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Background and Aims: In the digital age, Internet addiction (IA) was deemed an epidemic and few treatments had been effectively developed for it. Here, we proposed a solution-focused group counseling (SFGC) as a potentially solution to reduce Internet addiction among college students. The present study examined the short- and long-term effect of a five-week solution-focused group counseling intervention on Internet addiction. Methods: Thirty-two participants were recruited and randomly assigned to either the experimental or control group, and twenty-six participants completed the whole intervention. The experimental group (n = 14) received the intervention, while control group (n = 12) did not. The revised version of the Chinese Internet Addiction Scale (CIAS-R), the Future Time Perspective, and resting-state EEG were administered pre-intervention, post-intervention, and at two follow-up tests (one month and six months after intervention). Results: The results showed that the scores of the CIAS-R in the experimental group were significantly decreased after intervention, and these effects could be sustained for one month and six months follow-ups. Additionally, the intervention conducted an increase in future time perspective. EEG results further suggested that the alpha, beta, and gamma absolute power decreased after the intervention. Conclusion: These results from the pilot-study primarily suggested that solution-focused group counseling could be an effective intervention for Internet addiction. [ABSTRACT FROM AUTHOR]

Purpose: To study the influence of various doses of ropivacaine (Ropi) on postoperative analgesia, incidence of complications and stress factors in patients undergoing total knee arthroplasty (TKA). Methods: One hundred and fifty (150) patients who received TKA treatment in Ganzhou Hospital of Traditional Chinese Medicine from January 2017 to January 2019 were randomly assigned to low-dose Ropi (0.15%, group A), medium-dose Ropi (0.20%, group B) and high-dose Ropi (0.30%, group C), with 50 patients in each group. Changes in visual analogue scale (VAS) scores, MMSE scores, cognitive dysfunction, serum cortisol (Cor) and adverse reactions were determined before and after surgery. Results: Compared with group A, scores on rest visual analogue scale (RVAS) and passive visual analogue scale (PVAS) were significantly higher in low-dose and high-dose Ropi groups 24 and 48 h postoperatively (p < 0.05). Serum Cor levels in low-dose Ropi-treated patients were significantly lower than those in the other groups at 24 and 48 h after surgery (p < 0.05). The MMSE scores at 48 and 72 h after surgery were significantly higher in low-dose Ropi-treated patients than in the other 2 groups. The number of patients with cognitive impairment after surgery (POCD) was significantly higher in groups B and C than in A (p < 0.05). Conclusion: Low-dose Ropi exerts significant analgesic effect on elderly patients undergoing TKA, and improves their cognitive function without increasing stress response. Therefore, it should be further investigated on a larger scale for its potential as a candidate analgesic for patients after TKA. [ABSTRACT FROM AUTHOR]

DNA N6-adenine methylation (6mA), as a novel adenine modification existing in eukaryotes, shows essential functions in embryogenesis and mitochondrial transcriptions. ALKBH1 is a demethylase of 6mA and plays critical roles in osteogenesis, tumorigenesis, and adaptation to stress. However, the integrated biological functions of ALKBH1 still require further exploration. Here, we demonstrate that knockdown of ALKBH1 inhibits adipogenic differentiation in both human mesenchymal stem cells (hMSCs) and 3T3-L1 preadipocytes, while overexpression of ALKBH1 leads to increased adipogenesis. Using a combination of RNA-seq and N6-mA-DNA-IP-seq analyses, we identify hypoxia-inducible factor-1 (HIF-1) signaling as a crucial downstream target of ALKBH1 activity. Depletion of ALKBH1 leads to hypermethylation of both HIF-1α and its downstream target GYS1. Simultaneous overexpression of HIF-1α and GYS1 restores the adipogenic commitment of ALKBH1-deficient cells. Taken together, our data indicate that ALKBH1 is indispensable for adipogenic differentiation, revealing a novel epigenetic mechanism that regulates adipogenesis. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) are a recently identified class of phytohormones that regulate diverse developmental processes in land plants. However, the signaling mechanism of SLs in maize (Zea mays) remains largely unexplored. Here, we identified the maize gene DWARF 53 (ZmD53) and demonstrated that ZmD53 interacts with the SL receptors DWARF 14A/B (ZmD14A/B) in a rac-GR24-dependent manner. Transgenic maize plants expressing a gain-of-function mutant version of Zmd53 exhibited insensitivity to exogenous rac-GR24 treatment and a highly pleiotropic phenotype, including excess tillering and reduced tassel branching, indicating that ZmD53 functions as an authentic SL signaling repressor in maize. In addition, we showed that ZmD53 interacts with two homologous maize SPL transcription factors, UB3 and TSH4, and suppresses their transcriptional activation activity on TB1 to promote tillering. We also showed that UB2, UB3, and TSH4 can physically interact with each other and themselves, and that they can directly regulate the expression of TSH4, thus forming a positive feedback loop. Furthermore, we demonstrated that ZmD53 can repress the transcriptional activation activity of UB3 and TSH4 on their own promoters, thus decreasing tassel branch number. Our results reveal new insights into the integration of SL signaling and the miR156/SPL molecular module to coordinately regulate maize development. [ABSTRACT FROM AUTHOR]

