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This document discusses the challenges and methods for constructing fluorinated quaternary stereogenic centers in organic molecules, which are important in pharmaceuticals. The authors present a Pd-catalyzed allylic C–H alkylation method using an α-fluoroester for the construction of a C–F quaternary stereogenic center. They found that using a chiral phosphoramidite-palladium catalyst and 2,5-diphenylhydroquinone as an oxidant resulted in high yields and selectivities. The researchers also explored the substrate scope and proposed a plausible reaction mechanism. Overall, this study provides an efficient method for synthesizing fluorinated quaternary stereogenic centers. [Extracted from the article]

Objective: This study aims to screen for measures and lipid-derived indicators associated with insulin resistance (IR) in obese children and adolescents and develop a nomogram model for predicting the risk of insulin resistance. Methods: A total of 404 eligible obese children and adolescents aged 10–17 years were recruited for this study from a summer camp between 2019 and 2021. The risk factors were screened using the least absolute shrinkage and selection operator (LASSO)-logistic regression model, and a nomogram model was developed. The diagnostic value of the model was evaluated by plotting the receiver operator characteristic curve and calculating the area under the curve. Internal validation was performed using the Bootstrap method, with 1000 self-samples to evaluate the model stability. The clinical applicability of the model was assessed by plotting the clinical decision curve. Results: On the basis of the LASSO regression analysis results, three lipid-related derivatives, TG/HDL-c, TC/HDL-c, and LDL-c/HDL-c, were finally included in the IR risk prediction model. The nomogram model AUC was 0.804 (95% CI: 0.760 to 0.849). Internal validation results show a C-Index of 0.799, and the mean absolute error between the predicted and actual risks of IR was 0.015. The results of the Hosmer–Lemeshow goodness-of-fit test show a good model prediction (χ2 = 9.523, P = 0.300). Conclusion: Three early warning factors, TG/HDL-c, TC/HDL-c, and LDL-c/HDL-c, were screened, which can effectively predict the risk of developing IR in obese children and adolescents, and the nomogram model has an eligible diagnostic value. [ABSTRACT FROM AUTHOR]

Considerable signal crosstalk exists in the regulatory network of senescence and stress response. Numerous senescence‐associated genes are also involved in plant stress tolerance. However, the underlying mechanisms and application potential of these genes in stress‐tolerant crop breeding remain poorly explored. We found that overexpression of SENESCENCE‐SUPPRESSED PROTEIN PHOSPHATASE (SSPP), a negative regulator of leaf senescence, significantly improved plant salt tolerance by increasing reactive oxygen species (ROS) scavenging in both Arabidopsis and soybean. However, overexpression of SSPP severely suppressed normal plant growth, limiting its direct use in agriculture. We previously revealed that the N‐terminal 1–14 residues of ACS7 (termed 'N7') negatively regulated its protein stability through the ubiquitin/proteasome pathway, and the N7‐mediated protein degradation was suppressed by environmental and senescence signals. To avoid the adverse effects of SSPP, the N7 element was fused to the N‐terminus of SSPP. We demonstrated that N7‐SSPP fusion gene effectively rescued SSPP‐induced growth suppression but maintained enhanced salt tolerance in Arabidopsis and soybean. Particularly, N7‐SSPP enhanced tolerance to long‐term salt stress and increased seed yield in soybean. These results suggest that N7‐SSPP overcomes the disadvantages of SSPP on plant growth inhibition and effectively improves salt tolerance through enhanced ROS scavenging, providing an effective strategy of using posttranslational regulatory element for salt‐tolerant crop breeding. Numerous senescence‐associated genes are also involved in stress tolerance, but the underlying mechanisms and application potentials are poorly investigated. We found that SSPP, a negative regulator of leaf senescence, enhances plant salt tolerance through ROS scavenging. Fusing N7, a regulatory element in the N‐degron pathway, to SSPP rescued SSPP‐induced growth suppression but did not affect salt tolerance in Arabidopsis and soybean. Notably, N7‐SSPP enhanced long‐term salt tolerance and increased yield in soybean. This study supported that manipulation of key senescence‐associated genes can effectively modulate plant stress responses and provided an effective strategy of using regulatory elements in the N‐degron pathway for salt‐tolerant crop breeding. [ABSTRACT FROM AUTHOR]

Steel hollow structure section (HSS) chord-to-branch joints in Vierendeel trusses are concerned for their proneness to fracture due to imperfection in fabrication. In this paper, the stress intensity factors (SIFs) for HSS chord-to-branch joints are examined based on fracture mechanics and finite element modelling. Through a well-prepared sub-modelling strategy, the influences of geometric parameters related to the crack propagation behaviour are analysed and discussed. The crack front of the HSS chord-to-branch joint without the axial stress of the branch is shown to have notably high SIFs at the deepest point and the surface point. Alternatively, the concentration of highest SIFs at the deepest point of the elliptical arc of the crack becomes significant with the increase of the axial stress of the branch. The increase of the chord wall thickness is shown to be beneficial in the reduction of the SIFs for HSS chord-to-branch joints, especially for lower chord width ratio normalized by thickness. Conversely, the influence of the crack shape indicated by larger aspect ratio on the reduced SIFs becomes obvious and consistent for greater chord width ratio normalized by thickness. The SIFs for HSS chord-to-branch joints are decreased with the increase of the normalized crack depth with respect to the chord wall thickness, particular for shallow surface cracks. Such a trend becomes obvious for the joints with lower fillet weld leg length of equal leg fillet welds with respect to the chord wall thickness or with lower weld leg length along the HSS branch with respect to that along the chord. [ABSTRACT FROM AUTHOR]

Pregabalin (PGB) is widely used clinically; however, its pharmacokinetics (PK) has not been studied in pediatric patients with renal impairment (RI). To design optimized PGB regimens for pediatric patients with varying degrees of RI and predict exposure to PGB, physiologically based pharmacokinetic (PBPK) models of PGB were developed and verified, and its disposition was simulated in the healthy population and adults with RI. The simulated results from the PBPK models after single-dose and multi-dose administrations of PGB were consistent with the corresponding observed data based on the fold error values of less than 2. The area under curve ratios were 1.23 ± 0.06, 2.02 ± 0.10, 3.86 ± 0.21, and 9.92 ± 0.79 in pediatric patients with mild, moderate, severe, and end-stage RI, respectively. Based on the predictions for pediatric patients with moderate, severe, and end-stage RI, the maximum dose should not exceed 7, 3.5, and 1.4 mg/kg/day, respectively, among those weighing < 30 kg, and it should not exceed 5, 2.5, and 1 mg/kg/day, respectively, among those weighing > 30 kg. In conclusion, the developed PBPK model is a valuable tool for predicting PGB dosage for pediatric patients with RI. [ABSTRACT FROM AUTHOR]

