Mesenchymal stem cells derived from adipose tissue and umbilical cord reveal comparable efficacy upon radiation-induced colorectal fibrosis in rats.

Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including colorectal carcinoma (CRC), yet the concomitant radiation-induced colorectal fibrosis (RICF) has caused chronic toxicity and stenosis in the colorectal mucosa of patients. Mesenchymal stem/stromal cells (MSCs) with unique bidirectional immunoregulation and anti-fibrotic effect have been recognized as splendid sources for regenerative purposes including intestinal diseases. Herein, we are aiming to verify the feasibility and variations of MSC-based cytotherapy for the remission of RICF from the pathological features and the potential impact upon the transcriptomic signatures of RICF rats. For the purpose, we utilized our well-established RICF Sprague-Dawley (SD) rats by radiation for five weeks, and conducted consecutive intraperitoneal injection of two distinct MSCs for treatment, including MSCs derived from adult adipose tissue (AD-MSCs) and perinatal umbilical cord (UC-MSCs). On the one hand, the efficacy of AD-MSCs and UC-MSCs was assessed by diverse indicators, including weight change, pathological detections (e.g., H&E staining, Masson staining, EVG staining, IF staining, and IHC staining), and proinflammatory and fibrotic factor expression. On the other hand, we turned to RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses (e.g., GOBP, Venn Map, KEGG, and GSEA) to compare the impact of AD-MSC and UC-MSC treatment upon the gene expression profiling and genetic variations. RICF rats after consecutive AD-MSC and UC-MSC administration revealed comparable remission in histopathogenic features and significant suppression of diverse proinflammatory and fibrotic factors expression. Meanwhile, RICF rats after both MSC treatment revealed decrease and variations in the alterations in diverse gene expression and somatic mutations compared to RICF rats. Collectively, our data indicated the comparable therapeutic effect of AD-MSCs and UC-MSCs upon RICF in SD rats, together with the conservations in gene expression profiling and the diverse variations in genetic mutations. Our findings indicated the multifaceted impact of MSC infusion for the supervision of RICF both at the therapeutic and transcriptomic levels, which would provide novel references for the further evaluation and development of MSC-based regimens in future.

The function of brown adipose tissue at different sites of the body in Brandt's voles during cold acclimation.

Ambient temperatures have great impacts on thermoregulation of small mammals. Brown adipose tissue (BAT), an obligative thermogenic tissue for small mammals, is localized not only in the interscapular depot (iBAT), but also in supraclavicular, infra/subscapular, cervical, paravertebral, and periaortic depots. The iBAT is known for its cold-induced thermogenesis, however, less has been paid attention to the function of BAT at other sites. Here, we investigated the function of BAT at different sites of the body during cold acclimation in a small rodent species. As expected, Brandt's voles (Lasiopodomys brandtii) consumed more food and reduced the body mass gain when they were exposed to cold. The voles increased resting metabolic rate and maintained a relatively lower body temperature in the cold (36.5 ± 0.27 °C) compared to those in the warm condition (37.1 ± 0.36 °C). During cold acclimation, the uncoupling protein 1 (UCP1) increased in aBAT (axillary), cBAT (anterior cervical), iBAT (interscapular), nBAT (supraclavicular), and sBAT (suprascapular). The levels of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, were higher in cBAT and iBAT in the cold than in the warm group. The pAMPK/AMPK and pCREB/CREB were increased in cBAT and iBAT during cold acclimation, respectively. These data indicate that these different sites of BAT play the cold-induced thermogenic function for small mammals.

Plasma-activated water improves the accessibility of chitinase to chitin by decreasing molecular weight and breaking crystal structure.

Chitooligosaccharides, the hydrolysis products of chitin, have superior biological activities and application value to those of chitin itself; however, the ordered and highly crystalline structure of chitin renders its degradation by chitinase difficult. Herein, the effects of plasma-activated water (PAW) pre-treatment on the physicochemical properties, crystal structure, and enzymatic hydrolysis of chitin were investigated. The hydrolysis of PAW-pre-treated chitin (PAW activation time of 5 min) using chitinase from Vibrio harveyi (VhChit2) yielded 71 % more reducing sugar, compared with that from untreated chitin, with the degree of chitin hydrolysis increasing from 13 % without pre-treatment to 23 % post-treatment. Moreover, the amount of VhChit2 adsorbed by chitin increased from 41.7 to 58.2 mg/g. Fourier transform infrared spectrometry revealed that PAW could break the ß-1,4-glycosidic bonds of chitin (but had no effects on the hydrogen and amido bonds), thereby decreasing the molecular weight and crystallinity of the polysaccharide, which caused its structural damage and enhanced its enzymatic hydrolysis by chitinase. Consequently, PAW pre-treatment can be considered a simple, effective, and environmentally-friendly method for the biotransformation of chitin as its easier hydrolysis yields high-value products.

Perceived discrimination and youth vaping: The role of intersectional identities.

INTRODUCTION: Electronic cigarettes (also termed e-cigarette or vapes) often contain nicotine, an addictive psychoactive substance, which can have harmful effects during adolescence. Frequent experiences of discrimination are one risk factor shown to increase susceptibility to tobacco use, especially for individuals that identify as a social minority. Applying Intersectionality Theory, this research examined the relationship between youth experiences of discrimination and vape use at the intersection of race/ethnicity and sexual orientation. METHOD: Cross-sectional survey data from 4747 youth (ages 12-17) that participated in the 2022 Teens, Nicotine, and Tobacco Project (TNT) online survey were used to evaluate the impact of discrimination on vape use for lesbian, gay, bisexual, and/or queer/questioning (LGBQ+) youth of color. RESULTS: Multivariable regression analyses showed that identifying as both a sexual and racial/ethnic minority was a risk factor for experiencing discrimination. Frequent discrimination and reporting discrimination due to sexual orientation was associated with a greater likelihood of ever and current vaping. Path models supported that discrimination mediated the relationship between intersectional identity and vape use. LGBQ+ youth of color reported more frequent discrimination, which was associated with a greater likelihood of ever/current vape use. CONCLUSIONS: Intersectionality Theory aids in understanding how discrimination can exacerbate tobacco-related disparities for youth with multiple minority identities. Findings corroborate the importance of measuring discrimination in public health surveys. Effective tobacco interventions could incorporate strategies to cope with discrimination-related stress.

Anxiety in adolescents and subsequent risk of suicidal behavior: A systematic review and meta-analysis.

BACKGROUND: Suicide is a major public health concern, and anxiety is a prevalent developmental challenge in adolescents closely linked to suicidal behavior. This study aimed to assess the association between anxiety in adolescents and subsequent risk of suicidal behavior through a meta-analysis, offering crucial insights for suicide prevention. METHODS: Six bibliographic databases were comprehensively searched to clarify the association between adolescents anxiety and subsequent risk of suicidal behavior. We used a fixed-effects model to determine the total pooled effect size estimate and reported odds ratios and the corresponding 95 % confidence intervals. Subgroup analysis, sensitivity analysis and publication bias analysis were conducted with Stata version 15.1. RESULTS: The findings revealed a significant association between anxiety in adolescents and subsequent suicidal behavior (OR = 2.33, 95 % CI [2.00, 2.71]). Subgroup analyses indicated differences in mean effect size estimates based on clinical diagnoses and self-reported measures used to assess anxiety. The correlation strength between adolescent anxiety and subsequent suicidal behavior increased with a longer follow-up period. Furthermore, adolescents anxiety was associated with increased risk of subsequent suicidal ideation (OR = 1.97, 95 % CI [1.72, 2.25]) and attempts (OR = 3.56, 95 % CI [2.49, 5.07]). Finally, boys (OR = 2.41, 95 % CI [1.67, 3.47]) with anxiety had a greater risk of subsequent suicidal behavior than girls (OR = 2.02, 95 % CI [1.47, 2.78]). CONCLUSION: This study revealed that adolescents anxiety increases the risk of suicidal behavior, including suicidal ideation and attempts. Consequently, there is a critical need for timely interventions tailored to adolescents with anxiety to prevent future instances of suicide.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

Protein Allostery Study in Cells Using NMR Spectroscopy.

Protein allostery is commonly observed in vitro. But how protein allostery behaves in cells is unknown. In this work, a protein monomer-dimer equilibrium system was built with the allosteric effect on the binding characterized using NMR spectroscopy through mutations away from the dimer interface. A chemical shift linear fitting method was developed that enabled us to accurately determine the dissociation constant. A total of 28 allosteric mutations were prepared and grouped to negative allosteric, nonallosteric, and positive allosteric modulators. ∼ 50% of mutations displayed the allosteric-state changes when moving from a buffered solution into cells. For example, there were no positive allosteric modulators in the buffered solution but eight in cells. The change in protein allostery is correlated with the interactions between the protein and the cellular environment. These interactions presumably drive the surrounding macromolecules in cells to transiently bind to the monomer and dimer mutational sites and change the free energies of the two species differently which generate new allosteric effects. These surrounding macromolecules create a new protein allostery pathway that is only present in cells.

Association of Growth During Infancy With Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z-score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n=1400). Growth during infancy was calculated as change in weight z-score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z-score <-1.67; very high weight gain was a change in weight z-score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z-score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% confidence interval: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% confidence interval: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% confidence interval: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.

A feature-enhanced network for stroke lesion segmentation from brain MRI images.

Accurate and expeditious segmentation of stroke lesions can greatly assist physicians in making accurate medical diagnoses and administering timely treatments. However, there are two limitations to the current deep learning methods. On the one hand, the attention structure utilizes only local features, which misleads the subsequent segmentation; on the other hand, simple downsampling compromises task-relevant detailed semantic information. To address these challenges, we propose a novel feature refinement and protection network (FRPNet) for stroke lesion segmentation. FRPNet employs a symmetric encoding-decoding structure and incorporates twin attention gate (TAG) and multi-dimension attention pooling (MAP) modules. The TAG module leverages the self-attention mechanism and bi-directional attention to extract both global and local features of the lesion. On the other hand, the MAP module establishes multidimensional pooling attention to effectively mitigate the loss of features during the encoding process. Extensive comparative experiments show that, our method significantly outperforms the state-of-the-art approaches with 60.16% DSC, 36.20px HD and 85.72% DSC, 27.02px HD on two ischemic stroke datasets that contain all stroke stages and several sequences of stroke images. The excellent results that exceed those of existing methods illustrate the efficacy and generalizability of the proposed method. The source code is released on https://github.com/wu2ze2lin2/FRPNet.

Dealloying-Derived Self-Supporting Nanoporous Zinc Film with Optimized Macro/Microstructure for High-Performance Solar Steam Generation.

Solar steam generation (SSG) is a promising technology for the production of freshwater that can help alleviate global water scarcity. Nanostructured metals, known for their localized surface plasmon resonance effect, have generated significant interest, but low-cost metal films with excellent water evaporation properties are challenging. In this work, we present a one-step dealloying route for fabricating self-supporting black nanoporous zinc (NP-Zn) films with a bicontinuous ligament/channel structure, using Al-Zn solid solution alloys as the precursors. The influence of alloy composition on the formation and macro/microstructure of NP-Zn was investigated, and an optimal Al98Zn2 was selected. Additionally, in situ and ex situ characterizations were conducted to unveil the dealloying mechanism of Al98Zn2 and phase/microstructure evolution of NP-Zn during dealloying, including the phase transition of Al(Zn) → Zn, significant volume shrinkage (89.8%), and the development of high porosity (81.3%). The nanoscale ligament/channel structure and high porosity endow the NP-Zn films with good broadband absorption and superior hydrophilicity and, more importantly, give them excellent SSG performance. The NP-Zn2 film displays high evaporation efficiency, superior stability, and good seawater desalination performance. The efficient SSG performance, material abundance, and low cost suggest that NP-Zn films have promising applications in metal-based photothermal materials for SSG.

Identification and functional analysis of a chromosome 2D fragment harboring TaFPF1 gene with the potential for yield improvement using a late heading wheat mutant.

KEY MESSAGE: A chromosome fragment influencing wheat heading and grain size was identified using mapping of m406 mutant. The study of TaFPF1 in this fragment provides more insights into wheat yield improvement. In recent years, wheat production has faced formidable challenges driven by rapid population growth and climate change, emphasizing the importance of improving specific agronomic traits such as heading date, spike length, and grain size. To identify potential genes for improving these traits, we screened a wheat EMS mutant library and identified a mutant, designated m406, which exhibited a significantly delayed heading date compared to the wild-type. Intriguingly, the mutant also displayed significantly longer spike and larger grain size. Genetic analysis revealed that a single recessive gene was responsible for the delayed heading. Surprisingly, a large 46.58 Mb deletion at the terminal region of chromosome arm 2DS in the mutant was identified through fine mapping and fluorescence in situ hybridization. Thus, the phenotypes of the mutant m406 are controlled by a group of linked genes. This deletion encompassed 917 annotated high-confidence genes, including the previously studied wheat genes Ppd1 and TaDA1, which could affect heading date and grain size. Multiple genes in this region probably contribute to the phenotypes of m406. We further investigated the function of TaFPF1 using gene editing. TaFPF1 knockout mutants showed delayed heading and increased grain size. Moreover, we identified the direct upstream gene of TaFPF1 and investigated its relationship with other important flowering genes. Our study not only identified more genes affecting heading and grain development within this deleted region but also highlighted the potential of combining these genes for improvement of wheat traits.

Green Space and Internalizing or Externalizing Symptoms Among Children.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

Preparation of Ceramic Fiber Threads with Enhanced Abrasion Resistance Performance.

Ceramic fiber thread is one of the key components in flexible external thermal insulation blankets, and it has been applied in various fields as a flexible ceramic fibrous material with excellent deformability and high-temperature resistance. However, ceramic fiber threads are often subjected to reciprocating friction motion at specific bending angles, making them highly susceptible to abrade and fracture. Enhancing the abrasion resistance performance of ceramic fiber threads under bending conditions is the future trend and remains a significant challenge. Hence, we design and construct a novel polyurethane-modified coating on the ceramic fiber threads to improve their abrasion resistance performance. The effects of the types and concentrations of modifiers on the microstructure, abrasion resistance property, and tensile property of ceramic fiber threads are systematically investigated. The ceramic fiber threads, after modification with hexamethylene diisocyanate waterborne polyurethane (HDI-WPU) with a concentration of 3%, exhibit excellent abrasion resistance properties. The number of friction cycles at fracture of the modified ceramic fiber thread is more than three times, and the tensile strength is more than one and a half times, that of the original ceramic fiber thread, demonstrating the great potential of the HDI-WPU modifier for enhancing the abrasion resistance performance of ceramic fiber threads.

Astragaloside IV restrains pulmonary fibrosis progression via the circ_0008898/miR-211-5p/HMGB1 axis.

Pulmonary Fibrosis (PF) is a fatal lung disease with complicated pathogenesis. Astragaloside IV (ASV) has been discovered to alleviate PF progression, and the potential molecular mechanism of ASV in the development of PF need to be further clarified. Bleomycin (BLM) was used to construct PF in vivo model. Expression levels of circ_0008898, miR-211-5p, high mobility group protein B1 (HMGB1), alpha smooth muscle Actin (α-SMA) and Collagen I were examined by Quantitative real time polymerase chain reaction (qRT-PCR) and western blot. Cell survival was analyzed using Cell Counting Kit-8 (CCK-8) and EdU (5-ethynyl-2'-deoxyuridine) assay. The invasion abilities were investigated by transwell assay. The levels of inflammatory factors were tested via using Enzyme-linked immunosorbent assay (ELISA). The relationship between circ_0008898 or HMGB1 and miR-211-5p was identified by dual-luciferase reporter assay. The results showed that ASV attenuated BLM-induced pulmonary fibrosis in vivo. In vitro study, ASV alleviated TGF-ß1-induced fibrogenesis in HFL1 cells. Circ_0008898 was increased in TGF-ß1-induced HFL1 cells. ASV-induced impacts were abrogated by circ_0008898 overexpression in TGF-ß1-induced HFL1 cells. Mechanistically, circ_0008898 competitively bound to miR-211-5p to increase the expression of its target HMGB1. MiR-211-5p deficiency rescued ASV-mediated effects in TGF-ß1-induced HFL1 cells. In addition, HMGB1 overexpression partially overturned circ_0008898 interference-induced impacts in HFL1 cells upon TGF-ß1 treatment. In conclusion, our work manifested that ASV hindered PF process by mediating the circ_0008898/miR-211-5p/HMGB1 network.

