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Cardiac arrest (CA)-induced cerebral ischemia remains challenging with high mortality and disability. Neural stem cell (NSC) engrafting is an emerging therapeutic strategy with considerable promise that, unfortunately, is severely compromised by limited cell functionality after in vivo transplantation. This groundbreaking report demonstrates that metabolic glycoengineering (MGE) using the "Ac5ManNTProp (TProp)" monosaccharide analog stimulates the Wnt/β-catenin pathway, improves cell adhesion, and enhances neuronal differentiation in human NSCs in vitro thereby substantially increasing the therapeutic potential of these cells. For the first time, MGE significantly enhances NSC efficacy for treating ischemic brain injury after asphyxia CA in rats. In particular, neurological deficit scores and neurobehavioral tests experience greater improvements when the therapeutic cells are pretreated with TProp than with "stand-alone" NSC therapy. Notably, the TProp-NSC group exhibits significantly stronger neuroprotective functions including enhanced differentiation, synaptic plasticity, and reduced microglia recruitment; furthermore, Wnt pathway agonists and inhibitors demonstrate a pivotal role for Wnt signaling in the process. These findings help establishMGE as a promising avenue for addressing current limitations associated with NSC transplantation via beneficially influencing neural regeneration and synaptic plasticity, thereby offering enhanced therapeutic options to boost brain recovery following global ischemia. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation of iron deficiency (ID) indexes with eradication and recurrence of Helicobacter pylori (Hp) infection in children. Methods: This is a clinical comparative study. One hundred and twenty-six children who were first diagnosed as Hp infection in Baoding Children's Hospital (Hp infection group); and the control group included 200 children without Helicobacter Pylori infection (negative stool Hp antigen test and/or 13C-urea breath test) in local region at the same time from January 2020 to January 2022. Enrolled children were subjected to routine blood test, serum ferritin (SF), serum iron (SI) and total iron binding capacity (TIBC) detection. Meanwhile, children with Hp infection were given triple therapy for eradication and followed up for one year. Results: The levels of SI, SF and Hb in non-eradication group were lower than those in eradication group (P<0.05); while TIBC level in the former group was higher than that in the latter group (P<0.05). Furthermore, SF level in the recurrence group was lower than that in the non-recurrence group (P<0.05). While there was no significant difference in Hb, SI and TIBC levels between the recurrence group and the non-recurrence group (P>0.05). Conclusion: Low level of SF may be a risk factor for difficulty in eradication and recurrence after eradication in children with Hp infection. Meanwhile, low levels of Hb and SI are influential factors for difficulty in eradication in children with Hp infection. [ABSTRACT FROM AUTHOR]

Pinellia ternata is an important natural medicinal herb in China. However, it is susceptible to withering when exposed to high temperatures during growth, which limits its tuber production. Mitochondria usually function in stress response. The P. ternata mitochondrial (mt) genome has yet to be explored. Therefore, we integrated PacBio and Illumina sequencing reads to assemble and annotate the mt genome of P. ternata. The circular mt genome of P. ternata is 876 608 bp in length and contains 38 protein-coding genes (PCGs), 20 tRNA genes and three rRNA genes. Codon usage, sequence repeats, RNA editing and gene migration from chloroplast (cp) to mt were also examined. Phylogenetic analysis based on the mt genomes of P. ternata and 36 other taxa revealed the taxonomic and evolutionary status of P. ternata. Furthermore, we investigated the mt genome size and GC content by comparing P. ternata with the other 35 species. An evaluation of non-synonymous substitutions and synonymous substitutions indicated that most PCGs in the mt genome underwent negative selection. Our results provide comprehensive information on the P. ternata mt genome, which may facilitate future research on the high-temperature response of P. ternata and provide new molecular insights on the Araceae family. [ABSTRACT FROM AUTHOR]

Background: Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids. Result: In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. The sgRNA were designed based on the active site residues. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. The results showed that deletion of PcSE inhibited triterpene synthesis. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach. Conclusion: The findings from this study provide a foundation for further studies on heterologous biosynthesis of P. cocos secondary metabolites. Highlights: The gene of squalene epoxidase in P. cocos was identified. Molecular docking was used to predict the amino acid active site of PcSE. Establishment of a CRISPR/Cas9 gene editing system in P. cocos. Function validation of PcSE on triterpene synthesis by gene deletion. [ABSTRACT FROM AUTHOR]

Regular exercise is known to confer various health benefits, but the specific impact of exercise intensity on antioxidant capacity and immune function remains complex and incompletely understood. Our study investigates the impact of exercise intensity on antioxidant capacity and immune function in mice. Mice were subjected to various exercise intensities (low, moderate, high) on a treadmill. Antioxidant enzyme activity, oxidative stress markers, ROS production, hemoglobin, hematocrit, leukocyte counts, lymphocyte subsets, and phagocytic activities were assessed. Exercise intensity influenced antioxidant enzyme activity, with low and high intensities showing significant effects. High-intensity exercise led to increased lipid peroxidation but improved the glutathione redox ratio. Exercise, irrespective of intensity, significantly affected immune function, notably increasing leukocyte counts, T-cell and B lymphocyte subsets, and phagocytic activities. Even at lower intensities, exercise profoundly impacts antioxidant capacity and immune function. These findings highlight the relationship between exercise, oxidative stress, and immune modulation. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in cancer progression and prognosis. While extensive research has revealed mechanistic links between Fusobacterium nucleatum and colorectal cancer, a comprehensive review spanning its presence and metastatic implications in cancers beyond colorectal origin is conspicuously absent. This paper broadens our perspective from colorectal cancer to various malignancies associated with Fusobacterium nucleatum, including oral, pancreatic, esophageal, breast, and gastric cancers. Our central focus is to unravel the mechanisms governing Fusobacterium nucleatum colonization, initiation, and promotion of metastasis across diverse cancer types. Additionally, we explore Fusobacterium nucleatum's adverse impacts on cancer therapies, particularly within the domains of immunotherapy and chemotherapy. Furthermore, this paper underscores the clinical research significance of Fusobacterium nucleatum as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment. [ABSTRACT FROM AUTHOR]

As large language models (LLMs) like GPT become increasingly prevalent, it is essential that we assess their capabilities beyond language processing. This paper examines the economic rationality of GPT by instructing it to make budgetary decisions in four domains: risk, time, social, and food preferences. We measure economic rationality by assessing the consistency of GPT’s decisions with utility maximization in classic revealed preference theory. We find that GPT’s decisions are largely rational in each domain and demonstrate higher rationality score than those of human subjects in a parallel experiment and in the literature. Moreover, the estimated preference parameters of GPT are slightly different from human subjects and exhibit a lower degree of heterogeneity. We also find that the rationality scores are robust to the degree of randomness and demographic settings such as age and gender but are sensitive to contexts based on the language frames of the choice situations. These results suggest the potential of LLMs to make good decisions and the need to further understand their capabilities, limitations, and underlying mechanisms. [ABSTRACT FROM AUTHOR]

