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Nowadays, environmental pollution due to centralized industrialization has occurred rapidly around the world; thus, efficient remediation is in dire requirement. In this literature, the carbon aerogel material was fabricated using the lotus receptacle (LCA) via a hydrothermal treatment and N2-atmosphere pyrolysis. Characterization was conducted using various solid phase analyses to confirm the successful upcycling of carbon aerogel from the mentioned waste by-product. The synthesized material was consequently applied for the adsorption of diesel oil and methylene blue, yielding up to 80 and 99% removal efficiency for the two contaminants, respectively, wherein several factors such as the absorbent dose and dye concentration as well as the adsorption kinetic were also assessed. Besides, the electrochemical properties were additionally assessed to consummate the application of the material in the electrochemical field, which reveals the promising applicability of the fabricated LCA not only as an efficient adsorbent for wastewater treatment but also as a good capacitor with great sustainability even after 500 consecutive charging–discharging cycles. [ABSTRACT FROM AUTHOR]

Foxtail millet is typically dehulled before consumption or processing. However, foxtail millet bran also contains abundant phenolic compounds and other nutrients. Edible fungi have rich extracellular enzyme systems; are environmentally friendly and safe for consumption; and have been shown to effectively degrade lignin and cellulose. This study aimed to screen edible fungi that can effectively ferment undehusked foxtail millet, improving its nutritional value and antioxidant properties through solid‐state fermentation (SSF). The results demonstrated that fermentation utilizing Pleurotus geesteranus exhibited significant improvements in both the phenolic compound content and antioxidant properties of foxtail millet, with the optimal fermentation period determined to be 30 days. The physical and functional properties of fermented undehusked foxtail millet (FFM) flour were effectively improved, increasing crude protein, vitamin C, and crude polysaccharide contents by 11.46%, 27.78%, and 54.17%, respectively. In vitro scavenging activities of FFM were 73.19%, 93.86%, and 63.75% for 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS·+), and superoxide anion radicals (O2−), respectively. The total antioxidant capability (T‐AOC) and superoxide dismutase (SOD) activity of FFM were 1.01 mM Trolox equivalents (TE)/g and 89.05 U/g, respectively. Additionally, T‐AOC, SOD, and glutathione peroxidase (GSH‐Px) activities increased, whereas malondialdehyde (MDA) levels decreased in the heart, liver, and kidneys of mice treated with FFM flour, indicating enhanced antioxidant capacity. Therefore, fermentation with edible fungi is suitable for improving the nutritional composition and antioxidant properties of foxtail millet. [ABSTRACT FROM AUTHOR]

This study aimed to explore the potential link between coffee and tea consumption and the risk of deep vein thrombosis (DVT) through Mendelian randomization (MR) analysis. Employing the MR, we identified 33 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for coffee intake and 38 SNPs for tea intake. The investigation employed the inverse-variance weighted (IVW) method to evaluate the causal impact of beverage consumption on DVT risk. Additionally, MR-Egger and MR-PRESSO tests were conducted to assess pleiotropy, while Cochran's Q test gauged heterogeneity. Robustness analysis was performed through a leave-one-out approach. The MR analysis uncovered a significant association between coffee intake and an increased risk of DVT (odds ratio [OR] 1.008, 95% confidence interval [CI] = 1.001–1.015, P = 0.025). Conversely, no substantial causal effect of tea consumption on DVT was observed (OR 1.001, 95% CI = 0.995–1.007, P = 0.735). Importantly, no significant levels of heterogeneity, pleiotropy, or bias were detected in the instrumental variables used. In summary, our findings suggest a modestly heightened risk of DVT associated with coffee intake, while tea consumption did not exhibit a significant impact on DVT risk. [ABSTRACT FROM AUTHOR]

Although the suspension gap between a maglev train and its track is narrow, it has a significant impact on the aerodynamic performance of the train. This study investigated the effect of the suspension gap on the wake flow of a superconducting maglev train traveling at a speed of 600 km/h by comparing the aerodynamics and flow field structure of a tail car (TC) with suspension gaps of 8, 10, 12, and 14 cm. The results showed that with increasing suspension gap, the vortex structures in the wake region move closer to the TC, the airflow from the suspension gap inhibits the high-pressure region of the wake, and the pressure and velocity fluctuations significantly increase near the nose tip of the TC. Moreover, the suspension gap was found to have a significant impact on lift and almost no effect on drag. Increasing the suspension gap leads to a balance in the lift between the head car (HC) and the TC; as the gap continues to increase, the lift ratio of the HC and TC rapidly decreases. [ABSTRACT FROM AUTHOR]

• An innovative optimized interval-time-delayed grey model is proposed for small sample prediction problems. • The proposed interval time-delayed grey model outperforms the comparison models. • Two numerical cases, results analysis, future prediction and scenario analysis are performed. • Comparison of forecasted results with the construction waste goal in Jiangsu Province's 14th Five-Year Plan period. Nowadays, construction waste has become a global challenge that needs to be addressed, and its accurate prediction is crucial for subsequent treatment and policy development. However, current popular big data methods struggle to be effectively applied due to sample size limits. Meanwhile, the key issues of data uncertainty and time-delayed nature must be considered, the former of which can be addressed by interval prediction. Therefore, a novel interval time-delayed three-parameter discrete grey model for construction waste prediction is proposed in this study, whose time-delayed coefficient is optimized via optimization algorithms. Moreover, the relevant mathematical derivation and proof of this model are also described and discussed in detail in the research. Two case studies of the construction waste dataset are used to examine the effectiveness of the proposed model. Through a series of comparisons with other state-of-the-art models, the results show that the proposed model can improve the prediction performance with excellent prediction results. Meanwhile, this study also presents scenario analysis and discussions of the construction waste prediction results during the 14th Five-Year Plan period, and finds that the current policies and measures are difficult to achieve the future planning goals, and further policy development and implementation of measures are imminent. [ABSTRACT FROM AUTHOR]

RAD54B belongs to the SNF2/SWI2 superfamily, participating in homologous recombination repair. DNA damage is the central driver of aging, but there is no direct evidence of an association between RAD54B and vascular aging. The present study sought to investigate the role and mechanisms of RAD54B in endothelial senescence. In senescent animal models, including spontaneously hypertensive rats, normal aging mice, and D-gal-induced senescent mice, and senescent cell models induced by H2O2, D-gal, and culture, RAD54B was remarkably downregulated. Knockdown of RAD54B increased the expression of p53 and p21, increased the ratio of SA-β-gal-positive cells, and decreased the proportion of EdU-positive cells. Conversely, overexpression of RAD54B reversed the senescent phenotypes stimulated by H2O2 and delayed replicative endothelial senescence. Mechanistically, silencing RAD54B compensatorily increased the expression of RAD51/XRCC4, which remained unchanged in H2O2-induced senescence. RAD54B lacking the SNF2 domain could still reverse the increasing expression of p53/p21 induced by H2O2. RAD54B reduced γH2A.X expression and inhibited the expression and phosphorylation of CHK1. In conclusion, RAD54B exerts a direct protective effect against DNA damage through enhancing homologous recombination repair in endothelial senescence, resulting in inhibition of the downstream CHK1/p53/p21 pathway, suggesting that RAD54B may be a potential therapeutic target for vascular aging-associated diseases. [ABSTRACT FROM AUTHOR]

The significance of precise gold price forecasting is accentuated by its financial attributes, mirroring global economic conditions, market uncertainties, and investor risk aversion. However, predicting the gold price is challenging due to its inherent volatility, influenced by multiple factors, such as COVID-19, financial crises, geopolitical issues, and fluctuations in other metals and energy prices. These complexities often lead to non-stationary time series, rendering traditional time series modeling methods inadequate. Our paper presents a multi-objective optimization algorithm that refines the interval prediction framework with quantile regression deep learning in response to this issue. This framework comprehensively responds to gold's financial market dynamics and uncertainties with a screening process of various factors, including pandemic-related indices, geopolitical indices, the US dollar index, and prices of various commodities. The quantile regression deep-learning models optimized by multi-objective optimization algorithms deliver robust, interpretable, and highly accurate predictions for handling non-linear relationships and complex data structures and enhance the overall predictive performance. The results demonstrate that the QRBiLSTM model, optimized using the MOALO algorithm, delivers excellent forecasting performance. The composite indicator AIS reaches −15.6240 and −11.5581 at 90% and 95% confidence levels, respectively. This underscores the model's high forecasting accuracy and its potential to provide valuable insights for assessing future trends in gold prices. The deterministic and probabilistic forecasting framework for gold prices captures the market dynamics with the new pandemic index and comprehensively sets a new benchmark for predictive modeling in volatile market commodities like gold. [ABSTRACT FROM AUTHOR]