Ceftaroline fosamil is a fifth‐generation cephalosporin approved as a treatment for adults and children with community‐acquired bacterial pneumonia and acute bacterial skin and skin structure infections. However, its pharmacokinetics have not been fully evaluated in children with renal impairment. This study aimed to propose proper ceftaroline dosages optimized for the renally impaired pediatric population using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of ceftaroline was established and verified to simulate its disposition in the healthy population and renally impaired adults and to predict the exposure in renally impaired pediatric patients. Consistency was confirmed between simulated and observed data after intravenous administration of various ceftaroline regimens; fold errors were within the 2‐fold error range. Among 6‐year‐old children, healthy subjects had 1.5‐fold, 2‐fold, and 2.6‐fold lower areas under the plasma concentration–time curve (AUCs) than the moderate, severe, and end‐stage renally impaired patient groups, respectively; among 1‐year‐old children, healthy subjects had 1.5‐fold, 2.1‐fold, and 2.5‐fold lower AUCs than the respective renally impaired patient groups; among 1‐month‐old children, healthy subjects had 1.5‐fold, 1.8‐fold, and 2.2‐fold lower AUCs than the respective renally impaired patient groups. The proposed dosage should be adjusted to 8, 6, and 5 mg/kg every 8 hours for patients aged ≥2 years to <18 years (≤33 kg) with moderate, severe, and end‐stage renal impairment, respectively; 5, 4, and 3 mg/kg every 8 hours for patients aged 2 months to <2 years with moderate, severe, and end‐stage renal impairment, respectively; 4, 3.5, and 2.5 mg/kg every 8 hours for patients 0 to <2 months of age with moderate, severe, and end‐stage renal impairment, respectively. Furthermore, pharmacodynamic investigations demonstrated that adequate antimicrobial effects were attained at the proposed doses in 3 age groups. Hence, our PBPK model can be an effective tool to support ceftaroline dosage proposals for renally impaired pediatric patients. [ABSTRACT FROM AUTHOR]

One kind of PVA/PAA-based alkaline solid polyelectrolyte (ASPE) membrane with high conductivity and good mechanical property was prepared via the introduction of the micro-crystalline cellulose (MCC) as functional fillers. An ion conductivity of 95 mS cm−1 with high alkali resistance was achieved when the MCC content reached up to 5wt%, which is 4.5-fold higher than the control. SEM image showed a denser pore structure that is beneficial for the OH− conduction after MCC addition. X-ray diffraction further indicated a gradually decreased crystallinity of KOH with the addition of MCC. This means more content of KOH would exist in the ionic form in the remained water caused by the added MCC in the system. This leads to the increased content of OH− and the resulting ion conductivity. The window equals to 0.9 V and improved mechanical properties were observed after a 5wt% content of MCC was added in the ASPE membrane system. [ABSTRACT FROM AUTHOR]

Physiologically based pharmacokinetic (PBPK) modeling has unique advantages in investigating the pharmacokinetics of drugs in special populations. Our aim is to design optimized dosing regimens for ceftazidime in renally-impaired pediatric patients using PBPK modeling. Models for healthy and renally-impaired adults were developed, verified, and adapted for children to predict ceftazidime exposure in pediatric patients with varying degrees of renal impairment, capturing age- and weight-related pharmacokinetic changes. We derived a dosage-adjusted regimen for renally-impaired children based on pharmacokinetic data and evaluated the pharmacodynamics of ceftazidime. The PBPK models adequately predicted ceftazidime exposures in populations after single- and multi-dose administrations, with fold error values within 1.1 between simulated and observed data. In moderate, severe, and end-stage renally-impaired pediatric patients, the areas under the plasma concentration-time curves (AUCs) were 1.87-fold, 3.56-fold, and 6.19-fold higher, respectively, than in healthy children when treated with the same dose of 50 mg/kg. Pharmacodynamic verification indicated that the recommended doses of 28, 15, and 8 mg/kg administered three times daily (every 8 h) to pediatric patients with moderate, severe, and end-stage renal disease, respectively, were sufficient to attain the target of maintaining the free plasma concentration at or above minimum inhibitory concentration (MIC) during 70% of the dosing interval (70% fT > MIC: nearly 100% target attainment for susceptible MIC of 4 mg/L and >70% for intermediate MIC of 8 mg/L). Our PBPK model can be an effective tool to support dosing recommendations in pediatric patients with different degrees of renal impairment. [ABSTRACT FROM AUTHOR]

The insulin receptor (INSR) binds insulin to promote body growth and maintain normal blood glucose levels. While it is known that steroid hormones such as estrogen and 20- hydroxyecdysone counteract insulin function, the molecular mechanisms responsible for this attenuation remain unclear. In the present study, using the agricultural pest lepidopteran Helicoverpa armigera as a model, we proposed that the steroid hormone 20-hydroxyecdysone (20E) induces dephosphorylation of INSR to counteract insulin function. We observed high expression and phosphorylation of INSR during larval feeding stages that decreased during metamorphosis. Insulin upregulated INSR expression and phosphorylation, whereas 20E repressed INSR expression and induced INSR dephosphorylation in vivo. Protein tyrosine phosphatase 1B (PTP1B, encoded by Ptpn1) dephosphorylated INSR in vivo. PTEN (phosphatase and tensin homolog deleted on chromosome 10) was critical for 20E-induced INSR dephosphorylation by maintaining the transcription factor Forkhead box O (FoxO) in the nucleus, where FoxO promoted Ptpn1 expression and repressed Insr expression. Knockdown of Ptpn1 using RNA interference maintained INSR phosphorylation, increased 20E production, and accelerated pupation. RNA interference of Insr in larvae repressed larval growth, decreased 20E production, delayed pupation, and accumulated hemolymph glucose levels. Taken together, these results suggest that a high 20E titer counteracts the insulin pathway by dephosphorylating INSR to stop larval growth and accumulate glucose in the hemolymph. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of methylprednisolone in treating the coronavirus disease 2019 (COVID-19) patients. Methods: A retrospective cohort study was conducted, and all COVID-19 patients were recruited who were admitted to the Yichang Third People's Hospital from February 1st to March 31st, 2020. One-to-one propensity score matching (PSM) was used for minimizing confounding effects. The primary outcome was hospital mortality, with the secondary outcomes being the time needed for a positive SARS-CoV-2 nucleic acid test to turn negative and the length of hospital stay. Results: Totaling 367 patients with COVID-19 hospitalized at the Yichang Third People's Hospital were identified, of whom 276 were mild or stable COVID-19, and 67 were serious or critically ill. Among them, 255 patients were treated using methylprednisolone, and 188 did not receive any corticosteroid-related treatment. After PSM, no statistically significant difference was found in the baseline characteristics between the two groups. Regarding the outcomes, there also were no statistically significant difference between the two groups. Patients without the use of methylprednisolone were more quickly to obtain negative results of their nasopharyngeal swab tests of SARS-CoV-2 nucleic acid after treatment, compared to those receiving methylprednisolone. Conclusion: Methylprednisolone could not improve the prognosis of patients with COVID-19, and the efficacy and safety of the use of methylprednisolone in patients with COVID-19 still remain uncertain, thus the use of corticosteroids clinically in patients with COVID-19 should be with cautions. [ABSTRACT FROM AUTHOR]

