not reduce stroke (RR = 0.92, 95%CI = 0.54–1.58) and major cardiovascular events (MACE) (RR = 0.81, 95%CI = 0.65–1.02) risk. Sensitivity analysis results were stable. Safety was similar to the placebo group but had frequent injection-site reactions (RR = 6.56, 95%CI = 3.83–11.25), which were predominantly mild or moderate. A descriptive analysis of one RCT (ORION-5) was conducted due to different study designs, and suggested that inclisiran might be given semiannually from the beginning.Conclusion: Inclisiran is not beneficial for stroke or MACE prevention in ASCVD or patients at high risk of ASCVD but is associated with the reduction of MI. Given the limited number and quality of the available studies and the lack of a standardized definition for cardiovascular events, further studies are essential for confirming the results.

The thermal-electric conversion efficiency is a crucial metric for evaluating the performance of a thermoelectric generator (TEG). However, accurate measurement of this efficiency remains a significant challenge due to various factors that impact heat flow measurements. We have observed that temperature fluctuations during temperature control are the primary factor contributing to measurement errors in heat flow under vacuum conditions. To address this issue, we have developed a time-dependent theoretical model for the thermal-electric coupling of a TEG measurement system based on Fourier’s theory of heat conduction. This model allows us to investigate the effects of both temperature fluctuation and structural parameters on the measurement error of TEG performance. Furthermore, we have proposed an error correction scheme for TEG performance based on our theoretical and experimental findings. These insights provide a theoretical framework and technical guidance for more precise measurements of TEG performance.

In this study, we have designed and developed an implantable thermoelectric generator (TEG) module tailored for large-scale flue gas waste heat recovery. We also have established a test stand to simulate diverse operational conditions, and systematically examined the influence of different operating conditions, including flue gas temperature, flue gas velocity, and cooling water temperature, on the electrical performance of the TEG module. When the flue gas temperature is 139 °C, the flue gas flow rate is 3.4 m/s, and the cooling water temperature is 20 °C, the TEG module operates at its peak performance. It achieves an open-circuit voltage of 856.3 V and an output power of 150.58 W. Furthermore, the TEG module demonstrates a notable power generation capacity of 3.86 kW/m3 and a waste heat recovery capacity of 135.85 kW/m3. The results prove the TEG module as an effective solution for large-scale flue gas waste heat recovery in industrial settings, contributing to sustainable energy practices. This study supports the application of thermoelectric power generation in the industrial sector, offering significant potential for advancements in energy efficiency.

Recently, SnSe has attracted wide attention as a promising environment-friendly IV-VI thermoelectric material. Here, SnS is alloyed with Na-doped SnSe to decrease the thermal conductivity for better thermoelectric performance. Consistent with previous reports, the lattice constant and the band gap change linearly with increasing SnS, suggesting the formation of SnSe1-xSx solid solution. However, SnS nano-precipitations have been clearly observed, indicating the phase separation in the alloys. Moreover, the grain size decreases obviously with increasing SnS amount. The first-principles calculations show that the nano-precipitation is due to the positive formation energies for SnSe1-xSx in the small x region. Due to the structure engineering, the lattice thermal conductivity is greatly reduced in SnSe1-xSx samples, leading to a promising ZT of 1.35 for Na0.03Sn0.97Se0.7S0.3 at 816 K. Keywords: SnSe, Solid solution, Grain refinement, Thermal conductivity, Thermoelectric performance

Synergistic effect of band convergence and resonant level could be manipulated in SnTe by co-doping In and Hg, leading to a potential thermoelectric performance enhancement in a much wider temperature range. In this work we carefully investigated thermoelectric properties of the In-Hg co-doped SnTe, synthesized by a hot pressing method. With this co-doping the Seebeck coefficients of the co-doped samples were greatly improved (over 50 μVK−1) at the room temperature. Although power factors of the In-Hg co-doped SnTe were also able to be optimized, the peak ZT (0.9 at 850 K in Sn0.98Bi0.02Te-1%HgInTe2), however, is not high enough when comparing to other co-doped SnTe systems. This may be caused by the relatively high lattice thermal conductivity. An apparent competition between band convergence doping and resonant level doping was observed in our experiment. The results suggest that band engineering via co-doping should be further understood in order to optimize the thermoelectric properties inside the material system.

Pharmaceutical excipients (PEs) are substances included in drug formulations. Recent studies have revealed that some PEs can affect the activity of metabolic enzymes and drug transporters; however, the effects of PEs on CYP2C8 and its interaction potential with drugs remain unclear. In this study, we evaluated the effects of Tween 80 and EL−35 on CYP2C8 in vitro and further investigated their impacts on the PK of paclitaxel (PTX) in rats after single or multiple doses. The in vitro study indicated that Tween 80 and EL−35 inhibited CYP2C8 activity in human and rat liver microsomes. EL−35 also decreased the expression of CYP2C8 in HepG2 cells. In the in vivo study, Tween 80 did not alter the PK of PTX after single or multiple doses, whereas EL−35 administered for 14 days significantly increased the AUC and MRT of PTX. Further analysis indicated that multiple-dose EL−35 reduced the expression of Cyp2c22 and production of 6-OH-PTX in the rat liver. Our study suggested that short-term exposure to both PEs did not affect the PK of PTX in rats, but multiple doses of EL−35 increased the AUC and MRT of PTX by downregulating the hepatic expression of Cyp2c22. Such effects should be taken into consideration during drug formulation and administration.