Direct elimination of cccDNA remains a formidable obstacle due to the persistent and stable presence of cccDNA in hepatocyte nuclei. The silencing of cccDNA transcription enduringly is one of alternative strategies in the treatment of hepatitis B. Protein binding to cccDNA plays an important role in its transcriptional regulation; thus, the identification of key factors involved in this process is of great importance. In the present study, high mobility group nucleosome binding domain 1 (HMGN1) was screened out based on our biotin-avidin enrichment system. First, chromatin immunoprecipitation and fluorescent in situ hybridization assays confirmed the binding of HMGN1 with cccDNA in the nucleus. Second, functional experiments in HBV-infected cells showed that the promoting effect of HMGN1 on HBV transcription and replication depended on the functional region of the nucleosomal binding domain, while transfection of the HMGN1 mutant showed no influence on HBV compared with the vector. Third, further mechanistic exploration revealed that the silencing of HMGN1 increased the level of phosphorylase CLK2 and promoted H3 phosphorylation causing the reduced accessibility of cccDNA. Moreover, silenced HMGN1 was mimicked in HBV (r) cccDNA mouse model of HBV infection in vivo. The results showed that silencing HMGN1 inhibited HBV replication in vivo. In summary, our study identified that a host protein can bind to cccDNA and promote its transcription, providing a candidate strategy for anti-HBV targeting to interfere with the transcriptional activity of cccDNA microchromosomes. [Display omitted] • HMGN1 was confirmed a chromatin binding protein promoting cccDNA transcription in vitro and in vivo. • HMGN1 efficiently enhanced cccDNA accessibility by competitively combining with H1. • HMGN1 promoted cccDNA transcription by regulating histone 3 phosphorylation. • Histone phosphorylase CLK2 was responsible for HMGN1 mediated histone 3 phosphorylation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of Wuling powder (WP) on the pharmacokinetics of valproic acid (VPA) in epileptic rats. Methods: A model of epilepsy was established in SD rats by intraperitoneal injection of pentylenetetrazole (PTZ). Twelve epileptic rats were randomly divided into two groups: control group given oral VPA alone at a dose of 180 mg/kg VPA, and drug combination group orally given VPA (180 mg/kg) co-administered with WP at a dose of 200 mg/kg. Blood sample (0.5 mL) was collected at 15, 30, 60, 120, 240 and 720 min after drug administration for measurement of plasma concentrations of VPA using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: The AUC (0-480min) and maximum plasma concentrations (Cmax) of VPA in the drug combination group were significantly higher than those in the control group (p < 0.01). The half-time (t1/2) and time taken to attain maximum plasma VPA concentration (Tmax) in the combination group were extended, when compared to control group (p < 0.05). Conclusion: These results demonstrate that WP increases the plasma concentration of VPA and affects the pharmacokinetic properties of VPA in epileptic rats. Thus, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing WP to epileptic patients already taking VPA. [ABSTRACT FROM AUTHOR]

Internet addiction was considered as an epidemic in the digital age, and we have few effective treatments. Here, we proposed a solution-focused group counseling that could potentially reduce the Internet addiction among college students. The present study used behavior and resting state EEG to examine short-term and long-term effect of this intervention. Through questionnaire and structured interview, 32 participants were recruited and randomly assigned into the experimental group (n=16) and control group (n=16). The experimental group received a five-week solution-focused group counseling, while control group did not receive any intervention. The revised version of the Chinese Internet Addiction Scale (CIAS-R) and resting-state EEG were administered pre- and post-intervention, as well as two follow-up tests (one month and six months after intervention). Results showed that the scores of four dimensions of the CIAS-R in the experimental group were significantly decreased after intervention, and these effects could last for one month and six months follow-ups. EEG results suggested that the beta and gamma absolute power in the experimental group decreased after intervention. These results suggested that solution-focused group counseling could be an effective intervention on Internet addiction. [ABSTRACT FROM AUTHOR]

An advanced electrochemical sensor for the detection of enrofloxacin (ENR) based on the use of a modified electrode containing cadmium sulfide (CdS) nanoparticles (NPs) is reported. The CdS NPs were synthesized and characterized and then coated onto the electrode to fabricate a modified electrode that exhibited a lower limit of detection of 9.5 × 10−8 mol·L−1. This detection limit compares with a traditional electrode that exhibited a concentration detection range of 1.0 × 10−2 to 1.0 × 10−7 mol·L−1. This modified electrode demonstrated good selectivity, reproducibility, response time (<40 s), lifetime (up to 12 wk), and pH range (3.3‐7.2) for the determination of ENR in real samples (eg, pig urine). [ABSTRACT FROM AUTHOR]

Polar auxin transport, facilitated by the combined activities of auxin influx and efflux carriers to maintain asymmetric auxin distribution, is essential for plant growth and development. Here, we show that Arabidopsis (Arabidopsis thaliana) RopGEF1, a guanine nucleotide exchange factor and activator of Rho GTPases of plants (ROPs), is critically involved in polar distribution of auxin influx carrier AUX1 and differential accumulation of efflux carriers PIN7 and PIN2 and is important for embryo and early seedling development when RopGEF1 is prevalently expressed. Knockdown or knockout of RopGEF1 induces embryo defects, cotyledon vein breaks, and delayed root gravity responses. Altered expression from the auxin response reporter DR5rev:GFP in the root pole of RopGEF1-deficient embryos and loss of asymmetric distribution of DR5rev:GFP in their gravistimulated root tips suggest that auxin distribution is affected in ropgef1 mutants. This is reflected by the polarity of AUX1 being altered in ropgef1 embryos and roots, shifting from the normal apical membrane location to a basal location in embryo central vascular and root protophloem cells and also reduced PIN7 accumulation at embryos and altered PIN2 distribution in gravistimulated roots of mutant seedlings. In establishing that RopGEF1 is critical for AUX1 localization and PIN differential accumulation, our results reveal a role for RopGEF1 in cell polarity and polar auxin transport whereby it imapcts auxin-mediated plant growth and development. [ABSTRACT FROM AUTHOR]

Stem cells serve as the source of new cells for plant development. A group of stem cells form a stem cell niche (SCN) at the root tip and in the center of the SCN are slowly dividing cells called the quiescent center (QC). QC is thought to function as a signaling hub that inhibits differentiation of surrounding stem cells. Although it has been generally assumed that cell-to-cell communication provides positional information for QC and SCN maintenance, the tools for testing this hypothesis have long been lacking. Here we exploit a system that effectively blocks plasmodesmata (PD)-mediated signaling to explore how cell-to-cell communication functions in the SCN. We showed that the symplastic signaling between the QC and adjacent cells directs the formation of local auxin maxima and establishment of AP2-domain transcription factors, PLETHORA gradients. Interestingly we found symplastic signaling is essential for local auxin biosynthesis, which acts together with auxin polar transport to provide the guidance for local auxin enrichment. Therefore, we demonstrate the crucial role of cell-to-cell communication in the SCN maintenance and further uncover a mechanism by which symplastic signaling initiates and reinforces the positional information during stem cell maintenance via auxin regulation. [ABSTRACT FROM AUTHOR]

