Exaggerated sensitivity to threat and reduced medial prefrontal engagement during threat generalization in reactive aggressive adolescents.

Aggressive adolescents tend to exhibit abnormal fear acquisition and extinction, and reactive aggressive adolescents are often more anxious. However, the relationship between fear generalization and reactive aggression (RA) remains unknown. According to Reactive-Proactive Aggression Questionnaire (RPQ) scores, 61 adolescents were divided into two groups, namely, a high RA group (N = 30) and a low aggression (LA) group (N = 31). All participants underwent three consecutive phases of the Pavlovian conditioning paradigm (i.e., habituation, acquisition, and generalization), and neural activation of the medial prefrontal cortex (mPFC) was assessed by functional near-infrared spectroscopy (fNIRS). The stimuli were ten circles with varying sizes, including two conditioned stimuli (CSs) and eight generalization stimuli (GSs). A scream at 85 dB served as the auditory unconditioned stimulus (US). The US expectancy ratings of both CSs and GSs were higher in the RA group than in the LA group. The fNIRS results showed that CSs and GSs evoked lower mPFC activation in the RA group compared to the LA group during fear generalization. These findings suggest that abnormalities in fear acquisition and generalization are prototypical dysregulations in adolescents with RA. They provide neurocognitive evidence for dysregulated fear learning in the mechanisms underlying adolescents with RA, highlighting the need to develop emotional regulation interventions for these individuals.

Association between Marital Status and Cognitive Impairment in a Multi-Ethnic Asian Population.

OBJECTIVE: This study aims to examine the potential factors associated with marital status and determine the association between marital status and cognitive impairment in a multi-ethnic Asian population. METHOD: This study included 2321 participants from Singapore Multi-Ethnic Cohort revisit study (aged 40-89). Participants were classified into married and unmarried group at baseline and follow-up according to self-reported marital status. Mini-Mental Status Examination (MMSE) was administered, and cognitive impairment was defined as a MMSE <26. We conducted both cross-sectional and longitudinal analyses to examine the association of marital status at one time point as well as marital transition with cognitive impairment. RESULTS: Of the 2321 participants, a total of 1914 (82.5%) were married. The factors associated with marital status included younger age, male sex, higher household income, higher education, and higher physical activity levels. Additionally, married participants also had higher alternative healthy eating index (AHEI-2010) scores, and a lower burden of hypertension and diabetes. Among those who were married, the median (Q1, Q3) MMSE score was 29 (28,30) while those who were unmarried was 29 (27, 30) (p <0.01). Participants who had never been married had the highest odds of cognitive impairment compared to their married counterparts (Model III: OR=1.48, 95% CI: 1.03, 2.14). Older age (p-interaction value=0.003) and Indian ethnicity (p-interaction value=0.028) further strengthened these associations. CONCLUSION: Marriage was associated with lower odds of cognitive impairment. Marriage provides social support, companionship, and engagement in mentally stimulating activities contributing to better cognitive health. By identifying risk factors such as marital status, interventions and support systems can be developed to promote healthy cognitive aging.

Sigmoidal relationship between liver fat content and nonalcoholic fatty liver disease in Chinese adults.

PURPOSE: To explore the relationship between liver fat content (LFC) and nonalcoholic fatty liver disease (NAFLD) and determine the new threshold of LFC to diagnose NAFLD. METHODS: The data from questionnaire survey, general physical examination, laboratory examination, and image examination were collected. Multivariate regression analysis, receiver operating characteristic curve analysis, smooth curve fitting, and threshold effect analysis were performed using the R software to investigate the relationship between LFC and NAFLD and to identify the new threshold of LFC to diagnose NAFLD. RESULTS: The prevalence of NAFLD was 30.42%, with a significantly higher prevalence in men than in women. Regression analyses demonstrated that LFC odds ratio [95% confidence interval (CI)] was 1.28 (95% CI: 1.24-1.31) in fully-adjust model. Analysis of the LFC quartile, with Q1 as a reference, revealed that the odds ratios of NAFLD were 1.47 (95% CI: 1.08-1.99), 2.29 (95% CI: 1.72-3.06), and 10.02 (95% CI: 7.45-13.47) for Q2, Q3, and Q4 groups, respectively. Smooth curve fitting and threshold effect analysis displayed a nonlinear relationship between LFC and NAFLD, and the threshold was 4.5%. The receiver operating characteristic curve indicated that when LFC was 4.5%, the area under curve (95% CI) was 0.80 (0.79-0.82), and the sensitivity and specificity of LFC in diagnosing NAFLD were 0.64% and 0.82%, respectively. CONCLUSION: The relationship between LFC and NAFLD was sigmoidal, with an inflection point of 4.5%.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Transcriptomic and Proteomic Analyses Unveil the Role of Nitrogen Metabolism in the Formation of Chinese Cabbage Petiole Spot.

