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In the last few years, the rapid advancement of the Internet of Things (IoT) and the widespread adoption of smart cities have posed new challenges to computing services. Traditional cloud computing models fail to fulfil the rapid response requirement of latency‐sensitive applications, while mobile edge computing (MEC) improves service efficiency and customer experience by transferring computing tasks to servers located at the network edge. However, designing an effective computing offloading strategy in complex scenarios involving multiple computing tasks, nodes, and services remains a pressing issue. In this paper, a computing offloading approach based on Deep Reinforcement Learning (DRL) is proposed for large‐scale heterogeneous computing tasks. First, Markov Decision Processes (MDPs) is used to formulate computing offloading decision and resource allocation problems in large‐scale heterogeneous MEC systems. Subsequently, a comprehensive framework comprising the "end‐edge‐cloud" along with the corresponding time‐overhead and resource allocation models is constructed. Finally, through extensive experiments on real datasets, the proposed approach is demonstrated to outperform existing methods in enhancing service response speed, reducing latency, balancing server loads, and saving energy. [ABSTRACT FROM AUTHOR]

Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D‐ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)‐configured and (R)‐configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A‐ and D‐rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)‐glaziovine, (S)‐glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology. [ABSTRACT FROM AUTHOR]

Mixed reality technology can be applied to simulation training, improve surgical performance, enhance 3D game experience, and so on, attracting extensive attention of researchers. The perception of the user about head‐mounted display MR using HoloLens is critical, especially for precision applications such as virtual hoisting. Designing and adding appropriate depth cues in MR scenes is an effective way to improve users' depth perception. In this study, taking virtual hoisting training system as an example, the depth perception strategy of multi‐cue fusion is proposed to improve the perception effect. Based on the mechanism of human depth perception, five kinds of depth cues are designed. The depth perception effect of adding single cue is studied by perceptual matching experiment. Based on the principle of fuzzy clustering, a multiple‐cue comprehensive depth optimization strategy on viewing distance scale is proposed. Finally, the perceptual matching results demonstrate the effectiveness of the multi‐cue fusion strategy, and the average error is reduced by 20.68% compared with the single‐cue strategy, which can significantly improve the spatial depth perception. This research can provide a reference for improving users' depth perception in interactive MR simulation systems. [ABSTRACT FROM AUTHOR]

Sulfonated mesoporous polydivinylbenzene solid acid was prepared by in situ sulfonation method, and the physical chemical properties of this solid acid was characterized by XRD, BET, FT‐IR, etc. Acid density of sulfonated mesoporous polydivinylbenzene was characterized by acid base titration, and the result showed that the acid density was 1.58 mmol H+/g. The condensation of phenol and acetone was used as a probe reaction to investigate the catalytic performance of sulfonated mesoporous polydivinylbenzene as a solid acid. Results showed that the phenol conversion rate could approach theoretical conversion rate with Bisphenol‐A selectivity of 91 % at 90 °C. More importantly, sulfonated mesoporous polydivinylbenzene had good stability, and after repeated use for five times, the catalytic performance was not significantly reduced. [ABSTRACT FROM AUTHOR]

Demethylcantharidin (DEM) is a widely used antitumor drug; however, its poor tumor targeting and serious organotoxicity limit its application. The aim of this study was to develop a new drug delivery system for efficient delivery of DEM. Nanoemulsion based lipid nanoparticles containing demethylcantharidin (DNLNs) were prepared by loading nanoemulsions into lipid nanoparticles. The cells proliferation, apoptosis, cycle, and uptake were investigated by Cell counting kit‐8 (CCK‐8), flow cytometry, and in situ fluorescence assays, respectively. Then, we established the H22 tumor‐bearing mouse model to evaluate the antitumor efficacy of DNLNs and further studied its organ toxicity and distribution. DNLNs significantly inhibited the proliferation and promoted apoptosis of H22 cells, and H22 cells could take up more DNLNs. Compared with DEM, DNLNs had certain tumor‐targeting properties, and the tumor inhibition rate increased by 23.24%. Moreover, DNLNs can increase white blood cell count and reduce organ toxicity. This study paves the way for nanoemulsion‐based lipid nanoparticle (NLNs)‐efficient DEM delivery to treat liver cancer. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations between developmental trajectories of emotional problems and early adult alcohol use behaviors, while considering co‐occurring conduct problems, developmental change/timing, sex differences, and potential confounds.Participants were from the Twins Early Development Study (analytic N = 19,908 individuals). Emotional and conduct problems were measured by parent reports at child ages 4, 7, and 9 years and via self‐reports at ages 9, 11, and 16 years on the Strengths and Difficulties Questionnaire. Alcohol use behaviors (alcohol consumption and alcohol‐related problems) were self‐reported by the twins on the Alcohol Use Disorders Identification Test at age 22 years. Piecewise latent growth curve models described nonlinear developmental trajectories of emotional and conduct problems from ages 4 to 16. At age 22, alcohol use was regressed on emotional and conduct problems' intercepts and slopes from piecewise latent growth curve model and sex differences in regression coefficients were tested. Using twin modeling, Cholesky decompositions and direct path models were compared to test whether significant phenotypic associations were best explained by direct phenotypic influences or correlated genetic and environmental influences.Emotional problems had different associations with alcohol‐related problems versus alcohol consumption. After accounting for direct influences from conduct problems, emotional problems were not associated with alcohol‐related problems, while emotional problems at age 9 were negatively associated with alcohol consumption in males.Overall, findings did not support emotional problems as prospective risk factors for severe alcohol use above and beyond risks associated with conduct problems. Sex‐ and age‐specific links between emotional problems and alcohol consumption in early adulthood may be worthy of further exploration, particularly as twin analyses improved our confidence that such links may be underpinned by causal mechanisms. [ABSTRACT FROM AUTHOR]

Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non‐reproductive tissue‐originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single‐cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR‐211‐5p in gut‐derived circulating exosomes, which inhibited the expression of meiosis‐specific with coiled‐coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut‐derived exosomes in connecting the "gut‐testis" axis. [ABSTRACT FROM AUTHOR]