Pramipexole is the first‐line medication recommended by the British National Institute for Health and Care Excellence. Pramipexole is predominantly eliminated by renal excretion. The aim was to develop a physiologically based pharmacokinetic (PBPK) model of pramipexole, providing a basis for its individualized administration. The role of glomerular filtration and organic cation transporter 2 (OCT2) in renal tubular secretion was considered. Plasma concentration‐time profiles of pramipexole were predicted and validated, first in healthy populations and then in PD patients with varied renal function. Finally, the pharmacokinetics of PD patients with different degrees of renal impairment were predicted. The simulated pharmacokinetic parameters, including maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), time to maximum plasma concentration (tmax), and steady‐state trough plasma concentration values, obtained using the PBPK model were validated using fold error values, which were all smaller than 2. The successfully validated model supported that OCT2‐mediated tubular secretion was affected proportionally to changes in glomerular filtration for various degrees of renal impairment. The predicted AUC0‐inf values were increased 1.16‐, 1.76‐, 3.26‐, and 9.48‐fold in mild, moderate, and severe renal impairment and end‐stage renal disease (ESRD) subjects, resepctively, compared with PD patients with normal renal function. It appears that PD patients with mild renal impairment are unlikely to require dose adjustment (0.125 mg 3 times a day). The pramipexole dose should be reduced to approximately 0.125 mg twice daily, 0.125 mg once daily, and 0.0375 mg once daily in PD patients with moderate renal impairment, severe renal impairment, and ESRD, respectively. [ABSTRACT FROM AUTHOR]

A regio- and stereoselective iodolactonization of internal electron-deficient olefinic acids has been reported, which provides a straightforward access to a series of multi-functionalized seven-membered lactones containing two consecutive chiral centers. The ester substituents on the olefins played a key role in achieving high regioselectivity. This result was proved through experiments and DFT calculations. [ABSTRACT FROM AUTHOR]

Disorder of long non-coding RNAs (LncRNAs) is found in various types of cancers and demonstrated to be associated with tumor occurrence and development. Our study found that lncRNA insulin growth factor 2 antisense (IGF2-AS) is up-regulated in gastric adenocarcinoma (GAC) tissues and correlated with poor prognosis in patients with GAC. Cell counting kit-8 (CCK8), colony formation, wound healing and transwell assays revealed that knockdown of IGF2-AS in BGC823 and SGC7901 cells significantly suppressed cell proliferation, migration and invasion. While, overexpression of IGF2-AS in AGS and MGC803 cells exhibited the opposite effects. RNA-FISH and subcellular fractionation assay found that most IGF2-AS was distributed in the cytoplasm, suggesting that IGF2-AS functioned as a potential ceRNA. RNA binding protein immunoprecipitation (RIP) assays further confirmed this assumption. By informatics prediction and luciferase reporter assay, we found that IGF2-AS functioned as an efficient miR-503 sponge and the level of miR-503 showed an inverse correlation with IGF2-AS. Short stature homeobox 2 (SHOX2) is predicted and verified as a target of miR-503. Moreover, IGF2-AS expression exhibited a negative correlation with miR-503 and a positive correlation with IGF2-AS. Subsequent rescue assay revealed that down-regulation of miR-503 or restoration of SHOX2 canceled IGF2-AS depletion-induced depression in proliferation and motility of BGC823 and SGC7901 cells. Meanwhile, up-regulation of miR-503 or down-regulation of SHOX2 decreased IGF2-AS overexpression induced promotion in proliferation and motility of AGS and MGC803 cells. In vivo tumorigenicity assay showed that knockdown of IGF2-AS significantly reduced tumor volume. Taken together, our results demonstrated that IGF2-AS takes important regulatory parts in GAC development by functioning as a ceRNA to regulate SHOX2 via sponging miR-503. [ABSTRACT FROM AUTHOR]

This paper outlines an experimental study on the static and dynamic compressive creep behaviour of structural silicone adhesively bonded joints. The silicone adhesives are subjected to dynamic compressive loading, which is a common case for structural façade and hybrid glazing system. Typical crack propagation of adhesives, relations between compressive load (stress) and displacement (creep strain) are examined experimentally. It is shown that the test specimen with adhesives featured by lower hardness and higher elongation at break exhibit notable crack distribution concentrated in the middle of the crack surface. The compressive behaviour consists of three regions as initial elastic, nonlinear transition and post linear, in which the latter has notable strength increase with the increase of compressive deformation. The secant compressive modulus are measured based on compressive stress and creep strain relations. It is demonstrated that the joint has higher secant compressive modulus due to less crack propagation. All test joints exhibit significant degradation of strength and energy absorption, which can be well fitted in similar exponential forms with normalized cycle numbers for test joints with different adhesives. [ABSTRACT FROM AUTHOR]

Ticagrelor, a P2Y 12 receptor antagonist, has been highly recommended for use in acute coronary syndrome. The major active metabolite (AM) is similar to the parent drug, which exhibits antiplatelet activity. The inhibition of platelet aggregation (IPA) is used as an assay to demonstrate the anticoagulant efficacy of ticagrelor. In this study, we developed a physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of ticagrelor and its AM and combined this model with a pharmacodynamics model to reflect potential pharmacodynamic alterations in liver cirrhosis populations. The simulated results obtained using the PBPK model were validated by fold error values, which were all smaller than 2. Comparisons of exposure in different classifications of liver cirrhosis indicated that exposure to ticagrelor increased significantly with an increase in the degree of cirrhosis severity, whereas exposure to AM was decreased. The total concentration of ticagrelor and AM was related to the IPA included in the Sigmoid E max model. The PBPK model of ticagrelor and AM could predict the pharmacokinetics of all populations, and a combination of PD models was used to extrapolate for predicting unknown scenarios. Liver cirrhosis may result in prolonged IPA, depending on the severity degree of this disease. The combined PBPK model including IPA can reveal changes in pharmacokinetics and pharmacodynamics in populations affected by liver cirrhosis and indicate the risk potential. [ABSTRACT FROM AUTHOR]

A new strategy has been established for the synthesis of polysubstituted morpholin‐2‐ones through Stevens rearrangements of tertiary amines via in situ activation with epoxides. A range of α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines reacted with epoxides in the presence of zinc halide catalysts to afford structurally diverse allyl‐, allenyl‐, and benzyl‐substituted morpholin‐2‐ones, respectively, in moderate‐to‐good yields with high regioselectivity. The process involves [2,3]‐ and [1,2]‐Stevens rearrangements of quaternary ammonium ylide intermediates and constitutes a very convenient method to prepare polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds. Moreover, replacing epoxides with aziridines permitted the synthesis of polysubstituted piperazin‐2‐ones. New Stevens rearrangement: Zinc‐halide‐catalyzed ring‐opening of epoxides with α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines followed by [2,3]‐ and [1,2]‐Stevens rearrangements of the resulting quaternary ammonium ylide intermediates has been established as a convenient method to access polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds (see scheme). [ABSTRACT FROM AUTHOR]

An L-ascorbic acid (L-AA) biosensor based on an indium–gallium–zinc oxide (IGZO)/aluminum (Al) membrane modified by graphene oxide (GO) and magnetic beads (MBs) was produced and trusted to investigate its potential biosensor applications. An atomic force microscope, scanning electron microscope (SEM), and electrochemical impedance spectroscopy (EIS) were used to analyze electron transfer resistance (${R} _{\textsf {et}}$), surface roughness, and surface morphology. The experimental results show that the L-AA biosensor possessed the average sensitivity of 78.9 mV/decade with a linearity of 0.997. The experimental results from the EIS confirm that ${R} _{\textsf {et}}$ can be improved by the addition of GO and MBs. This paper opens a new window for the detection of L-AA based on MBs-ascorbate oxidase/GO/IGZO/Al sensing membranes. [ABSTRACT FROM AUTHOR]