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.

Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories.

Ginseng extracts improve circadian clock gene expression and reduce inflammation directly and indirectly through gut microbiota and PI3K signaling pathway.

Despite the potential benefits of herbal medicines for therapeutic application in preventing and treating various metabolic disorders, the mechanisms of action were understood incompletely. Ginseng (Panax ginseng), a commonly employed plant as a dietary supplement, has been reported to play its hot property in increasing body temperature and improving gut health. However, a comprehensive understanding of the mechanisms by which ginseng regulates body temperature and gut health is still incomplete. This paper illustrates that intermittent supplementation with ginseng extracts improved body temperature rhythm and suppressed inflammatory responses in peripheral metabolic organs of propylthiouracil (PTU)-induced hypothermic rats. These effects were associated with changes in gut hormone secretion and the microbiota profile. The in-vitro studies in ICE-6 cells indicate that ginseng extracts can not only act directly on the cell to regulate the genes related to circadian clock and inflammation, but also may function through the gut microbiota and their byproducts such as lipopolysaccharide. Furthermore, administration of PI3K inhibitor blocked ginseng or microbiota-induced gene expression related with circadian clock and inflammation in vitro. These findings demonstrate that the hot property of ginseng may be mediated by improving circadian clock and suppressing inflammation directly or indirectly through the gut microbiota and PI3K-AKT signaling pathways.

Monitoring the after-effects of ischemic stroke through EEG microstates.

BACKGROUND AND PURPOSE: Stroke may cause extensive after-effects such as motor function impairments and disorder of consciousness (DoC). Detecting these after-effects of stroke and monitoring their changes are challenging jobs currently undertaken via traditional clinical examinations. These behavioural examinations often take a great deal of manpower and time, thus consuming significant resources. Computer-aided examinations of the electroencephalogram (EEG) microstates derived from bedside EEG monitoring may provide an alternative way to assist medical practitioners in a quick assessment of the after-effects of stroke. METHODS: In this study, we designed a framework to extract microstate maps and calculate their statistical parameters to input to classifiers to identify DoC in ischemic stroke patients automatically. As the dataset is imbalanced with the minority of patients being DoC, an ensemble of support vector machines (EOSVM) is designed to solve the problem that classifiers always tend to be the majority classes in the classification on an imbalanced dataset. RESULTS: The experimental results show EOSVM get better performance (with accuracy and F1-Score both higher than 89%), improving sensitivity the most, from lower than 60% (SVM and AdaBoost) to higher than 80%. This highlighted the usefulness of the EOSVM-aided DoC detection based on microstates parameters. CONCLUSION: Therefore, the classifier EOSVM classification based on features of EEG microstates is helpful to medical practitioners in DoC detection with saved resources that would otherwise be consumed in traditional clinic checks.

Integrative physiological, metabolomic, and transcriptomic analysis reveals the drought responses of two apple rootstock cultivars.