In this paper, we study the evolution of the gradient flow minimizing the anisoperimetric ratio of convex plane curves. It is shown that for any closed embedded initial curve, which is smooth and convex, the flow exists for all time and the evolving curves converge smoothly to a homothety of boundary of the Wulff shape, which is determined by anisotropic function. [ABSTRACT FROM AUTHOR]

Food security is threatened by cadmium (Cd) contamination of rice fields. In-situ immobilization of Cd by silicon (Si) fertilizers is one of the crucial approaches to solving Cd contamination in rice fields. Various mineral Si fertilizers versus liquid Si fertilizers were compared in this study with in-situ field experiments to explore their effects and the regulating mechanisms on reducing Cd bioavailability in paddy fields as well as Cd absorption and transport in rice. The results showed that both the sprinkled mineral Si fertilizer and the foliar spray of liquid Si fertilizer significantly reduced the Cd concentration in brown rice, which was linked to reduced Cd availability in soils. Further analysis of the interaction between Si and Cd indicated that the reduced soil Cd availability and Cd accumulation in brown rice was mainly ascribed to an increase in soil pH and the available Si/Cd ratio. Among these Si fertilizers, LS and GS dominated by amorphous Si were more effective in controlling the accumulation of Cd in brown rice and declining the toxic risk of Cd on human health in rice consumption. In conclusion, Si fertilizer reduced Cd concentration in brown rice via increasing rhizosphere soil pH and available Si/Cd ratio. [ABSTRACT FROM AUTHOR]

Bacterial colonization and biofilm formation on the surface of materials can lead to serious bacterial infections and are highly detrimental to our health. Here, we prepared a water-insoluble HPL-DOSS complex by compounding hyperbranched polylysine (HPL) with docusate sodium salt (DOSS) and coated HPL-DOSS onto the surfaces of the commercial polypropylene (PP) and thermoplastic polyurethane (TPU) plastics to afford antibacterial PP-HD and TPU-HD plastics. PP-HD and TPU-HD showed excellent antibacterial activities against both Escherichia coli and MRSA. In addition, the bacterial residues on the PP-HD and TPU-HD surfaces were significantly reduced compared with the pristine PP and TPU surfaces, indicating that the HPL-DOSS surface coating had good anti-adhesive property against bacteria and helped to reduce the formation of biofilms. Meanwhile, both PP-HD and TPU-HD exhibited excellent biocompatibility, indicating that the HPL-DOSS complex could be used as a safe antimicrobial coating material to reduce bacterial infections on plastic surfaces. [ABSTRACT FROM AUTHOR]

Intercropping is an efficient way to utilize growth resources and for economic benefits. We evaluated the possibility of Zelkova schneideriana Hand. Mazz intercropping with maize (Zea mays L), wheat (Triticum aestivum L), rape (Brassica rapa C), and tall fescue (Festuca elata K). A total of 39 compounds were identified in Z. schneideriana root exudates by GC-MS analysis; 1,2-benzenedicarboxylic acid, bis (2-methylpropyl) ester had the highest content (50.36 %), followed by phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl- (21.56 %). Growth of the test crops was inhibited by root exudates, when applied at 4 mg·ml-1, however, promoted at 2 mg·ml-1. The strongest inhibition was observed in maize and the lowest in tall fescue. The physiological responses of the crops to the root exudates of Z. schneideriana showed similar treads. Malondialdehyde (MDA) content was the most sensitive parameter followed by relative electrical conductivity (REL) and chlorophyll (Chl) content, indicating the trait-specific responses. Rape growth was the most promoted at 2 mg·ml-1, followed by tall fescue. Rape was found the ideal specie for intercropping with Z. schneideriana, followed by tall fescue. [ABSTRACT FROM AUTHOR]

A center-fed circularly polarized stacked patch antenna (CF-CPSPA) with enhanced axial-ratio (AR) bandwidth is proposed in this paper. The antenna is composed of two microstrip patches, the lower patch consists of a circular pad, an elliptical-ring, and two branch lines connecting them, which is used to realize the center-fed condition, and the upper patch is an elliptical patch to achieve the wide band performance. Firstly, two center-fed linearly polarized stacked patch antennas with wide band are designed, one mode radiated with x polarization, and the other generates y polarized radiation. Next, the orthogonal modes of two linearly polarized antennas are combined together by a specific design. Finally, the approximate equal amplitude and quadrature phase difference of the introduced modes are achieved in the operating frequency band with proper parameters analysis. And the impedance bandwidth and 3dB AR bandwidth is improved to 30.4% and 16.5%. [ABSTRACT FROM AUTHOR]

Clinically, arsenic trioxide (ATO) was applied to the treatment of acute promyelocytic leukemia (APL) as a reliable and effective frontline drug. However, the administration regimen of AsIII was limited due to its fast clearance, short therapeutic window and toxicity as well. Based on CD71 overexpressed on APL cells, in present study, a transferrin (Tf)- modified liposome (LP) was established firstly to encapsulate As III in arsenic-nickel complex by nickel acetate gradient method. The As III -loaded liposomes (AsLP) exhibited the feature of acid-sensitive release in vitro. Tf-modified AsLP (Tf-AsLP) were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release As III which stimulated reactive oxygen species level and caspase-3 activity. Tf-AsLP prolonged half-life of As III in blood circulation, lowered systemic toxicity, and promoted apoptosis and induced cell differentiation at lesion site in vivo. Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect, accordingly, a Tf-modified RA liposome (Tf-RALP) was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy. As expected, the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model. Furthermore, APL orthotopic NOD/SCID mice model was established by 60 CO irradiation and HL-60 cells intravenously injection. The effect of co-administration (Tf- AsLP + Tf-RALP) was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells' apoptosis and differentiation in peripheral blood and bone marrow. Collectively, Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug. Moreover, Tf-AsLP combined with Tf-RALP could achieve better efficacy. Thus, transferrinmodified As III liposome would be a novel clinical strategy to improve patient compliance, with promising translation prospects. [ABSTRACT FROM AUTHOR]

On January 1,2021, the newly revised Archives Law of the People's Republic of China (hereinafter referred to as the new Archives Law) was officially implemented, providing legal protection for archive management, archive work and archive undertaking in the new era. Starting from the relevant provisions of the new Archives Law, the collection of precious meteorological archives was discussed, and it is believed that only on the basis of clarifying the definition, collection responsibility subject, collection scope, ways and methods of precious meteorological archives can the relevant units be convenient to practice and obtain substantive collection effect. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the extensive application of paclitaxel for injection (albumin-bound), its adverse reactions have also received increasing attention. AIM: This study aims to provide a reference for the safe use of albumin-bound paclitaxel in clinical practice; adverse drug events signals of albumin-bound paclitaxel were reviewed and identified by data mining of the Food and Drug Administration (FDA) adverse event reporting system (FAERS). METHODS: The reporting odds ratio method was used for the quantitative detection of signals from the data in the FDA public data program (OpenFDA) during 2004-2019 for the albumin-bound paclitaxel. RESULTS: According to the OpenFDA, 1659 adverse events (AEs) were identified for albumin-bound paclitaxel. AEs were mostly observed in females rather than males, aged 45-64 years. AEs involved 17 system organ classes, mainly blood and lymphatic, gastrointestinal, hepatobiliary, respiratory, thoracic, and mediastinal systems, and general AEs. Safety signals were found in 20 unexpected adverse drug reactions which are not listed on drug labels, mainly including macular edema and lymphopenia. CONCLUSION: Identifying and evaluating albumin-bound paclitaxel-associated AEs signals by mining FAERS may help evaluate the safety profiles of albumin-bound paclitaxel and reduce the risk of medical treatment. In the clinical application of albumin-bound paclitaxel in addition to the adverse reactions mentioned in the drug instructions, lymphocyte changes should be paid close attention to, and eye monitoring should be conducted regularly to avoid drug withdrawal or organ damage caused by adverse reactions. [ABSTRACT FROM AUTHOR]