This article reports a scoping review of emerging research on COVID-19 health communication. We reviewed and analyzed 206 articles published in 40 peer-reviewed communication journals between January 2020 to April 2021. Our review identified key study characteristics and overall themes and trends in this rapidly expanding field of research. Our review of health communication scholarship during the early stages of the COVID-19 pandemic suggests that health communication scholars have risen to the challenges and interrogated important issues in COVID-19 communication at the individual, group, organizational, and societal levels. We identified important gaps that warrant future research attention including experimental research that seeks to test the causal effects of communication, studies that evaluate communication interventions in under-served populations, research on mental health challenges imposed by the pandemic, and investigations on the promise of emerging communication technologies for supporting pandemic mitigation efforts. [ABSTRACT FROM AUTHOR]

Antioxidants are primarily responsible for the beneficial health effects of foxtail millet. This study evaluated a foxtail-millet-based composite antioxidant nutritive flour consisting of fermented foxtail millet, coarse grains, and fruit powders. The composition of the antioxidant nutritive flour was optimized, and it was found to be rich in antioxidant nutrients, such as phenolics (2.27 g/100 g), vitamin C (0.21 g/100 g), and polysaccharides (0.35 g/100 g). The results revealed that this composite nutritive flour has enhanced in vitro and in vivo physicochemical properties and higher antioxidant activities than commercial nutritive flour. The total antioxidant capability, superoxide dismutase (SOD) capability, and superoxide radical scavenging abilities were 0.84 mM Trolox equivalents/g, 38.29 U/g, and 42.02%, respectively. The activity of the antioxidant enzyme SOD and glutathione peroxidase increased, whereas malondialdehyde levels decreased in the liver, heart, and kidney of mice treated with the nutritive flour, indicating the potential antioxidant activity of this fermented foxtail-millet-based nutritive flour. [ABSTRACT FROM AUTHOR]

This article discusses the physiological and molecular responses of fruit crops to various environmental stresses, such as high temperatures, drought, waterlogging, and nutrient deficiencies. These adverse conditions can negatively impact fruit growth, yield, and quality. The article highlights the importance of understanding these response mechanisms in order to develop strategies for improving stress tolerance and selecting resistant varieties. The authors emphasize the significance of sustainable agriculture and the need for precise knowledge of physiological and molecular mechanisms to enhance fruit production. [Extracted from the article]

JZP458 is a recombinant Erwinia chrysanthemi asparaginase for patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who have developed hypersensitivity to Escherichia coli–derived asparaginases. A population pharmacokinetic (PopPK) model was developed for intramuscular (i.m.) JZP458 using serum asparaginase activity (SAA) data from 166 patients with ALL/LBL enrolled in a phase II/III study conducted in collaboration with the Children's Oncology Group (AALL1931; NCT04145531). The pharmacokinetics of i.m. JZP458 is best characterized by a one‐compartment model with mixed‐order absorption and linear elimination, with body surface area included as an allometric covariate on JZP458 SAA clearance and volume, and race (i.e., Black/African American) and disease subtype (i.e., T‐cell ALL) as covariates on JZP458 SAA clearance. The PopPK model was used to simulate SAA profiles to estimate the likelihood of achieving nadir SAA (NSAA) levels greater than or equal to 0.1 IU/mL with different dosing regimens. Model‐based simulations suggest when JZP458 is administered i.m. at 25/25/50 mg/m2 Monday/Wednesday/Friday (MWF), 92.1% of subjects (95% confidence interval [CI]: 90.9%, 93.3%) are expected to achieve the last 72‐h (after 50 mg/m2 dose) NSAA level greater than or equal to 0.1 IU/mL, and 93.8% (95% CI: 92.7%, 94.9%) are expected to achieve the last 48‐h (after 25 mg/m2 dose) NSAA level greater than or equal to 0.1 IU/mL. When JZP458 is administered 25 mg/m2 i.m. every 48 h, 93.8% (95% CI: 92.7%, 94.8%) are expected to achieve the last 48‐h NSAA level greater than or equal to 0.1 IU/mL. These data supported the i.m. dose of 25 mg/m2 every 48 h or 25/25/50 mg/m2 on a MWF dosing schedule in patients with ALL/LBL. [ABSTRACT FROM AUTHOR]

Protein fluorescence signals essential information about the conformational dynamics of proteins. Different types of intrinsic fluorophores reflect different protein local or global structural changes. Bovine Serum Albumin (BSA) is a transport protein that contains two intrinsic fluorophores: Tryptophan134 (Trp134) and Tryptophan213 (Trp213). This protein displays an interesting temperature dependence of the tryptophan fluorescence. However, the molecular mechanism of the temperature dependence is still unclear. In this work, we propose a generic rotamer model to explain this phenomenon. The model assumes the presence of rotamer‐specific fluorescence lifetimes. The fluorescence temperature dependence is caused by the population shifts between different rotamers due to thermal effects. As a proof of concept, we show that the tryptophan's two fluorescence lifetimes (휏1 = 0.4–0.5 ns and 휏2 = 2‐4 ns) are sufficient to qualitatively explain the fluorescence intensity change at different temperatures, both in buffer solution (water) and in the protein. To computationally verify our rotamer hypothesis, we use an all‐atom molecular dynamics simulation to study the effects of temperature on the two tryptophans' rotamer dynamics. The simulations show that Trp134 is more sensitive to temperature, consistent with experimental observations. Overall, the results support that the temperature dependence of fluorescence in the protein BSA is due to local conformational changes at the residue level. This work sheds light on the relationship between tryptophan's rotamer dynamics and its ability to fluorescence. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the antifibrotic effect of ZD6474 in human pterygium fibroblasts (HPFs) and angiogenesis in human umbilical vein endothelial cells (HUVECs) compared with mitomycin C (MMC). Methods: Pterygium and tenon fibroblasts were isolated from patients undergoing surgery to culture HPFs and human tenon fibroblasts (HTFs). The effects of ZD6474 on HPF, HTF, and HUVEC proliferation and migration were detected using CCK8 and wound-healing assays, respectively. Fibrosis and epithelial–mesenchymal transformation (EMT) were evaluated by western blotting [transforming growth factor beta (TGF-β)1/2 and snail] and immunofluorescence (vimentin and α-smooth muscle actin). The antiangiogenic effect of ZD6474 on HUVECs was assessed using a tube formation assay. To determine the potential mechanism, the expression of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) was evaluated by treatment with ZD6474 via western blotting. Results: ZD6474 robustly inhibited the proliferation and migration of HPFs rather than HTFs compared with those in the MMC group (**P < 0.01). In HPFs, fibrosis and EMT (vimentin, TGF-β1/2, and snail) were significantly reversed by ZD6474. MMC (>50 μg/mL) significantly reduced HTF viability, whereas ZD6474 (<5 μM/mL) did not decrease HTF viability. HUVEC proliferation and migration were clearly decreased, and tube formation was notably interrupted by ZD6474. Activation of p-AKT and p-mTOR was inhibited by ZD6474 treatment of HPFs and HUVECs. Conclusion: ZD6474 is more effective than MMC in reducing fibrosis and EMT in HPFs. In addition, ZD6474 was less toxic to HTFs. ZD6474 also exhibited antiangiogenic effects in HUVECs. This study may aid in the development of novel agents to prevent pterygium recurrence after pterygium excision. [ABSTRACT FROM AUTHOR]