Chinese cabbage is the most widely consumed vegetable crop due to its high nutritional value and rock-bottom price. Notably, the presence of the physiological disease petiole spot significantly impacts the appearance quality and marketability of Chinese cabbage. It is well known that excessive nitrogen fertilizer is a crucial factor in the occurrence of petiole spots; however, the mechanism by which excessive nitrogen triggers the formation of petiole spots is not yet clear. In this study, we found that petiole spots initially gather in the intercellular or extracellular regions, then gradually extend into intracellular regions, and finally affect adjacent cells, accompanied by cell death. Transcriptomic and proteomic as well as physiology analyses revealed that the genes/proteins involved in nitrogen metabolism exhibited different expression patterns in resistant and susceptible Chinese cabbage lines. The resistant Chinese cabbage line has high assimilation ability of NH4+, whereas the susceptible one accumulates excessive NH4+, thus inducing a burst of reactive oxygen species (ROS). These results introduce a novel perspective to the investigation of petiole spot induced by the nitrogen metabolism pathway, offering a theoretical foundation for the development of resistant strains in the control of petiole spot.

Exploring the relationship between digital transformation and green innovation: The mediating role of financing modes.

Green innovation is important and beneficial for the green development of enterprises. The development of digital technology could improve the asymmetry of information and affect the enterprise's financing modes. Currently, a definitive conclusion about the relationship between the digital transformation and green technology innovation has not reached. Additionally, studies have not yet fully explored the impact pathways of corporate digital transformation on green innovation through corporate financing modes. To fill this void, this study collected data of Chinese A-share listed companies from 2010 to 2020. The empirical analysis results showed that digital transformation significantly enhanced enterprises' green innovation abilities. Furthermore, mediating models were utilized to explore how enterprise financing modes mediate the impact of digital transformation on the enterprise green innovation. Results indicated that through internal financing and bank loans as "bridges", digital transformation promoted enterprise green innovation. However, digital transformation did not have a significant impact on enterprise green innovation through venture capital. Moreover, heterogeneity analyses revealed significant differences among different groups of enterprises. This study expands the research field related to digital transformation and enterprise green innovation by providing empirical evidence to uncover the impact of digital transformation on enterprise green innovation. Findings of this study contribute not only to enterprise managerial decision-makers to better leverage digital transformation through corporate financing to accelerate green innovation, but also to government policymakers to design policies to stimulate enterprise green innovation.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Integrating ATAC-seq and RNA-seq to identify differentially expressed genes with chromatin-accessible changes during photosynthetic establishment in Populus leaves.

Leaves are the primary photosynthetic organs, providing essential substances for tree growth. It is important to obtain an anatomical understanding and regulatory network analysis of leaf development. Here, we studied leaf development in Populus Nanlin895 along a development gradient from the newly emerged leaf from the shoot apex to the sixth leaf (L1 to L6) using anatomical observations and RNA-seq analysis. It indicated that mesophyll cells possess obvious vascular, palisade, and spongy tissue with distinct intercellular spaces after L3. Additionally, vacuoles fuse while epidermal cells expand to form pavement cells. RNA-seq analysis indicated that genes highly expressed in L1 and L2 were related to cell division and differentiation, while those highly expressed in L3 were enriched in photosynthesis. Therefore, we selected L1 and L3 to integrate ATAC-seq and RNA-seq and identified 735 differentially expressed genes (DEGs) with changes in chromatin accessibility regions within their promoters, of which 87 were transcription factors (TFs), such as ABI3VP1, AP-EREBP, MYB, NAC, and GRF. Motif enrichment analysis revealed potential regulatory functions for the DEGs through upstream TFs including TCP, bZIP, HD-ZIP, Dof, BBR-BPC, and MYB. Overall, our research provides a potential molecular foundation for regulatory network exploration in leaf development during photosynthesis establishment.

Identification of WUSCHEL-related homeobox gene and truncated small peptides in transformation efficiency improvement in Eucalyptus.