PYR-41 and thalidomide have therapeutic effects on inflammation-associated diseases with side effects such as tumorigenesis. Cross-presentation allows dendritic cells (DC) to present endogenous antigen and induce protective immunity against microbe infection and tumors. But, up to now, the effects of PYR-41 and thalidomide on cross-presentation are still uncertain. In this study, we investigated the effect and mechanism of PYR-41 and thalidomide on DC cross-presentation by observing Myddosome formation, endosomal recruitment of p97 and Sec61, NF-κB activation, and cross-priming ability. We demonstrated that the inhibition of endosomal recruitment of p97 and Sec61, together with attenuated NF-κB activation and Myddosome formation, contributes to PYR-41- and thalidomide-impaired cross-presentation and thereby reverses cross-activation of T cells. These observations suggest that NF-κB signaling and p97 and Sec61 molecules are candidates for dealing with the side effects of PYR-41 and thalidomide. [ABSTRACT FROM AUTHOR]

Manganese (Mn)-intolerant ‘Sour pummelo’ ( Citrus grandis ) and Mn-tolerant ‘Xuegan’ ( Citrus sinensis ) seedlings were irrigated for 17 weeks with 2 (control) or 600 μM (Mn-toxicity or −excess) MnSO 4 . C. sinensis had higher Mn-tolerance than C. grandis , as indicated by the higher photosynthesis rates in Mn-excess C. sinensis leaves. Under Mn-toxicity, Mn levels were similar between C. sinensis and C. grandis roots, but lower in C. sinensis leaves than in C. grandis leaves. This might be responsible for C. sinensis Mn-tolerance. Using two-dimensional electrophoresis, we identified more differentially abundant proteins (DAPs) in Mn-excess C. grandis than in Mn-excess C . sinensis leaves, which agrees with the higher Mn levels in Mn-excess C. grandis leaves. DAPs were mainly related to carbohydrate and energy metabolism, stress response, and protein and amino acid metabolism. DAPs involved in the cytoskeleton and signal transduction were found only in Mn-excess C. grandis leaves. We isolated more photosynthesis-related proteins with decreased abundances in Mn-excess C. grandis leaves than in Mn-excess C. sinensis leaves, which might account for the larger decrease in photosynthesis rates in C. grandis leaves. The abundances of proteins involved in reactive oxygen species (ROS) scavenging and photorespiration were increased in Mn-excess C. grandis leaves, while only proteins involved in ROS detoxification were increased in Mn-excess C. sinensis leaves. This agrees with the increased requirement for dissipating the excess absorbed light energy, which was higher in Mn-excess C. grandis leaves than Mn-excess C. sinensis leaves because Mn-toxicity inhibited photosynthesis to a greater degree in C. grandis leaves. [ABSTRACT FROM AUTHOR]

Lignin and ash material balances of SO 2 -ethanol–water (AVAP®) fractionation of sugarcane (SC) straw were thoroughly studied at various conditions. Most of straw lignin and ash dissolve in the liquor and 40–80% of lignin is precipitated after ethanol removal as a pure (∼99%) and sulfur-lean (<2%) fraction. Most of the acid-soluble ash and its elements (Na, K, Fe, Al) as well as large portion of silica are removed from the fiber phase. Straw lignin behavior exhibited differences compared to wood lignin including high apparent content in fiber, higher degree of sulfonation of dissolved lignin, and dense char-like precipitate formation upon ethanol removal. Variation in fractionation conditions did not have significant effect on lignin properties, while post-sulfonation was capable of changing its form from char-like to colloidal precipitate. [ABSTRACT FROM AUTHOR]

The sulfur balance of SO 2 -ethanol-water (AVAP®) fractionation of sugarcane (SC) straw was investigated. Hydrogen sulfite and sulfite anions are nearly absent in the liquors, despite cations present in straw, whose effect is thus limited to neutralization of lignosulfonic acids decreasing the acidity. Higher degree of sulfonation was observed for dissolved straw lignin compared to wood lignin (0.8–0.9 vs. 0.25 S/C9). Sulfur dioxide amounts of 0.9–1.2, 4.1–4.3 and 44–49 g per o.d. kg straw were bound to pulp, precipitated lignin and lignosulfonic acid, respectively, while the rest of SO 2 was recovered by distillation from the spent fractionation suspensions. [ABSTRACT FROM AUTHOR]

Levetiracetam is currently being used to treat epilepsy in pregnant women. The plasma concentration of levetiracetam drops sharply during pregnancy, and the inability of pregnant women to maintain therapeutic concentrations can lead to seizures. This study aimed to predict the changes in fetal and maternal plasma exposure to levetiracetam during pregnancy and provide advice on dose adjustment. The physiology-based pharmacokinetics (PBPK) model was developed using PK-Sim and Mobi software, and validated following comparison of the observed plasma concentration and pharmacokinetic parameters. The levetiracetam PBPK model for mother and the fetus at various stages of pregnancy was successfully established and verified. Predictions indicated that the area under the steady-state concentration-time curve for levetiracetam decreased to 83, 62, and 67% of baseline values in the first, second, and third trimesters, respectively. Based on PBPK predictions, the recommended dose of levetiracetam is 1.2, 1.6, and 1.5 times the baseline dose in the first, second, and third trimesters, respectively, not exceeding 4000 mg/day in the third trimester due to fetal safety. The levetiracetam PBPK model for pregnancy was successfully developed and validated, and could provide alternative levetiracetam dosing regimens across the stages of pregnancy. [Display omitted] [ABSTRACT FROM AUTHOR]

Bolted spherical joints, due to their prominent merits in installation, have been widely used in modern spatial structures. Despite significant research, there is a lack of understanding of their flexural fracture behaviour, which is important for the catastrophe prevention of the whole structure. Given the recent development to fill this knowledge gap, it is the objective of this paper to experimentally investigate the flexural bending capacity of the overall fracture section featured by a heightened neutral axis and fracture behaviour related to variable crack depth in screw threads. Accordingly, two full-scale bolted spherical joints with different bolt diameters were evaluated under three-point bending. The fracture behaviour of bolted spherical joints is first revealed with respect to typical stress distribution and fracture mode. A new theoretical flexural bending capacity expression for the fracture section with a heightened neutral axis is proposed and validated. A numerical model is then developed to estimate the stress amplification and stress intensity factors related to the crack opening (mode-I) fracture for the screw threads of these joints. The model is validated against the theoretical solutions of the thread-tooth-root model. The maximum stress of the screw thread is shown to take place at the same location as the test bolted sphere, while its magnitude can be greatly reduced with an increased thread root radius and flank angle. Finally, different design variants related to threads that have influences on the SIFs are compared, and the moderate steepness of the flank thread has been found to be efficient in reducing the joint fracture. The research findings could thus be beneficial for further improving the fracture resistance of bolted spherical joints. [ABSTRACT FROM AUTHOR]