The process conditions and antioxidant activity of ultra-high pressure assisted extraction of polysaccharides from Moringa oleifera seed husks were studied. Taking the yield of polysaccharides as the index, the effects of degree of crushing, extraction pressure, holding pressure time and material-to-liquid ratio on the yield of polysaccharides from Moringa oleifera seed husks were investigated. The optimal extraction conditions were determined by single-factor test and orthogonal test: a holding time of 10 min, a material-to-liquid ratio of 1:25, an extraction pressure of 350 MPa, and a polysaccharide yield of 0.264%. Its antioxidant activity can be determined by measuring the total antioxidant capacity and their ability to scavenge DPPH and ·OH radicals. The results showed that the IC50 of Moringa oleifera seed husk polysaccharides on DPPH and hydroxyl radicals were 0.0662 g/L and 0.0844 g/L, respectively. The total antioxidant capacity was 0.1826 mm/g (expressed as the equivalent concentration of ferrous sulfate). Compared with hot water extraction methods, ultra-high pressure assisted extraction methods can shorten extraction time, improve extraction efficiency. The water-soluble polysaccharides extracted from Moringa oleifera seed husks by ultra-high pressure assisted extraction technology also have higher antioxidant activity than that by hot water extraction method at the same concentration.

Abstract Background Micropapillary (MPP) adenocarcinoma is considered one of the most aggressive pathological types of lung adenocarcinoma (LADC). This retrospective study aimed to evaluate the prognostic significance and benefit of postoperative adjuvant therapy (PAT) in stage IA LADC patients with different proportions of MPP components. Materials and methods We retrospectively examined clinical stage IA LADC patients who underwent surgical resection between August 2012 and December 2019. In terms of the proportion of MPP components (TPM), the tumors were reclassified into three categories: MPP patterns absent (TPMN); low proportions of MPP components (TPML); and high proportions of MPP components (TPMH). The dates of recurrence and metastasis were identified based on physical examinations and were confirmed by histopathological examination. Results Overall, 505 (TPMN, n = 375; TPML, n = 92; TPMH, n = 38) patients harboring EGFR mutations were enrolled in the study. Male sex (P = 0.044), high pathological stage (P

IntroductionExposure to blue-enriched light from electronic devices is an emergent disruptor of human sleep, especially at particular times of day. Further dissection of this phenomenon necessitates modeling in a tractable model organism.MethodsThus, we investigated the effects of light color on sleep in Drosophila melanogaster. We measured sleep in red-eyed Canton-S (CS) and white-eyed w1118 flies in baseline 12:12 light/dark conditions and experimental conditions with light-color (blue, red, or green) exposure for all 12 h of daylight or 3 h in the morning or evening.ResultsBlue light reduced daytime and nighttime sleep in CS but not in w1118, potentially indicating a role for the compound eye in blue light’s effects on fruit fly sleep. Red light, especially in the evening, reduced sleep during exposure in both strains. Green light had minimal effects on sleep in CS flies, but evening exposure reduced sleep in w1118 flies, mimicking red light’s effects.DiscussionIn conclusion, light’s effects on sleep in D. melanogaster are dependent on wavelength and time-of-day. Future studies will aim to dissect these mechanisms genetically.

Abstract Background Patients with sepsis-associated encephalopathy (SAE) have higher mortality rates and longer ICU stays. Predictors of SAE are yet to be identified. We aimed to establish an effective and simple-to-use nomogram for the individual prediction of SAE in patients with sepsis admitted to pediatric intensive care unit (PICU) in order to prevent early onset of SAE. Methods In this retrospective multicenter study, we screened 790 patients with sepsis admitted to the PICU of three hospitals in Shandong, China. Least absolute shrinkage and selection operator regression was used for variable selection and regularization in the training cohort. The selected variables were used to construct a nomogram to predict the risk of SAE in patients with sepsis in the PICU. The nomogram performance was assessed using discrimination and calibration. Results From January 2017 to May 2022, 613 patients with sepsis from three centers were eligible for inclusion in the final study. The training cohort consisted of 251 patients, and the two independent validation cohorts consisted of 193 and 169 patients. Overall, 237 (38.7%) patients developed SAE. The morbidity of SAE in patients with sepsis is associated with the respiratory rate, blood urea nitrogen, activated partial thromboplastin time, arterial partial pressure of carbon dioxide, and pediatric critical illness score. We generated a nomogram for the early identification of SAE in the training cohort (area under curve [AUC] 0.82, 95% confidence interval [CI] 0.76–0.88, sensitivity 65.6%, specificity 88.8%) and validation cohort (validation cohort 1: AUC 0.80, 95% CI 0.74–0.86, sensitivity 75.0%, specificity 74.3%; validation cohort 2: AUC 0.81, 95% CI 0.73–0.88, sensitivity 69.1%, specificity 83.3%). Calibration plots for the nomogram showed excellent agreement between SAE probabilities of the observed and predicted values. Decision curve analysis indicated that the nomogram conferred a high net clinical benefit. Conclusions The novel nomogram and online calculator showed performance in predicting the morbidity of SAE in patients with sepsis admitted to the PICU, thereby potentially assisting clinicians in the early detection and intervention of SAE.