Background: The nuclear hormone receptor RORγ regulates transcriptional genes involved in the production of the pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This transcriptional activity of RORγ is modulated through a protein-protein interaction involving the activation function 2 (AF2) helix on the ligand binding domain of RORγ and a conserved LXXLL helix motif on coactivator proteins. Our goal was to develop a RORγ specific inverse agonist that would help down regulate pro-inflammatory gene transcription by disrupting the protein protein interaction with coactivator proteins as a therapeutic agent. Results: We identified a novel series of synthetic benzoxazinone ligands having an agonist (BIO592) and inverse agonist (BIO399) mode of action in a FRET based assay. We show that the AF2 helix of RORγ is proteolytically sensitive when inverse agonist BIO399 binds. Using x-ray crystallography we show how small modifications on the benzoxazinone agonist BIO592 trigger inverse agonism of RORγ. Using an in vivo reporter assay, we show that the inverse agonist BIO399 displayed specificity for RORγ over ROR sub-family members α and β. Conclusion: The synthetic benzoxazinone ligands identified in our FRET assay have an agonist (BIO592) or inverse agonist (BIO399) effect by stabilizing or destabilizing the agonist conformation of RORγ. The proteolytic sensitivity of the AF2 helix of RORγ demonstrates that it destabilizes upon BIO399 inverse agonist binding perturbing the coactivator protein binding site. Our structural investigation of the BIO592 agonist and BIO399 inverse agonist structures identified residue Met358 on RORγ as the trigger for RORγ specific inverse agonism. [ABSTRACT FROM AUTHOR]

Specific recognition of centromere-specific histone variant CENP-A-containing chromatin by CENP-N is an essential process in the assembly of the kinetochore complex at centromeres prior to mammalian cell division. However, the mechanisms of CENP-N recruitment to centromeres/kinetochores remain unknown. Here, we show that a CENP-A-specific RG loop (Arg80/Gly81) plays an essential and dual regulatory role in this process. The RG loop assists the formation of a compact "ladder-like" structure of CENP-A chromatin, concealing the loop and thus impairing its role in recruiting CENP-N. Upon G1/S-phase transition, however, centromeric chromatin switches from the compact to an open state, enabling the now exposed RG loop to recruit CENP-N prior to cell division. Our results provide the first insights into the mechanisms by which the recruitment of CENP-N is regulated by the structural transitions between compaction and relaxation of centromeric chromatin during the cell cycle. [ABSTRACT FROM AUTHOR]

DNA methylation at the C-5 position of cytosine (5mC) is one of the best-studied epigenetic modifications and plays important roles in diverse biological processes. Iterative oxidation of 5mC by the ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are selectively recognized and excised by thymine DNA glycosylase (TDG), leading to DNA demethylation. Functional characterization of Tet proteins has been complicated by the redundancy between the three family members. Using CRISPR/Cas9 technology, we generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (Tet triple knockout [TKO]). Whole-genome bisulfite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs at distally located enhancers and fine-tunes the transcription of genes associated with these regions. Functional characterization of Tet TKO ESCs revealed a role for Tet proteins in regulating the two-cell embryo (2C)-like state under ESC culture conditions. In addition, Tet TKO ESCs exhibited increased telomere-sister chromatid exchange and elongated telomeres. Collectively, our study reveals a role for Tet proteins in not only DNA demethylation at enhancers but also regulating the 2C-like state and telomere homeostasis. [ABSTRACT FROM AUTHOR]

After analyzing the current characteristics and problems of residential space in small towns in the Pearl River Delta Region (PRDR), combined with the New Urbanism theory and community construction methods, this paper puts forward a restructuring strategy of residential space, which includes the reorganization of residential space using the "community - residential quarter - neighborhood" model, the reform of the community management mode based on the "transformation from village council to resident committee," the restructuring of the multi-level community service system to meet the diversified social needs, and the construction of a mixed community addressing the issue of residential segregation and the aim to achieve community integration. [ABSTRACT FROM AUTHOR]

The body temperature is considered a universal cue by which the master clock synchronizes the peripheral clocks in mammals, but the mechanism is not fully understood. Here we identified two cold-induced RNA-binding proteins (RBPs), Cirbp and Rbm3, as important regulators for the temperature entrained circadian gene expression. The depletion of Cirbp or Rbm3 significantly reduced the amplitudes of core circadian genes. PAR-CLIP analyses showed that the 39UTR binding sites of Cirbp and Rbm3 were significantly enriched near the polyadenylation sites (PASs). Furthermore, the depletion of Cirbp or Rbm3 shortened 3'UTR, whereas low temperature (upregulating Cirbp and Rbm3) lengthened 3'UTR. Remarkably, we found that they repressed the usage of proximal PASs by binding to the common 39UTR, and many cases of proximal/distal PAS selection regulated by them showed strong circadian oscillations. Our results suggested that Cirbp and Rbm3 regulated the circadian gene expression by controlling alternative polyadenylation (APA). [ABSTRACT FROM AUTHOR]

Increased C02 and associated acidification in seawater, known as ocean acidification, decreases calcification of most marine calcifying organisms. However, there is little information available on how marine macroalgae would respond to the chemical changes caused by seawater acidification. We hypothesized that down-regulation of bicarbonate acquisition by algae under increased acidity and C02 levels would lower the threshold above which photosynthetically active radiation (PAR) becomes excessive. Juveniles of Ulva prolifera derived from zoospores were grown at ambient (390 gatm) and elevated (1000 patm) C02 concentrations for 80 days before the hypothesis was tested. Here, the C02-induced seawater acidification increased the quantum yield under low levels of light, but induced higher nonphotochemical quenching under high light. At the same time, the PAR level at which photosynthesis became saturated was decreased and the photosynthetic affinity for C02 or inorganic carbon decreased in the high-C02 grown plants. These findings indicated that ocean acidification, as an environmental stressor, can reduce the threshold above which PAR becomes excessive. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are 19- to 25-nucleotide-long small and noncoding RNAs now well-known for their regulatory roles in gene expression through posttranscriptional and translational controls. Mammalian hibernation is a physiological process involving profound changes in set-points for food consumption, body mass and growth, body temperature, and metabolic rate in which miRNAs may play important regulatory roles. In an initial study, we analyzed miRNAs in the liver of an extreme hibernating species, the Arctic ground squirrel (Spermophilus parryii), using massively parallel Illumina sequencing technology. We identified >200 ground squirrel miRNAs, including 18 novel miRNAs specific to ground squirrel and mir-506 that is fast evolving in the ground squirrel lineage. Comparing animals sampled after at least 8 days of continuous torpor (late torpid), within 5 h of a spontaneous arousal episode (early aroused), and 1-2 mo after hibernation had ended (nonhibernating), we identified differentially expressed miRNAs during hibernation, which are also compared with the results from two other miRNA profiling methods: Agilent miRNA microarray and real-time PCR. Among the most significant miRNAs, miR-320 and miR-378 were significantly underexpressed during both stages of hibernation compared with nonhibernating animals, whereas miR-486 and miR-451 were overexpressed in late torpor but returned in early arousal to the levels similar to those in nonhibernating animals. Analyses of their putative target genes suggest that these miRNAs could play an important role in suppressing tumor progression and cell growth during hibernation. High-throughput sequencing data and microarray data have been submitted to GEO database with accession: GSE19808. [ABSTRACT FROM AUTHOR]

This paper is concerned with a framework to compute the importance of webpages by using real browsing behaviors of Web users. In contrast, many previous approaches like PageRank compute page importance through the use of the hyperlink graph of the Web. Recently, people have realized that the hyperlink graph is incomplete and inaccurate as a data source for determining page importance, and proposed using the real behaviors of Web users instead. In this paper, we propose a formal framework to compute page importance from user behavior data (which covers some previous works as special cases). First, we use a stochastic process to model the browsing behaviors of Web users. According to the analysis on hundreds of millions of real records of user behaviors, we justify that the process is actually a continuous-time time-homogeneous Markov process, and its stationary probability distribution can be used as the measure of page importance. Second, we propose a number of ways to estimate parameters of the stochastic process from real data, which result in a group of algorithms for page importance computation (all referred to as BrowseRank). Our experimental results have shown that the proposed algorithms can outperform the baseline methods such as PageRank and TrustRank in several tasks, demonstrating the advantage of using our proposed framework. [ABSTRACT FROM AUTHOR]

Within the process of urban expansion through land requisition in China, farmers' defacto rights to collective land, including farmland and housing plots (zhaijidi), are forcibly acquired by the state and thereafter redistributed to private developers, to facilitate urban-based economic growth. Deprived of a secure livelihood, some landless farmers become trapped in poverty. Others find that the property rights restructuring in urbanised villages gives them an opportunity to earn rental income. However, the opportunities are not equally distributed and the processes are, in general, stacked against the interests of villagers. This paper analyses the impoverishment of farmers caught up in China's relentless urban expansion programme, using the perspectives of property rights and entitlements. It presents case studies of two villages in Xi'an to illustrate how farmers' entitlement sets and vulnerability to poverty have changed as a result of changes in land rights. [ABSTRACT FROM AUTHOR]

Since the 1990s, the introduction of a market economy and the process of rapid urbanization have been accompanied by a new urban poverty related to lay-offs and unemployment as well as by large-scale rural–urban migration, which is different from the traditional urban poverty of the ‘Three Nos’ (no relatives or dependants, no working capacity and no source of income). This article focuses on new urban poverty in China under market transition and discusses the causes of poverty creation. Instead of considering Chinese new urban poverty only as a result of market mechanisms, it argues that the state as the manipulator of institutions and policies does matter in the creation of new urban poverty, and that the cleavages between the old and new institutions further intensify it. Specifically, the following aspects of the creation of new urban poverty are examined in detail: the adjustment of industrial policy, the reform of state-owned enterprises, evolution of the household registration system, and the transformation of the welfare state. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the usefulness of optical coherence tomography angiography (OCTA) in assessing retinal microvascular structural changes in preterm-born children and compare them with those in term-born children. The Web of Science Library, Cochrane Library, PubMed, Embase, CNKI, Wanfang, VIP, and Sino Med databases were searched systematically to extract studies published till April 25, 2023. Two independent reviewers searched all the literature and completed the data extraction and quality assessment. Mean differences (MDs) with 95% confidence intervals (CIs) were used to assess the continuous estimates. STATA software (v15.1; StataCorp, College Station, TX) was used to analyze the data. Twelve published studies were eligible for inclusion in this study. The meta-analysis revealed that the foveal avascular zone (FAZ) area of preterm-born children was remarkably smaller than that of term-born children, with the laser photocoagulation (LP)-ROP group showing the most pronounced reduction. The foveal superficial capillary plexus vessel density (SCP-VD) and deep capillary plexus vessel density (DCP-VD) were remarkably higher in the preterm-born group than in the control group, with variations in subgroups (LP-ROP, anti-VEGF-ROP, SR-ROP, and Pre-T-ROP). The parafoveal SCP-VD was remarkably lower in preterm-born children compared to that of the controls, while no significant difference was identified in the parafoveal DCP-VD. Preterm-born children had a smaller FAZ area, higher foveal SCP-VD and DCP-VD, and lower parafoveal SCP-VD compared to their term-born counterparts. The parafoveal DCP-VD did not differ substantially between preterm- and term-born children. OCTA is an effective modality for assessing alterations in the retinal microvasculature in preterm children. [ABSTRACT FROM AUTHOR]

microRNA-21 (miR-21) is the most commonly upregulated miRNA in solid tumors. This cancer-associated microRNA (oncomiR) regulates various downstream effectors associated with tumor pathogenesis during all stages of carcinogenesis. In this study, we analyzed the function of miR-21 in noncancer cells of the tumor microenvironment to further evaluate its contribution to tumor progression. We report that the expression of miR-21 in cells of the tumor immune infiltrate, and in particular in macrophages, was responsible for promoting tumor growth. Absence of miR-21 expression in tumor- associated macrophages (TAMs), caused a global rewiring of their transcriptional regulatory network that was skewed toward a proinflammatory angiostatic phenotype. This promoted an antitumoral immune response characterized by a macrophage-mediated improvement of cytotoxic T-cell responses through the induction of cytokines and chemokines, including IL-12 and C-X-C motif chemokine 10. These effects translated to a reduction in tumor neovascularization and an induction of tumor cell death that led to decreased tumor growth. Additionally, using the carrier peptide pH (low) insertion peptide, we were able to target miR-21 in TAMs, which decreased tumor growth even under conditions where miR-21 expression was deficient in cancer cells. Consequently, miR-21 inhibition in TAMs induced an angiostatic and immunostimulatory activation with potential therapeutic implications. [ABSTRACT FROM AUTHOR]

Radiotherapy is a common therapeutic strategy used to treat esophageal squamous cell carcinoma (ESCC). However, tumor cells often develop radioresistance, thereby reducing treatment efficacy. Here, we aimed to identify the mechanisms through which ESCC cells develop radioresistance and identify associated biomarkers. Eca109 cells were exposed to repeated radiation at 2 Gy/fraction for a total dose of 60 Gy (Eca109R60/2Gy cells). MTT and colony formation assays were performed to measure cell proliferation and compare the radiation biology parameters of Eca109 and Eca109R60/2Gy cells. Cell cycle distributions and apoptosis were assessed by flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were employed to analyze the expression of HOX transcript antisense RNA (HOTAIR), in addition to biomarkers of the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Eca109R60/2Gy cells exhibited increased cell proliferation and clone formation, with significantly higher radiobiological parameters compared with the parental Eca109 cells. The Eca109R60/2Gy cells also exhibited significantly decreased accumulation in G2 phase and increased accumulation in S phase. Additionally, the apoptosis rate was significantly lower in Eca109R60/2Gy cells than in parental Eca109 cells. Finally, HOTAIR expression levels and SNAI1 and β-catenin mRNA and protein expression levels were significantly higher, whereas E-cadherin levels were significantly lower in Eca109R60/2Gy cells than in Eca109 cells. Therefore, our findings demonstrated that radioresistance was affected by the expression of HOTAIR and biomarkers of the EMT and CSCs. [ABSTRACT FROM AUTHOR]

Chromatin instability and protein homeostasis (proteostasis) stress are two well-established hallmarks of aging, which have been considered largely independent of each other. Using microfluidics and single-cell imaging approaches, we observed that, during the replicative aging of Saccharomyces cerevisiae, a challenge to proteostasis occurs specifically in the fraction of cells with decreased stability within the ribosomal DNA (rDNA). A screen of 170 yeast RNA-binding proteins identified ribosomal RNA (rRNA)-binding proteins as the most enriched group that aggregate upon a decrease in rDNA stability induced by inhibition of a conserved lysine deacetylase Sir2. Further, loss of rDNA stability induces age-dependent aggregation of rRNA-binding proteins through aberrant overproduction of rRNAs. These aggregates contribute to age-induced proteostasis decline and limit cellular lifespan. Our findings reveal a mechanism underlying the interconnection between chromatin instability and proteostasis stress and highlight the importance of cell-to-cell variability in aging processes. [ABSTRACT FROM AUTHOR]

The article focuses on dangling bond–free surface makes it extremely difficult to deposit gate dielectrics with high-quality interface in metal-oxide-semiconductor (MOS) field-effect transistors (FETs). It mentions ultrathin two-dimensional (2D) semiconductors are regarded as a potential channel material for low-power transistors with small subthreshold swing and low leakage current. It also mentions transferred metal gate (TMG) and back gate enable logic functions.

Linear magnetoelectric (ME) and nonlinear magnetoelectric effects are considered systematically in this paper. We have prepared 3 multi-push-pull magnetoelectric laminated composites Metglas/ PMNT/Metglas with n layers metglas (n=1, 2, and 3). When n increases from 1 to 3, the linear magnetoelectric charge coefficients increase from 1900 to 2200 and then to 2600 pC/Oe at 2Hz under their each optimal magnetic bias. By using these 3 ME composites, we have also prepared 3 ME sensors, the sensitivity of which are as low as 130, 168, and 199 pT√Hz at 1Hz for n=1, 2, and 3, respectively, via nonlinear modulation method. Therefore, the nonlinear ME charge coefficients decrease as layer numbers of metglas increase, which is different with the ME charge linear coefficient's increasing trend, also demonstrated coupled with the finite element analysis method. The factors that result in the higher nonlinear ME charge coefficient in ME composites with fewer metglas layers are analyzed and discussed in detail. [ABSTRACT FROM AUTHOR]

The stem cell niche (SCN) is critical in maintaining continuous postembryonic growth of the plant root. During their growth in soil, plant roots are often challenged by various biotic or abiotic stresses, resulting in damage to the SCN. This can be repaired by the reconstruction of a functional SCN. Previous studies examining the SCN's reconstruction often introduce physical damage including laser ablation or surgical excision. In this study, we performed a time-course observation of the SCN reconstruction in pWOX5:icals3m roots, an inducible system that causes non-invasive SCN differentiation upon induction of estradiol on Arabidopsis (Arabidopsis thaliana) root. We found a stage-dependent reconstruction of SCN in pWOX5:icals3m roots, with division-driven anatomic reorganization in the early stage of the SCN recovery, and cell fate specification of new SCN in later stages. During the recovery of the SCN, the local accumulation of auxin was coincident with the cell division pattern, exhibiting a spatial shift in the root tip. In the early stage, division mostly occurred in the neighboring stele to the SCN position, while division in endodermal layers seemed to contribute more in the later stages, when the SCN was specified. The precise re-positioning of SCN seemed to be determined by mutual antagonism between auxin and cytokinin, a conserved mechanism that also regulates damage-induced root regeneration. Our results thus provide time-course information about the reconstruction of SCN in intact Arabidopsis roots, which highlights the stage-dependent re-patterning in response to differentiated quiescent center. [ABSTRACT FROM AUTHOR]

Inositol-1,4,5-triphosphate (IP3) kinase B (ITPKB) is a ubiquitously expressed lipid kinase that inactivates IP3, a secondary messenger that stimulates calcium release from the endoplasmic reticulum (ER). Genome-wide association studies have identified common variants in the ITPKB gene locus associated with reduced risk of sporadic Parkinson's disease (PD). Here, we investigate whether ITPKB activity or expression level impacts PD phenotypes in cellular and animal models. In primary neurons, knockdown or pharmacological inhibition of ITPKB increased levels of phosphorylated, insoluble a-synuclein pathology following treatment with α-synuclein preformed fibrils (PFFs). Conversely, ITPKB overexpression reduced PFF-induced α-synuclein aggregation. We also demonstrate that ITPKB inhibition or knockdown increases intracellular calcium levels in neurons, leading to an accumulation of calcium in mitochondria that increases respiration and inhibits the initiation of autophagy, suggesting that ITPKB regulates α-synuclein pathology by inhibiting ER-to-mitochondria calcium transport. Furthermore, the effects of ITPKB on mitochondrial calcium and respiration were prevented by pretreatment with pharmacological inhibitors of the mitochondrial calcium uniporter complex, which was also sufficient to reduce α-synuclein pathology in PFF-treated neurons. Taken together, these results identify ITPKB as a negative regulator of α-synuclein aggregation and highlight modulation of ER-to-mitochondria calcium flux as a therapeutic strategy for the treatment of sporadic PD. [ABSTRACT FROM AUTHOR]

Purpose: To determine the inhibitory effects of Wuling mycelia, alone and in combination with valproic acid (VPA) on pentylenetetrazol (PTZ)-induced epileptic seizure in rats, and their protective effects on cognitive impairment. Methods: Sprague-Dawley rats were randomly divided into five groups: control (sham), model, Wuling mycelia, VPA and combination groups. Rats in Wuling mycelia group were given oral Wuling mycelia alone at a dose of 594 mg/kg, while those in VPA group were given oral VPA alone at a dose of 189 mg/kg. In the combination group, rats received oral VPA at a dose of 189 mg/kg co-administered with Wuling mycelia at a dose of 594 mg/kg. One hour after the treatments, the control group was injected with physiological saline intraperitoneally, while the other four groups were injected with PTZ solution once a day for 28 days. Subsequently, seizure intensity, cognitive impairment, neuronal loss and hippocampal expressions of IL-1β, NF-ΚB/p65 and TLR4 were determine in all groups. Results: Combined use of Wuling mycelium and VPA significantly reduced the frequency and the grade of seizures (p <0.01), and also decreased the degree of cognitive impairment (p <0.05). There were marked increases in neuronal damage and hippocampal expression levels of NF-ΚB/p65, TLR4 and IL- 1β (inflammatory cytokines) in the model group (p < 0.05). However, these changes were reversed in the combination treatment group (p < 0.05). Conclusion: Wuling mycelia is a potentially effective adjunct drug for the treatment of refractory epilepsy. The underlying mechanism might involve downregulations of NF-ΚB/p65, TLR4 and IL-1β. [ABSTRACT FROM AUTHOR]

The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells. Strikingly, the clinical response correlates with the frequency of CD4 cells in the infused T cells. Although in vitro studies suggested that EBV-specific CD4 cells develop cytotoxicity, they have not been comprehensively characterized and the molecular mechanism underlying their formation remains unknown. Our recent work, using a transgenic approach in mice, has revealed a central role for the EBV signaling molecule LMP1 in immune surveillance and transformation of EBV-infected B cells. The mouse model offers a unique tool for uncovering basic features of EBV immunity. Here, we show that LMP1 expression in B cells induces potent cytotoxic CD4 and CD8 T cell responses, by enhancing antigen presentation and costimulation by CD70, OX40 ligand, and 4-1BB ligand. Our data further suggest that cytotoxic CD4 cells hold superior therapeutic value for LMP1 (EBV)-driven lymphomas. These findings provide insights into EBV immunity, demonstrating that LMP1 signaling alone is sufficient to induce a prominent cytotoxic CD4 response, and suggest strategies for immunotherapy in EBVrelated and other cancers. [ABSTRACT FROM AUTHOR]

We report here an approach to redirecting somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts to epithelial-like cells with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting epithelial-like cells that can be further reprogrammed to endodermal progenitor cells. Interestingly, these cells can self-renew in vitro and further differentiate into albumin- producing hepatocytes that can rescue mice from acute liver injury. Our results demonstrate a rational approach to convert mouse embryonic fibroblasts to hepatocytes and suggest that this mechanism-driven approach may be generalized for other cells. [ABSTRACT FROM AUTHOR]

A novel method for proximity detection of moving targets (with high dielectric constants) using a large-scale (the size of each sensor is 31 cm × 19 cm) planar capacitive sensor system (PCSS) is proposed. The capacitive variation with distance is derived, and a pair of electrodes in a planar capacitive sensor unit (PCSU) with a spiral shape is found to have better performance on sensitivity distribution homogeneity and dynamic range than three other shapes (comb shape, rectangular shape, and circular shape). A driving excitation circuit with a Clapp oscillator is proposed, and a capacitance measuring circuit with sensitivity of 0.21 Vp Vp-PF is designed. The results of static experiments and dynamic experiments demonstrate that the voltage curves of static experiments are similar to those of dynamic experiments; therefore, the static data can be used to simulate the dynamic curves. The dynamic range of proximity detection for three projectiles is up to 60 cm, and the results of the following static experiments show that the PCSU with four neighboring units has the highest sensitivity (the sensitivities of other units are at least 4% lower); when the attack angle decreases, the intensity of sensor signal increases. This proposed method leads to the design of a feasible moving target detector with simple structure and low cost, which can be applied in the interception system. [ABSTRACT FROM AUTHOR]

Background Liver regeneration is a complex process regulated by many complex mechanisms involving cytokines, growth factors, metabolic networks, and so forth. Previous investigations have demonstrated that matrix metalloproteinase-9 (MMP-9) is an essential factor in liver regeneration. The present study aimed to explore the role of MMP-9 in epidermal growth factor receptor (EGFR) signaling and related proliferation signaling factors in a mouse partial hepatectomy (PH) model. Materials and methods MMP-9 knockout (KO) and wild-type mice were used to establish the PH model. Liver regeneration was analyzed based on proliferation cell nuclear antigen immunohistochemistry and liver weight to body weight ratio. Also, EGFR ligands, EGFR, and downstream factors were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot. Results MMP-9 KO mice showed a delayed hepatic regenerative response after PH. EGFR ligands, including heparin-binding epidermal growth factor and amphiregulin, were expressed at significantly lower levels between days 1 and 3 posthepatectomy in MMP-9 KO mice. MMP-9 KO mice also inhibited and delayed EGFR activation after PH. After PH, the expression of STAT3, NF-κB, and cyclinD1, all downstream of EGFR, was similar to EGFR activation. Conclusions Our data provide new evidence supporting a critical role of MMP-9 in liver regeneration after PH through activation of EGFR signaling. [ABSTRACT FROM AUTHOR]