Low-dimensional and computationally less-expensive reduced-order models (ROMs) have been widely used to capture the dominant behaviors of high-4dimensional systems. An ROM can be obtained, using the well-known proper orthogonal decomposition (POD), by projecting the full-order model to a subspace spanned by modal basis modes that are learned from experimental, simulated, or observational data, i.e., training data. However, the optimal basis can change with the parameter settings. When an ROM, constructed using the POD basis obtained from training data, is applied to new parameter settings, the model often lacks robustness against the change of parameters in design, control, and other real-time operation problems. This paper proposes to use regression trees on Grassmann manifold to learn the mapping between parameters and POD bases that span the low-dimensional subspaces onto which full-order models are projected. Motivated by the observation that a subspace spanned by a POD basis can be viewed as a point in the Grassmann manifold, we propose to grow a tree by repeatedly splitting the tree node to maximize the Riemannian distance between the two subspaces spanned by the predicted POD bases on the left and right daughter nodes. Five numerical examples are presented to comprehensively demonstrate the performance of the proposed method, and compare the proposed tree-based method to the existing interpolation method for POD basis and the use of global POD basis. The results show that the proposed tree-based method is capable of establishing the mapping between parameters and POD bases, and thus adapt ROMs for new parameters. [ABSTRACT FROM AUTHOR]

Variants of isocitrate dehydrogenase (IDH) 1 and 2 (IDH1/2) alter metabolism in cancer cells by catalyzing the NADPHdependent reduction of 2-oxoglutarate (2OG) to (2R)-hydroxyglutarate. However, it is unclear how derivatives of 2OG can affect cancer cell metabolism. Here, we used synthetic C3- and C4-alkylated 2OG derivatives to investigate the substrate selectivities of the most common cancer-associated IDH1 variant (R132H IDH1), of two cancer-associated IDH2 variants (R172K IDH2, R140Q IDH2), and of WT IDH1/2. Absorbancebased, NMR, and electrochemical assays were employed to monitor WT IDH1/2 and IDH1/2 variant-catalyzed 2OG derivative turnover in the presence and absence of 2OG. Our results reveal that 2OG derivatives can serve as substrates of the investigated IDH1/2 variants, but not of WT IDH1/2, and have the potential to act as 2OG-competitive inhibitors. Kinetic parameters reveal that some 2OG derivatives, including the natural product 3-methyl-2OG, are equally or even more efficient IDH1/2 variant substrates than 2OG. Furthermore, NMR and mass spectrometry studies confirmed IDH1/2 variant-catalyzed production of alcohols in the cases of the 3-methyl-, 3-butyl-, and 3-benzyl-substituted 2OG derivatives; a crystal structure of 3-butyl-2OG with an IDH1 variant (R132C/S280F IDH1) reveals active site binding. The combined results highlight the potential for (i) IDH1/2 variantcatalyzed reduction of 2-oxoacids other than 2OG in cells, (ii) modulation of IDH1/2 variant activity by 2-oxoacid natural products, including some present in common foods, (iii) inhibition of IDH1/2 variants via active site binding rather than the established allosteric mode of inhibition, and (iv) possible use of IDH1/2 variants as biocatalysts. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that perform multiple and important cellular functions. The protein investigated here belongs to class IA of the PI3Ks; it is a dimer consisting of a catalytic subunit, p110α, and a regulatory subunit, p85α, and is referred to as PI3Kα. The catalytic subunit p110α is frequently mutated in cancer. The mutations induce a gain of function and constitute a driving force in cancer development. About 80% of these mutations lead to single-amino-acid substitutions in one of three sites of p110α: two in the helical domain of the protein (E542K and E545K) and one at the C-terminus of the kinase domain (H1047R). Here, we report the cryo-electron microscopy structures of these mutants in complex with the p110α-specific inhibitor BYL-719. The H1047R mutant rotates its sidechain to a new position and weakens the kα11 activation loop interaction, thereby reducing the inhibitory effect of p85α on p110α. E542K and E545K completely abolish the tight interaction between the helical domain of p110α and the N-terminal SH2 domain of p85α and lead to the disruption of all p85α binding and a dramatic increase in flexibility of the adaptor-binding domain (ABD) in p110α. Yet, the dimerization of PI3Kα is preserved through the ABD-p85α interaction. The local and global structural features induced by these mutations provide molecular insights into the activation of PI3Kα, deepen our understanding of the oncogenic mechanism of this important signaling molecule, and may facilitate the development of mutant-specific inhibitors. [ABSTRACT FROM AUTHOR]

As fishbone multilateral wells are increasingly used in the development of oil and gas fields, the need for the optimal design of multilateral well parameters has become increasingly urgent. Although the establishment of multilateral well productivity models has taken a step forward due to recently contributed research results, there are still few studies on model verification; that is, these models lack verification, and their reliability is uncertain, which increases the difficulty of their promotion and application in practice. Therefore, based on a more comprehensive horizontal well productivity prediction model, a fishbone multilateral well productivity prediction model was established in this work. Taking an oil field in the Middle East as an example, multilateral well productivity prediction and parameters sensitivity analysis were carried out, and the results were compared with the simulation results determined by using CMG digital simulation software. The established model was verified in terms of branch length, branch angle, and branch output contribution. The conclusions reached by these two methods were consistent, which verified that the established model was reliable. [ABSTRACT FROM AUTHOR]

Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3Kα. The application of chemical cross-linking mass spectrometry (CXMS) facilitated the identification of the p85 domains BH, cSH2, and SH3 as well as their docking positions on the PI3Kα catalytic core. Binding of individual nanobodies to PI3Kα induced activation or inhibition of enzyme activity and caused conformational changes that could be correlated with enzyme function. Binding of nanobody Nb3-126 to the BH domain of p85α substantially improved resolution for parts of the PI3Kα complex, and binding of nanobody Nb3-159 induced a conformation of PI3Kα that is distinct from known PI3Kα structures. The analysis of CXMS data also provided mechanistic insights into the molecular underpinning of the flexibility of PI3Kα. [ABSTRACT FROM AUTHOR]