Venn diagrams serve as invaluable tools for visualizing set relationships due to their ease of interpretation. Widely applied across diverse disciplines such as metabolomics, genomics, transcriptomics, and proteomics, their utility is undeniable. However, the operational complexity has been compounded by the absence of standardized data formats and the need to switch between various platforms for generating different Venn diagrams. To address these challenges, we introduce the EVenn platform, a versatile tool offering a unified interface for efficient data exploration and visualization of diverse Venn diagrams. EVenn (http://www.ehbio.com/test/venn) streamlines the data upload process with a standardized format, enhancing the capabilities for multimodule analysis. This comprehensive protocol outlines various applications of EVenn, featuring representative results of multiple Venn diagrams, data uploads in the centralized data center, and step‐by‐step case demonstrations. Through these functionalities, EVenn emerges as a valuable and user‐friendly tool for the in‐depth exploration of multiomics data. Highlights: Comprehensive Venn functionality: EVenn introduces a unified platform with diverse Venn diagram tools, from interactive diagrams to network representations, catering to the intricate needs of multiomics data analysis across metabolomics, genomics, transcriptomics, and proteomics.Efficient data exploration: EVenn's data center streamlines exploration by supporting a standardized data format, allowing researchers to effortlessly upload and analyze data. The manuscript demonstrates its practical utility through representative results and detailed case demonstrations.User‐friendly interface: With a user‐friendly interface, EVenn simplifies the generation of various Venn diagrams, Euler diagrams, UpSet plots, and more. This protocol establishes EVenn as a valuable resource for researchers seeking a cohesive and accessible tool for multiomics data interpretation. [ABSTRACT FROM AUTHOR]

Green hydrogen production through electrochemical overall water splitting has suffered from sluggish oxygen evolution reaction (OER) kinetics, inferior conversion efficiency, and high cost. Herein, ultrafine PtIr clusters are synthesized via an electrodeposition method and decorated on the Co3O4 nanoflowers assembled by nanowires (PtIr‐Co3O4). The encouraging performances in electrochemical OER and hydrogen evolution reaction (HER) are achieved over the PtIr‐Co3O4 catalyst, with the overpotentials as low as 410 and 237 mV at 100 mA cm−2, respectively, outperforming the commercial IrO2 and Pt/C catalysts. Due to the ultralow loading of PtIr clusters, the PtIr‐Co3O4 catalyst exhibits 1270 A gIr−1 for OER at the overpotential of 400 mV. Our detailed analyses also show that the strong interactions between the ultrafine PtIr clusters and the Co3O4 nanoflowers enable the PtIr‐Co3O4 catalyst to afford 10 mA cm−2 for the overall water splitting at the potential of 1.57 V, accompanied by high durability for 100 h. [ABSTRACT FROM AUTHOR]

Ionic liquid salts (ILs) are generally recognized as additives in perovskite precursor solutions to enhance the efficiency and stability of solar cells. However, the success of ILs incorporation as additives is highly dependent on the precursor formulation and perovskite crystallization process, posing challenges for industrial‐scale implementation. In this study, a room‐temperature spin‐coated IL, n‐butylamine acetate (BAAc), is identified as an ideal passivation agent for formamidinium lead iodide (FAPbI3) films. Compared with other passivation methods, the room‐temperature BAAc capping layer (BAAc RT) demonstrates more uniform and thorough passivation of surface defects in the FAPbI3 perovskite. Additionally, it provides better energy level alignment for hole extraction. As a result, the champion n–i–p perovskite solar cell with a BAAc capping layer exhibits a power conversion efficiency (PCE) of 24.76%, with an open‐circuit voltage (Voc) of 1.19 V, and a Voc loss of ≈330 mV. The PCE of the perovskite mini‐module with BAAc RT reaches 20.47%, showcasing the effectiveness and viability of this method for manufacturing large‐area perovskite solar cells. Moreover, the BAAc passivation layer also improves the long‐term stability of unencapsulated FAPbI3 perovskite solar cells, enabling a T80 lifetime of 3500 h when stored at 35% relative humidity at room temperature in an air atmosphere. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder where oxidative stress, induced by ferroptosis, has been linked to neuronal damage and cognitive deficits. The objective of this study is to investigate if the potential therapeutic agent, Curculigoside (CUR), could ameliorate AD by inhibiting ferroptosis. The potential therapeutic targets, such as GPX4 and SLC7A11, were identified using weighted gene co‐expression network analysis (WGCNA). Concurrently, CUR was also screened against these potential targets using various analytical methods. For the in vivo studies, intragastric administration of CUR significantly ameliorated cognitive impairment in AD model mice induced by scopolamine and okadaic acid (OA). In vitro, CUR protected neuronal cells by altering the levels of ferroptosis‐related specific markers in OA and scopolamine‐induced neurotoxicity. The administration of CUR through intragastric route significantly reduced the levels of AD‐promoting factors (such as Aβ1–42, p‐tau) and ferroptosis‐promoting factors in the hippocampus and cortex of AD mice. Furthermore, CUR up‐regulated the expression of GPX4 and decreased the expression of SLC7A11 in the ferroptosis signaling pathway, thereby increasing the ratio of glutathione (GSH)/oxidized glutathione (GSSG) in vivo and vitro. In conclusion, the cumulative results suggest that the natural compound CUR may serve as a promising therapeutic agent to ameliorate AD by inhibiting ferroptosis. [ABSTRACT FROM AUTHOR]

Summary: Generating immersive virtual reality avatars is a challenging task in VR/AR applications, which maps physical human body poses to avatars in virtual scenes for an immersive user experience. However, most existing work is time‐consuming and limited by datasets, which does not satisfy immersive and real‐time requirements of VR systems. In this paper, we aim to generate 3D real‐time virtual reality avatars based on a monocular camera to solve these problems. Specifically, we first design a self‐attention distillation network (SADNet) for effective human pose estimation, which is guided by a pre‐trained teacher. Secondly, we propose a lightweight pose mapping method for human avatars that utilizes the camera model to map 2D poses to 3D avatar keypoints, generating real‐time human avatars with pose consistency. Finally, we integrate our framework into a VR system, displaying generated 3D pose‐driven avatars on Helmet‐Mounted Display devices for an immersive user experience. We evaluate SADNet on two publicly available datasets. Experimental results show that SADNet achieves a state‐of‐the‐art trade‐off between speed and accuracy. In addition, we conducted a user experience study on the performance and immersion of virtual reality avatars. Results show that pose‐driven 3D human avatars generated by our method are smooth and attractive. [ABSTRACT FROM AUTHOR]

The rapid development of optoelectronic devices with biomimetic synaptic behavior holds significant potential for neuromorphic visual applications. However, considerable challenges remain including convenient device fabrication and low toxicity materials innovation. Here, a heterojunction phototransistor is constructed using low‐toxic CuZnInSSe (CIZS) colloidal quantum dots and amorphous InGaZnO (IGZO), which demonstrates high specific detectivity of 3.4 × 1015 Jones in visible light spectrum. Moreover, it is found that the photoresponse speed can be controlled via a ligand exchange treatment, through that the response speed can be adjusted from 0.3 to 11 s. This enables the device to operate in two distinct modes: a typical fast sensing mode and a neuromorphic visual mode. In the neuromorphic visual mode, the device's synaptic behavior can be tuned by manipulating light pulse intensity, frequency, wavelength, and gate voltage. As a demonstration, a phototransistor array effectively implements image pre‐processing functions, including color recognition, visual memorizing, and forgetting. [ABSTRACT FROM AUTHOR]