Objectives. This study is aimed at investigating the difference of meibum chemokines in MGD subjects with different degrees of MGD and the correlations of meibum chemokines with ocular surface parameters. Methods. Twenty MGD subjects (MQ score > 8) and twenty MGD subjects (MQ score ≤ 8) were enrolled to examine ocular surface parameters, including meibomian gland function (MGE, MQ meibograde, and lid margin), tear stability (NIKBUT, FBUT, and LLT), tear secretion (SIT and TMH), OSDI questionnaire, and CFS. These subjects also obtained meibum samples, and then meibum chemokines (MIG, IFN-γ, IL-8, IP-10, and MCP-1) were examined and analyzed the correlations with ocular surface parameters. Results. MIG, IP-10, and MCP-1 were found clearly elevated in MGD subjects with higher MQ score than that in MGD subjects with low MQ score (MIG: p = 0.038 , IP-10: p = 0.019 , MCP-1: p = 0.040). The meibomian function was found mostly positively correlated with level of MIG (MGE: r = 0.600 , p < 0.001 ; MQ: r = 0.579 , p < 0.001) and IP-10 (MGE: r = 0.719 , p < 0.001 ; MQ: r = 0.601 , p < 0.001). The tear stability was found negatively correlated with the level of MIG (NIKBUT: r = − 0.438 , p = 0.005 ; LLT: r = − 0.464 , p = 0.003) and MCP-1 (NIKBUT: r = − 0.425 , p = 0.006 ; LLT: r = − 0.761 , p < 0.001). The OSDI was positively correlated with IL-8, IFN-γ, and MIG. Conclusion. Chemokines in meibum were significantly evaluated in MGD subjects suffering from severe meibomian gland quality. These findings indicate that chemokines play roles in the pathogenesis of MGD, and molecules targeted by chemokines may develop as novel agents for MGD therapy, perhaps through inhibiting inflammation in meibomian glands and microvascular in the eyelid margin. [ABSTRACT FROM AUTHOR]

Backgrounds: A new generic formulation of 3.5% lidocaine hydrochloride ophthalmic gel has been developed in China. This study aimed to evaluate the pharmacokinetics and effectiveness of this lidocaine hydrochloride gel for ocular surface anesthesia. Methods: In the pharmacokinetics study, the new form of 3.5% lidocaine hydrochloride gel or Akten™ 3.5% lidocaine hydrochloride gel was applied in eyes of 70 rabbits. The ocular tissues and plasma samples were collected after the application of 3.5% lidocaine hydrochloride gel or Akten lidocaine gel and analyzed using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to determine the concentration of lidocaine. A multicenter, randomized, double-blind prospective clinical trial was conducted in Chinese adults. Two hundred twenty participants were 1:1 randomized into the sham gel group or the lidocaine hydrochloride group. The primary efficacy endpoint was defined as the percentage of subjects achieving anesthesia by 5 min. Results: The animal pharmacokinetics study showed the lidocaine level was significantly higher in the choroid at 15 min and the vitreous body at 15 and 30 min; it was lower in tears at 8 h for 3.5% lidocaine hydrochloride gel than Akten (P ≤ 0.05). Our clinical trial showed that the percentage of subjects achieving anesthesia within 5 min in the lidocaine hydrochloride gel group was significantly higher than the sham gel group (86.92%-18.18%, P < 0.0001). The incidence of adverse events was relatively low and favorable for both groups. Conclusion: This new formulation of lidocaine hydrochloride gel, with pharmacokinetics similar to Akten, may exert a sustained, effective, and safe anesthetic effect. The clinical trial for this new generic formulation of lidocaine hydrochloride has been registered with the Drug Clinical Trial Registration and Information Publicity Platform established by State Food and Drug Administration of China (Registration No. CTR20160593). [ABSTRACT FROM AUTHOR]

Two years of data on cloud condensation nuclei (CCN) measured at the Liupan Mountain (LPS) Meteorological Station from August 2020 to November 2021 were analyzed in this study. The results show that the mean annual CCN concentration was 851 cm−3 and that the mean concentration of CCN increases with the supersaturation degree. The curves of the diurnal variation in CCN concentration show one peak and one valley, which correspond to the diurnal variation in the mixed-layer height and valley wind. Regarding seasonal variations, the CCN concentration, as well as the degree of internal mixing, is higher in the spring and winter, while the degree of external mixing is higher in the summer and autumn. The transport of CCN is closely related to the wind transport evolution, and the southeast and southwest sides of the LPS station contribute more to the CCN concentration in the spring and winter due to central heating in the wintertime. Though correlations between CCN concentration and pressure are scarce, the CCN concentration and temperature (or humidity) are positively (or negatively) correlated, especially in the spring. Furthermore, the 48-h backward trajectory analysis indicates that the sources in the northwest direction are a major contributor to the CCN concentration. The pollutants mainly came from the northwest and southwest sides, according to the analysis of potential sources using the PSCF and CWT approach. The study of CCN evolution and contribution area is beneficial for further research on the physical properties of cloud droplets, the influence of mountains on CCN changes and the role of CCN in terrain cloud precipitation, which are significant for the improvement of weather modification techniques. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta‐analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients. Materials and Methods: We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β‐cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis. Results: Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference −0.36, 95% confidence interval −0.61 to −0.10, I2 = 91.6%), increased fasting C‐peptide (weighted mean difference 0.08, 95% confidence interval −0.02 to 0.17, I2 = 88.8%) and had fewer adverse events compared with insulin alone. The inter‐study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C‐peptide, regardless of the duration of intervention and sample size. Conclusions: Sitagliptin combined with insulin can achieve better glycemic control and improve islet β‐cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well‐designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials. [ABSTRACT FROM AUTHOR]

Fresh Lentinus edodes (L. edodes) are prone to browning (including enzymatic and nonenzymatic browning), which affects their quality and leads to economic losses during later processing. This study explored various effective color protection methods (color protection reagent and/or blanching) for inhibiting the browning of L. edodes. First, a single‐factor experiment and a response surface method were used to optimize the concentration of the color retention reagent. The compound color retention reagent (comprising 0.1% phytic acid, 0.8% sodium citrate, and 0.5% d‐sodium erythorbate) had the smallest total color difference (ΔE) value, suggesting that the compound color reagent had a better inhibiting effect than the single agent. Following this, the blanching conditions were studied; the polyphenol oxidase (PPO) activity was the lowest when the blanching temperature was 90°C and blanching time 180 s, indicating that browning is likely to be minimal. Finally, comparing the oxidase activity and total color difference (ΔE) revealed that combining the two color protection methods inhibits browning better than using a single method (color protection reagent or blanching). In addition, the polysaccharide and vitamin C (VC) contents of L. edodes under optimal color protection conditions were determined, which were 0.96 and 2.54 g/100 g fresh weight (FW), respectively. The results demonstrated that this color protection method effectively inhibits browning, reduces the nutritional loss, and improves the quality of L. edodes. [ABSTRACT FROM AUTHOR]