BACKGROUND: The WUSCHEL-related Homeobox (WOX) genes, which encode plant-specific homeobox (HB) transcription factors, play crucial roles in regulating plant growth and development. However, the functions of WOX genes are little known in Eucalyptus, one of the fastest-growing tree resources with considerable widespread cultivation worldwide. RESULTS: A total of nine WOX genes named EgWOX1-EgWOX9 were retrieved and designated from Eucalyptus grandis. From the three divided clades marked as Modern/WUS, Intermediate and Ancient, the largest group Modern/WUS (6 EgWOXs) contains a specific domain with 8 amino acids: TLQLFPLR. The collinearity, cis-regulatory elements, protein-protein interaction network and gene expression analysis reveal that the WUS proteins in E. grandis involve in regulating meristems development and regeneration. Furthermore, by externally adding of truncated peptides isolated from WUS specific domain, the transformation efficiency in E. urophylla × E. grandis DH32-29 was significant enhanced. The transcriptomics data further reveals that the use of small peptides activates metabolism pathways such as starch and sucrose metabolism, phenylpropanoid biosynthesis and flavonoid biosynthesis. CONCLUSIONS: Peptides isolated from WUS protein can be utilized to enhance the transformation efficiency in Eucalyptus, thereby contributing to the high-efficiency breeding of Eucalyptus.

Mechanistic and thermal characterization of acupuncture for chemotherapy-induced peripheral neuropathy as measured by quantitative sensory testing.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising non-pharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST). METHODS: We conducted a randomized controlled trial of real acupuncture (RA) and sham acupuncture (SA) compared to usual care (UC) in cancer survivors with moderate-to-severe CIPN. Treatment response was assessed with QST measures of tactile and vibration detection thresholds in hands and feet, thermal detection, and pain thresholds at weeks 0, 8, and 12. Constrained linear mixed model (cLMM) regression was used for statistical analysis. RESULTS: 63 patients completed QST testing. At week 8, vibrational detection thresholds in feet were significantly lower in RA and SA (p = 0.019 and p = 0.046) than in UC, with no difference between RA and SA (p = 0.637). Both RA and SA also showed significantly higher cool thermal detection than UC (p = 0.008 and p = 0.013, respectively), with no difference between RA and SA (p = 0.790). No differences in tactile detection, vibrational detection in hands, warm thermal detection, and thermal pain thresholds were detected among the three arms at weeks 8 and 12. CONCLUSION: QST demonstrated different patterns in RA, SA, and UC. After eight weeks of RA, we observed significant improvements in the vibrational detection threshold in feet and cool thermal detection threshold in hands compared to UC. No significant differences were seen when compared to SA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03183037); June 9, 2017.

Specific gastrointestinal microbiota profiles in Chinese Tan sheep are associated with lauric acid content in muscle.

The biological mechanisms underlying meat quality remain unclear. Currently, many studies report that the gastrointestinal microbiota is essential for animal growth and performance. However, it is uncertain which bacterial species are specifically associated with the meat quality traits. In this study, 16S rDNA and metagenomic sequencing were performed to explore the composition and function of microbes in various gastrointestinal segments of Tan sheep and Dorper sheep, as well as the relationship between microbiota and meat quality (specifically, the fatty acid content of the muscle). In the ruminal, duodenal, and colonic microbiome, several bacteria were uniquely identified in respective breeds, including Agrobacterium tumefaciens, Bacteroidales bacterium CF, and several members of the family Oscillospiraceae. The annotation of GO, KEGG, and CAZYme revealed that these different bacterial species were linked to the metabolism of glucose, lipids, and amino acids. Additionally, our findings suggested that 16 microbial species may be essential to the content of fatty acids in the muscle, especially C12:0 (lauric acid). 4 bacterial species, including Achromobacter xylosoxidans, Mageeibacillus indolicus, and Mycobacterium dioxanotrophicus, were positively correlated with C12:0, while 13 bacteria, including Methanobrevibacter millerae, Bacteroidales bacterium CF, and Bacteroides coprosuis were negatively correlated with C12:0. In a word, this study provides a basic data for better understanding the interaction between ruminant gastrointestinal microorganisms and the meat quality traits of hosts.

Pontibacter kalidii sp. nov., isolated from rhizosphere soil of Kalidium foliatum.