Collagen is the most abundant component of mammalian extracellular matrices. As such, the development of materials that mimic the biological and mechanical properties of collagenous tissues is an enduring goal of the biomaterials community. Despite the development of molded and 3D printed collagen hydrogel platforms, their use as biomaterials and tissue engineering scaffolds is hindered by either low stiffness and toughness or processing complexity. Here, we demonstrate the development of stiff and tough biohybrid composites by combining collagen with a zwitterionic hydrogel through simple mixing. This combination led to the self-assembly of a nanostructured fibrillar network of collagen that was ionically linked to the surrounding zwitterionic hydrogel matrix, leading to a composite microstructure reminiscent of soft biological tissues. The addition of 5–15 mg mL−1 collagen and the formation of nanostructured fibrils increased the elastic modulus of the composite system by 40% compared to the base zwitterionic matrix. Most notably, the addition of collagen increased the fracture energy nearly 11-fold (Γ= 180 J m−2) and clearly delayed crack initiation and propagation. These composites exhibit elastic modulus (E= 0.180 MJ) and toughness (W*= 0.617 MJ m−3) approaching that of biological tissues such as articular cartilage. Maintenance of the fibrillar structure of collagen also greatly enhanced cytocompatibility, improving cell adhesion more than 100-fold with >90% cell viability. [ABSTRACT FROM AUTHOR]

The large scale of the power grid and its high voltage make the fault detection have not only heavy workload but also high risks. This paper briefly introduced the inspection robot system, edge computing technology, and support vector machine (SVM)-based image recognition algorithm. To enable the inspection robot system to actively adjust the algorithm parameters and maintain the accuracy of the algorithm, the SVM algorithm was improved by the incremental learning technology. Then, the non-improved and improved SVM algorithms were simulated in MATLAB software. A one-month experiment was carried out in a substation. The results showed that the improved SVM algorithm trained faster and had a high accuracy in the face of new samples. The substation experiment verified that the inspection robot system maintained the infrared image recognition accuracy of the faulty equipment for a long time after the application of the improved SVM algorithm, and the system had a smaller delay in transmitting command information after the application of edge computing. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor delta (PPARd) agonists have been shown to exert beneficial effects in liver disease and reduce total bile acid levels. The mechanism(s) whereby PPARd agonism reduces bile acid levels are, however, unknown, and therefore the aim of the present study was to investigate the molecular pathways responsible for reducing bile acid synthesis in hepatocytes, following treatment with the selective PPARd agonist, seladelpar. We show that administration of seladelpar to WT mice repressed the liver expression of cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme for bile acid synthesis, and decreased plasma 7a-hydroxy-4-cholesten-3-one (C4), a freely diffusible metabolite downstream of Cyp7a1. In primary mouse hepatocytes, seladelpar significantly reduced the expression of Cyp7a1 independent of the nuclear bile acid receptor, Farnesoid X receptor. In addition, seladelpar upregulated fibroblast growth factor 21 (Fgf21) in mouse liver, serum, and in cultured hepatocytes. We demonstrate that recombinant Fgf21 protein activated the c-Jun N-terminal kinase (JNK) signaling pathway and repressed Cyp7a1 gene expression in primary hepatocytes. The suppressive effect of seladelpar on Cyp7a1 expression was blocked by a JNK inhibitor as well as in the absence of Fgf21, indicating that Fgf21 plays an indispensable role in PPARd-mediated downregulation of Cyp7a1. Finally, reduction of CYP7A1 expression by seladelpar was confirmed in primary human hepatocytes. In conclusion, we show that seladelpar reduces bile acid synthesis via an FGF21-dependent mechanism that signals at least partially through JNK to repress CYP7A1. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV) infections continue to pose a global public health threat, with high mortality rates and sporadic outbreaks in Central and Western Africa. A quantitative understanding of the key processes driving EBOV assembly and budding could provide valuable insights to inform drug development. Here, we use a computational model to evaluate EBOV matrix assembly. Our model focuses on the assembly kinetics of VP40, the matrix protein in EBOV, and its interaction with phosphatidylserine (PS) in the host cell membrane. It has been shown that mammalian cells transfected with VP40-expressing plasmids are capable of producing virus-like particles (VLPs) that closely resemble EBOV virions. Previous studies have also shown that PS levels in the host cell membrane affects VP40 association with the plasma membrane inner leaflet and that lower membrane PS levels result in lower VLP production. Our computational findings indicate that PS may also have a direct influence on VP40 VLP assembly and budding, where a higher PS level will result in a higher VLP budding rate and filament dissociation rate. Our results further suggest that the assembly of VP40 filaments follow the nucleation-elongation theory, where initialization and oligomerization of VP40 are two distinct steps in the assembly process. Our findings advance the current understanding of VP40 VLP formation by identifying new possible mechanisms of PS influence on VP40 assembly. We propose that these mechanisms could inform treatment strategies targeting PS alone or in combination with other VP40 assembly steps. [ABSTRACT FROM AUTHOR]

Photosynthesis is the most important chemical reaction in the world. Improving photosynthetic efficiency has always been the most basic and logical way to increase crop yields. In recent years, many marvelous achievements have been made in rice and tobacco, but research on high photosynthetic efficiency in soybeans has stagnated. This chapter briefly introduces the principles of photosynthesis and the contribution of photosynthesis to soybean yield; reviews the progress of the photosynthates allocation within seeds and nodules, and the further effects of the photosynthates distribution on filling, yield and quality; reviews the contribution of the coordination of two essential elements of carbon and nitrogen between source and sink to soybean yield and nodules; summarizes the critical functions of the various of sugar transporters and key enzymes for carbon related metabolisms; summarizes the contribution of novel tools such as synthetic biology and phenomics to the improvements of soybean photosynthetic efficiency and prospects the potentials of combinations of multiple powerful tools to breed and cultivate soybean materials and varieties with excellent photosynthesis performance. We hope this review to provide new idea on soybean photosynthesis and shed light on the next green revolution of soybean industry. [ABSTRACT FROM AUTHOR]

In the United States and around the world, women’s reproductive health rights are under threat. In Malawi, abortion is almost entirely illegal; and pregnant women and girls oftentimes resort to drinking poison or using crude objects to self-induce abortions. Every year, hundreds of Malawian women and girls die from unsafe abortion. Yet, these deaths are needless and preventable. Empirical research clearly shows that maternal mortality caused by unsafe abortion can be prevented by having laws that allow for safe and legal termination of pregnancy. Maternal mortality caused by unsafe abortion can also be prevented by having strong financial investment in and awareness-raising of family planning services. This Article examines the harmful impacts of the “global gag rule” in the Malawi context. The rule conditions U.S. global health funding assistance for foreign aid recipients (including sexual and reproductive health NGOs in Malawi) on a recipient’s promise that it will not perform or support abortions as a method of family planning—even with non-U.S. funds or the NGO’s own funds. The policy further prohibits such NGOs from conducting advocacy around abortion, stifling much needed education and debate about a new abortion law that, if enacted, would save women’s lives. The policy has been rescinded by every Democratic president and reinstated by every Republican president, subjecting the rights and the lives of countless women and girls in Malawi and around the world to the political winds in the United States. This Article argues that legislation must be enacted to stop the policy once and for all. [ABSTRACT FROM AUTHOR]

Medication nonadherence (MNA) can lead to serious health ramifications and costs U.S. healthcare systems $290 billion annually. Understanding the reasons underlying patients' MNA is thus an urgent goal for researchers, practitioners, and the pharmaceutical industry in order to mitigate negative health and economic consequences. In recent years, patient engagement on social media sites has soared, making it a cost-efficient and rich information source that can complement prior survey studies and deepen the understanding of MNA. Yet these data remain untapped in existing MNA studies because of technical challenges such as long texts, decision-making based on negative sentiment, varied patient vocabulary, and the scarcity of relevant information. For this study, we developed a sentiment-enriched deep learning method (SEDEL) to address these challenges and extract reasons for MNA. We evaluated SEDEL using 53,180 reviews concerning 180 drugs and achieved a precision of 89.25%, a recall of 88.48%, and an F1 score of 88.86%. SEDEL significantly outperformed state-of-the-art baseline models. We identified nine categories of MNA reasons, which were verified by domain experts. This study contributes to IS research by devising a novel deep-learning-based approach for reason mining and by providing direct implications for the health industry and for practitioners regarding the design of interventions. [ABSTRACT FROM AUTHOR]

Objective: Changing insights regarding the extent of surgery for low‐risk papillary thyroid cancer (PTC) stir up discussions on the benefits and harms of thyroid lobectomy versus total thyroidectomy. The chance of needing postoperative thyroid hormone supplementation after thyroid lobectomy is still unclear. The purpose of this retrospective two‐center study was to identify the incidence and risk factors of postoperative thyroid‐stimulating hormone (TSH) elevation (>2.0 μIU/ml) after thyroid lobectomy for low‐risk PTC. Design and Methods: Medical records of 201 consecutive patients with low‐risk PTC from two tertiary centers who underwent thyroid lobectomy between 2015 and 2019 were retrospectively reviewed. Postoperative thyroid function tests were measured regularly and patients were prescribed levothyroxine if the TSH level was higher than 2.0 μIU/ml. Multivariable regression models were used to evaluate potential risk factors associated with postoperative TSH elevation after thyroid lobectomy. Results: At 6 weeks postoperatively, 85% had TSH level of >2 μIU/ml; this increased to 88% by 3–6 months. Receiver operating characteristic analysis identified preoperative TSH cut‐off (>1.7 μIU/ml) to predict postoperative TSH elevation. Multivariate analysis revealed that only a high preoperative TSH level (>1.7 μIU/ml) was an independent risk factor for a postoperative TSH level of >2 μIU/ml (odds ratio = 7.71; p <.001). Conclusion: Nearly 90% of the patients who underwent thyroid lobectomy for low‐risk PTC had a postoperative TSH level of >2 μIU/ml, necessitating thyroid hormone supplementation in accordance with current guidelines. This finding highlights that preoperative patient counseling should also focus on raising awareness about postoperative thyroid hormone supplementation for low‐risk PTC patients seeking thyroid lobectomy. [ABSTRACT FROM AUTHOR]

In this work, we reported the development of a nickel metal-organic framework nanosheet array on Timesh (Ni-MOF/TM) as an enzyme-free electrochemical sensing platform for H2O2 determination. The as-obtained sensor exhibited outstanding detection properties of H2O2, which might be gifted from the large specific surface area, abundant active sites of Ni-MOF nanoarrays. The sensor displayed a good linear range (0.8 µM-4.6× 10³ µM), a detection limit as low as 0.26 µM, a high sensitivity (307.5 µAmM-1cm-2), and a rapid response. Moreover, this enzyme-free sensor is promising for pointofcare (POC) testing of H2O2 in human serum attribute to the excellent performance of Ni-MOF and the simple preparation process of the sensor. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients.A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions.The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003).Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image.Methods: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients.A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions.The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003).Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image.Results: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients.A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions.The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003).Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image.Conclusion: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients.A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions.The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003).Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image.Graphical abstract: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients.A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions.The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003).Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image. [ABSTRACT FROM AUTHOR]

The resting brain consumes enormous energy and shows highly organized spontaneous activity. To investigate how this activity is manifest among single neurons, we analyzed spiking discharges of ~10,000 isolated cells recorded from multiple cortical and subcortical regions of the mouse brain during immobile rest. We found that firing of a significant proportion (~70%) of neurons conformed to a ubiquitous, temporally sequenced cascade of spiking that was synchronized with global events and elapsed over timescales of 5 to 10 s. Across the brain, two intermixed populations of neurons supported orthogonal cascades. The relative phases of these cascades determined, at each moment, the response magnitude evoked by an external visual stimulus. Furthermore, the spiking of individual neurons embedded in these cascades was time locked to physiological indicators of arousal, including local field potential power, pupil diameter, and hippocampal ripples. These findings demonstrate that the large-scale coordination of lowfrequency spontaneous activity, which is commonly observed in brain imaging and linked to arousal, sensory processing, and memory, is underpinned by sequential, large-scale temporal cascades of neuronal spiking across the brain. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases essential for growth and metabolism. Their aberrant activation is associated with many types of cancers. Here we used single-particle cryoelectron microscopy (cryo-EM) to determine three distinct conformations of full-length PI3Kα (p110α-p85α): the unliganded heterodimer PI3Kα, PI3Kα bound to the p110α-specific inhibitor BYL-719, and PI3Kα exposed to an activating phosphopeptide. The cryo-EM structures of unbound and of BYL-719-bound PI3Kα are in general accord with published crystal structures. Local deviations are presented and discussed. BYL-719 stabilizes the structure of PI3Kα, but three regions of low-resolution extra density remain and are provisionally assigned to the cSH2, BH, and SH3 domains of p85. One of the extra density regions is in contact with the kinase domain blocking access to the catalytic site. This conformational change indicates that the effects of BYL-719 on PI3Kα activity extend beyond competition with adenosine triphosphate (ATP). In unliganded PI3Kα, the DFG motif occurs in the "in" and "out" positions. In BYL-719-bound PI3Kα, only the DFG-in position, corresponding to the active conformation of the kinase, was observed. The phosphopeptide-bound structure of PI3Kα is composed of a stable core resolved at 3.8 Å. It contains all p110α domains except the adaptor-binding domain (ABD). The p85α domains, linked to the core through the ABD, are no longer resolved, implying that the phosphopeptide activates PI3Kα by fully releasing the niSH2 domain from binding to p110α. The structures presented here show the basal form of the full-length PI3Kα dimer and document conformational changes related to the activated and inhibited states. [ABSTRACT FROM AUTHOR]

Rolipram specifically inhibits phosphodiesterase (PDE) 4, thereby preventing inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to play a neuroprotective role in some central nervous system (CNS) diseases. However, the role of PDE4 and the potential protective effect of rolipram on the pathophysiological process of intracerebral haemorrhage (ICH) are still not entirely clear. In this study, a mouse model of ICH was established by the collagenase method. Rolipram reduced brain oedema, blood–brain barrier (BBB) leakage, neuronal apoptosis and inflammatory cytokine release and improved neurological function in our mouse model of ICH. Moreover, rolipram increased the levels of cAMP and silent information regulator 1 (SIRT1) and upregulated the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, these effects of rolipram could be reversed by the SIRT1 inhibitor sirtinol. In conclusion, rolipram can play a neuroprotective role in the pathological process of ICH by activating the cAMP/AMPK/SIRT1 pathway. [ABSTRACT FROM AUTHOR]