The development of heterogeneous base catalyst with acid resistance has become a major topic in the current research on the biodiesel production process. Halloysite nanotubes (HNTs) is supported with bimetallic of calcium and zinc for modification and labeled as HNTs-Ca/Zn to show both the acid and base characteristics. Further, this supported catalyst is used to produce biodiesel from the acidulated palm oil through catalyzing transesterification in one-step in this study. The HNTs-Ca/Zn catalyst, synthesized by the impregnation method, is characterized by TG-DTG, XRD, XPS, TEM, SEM-EDX, nitrogen adsorption-desorption, CO 2 /NH 3 -TPD, FTIR and Raman. The capability of the HNTs-Ca/Zn catalyst in catalyzing transesterification is investigated, where the maximum yield of 95.22% is achieved with the molar ratio of Zn to Ca of 1.5. The advantage of HNTs-Ca/Zn1.5 catalyst is prominent when the transesterification source oil is acidulated, where the biodiesel yield of 92.66% is obtained even at the acid value of 26.02 mg KOH g−1. Besides, reusability of the catalyst is acceptable, where the yield of 77.91% is maintained after the fourth reused cycle. Further, the Genetic Algorithm-Back Propagation (GA-BP) neural network is used to train and predict the transesterification parameters of the reaction temperature, catalyst amount and methanol to oil molar ratio. The prediction of the biodiesel yield is reasonable. At the predicted reaction parameters of 158 °C, catalyst amount of 7.1 wt.% and methanol to oil molar ratio of 15.5, the predicted biodiesel yield is 98.71%, where the experimental verification value is 98.60%. Therefore, the HNTs-Ca/Zn catalyst is considered to demonstrate exceptional catalytic performance and recyclability, offering the potential for biodiesel production. [Display omitted] • HNTs-Ca/Zn acid-base bifunctional catalysts are produced for biodiesel production. • The HNTs-Ca/Zn1.5 catalyst performs excellent acid resistance under 26.02 mg KOH g−1. • Transesterification parameters are optimized by the GA-BP neural network. • The maximum biodiesel yield of 98.60% is obtained under the optimum conditions. [ABSTRACT FROM AUTHOR]

During the sedimentary period of the Ordovician Yingshan Formation, the carbonate platform of the Gucheng area in the Tarim basin was characterized by a distally steepened ramp. Relative sea-level changes exerted a strong influence on the shoal facie dolomite reservoirs of the 3rd Member of the Ordovician Yingshan Formation (the Ying 3 member), sedimented in the context of a shallow water environment on the carbonate ramp. However, previous studies that lacked high-frequency sea-level changes in the Gucheng area prevent further dolomite reservoir characterization. The current work carries out systematic sampling based on the continuous core from the upper and middle parts of the Ying 3 member in two newly drilled exploration wells (GC17 and GC601) and a series of geochemistry analyses, such as C-O isotope, Sr isotope, and rare earth elements (REE), which helps to investigate the features of the shoal facies dolomite reservoir development against high-frequency sea-level changes. With the help of Fischer plots of these two wells, high-density δ13C data (sample interval is about 0.272 m) were merged to construct a comprehensive curve, contributing to characterizing the high-frequency sea-level changes of the upper and middle parts of the Ying 3 member in the Gucheng area and validating the relationship between the pore-vug vertical distribution and high-frequency sea-level changes. Results revealed that the porosity of dolomite reservoirs increased when the high-frequency sea-level fell and decreased when it rose. Furthermore, the karst surface can be found at the top of the upward-shallowing cycle during the high-frequency sea-level falling; the pore-vug reservoirs are concentrated below the karst exposure surface, and porous spaces are more developed closer to the top of the cycle. The high frequency sea-level curve built in this study can be used as a standard for further research of regional sea-levels in the Gucheng area, and this understanding is highly practical in the prediction of shoal facies carbonate reservoir in carbonate ramp. [ABSTRACT FROM AUTHOR]

The amyloid precursor protein (APP) is a ubiquitously expressed type 1 transmembrane protein mostly known for serving as a precursor to the amyloid-β peptide (Aβ), a culprit in Alzheimer disease (AD). However, APP also has important physiological functions by being implicated in, for instance, adhesion, signaling, neuronal development, and synaptic function. Human APP contains 2 N-glycosylation sites, at asparagine (N) 467 (N467) and N496. Here, we studied the role of N-glycosylation on APP trafficking and processing by constructing APP-SNAP plasmid vectors for wildtype APP and N-glycosylation site mutants in which N467 or N496 was replaced by glutamine (Q) and expressed these in HEK293T cells. Lack of either of the 2 N -glycans resulted in a reduction in the size of intracellular APP-SNAP-positive vesicles and a reduction of APP-SNAP in the plasma membrane and lysosomes. Importantly, loss of either of the 2 N -glycans resulted in elevated levels of intracellular as well as secreted Aβ42. These data suggest that N -glycans have a major impact on trafficking and processing of APP and could play an important role in the development of AD. [ABSTRACT FROM AUTHOR]

The exhalation of aerosols during musical performances or rehearsals posed a risk of airborne virus transmission in the COVID‐19 pandemic. Previous research studied aerosol plumes by only focusing on one risk factor, either the source strength or convective transport capability. Furthermore, the source strength was characterized by the aerosol concentration and ignored the airflow rate needed for risk analysis in actual musical performances. This study characterizes aerosol plumes that account for both the source strength and convective transport capability by conducting experiments with 18 human subjects. The source strength was characterized by the source aerosol emission rate, defined as the source aerosol concentration multiplied by the source airflow rate (brass 383 particle/s, singing 408 particle/s, and woodwind 480 particle/s). The convective transport capability was characterized by the plume influence distance, defined as the sum of the horizontal jet length and horizontal instrument length (brass 0.6 m, singing 0.6 m and woodwind 0.8 m). Results indicate that woodwind instruments produced the highest risk with approximately 20% higher source aerosol emission rates and 30% higher plume influence distances compared with the average of the same risk indicators for singing and brass instruments. Interestingly, the clarinet performance produced moderate source aerosol concentrations at the instrument's bell, but had the highest source aerosol emission rates due to high source airflow rates. Flute performance generated plumes with the lowest source aerosol emission rates but the highest plume influence distances due to the highest source airflow rate. Notably, these comprehensive results show that the source airflow is a critical component of the risk of airborne disease transmission. The effectiveness of masking and bell covering in reducing aerosol transmission is due to the mitigation of both source aerosol concentrations and plume influence distances. This study also found a musician who generated approximately five times more source aerosol concentrations than those of the other musicians who played the same instrument. Despite voice and brass instruments producing measurably lower average risk, it is possible to have an individual musician produce aerosol plumes with high source strength, resulting in enhanced transmission risk; however, our sample size was too small to make generalizable conclusions regarding the broad musician population. [ABSTRACT FROM AUTHOR]

Heat shock proteins (Hsps) are highly conserved proteins whose expression can be induced by high temperature and play an important role in a variety of biological processes. However, systematic identification of the Hsp60/10 and small Hsp (sHsp) gene family in rainbow trout has not yet been reported, and there is little available information about its roles in evolution in rainbow trout, a typical economical cold-water fish. In this study, we performed a comprehensive analysis of the rainbow trout Hsp60/10 and sHsp gene family and to investigate their expression profiles. A total of one Hsp60 gene, one Hsp10 gene, and ten sHsp genes were identified. According to RNA-seq analysis of rainbow trout liver and head kidney under heat stress, a total of six out of ten sHsp genes were significantly upregulated in liver and head kidney. Real-time RT-PCR (RT-qPCR) was used to quantitatively analyze the expression levels of these genes in different tissues of rainbow trout. Results showed that the expression of hspe1 and hspd1 was lowest in liver and gill, respectively, and highest in brain. In sHsp gene family, all genes are highly expressed in the liver and head kidney, but relatively low in the heart, spleen, brain, gills, and muscles. This systematic analysis provided valuable information about the diverse roles of Hsp60/10 and sHsp in the evolution of teleost fish, which will contribute to the functional characterization of Hsp60/10 and sHsp genes in further research. [ABSTRACT FROM AUTHOR]

We propose and demonstrate a widely tunable microwave photonic filter with controlled frequency agility, bandwidth reconfigurability and flexible switching functions. It is based on the self-interference microring aided by an asymmetric Mach–Zehnder interferometer, breaking the fundamental microring footprint limit and achieving a doubled free spectral range (123.2 GHz) with a strong out-of-band rejection. Simulation results show that a bandpass microwave photonic filter can be tuned across a 60 GHz frequency range with a varied 3-dB bandwidth from 2.13 GHz to 40.7 GHz in a cascaded dual-ring topology. Its RF out-of-band rejection ratio is improved by more than 60 dB in the high frequency region due to a perfect residual phase cancellation. A dual-band notch microwave photonic filter with an extinction ratio of about 50 dB and a frequency tunable range of about 27.7 GHz is also demonstrated, showing its broadly applicability. Our method highlights its suitability to improve chip-scale wideband and high-performance RF receiver systems. • Our design breaks the fundamental microring footprint limit and achieves a doubled FSR using dissipative tuning. • A bandpass MPF can be tuned across a 60 GHz frequency range with a varied 3-dB bandwidth from 2.13 GHz to 40.7 GHz. • Our design enables an RF out-of-band rejection ratio of more than 60 dB due to a perfect residual phase cancellation. [ABSTRACT FROM AUTHOR]