BACKGROUND: Isopropyl 4‐(2‐chloro‐6‐(1H‐1,2,4‐triazol‐1‐yl)benzamido)benzoate (TPB) was a 1,2,4‐triazole benzoyl arylamine derivative with excellent antifungal activity, especially against Gaeumannomyces graminis var. tritici (Ggt). Its mechanism of action was investigated by transmission electron microscopy (TEM) observation, assays of sterol composition, cell membrane permeability, intracellular ATP and mitochondrial membrane potential, and mPTP permeability, ROS measurement, RNA sequencing (RNA‐seq) analysis. RESULTS: TPB interfered with ergosterol synthesis, reducing ergosterol content, increasing toxic intermediates, and finally causing biomembrane disruption such as increasing cell membrane permeability and content leakage, and destruction of organelle membranes such as coarse endoplasmic reticulum and vacuole. Moreover, TPB destroyed the function of adenine nucleotide transferase (ANT), leading to ATP transport obstruction in mitochondria, inhibiting mPTP opening, inducing intracellular ROS accumulation and mitochondrial membrane potential loss, finally resulting in mitochondrial damage including mitochondria swelled, mitochondrial membrane dissolved, and cristae destroyed and reduced. RNA‐seq analyses showed that TPB increased the expression of ERG11, ERG24, ERG6, ERG5, ERG3 and ERG2 genes in ergosterol synthesis pathway, interfered with the expression of genes (NDUFS5, ATPeV0E, NCA2 and Pam17) related to mitochondrial structure, and inhibited the expression of genes (WrbA and GST) related to anti‐oxidative stress. CONCLUSIONS: TPB exhibited excellent antifungal activity against Ggt by inhibiting ergosterol synthesis and destroying ANT function. So, TPB was a novel compound with dual‐target mechanism of action and can be considered a promising novel fungicide for the control of wheat Take‐all. The results provided new guides for the structural design of active compounds and powerful tools for pathogen resistance management. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The Microbiome Protocols eBook (MPB) is a valuable resource that provides standardized wet-lab protocols for microbiome research. The first edition, launched in 2020, received widespread acclaim and featured 152 meticulously curated protocols. The MPB aims to bridge the gaps in microbiome protocols and facilitate progress in the field by addressing challenges in wet experiments and data analysis. The upcoming second edition will incorporate updates from the first edition and expand into new areas, covering innovative methodologies and emerging technologies. The MPB is an open-access resource that is easily accessible to all researchers. [Extracted from the article]

This article presents a study on the genome assembly of Syringa pinnatifolia, a shrub valued in traditional Chinese medicine for its volatile chemical constituents. The researchers aimed to elucidate the biosynthesis pathway of zerumbone, a compound found in S. pinnatifolia with various medicinal properties. Through genome sequencing and analysis, they identified the genes responsible for the production of key compounds in the pathway, including a terpene synthase (TPS) gene and a cytochrome P450 (CYP450) gene. The study provides insights into the biosynthesis of zerumbone in eudicots and expands our understanding of the functions of TPS and CYP450 enzymes. [Extracted from the article]

This article discusses a study that examines the impact of a high-fat diet on male fertility in mice. The researchers used single-cell RNA sequencing to analyze testis cells and found that a high-fat diet led to weight gain, glucose tolerance, and insulin resistance in the mice. The study also found that the high-fat diet impaired spermatogenesis by inhibiting testosterone synthesis through a specific pathway. Additionally, the researchers discovered that oxidized low-density lipoprotein played a role in impairing Leydig cell function. Overall, the study provides insights into the mechanisms by which a high-fat diet affects male fertility and suggests potential avenues for clinical treatment of infertility in obese men. [Extracted from the article]

A growing body of literature highlights the important role of paternal health and socioemotional characteristics in child development, from preconception through adolescence. Much of this research addresses the indirect effects of fathers, for instance, their influence on maternal behaviors during the prenatal period or via the relationship with their partner. However, emerging evidence also recognizes the direct role of paternal health and behavior for child health and adjustment across development. This critical review presents evidence of biological and sociocultural influences of fathers on preconception, prenatal, and postnatal contributions to child development. The National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program incorporates in its central conceptualization the impact of fathers on family and child outcomes. This critical synthesis of the literature focuses on three specific child outcomes in the ECHO program: health outcomes (e.g., obesity), neurodevelopmental outcomes (e.g., emotional, behavioral, psychopathological development), and positive health. We highlight the unique insights gained from the literature to date and provide next steps for future studies on paternal influences. [ABSTRACT FROM AUTHOR]

LncRNAs have gained increasing attention owing to their important regulatory roles on growth and stress responses of plants. However, the mechanisms underlying the functions of lncRNAs in fruit‐pathogen interaction are still largely unknown. In this study, a total of 273 lncRNAs responding to Botrytis cinerea infection were identified in tomato fruit, among which a higher percentage of antisense lncRNAs were targeted to the genes enriched in hydrolase activity. To ascertain the roles of these lncRNAs, seven hydrolase‐related transcripts were transiently knocked‐down by virus‐induced gene silencing. Silencing of lncRNACXE20 reduced the expression level of a carboxylesterase gene, further enhancing the resistance of tomato to B. cinerea. In contrast, silencing of lncRNACHI, lncRNAMMP, lncRNASBT1.9 and lncRNAPME1.9 impaired the resistance to B. cinerea, respectively. Further RT‐qPCR assay and enzymatic activity detection displayed that the attenuated resistance of lncRNAMMP and lncRNASBT1.9‐silenced plants was associated with the inhibition on the expression of JA‐related genes, while the decreased resistance of lncRNACHI‐silenced plants resulted in reduced chitinase activity. Collectively, these results may provide references for deciphering the mechanisms underlying specific lncRNAs to interfere with B. cinerea infection by regulating the expression of defence‐related genes or affecting hydrolase activity. Summary Statement: To add more references to the mechanisms underlying the interaction between fruit—Botrytis cinerea interaction, the lncRNAs induced by B. cinerea in tomato fruit were identified and their roles were preliminarily investigated. The results revealed that specific lncRNAs are involved in fruit—B. cinerea interaction by regulating the expression of defence‐related genes or affecting hydrolase activity. [ABSTRACT FROM AUTHOR]