Plasma-activated water (PAW) is a new sanitizer that has received considerable attention for application in food industries. This research aimed to evaluate the effect of PAW on the inactivation of Shewanella putrefaciens and quality attributes of Yellow River carp (Cyprinus carpio) fillets. The carp fillet samples were immersed in sterile deionized water (SDW) or SDW activated by plasma discharge for 120 s (PAW120) for 1.5, 3.0, 4.5, or 6.0 min. After being treated by PAW120 for 6 min, the population of S. putrefaciens on carp fillets was significantly (P < 0.05) decreased by 1.03 log CFU/g. Compared with SDW-treated samples, the L* value of PAW120–treated carp fillets was increased and the a* value was decreased after PAW120 treatment, whereas there was no significant (P > 0.05) difference in the b* value. Compared with SDW, PAW120 caused no significant (P > 0.05) changes in sensory properties and texture attributes of carp fillets including hardness, springiness, gumminess, and cohesiveness. However, 6-min PAW120 treatment caused a significant increase in the lipid oxidation level and a decrease in the pH value of the carp fillets. This work provides a basis for the potential application of PAW in the preservation of aquatic products. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is threatening the world with the symptoms of seasonal influenza. This study was conducted to investigate the patient characteristics and clinical value of blood markers to assess the severity of coronavirus disease 2019 (COVID-19).Methods: 187 patients, diagnosed with COVID-19 (non-severe and severe cases) and admitted to hospital between January 27th and March 8th of 2020, were enrolled in the present study.Results: A higher proportion of clinical symptoms, including cough, expectoration, myalgia, and fatigue were observed in the non-severe group. The level of white blood cell count, neutrophils, CRP, IL-6 and IL-8 were significantly increased, while the platelet count was remarkedly decreased in the severe group. The risk model based on lymphocyte, IL-6, IL-8, CRP and platelet counts had the highest area under the receiver operator characteristic curve (AUROC). The baseline of IL-6, IL-8 and CRP was positively correlated with other parameters except in the cases of lymphocyte, hemoglobin and platelet counts. The baseline of the platelet count was negatively correlated with other parameters except in the lymphocyte and hemoglobin counts. Additionally, there was no connection between the severity of COVID-19 and cultures of blood, sputum or catheter secretion.Conclusions: The present study suggested that high leucocyte and low platelets counts were independent predictive markers of the severity of COVID-19. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (ATO) combined with all trans retinoic acid (ATRA) is the first choice for the treatment of low and medium risk acute promyelocytic leukemia (APL). Clinical studies reported that the combination of ATO and ATRA could achieve a significant curative effect. However, the retinoic acid syndrome, serious drug resistance and the short half-life in vivo which lead to frequent and large dose administration limit the application of ATRA. In addition, the preparations of arsenic are conventional injections and tablets in clinic, which has poor patients' compliance caused by frequent long-term administration and serious side effects. In order to overcome the above limitations, a phospholipid phase separation gel (PPSG) loaded with ATO and ATRA was developed. ATO + ATRA-PPSG (AAP), as a biodegradable sustained-release delivery system, was the first achievement of co-delivery of hydrophilic ATO and lipophilic ATRA with high drug loading which is the main problem in the application of nano preparation. The prepared PPSG displayed high safety and biocompatibility. The drug in PPSG was released slowly and continuously in vivo and in vitro for up to 10 d, which could reduce the side effects caused by the fluctuation of blood drug concentration and solve the problem of the long treatment cycle and frequent administration. In vivo pharmacokinetics depicted that PPSG could improve the bioavailability, decrease the peak concentration, and prolong the t1/2 of ATO and ATRA. Particularly, AAP significantly inhibited the tumor volume, extended the survival period of tumor-bearing mice, and promoted the differentiation of APL cells into normal cells. Therefore, ATO + ATRA-PPSG not only could co-load hydrophilic ATO and lipophilic ATRA according to the clinical dosage, but also possessed the sustained-release and long-acting treatment effect which was expected to reduce administration time and ameliorate compliance of patients. Thus, it had great potential for clinical transformation and application. [ABSTRACT FROM AUTHOR]

Zonal winds in the stratosphere and mesosphere play important roles in the atmospheric dynamics and aeronomy. However, the direct measurement of winds in this height range is difficult. We present a dataset of the monthly mean zonal wind in the height range of 18-100 km and at latitudes of 50°S-50°N from 2002 to 2019, which is derived by the gradient balance wind theory and the temperature and pressure observed by the SABER instrument. The tide alias above 80 km at the equator is replaced by the monthly mean zonal wind measured by a meteor radar at 0.2°S. The dataset (named as BU) is validated by comparing with the zonal wind from MERRA2 (MerU), UARP (UraU), HWM14 empirical model (HwmU), meteor radar (MetU) and lidar (LidU) at seven stations from 53.5°N to 29.7°S. At 18-70 km, BU and MerU have (1) nearly identical zero wind lines, (2) year-to-year variations of the eastward/westward wind jets at middle and high latitudes, (3) the quasi-biennial oscillation (QBO) and semi-annual oscillation (SAO), especially the anormal QBO in early 2016. The comparisons among BU, UraU and HwmU show good agreement in general below 80 km. Above 80 km, the agreements among BU, UraU, HwmU, MetU and LidU are good in general, except some discrepancies at limited heights and months. The BU data are archived as netCDF files and can be available at https://dx.doi.org/10.12176/01.99.00574 (Liu et al., 2021). [ABSTRACT FROM AUTHOR]

Malawi has a duty to ensure that all Malawian boys and girls are protected from sexual violence and that justice is served on sexual abusers. Yet, sexual violence against children in Malawi is pervasive, and survivors face significant barriers in their quest for justice. The Constitution of Malawi and the country's legal obligations under various human rights treaties necessitate a detailed look at the gaps and inconsistencies in the laws that fuel rape culture and that grant impunity to sex offenders. Interview accounts by affected persons, children's and women's rights advocates, community leaders, and other stakeholders in Malawi also sound a chorus of voices calling for legislative change. This article argues that the current Malawian laws on sexual offenses relating to children-namely the laws in the Penal Code on "defilement" (i.e., statutory rape), incest, and sex with minors under one's care or protection-fail to protect adequately and equally all girls and boys under the age of 18 from sexual abuse and exploitation. Further, the law on statutory rape over-criminalizes sex between consenting teenagers, and the Child Care, Protection and Justice Act treats consensual teenage sex as a serious offense. This article proposes several key amendments to the Malawi Penal Code and the Child Care, Protection and Justice Act. If enacted, these amendments would help to align the protection of children with their rights guaranteed by the Constitution and international human rights treaties. [ABSTRACT FROM AUTHOR]