Colored polymer anti-skid thin layers are widely used on urban roads to enhance driving safety, improve road aesthetics, and mitigate the urban heat island effect. However, in thin layers constructed by the spreading method, the adhesion of cementitious material to the aggregate is often weak. This leads to early-stage spalling of surface aggregates, thereby reducing the anti-skid performance of the layer. To investigate the factors contributing to spalling, this study examines the embedding behavior of ceramic particles and assesses how the fluidity of the cementitious material and aggregate shape characteristics influence the embedding depth. Using a rotational viscosity test, it is concluded that a cementitious mix ratio of adhesive/powder filler/sand filler = 1:0.5:1 or 1:0.5:1.5 facilitates effective aggregate embedding. Testing the embedding depth of aggregates with the same particle size across different cementitious materials revealed that higher cementitious viscosity results in a reduced aggregate embedding depth. Geometric parameter data for aggregate particles were extensively collected using an image acquisition device, and quantitative analysis identified the shape characteristics influencing the embedding depth. A gray correlation analysis determined that the impact of the shape characteristics on embedding depth follows the order of roundness factor > prism factor > axial coefficient.

The Seebeck coefficient describes the temperature gradient-induced voltage in thermoelectrics. Usually, obtaining a high Seebeck coefficient within a wide temperature range is difficult as it is limited by the Goldsmid-Sharp relationship. In this work, the thermoelectric performance of the PbSe--AgSbSe2 alloy is optimized by SbCl3 doping. Interestingly, the observed Seebeck coefficient hardly varies as temperature increases from 300 K to 830 K, and its absolute value is at a high level of more than 250 mV K-1. By measuring the Hall effect, the anomalous Seebeck coefficient is attributed to the strongly temperature-dependent carrier concentration, which increases from 0.38 - 1019 cm-3 at 300 K to 3.91 - 1019 cm-3 at 830 K. Besides the high Seebeck coefficient, the alloyed compounds exhibit very low thermal conductivity, down to 0.59 W m-1 K-1 at 830 K. Finally, the peak ZT reaches 1.12 at 830 K. It is predicted that the performance of the alloys could be further improved by enhancing the carrier concentration. [ABSTRACT FROM AUTHOR]

Colitis causes inflammation, diarrhoea, fever, and other serious illnesses, posing a serious threat to human health and safety. Current medications for the treatment of colitis have serious side effects. Therefore, the new strategy of creating a defence barrier for immune function by adding anti-inflammatory foods to the daily diet is worth advocating for. Low-molecular weight oyster peptides (LOPs) are a natural food with anti-inflammatory activity extracted from oysters, so intervention with LOPs is likely to be an effective preventive solution. The aim of this study was to investigate the preventive effect of LOPs on lipopolysaccharide (LPS)-induced acute colitis inflammation in mice and its underlying mechanism. The results showed that LOPs not only inhibited the colonic histopathy in mice induced by LPS-induced inflammation but also reduced the inflammatory response in the blood. In addition, LOPs significantly increased the number of beneficial bacteria (Alistipes, Mucispirillum, and Oscillospira), decreased the number of harmful bacteria (Coprobacillus, Acinetobater) in the intestinal microbiota, and further affected the absorption and utilisation of short-chain fatty acids (SCFAs) in the intestinal tract. In conclusion, dietary supplementation with LOPs is a promising health-promoting dietary supplement and nutraceutical for the prevention of acute colitis by reducing the inflammatory response and modulating the intestinal microbial communities.

Abstract Purpose Growing evidence has demonstrated an indispensable role for N6‐methyladenosine (m6A) in human diseases, but the copy number variations (CNVs) of m6A regulatory genes in bladder cancer (BLCA) remains largely unknown. Methods We investigated the CNVs on all known m6A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. Results CNV events of m6A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer‐related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6A regulatory genes were correlated with specific kinds of immune infiltrates. Conclusions There are significant correlations between m6A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.

Purpose: This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions. Methods: In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%; n = 224) and a validation set (ca. 30%; n = 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan–Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors. Results: Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12–63.86) in the high-risk group and 83.0% (95%CI, 76.31–90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model. Conclusion: The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance.