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Xue-hua Xu,1,* Jie-rong Cai,2,* Hui-feng Fan,1,* Ting-ting Shi,1 Di-yuan Yang,1 Li Huang,3 Dong-wei Zhang,1 Gen Lu1 1Department of Respiratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pediatrics, Guangzhou Panyu District Central Hospital, Guangdong, Guangdong, People’s Republic of China; 3Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gen Lu, Department of Respiratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China, Tel +86 20 38076135, Fax +86 20 38076626, Email lugen5663330@sina.comPurpose: Plastic bronchitis (PB), a rare complication of respiratory infection characterized by the formation of casts in the tracheobronchial tree, can lead to airway obstruction and severe condition. Adenovirus is one of the common pathogens of PB caused by infection. This study aimed to evaluate the clinical features and risk factors for PB in children with severe adenovirus pneumonia.Methods: A retrospective study of children with severe adenovirus pneumonia with bronchoscopy results at Guangzhou Women and Children’s Hospital between January 2018 and January 2020 was performed. Based on bronchoscopy, we divided children with severe adenovirus pneumonia into two groups: PB and non-PB. Binary logistic regression analysis was used to identify independent risk factors for PB in patients with severe adenovirus pneumonia after univariate analysis.Results: Our study examined 156 patients with severe adenovirus pneumonia with bronchoscopy results in hospital. Among them, 18 developed PB and 138 did not. On multivariate analysis, the independent risk factors of PB in children with severe adenovirus pneumonia were history of allergies (OR 10.147, 95% CI 1.727– 59.612; P=0.010), diminished breath sounds (OR 12.856, 95% CI 3.259– 50.713; P=0.001), and increased proportion of neutrophils (> 70%; OR 8.074, 95% CI 1.991– 32.735; P=0.003).Conclusion: Children with severe adenovirus pneumonia with a history of allergies, diminished breath sounds, and increased the proportion of neutrophils > 70% may show higher risk of PB.Keywords: plastic bronchitis, severe adenovirus pneumonia, risk factors, children

The quinazoline scaffold serves as a fundamental framework, demonstrating potent anti-tumor activity. Employing the pharmacophore-based scaffold hopping principle, we successfully synthesized a series of FAK/PLK1 inhibitors incorporating the quinazoline scaffold. The synthesized compounds were characterized using 1 H NMR, 13 C NMR, and HRMS techniques. Through computer-assisted screening and antitumor activity tests, the majority of the compounds demonstrated significant inhibitory effects against various cancer cell lines. Notably, compound 3m exhibited remarkable anticancer activity by inducing G2/M phase cell cycle arrest, apoptosis, as confirmed by western blot assay, cellular fluorescence staining, and transcriptomics testing. Docking simulation was performed to determine the probable binding conformation of compound 3m within the active sites of FAK and PLK1. This compound emerged as a highly promising lead compound during our screening process, displaying high efficiency., Competing Interests: Declarations. Conflict of interest: The authors have affirmed that they do not have any financial or interpersonal conflicts that would have impacted to influence the presented and discussed work in this paper. The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in childhood. There is growing evidence that both preterm birth and maternal education levels substantially affect the likelihood of ADHD in children. However, there are limited systematic reviews and meta-analyses examining these associations., Aim: To systematically review and conduct a meta-analysis on the association of preterm birth and maternal education level on the risk of ADHD in children., Methods: We conducted a comprehensive literature search across MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library, including studies published up to June 17, 2024. Data synthesis was performed using random-effect models, and the quality of studies was assessed using the Newcastle-Ottawa Scale., Results: This study included twelve studies, which revealed a significant association between premature delivery and an increased risk of ADHD in children [odds ratio (OR) = 2.76, 95% confidence interval (CI): 2.52-3.04, P < 0.001, I² = 1.9%). Conversely, higher maternal education levels were significantly associated with a reduced risk of ADHD in children (OR = 0.59, 95%CI: 0.48-0.73, P < 0.001, I² = 47.1%). Subgroup analysis further indicated that maternal education levels significantly influenced ADHD risk, particularly in studies conducted in China (OR = 0.59, 95%CI: 0.46-0.75, P < 0.001, I² = 81.2%), while no significant association was observed in studies from other regions (OR = 1.25, 95%CI: 0.66-2.40, P = 0.495, I² = 92.3%). The sensitivity analysis confirmed the robustness of our findings, showing no significant publication bias., Conclusion: This study found that preterm birth significantly increases the risk of ADHD in children, while a higher maternal education level serves as a protective factor against ADHD. To reduce the incidence of ADHD in children, public health policies should focus on early intervention for preterm infants and improving maternal education levels., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Due to it containing cellulose, hemicellulose, and lignin with abundant specific functional groups which could interact with organic dyes, garlic peel (GP) might be used as an efficient biosorbent. The aim of this study is to evaluate the adsorption performances of GP-based bio-adsorbents and obtain optimum preparation conditions., Methods: GP-based bio-adsorbents were prepared by thermal pyrolysis under different temperatures (150-400 °C). The morphologies, chemical states, and surface functional groups of the adsorbents were analyzed by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). Batch experiments were conducted to investigate the adsorption of methylene blue (MB) under various conditions, including contact time, contact temperature, initial dye concentration, and initial pH value. The equilibrium adsorption data were fitted to different kinetic and isothermal models, and the adsorption thermodynamics were also calculated. Significant Findings: The physicochemical properties of the GP-based bio-adsorbents were primarily dominated by the pyrolysis temperature, because their morphologies and surface functional groups of GP-based bio-adsorbents significantly varied with the changes in pyrolysis temperature. The adsorption capacity of GP materials for MB decreased as the pyrolysis temperature increased. At an initial concentration of 50.00 mg L -1 , GP150 possessed a higher adsorption capacity of 167.74 mg g -1 toward MB. The possible adsorbate-adsorbent interactions, including electrostatic attraction, hydrogen bonding, and π-π stacking, were recognized. After 10 consecutive adsorption-desorption cycles, GP150 maintained a high removal rate (88%) for MB, demonstrating its excellent adsorption performance, good reusability, and potential application in the treatment of MB-contaminated water.

Pregnancy requires metabolic adaptations in order to meet support fetal growth with nutrient availability. In this study, the influence of pregnancy on metabolically active organs (adipose tissues in particular) was investigated. Our results showed that maternal weight and adipose mass presented dynamic remodeling in the periparturient mice. Meanwhile, pregnancy mice displayed obvious glucose intolerance and insulin resistance in late pregnancy as compared to non-pregnancy, which were partially reversed at parturition. Further analyses revealed that different fat depots exhibited site-specific adaptions of morphology and functionality as pregnancy advanced. Brown and inguinal white adipose tissue (BAT and IngWAT) exhibited obviously decreased thermogenic activity; by contrast, gonadal white adipose tissue (GonWAT) displayed remarkably increased lipid mobilization. Notably, we found that mammary gland differentiation was enhanced in IngWAT, followed by BAT but not in GonWAT. These result indicated that brown and white adipose tissues might synergistically play a crucial role in maintaining the maximum of energy supply for mother and fetus, which facilitates the mammary duct luminal epithelium development as well as the growth and development of fetus. Accompanied with adipose adaptation, however, our results revealed that the liver and pancreas also displayed significant metabolic adaptability, which together tended to trigger the risk of maternal metabolic diseases. Importantly, pregnancy-dependent obesity in our mice model resembled the disturbed metabolic phenotypes of pregnant women such as hyperglyceridemia and hypercholesterolemia. Our findings in this study could provide valuable clues for better understanding the underlying mechanisms of metabolic maladaptation and facilitate the development of the prevention and treatment of metabolic diseases.

The capsule-associated protein 10 gene ( CAP10 ) is indispensable due to its involvement in pod formation and virulence maintenance in Cryptococcus neoformans . The function of the CAP10 gene in nematode-predatory fungi remains unreported. As a typical nematode-trapping fungus, Dactylellina haptotyla efficiently captures nematodes using adhesive knobs, which has potential applications in the biological control of plant-parasitic nematodes. In this study, we investigated the function of DHXT1 (a CAP10 homologous protein) in D. haptotyla -nematode interactions based on the disruption and overexpression of DHXT1 , phenotypic analysis and metabolomic analysis. As a result, it was shown that the disruption of the DHXT1 gene causes a marked decrease in the number of adhesive knobs, and on the contrary, the overexpression of the DHXT1 gene causes a substantial increase in the number of adhesive knobs. Interestingly, the variety of metabolites increased with the disruption of the DHXT1 and decreased with the overexpression of the DHXT1 gene. The results suggest that DHXT1 effects pathogenicity through its involvement in adhesive knobs' formation and metabolite synthesis and serves as a key virulence factor in D. haptotyla .

The aim of this study was to investigate the potential mechanism by which cryptotanshinone(CTS) may exert its anti-myo-cardial ischemic effect through the regulation of macrophage polarization via the dendritic cell-associated C-type lectin 1(Dectin-1) signaling pathway. Male C57BL/6 mice, aged six weeks, were utilized to establish myocardial ischemia models and were subsequently divided into five groups: sham, model, CTS low-dose(21 mg·kg~(-1)·d~(-1)), CTS high-dose(84 mg·kg~(-1)·d~(-1)), and dapagliflozin(0.14 mg·kg~(-1)·d~(-1)). The cardiac function, serum enzyme levels, Dectin-1 expression, macrophage polarization, and neutrophil infiltration in the myocardial infarction area were assessed in each group. An in vitro model of M1-type macrophages was constructed using lipopolysaccharide/interfe-ron-γ(LPS/IFN-γ) stimulated RAW264.7 cells to investigate the impact of CTS on macrophage polarization and to examine alterations in key proteins within the Dectin-1 signaling pathway. In the CTS group, compared to the model group mice, there was a significant improvement in the cardiac function and myocardial injury, along with a notable increase in the ratio of M2/M1-type macrophages in the myocardial infarcted area and a decrease in neutrophil infiltration. Additionally, Dectin-1 exhibited low expression. The results of in vitro experiments demonstrated that CTS can decrease the expression of M1-type marker genes and increase the expression of M2-type marker genes. Besides, it can decrease the levels of Dectin-1 and the phosphorylation of its associated proteins, including spleen tyrosine kinase(Syk), protein kinase B(Akt), nuclear factor-kappaB p65(NF-κB p65), and extracellular signal-regulated protein kinases(ERK1/2). Additionally, CTS was found to enhance the phosphorylation of signal transducer and activator of transcription-6(STAT6). The above results suggest that CTS exerts its anti-myocardial ischemic injury effect by regulating macrophage polarization through the Dectin-1 signaling pathway.

Objective: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of K ATP depolarization and K + repolarization. It is well known that glucose stimulates insulin secretion from pancreatic β-cells, mainly via the K ATP depolarization channel, but whether other nutrients directly regulate the repolarization K + channel to promote insulin secretion is unknown., Methods: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K + channels and scRNA-seq in a pancreatic β cell line to identify genes associated with insulin secretion., Results: The expression levels of insulin genes were significantly increased after all-K + channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K + channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with β-cell-specific deletion of Kcnh6., Conclusions: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel., Competing Interests: Declaration of competing interest All authors declared that no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Globally, liver cancer ranks among the most lethal cancers, with chemotherapy being one of its primary treatments. However, poor selectivity, systemic toxicity, a narrow treatment window, low response rate and multidrug resistance limit its clinical application. Liver-targeted nanoparticles (NPs) exhibit excellent targeted delivery ability and promising effectivity in treating liver cancer. The present study aimed to investigate the liver-targeting and anti-liver cancer effect of artesunate (ART)-loaded and glycyrrhetinic acid (GA)-decorated polyethylene glycol (PEG)-poly (lactic-co-glycolic acid) (PLGA) (ART/GA-PEG-PLGA) NPs. GA-coated NPs significantly increased hepatoma-targeted cellular uptake, with micropinocytosis and caveolae-mediated endocytosis as its chief internalization pathways. Moreover, ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells, mainly via the induction of a high level of reactive oxygen species, decline in mitochondrial membrane potential and induction of cell cycle arrest. Additionally, ART/GA-PEG-PLGA NPs induced internal apoptosis pathways by upregulating the activity of cleaved caspase-3/7 and expression of cleaved poly (ADP-Ribose)-polymerase and Phos-p38 mitogen-activated protein kinase in HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Finally, ART/GA-PEG-PLGA NPs promoted the liver-targeting distribution of ART, increased the retention time and promoted its antitumour effects in vivo . Therefore, ART/GA-PEG-PLGA NPs afforded excellent hepatoma-targeted delivery and anti-liver cancer efficacy, and thus, they may be a promising strategy for treating liver cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Pan et al.)

Pattern recognition receptor-mediated innate immunity is critical for host defense against viruses. A growing number of coding and noncoding genes are found to encode microproteins. However, the landscape and functions of microproteins in responsive to virus infection remain uncharacterized. Here, we systematically identified microproteins that are responsive to vesicular stomatitis virus infection. A conserved and endoplasmic reticulum-localized membrane microprotein, MAVI1 (microprotein in antiviral immunity 1), was found to interact with mitochondrion-localized MAVS protein and inhibit MAVS aggregation and type I interferon signaling activation. The importance of MAVI1 was highlighted that viral infection was attenuated and survival rate was increased in Mavi1- knockout mice. A peptide inhibitor targeting the interaction between MAVI1 and MAVS activated the type I interferon signaling to defend viral infection. Our findings uncovered that microproteins play critical roles in regulating antiviral innate immune responses, and targeting microproteins might represent a therapeutic avenue for treating viral infection.

Inner Mongolia autonomous region of China and Mongolia are the primary regions where Chinese and Mongolian medicine and its medicinal plant resources are distributed. In this study, 133 families, 586 genera, and 1 497 species of medicinal plants in Inner Mongolia as well as 62 families, 261 genera, and 467 species of medicinal plants in Mongolia were collected through field investigation, specimen collection and identification, and literature research. And the species, geographic distribution, and influencing factors of the above medicinal plants were analyzed. The results revealed that there were more plant species utilized for medicinal reasons in Inner Mongolia than in Mongolia. Hotspots emerged in Hulunbuir, Chifeng, and Tongliao of Inner Mongolia, while there were several hotspots in Eastern province, Sukhbaatar province, Gobi Altai province, Bayankhongor province, Middle Gobi province, Kobdo province, South Gobi province, and Central province of Mongolia. The interplay of elevation and climate made a non-significant overall contribution to the diversity of plant types in Inner Mongolia and Mongolia. The contribution of each factor increased significantly when the vegetation types of Inner Mongolia and Mongolia were broadly divided into forest, grassland and desert. Thus, the distribution of medicinal plant resources and vegetation cover were jointly influenced by a variety of natural factors such as topography, climate and interactions between species, and these factors contributed to and constrained each other. This study provided reference for sustainable development and rational exploitation of medicinal plant resources in future.

Cerebrospinal fluid (CSF) is an important sample source for diagnosing diseases in the central nervous system (CNS), but collecting and injecting CSF in small animals is technically challenging and often results in high mortality rates. Here, we present a cost-effective and efficient method for accessing the CSF in live rodents for fluid collection and infusion purposes. The key element of this protocol is a metal needle tool bent at a unique angle and length, allowing the successful access of the CSF through the foramen magnum. With this method, we can collect 5-10 µL of the CSF from mice and 70-100 µL from rats for downstream analyses, including mass spectrometry. Moreover, our minimally-invasive procedure enables iterative CSF collection from the same animal every few days, representing a significant improvement over prior protocols. Additionally, our method can be used to inject solutions into mice cisterna magna with high success rates and high postoperative recovery rates. In summary, we provide an efficient and minimally-invasive protocol for collecting and infusing reagents into the CSF in live rodents. We envision this protocol will facilitate biomarker discovery and drug development for diseases in the central nervous system.

Background: Human adenovirus (HAdV) is one of the most common viruses causing respiratory infections among young children. Most adenovirus infections are mild and self-limited; however, these infections may occasionally cause severe pneumonia and even death. The mortality risk factors for severe adenovirus pneumonia are not completely clear. This study aimed to evaluate the mortality risk factors in children with severe adenovirus pneumonia., Methods: A retrospective study of children with severe adenovirus pneumonia hospitalized in Guangzhou Women and Children's Hospital between July 2018 and January 2020 was performed. Binary logistic regression analysis was used to identify independent mortality risk factors for severe adenovirus pneumonia after univariate analysis., Results: Our study included 189 patients (123 males and 66 females). Among them, 13 patients did not survive with a mortality of 6.88%. In multivariate analysis, the independent mortality risk factors in children with severe adenovirus pneumonia were age less than 1 year (OR = 18.513, 95% CI: 2.157-158.883, p = 0.008), hypoxia (OR = 62.335, 95% CI: 2.385-1629.433, p = 0.013), and thrombocytopenia (platelet <100∗10ˆ9/L) (OR = 13.324, 95% CI: 1.232-144.075, p = 0.033)., Conclusions: In children with severe adenovirus pneumonia who are younger than one year old, hypoxia and platelet counts less than 100∗10ˆ9/L represent mortality risk factors., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and that there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The design and preparation of cheaper, greener and more efficient adsorbents is essential for the removal of pollutants by adsorption. In this study, biochar was prepared from peel of Brassica juncea var. gemmifera Lee et Lin (PoBJ) using a facile, low-temperature and vacuum pyrolysis, and the adsorption mechanism toward organic dyes in aqueous solution was elucidated. The adsorbent was characterized by XPS, FT-IR and SEM, and zeta potential techniques. The adsorption ability of PoBJ biochar for cationic dyes (methylene blue, brilliant green, calcein-safranine, azure I, rhodamine B), anionic dyes (alizarin yellow R), and neutral dyes (neutral red) revealed that the biochar exhibited adsorption selectivity toward cationic dyes. The effects of different factors on the adsorption performance of PoBJ biochar, as well as the adsorption kinetics and thermodynamics, were further investigated by using methylene blue as the model adsorbate. These factors included temperature, pH, contact time and dye concentration. The experimental results showed that BJ280 and BJ160 (prepared at 280 °C and 160 °C, respectively) possessed relatively higher adsorption capacity of 192.8 and 167.40 mg g -1 for methylene blue (MB), respectively, demonstrating the possibility of utilization of PoBJ biochar as a superior bio-adsorbent. The experimental data of BJ160 toward MB were correlated with various kinetic and isothermal models. The results indicated that the adsorption process was consistent with the Langmuir isotherm model and nonlinear pseudo-second-order kinetic model. Thermodynamic parameters indicated that the adsorption of MB onto BJ160 was exothermic. Thus, the low-temperature prepared PoBJ biochar was an environmentally friendly, economic and efficient cationic dye adsorbent.

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by the reduction of both CD4+ CTLs and the reduction of orbital inflammation, adipogenesis, and fibrosis. CD4+ CTLs from patients with active GO showed upregulation of the mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and the clinical activity score in steroid-refractory patients with GO. Single-cell RNA-Seq revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

Inducing clear ferroelectricity in the quantum paraelectric SrTiO 3 is important for triggering methods to discover hidden phases in condensed matter physics. Several methods such as isotope substitution and freestanding membranes could introduce ferroelectricity in SrTiO 3 toward nonvolatile memory applications. However, the stable transformation from quantum paraelectric SrTiO 3 to ferroelectricity SrTiO 3 at room temperature still remains challenging. Here, we used multiple nano-engineering in (SrTiO 3 ) 0.65 /(CeO 2 ) 0.35 films to achieve an emergent room-temperature ferroelectricity. It is shown that the CeO 2 nanocolumns impose large out-of-plane strains and induce Sr/O deficiency in the SrTiO 3 matrix to form a clear tetragonal structure, which leads to an apparent room-temperature ferroelectric polarization up to 2.5 μC/cm 2 . In collaboration with density functional theory calculations, it is proposed that the compressive strains combined with elemental deficiency give rise to local redistribution of charge density and orbital order, which induce emergent tetragonality of the strained SrTiO 3 . Our work thus paves a pathway for architecting functional systems in perovskite oxides using a multiple nano-design.

Plant-pathogenic fungi are responsible for many of the most severe crop diseases in the world and remain very challenging to control. Improving current protection strategies or designating new measures based on an overall understanding of molecular host-pathogen interaction mechanisms could be helpful for disease management. The attachment and penetration of the plant surface are the most important events among diverse plant-fungi interactions. Fungi evolved as small but incredibly powerful infection structure appressoria to facilitate attachment and penetration. Appressoria are indispensable for many diseases, such as rusts, powdery mildews, and blast diseases, as well as devastating oomycete diseases. Investigation into the formation of plant-pathogen appressoria contributes to improving the understanding of the molecular mechanisms of plant-pathogen interactions. Fungal host attachment is a vital step of fungal pathogenesis. Here, we review recent advances in the molecular mechanisms regulating the formation of appressoria. Additionally, some biocontrol agents were revealed to act on appressorium. The regulation of fungal adhesion during the infective process by acting on appressoria formation is expected to prevent the occurrence of crop disease caused by some pathogenic fungi.

Objective: The present study aims to investigate the alterations of serum proteomic and metabolomic profiles in Chinese patients with severe and active Graves' Orbitopathy (GO)., Materials and Methods: Thirty patients with GO and 30 healthy volunteers were enrolled. The serum concentrations of FT3, FT4, T3, T4, and thyroid-stimulating hormone (TSH) were analyzed, after which TMT labeling-based proteomics and untargeted metabolomics were performed. Metabo- Analyst and Ingenuity Pathway Analysis (IPA) was used for integrated network analysis. A nomogram was established based on the model to explore the disease prediction ability of the identified feature metabolites., Results: One hundred thirteen proteins (19 up-regulated and 94 down-regulated) and 75 metabolites (20 increased and 55 decreased) were significantly altered in GO compared to the control group. By combining the lasso regression, IPA network, and protein-metabolite-disease sub-networks, we extracted feature proteins (CPS1, GP1BA, and COL6A1) and feature metabolites (glycine, glycerol 3-phosphate, and estrone sulfate). The logistic regression analysis revealed that the full model with the prediction factors and three identified feature metabolites had better prediction performance for GO compared to the baseline model. The ROC curve also indicated better prediction performance (AUC = 0.933 vs. 0.789)., Conclusion: A new biomarker cluster combined with three blood metabolites with high statistical power can be used to discriminate patients with GO. These findings provide further insights into the pathogenesis, diagnosis, and potential therapeutic targets for this disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves' ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis., 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 Shi, Zhao, Xin, Hou, Wang, Xie, Li and Yang.)

Mutations in KCNH6 has been proved to cause hypoinsulinemia and diabetes in human and mice. Cisapride is a stomach-intestinal motility drug used to treat gastrointestinal dysfunction. Cisapride has been reported to be a potential inhibitor of the KCNH family, but it remained unclear whether cisapride inhibited KCNH6. Here, we discovered the role of cisapride on glucose metabolism, focusing on the KCNH6 potassium channel protein. Cisapride reduced blood glucose level and increased serum insulin secretion in wild-type (WT) mice fed standard normal chow/a high-fat diet or in db/db mice, especially when combined with tolbutamide. This effect was much stronger after 4 weeks of intraperitoneal injection. Whole-cell patch-clamp showed that cisapride inhibited KCNH6 currents in transfected HEK293 cells in a concentration-dependent manner. Cisapride induced an increased insulin secretion through the disruption of intracellular calcium homeostasis in a rat pancreatic β-cell line, INS-1E. Further experiments revealed that cisapride did not decrease blood glucose or increase serum insulin in KCNH6 β-cell knockout (Kcnh6-β-KO) mice when compared with WT mice. Cisapride also ameliorated glucose-stimulated insulin secretion (GSIS) in response to high glucose in WT but not Kcnh6-β-KO mice. Thus, our data reveal a novel way for the effect of KCNH6 in cisapride-induced hypoglycemia., 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 Lu, Shi, Yuan, Xie, Zhao, Zhu and Yang.)

Manipulating ferroic orders and realizing their coupling in multiferroics at room temperature are promising for designing future multifunctional devices. Single external stimulation has been extensively proved to demonstrate the ability of ferroelastic switching in multiferroic oxides, which is crucial to bridge the ferroelectricity and magnetism. However, it is still challenging to directly realize multi-field-driven magnetoelectric coupling in multiferroic oxides as potential multifunctional electrical devices. Here, novel magneto-electric-optical coupling in multiferroic BiFeO 3 -based thin films at room temperature mediated by deterministic ferroelastic switching using piezoresponse/magnetic force microscopy and aberration-corrected transmission electron microscopy are shown. Reversible photoinduced ferroelastic switching exhibiting magnetoelectric responses is confirmed in BiFeO 3 -based films, which works at flexible strain states. This work directly demonstrates room-temperature magneto-electric-optical coupling in multiferroic films, which provides a framework for designing potential multi-field-driven magnetoelectric devices such as energy conservation memories., (© 2022 Wiley-VCH GmbH.)

Purpose: To compare the dosimetric differences between intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in the treatment of male and female thymoma., Material and Methods: This single-institutional analysis included 20 patients with thymoma treated with RT between January 2017 and December 2020. Twenty patients were retrospectively planned for IMRT (IMRT1 with an average field angle of 216°, 288°, 0°, 72°,and 144°; IMRT2 with fan-shaped field angles of 280°, 320°, 0°, 40°, and 80°) and VMAT (VMAT1 with two arcs ranging form 280° to 80°,clockwise and then counterclockwise; VMAT2 with two 360° arcs). The plans for all investigated RT modalities were optimized for a prescriptional dose of 50Gy and fractional dose of 2.0Gy. Planning target volume (PTV) and organs-at-risk (OARs: heart, breasts, lungs, spinal cord, and esophagus) dosimetric parameters were compared., Results: All plans met the preparation aims for all the included metrics. There was little difference in the median values of PTV parameters (D 2% , D 98% , D mean , homogeneity index[HI], and conformity index [CI]). The CI of the VMAT2 plan was the closest to 1 in both therapy groups. The monitor unit (MU) of IMRT2 and the estimated total delivery time of VMAT1 were the lowest in both therapy groups and were statistically significant. In the male group, the lung parameters (D mean , V 5Gy , V 10Gy , and V 20Gy ) for VMAT1 were the lowest and showed statistical significance. In the female group, the lung parameters (D mean , V 5Gy , V 10Gy , and V 20Gy ) and bilateral breast parameters (Dmean, V 5Gy , V 10Gy , and V 20Gy ) of IMRT2 were the lowest and showed statistical significance., Conclusions: In male thymoma patients undergoing postoperative RT (PORT) treatment, the choice of fan-shaped VMAT may be a better option for protecting the lungs. For female thymoma patients receiving PORT, fan-shaped IMRT can better protect the lungs and breasts. The fan-shaped field performed better than the average and the full arc fields in PORT for thymoma., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Inflammatory cytokines contribute to the development of osteoporosis with sophisticated mechanisms. Globally alteration of long-chain non-coding RNA was screened in osteoporosis, while we still know little about their functional role in the inflammatory cytokine secretion. In this study, we collected the peripheral blood mononuclear cells (PBMCs) from post-menopausal osteoporosis patients to measure lncRNA MIAT (lncMIAT) expression levels, and explored the molecular mechanism of lncMIAT induced inflammatory cytokine secretion. We identified increased lncMIAT expression in the PBMCs of post-menopausal osteoporosis patients, which was an important predictive biomarker for the diagnosis. LncMIAT expression in PBMCs was positively correlated with the inflammatory cytokine secretion. Mechanism study indicated that lncMIAT increased the expression levels of p38MAPK by crosstalk with miR-216a in PBMCs. The lncMIAT/miR-216a/p38MAPK signaling contributed predominantly to the increased inflammatory cytokine secretion in the PBMCs from postmenopausal osteoporosis. In conclusion, we identified that increased lncMIAT in PBMCs induced inflammatory cytokine secretion, which contributed to the development of post-menopausal osteoporosis. lncMIAT/miR-216a axis was critical for the regulation of AMPK/p38MAPK signaling, which may be a promising therapeutic target for osteoporosis treatment by inflammatory cytokine inhibition.

Objective: To understand the incidence trend of liver cancer in China from 2005 to 2016, and explore the correlation between the incidence trend of liver cancer and the incidence trend of hepatitis B. Methods: The incidence data of liver cancer in China from 2005 to 2016 were collected from the Annual Report of Cancer Registry in China. The incidence data of hepatitis B were collected from China Public Health Science Data Center. World standardized incidence rate (WSR) was calculated according to the World Segi's population. Joinpoint regression model was used to analyze the trend of WSR of liver cancer [measured by average annual percentage change (AAPC)]. The age-period-cohort model was fitted to analyze the age, period and cohort effects in people aged 20- years and above. Pearson correlation coefficient was used to explore the correlation between the incidence of liver cancer and the incidence of hepatitis B. Results: The crude incidence of liver cancer in China showed a trend of first increase before 2009 and then relatively stable. The world standardized morbidity rate of liver cancer in China decreased from 19.11 per 100 000 in 2005 to 17.74 per 100 000 in 2016 (AAPC=-0.5%, 95% CI : -1.3%-0.3%, P =0.240). The incidence of liver cancer in male decreased significantly (AAPC=-1.0%, 95% CI : -1.5%--0.5%, P =0.001). The incidence of liver cancer in women increased from 2005 to 2010 [annual percentage change (APC)=1.7%, 95% CI : -0.1%-3.4%, P =0.059] but showed a significant decrease trend from 2010 to 2016 (APC=-1.6%, 95% CI : -2.3%--1.0%, P =0.001). From 2005 to 2016, the incidence of liver cancer showed a decreasing trend in urban areas (AAPC=-0.3%, 95% CI : -0.8%-0.3%, P =0.316) and rural areas (AAPC=-3.9%, 95% CI : -4.4%--3.3%, P <0.001). Risk for liver cancer increased with age, while the period effect showed a trend of first increase then decrease and cohort effect showed a decrease trend. The morbidity rates of both hepatitis B and liver cancer showed decrease trends from 2009 to 2016, and there was a significant correlation ( r =0.71, 95% CI : 0.01-0.94, P =0.048). Conclusions: From 2005 to 2016, the morbidity rate of liver cancer in China showed a decrease trend, and there were significant gender and urban-rural area specific differences. Age effect had a great impact on the risk for liver cancer. With the progress of population aging in China, liver cancer is still a public health problem, to which close attention needs to be paid.

Ferroelectric ultrathin films have great potential in electronic devices and device miniaturization with the innovation of technology. In the process of product commercialization, understanding the domain evolution and topological properties of ferroelectrics is a prerequisite for high-density storage devices. In this work, a series of ultrathin PbTiO 3 (PTO) films with varying thicknesses were deposited on cubic KTaO 3 substrates by pulsed laser deposition and were researched by Cs-corrected scanning transmission electron microscopy (STEM), reciprocal space mapping (RSM), and piezoresponse force microscopy (PFM). RSM experiments indicate the existence of a / c domains and show that the lattice constant varies continuously, which is further confirmed by atomic-scale STEM imaging. Diffraction contrast analysis clarifies that with the decrease in PTO film thickness, the critical thickness for the formation of a / c domains could be missing. When the thickness of PTO films is less than 6 nm, the domain configurations in the ultrathin PTO films are the coexistence of a / c domains and bowl-like topological structures, where the latter ones were identified as convergent and divergent types of meron. In addition, abundant 90° charged domain walls in these ultrathin PTO films were identified. PFM studies reveal clear ferroelectric properties for these ultrathin PTO films. These results may shed light on further understanding the domain evolution and topological properties in ultrathin ferroelectric PTO films.

Background: Graves' orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include Clinical Activity Score (CAS), CT, and MRI. These approaches are mainly associated with orbital muscles; however, there are not many studies that focus on the lacrimal gland inflammation of GO patients., Objective: The aim of this study is to assess the usefulness of 99mTc-DTPA single-photon emission (SPE) CT/CT in evaluating the lacrimal gland inflammation in GO, as compared with other methods., Methods: A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical-endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed., Results: The lacrimal glands in patients with GO were significantly larger in all measured dimensions (P < 0.001) on CT scans relative to those in controls. Increased lacrimal gland diethylene triamine pentaacetic acid (DTPA) uptake ratios (P < 0.001) were displayed in active GO patients compared to controls and were also correlated with thyrotropin receptor antibody levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients., Conclusions: These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas1 receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. Ace2 knockout mice ( Ace2 -/y ) and Mas1 knockout mice ( Mas1 -/- ) displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from Mas1 -/- display metabolic abnormalities consistent with those seen in the Ace2 and Mas1 knockout mice. In contrast, impaired thermogenesis of Lepr db/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of Ace2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids, and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel potential therapeutic targets for the treatment of metabolic disorders., Competing Interests: XC, TS, CZ, WJ, LS, YZ, JL, FY, CR, AX, JY No competing interests declared

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cervical cancer is a common gynecological cancer among women worldwide., Objective: To determine the effects of 6 MV and 10 MV volumetric-modulated arc therapy (VMAT) photon beams on the target volume (TV) planning and critical organs in cases of cervical cancer., Methods: Fifty patients with carcinoma of the cervix who underwent radiotherapy were selected. The transverse diameter (T) of the cross section of the upper edge of the sacroiliac joint on computerized tomography (CT) images of the patients was measured, and the mean value was calculated as 34 cm. All patients were divided into two groups: Group A (T < 34 cm) and Group B (T > 34 cm). The VMAT plans were generated using 6 MV and 10 MV plans separately. The prescription dose was 47.5 Gy, and the daily dose was 1.9 Gy., Results: In Group A, the planning target volume (PTV) dose assessment parameters of 6 MV and 10 MV plans and their homogeneity and conformity indices were not statistically significantly different. A significant difference was observed between the 6 MV and 10 MV plans for the PTV dose assessment parameters and the homogeneity index of the plans for Group B. The monitor units (MUs) of the 10 MV plans were lower than in the 6 MV plans in both Groups A and B, and the difference was statistically significant. The assessment parameter V40 Gy of both the rectum and bladder in the 6 MV plans was smaller than the corresponding parameter in the 10 MV plans in Group A; in Group B, the assessment parameter V50 Gy of the rectum in the 10 MV plans was smaller than in the 6 MV plans., Conclusion: When T < 34 cm, 6 MV energy is more suitable for the external irradiation of cervical cancer. When T > 34 cm, 10 MV energy is more suitable for cervical cancer radiotherapy. Therefore, 10 MV should be considered for patients with a large abdominal size.

Background: Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia., Methods: This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1-9 days of the illness course) and the late BAL layer (received BAL within 10-14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups., Results: Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p < 0.05). However, in the severe group, there were no statistically significant differences in the fever and hospital duration between patients who received BAL early and those who received BAL later. However, the need for mechanical ventilation and the incidence of BAL complications, such as new need for oxygen, were higher in patients who received BAL early than in those who received BAL later in the severe group (p < 0.05)., Conclusion: For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications., (© 2021. The Author(s).)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common global chronic liver disease. Jiuzhuan Huangjing Pills (JHP) have been used for the treatment of human disease for over a thousand years, but their efficacy and underlying mechanism(s) of action against MAFLD are unknown. We investigated the alleviating effects of JHP on high-fat diet (HFD)-induced MAFLD., Methods: In vitro and in vivo methods were used to evaluate the effects of JHP on MAFLD. L02 adipocyte models were induced by fat emulsion and adipocytes were treated with JHP for 24 h. MAFLD rat models were induced by HFD-feeding and were intragastrically administered JHP for 12 weeks. Changes in fat accumulation, L02 cell damage, body weight, food intake, histological parameters, organ indexes, biochemical parameters, and mitochondrial indicators including ultrastructure, oxidative stress, energy metabolism, and fatty acid metabolism were investigated., Results: JHP attenuated the increase in levels of total cholesterol, triglyceride, low density lipoprotein cholesterol, alanine transaminase, and aspartate transaminase levels, and significantly increased high density lipoprotein cholesterol. JHP up-regulated levels of glutathione (GSH) and superoxide dismutase (SOD), and down-regulated malondialdehyde (MDA). JHP afforded protection to the mitochondrial ultrastructure, and inhibited the HFD-induced increase in MDA and the reduction of SOD, GSH, ATP synthase, and complex I and II, in liver mitochondria. JHP regulated the expression of β-oxidation genes, including acyl-CoA dehydrogenase, cyl-CoA dehydrogenase long chain, carnitine palmitoyltransferase 1A, carnitine palmitoyltransferase 1B, peroxisomal proliferator-activated receptor-gamma coactivator-1α and peroxide proliferator activated receptor α., Conclusion: JHP alleviates HFD-induced MAFLD through the protection of mitochondrial function., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels., (© 2021. The Author(s).)

The sustainable use of medicinal plants is the foundation of the inheritance of traditional Chinese medicine(TCM) and the acquisition of information on medicinal plants is the basis for the development of TCM. The traditional methods of investigating medicinal plant resources are disadvantageous in strong subjectivity and poor timeliness, making it difficult to real-time monitor medicinal plant resources. In recent years, remote sensing technology has become an important means of obtaining information on medicinal plants. The application of this technology has made up for the shortcomings of traditional methods. The open-access remote sensing data with medium spatial resolution satellites provide an opportunity for extracting information on medicinal plant resources. This study firstly introduced the principles of remote sensing technology, summarized the satellites and the parameters commonly used in the field of medicinal plant resources, and compared the survey methods of remote sensing technology with traditional methods. Secondly, it reviewed the applications of remote sensing technology in the extraction of information on the cultivation of medicinal plants and the common methods for extracting the planting structure information of medicinal plants based on remote sensing technology. Thirdly, the applications of remote sensing technology in the investigation and monitoring of medicinal plants were further analyzed with the research objects divided into wild and cultivated medicinal plants according to the characteristics of the habitats. Finally, it pointed out the key unsolved technical problems in the remote sensing monitoring of medicinal plant resources, and proposed solutions for the intelligent information processing of medicinal plants based on remote sensing big data, which is expected to provide references for the development of remote sensing technology in derivative application in medicinal plant resources.

Fe₄N nanopowders were prepared using specially-made high-pressure gas-solid reaction equipment, and their composition, morphology, and magnetic properties were analyzed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). An average particle size of 35 nm was obtained at 0.4 MPa, an ammonia-to-hydrogen ratio of 3:1, 623 K, in an ammonia solution for 2 h. The hysteresis loop displayed a thin and narrow shape at 673 K during VSM tests. The saturation magnetization ( Ms ) reached 169.80 emu/g.

Southwestern China is an important ecologically resource area and ecologically fragile area in China, which plays an important role in the national project of "Clear Waters and Green Mountains". Based on land use data set with a 1 km spatial resolution and combined with land use transfer matrix, we analyzed the characteristics and driving forces of land use change in Southwest China from 2000 to 2015. Based on the MODIS remote sensing index, we calculated the vegetation coverage in Southwest China using the dimidiate pixel model, and analyzed the changes of the normalized vegetation index (NDVI) and vegetation coverage. Results showed that the main land types were woodland, cropland and grassland. The built-up land area increased by 5874 km 2 (55.8%), the cropland area decreased by 6211 km 2 , and grassland decreased by 2099 km 2 . From 2000 to 2015, the area that had been changed to built-up land was the largest, mainly from cropland (contributed 68.2%), woodland (contributed 19.2%) and grassland (contributed 13.1%). The transformed areas were mostly close to urban area. The area and rate for the transformation of cropland were 7079 km 2 and 2.2% respectively, accounting for 46.0% of all the transferred out areas. Most of the woodland were transformed from grassland (61.8%), mainly distributed in central and southern Guizhou and western Yunnan. Both NDVI and vegetation coverage were significantly increased, indicating that the whole region was greening. NDVI of both natural vegetation and cropland increased significantly, while the NDVI of areas with expanded build-up land decreased. Therefore, natural vegetation and cropland dominated the vegetation change in this region. Results of the resi-dual analysis showed that both climate change and human activities contributed significantly to the greening trend.

Background: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear., Objective: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively., Methods: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing., Results: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified&#95; Lachnospiraceae, unidentified&#95;Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family., Conclusions: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

Dabie Mountain in Anhui province is a genuine producing area of Poria cocos, commonly known as Anling. Jinzhai county in Anhui province is a traditional producing area of P. cocos, and it is also a key county for poverty alleviation in Dabie Mountains. Poverty alleviation of traditional Chinese medicine producing area is an important measure to implement the major strategic deployment of the central government. The planting of P. cocos is helpful to promote the development of traditional Chinese medicine industry in Dabie Mountains and help poverty alleviation. P. cocos is a saprophytic fungus with special demands on soil and ecological environment, and its planting appears a scattered and irregular distribution. Traditional investigation methods are time-consuming and laborious, and the results are greatly influenced by subjective factors. In order to obtain the suitable planting area of P. cocos in Jinzhai county, according to the field survey, the research team has explored the regional, biological characteristics and cultivation methods of P. cocos in the county, and obtained the altitude distribution area suitable for the growth of P. cocos. Then, the MaxEnt niche model was used to analyze the relationship between ecological factors and distribution areas, and the potential distribution zoning of P. cocos in Jinzhai county was studied. Combined with the characteristics of P. cocos planting pattern, taking ZY-3 remote sensing image as the data source, the maximum likelihood method was used to extract the area that could be used for P. cocos cultivation in Jinzhai county, and the reason why artificial planting P. cocos was mainly distributed in the west of Jinzhai county was analyzed. The suitable regional classification of P. cocos in Jinzhai county was obtained by superposition of suitable altitude distribution area, MaxEnt analysis and area extracted from remote sensing image, which provided data support for the planting planning of P. cocos in Jinzhai county.

Polygonatum cyrtonema is a famous bulk medicinal material which is the medicinal and edible homologous. With the implementation of the traditional Chinese medicine industry to promote precise poverty alleviation, the planting area of P. cyrtonema in Jinzhai is becoming larger and larger in recent years. Jinzhai is located in the Dabie Mountainous area, which is the largest mountain area and county in Anhui Province. The cultivation of P. cyrtonema is scattered, and the traditional Chinese medicine resources investigation is not only inefficient and accurate. In this study,the &quot;Resource 3&quot;(ZY-3) remote sensing image was used as the best observation phase,and the method of support vector machine classification was used. The method of parallelepiped, minimum distance, mahalanob is distance, maximum likelihood classification and neural net were used to classify and recognize the P. cyrtonema in the whole region. In order to determine the accuracy and reliability of classification results, the accuracy of six supervised classification results was evaluated by confusion matrix method, and the advantages and disadvantages of six supervised classification methods for extracting P. cyrtonema field planting area were compared and analyzed. The results showed that the method of support vector machine classification was more appropriate than that using other classification methods. It provides a scientific basis for monitoring the planting area of P. cyrtonemain field.

Objective: To investigate positioning error analysis of the Fraxion localization system in the intracranial stereotactic radiotherapy of tumors., Methods: 64 patients were divided into two groups: a control group (36 patients with the standard thermoplastic mask) and a model group (28 patients with the Fraxion localization system). 3D images of the treated position were obtained by cone-beam computed tomography (CBCT). Positioning errors were obtained by, respectively, registering these two sets of CBCT images to planning CT images, using a 6°-freedom robotic patient positioning system (HexaPOD Evo RT System). The changes in positioning errors with the Fraxion localization system and with the standard thermoplastic mask were analyzed., Results: CBCT scan results of the model group showed that the mean of linear error of three directions [superior-inferior (SI), lateral (LAT), and anterior-posterior (AP)] was 0.710 ± 0.676 mm, 0.817 ± 0.687 mm, and 0.710 ± 0.685 mm, respectively. The corresponding PTV was 1.23 mm, 1.26 mm, and 1.36 mm. The differences between the 3D images and the planned CT images were significant (p < 0.001)., Conclusion: The Fraxion radiotherapy system can not only improve the positioning accuracy and reduce positioning errors but also narrow the PTV margin and reduce the radiated volume of normal tissue.

Nonalcoholic fatty liver disease (NAFLD) is the most general liver disease characterized by a continuum of liver abnormalities ranging from simple fatty liver to advanced stage of nonalcoholic steatohepatitis, cirrhosis, and even hepatocellular carcinoma. The pathological drivers of NAFLD are complex and largely undefined. It is increasingly identified that the imbalance between renin-angiotensin system and ACE2/Ang-(1-7)/Mas axis, as well as mitochondrial dysfunction associated with NAFLD. However, no known empirical research has focused on exploring the effect of the regulation of mitochondrial respiration chain activity by Ang-(1-7)/Mas on the prevention of NAFLD. Here, we evaluated the interaction and relevance of hepatic Ang-(1-7)/Mas-axis challenge with glucolipid metabolism and mitochondrial condition in vivo and in vitro. In this context, we found that Mas deletion in mice contributed to the severe glucose intolerance, insulin resistance, and hepatic steatosis which accompanied by elevated levels of serum/ hepatic alanine aminotransferase, aspartate aminotransferase, and triglycerides, as well as the mitochondrial dysfunction. Whereas forced upregulation of Mas or Ang-(1-7) administration could significantly attenuate these consequences by downregulating the expression of hepatic lipogenic proteins and enzymes for gluconeogenesis. Furthermore, activation of Ang-(1-7)/Mas arm could improve the IRS-1/Akt/AMPK pathway and enhance the mitochondrial energy utilization. Considered together, it is becoming extremely hopeful to provide a new perspective for Ang-(1-7)/Mas axis for the therapeutics of NAFLD., (© 2020 Federation of American Societies for Experimental Biology.)

Identification of Chinese medicinal materials is a fundamental part and an important premise of the modern Chinese medicinal materials industry. As for the traditional Chinese medicinal materials that imitate wild cultivation, due to their scattered, irregular, and fine-grained planting characteristics, the fine classification using traditional classification methods is not accurate. Therefore, a deep convolution neural network model is used for imitating wild planting. Identification of Chinese herbal medicines. This study takes Lonicera japonica remote sensing recognition as an example, and proposes a method for fine classification of L. japonica based on a deep convolutional neural network model. The GoogLeNet network model is used to learn a large number of training samples to extract L. japonica characteristics from drone remote sensing images. Parameters, further optimize the network structure, and obtain a L. japonica recognition model. The research results show that the deep convolutional neural network based on GoogLeNet can effectively extract the L. japonica information that is relatively fragmented in the image, and realize the fine classification of L. japonica. After training and optimization, the overall classification accuracy of L. japonica can reach 97.5%, and total area accuracy is 94.6%, which can provide a reference for the application of deep convolutional neural network method in remote sensing classification of Chinese medicinal materials.