Peanut skin (PS) contains various flavonoids and phenols that have antitumor and antioxidant effects. However, no research has been conducted on PS and hepatocellular carcinoma (HCC). Therefore, this study sought to explore the potential mechanism of PS in treating HCC. PS was searched for in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SYMMAP databases. HCC targets were searched for in five major databases. Protein‐protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking and molecular dynamics simulation were used for verification. Furthermore, in vitro experiments were used to verify the regulation of PS on human HCC (HepG2) cells. Ten ingredients and 95 common targets were identified for PS and HCC, respectively. The key targets of ingredients mainly relate to pathways such as hepatitis B, lipid and atherosclerosis, advanced glycation end products (AGEs)‐AGE receptors (RAGEs) signaling pathway in diabetic complications, interleukin‐17 (IL‐17) signaling pathway, mitogen activated kinase‐like protein (MAPK) signaling pathway, the PI3K‐Akt signaling pathway. In addition, the molecular docking and molecular dynamics simulation analysis indicated the ingredients had strong binding ability with the targets. Moreover, in vitro experiments confirmed that luteolin can promote the apoptosis of HepG2 cells by controlling the expression of phosphorylated protein‐tyrosine kinase (p‐AKT). This study provides preliminary evidence that PS produces a marked effect in regulating multiple signaling pathways in HCC through multiple ingredients acting on multiple core genes, including AKT serine/threonine kinase 1 (AKT1), MYC, caspase 3 (CASP3), estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), jun proto‐oncogene(JUN), and provides the basis for follow‐up research to verify the mechanism of action of PS in treating HCC. [ABSTRACT FROM AUTHOR]

Summary: Redirected walking (RDW) provides an immersive user experience in virtual reality applications. In RDW, the size of the physical play area is limited, which makes it challenging to design the virtual path in a larger virtual space. Mainstream RDW approaches rigidly manipulate gains to guide the user to follow predetermined rules. However, these methods may cause simulator sickness, boundary collision, and reset. Static mapping approaches warp the virtual path through expensive vertex replacement in the stage of model pre‐processing. They are restricted to narrow spaces with non‐looping pathways, partition walls, and planar surfaces. These methods fail to provide a smooth walking experience for large‐scale open scenes. To tackle these problems, we propose a novel approach that dynamically redirects the user to walk in a non‐linear virtual space. More specifically, we propose a Bezier‐curve‐based mapping algorithm to warp the virtual space dynamically and apply multiperspective fusion for visualization augmentation. We conduct comparable experiments to show its superiority over state‐of‐the‐art large‐scale redirected walking approaches on our self‐collected photogrammetry dataset. [ABSTRACT FROM AUTHOR]

Amorphous metal oxide semiconductors (AOS), especially indium‐gallium‐zinc oxide (IGZO), have been studied and applied in sensing, display and other industrial fields, including phototransistors, because of their outstanding electronic properties. [1] [2] However, due to its much low visible light response and limited mobility, IGZO could not match the rapidly developing application needs of phototransistor. [3] The construction of photo‐TFT (thin film transistor) with better electronical performance and stronger light response has become a key issue.[4] Therefore, indium‐zinc oxide (IZO) with relative high mobility (15~20 cm2 /V.s) and perovskite with high photosensitivity come into view.[5] In this study, we report a Ruddlesden‐Popper (RP) quasi‐two‐dimensional (quasi‐2D) perovskite‐IZO phototransistor with heterostructure. A quasi‐2D perovskite layer is spin‐coated on the high‐mobility IZO channel TFT, which enables ultralow off‐state dark current of 10‐12 A, high responsivity and detectivity under visible light, especially high responsivity and detectivity of 1480 A/W and 2.21×10 14 Jones under 525 nm green light illumination. [ABSTRACT FROM AUTHOR]

We examined whether folate‐fortified maize (FFM) improves the health of rural women of childbearing age and whether the health intervention is associated with the consumer willingness‐to‐pay (WTP) for FFM. First, a randomized single‐blind FFM intervention trial was conducted in rural childbearing‐aged women. Participants (n = 55) consumed one stalk of either FFM (treatment group) or ordinary maize (control group) daily. This dietary intervention lasted for 2 months, during which we assessed the participants' serum folate levels at baseline, mid stage (after 1 month), and final stage (after 2 months) to evaluate the health effect of FFM. We found that the serum folate level in the treatment group (13.31 ng/mL) was 3.40 ng/mL higher than that in the control group (9.91 ng/mL) in the final stage of the study. These findings suggest that regular dietary FFM intake significantly increased serum folate levels in rural Chinese women. Second, we further expanded our study by involving 181 local rural women with similar demographic characteristics to participate in a Becker–DeGroot–Marschak (BDM) bidding experiment to measure their WTPs for FFM. Results showed that local consumers were willing to pay 2.82 Chinese Yuan (CNY) per stalk of FFM, approximately 1.21 CNY higher than the price of ordinary maize. And women who participated in and completed the intervention trial had a higher preference for FFM during the evaluation. We provide evidence on the health improvement effect of biofortified foods and shed light on the associated consumer valuation and policy implementation. [ABSTRACT FROM AUTHOR]

Calcium channel blocker (CCB) is known to possess antibacterial effects. We aimed to apply network pharmacology (docking and protein–protein interaction [PPI] analyses) to predict the potential targets and mechanisms of CCB against Pseudomonas aeruginosa (PA) as well as to verify the effect of these drugs. The chemical structures of three CCBs were obtained through the Drug Bank platform. The potential channel proteins, efflux pump proteins and ion channel proteins of CCB against bacteria were derived from the literature. These proteins were collected through the PDB and Uniprot platform. The binding mode of the docking complexes was simulated by the CB‐Dock platform and Discovery Studio 2019 Client software. The PPI network was constructed by the String platform and Cytoscape 3.8.2 platform. GO was explained by the PANTHER platform. The pathway diagram was drawn with the Pathway Builder Tool 2.0 software. The inhibitory effect of CCB on PA was verified through antibacterial experiments. Finally, 76 proteins were obtained: the iron channel protein of PA demonstrated a good docking relationship with all three CCBs, and the optimum binding energy was approximately −9.0 kcal/mol. GO analysis (biological process [BP], cellular component [CC], and molecular function [MF]) of protein genes showed a good docking relationship (optimum binding energy <−8.0 kcal/mol). The MF annotation results indicated that the target of CCB may be present on the PA membrane protein. The ion channel protein PPI enrichment p‐value was 6.65e‐08, and PfeA showed the strongest correlation. The experimental results suggested that CCB could inhibit the growth of PA. CCB might be an effective and interesting antimicrobial treatment strategy as CCB can potentially inhibit the growth of PA. [ABSTRACT FROM AUTHOR]