A Gram-negative, aerobic, gliding motile, rod-shaped bacterium, designated XAAS-72T, was isolated from the rhizosphere soil of Kalidium foliatum sampled in the Xinjiang Uyghur Autonomous Region, PR China. Cells grew at 4-45 °C, pH 5.0-8.0 and 0-8% NaCl, with optimal growth at 20-30 °C, pH 6.0-7.0 and 1-2 % NaCl. Strain XAAS-72T is closely related to members of the genus Pontibacter, namely Pontibacter korlensis CCTCC AB 206081T (97.6%) and Pontibacter flavimaris ACCC 19859T (97.2 %), and <94.6 % related to other currently described Pontibacter strains. The average nucleotide identity values between XAAS-72T and P. korlensis CCTCC AB 206081T and P. flavimaris ACCC 19859T were 77.9 and 86.9 %, respectively; the corresponding digital DNA-DNA hybridization values were 21.7 and 31.8 %. Menaquinone-7 was the predominant respiratory menaquinone. The polar lipids consisted of phosphatidylethanolamine, two unidentified aminophospholipids, two unidentified glycolipids and five unidentified lipids. The major cellular fatty acids were summed feature 4 (containing iso-C17 : 1 I/anteiso-C17 : 1 B), summed feature 3 (containing C16 : 1 ω7c/C16 : 1 ω6c) and iso-C15 : 0. The genome length of strain XAAS-72T was 5 054 860 bp with a genomic DNA G+C content of 54.5 mol%. The phenotypic and genotypic data suggest that strain XAAS-72T represents a novel species of the genus Pontibacter, for which the name Pontibacter kalidii sp. nov. is proposed. The strain is XAAS-72T (CGMCC 16594T=KCTC 72095T).

Dietary supplementation of synbiotic Leuconostoc mesenteroide B4 and dextran improves immune regulation and disease resistance of Penaeus vannamei against Vibrio parahaemolyticus.

White shrimp (Penaeus vannamei) is an important culture species in Taiwan but often encounters disease infection by Vibrio parahaemolyticus that cause acute hepatopancreatic necrosis disease (AHPND). This study investigates the effects of dietary supplementation of Leuconostoc mesenteroide B4 and its fermentate (dextran) on the immune response, intestinal morphology, disease resistance, and immune-related gene expression in white shrimp. In comparison to the control group, the shrimp fed with a diet containing B4+dextran (107 CFU B4/g feed and 0.05% dextran) for 14, 28, 42 and 56 days had a significantly higher feed efficiency, weight gain and specific growth rate. A significantly higher villus height in the intestine and higher survival rate after challenging with V. parahaemolyticus was recorded for the B4+dextran group. Flow cytometry analysis demonstrated that the group that had ingested B4+dextran had a higher total hemocyte count and a higher proportion of semi-granulocytes, but a lower percentage of granulocytes compared to the control group. The shotgun metagenomic results in the midgut revealed that Leuco. mesenteroides was barely found in the midgut of the shrimp, suggesting that this microbe and its transient presence in the midgut is not the direct mechanism underlying the improved shrimp growth in the treated sample. Instead, dextran, a key ingredient in the B4 fermentate, on the dynamic of the microbial populations in shrimp, possibly promoting the diversity of gut microbes, especially the beneficial microbes, and thereby rendering protection against AHPND. In terms of comparing the gene expression between the control and synbiotic groups, pre- and post-bacterial challenge, a higher expression level of immune genes was mostly found in the B4+dextran group after challenging it with V. parahaemolyticus (group B4+dextran-VP) in the hepatopancreas and hemocyte. In contrast, the transcript level of immune-related genes was found to be higher in the B4+dextran group than other combinations in the midgut. Taken together, this study found that dietary addition of synbiotic Leuco. mesenteroides B4 and dextran can improve the growth performance, intestinal morphology and microbiome, regulation of immune genes and disease resistance against V. parahaemolyticus infection in white shrimp.

Resilience and probiotic interventions to prevent and recover from shrimp gut dysbiosis.

To counter the recurrent outbreaks of bacterial (acute hepatopancreatic necrosis disease; AHPND) and viral (white spot disease; WSD) shrimp diseases, which still remain a threat to the global industry, shrimp gut microbiota research has been gaining more attention in recent years, and the use of probiotics in aquaculture has had promising results in improving shrimp gut health and immunity. In this review based on our studies on AHPND and WSD, we summarize our current understanding of the shrimp gastrointestinal tract and the role of the microbiota in disease, as well as effects of probiotics. We focus particularly on the concept of microbiota resilience, and consider strategies that can be used to restore shrimp gut health by probiotic intervention at a crucial time during gut microbiota dysbiosis. Based on the available scientific evidence, we argue that the use of probiotics potentially has an important role in controlling disease in shrimp aquaculture.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

Photonic generation of frequency-doubling Nyquist pulses using external modulation.

In this paper, an approach to generate frequency-doubling sinc-shaped optical Nyquist pulses based on external modulation is proposed and demonstrated. First, four flat optical frequency comb (OFC) lines are obtained after optical carrier suppression modulation in a dual-electrode Mach-Zehnder modulator. Then an optical interleaver is introduced to split the phase-locked OFC into two paths, of which one is transmitted to a dual-parallel Mach-Zehnder modulator for quadrupling RF modulation and another is applied to the remodulated signal to acquire comb lines with equal intervals. Thus, a phase-locked 12-line flat OFC with equal frequency intervals and corresponding Nyquist pulses is finally obtained, and Nyquist pulses at 2.5 GHz, 5 GHz, 10 GHz, and 15 GHz are achieved.

