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Abstract BackgroundThere are many problems associated with systematic reviews of traditional Chinese medicine (TCM), such as considering “integrated traditional Chinese and Western medicine” or treatment methods as intervention measures without considering the differences in drug use, disregarding dosage and courses of treatment, disregarding interindividual differences in control groups, etc. Classifying a large number of heterogeneous intervention measures into the same measure is easy but results in inaccurate results. In April 2023, Cochrane launched RevMan Web to digitalize systematic reviews and meta-analyses. We believe that this web-based working model helps solve the abovementioned problems. ObjectiveThis study aims to (1) develop a web-based platform that is more suitable for systematic review and meta-analysis of TCM and (2) explore the characteristics and future development directions of this work through the testing of digital workflow. MethodsWe developed TCMeta (Traditional Chinese Medicine Meta-analysis)—a platform focused on systematic reviews of TCM types. All systematic review–related work can be completed on the web, including creating topics, writing protocols, arranging personnel, obtaining literature, screening literature, inputting and analyzing data, and designing illustrations. The platform was developed using the latest internet technology and can be continuously modified and updated based on user feedback. When screening the literature on the platform, in addition to the traditional manual screening mode, the platform also creatively provides a query mode where users input keywords and click on Search ResultsWe used some test data in TCMeta to simulate data processing in a systematic review. In the literature screening stage, researchers could rapidly screen 19 sources of literature from among multiple sources with the manual screening mode. This traditional method could result in bias due to differences in the researchers’ cognitive levels. The query mode is much more complex and involves inputting of data regarding drug compatibility, dosage, syndrome type, etc; different query methods can yield very different results, thus increasing the stringency of screening. We integrated data analysis tools on the platform and used third-party software to generate graphs. ConclusionsTCMeta has shown great potential in improving the quality of systematic reviews of TCM types in simulation tests. Several indicators show that this web-based mode of working is superior to the traditional way. Future research is required to focus on validating and refining the performance of TCMeta, emphasizing the ability to handle complex data. The system has good scalability and adaptability, and it has the potential to have a positive impact on the field of evidence-based medicine.

As a key factor in tumorigenesis, progression, recurrence and metastasis, the biological properties, metabolic adaptations and immune escape mechanisms of CSCs are the focus of current oncological research. CSCs possess self-renewal, multidirectional differentiation and tumorigenicity, and their mechanisms of action can be elucidated by the clonal evolution, hierarchical model and the dynamic CSCs model, of which the dynamic model is widely recognized due to its better explanation of the function and origin of CSCs. The origin hypothesis of CSCs involves cell-cell fusion, horizontal gene transfer, genomic instability and microenvironmental regulation, which together shape the diversity of CSCs. In terms of classification, CSCs include primary CSCs (pri-CSCs), precancerous stem cells (pre-CSCs), migratory CSCs (mig-CSCs), and chemo-radiotherapy-resistant CSCs (cr-CSCs and rr-CSCs), with each type playing a specific role in tumor progression. Surface markers of CSCs, such as CD24, CD34, CD44, CD90, CD133, CD166, EpCAM, and LGR5, offer the possibility of identifying, isolating, and targeting CSCs, but the instability and heterogeneity of their expression increase the difficulty of treatment. CSCs have adapted to their survival needs through metabolic reprogramming, showing the ability to flexibly switch between glycolysis and oxidative phosphorylation (OXPHOS), as well as adjustments to amino acid and lipid metabolism. The Warburg effect typifies their metabolic profiles, and altered glutamine and fatty acid metabolism further contributes to the rapid proliferation and survival of CSCs. CSCs are able to maintain their stemness by regulating the metabolic networks to maintain their stemness characteristics, enhance antioxidant defences, and adapt to therapeutic stress. Immune escape is another strategy for CSCs to maintain their survival, and CSCs can effectively evade immune surveillance through mechanisms such as up-regulating PD-L1 expression and promoting the formation of an immunosuppressive microenvironment. Together, these properties reveal the multidimensional complexity of CSCs, underscoring the importance of a deeper understanding of the biology of CSCs for the development of more effective tumor therapeutic strategies. In the future, therapies targeting CSCs will focus on precise identification of surface markers, intervention of metabolic pathways, and overcoming immune escape, with the aim of improving the relevance and efficacy of cancer treatments, and ultimately improving patient prognosis.

Aspect-level sentiment classification (ALSC) struggles with correctly trapping the aspects and corresponding sentiment polarity of a statement. Recently, several works have combined the syntactic structure and semantic information of sentences for more efficient analysis. The combination of sentence knowledge with graph neural networks has also proven effective at ALSC. However, there are still limitations on how to effectively fuse syntactic structure and semantic information when dealing with complex sentence structures and informal expressions. To deal with these problems, we propose an ALSC fusion network that combines graph neural networks with a simultaneous consideration of syntactic structure and semantic information. Specifically, our model is composed of a syntactic attention module and a semantic enhancement module. First, the syntactic attention module builds a dependency parse tree with the aspect term being the root, so that the model focuses better on the words closely related to the aspect terms, and captures the syntactic structure through a graph attention network. In addition, the semantic enhancement module generates the adjacency matrix through self-attention, which is processed by the graph convolutional network to obtain the semantic details. Lastly, the extracted features are merged to achieve sentiment classification. As verified by experiments, the model we propose can effectively enhance ALSC’s behavior.

Designing reasonable commercial transportation space is of great significance to enhancing the overall value of commerce. This study takes the classic cases of three typical plans of commercial wholesale centres (CWCs) as the research object, uses space syntax to analyse the connectivity of the architecture of the traffic space, simulates the current situation of the pedestrian flow distribution through ArcGIS, and constructs a multiple regression model for the association between connectivity and pedestrian flow distribution. The results of this study show that for CWCs with a single business type and a focus on traffic efficiency, the distribution of the pedestrian flow is most affected by the main entrance and the vertical traffic distribution. For different types of planes, when the commercial traffic space has strong symmetry, its group relationship is more concise. While a uniform form is more conducive to achieving a balanced distribution of commercial traffic, the asymmetry of the plan layout helps to establish a psycho-spatial map for the visitors. In addition, the commercial value of the first floor is greatly influenced by the layout of the building entrance, and the commercial value of the second floor is greatly influenced by the location of the vertical transportation. In conclusion, when commercial building development planning is in the stage of traffic flow design, the use of space connectivity traffic data can assist in the selection of construction plans and predict the distribution of the economic value in CWCs.

BackgroundModern medical research shows that a rationally planned landscape environment helps patients recover. With the growing number of hospital patients and the tightening of per capita medical landscape land, the use of limited landscape resources to serve patients has become challenging.MethodsThis study focused on the landscape environment of 10 hospitals in Guangdong Province, China. Based on the KANO theoretical model, a survey questionnaire was designed and administered to 410 participants. The data were analyzed based on demand attributes, importance, sensitivity, and group differences.ResultsThe maintenance requirements were the most important item in the sensitivity ranking. Furthermore, the analysis revealed that the users need a safe, quiet, and private environment, owing to their higher requirements, including visual healing, rehabilitation activities, shading and heat preservation, and medical escort. Moreover, adolescents and older adult patients have common and contradictory environmental needs. For example, the landscape environment should provide both an active space and a quiet rehabilitation environment.ConclusionThis study evaluates how landscape resources can be better utilized from the perspective of the user and expands the theory of healing landscapes, which has practical implications for hospital renovation and landscape environment strategies.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes pediatric COVID-19 (pCOVID-19). The relationship of the systemic tissue injury to the pathophysiology of MIS-C is poorly defined. We leveraged the high sensitivity of epigenomics analyses of plasma cell-free DNA (cfDNA) and plasma cytokine measurements to identify the spectrum of tissue injury and glean mechanistic insights. Compared with pediatric healthy controls (pHCs) and patients with pCOVID-19, patients with MIS-C had higher levels of cfDNA primarily derived from innate immune cells, megakaryocyte-erythroid precursor cells, and nonhematopoietic tissues such as hepatocytes, cardiac myocytes, and kidney cells. Nonhematopoietic tissue cfDNA levels demonstrated significant interindividual variability, consistent with the heterogenous clinical presentation of MIS-C. In contrast, adaptive immune cell–derived cfDNA levels were comparable in MIS-C and pCOVID-19 patients. Indeed, the cfDNA of innate immune cells in patients with MIS-C correlated with the levels of innate immune inflammatory cytokines and nonhematopoietic tissue–derived cfDNA, suggesting a primarily innate immunity–mediated response to account for the multisystem pathology. These data provide insight into the pathogenesis of MIS-C and support the value of cfDNA as a sensitive biomarker to map tissue injury in MIS-C and likely other multiorgan inflammatory conditions.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, represents a spectrum of nonalcoholic hepatic steatosis, nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. Recent studies have revealed that the gut-liver axis is associated with the development of NAFLD. Intervention measures such as exercise, diet, microecological preparations, antibiotics, fecal microbiota transplantation and bacteriophage can alleviate NAFLD by improving intestinal microbiota. We reviewed recent advances in the relationship and mechanism between intestinal microbiota and NAFLD as well as treatment of NAFLD targeting the intestinal microbiota, and summarized that intestinal microbiota is closely related to NAFLD, and the regulation of intestinal microbiota can be used as a new target for NAFLD treatment, which will provide new ideas and references for clinicians in the diagnosis and treatment of NAFLD.

Ganoderma lucidum possesses anti-inflammatory, antioxidant, and immunomodulatory properties. We evaluated the anti-inflammatory and anti-melanogenesis effects of G. lucidum alone (S1), G. lucidum and Polygonatum odoratum (S2), and G. lucidum and P. ginseng (S3) using an ultraviolet B-irradiated HaCaT cell model and a prostaglandin 2 (PGE2)-treated B16-F10 melanocyte model. S3 inhibited PGE-2 and LL-37 secretion in HaCaT cells and melanin and tyrosinase expression in B16-F10 cells. Furthermore, LC/MS/MS results revealed that the levels of 70 components were higher in S3 than in S1 and S2. These results demonstrate that G. lucidum and P. ginseng co-culture fermentation broth possess in vitro anti-inflammatory and anti-melanogenesis effects; it can be used in the skin care industry.

Shale hydration and expansion during drilling can lead to wellbore instability, sticking, and frequent leakage accidents. To prevent these issues, an ionic liquid (IL) inhibitor solution was synthesized using DL‐alanine and 98% concentrated sulphuric acid as raw materials. The optimum composition and effect of the synthesized inhibitor in oilfield water‐based drilling fluids were evaluated through anti‐expansion, linear expansion rate, water washing resistance, and clay hydration dispersion experiments. The inhibition mechanism was investigated by thermogravimetric analysis, infrared spectroscopy, zeta potential, contact angle, and X‐ray diffraction analysis. The results show that the optimum IL consists of a 1:1 molar ratio of DL‐alanine to concentrated sulphuric acid synthesized under a reaction temperature and time of 70°C and 18 h, respectively. The resulting DL‐alanine IL exhibited the best inhibitory effect on the hydration, dispersion, and expansion of clay at a concentration of 0.5% in aqueous solution, and its linear expansion rate was only 18.49%. After adding a quantitative amount of clay to different concentrations of DL‐alanine IL aqueous solution, the expansion volume of the clay decreased and the water washing resistance significantly improved. These results provide a theoretical basis for improving the safety and efficiency of shale horizontal well drilling operations. [ABSTRACT FROM AUTHOR]

GLI repression has been presumed to be the default transcriptional state and important for pre-patterning tissues. Challenging current models, the authors show that GLI3 repression is inert in the limb bud before the onset of Hedgehog signaling.

Abstract Background Spinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) and other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies for generating iPSC-derived disease models that closely recapitulate the genetic and phenotypic complexity of ALS. An important application of these models is to understand molecular mechanisms of action of FDA-approved ALS drugs that only show modest clinical efficacy. Novel mechanistic insights will help us design optimal therapeutic strategies together with predictive biomarkers to achieve better efficacy. Methods We induce efficient MN differentiation from iPSCs in 4 days using synthetic mRNAs coding two transcription factors (Ngn2 and Olig2) with phosphosite modification. These MNs after extensive characterization were applied in electrophysiological and neurotoxicity assays as well as transcriptomic analysis, to study the neuroprotective effect and molecular mechanisms of edaravone, an FDA-approved drug for ALS, for improving its clinical efficacy. Results We generate highly pure and functional mRNA-induced MNs (miMNs) from control and ALS iPSCs, as well as embryonic stem cells. Edaravone alleviates H2O2-induced neurotoxicity and electrophysiological dysfunction in miMNs, demonstrating its neuroprotective effect that was also found in the glutamate-induced miMN neurotoxicity model. Guided by the transcriptomic analysis, we show a previously unrecognized effect of edaravone to induce the GDNF receptor RET and the GDNF/RET neurotrophic signaling in vitro and in vivo, suggesting a clinically translatable strategy to activate this key neuroprotective signaling. Notably, edaravone can replace required neurotrophic factors (BDNF and GDNF) to support long-term miMN survival and maturation, further supporting the neurotrophic function of edaravone-activated signaling. Furthermore, we show that edaravone and GDNF combined treatment more effectively protects miMNs from H2O2-induced neurotoxicity than single treatment, suggesting a potential combination strategy for ALS treatment. Conclusions This study provides methodology to facilitate iPSC differentiation and disease modeling. Our discoveries will facilitate the development of optimal edaravone-based therapies for ALS and potentially other neurodegenerative diseases. Graphical abstract