BACKGROUND: Drought is considered the main environmental factor restricting apple production and thus the development of the apple industry. Rootstocks play an important role in enhancing the drought tolerance of apple plants. Studies of the physiology have demonstrated that 'ZC9-3' is a strong drought-resistant rootstock, whereas 'Jizhen-2' is a weak drought-resistant rootstock. However, the metabolites in these two apple rootstock varieties that respond to drought stress have not yet been characterized, and the molecular mechanisms underlying their responses to drought stress remain unclear. RESULTS: In this study, the physiological and molecular mechanisms underlying differences in the drought resistance of 'Jizhen-2' (drought-sensitive) and 'ZC9-3' (drought-resistant) apple rootstocks were explored. Under drought stress, the relative water content of the leaves was maintained at higher levels in 'ZC9-3' than in 'Jizhen-2', and the photosynthetic, antioxidant, and osmoregulatory capacities of 'ZC9-3' were stronger than those of 'Jizhen-2'. Metabolome analysis revealed a total of 95 and 156 differentially accumulated metabolites in 'Jizhen-2' and 'ZC9-3' under drought stress, respectively. The up-regulated metabolites in the two cultivars were mainly amino acids and derivatives. Transcriptome analysis revealed that there were more differentially expressed genes and transcription factors in 'ZC9-3' than in 'Jizhen-2' throughout the drought treatment. Metabolomic and transcriptomic analysis revealed that amino acid biosynthesis pathways play key roles in mediating drought resistance in apple rootstocks. A total of 13 metabolites, including L-α-aminoadipate, L-homoserine, L-threonine, L-isoleucine, L-valine, L-leucine, (2S)-2-isopropylmalate, anthranilate, L-tryptophan, L-phenylalanine, L-tyrosine, L-glutamate, and L-proline, play an important role in the difference in drought resistance between 'ZC9-3' and 'Jizhen-2'. In addition, 13 genes encoding O-acetylserine-(thiol)-lyase, S-adenosylmethionine synthetase, ketol-acid isomeroreductase, dihydroxyacid dehydratase, isopropylmalate isomerase, branched-chain aminotransferase, pyruvate kinase, 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase, N-acetylglutamate-5-P-reductase, and pyrroline-5-carboxylate synthetase positively regulate the response of 'ZC9-3' to drought stress. CONCLUSIONS: This study enhances our understanding of the response of apple rootstocks to drought stress at the physiological, metabolic, and transcriptional levels and provides key insights that will aid the cultivation of drought-resistant apple rootstock cultivars. Especially, it identifies key metabolites and genes underlying the drought resistance of apple rootstocks.

Transcriptome-Based Identification of Candidate Flowering-Associated Genes of Blueberry in a Plant Factory with Artificial Lighting (PFAL) under Short-Day-Length Conditions.

In blueberry (Vaccinium corymbosum L.), a perennial shrub, flower bud initiation is mediated by a short-day (SD) photoperiod and buds bloom once the chilling requirement is satisfied. A plant factory with artificial lighting (PFAL) is a planting system that can provide a stable and highly efficient growing environment for blueberry production. However, the characteristics of bud differentiation of blueberry plants inside PFAL systems are poorly understood. To better understand flower bud initiation and the flowering mechanism of blueberry in PFAL systems, the anatomical structure of apical buds under SD conditions in a PFAL system was observed using the southern highbush cultivar 'Misty' and a transcriptomic analysis was performed to identify the candidate flowering genes. The results indicated that the apical bud of 'Misty' differentiated gradually along with SD time course and swelled obviously when chilling was introduced. A total of 39.28 Gb clean data were generated, and about 20.31-24.11 Mb high-quality clean reads were assembled, yielding a total of 17370 differentially expressed genes (DEGs), of which 9637 were up-regulated and 7733 were down-regulated. Based on the functional annotation, 26 DEGs were identified including 20 flowering-related and 6 low-temperature DEGs, out of which the expressive level of four flowering-related DEGs (VcFT2, VcFPA, VcFMADS1, and VcCOP1) and two low-temperature-induced DEGs (VcTIL-1 and VcLTI 65-like) were confirmed by qRT-PCR with a good consistency with the pattern of transcriptome. Functional analysis indicated that VcFT2 was highly conserved with nuclear and cytoplasmic subcellular localization and was expressed mainly in blueberry leaf tissue. In Arabidopsis, ectopic overexpression of VcFT2 results in an early flowering phenotype, indicating that VcFT2 is a vital regulator of the SD-mediated flowering pathway in blueberry. These results contribute to the investigation of photoperiod-mediated flowering mechanisms of blueberry in PFAL systems.