• Aluminum (Al) affected the contents of N-containing compounds in Citrus. • Al affected the activities of N metabolism–related enzymes in Citrus. • Al differentially affected N metabolism between Citrus sinensis and C. grandis. • Increased leaf GOGAT might be an index of Al–tolerance in Citrus plants. Citrus are mostly planted in tropical/subtropical acidic soil areas, and are susceptible to aluminum (Al) toxicity, which affects tree growth and fruit quality. However, the effects of Al stress on the nitrogen (N) metabolism in different Al-tolerant Citrus varieties, and whether N metabolism is related to Al-tolerance in different Citrus varieties, were remained unveiled. In the current study, Al-tolerant "Xuegan" (Citrus sinensis) and Al-sensitive "Sour pummelo" (C. grandis), were irrigated with different nutrient solutions with or without Al. Al decreased the dry weights (DW) of leaves, stems and roots, as well as the N content, the N accumulation, total soluble proteins (TSPs) and total free amino acids (TFAAs) of different tissues of C. grandis , but it increased the ratio of root DW to shoot DW. In contrast, Al did not change the parameters mentioned above, except for decreasing the content and accumulation of N in C. sinensis roots. Al did not change the content of NO 3 – in different position leaves and roots, but decreased the content of NH 4 + in C. grandis. Al decreased the content of NO 3 – in different position leaves and roots, but except for the lower leaf, Al did not change that of NH 4 + in C. sinensis. Although Al affected the activities and gene expression levels of N metabolism–related enzymes in the leaves and roots of these two Citrus species, the effects of Al on these parameters were more pronounced in C. grandis than in C. sinensis. Results from correlation analysis (CoA) and principal components analysis (PCA) indicated that the increased root DW/shoot DW and NO 3 --N content in the roots and middle/upper leaves might be the related indicators of Al toxicity, whereas the enhanced activity of leaf GOGAT might be related to the Al–tolerance in Citrus plants. In conclusion, this study preliminarily revealed that the impact of Al on N metabolism and the response of N metabolism–related indicators to Al stress in Citrus , providing scientific reference for high-yield and high-quality cultivation of Citrus grown in acidic soil areas. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • An acid-base bifunctional SW-Ca3 catalyst was successfully synthesized. • TPD shows that the prepared catalyst has excellent acidity and alkalinity. • Effect of various reaction conditions on biodiesel yield has been detected by RSM. • The maximum biodiesel yield of 87.67% was obtained with a 4% oleic acid addition. • The physicochemical properties of the produced biodiesel comply with ASTM D 6751. Conventional solid base catalysts are difficult to adapt to the low-grade oil used in the industrial production of biodiesel due to the high acidity. In this paper, an acid-base bifunctional catalyst loaded with CaO from the solid waste of blast furnace dust was prepared to produce biodiesel by transesterification. Meanwhile, palm oil with oleic acid was used to simulate acid oil. The catalysts were characterized by XRD, XPS, BET, SEM-EDX, CO 2 -TPD and NH 3 -TPD. The biodiesel produced was tested and found to be compliant with ASTM D 6751. the response surface method based on the Central composite design (RSM-CCD) is used to optimize key parameters for the production of biodiesel. Under the optimal experimental conditions (i.e., methanol to oil ratio of 15.24, catalyst dosage of 7.96%, reaction temperature of 148.95 °C and reaction duration of 2 h, even with the oleic acid addition of 4%) the yield of biodiesel prepared by SW-CaO catalyst was 87.67%. [ABSTRACT FROM AUTHOR]

The CaAl-LDHs exhibited the saturated mineralization capacity of 588.23 mg/g and a removal efficiency of >99% for Cu2+ in aqueous solution. Besides the isomorphic substitution mechanism, the dissolution-recombination mechanism was demonstrated. To avoid the secondary pollution of Cu2+, the structured adsorbent of CaAl-LDHs/PAN showed removal efficiency of 95% towards Cu2+ in 7 days in soil experiments, and complete removal of the mineralized products of Cu2+ from the soil can be achieved. [Display omitted] • The CaAl-LDHs exhibited the saturated mineralization capacity of 588.23 mg/g towards Cu2+ and a removal efficiency of >99 % in aqueous solution. • The co-existence of CaAl-LDHs and CuAl-LDHs in only 5 min, demonstrating the dissolution-recombination mechanism. • The CaAl-LDHs/PAN showed high removal efficiency of 95 % towards Cu2+ in 7 days in Cu2+ contaminated soil. • The complete removal of Cu2+ from soil can be achieved by the CaAl-LDHs/PAN filter bag. The in-situ mineralization is regarded as one of the most promising remediation technologies for heavy metals removal. Herein, the CaAl-LDHs (LDHs = layered double hydroxides) with the particle size of ∼3 μm were successfully synthesized, which exhibited the saturated mineralization capacity of 588.23 mg/g and a removal efficiency of >99 % for Cu2+ ions in aqueous solution. The mineralization equilibrium can be reached in 150 min. Detailed quasi-situ XRD and HRTEM results revealed that besides the isomorphic substitution mechanism, the dissolution-recombination mechanism can be observed, as evidenced by the co-existence of CaAl-LDHs and CuAl-LDHs in only 5 min. Meanwhile, the CaAl-LDHs can be packaged into the polyacrylonitrile (PAN) membranes and the resultant CaAl-LDHs/PAN showed removal efficiency of 95 % towards Cu2+ in 7 days of column leaching experiment. Such filter bags can be easily taken away, resulting in the complete removal of Cu2+ from soil. [ABSTRACT FROM AUTHOR]

The structure of the blade's leading edge significantly affects the centrifugal pump as turbines (PATs) performance. This paper has attempted to investigate the hydraulic performance and pressure pulsations characteristics of PATs with bionic tubercle leading edge impellers by numerical calculation and experiment methods. The results showed that the bionic tubercles structure at the leading edge of the blade does not change the PAT's best efficiency point and helps improve the energy recovery efficiency under all operating conditions, especially with efficiency increased by 6.04 % under the over-load operation condition. Moreover, the bionic tubercles structure at the blade's leading edge can improves the impeller's local flow characteristics and effectively reduces the amplitude of dominant frequency in the main domains of PATs. The maximum reduction amplitude of pressure pulsations in the impeller with the bionic tubercle leading-edge under 0.7 Q b , Q b , and 1.3 Q b operating conditions is 29.8 %, 23.3 % and 61.1 %, respectively. This research provides a reference for the use of bionic blades to improve the energy recovery efficiency and operation stability of PATs. [ABSTRACT FROM AUTHOR]

The structure of the blade's leading edge significantly affects the centrifugal pump as turbines (PATs) performance. This paper has attempted to investigate the hydraulic performance and pressure pulsations characteristics of PATs with bionic tubercle leading edge impellers by numerical calculation and experiment methods. The results showed that the bionic tubercles structure at the leading edge of the blade does not change the PAT's best efficiency point and helps improve the energy recovery efficiency under all operating conditions, especially with efficiency increased by 6.04 % under the over-load operation condition. Moreover, the bionic tubercles structure at the blade's leading edge can improves the impeller's local flow characteristics and effectively reduces the amplitude of dominant frequency in the main domains of PATs. The maximum reduction amplitude of pressure pulsations in the impeller with the bionic tubercle leading-edge under 0.7 Q b , Q b , and 1.3 Q b operating conditions is 29.8 %, 23.3 % and 61.1 %, respectively. This research provides a reference for the use of bionic blades to improve the energy recovery efficiency and operation stability of PATs. [ABSTRACT FROM AUTHOR]

