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To investigate the molecular mechanism of the defense response of "Cabernet Sauvignon" grapes to feeding by Apolygus lucorum , high-throughput sequencing technology was used to analyze the transcriptome of grape leaves under three different treatments: feeding by A. lucorum , puncture injury, and an untreated control. The research findings indicated that the differentially expressed genes were primarily enriched in three aspects: cellular composition, molecular function, and biological process. These genes were found to be involved in 42 metabolic pathways, particularly in plant hormone signaling metabolism, plant-pathogen interaction, MAPK signaling pathway, and other metabolic pathways associated with plant-induced insect resistance. Feeding by A. lucorum stimulated and upregulated a significant number of genes related to jasmonic acid and calcium ion pathways, suggesting their crucial role in the defense molecular mechanism of "Cabernet Sauvignon" grapes. The consistency between the gene expression and transcriptome sequencing results further supports these findings. This study provides a reference for the further exploration of the defense response in "Cabernet Sauvignon" grapes by elucidating the expression of relevant genes during feeding by A. lucorum ., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest., (© 2024 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga 2 STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga 2 STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga 2 STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga 2 STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga 2 STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga 2 STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga 2 STe devices.

Background: Clinicians working with patients at risk of suicide often experience high stress, which can result in negative emotional responses (NERs). Such negative emotional responses may lead to less empathic communication (EC) and unintentional rejection of the patient, potentially damaging the therapeutic alliance and adversely impacting suicidal outcomes. Therefore, clinicians need training to effectively manage negative emotions toward suicidal patients to improve suicidal outcomes., Methods: This study investigated the impact of virtual human interaction (VHI) training on clinicians' self-awareness of their negative emotional responses, assessed by the Therapist Response Questionnaire Suicide Form, clinicians' verbal empathic communication assessed by the Empathic Communication and Coding System, and clinical efficacy (CE). Clinical efficacy was assessed by the likelihood of subsequent appointments, perceived helpfulness, and overall interaction satisfaction as rated by individuals with lived experience of suicide attempts. Two conditions of virtual human interactions were used: one with instructions on verbal empathic communication and reminders to report negative emotional responses during the interaction (scaffolded); and the other with no such instructions or reminders (non-scaffolded). Both conditions provided pre-interaction instructions and post-interaction feedback aimed at improving clinicians' empathic communication and management of negative emotions. Sixty-two clinicians participated in three virtual human interaction sessions under one of the two conditions. Linear mixed models were utilized to evaluate the impact on clinicians' negative emotional responses, verbal empathic communication, and clinical efficacy; and to determine changes in these outcomes over time, as moderated by the training conditions., Results: Clinician participants' negative emotional responses decreased after two training sessions with virtual human interactions in both conditions. Participants in the scaffolded condition exhibited enhanced empathic communication after one training session, while two sessions were required for participants in the non-scaffolded condition. Surprisingly, after two training sessions, clinical efficacy was improved in the non-scaffolded group, while no similar improvements were observed in the scaffolded group., Conclusion: Lower clinical efficacy after virtual human interaction training in clinicians with higher verbal empathic communication suggests that nonverbal expressions of empathy are critical when interacting with suicidal patients. Future work should explore virtual human interaction training in both nonverbal and verbal empathic communication., (© 2024. The Author(s).)

Piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymer, poly(vinylidene fluoride- co -trifluoroethylene) (P(VDF-TrFE)), have attracted considerable attention due to their potential in flexible, biocompatible energy harvesting and sensing devices. However, their limited piezoelectric performance hinders their widespread application. Inspired by the concept of morphotropic phase boundary (MPB) prevalent in high-performance piezoelectric ceramics, we successfully constructed MPB in the piezoelectric polymer P(VDF-TrFE) through size-dependent interface effects. We provided direct structural evidence using atomic force microscopy-infrared spectroscopy (AFM-IR) and significantly improved the piezoelectric performance of P(VDF-TrFE). The emergence of MPB is attributed to the interface effect induced by electrostatic interactions between ZnO fillers and the -CH 2 , -CF 2 , and -CHF groups in P(VDF-TrFE). This interaction drives a concomitant competition between the all-trans β phase (normal ferroelectric) and the 3/1 helical phase (relaxor), resulting in enhanced piezoelectric responses in the transition region. By coupling the MPB effect with a porous structure, we developed a piezoelectric nanogenerator (PENG) that surpasses the electrical output limitation of current P(VDF-TrFE)-based PENGs. The fabricated PENG exhibits superior piezoelectric outputs (6.9 μW/cm 2 ), impressive pressure sensitivity (2.3038 V/kPa), ultrafast response time (4.3 ms), and recovery time (46.4 ms)─notably, without the need for additional poling treatment. In practical applications, the constructed PENG can efficiently generate characteristic signals in response to various human movements and harvest biomechanical energy. This work offers insight into utilizing interface-induced MPB and proposes a simple, scalable approach for developing high-performance self-polarized piezoelectric polymer films for self-powered sensing systems toward human-machine interaction.

High-fat diet (HFD)-induced fatty liver disease is a deteriorating risk factor for Alzheimer's disease (AD). Mitigating fatty liver disease has been shown to attenuate AD-like pathology in animal models. However, it remains unclear whether enhancing Aβ clearance through immunotherapy would in turn attenuate HFD-induced fatty liver or whether its efficacy would be compromised by long-term exposure to HFD. Here, the therapeutic potentials of an anti-Aβ antibody, NP106, was investigated in APP/PS1 mice by HFD feeding for 44 weeks. The data demonstrate that NP106 treatment effectively reduced Aβ burden and pro-inflammatory cytokines in HFD-fed APP/PS1 mice and ameliorated HFD-aggravated cognitive impairments during the final 18 weeks of the study. The rejuvenating characteristics of microglia were evident in APP/PS1 mice with NP106 treatment, namely enhanced microglial Aβ phagocytosis and attenuated microglial lipid accumulation, which may explain the benefits of NP106. Surprisingly, NP106 also reduced HFD-induced hyperglycemia, fatty liver, liver fibrosis, and hepatic lipids, concomitant with modifications in the expressions of genes involved in hepatic lipogenesis and fatty acid oxidation. The data further reveal that brain Aβ burden and behavioral deficits were positively correlated with the severity of fatty liver disease and fasting serum glucose levels. In conclusion, our study shows for the first time that anti-Aβ immunotherapy using NP106, which alleviates AD-like disorders in APP/PS1 mice, ameliorates fatty liver disease. Minimizing AD-related pathology and symptoms may reduce the vicious interplay between central AD and peripheral fatty liver disease, thereby highlighting the importance of developing AD therapies from a systemic disease perspective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis., Methods: Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice., Results: THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis., Conclusions: THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies., (© 2024. The Author(s).)

Objective: Working with suicidal patients can elicit negative emotional responses that can impede clinicians' empathy and affect clinical outcomes. Virtual human interactions represent a promising tool to train clinicians. The present study investigated the impact of virtual human interaction training to enhance clinicians' emotional self-awareness and empathy when working with suicidal patients., Methods: Clinicians were randomly assigned into two groups. Both groups interviewed a virtual patient presenting with a suicidal crisis; clinicians in the intervention condition (n = 31) received immediate feedback about negative emotional responses and empathic communication, whereas those in the control condition (n = 33) did not receive any feedback. All clinicians interviewed a second virtual patient 1 week later. Clinicians' emotional response to the two virtual patients and their empathic communication with each of them were assessed immediately after each interaction. Linear mixed models were used to assess change in clinicians' emotional response and verbal empathy between the two interactions across conditions., Results: Clinicians' emotional responses toward the suicidal virtual patients were unchanged in both conditions. Clinicians in the intervention condition presenting low empathy level with the first virtual patient showed higher empathy level with the second virtual patient than with the first (B = 1.15, SE = 0.25, p < 0.001, 95% CI [0.42, 1.89])., Conclusions: This work demonstrates the feasibility of using virtual human interactions to improve empathic communication skills in clinicians with poor empathy skills. Further refinement of this methodology is needed to create effective training modules for a broader array of clinicians., (© 2023. The Author(s), under exclusive licence to American Association of Chairs of Departments of Psychiatry, American Association of Directors of Psychiatric Residency Training, Association for Academic Psychiatry and Association of Directors of Medical Student Education in Psychiatry.)

Several studies have demonstrated suppression of aortic atherosclerosis by insulin like growth factor-1 (IGF-1) in hypercholesterolemic rabbits. Though a recent study has reported that IGF-1 exerts anti-atherogenic effects in coronary arteries, the mechanisms of IGF-1 in coronary arteries need to be further verified. Studies about insulin like growth factor binding protein-2 (IGFBP-2) in atherosclerosis are rarely. The objective of this study is to examine the effects of IGF-1 and IGFBP-2 on the atherosclerosis development in the aorta and coronary arteries of the high-cholesterol diet (HCD)-fed rabbits. New Zealand white rabbits were fed either normal chow (n = 5) or a diet containing 1.0 % cholesterol (n = 18) for 12 weeks. Cholesterol-fed rabbits were given IGF-1 or IGFBP-2 or saline intravenously (each n = 6) for 10 weeks. The results revealed that IGF-1 decreased total cholesterol (TC) and low-density lipoprotein (LDL) levels (p < 0.05), whereas IGFBP-2 did not. IGF-1 significantly attenuated atherosclerotic lesions and reduced accumulated macrophages within the coronary artery plaques, whereas IGFBP-2 deteriorated these changes. Moreover, IGF-1 reduced serum platelet-activating factor acetylhydrolase levels, C reactive protein (CRP), and inhibited the protein expression levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). IGFBP-2 elevated serum 8-hydroxy-2'-deoxyguanosine levels, CRP, and promoted the protein expression levels of TNF-α and IL-6. In conclusion, IGF-1 can substantially suppress plaque formation in coronary arteries with a marked inhibition of macrophage accumulation likely via its anti-inflammatory properties, whereas IGFBP-2 plays an opposite effect on atherosclerosis. The present study highlighted a theoretical basis for pharmacological treatment of atherosclerosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Wi-Fi fingerprinting has been a popular indoor localization due to the widespread layout of indoor WLAN. However, the signal fluctuations in the complex environments make it difficult to maintain high accuracy localization for the received signal strength (RSS) fingerprinting. Various positioning solutions have emerged to address this challenge, either working in stand-alone mode or in collaborative mode. In the former case, the user only utilizes his own RSS observation to request location service, while the latter usually requires information transfer between users. Considering the spatial correlation of wireless signal distribution, we propose an online joint localization scheme (JointLoc) that does not require direct interaction between users. The fact that the signals observed by users in physical proximity characterize the surroundings is used by JointLoc to identify neighboring users for joint localization. Besides this, JointLoc further integrates a novel subset-based localization scheme, thus the influence of anomalous RSS signals is eliminated before making the final location decision. We have fully evaluated the performance of JointLoc in two RSS datasets collected in real environments. Compared with conventional algorithms and the latest ones, results show that JointLoc is robust against signal fluctuations, and achieves good localization accuracy., (© 2023. The Author(s).)

Leaf stacking fermentation involves enzymatic actions of many microorganisms and is an efficient and environmentally benign process for degrading macromolecular organic compounds. We investigated the dynamics of metabolite profiles, bacterial and fungal communities and their interactions during fermentation using cigar leaves from three geographic regions. The results showed that the contents of total sugar, reducing sugar, starch, cellulose, lignin, pectin, polyphenol and protein in cigar tobacco leaves was significantly decreased during fermentation. Notably, the furfural, neophytadiene, pyridine, benzyl alcohol, geranylacetone, 3-hydroxy-2-butanone, N-hexanal, 3-Methyl-1-butanol and 2,3-pentanedione were important features volatile aroma compounds during fermentation. The α-diversity of fungi and bacteria initially increased and then decreased during fermentation. An analysis of variance showed that microbial diversity was influenced by fermentation stages and growing locations, in which the all stages had greater impacts on α- and β-diversity than all regions. Microbiome profiling had identified several core bacteria including Sphingomonas, Bacillus, Staphylococcus, Pseudomonas, Ralstonia, Massilia and Fibrobacter. Fungal biomarkers included Aspergillus, Penicillium, Fusarium, Cladosporium and Trichomonascus. Interestingly, the molecular ecological networks showed that the core taxa had significant correlations with metabolic enzymes and physicochemical properties; bacteria and fungi jointly participated in the carbohydrate and nitrogen compound degrading and volatile aroma compound chemosynthesis processes during fermentation. These studies provide insights into the coupling of material conversion and microbial community succession during leaf fermentation., (© 2023. The Author(s).)

In recent years, the two-dimensional (2D) semiconductor α-In 2 Se 3 has great potential for applications in the fields of electronics and optoelectronics due to its spontaneous iron electrolysis properties. Through ab initio electronic structure calculations and quantum transport simulations, the interface properties and transport properties of α-In 2 Se 3 /Au contacts with different polarization directions are studied, and a two-dimensional α-In 2 Se 3 asymmetric metal contact design is proposed. When α-In 2 Se 3 is polarized upward, it forms an n-type Schottky contact with Au. While when α-In 2 Se 3 is polarized downward, it forms a p-type Schottky contact with Au. More importantly, significant rectification effect is found in the asymmetric Au/α-In 2 Se 3 /Au field-effect transistor. The carrier transports under positive and negative bias voltages are found to be dominated by thermionic excitation and tunneling, respectively. These findings provide guidance for the further design of 2D α-In 2 Se 3 -based transistors., (© 2023. The Author(s).)

Triboelectric nanogenerators (TENGs) are promising for a variety of applications that require a reliable output performance and stability. In this work, by utilizing the synergistic effect of lithium chloride (LiCl) and MXene, poly(vinyl alcohol) (PVA) based composite films with humidity-sensitive properties were prepared and employed as a friction layer to achieve self-powered TENGs with enhanced output performance under high humidity. The composite material demonstrates exceptional and stable output performance in the humidity range of 30-95% while exhibiting a strong linear correlation with increasing relative humidity (RH). At 95% RH, its short-circuit current increases up to 31.91 μA, which is three times the output of the TENG fabricated by PVA and PTFE (P-TENG). The rich hydroxyl group in PVA, the strong hygroscopicity of LiCl, and the microcapacitor network provided by MXene nanosheets significantly improve the water absorption capacity and surface roughness of the composite material, resulting in an excellent triboelectric output of TENG. Short-circuit current of the TENG in a wide range of RH (from 50% to 98%) responds very sensitively to humidity fluctuations in the environment and superior adsorption-desorption performance as humidity decreases. Furthermore, TENG regarded as a power supply in high humidity conditions was realized and it can light up 240 LEDs instantaneously with the transfer charge density of TENG reaching 194.37 μC m -2 . This technology presents an effective method for stable energy harvesting and self-powered sensing in fog, the ocean, and other high-humidity environments.