Objective: An experiment was conducted to investigate the effects of Achyranthes japonica extracts (AJE) on the growth performance, nutrient digestibility, fecal microbial shedding, and fecal gas emission of growing pigs. Methods: A total of 180 ([LandracexYorkshire]xDuroc) growing pigs with initial body weight (BW) of 23.94±1.54 kg were used in this study to investigate the effects of AJE as a feed additive. Dietary treatments included: i) CON (basal diet), ii) TRT1 (basal diet+0.05% AJE), and iii) TRT2 (basal diet+0.10% AJE). Results: As a result of the dietary supplementation of 0% to 0.10% AJE, a linear increase of BW (p<0.05) on d 21 and 42, a linear increase of average daily gain (ADG) (p<0.05) during d 21 to 42, a trend in linear increase of ADG (p<0.10) during d 0 to 21 and d 0 to 42, a linear increase of gain to feed ratio (G:F) (p<0.05) during d 0 to 42, and a tendency in the linear increase of G:F during d 21 to 42 were observed in this study. Additionally, dietary supplementation of 0% to 0.10% AJE had a linear increase (p<0.05) on the apparent total tract digestibility of dry matter (DM) and energy, a linear increase (p<0.05) on lactic acid bacteria counts, a tendency in reducing (linear effect, p<0.10) coliform bacteria counts, and a linear decrease (p<0.05) in excreta H2S emission content in growing pigs. Conclusion: In conclusion, the results suggested that AJE had the potential to enhance growth performance, DM and energy digestibility, and fecal lactic acid bacteria counts, and decrease the fecal coliform bacteria counts and excreta H2S emission in growing pigs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the reliability of quantitative analysis of dynamic stretching muscle stiffness using shear wave elas-tography (SWE), and to evaluate the influence of stretched levels and region of interest (ROI) sizes on the repeatability of SWE measurements.Materials and Methods: SWE videos of the gastrocnemius medius were collected during ankle movement from plantar flexion (PF) 40° to dorsiflexion (DF) 30°. Shear wave imageswere collected of ankle angles at PF 25°, 0°, DF 15°, and DF 30°, representing the slack status, mildly stretched level, moderately stretched level, and maximal stretched level of the gastrocnemius medius, respectively. ROI circles with diameters of 2 mm, 5 mm, and 8 mm were applied to measure the shear modulus. Intra-observer, and inter-observer repeatability of the measurements were compared among different stretched levels and ROI sizes.Results: Twenty-one healthy volunteers were enrolled. Muscle stiffness increased as the ankle DF increased. Intraclass correlation coefficients (ICCs) of intra-observer and inter-observer repeatability obtained for ROI sizes of 2 mm, 5 mm and 8 mm indicated good to excellent repeatability at all stretched levels.Conclusions: Shear wave elastography appeared to be a reliable tool to evaluate the dynamic stretching muscle stiffness with satisfactory repeatability at various stretched levels of gastrocnemius medius. Good to excellent repeatability was found using different ROI sizes. [ABSTRACT FROM AUTHOR]

The article offers information on regulating the reactivity of black phosphorus via protective chemistry. It mentions that rationally regulating the reactivity of molecules or functional groups as common in organic chemistry, both in laboratory and industry synthesis. It demonstrates a protective chemistry– based methodology for regulating black phosphorus reactivity.

We have demonstrated and developed a W-band 30 W continuous-wave folded waveguide traveling wave tube (CW FWTWT) with 13.5-kV operation voltage and 4.8 dB gain flatness. In this paper, we quantitatively study the relationship between operating voltage and the key geometric dimensions of a folded waveguide, which is the key to the design of the low-voltage TWT. In addition, problems of improving beam transmission and suppressing oscillations are also studied, and the related design methodologies of the long-range electron gun, periodic permanent magnet (PPM) focusing system, low-voltage standing wave ratio (VSWR) coupling system, and horseshoe attenuator are discussed. On the basis of the above analysis, we have designed and fabricated two types of W-band CW TWTs. The test results show that beam transmissions are over 98.5% at DC and better than 96.5% at the highest peak RF power. Measured saturated output powers are greater than 33.6 W with saturated gain more than 42.2 dB within frequency range of 91–99 GHz, and an improved gain flatness of 4.8 dB is achieved. [ABSTRACT FROM AUTHOR]

Clay often has severe detrimental impacts on cement-based materials. Therefore, it is necessary to investigate the mechanism causing the deterioration to improve the service life of cement-based materials. Based on accurate dimensional analysis, a mechanism that influences clay is proposed: the intercalation of the side chains of superplasticizer molecules in the interlayer space of the clay. To lessen this harmful effect, a new clay-resistant admixture (CRA) possessing cationic groups of small molecular size was synthesized through a novel dimensional design. The length and width of the side chains of this superplasticizer molecule were 9.50-17.50 and 0.25-0.40 nm, respectively, with a radius of ~3.74 nm in solvent, which is larger than the interlayer spacing of montmorillonite (i.e. 1.09-2.14 nm). The longitudinal and latitudinal lengths of the CRA molecule were 0.468 and 9.456 nm, respectively, ensuring intercalation in the interlayer of montmorillonite. The increase in interlayer spacing of the clay was 0.364 nm following addition of polycarboxylate superplasticizer (PCE) plus CRA and 0.632 nm following addition of PCE, which suggests that the CRA plays the role of a 'sacrificial agent' that is preferentially intercalated into the interlayer space of clay to further prevent the side chains of the superplasticizer molecules from entering the interlayer. The aim of this study was to propose a suitable means of synthesizing a new CRA to address the impact of clay through dimensional design and mechanism analysis, which contributes to the theoretical study and technological improvement of cement-based materials. [ABSTRACT FROM AUTHOR]

Clay often has severe detrimental impacts on cement-based materials. Therefore, it is necessary to investigate the mechanism causing the deterioration to improve the service life of cement-based materials. Based on accurate dimensional analysis, a mechanism that influences clay is proposed: the intercalation of the side chains of superplasticizer molecules in the interlayer space of the clay. To lessen this harmful effect, a new clay-resistant admixture (CRA) possessing cationic groups of small molecular size was synthesized through a novel dimensional design. The length and width of the side chains of this superplasticizer molecule were 9.50-17.50 and 0.25-0.40 nm, respectively, with a radius of ~3.74 nm in solvent, which is larger than the interlayer spacing of montmorillonite (i.e. 1.09-2.14 nm). The longitudinal and latitudinal lengths of the CRA molecule were 0.468 and 9.456 nm, respectively, ensuring intercalation in the interlayer of montmorillonite. The increase in interlayer spacing of the clay was 0.364 nm following addition of polycarboxylate superplasticizer (PCE) plus CRA and 0.632 nm following addition of PCE, which suggests that the CRA plays the role of a 'sacrificial agent' that is preferentially intercalated into the interlayer space of clay to further prevent the side chains of the superplasticizer molecules from entering the interlayer. The aim of this study was to propose a suitable means of synthesizing a new CRA to address the impact of clay through dimensional design and mechanism analysis, which contributes to the theoretical study and technological improvement of cement-based materials. [ABSTRACT FROM AUTHOR]