Simple Summary: Soybean is a prominent grain and oil crop in the world. The production of soybean is threatened by weed competition. Recently, CRISPR/Cas9-mediated base editing, which can cause irreversible nucleotide changes in target loci, has been widely used in basic plant science and breeding. However, until now, herbicide-resistant traits in soybean have not been created by the base editor. The objective of this study was to modify different AHAS homologous alleles by base editor to generate a novel AHAS-inhibiting herbicide-resistant soybean. Our results showed that the GmAHAS4 P180S mutants have apparent resistance to AHAS-inhibiting herbicides, which will be beneficial for weed control in soybean production. Weeds cause the largest yield loss in soybean production. The development of herbicide-resistant soybean germplasm is of great significance for weed control and yield improvement. In this study, we used the cytosine base editor (BE3) to develop novel herbicide-resistant soybean. We have successfully introduced base substitutions in GmAHAS3 and GmAHAS4 and obtained a heritable transgene-free soybean with homozygous P180S mutation in GmAHAS4. The GmAHAS4 P180S mutants have apparent resistance to chlorsulfuron, flucarbazone-sodium, and flumetsulam. In particular, the resistance to chlorsulfuron was more than 100 times that of with wild type TL-1. The agronomic performance of the GmAHAS4 P180S mutants showed no significant differences to TL-1 under natural growth conditions. In addition, we developed allele-specific PCR markers for the GmAHAS4 P180S mutants, which can easily discriminate homozygous, heterozygous mutants, and wild-type plants. This study demonstrates a feasible and effective way to generate herbicide-resistant soybean by using CRISPR/Cas9-mediated base editing. [ABSTRACT FROM AUTHOR]

Kinetics of SO 2 –ethanol–water (AVAP®) fractionation was determined for sugarcane (SC) straw in terms of pulp composition (non-carbohydrate components, cellulose, hemicelluloses) and properties (kappa number, pulp intrinsic viscosity in CED and cellulose degree of polymerization). Effect of temperature (135–165 °C) and time (18–118 min) was studied at fixed liquor composition (SO 2 /ethanol/water = 12:22.5:65.5, w/w) and a liquor-to-solid ratio (4 L kg −1 ). Interpretation is given in terms of major fractionation reactions, removal of non-carbohydrate components and xylan, as well as acid hydrolysis of cellulose, and is compared to other lignocellulosic substrates (beech, spruce and wheat straw). Overall, SO 2 –ethanol–water process efficiently fractionates SC straw by separating cellulose from both non-carbohydrate components and xylan while reducing cellulose DP. [ABSTRACT FROM AUTHOR]

In this paper, a direct laser deposition (DLD) process was used to print ASTM A131 EH36 high strength low alloy steel samples in four different orientations, namely, horizontal 0° (XY_0°) & 45° (XY_45°) and vertical 90° (XZ_90°) & 45° (XZ_45°), with an EH36 steel powder. The microstructures, mechanical properties and fracture behavior of the printed materials, were evaluated in detail. Tensile, charpy impact and fatigue tests were conducted to measure the mechanical properties of the materials. The results showed that all the EH36 steel samples printed in the four orientations satisfied the ASTM standards for the tensile and charpy impact properties of EH36 steel. The microstructures of the EH36 steel samples and the thermal cycles encountered in the different build orientations could be tuned by controlling the printing process parameters and scanning method. The microstructure was closely correlated with the mechanical properties of the built samples. The fatigue fracture mechanism of the printed EH36 steel samples was also proposed. Additive manufacturing of near net shape coupons along 4 orientations using EH36 steel powder. [Display omitted] • A131 EH36 steel samples were printed in different orientations through LAAM process. • The tensile, charpy impact and fatigue properties of the samples were evaluated. • The microstructure and mechanical properties of the samples were closely correlated to in-process scanning methods. • The fatigue failure mechanism of the LAAMed EH36 steel was reported for the first time. [ABSTRACT FROM AUTHOR]

In this study, a type of alkaline solid polyelectrolyte (ASPE) membrane was developed via the introduction of microcrystalline cellulose (MCC) and its modified product (QMCC) into the polyvinyl alcohol (PVA) matrix. In this process, green NaOH/urea-based solvent was used to achieve a good dispersion of MCC in the PVA matrix; meanwhile, the OH− groups in the NaOH/urea-based solvent provided an alkaline environment for good ion conductivity. Compared to the MCC-incorporated ASPE, further improved conductivity was achieved when the MCC was modified with quantitative quaternary ammonium salt. TGA showed that the addition of QMCC improved the water retention of the matrix, which was beneficial to the OH− conduction in the system. Compared to the control (50 mS cm−1), a maximum conductivity of 238 mS cm−1 was obtained after the incorporation of QMCC in the PVA matrix. Moreover, the tensile strength of the polymer electrolyte were also significantly increased with the addition of QMCC. Finally, this developed ASPE membrane was used in assembling a flexible Zn–air battery and showed a promising potential in the development of flexible electronic devices. [ABSTRACT FROM AUTHOR]

• Substrate stiffness influences the osteogenesis of SMCs. • Transforming growth factor-β1 involves in the osteogenesis of SMCs. • SMCs on the substrate of intermediate stiffness show higher osteogenesis level. Vascular stiffening occurs with advanced age and under pathological conditions such as vascular calcification, during which the osteogenesis of smooth muscle cells (SMCs) plays a key role. However, whether the stiffness of cellular microenvironment influences osteogenic responses in vascular SMCs is not well understood. Here, we cultured SMCs on the poly(dimethylsiloxane) (PDMS) substrates with varying stiffness from 0.363 to 2.327 MPa. The cell osteogenic transdifferentiation was induced by β-glycerophosphate. Our findings demonstrated that the extent of osteogenesis in SMCs varied with the substrate stiffness. On three substrate stiffness, cells on the intermediate one (0.909 MPa) showed the highest extent of the osteogenesis based on the expression of osteogenic markers and calcium deposition. Transforming growth factor-β1 and autophagy were involved in this stiffness-dependent process. This work highlights the importance of substrate stiffness to the osteogenesis of vascular SMCs, giving new scientific information for understanding of SMCs-mediated vascular calcification and designing of vascular implants. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study on the fatigue life estimation of off-centrally cracked aluminum plates. Typical theoretical equations for off-central, central and edge cracks were reviewed and compared in terms of their sensitive parameters and applicability. A finite element model has been validated in its capacity in modelling the influences of eccentricity and crack size on the boundary correction coefficients. The Forman equation has been employed along with numerical results for the prediction of fatigue lives. Based on the test data, the fatigue life results of aluminum plates with and without patched laminate repair have been compared with codified fatigue classes. It is demonstrated that the repair at the crack tip close to the plate edge is effective in the fatigue life improvement for off-centrally crackedaluminum plates. [ABSTRACT FROM AUTHOR]

Regenerated cellulosic fibers were successfully spun from various waste cellulose sources (cotton linter, bagasse, and cardboard) suitable for use as a textile fibers using a wet spinning process with an ionic liquid/dimethyl sulfoxide (IL/DMSO) mixture as the solvent. The solubility of the waste cellulose sources in IL/DMSO varies according to the source of the raw material. Regenerated fibers can be spun from all the waste feedstock, the spinnability and fiber tensile strength is governed by the DP and chemical composition of the cellulose. The structural properties of the spun fibers are determined by x-ray diffraction, thermalgravimetric analysis, and scanning electron microscope. The results reveal that the properties of the starting materials and thus how the waste feed streams are pretreated have a significant impact on the mechanical properties, crystallite structure, thermal stability, and the morphology of the fibers. [ABSTRACT FROM AUTHOR]