17-Allylamino-17-demethoxygeldanamycin (17-AAG), a typical Hsp90 inhibitor derived from geldanamycin (GA), has entered Phase III clinical trials for cancer therapy. However, it has several significant limitations such as poor solubility, limited bioavailability and unacceptable hepatotoxicity. In this study, the anticancer activity and mechanism of SNX-25a, a novel Hsp90 inhibitor, was investigated comparing with that of 17-AAG. We showed that SNX-25a triggered growth inhibition more sensitively than 17-AAG against many human cancer cells, including K562, SW-620, A375, Hep-2, MCF-7, HepG2, HeLa, and A549 cell lines, especially at low concentrations (<1 µM). It showed low cytotoxicity in L-02, HDF and MRC5 normal human cells. Compared with 17-AAG, SNX-25a was more potent in arresting the cell cycle at G2 phase, and displayed more potent effects on human cancer cell apoptosis and Hsp90 client proteins. It also exhibited a stronger binding affinity to Hsp90 than 17-AAG using molecular docking. Considering the superiority effects on Hsp90 affinity, cell growth, cell cycle, apoptosis, and Hsp90 client proteins, SNX-25a is supposed as a potential anticancer agent that needs to be explored in detail. [ABSTRACT FROM AUTHOR]

Background: Recombination plays an important role in the maintenance of genetic diversity in many types of organisms, especially diploid eukaryotes. Recombination can be studied and used to map diseases. However, recombination adds a great deal of complexity to the genetic information. This renders estimation of evolutionary parameters more difficult. After the coalescent process was formulated, models capable of describing recombination using graphs, such as ancestral recombination graphs (ARG) were also developed. There are two typical models based on which to simulate ARG: back-in-time model such as ms and spatial model including Wiuf&Hein’s, SMC, SMC’, and MaCS. Results: In this study, a new method of modeling coalescence with recombination, Spatial Coalescent simulator (SC), was developed, which considerably improved the algorithm described by Wiuf and Hein. The present algorithm constructs ARG spatially along the sequence, but it does not produce any redundant branches which are inevitable in Wiuf and Hein’s algorithm. Interestingly, the distribution of ARG generated by the present new algorithm is identical to that generated by a typical back-in-time model adopted by ms, an algorithm commonly used to model coalescence. It is here demonstrated that the existing approximate methods such as the sequentially Markov coalescent (SMC), a related method called SMC′, and Markovian coalescent simulator (MaCS) can be viewed as special cases of the present method. Using simulation analysis, the time to the most common ancestor (TMRCA) in the local trees of ARGs generated by the present algorithm was found to be closer to that produced by ms than time produced by MaCS. Sample-consistent ARGs can be generated using the present method. This may significantly reduce the computational burden. Conclusion: In summary, the present method and algorithm may facilitate the estimation and description of recombination in population genomics and evolutionary biology. [ABSTRACT FROM AUTHOR]

Over 100 point mutations in the rhodopsin gene have been associated with retinitis pigmentosa (RP), a family of inherited visual disorders. Among these, we focused on characterizing the S186W mutation. We compared the thermal properties of the S186W mutant with another RP-causing mutant, D190N, and withWTrhodopsin. To assess thermal stability, we measured the rate of two thermal reactions contributing to the thermal decay of rhodopsin as follows: thermal isomerization of 11-cis-retinal and hydrolysis of the protonated Schiff base linkage between the 11-cisretinal chromophore and opsin protein.Weused UV-visible spectroscopy andHPLCto examine the kinetics of these reactions at 37 and 55 °C for WT and mutant rhodopsin purified from HEK293 cells. Compared with WT rhodopsin and the D190N mutant, the S186W mutation dramatically increases the rates of both thermal isomerization and dark state hydrolysis of the Schiff base by 1-2 orders of magnitude. The results suggest that the S186W mutant thermally destabilizes rhodopsin by disrupting a hydrogen bond network at the receptor's active site. The decrease in the thermal stability of dark state rhodopsin is likely to be associated with higher levels of dark noise that undermine the sensitivity of rhodopsin, potentially accounting for night blindness in the early stages of RP. Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients. [ABSTRACT FROM AUTHOR]

Astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV), due to the high energies and long distances involved. In quantum theory of gravity, one may expect the modification of the dispersion relation between energy and momentum for photons, which can be probed with the time lag (the arrival time delay between light curves in different energy bands) of gamma-ray bursts (GRBs). In this paper, by using the detailed time delay measurements of GRB 160625B at different energy bands, as well as 23 time delay GRBs covering the redshift range of z = 0.168–2.5 (which were measured at different energy channels from the light curves), we propose an improved model-independent method (based on the newly compiled sample of H(z) measurements) to probe the energy-dependent velocity due to the modified dispersion relation for photons. In the framework of a more complex and reasonable theoretical expression to describe the time delays, our results imply that the intrinsic time lags can be better described with more GRB time delay data. More importantly, through direct fitting of the time delay measurements of a sample of GRBs, our limit on the LIV energy scale is comparable to that with unknown constant for the intrinsic time lag, much lower than the Planck energy scale in both linear LIV and quadratic LIV cases. [ABSTRACT FROM AUTHOR]

Cosmological applications of H ii galaxies and giant extragalactic H ii regions (GEHRs) to construct the Hubble diagram at high redshifts require knowledge of the “L–σ” relation of the standard candles used. In this paper, we study the properties of a large sample of 156 sources (25 high-z H ii galaxies, 107 local H ii galaxies, and 24 GEHRs) compiled by Terlevich et al. Using the cosmological distances reconstructed through two new cosmology-independent methods, we investigate the correlation between the Hβ emission-line luminosity L and the ionized gas velocity dispersion σ. The method is based on non-parametric reconstruction using the measurements of Hubble parameters from cosmic clocks, as well as the simulated data of gravitational waves from the third-generation gravitational wave detector (the Einstein Telescope, ET), which can be considered as standard sirens. Assuming the relation between emission-line luminosity and ionized gas velocity dispersion, , we find that the full sample provides a tight constraint on the correlation parameters. However, similar analysis done on three different subsamples seems to support the scheme of treating H ii galaxies and GEHRs with distinct strategies. Using the corrected “L–σ” relation for the H ii observational sample beyond the current reach of Type Ia supernovae, we obtain values of the matter density parameter, Ωm = 0.314 ± 0.054 (calibrated with standard clocks) and Ωm = 0.311 ± 0.049 (calibrated with standard sirens), in the spatially flat ΛCDM cosmology. [ABSTRACT FROM AUTHOR]