Background and Aim: The involvement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-2 (IGFBP-2) following acute coronary syndrome (ACS) is rarely studied in clinical practice. Therefore, we sought to evaluate the relationship between IGF-1 and IGFBP-2 concentrations at admission and risk stratification based on the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients with ACS., Methods and Results: In all, 304 patients diagnosed with ACS were included in this study. Plasma IGF-1 and IGFBP-2 were measured using commercially available ELISA kits. The TIMI risk score was calculated and the study population was stratified into high (n = 65), medium (n = 138), and low (n = 101) risk groups. Levels of IGF-1 and IGFBP-2 were analyzed for their predictive ability of risk stratification based on the TIMI risk scores. Correlation analysis showed that IGF-1 levels were negatively correlated with TIMI risk levels (r = -0.144, p = 0.012), while IGFBP-2 levels were significantly and positively correlated with TIMI risk levels (r = 0.309, p < 0.001). In multivariate logistic regression analysis, IGF-1 (odds ratio [OR]: 0.995; 95% confidence interval [CI]: 0.990-1.000; p = 0.043) and IGFBP-2 (OR: 1.002; 95%CI: 1.001-1.003; p < 0.001) were independent predictors of high TIMI risk levels. In receiver operating characteristic curves, the area under the curve values for IGF-1 and IGFBP-2 in the prediction of high TIMI risk levels were 0.605 and 0.723, respectively., Conclusions: IGF-1 and IGFBP-2 levels are excellent biomarkers for risk stratification in patients with ACS, which provides further guidance for clinicians to identify patients at high risk and to lower their risk., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Measuring the isotopic composition of Hg in natural waters is challenging due to the ultratrace level of aqueous Hg (ng L -1 ). At least 5 ng of Hg mass is required for Hg isotopic analysis. Given the low Hg concentration in natural waters, a large volume of water (>10 L) is typically needed. The conventional grab sampling method is time-consuming, laborious, and prone to contamination during transportation and preconcentration steps. In this study, a DGT (diffusive gradients in thin films) method based on aminopropyl and mercaptopropyl bi-functionalized SBA-15 nanoparticles was developed and extended to determine the concentration and isotopic composition of aqueous Hg for the first time. The results of laboratory analysis showed that Hg adsorption by DGT induces ∼ -0.2‰ mass-dependent fractionation (MDF) and little mass-independent fractionation (MIF). The magnitude of MDF exhibits a dependence on the diffusion-layer thickness of DGT. Since Hg-MDF can occur in a broad range of environmental processes, monitoring the δ 202 Hg of aqueous Hg using the DGT method should be performed with caution. Field results show consistent MIF signatures (Δ 199 Hg) between the DGT and conventional grab sampling method. The developed DGT method serves as a passive sampling method that effectively characterizes the MIF of Hg in waters to understand the biogeochemical cycle of Hg at contaminated sites.

Changes in volatile metabolites during cigar tobacco leaves fermentation as well as the metabolic pathways of metabolites with significant differences were investigated to determine the influence of cigar tobacco leaves fermentation on its flavor. The volatile substances in cigar tobacco leaves at different stages were detected by headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), and the main differences in volatile substances in cigar tobacco leaves at different fermentation stages of Yunxue1 in Yuxi production area were analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The results show that in the process of cigar tobacco leaves fermentation (YXF0, YXF1, YXF2, YXF3, YXF4, YXF5), a total of 613 volatile metabolites were detected, and a significant difference was found in 263 kinds of metabolites. Among them, the main upregulated differential metabolites were 1,3,6,10-Cyclotetradecatetraene, 3,7,11-trimethyl-14-(1-methylethyl)-, [ S -(E,Z,E,E)]-, Benzoic acid, Benzaldehyde, etc. While the main downregulated differential metabolites included beta.-Myrcene, trans -Farnesol, etc. The metabolites with significant differences are mainly concentrated in the biosynthesis of monoterpenes, diterpenes, sesquiterpenes and triterpenes, the degradation metabolism of amino acids, such as valine, leucine and isoleucine, and the biosynthesis of phenylpropyl. There were 8 different metabolites in 5 groups, including 4- (1-methylethyl) -1-cyclohexene-1-formaldehyde、2, 4-dihydroxyacetophenone、2-methylbutyl 3-methylbutyrate and methylpyrazine, all of which showed upregulation trend during fermentation. In the fermentation process, volatile metabolites participate in various synthesis and degradation pathways. The biosynthesis pathway of terpenes and amino acid synthesis and degradation pathway are connected to produce various terpenes, aldehydes and other substances, such as 1,3,6,10-Cyclotetradecatetraene, 3,7,11-trimethyl-14-(1-methylethyl)-, [ S -(E,Z,E,E)]-、benzaldehyde and 4-hydroxybenzaldehyde, which are conducive to the overall flavor and quality of cigar tobacco leaves., Competing Interests: There are no conflicts of interest in the submission of this manuscript, and manuscript is approved by all authors for publication., (© 2023 The Authors. Published by Elsevier B.V.)

Background: This study aimed to analysis the clinical characteristics and prognosis of acute STEMI in patients aged ≤ 45 years., Methods: Seven hundred and one patients with STEMI from Liaocheng People's Hospital from January 2018 to March 2021 were included in this study. Clinical characteristics, management, and outcomes (average follow-up: 11.5 months) were compared between patients aged ≤ 45 years and those aged > 45 years., Results: Of the patients with STEMI who underwent primary percutaneous coronary intervention, 108 (15.4%) were aged ≤ 45 years. Compared to the older group, the younger patient group included more males, current smokers, and those with alcohol use disorder (AUD) or a family history of ischaemic heart disease (IHD). The culprit vessel in young patients was the left anterior descending (LAD) artery (60% vs. 45.9%, P = 0.031), which may have been due to smoking (odds ratio, 3.5; 95% confidence interval: 1.12-10.98, P = 0.042). Additionally, young patients presented with higher low-density lipoprotein and lower high-density lipoprotein levels than older patients; uric acid levels were also significantly higher in younger patients than that in the older group. Diabetes showed a trend toward major adverse cardiovascular events (MACE) in both groups; age and sex were both independent predictors of MACE in older patients., Conclusion: More patients who were smokers, had AUD, or a family history of IHD were present in the young patient group. Hyperuricaemia (but not dyslipidaemia) was a prevalent risk factor in patients aged ≤ 45 years. Diabetes should be controlled to reduce cardiovascular events in young patients., (© 2023. The Author(s).)

In the natural ecosystem, plants usually grow at high vegetation density for yield maximization. The high-density planting triggers a variety of strategies to avoid canopy shade and competes with their neighbors for light and nutrition, which are collected termed shade avoidance responses. The molecular mechanism underlying shade avoidance and nutrition has expanded largely in the past decade; however, how these two responses intersect remains poorly understood. Here, we show that simulated shade undermined Pi starvation response and the phytohormone JA is involved in this process. We found that the JA signaling repressor JAZ proteins directly interact with PHR1 to repress its transcriptional activity on downstream targets, including phosphate starvation induced genes. Furthermore, FHY3 and FAR1, the negative regulators of shade avoidance, directly bind to promoters of NIGT1.1 and NIGT1.2 to activate their expression, and this process is also antagonized by JAZ proteins. All these results finally result in attenuation of Pi starvation response under shade and Pi-depleted conditions. Our findings unveil a previously unrecognized molecular framework whereby plants integrate light and hormone signaling to modulate phosphate responses under plant competition., Competing Interests: The authors have no conflict of interest to declare., (© 2023 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Germplasm resources are the source of herbal medicine production. The cultivation of superior germplasm resources helps to resolve the conflict between long-term population persistence and growing market demand by consistently producing materials with high quality. The fern species Cibotium barometz is the original plant of cibotii rhizoma ("Gouji"), a traditional Chinese medicine used in the therapy of pain, weakness, and numbness in the lower extremities. Long-history medicinal use has caused serious wild population decline in China. Without sufficient understanding of the species and lineage diversity of Cibotium , it is difficult to propose a targeted conservation scheme at present, let alone select high-quality germplasm resources. In order to fill such a knowledge gap, this study sampled C. barometz and relative species throughout their distribution in China, performed genome skimming to obtain plastome data, and conducted phylogenomic analyses. We constructed a well-supported plastome phylogeny of Chinese Cibotium , which showed that three species with significant genetic differences are distributed in China, namely C. barometz , C. cumingii , and C. sino-burmaense sp. nov., a cryptic species endemic to NW Yunnan and adjacent regions of NE Myanmar. Moreover, our results revealed two differentiated lineages of C. barometz distributed on the east and west sides of a classic phylogeographic boundary that was probably shaped by monsoons and landforms. We also evaluated the resolution of nine traditional barcode loci and designed five new DNA barcodes based on the plastome sequence that can distinguish all these species and lineages of Chinese Cibotium accurately. These novel findings on a genetic basis will guide conservation planners and medicinal plant breeders to build systematic conservation plans and exploit the germplasm resources of Cibotium in China., Competing Interests: Author L-MT was employed by the company Guangxi Forestry Industry Group Stock Corporation, Nanning, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Liang, Wu, Tang, Qin, Chen, Huang, Li and Zhang.)