Tongue squamous cell carcinoma (TSCC) is a malignant tumor. Long noncoding RNAs (lncRNAs) have been proved to be involved in the regulation of the progression of various cancers. However, the mechanism of lncRNA urothelial cancer-associated 1 (UCA1) in the progression of TSCC remains unclear. The expression levels of UCA1, microRNA-138-5p (miR-138-5p), and CC chemokine receptor 7 (CCR7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion were detected using colony formation assay and transwell assay, respectively. Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related proteins and CCR7 protein. Moreover, the extracellular acidification rate (ECAR) of cells was measured by the Seahorse XF Extracellular Flux Analyzer, and the adenosine triphosphate (ATP) level, glucose uptake, and lactate produce of cells were tested by their corresponding assay kits. Further, the dual-luciferase reporter assay was used to confirm the interaction between miR-138-5p and UCA1 or CCR7. In addition, the effect of UCA1 on TSCC tumor growth in vivo was evaluated by animal experiments. We found that UCA1 and CCR7 were upregulated, while miR-138-5p was downregulated in TSCC tissues. Silenced UCA1 restrained the proliferation, migration, invasion, and glycolysis metabolism of TSCC cells. Similarly, knockdown of CCR7 also could suppress the progression of TSCC. Besides, UCA1 overexpression promoted TSCC progression, while this promotion effect could be reversed by CCR7 silencing. miR-138-5p could be sponged by UCA1 and could target CCR7. Additionally, miR-138-5p overexpression could reverse the promotion effect of overexpressed UCA1 on TSCC progression. Furthermore, the UCA1 knockdown reduced TSCC tumor growth in vivo. In conclusion, lncRNA UCA1 might function as an oncogene in TSCC through regulating the miR-138-5p/CCR7 axis, providing a new biomarker for TSCC treatment.

Background: Some antibodies and autoreactive antibodies are associated with the severity of infectious diseases. The roles of humoral responses to lung inflammation in children with human adenovirus (HAdVs) pneumonia remain unknown., Patients and Methods: A retrospective study was done to compare plasma immunoglobulin E (IgE) levels between HAdVs pneumonia patients and healthy children by searching the electronic medical record system of Guangzhou Women and Children's Medical Center. Then, a prospective study was performed for children with HAdVs pneumonia who needed flexible bronchoscopy for examination and treatment purposes during July 2017 to July 2019. We examined the IgE and autoreactive IgE levels in plasma and bronchoalveolar lavage fluid (BALF) of these children to explore their role in HAdVs pneumonia., Results: A significantly higher level of IgE was found in plasma from children hospitalized with HAdVs pneumonia compared with that from healthy children in the same age range. Furthermore, the levels of IgE, double-stranded DNA (dsDNA), and double-stranded DNA-specific immunoglobulin E (dsDNA-IgE) in BALF were increased compared to plasma in children with HAdVs pneumonia. The levels of IgE, dsDNA, and dsDNA-IgE in BALF were significantly higher in the severe group compared to the non-severe group. The ability of IgE in BALF to recognize dsDNA was verified by the ELISPOT test., Conclusions: Our findings indicate that IgE and dsDNA-IgE in BALF may contribute to lung injury caused by HAdVs, especially in severe cases. Elevated dsDNA-IgE may serve as an indicator of severity in children with HAdVs pneumonia., Competing Interests: Declaration of Competing Interest All authors report no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

We study a simplified version of the Sachdev-Ye-Kitaev (SYK) model with real interactions by exact diagonalization. Instead of satisfying a continuous Gaussian distribution, the interaction strengths are assumed to be chosen from discrete values with a finite separation. A quantum phase transition from a chaotic state to an integrable state is observed by increasing the discrete separation. Below the critical value, the discrete model can well reproduce various physical quantities of the original SYK model, including the volume law of the ground-state entanglement, level distribution, thermodynamic entropy, and out-of-time-order correlation (OTOC) functions. For systems of size up to N=20, we find that the transition point increases with system size, indicating that a relatively weak randomness of interaction can stabilize the chaotic phase. Our findings significantly relax the stringent conditions for the realization of SYK model, and can reduce the complexity of various experimental proposals down to realistic ranges., (Copyright © 2020 Science China Press. Published by Elsevier B.V. All rights reserved.)

Mitochondria are the 'engine' of cells. Mitochondrial dysfunction is an important mechanism in many human diseases. Many natural products could remedy the mitochondria to alleviate mitochondria-involved diseases. In this review, we summarized the current knowledge of the relationship between the mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represents an attractive strategy for a mitochondria-involved disorder therapy. Moreover, investigating the mitochondrial regulation of natural products can potentiate the in-depth comprehension of the mechanism of action of natural products., Competing Interests: The authors declare that there is no duality of interest associated with this manuscript., (Copyright © 2020 Jian-Kang Mu et al.)

Background: The pathogenesis underlying the alterations of orbital architecture in Graves' orbitopathy (GO) is not yet fully understood. The present study aimed to investigate the association of DNA methylation in peripheral blood and orbital volumetry in Chinese patients with GO., Methods: A total of 35 GO subjects (70 orbits) were subjected to computed tomography (CT) scan. The total cross-sectional area of the extraocular muscles (orbital muscles, OM), total orbit area (TOA), and the exophthalmometry were measured, and OM/TOA ratio was calculated. Targeted bisulfite sequencing was performed on seven candidate genes., Results: No significant correlation was established between the DNA methylation levels of these genes and exophthalmometry. The MBP methylation level was found to be correlated with OM/TOA ratio (P<0.05). Multiple linear regression analysis on parameters, including age, sex, TRAb, duration of GO, and DNA methylation levels of seven genes with OM/TOA ratio confirmed that MBP and OM/TOA ratio had a significant correlation (P<0.05). The partial least squares analysis showed that the top three genes with the highest loadings were MBP, BOLL, and BECN1, and OM/TOA ratio affected the DNA methylation block than exophthalmometry., Conclusions: This study provided preliminary evidence that MBP is a potential gene associated with OM enlargement in GO patients according to the combination of DNA methylation sequencing and orbital CT measurement.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective mechanical circulatory support modality that rapidly restores systemic perfusion for circulatory failure in patients. Given the huge increase in VA-ECMO use, its optimal management depends on continuous and discrete hemodynamic monitoring. This article provides an overview of VA-ECMO pathophysiology, and the current state of the art in hemodynamic monitoring in patients with VA-ECMO., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.186). The series “Hemodynamic Monitoring in Critically Ill Patients” was commissioned by the editorial office without any funding or sponsorship. GWT served as the unpaid Guest Editor of the series and serves as an unpaid Section Editor of Annals of Translational Medicine from May 2018 to Sep 2020. The other authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)