In this paper, we present a scheme to investigate the opacity of the universe in a cosmological-model-independent way, with the combination of current and future measurements of an SN Ia sample and galactic-scale strong gravitational lensing systems with SNe Ia acting as background sources. The observational data include the current newly compiled SNe Ia data (Pantheon sample) and a simulated sample of SNe Ia observed by the forthcoming Large Synoptic Survey Telescope (LSST), which are taken for luminosity distances (DL) possibly affected by the cosmic opacity, as well as strongly lensed SNe Ia observed by the LSST, which are responsible for providing the observed time-delay distance unaffected by the cosmic opacity. Focusing on only one specific type of standard cosmological probe, this provides an original method to measure cosmic opacity at high precision. Working on the simulated sample of strongly lensed SNe Ia observed by the LSST in the 10 yr z-band search, our results show that, with the combination of the current newly compiled SNe Ia data (Pantheon sample), there is no significant deviation from the transparency of the universe at the current observational data level. Moreover, strongly lensed SNe Ia in a 10 yr LSST z-band search would produce more robust constraints on the validity of cosmic transparency, with a larger sample of unlensed SNe Ia detected in the future LSST survey. We have also discussed the ways in which our methodology could be improved, with the combination of current and future available data in the gravitational wave and electromagnetic domain. [ABSTRACT FROM AUTHOR]

Strong gravitational lensing systems (SGL) encode cosmology information in source/lens distance ratios as , which can be used to precisely constrain cosmological parameters. In this paper, based on future measurements of 390 strong-lensing systems from the forthcoming Large Synoptic Survey Telescope (LSST) survey, we have successfully reconstructed the distance ratio (with the source redshift zs ∼ 4.0) directly from the data without assuming any parametric form. A recently developed method based on a model-independent reconstruction approach, Gaussian Processes, is used in our study of these strong-lensing systems. Our results show that independent measurement of the matter density parameter (Ωm) can be expected from such strong-lensing statistics. More specifically, one can expect Ωm to be estimated at the precision of ΔΩm ∼ 0.015 in the concordance ΛCDM model, which provides comparable constraints on Ωm with Planck 2015 results. In the framework of modified gravity theory (Dvali–Gabadadze–Porrati), 390 detectable galactic lenses from the future LSST survey can lead to stringent fits of ΔΩm ∼ 0.030. Finally, we have discussed three possible sources of systematic errors (sample incompleteness, the determination of length of lens redshift bin, and the choice of lens redshift shells), and quantified their effects on the final cosmological constraints. Our results strongly indicate that future strong-lensing surveys, with the accumulation of a larger and more accurate sample of detectable galactic lenses, will considerably benefit from the methodology described in this analysis. [ABSTRACT FROM AUTHOR]

The micro-luminescence spectra of the diluted magnetic semiconductor (DMS) can reflect the spin–exciton interaction and related relaxation process. Here the micro-photoluminescence (micro-PL) spectra and PL lifetime measurements have been done on an individual ferromagnetic (FM)-coupled cobalt (Co) doped zinc selenide (ZnSe) nanowire. There occurs a double-peak profile in its near bandedge emission spectrum: the first peak is from free exciton (FX) and the second comes from magnetic polaron (MP). In their temperature dependent PL spectra, the MP emission peak demonstrates obviously temperature-independent behavior, in contrast to the behaviors of FX and reported exciton MP in nanobelt. It is found that in this Co(II) doped ZnSe nanowires, this MP’s temperature-independent emission is related to the coupling between exciton and a FM nanocluster (↑↑↓). The nanocluster is likely due to the interaction of Se vacancies of the wide bandgap semiconductors with the antiferromagnetic (AFM) arrangement transition metal (TM) ions in these Se-deficient Co doped ZnSe nanowires. These results reflect that the AFM coupling TM ions pair can give rise to FM behavior with the involvement of positive charge defect, also indicating that the micro-luminescence detection can be used to study the magnetic coupling in DMS. [ABSTRACT FROM AUTHOR]

The article discusses a study that was conducted to examine the role of MED23 in lung cancer. The study used viral-mediated shRNA to inhibit Med23 expression in human lung cancer cell lines in combination with a Ras mutation. The findings of the study indicate that MED23 controls the proliferation of lung cancer cells in a Ras-dependent manner. It also revealed that Med23 deficiency in fibroblasts inhibited oncogenic transformation by Ras.

The Mediator complex functions as a control center, orchestrating diverse signaling, gene activities, and biological processes. However, how Mediator subunits determine distinct cell fates remains to be fully elucidated. Here, we show that Mediator MED23 controls the cell fate preference that directs differentiation into smooth muscle cells (SMCs) or adipocytes. Med23 deficiency facilitates SMC differentiation but represses adipocyte differentiation from the multipotent mesenchymal stem cells. Gene profiling revealed that the presence or absence of Med23 oppositely regulates two sets of genes: the RhoA/MAL targeted cytoskeleton/SMC genes and the Ras/ELK1 targeted growth/adipogenic genes. Mechanistically, MED23 favors ELK1-SRF binding to SMC gene promoters for repression, whereas the lack of MED23 favors MAL-SRF binding to SMC gene promoters for activation. Remarkably, the effect of MED23 on SMC differentiation can be recapitulated in zebrafish embryogenesis. Collectively, our data demonstrate the dual, opposing roles for MED23 in regulating the cytoskeleton/SMC and growth/adipogenic gene programs, suggesting its "Ying-Yang" function in directing adipogenesis versus SMC differentiation. [ABSTRACT FROM AUTHOR]