Background and Aims: Human bone marrow mesenchymal stem cells (hBMSCs) are important for developing a dual-humanized mouse model to clarify disease pathogenesis. We aimed to elucidate the characteristics of hBMSC transdifferentiation into liver and immune cells., Methods: A single type of hBMSCs was transplanted into immunodeficient Fah-/- Rag2-/- IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF). Liver transcriptional data from the hBMSC-transplanted mice were analysed to identify transdifferentiation with traces of liver and immune chimerism., Results: Mice with FHF were rescued by implanted hBMSCs. Human albumin/leukocyte antigen (HLA) and CD45/HLA double-positive hepatocytes and immune cells were observed in the rescued mice during the initial 3 days. The transcriptomics analysis of liver tissues from dual-humanized mice identified two transdifferentiation phases (cellular proliferation at 1-5 days and cellular differentiation/maturation at 5-14 days) and ten cell lineages transdifferentiated from hBMSCs: human hepatocytes, cholangiocytes, stellate cells, myofibroblasts, endothelial cells and immune cells (T/B/NK/NKT/Kupffer cells). Two biological processes, hepatic metabolism and liver regeneration, were characterized in the first phase, and two additional biological processes, immune cell growth and extracellular matrix (ECM) regulation, were observed in the second phase. Immunohistochemistry verified that the ten hBMSC-derived liver and immune cells were present in the livers of dual-humanized mice., Conclusions: A syngeneic liver-immune dual-humanized mouse model was developed by transplanting a single type of hBMSC. Four biological processes linked to the transdifferentiation and biological functions of ten human liver and immune cell lineages were identified, which may help to elucidate the molecular basis of this dual-humanized mouse model for further clarifying disease pathogenesis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Self-assembled nanogratings, inscribed by femtosecond laser writing in volume, are demonstrated in multicomponent alkali and alkaline earth containing alumino-borosilicate glasses. The laser beam pulse duration, pulse energy, and polarization, were varied to probe the nanogratings existence as a function of laser parameters. Moreover, laser-polarization dependent form birefringence, characteristic of nanogratings, was monitored through retardance measurements using polarized light microscopy. Glass composition was found to drastically impact the formation of nanogratings. For a sodium alumino-borosilicate glass, a maximum retardance of 168 nm (at 800 fs and 1000 nJ) could be measured. The effect of composition is discussed based on SiO 2 content, B 2 O 3 /Al 2 O 3 ratio, and the Type II processing window is found to decrease as both (Na 2 O + CaO)/Al 2 O 3 and B 2 O 3 /Al 2 O 3 ratios increase. Finally, an interpretation in the ability to form nanogratings from a glass viscosity viewpoint, and its dependency with respect to the temperature, is demonstrated. This work is brought into comparison with previously published data on commercial glasses, which further indicates the strong link between nanogratings formation, glass chemistry, and viscosity.

Preliminary studies have confirmed that ambient air pollutant concentrations are significantly influenced by the COVID-19 lockdown measures, but little attention focus on the long term impacts of human countermeasures in cities all over the world during the period. Still, fewer have addressed their other essential properties, especially the cyclical response to concentration reduction. This paper aims to fill the gaps with combined methods of abrupt change test and wavelet analysis, research areas were made of five cities, Wuhan, Changchun, Shanghai, Shenzhen and Chengdu, in China. Abrupt changes in contaminant concentrations commonly occurred in the year prior to the outbreak. The lockdown has almost no effect on the short cycle below 30 d (days) for both pollutants, and a negligible impact on the cycle above 30 d. PM 2.5 (fine particulate matter) has a stable short-cycle nature, which is greatly influenced by anthropogenic emissions. The analysis revealed that the sensitivity of PM 2.5 to climate is increased along with the concentrations of PM 2.5 were decreasing by the times when above the threshold (30-50 μg m -3 ), and which could lead to PM 2.5 advancement relative to the ozone phase over a period of 60 d after the epidemic. These results suggest that the epidemic may have had an impact earlier than when it was known. And significant reductions in anthropogenic emissions have little impact on the cyclic nature of pollutants, but may alter the inter-pollutant phase differences during the study period., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

The development of low-dimensional multifunctional devices has become increasingly important as the size of field-effect transistors decreases. In recent years, the two-dimensional (2D) semiconductor In 2 Se 3 has emerged as a promising candidate for applications in the fields of electronics and optoelectronics owing to its remarkable spontaneous polarization properties. Through first-principles calculations, the effects of the polarization direction and biaxial tensile strain on the electronic and contact properties of In 2 Se 3 /Au heterostructures are investigated. The contact type of In 2 Se 3 /Au heterostructures depends on the polarization direction of In 2 Se 3 . The more charge transfers from the metal to the space charge region, the biaxial tensile strain increases. Moreover, the upward polarized In 2 Se 3 in contact with Au maintains a constant n-type Schottky contact as the biaxial tensile strain increases, with a barrier height Φ SB,n of only 0.086 eV at 6% strain, which is close to ohmic contact. On the other hand, the downward polarized In 2 Se 3 in contact with Au can be transformed from p-type to n-type by applying a biaxial tensile strain. Our calculation results can provide a reference for the design and fabrication of In 2 Se 3 -based field effect transistors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Functional bioengineered livers (FBLs) are promising alternatives to orthotopic liver transplantation. However, orthotopic transplantation of FBLs has not yet been reported. This study aimed to perform the orthotopic transplantation of FBLs in rats subjected to complete hepatectomy. FBLs were developed using rat whole decellularized liver scaffolds (DLSs) with human umbilical vein endothelial cells implanted via the portal vein, and human bone marrow mesenchymal stem cells (hBMSCs) and mouse hepatocyte cell line implanted via the bile duct. FBLs were evaluated in terms of endothelial barrier function, biosynthesis, and metabolism and orthotopically transplanted into rats to determine the survival benefit. The FBLs with well-organized vascular structures exhibited endothelial barrier function, with reduced blood cell leakage. The implanted hBMSCs and hepatocyte cell line were well aligned in the parenchyma of the FBLs. The high levels of urea, albumin, and glycogen in the FBLs indicated biosynthesis and metabolism. Orthotopic transplantation of FBLs achieved a survival time of 81.38 ± 4.263 min in rats ( n = 8) subjected to complete hepatectomy, whereas control animals ( n = 4) died within 30 min ( p < 0.001). After transplantation, CD90-positive hBMSCs and the albumin-positive hepatocyte cell line were scattered throughout the parenchyma, and blood cells were limited within the vascular lumen of the FBLs. In contrast, the parenchyma and vessels were filled with blood cells in the control grafts. Thus, orthotopic transplantation of whole DLS-based FBLs can effectively prolong the survival of rats subjected to complete hepatectomy. In summary, this work was the first to perform the orthotopic transplantation of FBLs, with limited survival benefits, which still has important value for the advancement of bioengineered livers.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a syndrome with high short-term mortality. The mechanism of the transcription factor ETS2 in ACLF remains unclear. This study aimed to clarify the molecular basis of ETS2 in ACLF pathogenesis. Peripheral blood mononuclear cells from patients with HBV-ACLF (n = 50) were subjected to RNA sequencing. Transcriptome analysis showed that ETS2 expression was significantly higher in ACLF patients than in patients with chronic liver diseases and healthy subjects (all p < 0.001). Area-under-ROC analysis of ETS2 demonstrated high values for the prediction of 28-/90-day mortality in ACLF patients (0.908/0.773). Significantly upregulated signatures of the innate immune response (monocytes/neutrophils/inflammation-related pathways) were observed in ACLF patients with high ETS2 expression. Myeloid-specific ETS2 deficiency in liver failure mice resulted in deterioration of biofunctions and increased expression of pro-inflammatory cytokines (IL-6/IL-1β/TNF-α). Knockout of ETS2 in macrophages confirmed the downregulation of IL-6 and IL-1β caused by both HMGB1 and lipopolysaccharide, and an NF-κB inhibitor reversed the suppressive effect of ETS2. ETS2 is a potential prognostic biomarker of ACLF patients that alleviates liver failure by downregulating the HMGB1-/lipopolysaccharide-triggered inflammatory response and may serve as a therapeutic target for ACLF., (© 2023 Wiley Periodicals LLC.)