This study extends previous research by examining the mental health issues of international mainland Chinese college students in Thailand. The research specifically proposed that mental health issues originate from the relationship between life adaptation and mental health disorders, and this study was conducted to test this assertion. Nine hundred international mainland Chinese college students in Thailand participated in an online survey. The results showed that life adaptation in respect of family relationships, interpersonal relationships, emotions, and learning had a positive effect on mental health disorders and that female and junior students who stayed in Thailand for 1 to 2 years were likely to have significant mental health issues. [ABSTRACT FROM AUTHOR]

Limited endoscopic sphincterotomy (EST) combined with endoscopic papillary balloon dilation (EPBD) is widely used. However, the optimal duration of small balloon dilation in choledocholithiasis remains controversial. We aimed to determine the optimal duration for 10 mm diameter balloon dilation after limited EST in choledocholithiasis. In this randomized controlled clinical trial, 320 patients were randomly assigned to receive small balloon dilation (10 mm in diameter) for 1 min (n = 160) or 3 min (n = 160) after deep bile duct cannulation. No significant difference in success rate of stone extraction between the two groups was observed. The incidence of post-ERCP pancreatitis (PEP) was higher in the 1 min group (10.6%) than in the 3 min group (4.4%) (P = 0.034). The logistic regression analysis showed that guidewire into the pancreatic duct, cannulation time > 5 min and 1 min balloon dilation were independent risk factors for PEP. There were no significant differences in other post-ERCP adverse events such as acute cholangitis, bleeding, perforation, etc. between the two groups. In conclusion, 3 min in duration was determined to be the optimal dilation condition for the removal of common bile duct stones. [ABSTRACT FROM AUTHOR]

Ertapenem is a widely used antibiotic; however, its pharmacokinetics has not been fully evaluated in children with renal impairment. A physiologically based pharmacokinetic (PBPK) model of ertapenem was established and validated to simulate its disposition in the healthy population and adults with renal impairment, as well as to predict the exposure in pediatric patients with renal impairment. The simulated PBPK modeling results and the observed data of ertapenem after intravenous administration of various regimens were consistent according to the fold error values of less than 2. Furthermore, %T > MIC of ertapenem was evaluated using the PBPK model. The C max was not significantly changed in pediatric patients with renal impairment compared to healthy children. However, the AUC was 1.42-fold, 1.84-fold, 2.37-fold, and 3.52-fold higher in mild, moderate, severe renal impairment, and end-stage renal disease, respectively, than that in healthy children and the doses of ertapenem were reduced to 13 mg/kg b.i.d, 9 mg/kg b.i.d, 6 mg/kg b.i.d, and 5 mg/kg b.i.d, respectively. The probability of achieving 40%T > MIC (MIC ≤ 4 μg/mL) was nearly 100% throughout the recommended dosing interval. In conclusion, our model can be used as a tool to generate better predictions for the most effective ertapenem dosing in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Risk evaluation of lymph node metastasis (LNM) in superficial colorectal cancer resected by endoscopic surgery is critical for determining subsequent therapeutic strategies, but the role of existing clinical methods, including computed tomography, remains limited. Methods: Features of the nomogram were determined by logistic regression analysis, and the performance was validated by calibration plots, ROC curves and DCA curves in both the training set and the validation set. Results: A total of 608 consecutive superficial CRC cases were randomly divided into 426 training and 182 validation cases. Univariate and multivariate logistic regression analyses revealed that age < 50, tumour budding, lymphatic invasion and lower HDL levels were risk factors for LNM. Stepwise regression and the Hosmer‒Lemeshow goodness of fit test showed that the nomogram had good performance and discrimination, which was validated by ROC curves and calibration plots. Internal and external validation demonstrated that the nomogram had a higher C-index (training group, 0.749, validation group, 0.693). DCA and clinical impact curves graphically show that the use of the nomogram to predict LNM had remarkable predictive power. Finally, in comparison with CT diagnosis, the nomogram also visually showed higher superiority, as demonstrated by ROC, DCA and clinical impact curves. Conclusion: Using common clinicopathologic factors, a noninvasive nomogram for individualized prediction of LNM after endoscopic surgery was conveniently established. Nomograms have great superiority in the risk stratification of LNM compared with traditional CT imaging. [ABSTRACT FROM AUTHOR]

Aim: To assess the methodological and reporting quality of paediatric clinical practice guidelines (CPGs) in National Guideline Clearinghouse (NGC) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and Reporting Items for Practice Guidelines in Healthcare (RIGHT) standard.Methods: We identified all published CPGs through the NGC, and search records were screened in duplicate for inclusion. Two researchers evaluated the methodological and reporting quality of paediatric CPGs using the AGREE II instrument and RIGHT standard. STATA version 12.0 and SPSS version 22.0 software were used to analyse the related data.Results: A total of 50 paediatric CPGs were included. The scores for all six domains by AGREE II instrument were presented as follows: scope and purpose (85.6 ± 9.59), stakeholder involvement (69.15 ± 19.32), rigour of development (73.19 ± 17.18), clarity of presentation (78.51 ± 14.36), applicability (54.61 ± 22.63) and editorial independence (68.42 ± 13.06). In the seven domains of the RIGHT standard, the reporting rate of the recommendation domain was the lowest (52.86%).The highest reporting rate was the other information domain, which was 68%.There was a high correlation between reporting the completeness of CPGs using the AGREE II instrument and RIGHT standard (r = 0.77, P < 0.001).Conclusions: The paediatric CPGs from NGC have good quality. There was a high correlation in the completeness of reporting for paediatric CPGs using the AGREE II instrument and RIGHT standard. It could be concluded that the CPGs of good methodological quality have good reporting quality. Maybe the researcher should effectively combine the AGREE II instrument and RIGHT standard in the development process of CPGs. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasis (HHT) and juvenile polyposis syndrome (JPS) are both relatively rare hereditary disorders. It has been reported that patients with SMAD4 mutations may suffer from both HHT and JPS, defined as JPS/HHT. To improve the understanding and diagnosis of these diseases, we herein report a case of a 17-year-old male with abdominal pain and hematochezia. Low-tension computed tomography (CT) of the small intestine showed intussusception. Combined with the patient's medical history of nasal bleeding and pulmonary arteriovenous fistula (pAVF) embolism, a final diagnosis of JPS/HHT was reached, according to the Curaçao Diagnostic Criteria. The possibility of JPS/HHT should be considered in patients with epistaxis and intussusception. [ABSTRACT FROM AUTHOR]

Th article reports on the perioperative medications during endoscopic submucosal dissection (ESD) for gastric lesions. Topics discussed include the indications and contraindications of gastric ESD, complications of ESD, and diagnosis of perforation. Also being discussed are the aim and types of perioperative medications.