To tackle the increasingly complex electromagnetic (EM) pollution environment, the application-oriented electromagnetic wave (EMW) absorption materials with ultra-thin, lightweight and strong tolerance to harsh environment are urgently explored. Although graphene aerogel-based lightweight EMW absorbers have been developed, thinner thickness and more effective polarization loss strategies are still essential. Based on the theory of EMW transmission, this work innovatively proposes a high attenuation design strategy for obtaining ultra-thin EMW absorption materials, cobalt selenide (CoSe2) is determined as animportant part of ultra-thin absorbers. In order to obtain a dielectric parameter range that satisfies the ultra-thin absorption characteristics and improve the lightweight properties of EMW absorption materials, a composite of CoSe2 modified N-doped reduced graphene oxide (N-RGO/CoSe2) is designed. Meanwhile, the controllable introduction of defect engineering into RGO can activate Schottky heterointerfaces of composites to generate a strong interfacial polarization effect, achieving ultra-thin characteristics while significantly improving the EM loss capability. In addition, infrared thermal images and anti-icing experiments show that the composite has good corrosion resistance, infrared stealth, and thermal insulation properties. Therefore, this work provides an effective strategy for obtaining thin-thickness, light-weight, and high-performance EMW absorption materials, embodying the advantages of N-RGO/CoSe2 composites in practical applications. [ABSTRACT FROM AUTHOR]

Single‐crystalline metal halide perovskite, due to its large X‐ray attenuation coefficient, high carrier mobility, and facile fabrication properties, is considered as a promising candidate material for direct X‐ray detectors. Despite the rapid development of high‐sensitivity perovskite detectors, their practical application is still hindered by their high dark current levels and the lack of effective approach for assembling the perovskite photodetectors on thin‐film transistor (TFT) backplane. Herein, it is shown that, by using a supersaturated 2D perovskite precursor as a wet‐fusing intermedia, a high‐performance 2D/3D perovskite detector can be fabricated and simultaneously attached to the TFT backplane. The assembled 2D/3D heterostructure perovskite detector shows low dark current density, high sensitivity, and low dose detection limit. This work provides a viable route to realize a low‐dose, high‐resolution direct X‐ray image sensor based on perovskite photodetectors. [ABSTRACT FROM AUTHOR]

Summary: FERONIA (FER) is a receptor‐like kinase showing versatile functions during plant growth, development, and responses to environmental stimuli. However, its functions during the interaction between fruit and necrotrophic fungal pathogens are still unclear.Combining reverse genetic approaches, physiological assays, co‐immunoprecipitation, protein phosphorylation identification, and site‐directed mutagenesis, we reported a tomato FER homolog SlFERL (Solanum lycopersicum FERONIA Like) involved in the immune responses to Botrytis cinerea invasion.The results indicated that SlFERL extracellular domain recognized and interacted with the secreted virulence protein BcPG1 from B. cinerea, further revealed that SlFERL triggered downstream signaling by phosphorylating SlMAP3K18 at Thr45, Ser49, Ser76, and Ser135. Moreover, we verified that SlMAP2K2 and SlMAP2K4 synergistically contributed to immune response of tomato to B. cinerea, in which SlFERL‐SlMAP3K18 module substantially modulated protein level and/or kinase activity of SlMAP2K2/SlMAP2K4.These findings reveal a new pattern‐triggered immune pathway, indicating that SlFERL participates in the immune responses to B. cinerea invasion via recognizing BcPG1 and fine‐tuning MAPK signaling. [ABSTRACT FROM AUTHOR]

Iron overload is a risk factor for postmenopausal osteoporosis (PMOP) and lowering iron levels to regulate the labile plasma iron is the preferred therapy. Icariin (ICA), baohuoside I (BHS) and icaritin (ICT) are three flavonoids obtained from Epimedii Folium that are efficient in facilitating osteogenesis. In this study, an active flavonoid with dual effects of reversing iron overload and promoting osteogenesis was screened based on pharmacokinetics, iron complexation properties and the potential to downregulate iron overload, reversing PMOP. As a result, the in vivo absorption of three compounds was ICA > ICT > BHS, while the exposure in muscle and bone was BHS > ICT > ICA. In vitro complexation showed that only ICT complexed with Fe (III) at a 1:1 ratio on 3‐OH and the ICT–Fe (III) complex (m/z 424.3750) was identified by UPLC–Q‐TOF–MS. In vivo dynamic detection also showed that the concentration of ICT–Fe (III) complexes varied with the concentration of ICT in plasma. The behavioral blunting and bone loss in zebrafish induced by Fe (III) were significantly reversed by ICT in a dose‐dependent manner. Pharmacokinetic–pharmacodynamic analysis showed that ICT was negatively correlated with serum ferritin and positively correlated with osteogenic markers including alkaline phosphatase, osteocalcin and osteoprotegerin. Bone loss in ovariectomized rats was significantly altered after ICT intervention, with reduced serum ferritin levels and improved osteogenic marker levels. These results demonstrated that ICT had favorable musculoskeletal penetration and iron complexation capability to shrink labile plasma iron, showing superior performance in anti‐PMOP through the dual effects of reversing iron overload and promoting osteogenesis. [ABSTRACT FROM AUTHOR]

Summary: As various algorithms and models spring up, object detection‐based deep learning for image analysis has become an established technology in the field of computer vision. Furthermore, object detection for high‐resolution videos derived from ubiquitous surveillance cameras draws many researchers' attention due to its practical significance and the challenge on detecting accuracy and speed. Existing object detection methods mainly resize and compress each frame in the video and then apply the detection algorithm, but with the method, the detection for small objects in dense scenes is far from satisfactory in terms of accuracy because small objects are reduced to pixel‐level sizes in compressed frame images. In order to fix this issue, we propose AROD, a parallel detection framework based on adaptive image cropping. Unlike the traditional first‐compression‐and‐then‐detection methods, AROD adopts adaptive image cropping for distributed parallel detection. In this way, AROD significantly improves the accuracy of small object detection in dense scenes with acceptable overhead. In our experimental evaluation, YOLOv2‐tiny model equipped with AROD reaches 29.29 FPS along with high detection accuracy. Experimental results verify that AROD ensures the high throughput of real‐time video analytics while maintaining high detection accuracy. [ABSTRACT FROM AUTHOR]

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground‐glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non‐smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow‐up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4‐ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow‐up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4‐ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non‐smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow‐up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans. [ABSTRACT FROM AUTHOR]

Surface‐enhanced Raman spectroscopy (SERS) has shown highly promising for existing cancer screening. However, previous "proof‐of‐concept" studies ignored the natural imbalance of cancer types in the population, leading the model to be biased toward learning more features in majority class during the learning process at the expense of ignoring minority class. Herein, a power‐law‐based synthetic minority oversampling technique (PL‐SMOTE) method is proposed to guide the resampling of multiclass serum SERS data by analyzing the long‐tailed (power‐law) distribution of cancer prevalence in the population. The proposed PL‐SMOTE method balances the number of minorities to resample and the number of overlaps between classes by introducing modulating factor. Modeling on resampled datasets synthesized by PL‐SMOTE verifies the effectiveness of proposed PL‐SMOTE method. After further fine‐tuning, the parameters of the deep neural network model and PL‐SMOTE method, an optimal cancer screening model with an optimal macroaveraged Recall score of 97.24% and an optimal macroaveraged F2‐Score of 97.38% is obtained. A new method for multiclass imbalanced resampling is provided, which has significant improvement on model performance in terms of SERS cancer screening. The method also inspires in other multiclass imbalanced scenario, such as biological medicine, abnormal detection, and disaster prediction. [ABSTRACT FROM AUTHOR]