Developing functional ductal organoids (FDOs) is essential for liver regenerative medicine. We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds (DLSs) with primary cholangiocytes isolated from mouse bile ducts. The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification. FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers. Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14. The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers. Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylated α-tubulin. The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems. The metabolomics analysis with 1075 peak pairs showed that serotonin, as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction, was specifically expressed in FDOs during the whole period of culture. Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening, which paves the way for future clinical therapeutic applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: While insulin-like growth factor 1 (IGF-1) exerts a cardioprotective effect in the setting of atherosclerosis, insulin-like growth factor binding protein 2 (IGFBP-2) is involved in metabolic syndrome. Although IGF-1 and IGFBP-2 are known to be predictors for mortality in patients with heart failure, their use in clinic as prognostic biomarkers for acute coronary syndrome (ACS) requires investigation. We evaluated the relationship between IGF-1 and IGFBP-2 levels at admission and the risk of major adverse cardiovascular events (MACEs) in patients with ACS., Methods: A total of 277 ACS patients and 42 healthy controls were included in this prospective cohort study. Plasma samples were obtained and analyzed at admission. Patients were followed for MACEs after hospitalization., Results: Among patients who suffered acute myocardial infarction, plasma levels of IGF-1 and IGFBP-2 were lower and higher, respectively, as compared to healthy controls (both p  < 0.05). The mean follow-up period was 5.22 (1.0-6.0) months and MACEs incidence was 22.4% (62 of 277 patients). Kaplan-Meier survival analysis revealed that patients with low IGFBP-2 levels had a greater event-free survival rate than patients with high IGFBP-2 levels ( p  < 0.001). Multivariate Cox proportional hazards analysis revealed IGFBP-2, but not IGF-1, to be a positive predictor of MACEs (hazard ratio 2.412, 95% CI 1.360-4.277; p  = 0.003)., Conclusion: Our findings suggest that high IGFBP-2 levels are associated with the development of MACEs following ACS. Moreover, IGFBP-2 is likely an independent predictive marker of clinical outcomes in ACS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Yu, Zhao, Mo, Liu, Han, Li and Yao.)

Background: Known for its rich history and culture, Qingdao is a typical symbol of Chinese maritime culture. Its unique genetic landscape has aroused interest among geneticists and forensic scientists. However, the genetic landscape of Qingdao has never been uncovered., Aim: This investigation intends to provide light on Qingdao's paternal genetic diversity and its evolutionary connections to other Han subgroups., Subjects and Methods: The genetic polymorphisms of 41 Y-chromosomal short tandem repeat (STR) loci in the Qingdao Han were investigated using SureID ® PathFinder Plus Kit. Phylogenetic studies were performed using genotype data from 52 East Asian groups at 23 common Y-STR loci. A multidimensional scaling plot and cladogram were constructed. Linear Discriminant Analysis (LDA) was carried out for predicting categories among the Han people. The k-nearest neighbour (kNN) algorithm was utilised to designate Y-SNP haplogroups for each haplotype., Results: The Qingdao Han were genetically far from the Tibeto-Burman populations and close with the Han people from northern China. LDA indicated a deep integration among the present-day Han people. By the kNN model, the predicted O2a2 and O2a1 were shown to be the predominant Y-SNP haplogroups., Conclusions: This study would be helpful for reconstructing the patrilineal history in China and establishing a more comprehensive Y-STR database.

Microchannels fabricated by femtosecond laser-assisted chemical etching are of great use in biochemical analysis. In this paper, we study the morphology change of etched microchannels in fused silica by controlling the laser scan speed, and we find a significant difference between the chemical etched length and volume. The fabricated microchannels would gradually become tapered along the scan direction, which influences the flow of the hydrofluoric (HF) reagent and the etching rate. As a result, the difference ratios of the etched length and volume, respectively, reach -5.56 % and -41.83 % followed by the scan speed increasing from 5 to 200 µm/s. Microchannels with polarization independence and better aspect ratio could be obtained in a high-speed-scan mode. We suggest that laser-induced structural transformation from interconnected microcracks to nanogratings could be responsible for this change. Aforementioned results offer a feasible approach to achieve polarization-independent microchannels, which is in favor of accelerating the fabrication of three-dimensional microfluidic devices.

Purpose: Acute coronary syndrome (ACS) has a high incidence and mortality rate worldwide, which has a considerable negative impact on the global economy. This study aimed to identify a group of ACS patients at a high risk of recurrent adverse cardiac events using the plasma NLRP3 inflammasome., Patients and Methods: ACS patients admitted to Liaocheng People's Hospital between June 2021 and March 2022 were enrolled in this study. Patients were divided into low (levels < 3.84 ng/mL) and high (levels ≥ 3.84 ng/mL) groups based on the median NLRP3 inflammasome levels. The patients were divided into three groups according to the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P): low (scores ≤ 2 points), intermediate (scores = 3 points), and high (score ≥ 4 points) risk. We investigated the relationship between NLRP3 inflammasome and laboratory indicators. Additionally, we examined whether the NLRP3 inflammasome was an independent predictor of high TRS-2P and explored the applicability of the plasma NLRP3 inflammasome for predicting high TRS-2P., Results: Logistic regression analysis revealed that NLRP3 inflammasome was an independent predictor of high TRS-2P (odds ratio [OR]:2.013; 95% confidence interval [CI]: 1.174-3.452). The area under the receiver operating characteristic curve value of the NLRP3 inflammasome was 0.674 (95% CI: 0.611-0.737; P < 0.001)., Conclusion: NLRP3 inflammasome levels are an independent predictive factor for high TRS-2P levels, which indicates that the NLRP3 inflammasome may help predict the prognosis of ACS patients., Competing Interests: The authors declare no conflicts of interest associated with this study., (© 2022 Mo et al.)