• A bionic tunnel portal model was constructed based on the characteristics of shark gills. • The dependence of the micro-pressure wave on the opening ratio and oblique cutting angle of the bionic shark gill tunnel portal was elucidated. • The relationship between jet-stream energy and micro-pressure wave was studied. In this study, the bionic principle is used to relieve the micro-pressure waves (MPWs) at the tunnel exit. A bionic shark gill tunnel portal with holes was studied, and the effects of the opening ratios and oblique cutting angles of the bionic shark gill opening tunnel portal on the initial compression wave (ICW) and MPW induced by a high-speed train (HST) passing through the tunnel are examined. The results show that when the opening ratio of the bionic shark gill tunnel portal is 24%, the highest mitigation effect on the ICW pressure gradient and MPW is observed. In addition, the high-pressure region of the ICW in the tunnel decreased with increasing opening ratio. The greatest mitigation effect on the ICW pressure gradient and MPW is obtained for the oblique cutting angle of the bionic hole on the tunnel portal (with an opening ratio of 24%) of 16°, because the oblique cutting angle facilitates the expulsion of the jet-stream from the bionic hole at the tunnel portal. [ABSTRACT FROM AUTHOR]

Cotton fabrics (CF) with high flame retardancy and antibacterial performance are attracting more and more attention in the practical applications, e.g. home decorations. In this work, a novel Ag-mediated organic-inorganic phosphorus-hybrid coating (5BL/Ag-D) was developed using polyethylene imine (PEI)/ammonium polyphosphate (APP) polyelectrolyte bilayer and Ag-phosphoryl triazole complex (Ag D) via dip-coating method for flame-retardant CF with the antibacterial property. Interestingly, limiting oxygen index (LOI) of CF/5BL/Ag-D was sharply promoted to 33.5 % from 18.6 % of CF. Besides, CF/5BL/Ag-D could self-extinguish in the vertical burning test with afterflame time and afterglow time as low as 0 s. More importantly, as revealed in the cone calorimeter tests (CCT), the heat release involving peak heat release rate (PHRR) and total heat release (THR) of CF/5BL/Ag-D decreased from 193.8 kW/m2 and 14.8 MJ/m2 of CF to merely 16.7 kW/m2 and 3.2 MJ/m2, respectively. In addition, owing to the presence of Ag+, CF/5BL/Ag-D was endowed with the desired antibacterial property, and the bacteriostatic rates of CF/5BL/Ag-D on escherichia coli (E. coli) and staphylococcus aureus (S. aureus) were up to 94.7 % and 95.1 %, respectively. Moreover, the softness, the whiteness and the mechanical properties of CF/5BL/Ag-D were comparable to those of CF. In general, this work provides a promising approach to prepare Ag-mediated organic-inorganic phosphorus-hybrid coating for multifunctional cotton fabrics. • A novel Ag-mediated organic-inorganic P-hybrid coating (5BL/Ag-D) was developed. • PHRR and THR of CF/5BL/Ag-D decreased to merely 16.7 kW/m2 and 3.2 MJ/m2. • The bacteriostatic rates of CF/5BL/Ag-D on E. coli and S. aureus were 94.7 % and 95.1 %. • The whiteness and tensile strength of CF/5BL/Ag-D were enhanced with respect to CF. [ABSTRACT FROM AUTHOR]

In order to clarify the characteristics of pore-throat in tight sandstone reservoirs in the Dibei area of the Kuqa Depression in the Tarim Basin (Northwest China) and to make clear its impact on reservoir quality and productivity, microscopic observation and quantitative analysis of 310 tight sandstones in the Kuqa Depression are carried out by using various methods. Microscopic observation shows that the shapes of the pores are flat, oval, and long-narrow. A great number of throats connect the nanoscale pores in the form of a network. Quantitative analyses including RCMP (rate-controlled mercury penetration), HPMI (high-pressure mercury injection), NA (nitrogen adsorption), and routine and stress-dependent core analysis show that the peak of pores radius ranges from 125 μm to 150 μm, and the throat radius is in the range of 1 μm-4 μm. The throat space accounts for about 2/3 of the total space of the tight sandstones, which is the major storage space for natural gas. The space shape has a great influence on the reservoir seepage capacity, particularly under the condition of overburden pressure. The pores with throat radius greater than 300 nm have free fluid, and they contribute more than 98% of the reservoir permeability. The pore spaces with throat radius among 300 nm-52 nm can release fluids by reservoir stimulation. The pore-throats with radius < 52 nm cannot release the irreducible hydrocarbon fluids. In addition, formation pressure is easy to destroy tight sandstone reservoir. The research results will provide insights into the efficient recovery of natural gas in tight sandstones. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer deaths. Although targeted therapies and programmed cell death protein 1 (PD-1) blockade have offered great advances, five-year survival rates remained low. Diagnosis of lung cancer at an earlier stage is the most efficient approach to improve survival. Tumor associated autoantibodies (TAAb) have been proven a promising innovative biomarker of lung cancer. We aimed to comprehensively evaluate the sensitivity, specificity, and accuracy of TAAbs in lung cancer detection, especially in early-stage patients, through a multicenter prospective observational clinical trial, and to screen out the novel combination of TAAbs with the best detection value for Chinese population. We aimed to enroll 1,400 participants from three clinical centers and divide into two cohorts. One cohort is participants with newly pathologically confirmed lung cancer as the case cohort, and the other is participants with benign nodules, matched healthy controls and other benign lung diseases as the control cohort. Cases and controls were randomly distributed into training or validation set. The level of 14 autoantibody candidates in their plasma were detected. A Monte-Carlo Simulated Annealing method was implemented to develop a composite panel of autoantibodies to distinguish between matched lung cancer cases and controls in the training set. The newly developed autoantibody panel was tested in the validation set for sensitivity, specificity and accuracy. This is the first and largest clinical trial designed to develop a novel autoantibody panel for lung cancer detection specifically for Chinese people. We performed a multicenter, prospective, observational study to find a novel panel of autoantibody markers that can help the diagnosis of lung cancer and the characterization of pulmonary nodules in Chinese population. The results may help to provide evidence-based recommendations to clinicians for lung cancer early detection and pulmonary nodule management. This study is registered in the ClinicalTrials.gov (NCT04216511). [ABSTRACT FROM AUTHOR]

JZP‐458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme expected to lack immunologic cross‐reactivity to Escherichia coli–derived asparaginases. It is being developed as part of a multiagent chemotherapeutic regimen to treat acute lymphoblastic leukemia or lymphoblastic lymphoma patients who develop E coli–derived asparaginase hypersensitivity. A population pharmacokinetic (PopPK) model was developed for JZP‐458 using serum asparaginase activity (SAA) data from a phase 1, single‐dose study (JZP458‐101) in healthy adults. Effects of intrinsic covariates (body weight, body surface area, age, sex, and race) on JZP‐458 PK were evaluated. The model included SAA data from 24 healthy adult participants from the phase 1 study who received JZP‐458: intramuscular (IM) data at 12.5 mg/m2 (N = 6) and 25 mg/m2 (N = 6), and intravenous (IV) data at 25 mg/m2 (N = 6) and 37.5 mg/m2 (N = 6). Model simulations of adult and pediatric SAA profiles were performed to explore the likelihood of achieving a therapeutic target nadir SAA (NSAA) level ≥0.1 IU/mL based on different administration strategies. PopPK modeling and simulation suggest JZP‐458 is expected to achieve 72‐hour NSAA levels ≥0.1 IU/mL in 100% of adult or pediatric populations receiving IM administration at 25 mg/m2, and in 80.9% of adult and 94.5% of pediatric populations receiving IV administration at 37.5 mg/m2 on a Monday/Wednesday/Friday (M/W/F) dosing schedule. Based on these results, the recommended starting dose for the phase 2/3 pivotal study is 25 mg/m2 IM or 37.5 mg/m2 IV on a M/W/F dosing schedule in pediatric and adult patients. [ABSTRACT FROM AUTHOR]