Mitochondrial genomes (mitogenomes) are valuable resources in molecular and evolutionary studies, such as phylogeny and population genetics. The complete mitogenomes of two crocodile newts, Tylototriton broadoridgus and Tylototriton gaowangjienensis, were sequenced, assembled, and annotated for the first time using next-generation sequencing. The complete mitogenomes of T. broadoridgus and T. gaowangjienensis were 16,265 bp and 16,259 bp in lengths, which both composed of 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and 1 control region. The two mitogenomes had high A + T content with positive AT-skew and negative GC-skew patterns. The ratio of non-synonymous and synonymous substitutions showed that, relatively, the ATP8 gene evolved the fastest and COI evolved the slowest among the 13 PCGs. Phylogenetic trees from BI and ML analyses resulted in identical topologies, where the Tylototriton split into two groups corresponding to two subgenera. Both T. broadoridgus and T. gaowangjienensis sequenced here belonged to the subgenus Yaotriton, and these two species shared a tentative sister group relationship. The two mitogenomes reported in this study provided valuable data for future molecular and evolutionary studies of the genus Tylotoriton and other salamanders. [ABSTRACT FROM AUTHOR]

Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species (ROS). Herein, an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate (EC) is designed via phenylboronic esters with improved solubility for the alleviation of uveitis. The antioxidative 4-hydroxybenzyl alcohol (HBA) and EC can be released from the macromolecular EC prodrug under the stimulation of ROS, which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way. The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model. Overall, this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS, but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases. [ABSTRACT FROM AUTHOR]

Mussel‐inspired polydopamine (PDA) coating has been proved to be a universal surface modification strategy with remarkable versatility and active post‐modification ability. However, the traditional preparation of PDA coating shows low polymerization efficiency and alkaline environment dependency. Herein, a robust method to accelerate the in situ generation of PDA coating based on a photosensitizer entrapped substrate is reported. It is demonstrated that the chlorin e6 (Ce6)‐incorporated substrates induce sustained reactive oxygen species (ROS) production via laser irradiation at 660 nm, which dramatically promotes the preparation of PDA coating even in acidic conditions. The thickness of the PDA coating reaches over 4 nm with only 10 min irradiation (pH 6). Patterned PDA coatings can also be achieved by using a photomask. The functionality of this interfacial ROS‐induced PDA coating including photothermal ability and secondary modification ability is also verified. The obtained PDA coating realizes the reduction of Ag+ to Ag NPs, which shows excellent antibacterial ability. This interfacial ROS generation strategy offers a facile and efficient way to construct the PDA coating and expands the potential applications in the biomedical field. [ABSTRACT FROM AUTHOR]

Magnetoelectric hysteresis behavior for four particulate multiferroic composites with different coercivities of magnetic hysteresis loops has been investigated, and the results show that the magnetoelectric hysteresis are deeply affected by the bias magnetic field and test period. The bias magnetic field dependence of ME hysteresis loops is associated with magnetic hysteresis loops, and the sample with large coercivity of magnetic hysteresis loops has high coercive field of magnetoelectric hysteresis loops. The test time hysteresis caused by fast varying bias magnetic field can be eliminated by prolonging test period. These findings provide some ideas not only for practical applications but also for the examination of magnetoelectric effect. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment‐related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36‐fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration–time curve was predicted to increase 1.25‐fold, 1.95‐fold, and 2.82‐fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12‐hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between necrotic collections on endoscopic ultrasound (EUS) and outcomes of the endoscopic transmural step‐up approach in necrotizing pancreatitis (NP). Methods: Adult NP patients who had undergone endoscopic transmural step‐up approach, endoscopic transmural drainage or endoscopic transmural necrosectomy, were retrospectively enrolled, and divided into groups 1, 2 and 3 based on the amount of solid necrotic debris (quantified as a percentage of the total collection size of <30%, 30%‐50%, and >50%). Results: A total of 134 patients were included, of whom 52, 59 and 23 patients were categorized into groups 1, 2 and 3. Patients with more solid necrotic debris required more necrosectomy sessions (group 3 vs group 2 vs group 1: 2.0 vs 1.0 vs 1.0, P < 0.001), were more likely to experience stent occlusion (group 3 vs group 2 vs group 1: 34.8% vs 16.9% vs 9.6%, P = 0.011), and had a longer hospitalization (group 3 vs group 2 vs group 1: 40.0 d vs 28.0 d vs 25.5 d, P = 0.015). High procalcitonin level (adjusted odds ratio [aOR] 6.14, 95% confidence interval [CI] 1.40–26.94, P = 0.016) and any organ failure (aOR 11.51, 95% CI 2.42‐54.78, P = 0.002) were independently associated with clinical failure of endoscopic transmural step‐up approach. Conclusions: More solid necrotic debris on EUS is related to more necrosectomy sessions, higher incidence of stent occlusion and longer hospitalization. A nomogram combining procalcitonin and any organ failure performs well in predicting clinical failure of endoscopic transmural step‐up approach. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is multifactorial that lifestyle, genetic, and environmental factors contribute to its onset and progression, thereby posing a challenge for therapeutic intervention. Nanoplastic (NP) is emerged as a novel environmental metabolism disruptor but the etiopathogenesis remains largely unknown. In this study, C57BL/6 J mice were fed with normal chow diet (NCD) and high-fat diet (HFD) containing 70 nm polystyrene microspheres (NP). We found that dietary-derived NP adsorbed proteins and agglomerated during the in vivo transportation, enabling diet-induced hepatic steatosis to NASH. Mechanistically, NP promoted liver steatosis by upregulating Fatp2. Furthermore, NP stabilized the Ip3r1, and facilitated ER-mitochondria contacts (MAMs) assembly in the hepatocytes, resulting in mitochondrial Ca2+ overload and redox imbalance. The redox-sensitive Nrf2 was decreased in the liver of NP-exposed mice, which positively regulated miR26a via direct binding to its promoter region [−970 bp to −847 bp and −318 bp to −176 bp ]. NP decreased miR26a simultaneously upregulated 10 genes involved in MAMs formation, lipid uptake, inflammation, and fibrosis. Moreover, miR26a inhibition elevated MAMs-tether Vdac1, which promoted the nucleus translocation of NF-κB P65 and Keap1 and functionally inactivated Nrf2, leading to a vicious cycle. Hepatocyte-specific overexpressing miR26a effectively restored ER-mitochondria miscommunication and ameliorated NASH phenotype in NP-exposed and Keap1-overexpressed mice on HFD. The hepatic MAM-tethers/Nrf2/miR26a feedback loop is an essential metabolic switch from simple steatosis to NASH and a promising therapeutic target for oxidative stress-associated liver damage and NASH. [Display omitted] • NP is a novel environmental metabolism disruptor that can propel NAFL to NASH. • NP stimulates MAMs assembly in the hepatocytes via binding and stabilizing Ip3r1. • MAMs-tether Vdac1-mediated Keap1 nuclear translocation triggers oxidative injury. • Redox-sensing miR26a is a critical molecular switch for NAFL-NASH transition. [ABSTRACT FROM AUTHOR]