Background: The pathophysiology of hepatitis B-related liver cirrhosis (HBV-LC) remains unclear. This study aimed to explore the disease mechanisms using topological analysis of the miRNA/mRNA network., Methods: Paired miRNA/mRNA sequencing was performed with thirty-three peripheral blood mononuclear cell samples (LC, n = 9; chronic hepatitis B, n = 12; normal controls, n = 12) collected from a prospective cohort to identify the miRNA/mRNA network. Topological features and functional implications of the network were analyzed to capture pathophysiologically important miRNAs/mRNAs, whose expression patterns were confirmed in the validation group (LC, n = 15; chronic hepatitis B, n = 15; normal controls, n = 10), and functional potentials initiating fibrogenesis were demonstrated in vitro., Results: The miRNA/mRNA network contained 3121 interactions between 158 differentially expressed (DE) miRNAs and 442 DE-mRNAs. The topological analysis identified a core module containing 99 miRNA/mRNA interactions and two hub nodes (miR-20a-5p/miR-340-5p), which connected to 75 DE-mRNAs. The expression pattern along the disease progression of the core module was found associated with a continuous increase in wound healing, inflammation, and leukocyte migration but an inflection of immune response and lipid metabolic regulation, consistent with the pathophysiology of HBV-LC. MiR-20a-5p/miR-340-5p were found involved in macrophage polarization and hepatic stellate cell (HSC) activation in vitro (THP-1, LX-2 cell lines), and their expression levels were confirmed in the validation group independently., Conclusion: Topological analysis of the miRNA/mRNA network in HBV-LC revealed the association between fibrosis and miR-20a-5p/miR-340-5p involving initiating activations of macrophage and HSC. Further validations should be performed to confirm the HSC/macrophage activations and the interactions between miR-20a-5p/miR-340-5p and their potential targets, which may help to develop non-invasive prognostic markers or intervention targets for HBV-LC., (© 2022. The Author(s).)

Background: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients., Methods: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT., Findings: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated., Interpretation: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT., Funding: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program)., Competing Interests: None of the authors have competing interests to declare., (© 2022 The Author(s).)

Vascularization is a critical but challenging process in developing functional bioengineered livers with the decellularized liver scaffolds (DLSs) and the process is accompanied by cell-specific metabolic alterations. To elucidate the dynamic alterations of metabolites during vascularization, rat DLSs were vascularized with human umbilical vein endothelial cells and liquid chromatography mass spectrometry-based metabolomics was performed on culture supernatants collected at 0, 1, 3, 7, 14, and 21 days. Overall, 1698 peak pairs or metabolites were detected in the culture supernatants, with 309 metabolites being positively identified. The orthogonal partial least-squares discriminant analysis and functional enrichment analysis revealed three phases that could be clearly discriminated, including Phase D1 (cell proliferation and migration), Phase D3D7 (vascular lumen formation), and Phase D14D21 (functional endothelial barrier formation). Seventy-two common differentially abundant metabolites of known identity were detected in these three phases when compared with Day 0. Of these metabolites, a high level of β-Alanine indicated a better degree of vascularization and 14 days of in vitro dynamic culture is required to develop a functionalized vascular structure. These results enriched our understanding of the metabolic mechanism of DLS vascularization and indicated that β-Alanine could function as a potential predictor of the patency of vascularized bioengineered livers., (© 2022 Wiley Periodicals LLC.)

The plants' internal circadian clock can strongly influence phytochrome signaling in response to the changes in the external light environment. Phytochrome A (phyA) is the photoreceptor that mediates various far-red (FR) light responses. phyA signaling is modulated by FHY3 and FAR1, which directly activate the transcription of FHY1 and FHL, whose products are essential for light-induced phyA nuclear accumulation and subsequent light responses. However, the mechanisms by which the clock regulates phyA signaling are poorly understood. Here, we discovered that FHY1 expression is diurnally regulated, peaking in the middle of the day. Two Arabidopsis core clock components, CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and TIMING OF CAB EXPRESSION1 (TOC1), repress FHY3/FAR1-mediated FHY1/FHL activation. Consistently, the specific expression pattern of FHY1 under diurnal conditions is altered in cca1-1 , toc1-101 , CCA1 , and TOC1 overexpression plants. Furthermore, far-red induced gene expression and particularly nuclear accumulation of phyA are compromised in TOC1 and CCA1 overexpression seedlings. Our results therefore revealed a previously unidentified FHY1 expression pattern in diurnal cycles, which is negatively regulated by CCA1 and TOC1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Sun, Yao, Zheng, Cao and Wang.)

The house mouse or Mus musculus has become a premier mammalian model for genetic research due to its genetic and physiological similarities to humans. It brought mechanistic insights into numerous human diseases and has been routinely used to assess drug efficiency and toxicity, as well as to predict patient responses. To facilitate molecular mechanism studies in mouse, we present the Mouse Interactome Database (MID, Version 1), which includes 155,887 putative functional associations between mouse protein-coding genes inferred from functional association evidence integrated from 9 public databases. These putative functional associations are expected to cover 19.32% of all mouse protein interactions, and 26.02% of these function associations may represent protein interactions. On top of MID, we developed a gene set linkage analysis (GSLA) web tool to annotate potential functional impacts from observed differentially expressed genes. Two case studies show that the MID/GSLA system provided precise and informative annotations that other widely used gene set annotation tools, such as PANTHER and DAVID, did not. Both MID and GSLA are accessible through the website http://mouse.biomedtzc.cn., Competing Interests: The authors have declared that no competing interests exist.

Diabetes is a risk factor for Alzheimer's disease (AD), a chronic neurodegenerative disease. We and others have shown prediabetes, including hyperglycemia and obesity induced by high fat and high sucrose diets, is associated with exacerbated amyloid beta (Aβ) accumulation and cognitive impairment in AD transgenic mice. However, whether hyperglycemia reduce glial clearance of oligomeric amyloid-β (oAβ), the most neurotoxic Aβ aggregate, remains unclear. Mixed glial cultures simulating the coexistence of astrocytes and microglia in the neural microenvironment were established to investigate glial clearance of oAβ under normoglycemia and chronic hyperglycemia. Ramified microglia and low IL-1β release were observed in mixed glia cultures. In contrast, amoeboid-like microglia and higher IL-1β release were observed in primary microglia cultures. APPswe/PS1dE9 transgenic mice are a commonly used AD mouse model. Microglia close to senile plaques in APPswe/PS1dE9 transgenic mice exposed to normoglycemia or chronic hyperglycemia exhibited an amoeboid-like morphology; other microglia were ramified. Therefore, mixed glia cultures reproduce the in vivo ramified microglial morphology. To investigate the impact of sustained high-glucose conditions on glial oAβ clearance, mixed glia were cultured in media containing 5.5 mM glucose (normal glucose, NG) or 25 mM glucose (high glucose, HG) for 16 days. Compared to NG, HG reduced the steady-state level of oAβ puncta internalized by microglia and astrocytes and decreased oAβ degradation kinetics. Furthermore, the lysosomal acidification and lysosomal hydrolysis activity of microglia and astrocytes were lower in HG with and without oAβ treatment than NG. Moreover, HG reduced mitochondrial membrane potential and ATP levels in mixed glia, which can lead to reduced lysosomal function. Overall, continuous high glucose reduces microglial and astrocytic ATP production and lysosome activity which may lead to decreased glial oAβ degradation. Our study reveals diabetes-induced hyperglycemia hinders glial oAβ clearance and contributes to oAβ accumulation in AD pathogenesis., Competing Interests: The authors have declared that no competing interests exist.