L‐asparaginase has been an important component of acute lymphoblastic leukemia (ALL) therapy for over 40 years, and is standard therapy during ALL induction and consolidation treatment. L‐asparaginases are immunogenic and can induce hypersensitivity reactions; inability to receive asparaginase has been associated with poor patient outcomes. There are L‐asparaginases of varied bacterial origins, with the most commonly used being Escherichia coli (E. coli); therefore, to ensure that patients who develop hypersensitivity to E. coli‐derived asparaginases receive an adequate therapeutic course, alternative preparations are warranted. JZP‐458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme with no immunologic cross‐reactivity to E. coli‐derived asparaginases. To evaluate the safety, tolerability, and pharmacokinetics (PK) of a single dose of JZP‐458, a randomized, single‐center, open‐label, phase I study was conducted with JZP‐458 given via i.m. injection or i.v. infusion to healthy adult volunteers. At the highest doses tested for each route of administration (i.e., 25 mg/m2 i.m. and 37.5 mg/m2 i.v.), JZP‐458 achieved serum asparaginase activity (SAA) levels ≥ 0.1 IU/mL at 72 hours postdose for 100% of volunteers. Bioavailability for i.m. JZP‐458 was estimated at 36.8% based on SAA data. All dose levels were well‐tolerated, with no unanticipated adverse events (AEs), no serious AEs, and no grade 3 or higher AEs. Based on PK and safety data, the recommended JZP‐458 starting dose for the pivotal phase II/III study in adult and pediatric patients is 25 mg/m2 i.m. and 37.5 mg/m2 i.v. on a Monday/Wednesday/Friday dosing schedule. [ABSTRACT FROM AUTHOR]

The best efficiency point prediction of the pump as turbine (PAT) is one of the key issues for its application. In the present paper, a theoretical method based on the impeller-volute matching principle was proposed to predict the best efficiency point of PAT and validated by three centrifugal pumps with specific speeds from 58.7 to 129.6 with an error of less than 5%. In the next step, a single-stage centrifugal pump with specific speed of 90 under normal rotation speed was investigated by experiment and the best efficiency point for pump and turbine modes were obtained. The experimental results of the head and discharge conversion factors and the predicted results obtained through theoretical or statistical methods were compared to verify further the effectiveness of the method proposed in this paper. The performance curves of the pump and turbine modes were predicted using numerical methods and verified by experiment. The hydraulic loss of the main components was calculated to obtain a deeper understanding of the variations of best efficiency point of PAT under different rotation speeds. Finally, the best efficiency point of PAT under different rotation speeds predicted by the theoretical and statistical methods was compared with the numerical results. • Impeller-volute matching for performance prediction of pump as turbine is proposed. • The numerical and experimental investigations of pump and PAT are performed. • Losses of the main components of PAT under different rotation speeds are analyzed. • PAT performance prediction by theoretical, experimental, and numerical are compared. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a rising global public health concern due to its prevalence. Danning Tablets (DNt), a composite prescription of Chinese herbal medicine, shows significant curative effects on NAFLD in clinical application. This study aimed to decipher the bioactive substances and potential mechanisms of action of DNt in the treatment of NAFLD, applying an integrated network pharmacology approach. First, the bioactive compounds of DNt were screened based on their pharmacokinetic properties, and the corresponding drug targets were predicted. Then, the NAFLD-related targets were collected. The overlapping targets between the putative targets of DNt and NAFLD-related targets were identified as the potential therapeutic targets of DNt against NAFLD. Subsequently, the networks were constructed and analyzed, and the key bioactive compounds and targets were screened out depending on their importance in the networks. Functional enrichment analysis was carried out to elucidate the potential mechanisms of DNt acting on NAFLD. Finally, a molecular docking simulation was implemented to assess the potential binding affinity between the key targets and the bioactive compounds. As a result, 43 bioactive compounds of DNt and 69 putative targets were identified. Based on the network analysis, we found seven key bioactive compounds (quercetin, ß-sitosterol, luteolin, kaempferol, supraene, curcumenolactone C, and stigmasterol) of DNt might treat NAFLD via intervening IL6, MAPK8, VEGFA, CASP3, ALB, APP, MYC, PPARG, and RELA. The functional enrichment analysis revealed that DNt might affect NAFLD by modulating the signaling pathways involved in lipid metabolism, inflammation, oxidation, insulin resistance (IR), atherosclerosis, and apoptosis. Furthermore, most key bioactive compounds might bind firmly with the key targets. This study predicted the multicomponent, multitarget, and multipathway mechanisms of DNt in the treatment of NAFLD from a holistic perspective. DNt could be a promising agent for NAFLD, but further experimental verifications are still needed. [ABSTRACT FROM AUTHOR]

Enhanced Hastelloy alloy diffusion bonding was investigated via introducing nanostructured Ni surface layer. Because the bonding temperature was significantly higher than the nanostructured Ni destabilization temperature, rapidly complete recrystallization and dramatic grain growth occurred. The beneficial effect of high-density short-circuit defects provided by nanocrystalline on enhanced diffusion ought to be limited. However, significantly accelerated diffusion was still observed in the joint. The unique contribution of the nanostructured layer in evolving microstructure is to promote the formation of diffusion-induced recrystallization at the interface, where solute elements could diffuse rapidly along the moving boundaries at a rate several orders of magnitude larger than static grain boundaries. The retained ultrafast atomic diffusion paths result in a bonding temperature of 250 °C–350 °C lower than the conventional diffusion bonding approach. The tensile strength of the achieved joint reached 833 MPa, which was nearly equal to that of the as-delivered substrate. [Display omitted] [ABSTRACT FROM AUTHOR]

• Proposed a hybrid Grey Markov model optimized by GWO algorithm. • Proposed model makes up for the defect of empirical division of state intervals. • Discussion relationship between numbers of state intervals and prediction accuracy. • The proposed hybrid model demonstrates higher prediction accuracy. • The coal consumption from 2021 to 2025 at three speeds is predicted. Accurate prediction of coal consumption is crucial to the structural adjustment and high-quality development of the coal industry, and provides an effective basis for the government to formulate energy strategies. To enhance the prediction accuracy, a hybrid prediction model combining grey wolf optimization algorithm and grey Markov model (GWO_Markov_DNGM) is proposed in this study, which introduces the idea of Markov interval division in order to make up the defect of obtaining interval by experience in the past. In this research, coal consumption in Hebei Province from 2001 to 2020 is used as an example to verify the accuracy of the model and the results show that the proposed model has higher accuracy than the comparison models, including ARIMA, GM (1, 1), DGM (1, 1), DNGM (1, 1) and the grey Markov model with equidistant division of state interval. In addition, this study also discusses the influence of numbers of state intervals on the prediction accuracy of the proposed model, which further illustrates the high prediction accuracy of the proposed hybrid model. Finally, the proposed model is employed to predict the coal consumption of Hebei Province under three scenarios from 2021 to 2025, and several suggestions are put forward. [ABSTRACT FROM AUTHOR]