Purpose: MET is a notable driver gene in the diversity of aberrations with clinical relevance, including exon 14 skipping, copy number gain, point mutations, and gene fusions. Compared with the former two, MET fusions are severely under‐reported, leaving a series of unanswered questions. In this study, we addressed this gap by characterizing MET fusions in a large, real‐world Chinese cancer population. Methods: We retrospectively included patients with solid tumors who had DNA‐based genome profiles acquired through targeted sequencing from August 2015 to May 2021. MET fusion‐positive (MET+) patients were subsequently selected for clinical and molecular characterization. Results: We screened 79,803 patients across 27 tumor types and detected 155 putative MET fusions from 122 patients, resulting in an overall prevalence of 0.15%. Lung cancer comprised the majority of MET+ patients (92, 75.4%). Prevalence was markedly higher in liver cancer, biliary tract cancer, and renal cancer (range 0.52%–0.60%). It was lower in ovarian cancer (0.06%). A substantial proportion (48/58, 82.8%) of unique partners were reported for the first time. High heterogeneity was observed for partners, with ST7, HLA‐DRB1, and KIF5B as the three most common partners. Mutational landscape analysis of lung adenocarcinoma (n = 32) revealed a high prevalence of TP53 in MET+ alterations, EGFR L858R, EGFR L861Q, and MET amplification. Conclusion: To our knowledge, this is currently the largest study in characterizing MET fusions. Our findings warrant that further clinical validation and mechanistic study may translate into therapeutic avenues for MET+ cancer patients. [ABSTRACT FROM AUTHOR]

Identifying and characterizing charge heterogeneity is essential for the successful development and production of biopharmaceuticals. Imaged capillary isoelectric focusing technology based on isoelectric point differentiation has been becoming the gold standard of quality and manufactory process control in the biopharmaceutical industry due to its high‐resolution characterization of protein charge variants with high throughput. Fluorocarbon‐coated capillaries are widely used in the imaged capillary isoelectric focusing to suppress the electroosmotic flow and minimize the protein adsorption onto the fused silica capillary inner surface. Additionally, polymers such as methylcellulose are usually added to the sample solution to serve as a dynamic capillary coating that improves the peak shape and resolution during the imaged capillary isoelectric focusing separation, especially for complex proteins. However, the addition of methylcellulose tends to result in tedious operation, "spike peaks" from bubble generation, and frequent capillary blockage during the imaged capillary isoelectric focusing separation. In addition, methylcellulose is not compatible with mass spectrometry and easily produces the contamination of mass spectrometry ion source when carrying out imaged capillary isoelectric focusing—mass spectrometry direct coupling. Recently, a new imaged capillary isoelectric focusing method was developed employing a methylcellulose‐coated capillary cartridge, to avoid the addition of methylcellulose which is then present throughout the whole analysis. When applied to protein drug characterization the established imaged capillary isoelectric focusing method demonstrated high repeatability, stable coatings, outstanding separation efficiency, and excellent isoelectric point differentiation. In addition, we compared imaged capillary isoelectric focusing separation using the methylcellulose‐coated capillary with that utilizing the routinely coated capillary such as fluorocarbon, illustrating that methylcellulose coating provided consistent results and could be seamlessly integrated into an existing drug discovery process. Finally, the methylcellulose‐coated fused silica capillary was applied to imaged capillary isoelectric focusing—mass spectrometry for characterizing protein charge variants allowing reliable identification of mass spectrometry after imaged capillary isoelectric focusing separation. This can greatly simplify the operation steps and prevent the contamination of mass spectrometry ion source that often results from using routinely coated capillaries ultimately making this an essential innovation of imaged capillary isoelectric focusing—mass spectrometry that greatly improves the imaged capillary isoelectric focusing compatibility with mass spectrometry. [ABSTRACT FROM AUTHOR]

Rationale: Fc‐fusion proteins represent a successful class of biopharmaceutical products, which combine the tailored pharmacological properties of biological ligands with the multiple functions of the fragment crystallizable domain of immunoglobulins. There is great diversity in terms of possible biological ligands creating highly diverse structures, therefore the analytical characterization of fusion proteins is far more complex than that of monoclonal antibodies and requires the use and development of additional product‐specific methods over conventional generic/platform methods. Methods: Employing etanercept analogues as studied fusion proteins, the Orbitrap mass analyzer with ultra‐high performance liquid chromatography (UHPLC–MS) and imaged capillary isoelectric focusing (icIEF) were utilized for the in‐depth fusion protein characterization. Results: The amino acid sequence coverage, peptide mapping, and post‐translational modifications of etanercept analogues were analyzed by UHPLC–MS. The post‐translational modification results were complemented by imaged capillary isoelectric focusing to produce quality research on etanercept analogues. Conclusions: The developed workflow integrating UHPLC–MS and icIEF provided an innovative strategy for characterizing complex fusion proteins in the process of quality control and manufacturing. [ABSTRACT FROM AUTHOR]

White‐light‐emitting carbon dots (WCDs) show innate advantages as phosphors in white light‐emitting diodes (WLEDs). For WLEDs, the color rendering index (CRI) is the most important metric to evaluate its performance. Herein, WCDs are prepared by a facile one‐step solvothermal reaction of trimellitic acid and o‐phenylenediamine. It consists of four CDs identified by column chromatography as blue, green, yellow, red, and thus white light is a superposition of these four types of light. The mixture of the four CDs undergoes Förster resonance energy transfer to induce the generation of white light. The photoluminescence of WCDs originates from the synergistic effect of carbon core and surface states. Thereinto, the carbon core states dominate in RCDs, and the increase of amide contents and degree of conjugation promote the redshift of the emission spectra, which is further confirmed by theoretical calculations. In addition, a high CRI of 97 is achieved when the WCDs are used as phosphors to fabricate WLEDs, which is almost the highest value up to now. The multicolor LEDs can also be fabricated by using the four multicolor CDs as phosphors, respectively. This work provides a novel approach to explore the rapid preparation of low‐cost, high‐performance WCDs and CDs‐based WLEDs. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the efficacy and safety of osimertinib combined with anlotinib in the treatment of advanced non‐small‐cell lung cancer (NSCLC) after drug resistance, and to explore the related factors affecting the efficacy. Methods: The clinical data of 34 patients with advanced NSCLC who received osimertinib combined with anlotinib as three or more lines of treatment in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2019 to March 2022 were collected, and the therapeutic efficacy and safety were analyzed. Results: A total of 34 advanced NSCLC patients met the inclusion criteria. The objective response rate was 20.6%, the disease response rate was 88.2%, the median overall survival was 19.0 months, and the median progression‐free survival was 6.0 months. The common adverse events were mainly grade 1–2, and only three cases (11.1%) of adverse events were grade 3, including hypertension, proteinuria, and vomiting. No grade 4 or above adverse events were observed. Multivariate Cox regression analysis showed that the Eastern Cooperative Oncology Group Performance Status score and bone metastasis were independent prognostic factors for osimertinib combined with anlotinib as three or more lines of treatment in advanced NSCLC. Conclusions: Osimertinib combined with anlotinib as three or more lines of treatment in advanced NSCLC was effective and adverse events were tolerable. [ABSTRACT FROM AUTHOR]