Background: 'Gold Finger' is a grape cultivar with a finger-like shape and a milk flavor. The process by which its aroma profile evolves during ripening is unclear. Thus, changes in the free and bound volatile compounds present in 'Gold Finger' grapes during ripening were investigated using headspace sampling-solid-phase microextraction-gas chromatography-mass spectroscopy (HS-SPME-GC-MS)., Results: A total of 83 volatile aroma components were identified in the grapes, with aldehydes, esters, acids, and alcohols being the main components. The total aroma compound content exhibited significant differences between the bound and free forms. The total content of bound volatile compounds did not change significantly during fruit development, although the free aroma compound content was significantly higher than the bound content. The total content of free aldehydes, free alcohols, bound norisoprenoids, and ketones gradually increased for up to 70 days after flowering (DAF), while the total free ester, terpene, and acid content decreased. The characteristic aroma compounds of 'Gold Finger' grapes were identified as hexanal, (E)-2-hexenal, and ethyl hexanoate., Conclusions: These results give a foundation for the further development of 'Gold Finger' grapes and provide a theoretical basis for the selection and breeding of novel aromatic grape varieties. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Cortical processing depends on finely tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered inhibition associated with treatment-resistant major depressive disorder (depression), which is implicated in cognitive deficits and rumination, but the link remains to be better established mechanistically in humans. Here we test the effect of reduced somatostatin interneuron-mediated inhibition on cortical processing in human neuronal microcircuits using a data-driven computational approach. We integrate human cellular, circuit, and gene expression data to generate detailed models of human cortical microcircuits in health and depression. We simulate microcircuit baseline and response activity and find a reduced signal-to-noise ratio and increased false/failed detection of stimuli due to a higher baseline activity in depression. We thus apply models of human cortical microcircuits to demonstrate mechanistically how reduced inhibition impairs cortical processing in depression, providing quantitative links between altered inhibition and cognitive deficits., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics., Methods: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs)., Results: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis., Conclusions: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The majority of suicide attempters do not disclose suicide ideation (SI) prior to making an attempt. When reported, SI is nevertheless associated with increased risk of suicide. This paper implemented machine learning (ML) approaches to assess the degree to which current and lifetime SI affect the predictive validity of the Suicide Crisis Syndrome (SCS), an acute condition indicative of imminent risk, for near-term suicidal behaviors (SB )., Methods: In a sample of 591 high-risk inpatient participants, SCS and SI were respectively assessed using the Suicide Crisis Inventory (SCI) and the Columbia Suicide Severity Rating Scale (C-SSRS). Two ML predictive algorithms, Random Forest and XGBoost, were implemented and framed using optimism adjusted bootstrapping. Metrics collected included AUPRC, AUROC, classification accuracy, balanced accuracy, precision, recall, and brier score. AUROC metrics were compared by computing a z-score., Results: The combination of current SI and SCI showed slightly higher predictive validity for near-term SB as evidenced by AUROC metrics than the SCI alone, but the difference was not significant (p<0.05). Current SI scored the highest amongst a chi square distribution in regards to predictors of near-term SB., Conclusion: The addition of SI to the SCS does not materially improve the model's predictive validity for near-term SB, suggesting that patient self-reported SI should not be a requirement for the diagnosis of SCS., (Copyright © 2021. Published by Elsevier B.V.)

Currently, polymyxin B has been widely used in the treatment of multidrug-resistant Gram-negative pathogen infections. Due to the limited pharmacokinetic/pharmacodynamic data, the optimal dosage regimen for the recently proposed therapeutic target of the area under the concentration-time curve over 24 h in steady state divided by the minimum inhibitory concentration 50-100 mg⋅h/L has not yet been established. Moreover, most studies have focused on critically ill patients, yet there have been no studies in the field of renal transplantation. To optimize the dosage strategy and reduce the risk of toxicity, a population pharmacokinetics model of polymyxin B with the Phoenix NLME program was developed in our study. A total of 151 plasma samples from 50 patients were collected in the present study. Polymyxin B plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. A one-compartment model adequately described the data, and the clearance and volume of distribution were 1.18 L/h and 12.09 L, respectively. A larger creatinine clearance was associated with increased clearance of polymyxin B ( p < 0.01). Monte Carlo simulation showed that a regimen of a 75 mg loading dose with a 50 mg maintenance dose was a better option to achieve an optimal therapeutic effect (minimum inhibitory concentration ≤1 mg/L) and to reduce the incidence of side effects for patients with renal impairments. The developed model suggested that dosing adjustment should be based on renal function in renal transplant patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Deng, Zhu, Liu, Xu, Li, Xie, Yao, Yang, Zhang and Zhou.)

Aims: The prognostic value of plasma D-dimer in patients with coronary artery disease (CAD) remains controversial. The study is aimed at investigating the relationship between plasma D-dimer levels and in-hospital heart failure (HF) in ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI)., Methods: STEMI patients who underwent pPCI were enrolled in this study. Venous blood samples were collected from patients on admission before pPCI procedure. The study endpoint was the occurrence of in-hospital HF. The participants were divided into two groups according to plasma D-dimer levels and further compared baseline D-dimer levels between male and female. Logistic regression and receiver operating characteristic (ROC) curves were performed to evaluate the relationship of D-dimer and in-hospital HF., Results: A total of 778 patients were recruited in the study, of which 539 (69.3%) patients had normal D-dimer levels (≤0.5 mg/L) while 239 (30.7%) had increased D-dimer levels (>0.5 mg/L). The female patients have higher D-dimer levels and higher incident rate of in-hospital HF than that in male patients ( p < 0.001). The multivariate logistic regression model revealed that D-dimer was an independent predictor for in-hospital HF in overall population (adjusted odds ratio [OR]: 1.197, 95% CI: 1.003-1.429, and p = 0.046) and female patients (adjusted OR: 1.429, 95% CI: 1.083-1.885, and p = 0.012)., Conclusion: Increased plasma D-dimer levels were an independent risk factor for incidence of in-hospital HF in STEMI patients who underwent pPCI, especially in female patients, which provides guidance for clinicians in identifying patients at high risk of developing HF and lowering their risk., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Li Li et al.)

This study investigated the effects of foliar application of fulvic acid antitranspirant (FA-AT) on Cabernet Sauvignon (CS) and Riesling grapes and wines in a warm viticulture region of China. FA-AT controlled the contents of total soluble solids, fructose and glucose in mature grapes and alcohol in wines. FA-AT improved total phenols and flavonoids in Riesling grapes, and total tannin and individual flavanols in CS grapes and wine, while reducing total individual phenolic acids and flavonols in CS wine. Increased volatiles in CS grapes (hexyl acetate, linalool) and wine (isoamyl alcohol, 1-hexanol, 2-phenylethanol) detected by SPME-GC-MS can contribute to the fruity and floral aroma. FA-AT reduced the accumulation of anthocyanins in CS grapes and wine without an eventual reduction in the tonality of wine by sensory analysis, and improved the taste and balance of Riesling wine. Overall, FA-AT can improve the quality of grapes and wines produced in warm viticulture regions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The single-phase binary nickel vanadate Ni2V2O7 was successfully synthesized by a simple solid-state method to explore novel anode materials for lithium-ion batteries. After an activation process, the Ni2V2O7 electrode exhibited excellent electrochemical performance with a stable, high specific capacity of about 960 mA h g-1 at a current density of 100 mA g-1, which is attributed to the multiple valence states and the synergistic effect of the transition elements V and Ni. Even at a high current density of 2000 mA g-1, a stable specific capacity of about 400 mA h g-1 was still obtained. Considering the influence of the activation process on the electrochemical performance of the Ni2V2O7 electrode, we studied the origin of the excellent electrochemical performance, where the improved lithium diffusion coefficient and increased pseudocapacitive contribution caused by the activation process led to a significant improvement in the electrochemical performance, including rate capacity and cycle stability. By combining in situ X-ray diffraction (XRD) and ex situ X-ray photoelectron spectroscopy (XPS) methods, for the first time, we illustrate the detailed lithium storage mechanism of the Ni2V2O7 electrode during the lithium insertion/extraction process.