Conformable Electrode Arrays for Wearable Neuroprostheses.

Wearable electrode arrays can selectively stimulate muscle groups by modulating their shape, size, and position over a targeted region. They can potentially revolutionize personalized rehabilitation by being noninvasive and allowing easy donning and doffing. Nevertheless, users should feel comfortable using such arrays, as they are typically worn for an extended time period. Additionally, to deliver safe and selective stimulation, these arrays must be tailored to a user's physiology. Fabricating customizable electrode arrays needs a rapid and economical technique that accommodates scalability. By leveraging a multilayer screen-printing technique, this study aims to develop personalizable electrode arrays by embedding conductive materials into silicone-based elastomers. Accordingly, the conductivity of a silicone-based elastomer was altered by adding carbonaceous material. The 1:8 and 1:9 weight ratio percentages of carbon black (CB) to elastomer achieved conductivities between 0.0021-0.0030 S cm-1 and were suitable for transcutaneous stimulation. Moreover, these ratios maintained their stimulation performance after several stretching cycles of up to 200%. Thus, a soft, conformable electrode array with a customizable design was demonstrated. Lastly, the efficacy of the proposed electrode arrays to stimulate hand function tasks was evaluated by in vivo experiments. The demonstration of such arrays encourages the realization of cost-effective, wearable stimulation systems for hand function restoration.

Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner.

Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aß-overexpressing fruit flies, and silencing NRF2 abolishes OST's antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aß-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aß and that NRF2 is necessary for OST's antagonism.

Isosteviol sodium attenuates high fat/high cholesterol-induced myocardial dysfunction by regulating the Sirt1/AMPK pathway.

A fat-rich diet triggers obesity, and promotes cardiomyocyte injury. Till now, no prior investigations suggested a beneficial role of Isosteviol Sodium (STVNa) in cardiac activity in high fat diet (HFD)-exposed obese rats. However, there is evidence that STVNa accelerates healing of multiple tissue injuries. Herein, we explored the underlying mechanism behind the STVNa-based protection against HFD-induced myocardial dysfunction (MCD) in a rat model of myocardial injury. We employed dosages of 1, 10, and 20 mg/kg STVNa to treat MCD in rats fed with a HFD. Based on our results, STVNa repressed MCD (as indicated by ecocardiographic analysis), myocardium function, pathological structure, and myocardial enzymes. Mechanistically, the STVNa-mediated protection against HFD-induced MCD involved inhibition of inflammation and oxidative stress. Furthermore, using Western blot analysis, we revealed that the critical members of the Sirt1/AMPK network were markedly activated in the STVNa-treated group, relative to HFD-fed controls. Collectively, these evidences suggested that the STVNa offered strong protection against HFD-induced MCD. Moreover, this effect was mediated by the activation of the Sirt1/AMPK network, which, in turn, promoted lipid metabolism.

PdeHCA2 affects biomass in Populus by regulating plant architecture, the transition from primary to secondary growth, and photosynthesis.

MAIN CONCLUSION: PdeHCA2 regulates the transition from primary to secondary growth, plant architecture, and affects photosynthesis by targeting PdeBRC1 and controlling the anatomy of the mesophyll, and intercellular space, respectively. Branching, secondary growth, and photosynthesis are vital developmental processes of woody plants that determine plant architecture and timber yield. However, the mechanisms underlying these processes are unknown. Here, we report that the Populus transcription factor High Cambium Activity 2 (PdeHCA2) plays a role in the transition from primary to secondary growth, vascular development, and branching. In Populus, PdeHCA2 is expressed in undifferentiated provascular cells during primary growth, in phloem cells during secondary growth, and in leaf veins, which is different from the expression pattern of its homolog in Arabidopsis. Overexpression of PdeHCA2 has pleiotropic effects on shoot and leaf development; overexpression lines showed delayed growth of shoots and leaves, reduced photosynthesis, and abnormal shoot branching. In addition, auxin-, cytokinin-, and photosynthesis-related genes were differentially regulated in these lines. Electrophoretic mobility shift assays and transcriptome analysis indicated that PdeHCA2 directly up-regulates the expression of BRANCHED1 and the MADS-box gene PdeAGL9, which regulate plant architecture, by binding to cis-elements in the promoters of these genes. Taken together, our findings suggest that HCA2 regulates several processes in woody plants including vascular development, photosynthesis, and branching by affecting the proliferation and differentiation of parenchyma cells.