A carrier ampholyte is a molecule containing both acid and base functionality that is critical for imaged capillary isoelectric focusing. The quality of an imaged capillary isoelectric focusing separation for protein charge variants' characterization is highly dependent on attributes of the carrier ampholytes used including baseline signal, linearity of the pH gradient, pI discrimination, and consistency between manufactured lots. AESlytes are a high‐resolution carrier ampholyte series that have been developed for the high‐resolution and selective characterization of diverse and complex protein drugs including diverse fusion proteins, antibody‐drug‐conjugate, bi‐specific antibodies, and viral proteins. While routine commercial ampholytes usually cannot solve such challenges, AESlytes demonstrate a reduction in baseline noise and distinguishably increased consistency between lots as compared to other commercial ampholytes. Here we apply AESlytes for the imaged capillary isoelectric focusing separation of several commercial fusion proteins and biosimilars with excellent repeatability. In addition, AESlytes with narrow‐range pH were employed directly coupled to a mass spectrometer for optimizing the separation resolutions allowing more reliable and accurate protein charge variant identification. Our study demonstrates that innovative high‐resolution carrier ampholytes as critical reagents play an essential role in high‐performance imaged capillary isoelectric focussing and tandem mass spectrometry analysis the routinely commercial ampholytes cannot achieve, especially for extremely complex protein drugs. [ABSTRACT FROM AUTHOR]

Monolithic integration of perovskite materials and their optoelectronic devices with well‐developed thin‐film transistor (TFT) backplane is leading to new applications in displays and image sensors. Herein, a scalable polyimide assisted patterning approach for monolithic integration of perovskite based high‐sensitive phototransistor array on indium gallium zinc oxide (IGZO) active matrix backplane is introduced. Polyimide vias are first formed by conventional photolithography process, through which uniform perovskite films of arbitrary patterns with feature size less than 20 µm are fabricated by spin‐on‐patterning method. Using this technique, patterns of quasi 2D perovskite photoabsorbing layer are precisely deposited onto the channel area of the photosensing IGZO TFT, forming high‐performance phototransistors with responsivity and detectivity reaching 835.7 A W−1 and 5.4 × 1012 Jones, respectively. An image sensor with 8 × 8 pixels array containing both photosensing perovskite/IGZO transistors and switching IGZO transistors is demonstrated, in which the switching IGZO transistor elements on the backplane are protected by the non‐patterned region of the polyimide encapsulation layer. This whole fabrication process is compatible with TFT manufacturing process and will significantly reduce the cost needed for constructing next generation high‐resolution image sensors. [ABSTRACT FROM AUTHOR]

Although phylogenetic distance between native and exotic species has a close link with their interactions, it is still unclear how environmental stresses and species interactions influence the relationship between phylogenetic distance and biological invasions. Here we assessed the effect of invader–native phylogenetic distance on the growth of the invader (Symphyotrichum subulatum) under three levels of drought (no, moderate, or intense drought). Under no drought, interspecific competition between close relatives was the dominant process and native communities more closely related to the invader showed higher resistance to invasion, supporting Darwin's naturalization hypothesis. In contrast, under intense drought, facilitation between close relatives by mutualism with arbuscular mycorrhizal fungi (AMF) became more important, and the invader became more successful in their more closely related native communities, supporting the preadaptation hypothesis. The colonization rate of AMF of the invader was higher in more closely related native communities regardless of the drought treatment, but it was only positively related to invader biomass under intense drought. Therefore, the shift of species interactions from competition to facilitation may be ascribed to the promotion of AMF to invasion occurring under intense drought, which leads to the effect of closely related natives on the invader shifting from negative to positive. Our results provide a new angle to resolve Darwin's naturalization conundrum from the change of species interactions along a stress gradient, and provide important clues for invasion management when species interactions change in response to global climatic change. [ABSTRACT FROM AUTHOR]

Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti‐bacterial, anti‐tumour, anti‐inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin. [ABSTRACT FROM AUTHOR]

Fragrant rice has unique aroma characteristics appreciated by many consumers. In order to extract exclusive flavour fingerprints from Guangxi fragrant rice and to further verify its effectiveness by allowing the rapid identification of fragrant rice from two main production regions (Guangxi and Wuchang), gas chromatography‐ion mobility spectrometry (GC‐IMS) technology was applied to analyse flavour components of 53 fragrant rice samples. Based on the two‐dimensional GC‐IMS map, characteristic variables of flavour components from Guangxi fragrant rice were screened via image pretreatment and automatic threshold segmentation algorithm. The extracted variables were further processed by using principal component analysis and quadratic discriminant analysis to establish a non‐linear model for discriminating two types of fragrant rice. The results showed that a total of 46 characteristic variables were extracted from Guangxi fragrant rice, and the first two principal components showed that the two types of rice samples had their own corresponding regions. 2‐Butanone, 2‐heptanone, pinene, 1‐heptanal, 2‐methyl‐1‐butanol acetate and octanal were the key different flavour components. The established model had an excellent recognition rate, which could be used to determine the geographical region of fragrant rice. The proposed method could achieve quick, non‐destructive and accurate analysis of fragrant rice geographical properties. It can be further applied in feature extraction from the two‐dimensional fingerprint map generated by other similar combined instruments. [ABSTRACT FROM AUTHOR]

Being sessile in soil, plant cells rely on cell‐surface receptors to sense and transduce environmental stimulus signals into intracellular responses. FERONIA (FER), a Catharanthus roseus receptor‐like kinase 1‐like protein, has emerged as a versatile regulator of plant growth, development, and stress responses. In recent years, accumulating studies have witnessed rapid advances in dissecting the mechanisms underlying the interaction between FER and its partners in response to pathogen invasion, particularly regulation of immune complex formation and signalling. Moreover, hormonal signalling, rhizosphere microbiota and other constituents are also extensively involved in these processes. [ABSTRACT FROM AUTHOR]