A systematic way is proposed to fully characterize omnidirectional antennas by measuring their complex normalized effective height (CNEH). Usually, antennas are utilized to convert the voltage waves in a waveguide into the vectorial electromagnetic fields in free space and vice versa; however, this conversion relationship cannot be fully expressed with the traditional antenna parameters, e.g., the antenna gain, and so on, because they are not vectorial and possess no phase information. CNEH is a versatile parameter, which can reveal accurately the relationship between the voltage waves in waveguides and the radiated fields in free space. The feature makes it particularly useful for the distributed antenna system or multi-probe array system. The measurement of a CNEH usually uses the far-field method; however, it is a challenge for omnidirectional antennas. We propose a novel method to precisely generate CNEHs based on the broadband calculable antennas. Experimental results show that the difference in transmission coefficient between a pair of calculate dipole antennas resonating at 90 MHz is less than 0.2 dB for amplitude and 2° for phase from 20 to 330 MHz; equivalently, the difference in CNEHs generated from calculable dipole antennas (CDAs) between measurements and calculations will be half of the above results. The key points for CDAs to achieve the superior performance are briefly introduced. Eventually, a way to calibrate the CNEHs of any omnidirectional antennas is illustrated by experiments. Some common antenna parameters are calculated from the CNEH; thus, we present a method to get many antenna parameters by one measurement. [ABSTRACT FROM AUTHOR]

Study Design: Basic science.Objective: The aim of this study was to examine the effect of vascular endothelial growth factor (VEGF)-transfected bone marrow mesenchymal stem cells (BMSCs) on the recovery of motor and sensory functions of rats with spinal cord injury (SCI).Summary Of Background Data: There is no effective treatment to protect against SCI. BMSCs have been widely applied to the treatment of nervous system damage due to the function of prompt neurite growth and inhibition of demyelination following injury.Methods: VEGF-transfected BMSCs were injected to rats with SCI and the recovery of motor and sensory functions was observed. The Basso, Beattie, and Bresnahan, mechanical withdrawal threshold and thermal withdraw latency grading was conducted to assess the recovery status of motor and sensory functions of the SCI rats. The expression of VEGF, CD31, and NF200 was detected by immunofluorescence.Results: The recovery of the rat motor and sensory functions in the VEGF-transfected BMSC (BMSC-VEGF) group was higher than those of the other groups with the exception of the Sham group (P < 0.05). The expression of the CD31 and NF200 proteins in the rat SCI regions was the highest in the BMSC-VEGF group, whereas the survival of BMSC in the BMSC-VEGF group was increased compared with that in the BMSC-Ad group. In addition, the injection of VEGF-transfected BMSCs can improve the angiogenesis of the injured area and retain the survival of injected cells and neurons.Conclusion: The injection of BMSC-VEGF improved the recovery of motor function in SCI rats.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

The presence of surface cracks has a great influence on the formation of transient saturated zones, which are one of the main factors affecting the stability of colluvial soil slopes during rainfall. This paper aims to examine how the distribution characteristics, such as depth (h), angle (θ), and location of surface cracks, influence the development of transient saturated zones. For this reason, a series of numerical simulations involving colluvial soil slopes is performed. The results show that the development of transient saturated zones in a slope with a crack and that in an intact slope are quite different. In a cracked slope, rainwater infiltrates into the slope along the crack and forms a transient saturated zone at the crack tip. It is found that the smaller the crack depth is, the easier it is for the transient saturated zone at the crack tip to connect with that in the shallow layer, leading to an increase in the area of the transient saturated zone in the shallow layer. Moreover, the larger the crack angle is, the more easily the transient saturated zone at the crack tip connects with both the transient saturated zone in the shallow layer and the groundwater, forming a transient saturated zone that penetrates the entire colluvium. In addition, the lower the location of the crack along the slope surface is, the shorter the time is for the formation of a transient saturated zone at the crack tip, and the larger the area of the transient saturated zone. [ABSTRACT FROM AUTHOR]

Video sharing social media platforms, such as YouTube, offer an effective way to deliver medical information. Few studies have identified evidence-backed digital therapeutics with technology-enabled interventions to improve the ease with which patients can retrieve medical information to manage chronic conditions. We propose an interdisciplinary lens that synthesizes deep learning methods with themes emphasized in Information Systems and Healthcare Informatics research to examine user engagement with encoded medical information in YouTube videos. We first use a bidirectional long short-term memory method to identify medical terms in videos and then classify videos based on whether they encode a high or low degree of medical information. We then employ principal component analysis on aggregate video data to discover three dimensions of collective engagement with videos: nonengagement, selective attention-driven engagement, and sustained attention-driven engagement. Videos with low medical information result in nonengagement; at the same time, videos with a greater amount of encoded medical information struggle to maintain sustained attention-driven engagement. Our study provides healthcare practitioners and policymakers with a nuanced understanding of how users engage with medical information in video format. Our research also contributes to enhancing current public health practices by promoting normative guidelines for educational video content enabling management of chronic conditions. [ABSTRACT FROM AUTHOR]

Clay often has severe detrimental impacts on cement-based materials. Therefore, it is necessary to investigate the mechanism causing the deterioration to improve the service life of cement-based materials. Based on accurate dimensional analysis, a mechanism that influences clay is proposed: the intercalation of the side chains of superplasticizer molecules in the interlayer space of the clay. To lessen this harmful effect, a new clay-resistant admixture (CRA) possessing cationic groups of small molecular size was synthesized through a novel dimensional design. The length and width of the side chains of this superplasticizer molecule were 9.50-17.50 and 0.25-0.40 nm, respectively, with a radius of ~3.74 nm in solvent, which is larger than the interlayer spacing of montmorillonite (i.e. 1.09-2.14 nm). The longitudinal and latitudinal lengths of the CRA molecule were 0.468 and 9.456 nm, respectively, ensuring intercalation in the interlayer of montmorillonite. The increase in interlayer spacing of the clay was 0.364 nm following addition of polycarboxylate superplasticizer (PCE) plus CRA and 0.632 nm following addition of PCE, which suggests that the CRA plays the role of a 'sacrificial agent' that is preferentially intercalated into the interlayer space of clay to further prevent the side chains of the superplasticizer molecules from entering the interlayer. The aim of this study was to propose a suitable means of synthesizing a new CRA to address the impact of clay through dimensional design and mechanism analysis, which contributes to the theoretical study and technological improvement of cement-based materials. [ABSTRACT FROM AUTHOR]

For discretized elliptic equations, we develop a new factorization update algorithm that is suitable for incorporating coefficient updates with large support and large magnitude in subdomains. When a large number of local updates are involved, in addition to the standard factors in various (interior) subdomains, we precompute some factors in the corresponding exterior subdomains. Exterior boundary maps are constructed hierarchically. The data dependencies among tree-based interior and exterior factors are exploited to enable extensive information reuse. For coefficient updates in a subdomain, only the interior problem in that subdomain needs to be refactorized and there is no need to propagate updates to other tree nodes. The combination of the new interior factors with a chain of existing factors quickly provides the new global factor and thus an effective solution algorithm. The introduction of exterior factors avoids updating higher-level subdomains with large system sizes and makes the idea suitable for handling multiple occurrences of updates. The method can also accommodate the case when the support of updates changes to different subdomains. Numerical tests demonstrate the efficiency and especially the advantage in complexity over a standard factorization update algorithm. [ABSTRACT FROM AUTHOR]