Hutai-8 (Vitis vinifera × Vitis labrusca) is a table grape widely cultivated in China. In order to determine the changes in volatile profile and aroma potential during berry ripening, a total of 84 free and 73 bound aroma compounds were identified and quantified using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). Aldehydes and esters were found to be the main volatile compounds in Hutai-8. They accumulated up to 70 days after flowering (DAF) and then decreased. Bound esters and alcohols were prominent. The concentration of bound esters in Hutai-8 at DAF80 was 714.90 µg/L. β-Damascenone, hexanal, (E)-2-hexenal, (E,Z)-2,6-nonadienal, (E)-2-nonenal, and ethyl octanoate significantly contributed to the volatile profile of Hutai-8. The odor activity value (OAV) of hexanal was the highest at DAF80, reaching 351.51. β-Damascenone mainly appeared midway through the maturation process, reaching a concentration of 12.79 µg/L. The majority of free components reached a maximum in DAF70, while the bound components continuously accumulated throughout the mature period. These results suggest that in addition to being a table grape, Hutai-8 has potential for brewing and other processing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Antimony (Sb), a priority pollutant listed by the U.S. Environmental Protection Agency (USEPA), can cause adverse effects on human health, with particular impacts on skin, eyes, gastrointestinal tract, and respiratory system. In this study, a database of Sb concentrations in the global atmosphere was developed through a survey of measurements published in more than 600 articles, which was then used to assess the health risks of Sb exposure based on a USEPA assessment model. Most measurements showed Sb concentrations of less than ∼10 ng m -3 , but those at several contaminated sites exhibited Sb concentrations of more than 100 ng m -3 . For measurements conducted in urban environments, Sb concentrations in the total suspended particles (TSP) and particles of less than 10 (PM 10 ) or 2.5 μm (PM 2.5 ) were the highest in Asia, followed by Europe, South America, and North America. Sb concentrations were generally higher in winter and fall than during other seasons in TSP and PM 10 samples. A significant correlation was observed between Sb and As in TSP and PM 2.5 on a global scale. Sb was mainly derived from anthropogenic sources, especially traffic emission, industrial emission, and fossil combustion. Hazard quotients (HQ) of Sb in TSP, PM 10 , and PM 2.5 were higher for children than adults because of their lighter body weight, inferior physical resistance, and higher ingestion probability. The global database for atmospheric Sb concentrations demonstrates a relatively low noncarcinogenic risk in most regions. Long-term monitoring is still required to identify the sources and growth potentials of Sb so that effective control policies can be established., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

In agricultural lands with selenium (Se) deficiency, bioavailability of Se in plants is low. Residents from large-scale agricultural production areas with Se deficiency often suffer from endemic diseases because of consumption of agricultural products lacking in Se. One such area in Northeast China where Keshan disease and Kashin-Beck disease originated, was selected for investigating the geochemistry, influencing factors, and risks of Se in the agroecosystems. Analysis of field samples indicates that the Se deficiency in soil is significantly reduced compared with that of several decades ago, and 62.6% of soils are now Se-sufficient in the southern Songnen Plain. However, Se in crop products remains low due to weak soil-plant transfer, resulting in high risks of Se deficiency related diseases in the rural population of this area. Structural equation modeling, principal component analysis, and other statistical analyses revealed that climate conditions and soil physical and chemical properties are the key factors influencing the spatial distribution of soil Se. Extensive use of agricultural fertilizers may indirectly inhibit the migration of Se from soil to plants. Ensuring sufficient Se contents in agricultural products to meet the minimum daily requirements of residents remains a challenge in Se-deficient areas, especially in the increased agricultural production environment in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

To facilitate biomedical studies of disease mechanisms, a high-quality interactome that connects functionally related genes is needed to help investigators formulate pathway hypotheses and to interpret the biological logic of a phenotype at the biological process level. Interactions in the updated version of the human interactome resource (HIR V2) were inferred from 36 mathematical characterizations of six types of data that suggest functional associations between genes. This update of the HIR consists of 88 069 pairs of genes (23.2% functional interactions of HIR V2 are in common with the previous version of HIR), representing functional associations that are of strengths similar to those between well-studied protein interactions. Among these functional interactions, 57% may represent protein interactions, which are expected to cover 32% of the true human protein interactome. The gene set linkage analysis (GSLA) tool is developed based on the high-quality HIR V2 to identify the potential functional impacts of the observed transcriptomic changes, helping to elucidate their biological significance and complementing the currently widely used enrichment-based gene set interpretation tools. A case study shows that the annotations reported by the HIR V2/GSLA system are more comprehensive and concise compared to those obtained by the widely used gene set annotation tools such as PANTHER and DAVID. The HIR V2 and GSLA are available at http://human.biomedtzc.cn., (© The Author(s) 2021. Published by Oxford University Press.)

CsPbX 3 (X = Cl, Br, and I) quantum dots (QDs) and Cu 2+ -doped CsPbCl 3 QDs with different Cu-to-Pb molar ratios were synthesized via a solvent-based thermal synthesis method. The photoluminescence (PL) properties of these Cu 2+ -doped CsPbCl 3 QDs were also investigated in this study. The results showed that with the increase in the Cl - concentration the surface defects of CsPb(Cl/Br) 3 QDs increased, which resulted in an increase in the non-radiative recombination of excitons and weakened the PL intensity. Moreover, Cu 2+ -doped CsPbCl 3 QDs maintained the cubic crystal structure of the initial phases. Owing to the doping of Cu 2+ ions, the surface defects of CsPbCl 3 QDs were effectively eliminated, which facilitated the excitonic recombination via a radiative pathway. The PL quantum yields (PLQYs) of Cu 2+ -doped CsPbCl 3 QDs were increased to 51%, showing great photostability. From the results, it is believed that Cu:CsPbCl 3 QDs can be widely used in optoelectronic devices., Competing Interests: The authors have declared that no conflicting interests exist., (This journal is © The Royal Society of Chemistry.)

The bHLH transcription factors play pivotal roles in plant growth and development, production of secondary metabolites and responses to various environmental stresses. Although the bHLH genes have been well studied in model plant species, a comprehensive investigation of the bHLH genes is required for tobacco with newly obtained high-quality genome. In the present study, a total of 309 NtbHLH genes were identified and can be divided into 23 subfamilies. The conserved amino acids which are essential for their function were predicted for the NtbHLH proteins. Moreover, the NtbHLH genes were conserved during evolution through analyzing the gene structures and conserved motifs. A total of 265 NtbHLH genes were localized in the 24 tobacco chromosomes while the remained 44 NtbHLH genes were mapped to the scaffolds due to the complexity of tobacco genome. Moreover, transcripts of NtbHLH genes were obviously tissue-specific expressed from the gene-chip data from 23 tobacco tissues, and expressions of 20 random selected NtbHLH genes were further confirmed by quantitative real-time PCR, indicating their potential functions in the plant growth and development. Importantly, overexpressed NtbHLH86 gene confers improve drought tolerance in tobacco indicating that it might be involved in the regulation of drought stress. Therefore, our findings here provide a valuable information on the characterization of NtbHLH genes and further investigation of their functions in tobacco., Competing Interests: The authors declare no conflict of interest., (© 2021 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

The effect of Ti and B microalloying on the hardenability, prior austenite grain size (PAGS), mechanical properties, and sulfide stress cracking (SSC) of C110 grade steel was studied by Jominy testing, static tensile testing, an optical microscope (OM), scanning electron microscopy (SEM) and double cantilever beam (DCB) testing. The results show that the addition of 0.015% Ti and 0.002% B into a medium-carbon Fe-Cr-Mo-Nb-V steel increased the hardenability and refined the PAGS and quenched martensite packets, and the size of carbides was reduced. It is believed that these behaviors are responsible for the improvement in the threshold stress intensity factor K ISSC .