Background: The majority of the human genome is transcribed in the form of long non-coding (lnc) RNAs. While these transcripts have attracted considerable interest, their molecular mechanisms of function and biological significance remain controversial. One of the main reasons behind this lies in the significant challenges posed by lncRNAs requiring the development of novel methods and concepts to unravel their functionality. Existing methods often lack cross-validation and independent confirmation by different methodologies and therefore leave significant ambiguity as to the authenticity of the outcomes. Nonetheless, despite all the caveats, it appears that lncRNAs may function, at least in part, by regulating other genes via chromatin interactions. Therefore, the function of a lncRNA could be inferred from the function of genes it regulates. In this work, we present a genome-wide functional annotation strategy for lncRNAs based on identification of their regulatory networks via the integration of three distinct types of approaches: co-expression analysis, mapping of lncRNA-chromatin interactions, and assaying molecular effects of lncRNA knockdowns obtained using an inducible and highly specific CRISPR/Cas13 system. Results: We applied the strategy to annotate 407 very long intergenic non-coding (vlinc) RNAs belonging to a novel widespread subclass of lncRNAs. We show that vlincRNAs indeed appear to regulate multiple genes encoding proteins predominantly involved in RNA- and development-related functions, cell cycle, and cellular adhesion via a mechanism involving proximity between vlincRNAs and their targets in the nucleus. A typical vlincRNAs can be both a positive and negative regulator and regulate multiple genes both in trans and cis. Finally, we show vlincRNAs and their regulatory networks potentially represent novel components of DNA damage response and are functionally important for the ability of cancer cells to survive genotoxic stress. Conclusions: This study provides strong evidence for the regulatory role of the vlincRNA class of lncRNAs and a potentially important role played by these transcripts in the hidden layer of RNA-based regulation in complex biological systems. [ABSTRACT FROM AUTHOR]

Capping ligands are indispensable for the preparation of metal‐halide‐perovskite (MHP) nanocrystals (NCs) with good stability; however, the long alkyl‐chain capping ligands in conventional MHP NCs will be unfavorable for CO2 adsorption and hinder the efficient carrier separation on the surface of MHP NCs, leading to inferior catalytic activity in artificial photosynthesis. Herein, CsPbBr3 nanocrystals with short‐chain glycine as ligand are constructed through a facile ligand‐exchange strategy. Owing to the reduced hindrance of glycine and the presence of the amine group in glycine, the photogenerated carrier separation and CO2 uptake capacity are noticeably improved without compromising the stability of the MHP NCs. The CsPbBr3 nanocrystals with glycine ligands exhibit a significantly increased yield of 27.7 μmol g−1 h−1 for photocatalytic CO2‐to‐CO conversion without any organic sacrificial reagents, which is over five times higher than that of control CsPbBr3 NCs with conventional long alkyl‐chain capping ligands. [ABSTRACT FROM AUTHOR]

Zinc-air batteries have garnered significant attention owing to their high energy density and substantial anode active substance storage. Despite their potential advantages, the application of zinc-air batteries has been hindered in various domains by rapid performance degradation and reduced service life caused by zinc dendrite growth during cycling. This study presents a method of alloying zinc anodes with rare earth metals, such as Ce and Yb, as well as alkaline earth metal Mg to mitigate the growth of zinc dendrites. This is achieved by altering the anisotropy modulus and intensity at the interface energy of the zinc anode. This approach was verified using a COMSOL phase-field model based on an experimental study. The findings demonstrate that the optimal suppression of zinc dendrite growth was achieved with the anisotropy modulus of 6 and the inhibition efficiency is 35%. Moreover, the degree of anisotropic intensity exhibited by the interfacial energy was inversely proportional to the inhibition of zinc dendrite growth. The most effective approach to inhibit dendrite growth involved using a zinc anode composition of 98% Zn–2% Mg and 93.5% Zn–6.5% Yb. The addition of Ce into the zinc anode was found to increase the anisotropy modulus of the anode interface energy, changing the direction and decreasing the height of zinc dendrite growth. Similarly, the addition of Yb to the zinc anode decreased the anisotropic intensity of the interface energy, thereby impeding the growth of the main stem dendrite. [Display omitted] • Adding Ce increased the IEA modulus of the zinc anode, altering dendrite growth direction and decreasing height. • Adding Yb decreased the IEA intensity of the zinc anode, hindering main stem dendrite growth. • Optimal dendrite suppression was achieved with an IEA modulus of 6, yielding a 35% inhibition efficiency. • There is an inverse relationship between the IEA intensity and the inhibition of zinc dendrite growth. [ABSTRACT FROM AUTHOR]

Excessive sulfur and nitrogen deposition is a threat to natural ecosystems. This study investigated the spatio-temporal changes of wet sulfur and nitrogen deposition in Jiuzhaigou to understand the responses of wet deposition chemistry to local and national air pollutant emission changes and to assess relevant ecological risks. The results show that local emission sources (e.g., tourism, post-earthquake reconstruction, and vegetation damages) largely elevated the concentrations of SO 4 2−, NO 3 −, NH 4 +, and Ca2+ at the non-background sites during 2021–2022; However, the gaps of annual sulfur and nitrogen wet deposition fluxes among the background, semi-background, and non-background sites were reduced by annual precipitation. The pH was also higher at the non-background sites due to stronger acid neutralization capacities from crustal dust there, and acid precipitation (pH < 5.6) was not detected at all the sites. During the 2010 to 2022 period, the wet deposition of SO 4 2− and TIN (i.e. total inorganic nitrogen) and the equivalent ratio of SO 4 2−: NO 3 − generally presented a declining trend at the background and semi-background sites, as a result of regional and national emission reductions. The TIN reduction from 2015 to 2016 to 2021–2022 at the background site was more from wet NH 4 + deposition and the site's NO 3 − concentrations and fluxes were relatively stable. Compared to the critical loads (CLs) of sulfur and nitrogen for acidification and eutrophication, the annual wet and wet+dry deposition fluxes of sulfur and nitrogen were lower in almost the entire watershed, except for the CL min of nitrogen for acidification in considerable areas. However, all the wet deposition samples were calcite-unsaturated and had annual TIN concentrations higher than the national environmental standard of total nitrogen for surface water. More field investigations are needed to better assess the ecological risks. [Display omitted] • Acid precipitation (pH < 5.60) was not observed during 2021–2022. • National emission controls decreased acid deposition at the background site. • Local human emissions enhanced acid deposition at the non-background sites. • Alkaline dust well buffered the acidity of precipitation. • CLs were not violated in almost the entire watershed, except for the CL min of nitrogen for acidification. [ABSTRACT FROM AUTHOR]

The aim of this study is to find out the degradation of dynamic behaviour of bridge girders with trapezoidal profiled webs when subjected to different vehicle moving loads. Finite element modelling based parametric analysis is demonstrated to be desirable in capturing the dynamic deflection and stress state of critical structural details of girders. The model is validated in the modal analysis through a comparison with theoretical eigenfrequencies. The vibration characteristics are shown to be significantly affected by the corrugation details. The structural service life results of analysed bridge girders are in close agreement with experimental data. It is shown that the dynamic nodal velocity and deflection of analysed bridge girders are greatly affected by the magnitude of the load corresponding to the overload of the vehicle in contrast to the vehicle travel speed. Similar observations can be made for the fatigue life prediction analysis related to the crack initiation when unfavourable effects of the overload vehicle are concerned. Presented analytical results using a fracture mechanics approach could be taken as a good basis for the service life assessment of related bridges with the desired level of performance or functionality. [ABSTRACT FROM AUTHOR]