To design an ocular drug delivery system is challenging due to the limited space of the ocular surface and high sensitivity of the cornea. Here, we developed a lacrimal duct drug delivery system, which was non-invasive and could cause no foreign body sensation. Based on hydrogels, our drug-loaded lacrimal plugs had ideal and adjustable properties of mechanical characteristics, swelling ratio and degradation rates. They also showed better biocompatibility and the feasibility of loading various drugs to treat different ocular diseases, compared to the commonly-used plug products. Our drug-loaded lacrimal plugs exhibited sustained and stable drug releasing profiles both in vitro and in vivo for up to three months. To test the therapeutic effect, FK506 loaded plugs and cyclosporine A loaded plugs were used to treat the rat allergic conjunctivitis model and rabbit dry eye model, respectively, which both demonstrated satisfactory long-term efficacy. This study illustrated a lacrimal plug drug delivery system with the potential application in the long-term treatments of a variety of ocular surface diseases. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusions: As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Pump as turbine (PAT) is a type of energy recovery equipment. However, the mechanism of performance degradation when it deviates from the design working condition is inadequately reported. Hence, the steady performance of a centrifugal PAT with a design specific speed (n s d = 3.65 n d Q d ∕ H d 0.75 ) of 90 was simulated by ANSYS-CFX 18.0. The shear stress transport (SST) k-ω turbulence model was used to close the Reynolds-averaged Navier–Stokes (RANS) equations and the simulation results of performance were verified by comparing the experimental. To explore the energy loss mechanism of the PAT under different flow conditions, the energy loss of each part of PAT was calculated by the enstrophy dissipation method, which not only accurately calculate the energy loss but also diagnose where and how hydraulic loss occurs. Compared with the traditional pressure drop assessment method, the enstrophy dissipation method has higher prediction accuracy for the rotating domain, almost the same prediction accuracy in the static domain. The energy loss of the PAT mainly occurs in the cavity, volute and impeller. Hydraulic loss is dominated by fluctuating enstrophy dissipation power and wall enstrophy dissipation power. Adverse flow phenomena such as backflow and shock flow could evidently increase the volume and wall enstrophy dissipation rates. Therefore, the proposed method can be used intuitively to provide a reference for PAT performance optimization and actual operation regulation. • Enstrophy dissipation theory was applied to predict energy loss of pump as turbine. • The proportion of enstrophy dissipation components of PAT was investigated. • The relationship between flow characteristic and enstrophy dissipation was revealed. • Enstrophy method calculates losses more effectively than pressure drop method. [ABSTRACT FROM AUTHOR]

This article presents the design and demonstration of a high-bandwidth antenna-in-package (AiP) module focusing on low-loss interconnects and Yagi–Uda antenna performance fabricated on a 100- $\mu \text{m}$ low coefficient-of-thermal-expansion (CTE) glass for the 28-GHz band. It shows the modeling, design, and characterization of key technology building blocks along with the process development of advanced 3-D glass packages. The building blocks include impedance-matched antenna-to-die signal transitions, Yagi–Uda antenna, and 3-D active–passive integration with backside die assembly on 100- $\mu \text{m}$ glass substrates. The design and stack-up optimization of antenna-integrated millimeter-wave (mm-wave) modules is discussed. Process development to achieve high-density interconnects and precise dimensional control in multilayered thin glass-based packages is also described. The characterization results of the key technology building blocks show an insertion loss of 0.021 dB per through-package via (TPV), leading to the whole-chain loss of less than 1 dB and a return loss lower than 20 dB. The fabricated Yagi–Uda antenna features high repeatability of wide bandwidth due to the process control enabled by glass substrates. The antenna measurements show a bandwidth of 28.2%, which covers the entire 28-GHz fifth-generation (5G) frequency bands (n257, n258, and n261). The flip-chip assembled low-noise amplifier with 80- $\mu \text{m}$ solder balls shows a maximum gain of 20 dB as desired. The performance of the glass-based package integrated antennas is benchmarked to other 5G substrate technologies, such as organic laminates or co-fired ceramic-based substrates. [ABSTRACT FROM AUTHOR]

Pursuing the limit of solid volume fraction of suspension and packing density of compacts is an important issue in industry such as ceramic processing. In present manuscript, the experiment results show that a very high solid volume content (82%) in suspension and a high packing density (92%) of compacts can be obtained, by using spherical particles to optimize particle size distribution. The proposed model can well predict the maximum solid fraction of mixtures at a given volume fraction of smaller particles. The correlation between viscosity and solid volume fraction could be expressed by an exponential equation. About the green bodies prepared from suspensions, the green density has important influence on sintered body density especially on the initial sintering stage. And dense sintered body with amorphous phase could be obtained at sintering temperature of 1100 °C. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation. [ABSTRACT FROM AUTHOR]

Background. The heat shock protein 90 (HSP90s) family is composed of molecular chaperones composed of four isoforms in humans, which has been widely reported as unregulated in various kinds of cancers. Nevertheless, the role of each HSP90s isoform in prognosis and immune infiltration in distinct subtypes of breast cancer (BRAC) remains unclear. Methods. Public online databases including the Oncomine, UALCAN, Kaplan-Meier Plotter, Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GeneMANIA, and Database for Annotation, Visualization, and Integrated Discovery (DAVID) were integrated to perform bioinformatic analyses and to explore the possible associations among HSP90s gene expression, prognosis, and immune infiltration in BRAC. Results. The mRNA expression of all HSP90s members was elevated in distinct clinical stages and subtypes of BRAC, compared with the normal breast tissue (P < 0.05). Overexpressed HSP90AA1 was associated with poor prognosis, particularly, both short overall survival (OS) and release-free survival (RFS) in Basal-like BRAC patients; overexpressed HSP90AB1 and HSP90B1 were both associated with poor RFS in Luminal A BRAC patients, while overexpressed TRAP1 was associated with favorable RFS in Luminal A BRAC patients. Moreover, HSP90s gene expression in BRAC showed correlations with the infiltration of CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs), as well as the activation of tumor-associated macrophages (TAMs), DCs, and CD4+ helper T (Th) cells. The underlying mechanisms of HSP90s modulating tumor-infiltrating immune cells (TIICs) might be related with their functions in antigen processing and presentation, major histocompatibility complex (MHC) binding, and assisting client proteins. Conclusion. This study demonstrated that HSP90s family genes were overexpressed and might be serve as prognostic biomarkers in subtypes of BRAC. It might be a novel breakthrough point of BRAC treatment to regulate immune infiltration in BRAC microenvironment for more effective anticancer immunity through pharmacological intervention of HSP90s. [ABSTRACT FROM AUTHOR]

Social norm-based messages have been widely used for persuasion. However, the current trend that research focuses on using social norm theories rather than theorizing about social norms may hinder theory advancement. Although there are efforts theorizing moderators in norm–behavior relationship, the empirical studies testing the theories have yielded mixed findings, and the unclear focus on social norm-based messages versus perceived norms may impede theorizing the communication process regarding social norm-based persuasion. To bridge this gap, our study takes an inductive approach based on 85 studies to create a framework of moderators in social norm-based message persuasiveness. The framework identifies five factors moderating the effect of descriptive norm messages on behavioral intentions and two factors for injunctive norm messages. This framework lays a foundation for theorizing the mechanism of social norm-based message persuasiveness, highlights empirically supported conditions for message persuasiveness, and offers practical implications for designing targeted social norm-based messages. [ABSTRACT FROM AUTHOR]

Background: The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio constitutes a strong risk predictor of cardiovascular events. However, the association between this ratio and cardiovascular death in peritoneal dialysis (PD) patients is uncertain. The study aimed to investigate whether a high LDL-C/HDL-C ratio could predict both cardiovascular and all-cause mortalities in patients on PD. Methods: A total of 1616 incident patients on PD included from January 1, 2006 to December 31, 2013 were followed up with until 31 December 2018 in this single-center prospective cohort study. Participants were divided into three categories according to LDL-C/HDL-C ratio tertile. The primary endpoint was cardiovascular mortality; the secondary endpoint was all-cause mortality. Results: The mean age of the study cohort was 47.5 years and the mean body mass index (BMI) was 21.6 kg/m2. During a median follow-up period of 47.6 months, 492 patients died, including 246 (50.0%) due to cardiovascular disease (CVD). A multivariate analysis revealed that the highest LDL-C/HDL-C ratio tertile was significantly associated with increased CVD mortality [hazard ratio (HR): 1.69, 95% CI: 1.24–2.29; P = 0.001] and all-cause mortality (HR: 1.46, 95% CI: 1.18–1.81; P = 0.001) relative to the lowest tertile. After adjusting for covariates, the HRs of cardiovascular and all-cause mortalities were 1.84 (95% CI: 1.25–2.71; P = 0.002) and 1.35 (95% CI: 1.03–1.77; P = 0.032). Subgroup analysis showed that the risk of CVD death rose with a higher LDL-C/HDL-C ratio among PD patients who were female, younger than 65 years old, without being malnourished (BMI ≥ 18.5 kg/m2 or albumin ≥35 g/L), and with a history of diabetes or CVD, respectively. Conclusions: A high LDL-C/HDL-C ratio is an independent risk factor for both cardiovascular and all-cause mortalities among PD patients. [ABSTRACT FROM AUTHOR]