The cartilage repair and regeneration show inadequate self‐healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell‐carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell‐based cartilage‐regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal‐sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell‐based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow‐derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF‐β1 and efficiently regulate cartilage‐specific and inflammatory‐related gene expressions. Finally, the cartilage‐regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF‐β1‐SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration. [ABSTRACT FROM AUTHOR]

Summary: The plant receptor‐like kinase FERONIA (FER) functions in the response to multiple extracellular signals, thereby regulating diverse cellular processes, such as polarized cell growth, hormone signaling and responses to pathogens.Here, we reported that in Arabidopsis thaliana, flagellin peptide flg22 stimulus significantly promoted the lateral mobility and dissociation of FER from the plasma membrane by inducing the association of FER with membrane microdomain components.FER underwent constitutive endocytosis and recycling in a brefeldin A (BFA)‐sensitive manner via a clathrin‐mediated pathway. Following flg22 elicitation, FER localized to bona fide endosomes via two distinct endocytic routes, showing differential sensitivity to BFA.These results at the single‐particle level confirm that FER acts as an essential regulator during flg22 perception and immune activation, thus broadening our understanding of location‐specific protein dynamics and membrane trafficking in receptor/receptor kinase signaling. [ABSTRACT FROM AUTHOR]

Transparency Ecosystem for Research and Journals in Medicine (TERM) Working Group summarized the essential recommendations that should be considered to review and publish a high‐quality guideline. These recommendations from editors and reviewers included the ten components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting, and external review. TERM Working Group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), recommends guideline authors, editors, and peer reviewers use them for high‐quality guidelines. [ABSTRACT FROM AUTHOR]

Background: Listeria monocytogenes (Lm) present in farming soil and food‐processing facilities threatens food safety, but little is known about the carriage of Lm by wildlife. Objectives: We estimated the prevalence of faecal Lm shedding among wildlife admitted to a veterinary medical teaching hospital in central New York and characterized a subset of the Lm isolates. Methods: Wildlife samples were collected between May 2018 and December 2019. We characterized the Lm isolates by assessing the growth at three temperatures approximating the body temperatures of reptiles (25°C), mammals (37°C), and birds (42°C) and identifying genotypic characteristics related to transmission and virulence. Results: The apparent prevalence of faecal Lm shedding was 5.6% [18/324; 95% confidence interval (CI), 3.3%–8.6%]. Among 13 isolates that represented two lineages and 11 clonal complexes, three and five isolates were grouped into the same SNP clusters with human clinical isolates and environmental isolates, respectively. However, specific SNP difference data showed that Lm from wildlife was generally not closely related (>22 SNP differences) to Lm from human clinical sources and the food‐processing environment. While the stress response locus SSI‐2 was absent, SSI‐1 was found in four isolates. Virulence genes prfA, plcA, hly, mpl, actA, plcB, inlA, inlB, inlC, inlE, inlH, inlJ, and inlK were present, without any premature stop codons, in all isolates. Virulence loci Listeria pathogenicity island 3 (LIPI‐3) and LIPI‐4, which have been linked to hypervirulence, and inlG were found in four, three, and seven isolates, respectively. Conclusions: Wildlife represents a potential reservoir for genetically diverse and putatively hypervirulent Lm strains. No statistically significant association between growth parameters and hosts was observed. However, compared to lineage I isolates, lineage II isolates showed significantly (p < 0.05) faster growth at 25°C and significantly slower growth at 42°C, suggesting that wildlife Lm isolates that belong to lineages I and II differ in their ability to grow at 25°C and 42°C. [ABSTRACT FROM AUTHOR]

Two‐phase designs measure variables of interest on a subcohort where the outcome and covariates are readily available or cheap to collect on all individuals in the cohort. Given limited resource availability, it is of interest to find an optimal design that includes more informative individuals in the final sample. We explore the optimal designs and efficiencies for analyses by design‐based estimators. Generalized raking is an efficient class of design‐based estimators, and they improve on the inverse‐probability weighted (IPW) estimator by adjusting weights based on the auxiliary information. We derive a closed‐form solution of the optimal design for estimating regression coefficients from generalized raking estimators. We compare it with the optimal design for analysis via the IPW estimator and other two‐phase designs in measurement‐error settings. We consider general two‐phase designs where the outcome variable and variables of interest can be continuous or discrete. Our results show that the optimal designs for analyses by the two classes of design‐based estimators can be very different. The optimal design for analysis via the IPW estimator is optimal for IPW estimation and typically gives near‐optimal efficiency for generalized raking estimation, though we show there is potential improvement in some settings. [ABSTRACT FROM AUTHOR]

Background: To evaluate the initial safety and efficacy of femtosecond laser‐assisted minimal invasive lamellar keratoplasty (FL‐MILK) for advanced keratoconus. Methods: Twenty‐two patients (22 eyes) with advanced keratoconus were included in this prospective study. All the involved eyes underwent FL‐MILK. The femtosecond laser was used to create an intrastromal pocket with a 2.3 mm incision in the recipient cornea. Then a stromal button with a diameter of 9.0 mm and a depth of 200 μm was gently inserted into the intrastromal pocket through the 2.3 mm incision and flattened. No sutures were applied. Follow‐up was conducted for 24 months. Results: Twenty‐two patients completed follow‐up data for 12 months, 16 patients had 24 months follow‐up. No epithelial implantation, infection or allogeneic rejection were observed during the follow‐up. Based on baseline values, postoperative 12 months values and postoperative 24 months values, clinical significantly improvement was recorded in corrected distance visual acuity (CDVA) (0.40 ± 0.18 logMAR vs. 0.30 ± 0.12 logMAR and 0.23 ± 0.13 logMAR), the anterior central corneal elevation (29.14 ± 15.33 μm vs. 14.45 ± 13.75μm and 11.38 ± 8.33 μm), and corneal higher‐order aberrations (3.536 ± 1.503 vs. 2.761 ± 1.517 and 0.994 ± 0.391). Corneal biomechanical properties in all eyes improved significantly. SP‐A1 increased from 48.64 ± 12.87 preoperatively to 87.26 ± 21.01 postoperative 12 months and 88.77 ± 18.26 postoperative 24 months; deformation amplitude (DA) decreased from 1.36 ± 0.15 preoperatively to 1.21 ± 0.12 postoperative 12 months and 1.19 ± 0.19 postoperative 24 months. Conclusions: Initial experience suggests that this minimally invasive transplantation may be a feasible option for advanced keratoconus. A larger cohort and longer follow‐up are required to validate our results and establish long‐term safety and efficacy of the procedure. [ABSTRACT FROM AUTHOR]