HIV-1 infection in memory CD4+ T cells forms a latent reservoir that is a barrier to cure. Identification of immune biomarkers that correlate with HIV-1 reservoir size may aid with evaluating efficacy of HIV-1 eradication strategies, towards ART-free remission and cure. In adults living with non-perinatal HIV-1, the immune exhaustion marker PD-1 on central memory CD4+ T cells (Tcm) correlates with measures of HIV-1 reservoir size. Immune correlates of HIV-1 are less defined in adolescents and young adults with perinatal HIV-1. With multi-parameter flow cytometry, we examined immune activation (CD69, CD25, HLA-DR), and exhaustion (PD-1, TIGIT, TIM-3 and LAG-3) markers on CD4+ T cell subsets (naïve (Tn), central memory (Tcm), and the combination (Ttem) of transitional (Ttm) and effector memory (Tem) cells, in 10 adolescents and young adults living with perinatal HIV-1 (median age 15.9 years; median duration of virologic suppression 7.0 years), in whom HIV-1 reservoir size was measured with the Intact Proviral HIV-1 DNA Assay (IPDA) and an enhanced Tat/Rev limiting dilution assay (TILDA). RNA-seq was also performed on the unstimulated CD4+ T cells. The median total HIV-1 DNA concentration in memory CD4+ T cells was 211.90 copies per million CD4+ T cells. In the 7 participants with subtype B HIV-1 infection, the median intact proviral DNA load was 7.96 copies per million CD4+ T cells. Levels of HLA-DR and TIGIT on the Ttem were correlated with total HIV-1 DNA (r=0.76, p=0.015) and (r=0.72, p=0.023), respectively, but not with intact proviral load or induced reservoir size. HIV-1 DNA load was also positively correlated with transcriptional clusters associated with HLA-DR expression by RNA-seq. In contrast, PD-1 expression on Tcm was inversely correlated with total HIV-1 DNA (r=-0.67, p=0.039). Reservoir size by IPDA and TILDA were correlated (r=0.81, p=0.036). Thus, in this cohort of youths with long-standing treated perinatal infection, HLA-DR and TIGIT on Ttem were the key correlates of HIV-1 infected cell frequencies by total HIV-1 DNA, and not PD-1. Total HIV-1 DNA was negatively correlated with PD-1 expressing Tcm. These differences in longstanding perinatal HIV-1 infection compared with adult infection requires further study in larger cohorts.

IntroductionSea buckthorn (Hippophae rhamnoides) seed oil is rich in unsaturated fatty acids, and is thus susceptible to oxidation and rancidity. Microencapsulation technology allows the effective protection of active substances, thereby prolonging the deterioration time and shelf life.MethodsIn this study, H. rhamnoides microcapsules were prepared using a spray-drying method, and the microencapsulation parameters were optimized. The morphological characteristics, structural parameters, and stability of the microcapsules were determined using scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and oil oxidation stability testing.ResultsBased on encapsulation efficiency (EE, %) and the particle size (D50) of the microcapsules, the optimal preparation conditions were characterized as a wall material consisting of soy protein isolate and soybean polysaccharide (2:3), a wall concentration of 15%, a core-to-wall ratio of 1:3, and an inlet temperature of 160°C. Under these optimal conditions, the encapsulation efficiency was 95.30 ± 2.67%, with a yield of 57.03 ± 3.71% and a particle size of 7.96 ± 1.04 μm.DiscussionFurthermore, the effectiveness of microencapsulation in protecting the biological activity of H. rhamnoides seed oil was confirmed by an antioxidation test. Thus, the results of this study showcase the successful microencapsulation of H. rhamnoides seed oil, thereby significantly improving its stability.

Abstract Metal‐organic frameworks (MOFs) have shown numerous potentials as promising materials to address real‐world problems. However, their practical utilization in commercial products was largely limited by the lack of downstream processing methodologies to transform MOF powders into functional products. In this study, a commercially viable solution for the general synthesis of MOF‐fabric composites was introduced. On account of coordination bonding between poly(acrylic acid) and MOF substrates, MOF powders securely adhered onto the surface of fabric materials via a drip cast method to give MOF‐fabric composites easily. This strategy can be applied to different MOF types, as well as a wide variety of fabric materials. The prepared materials showed excellent bacterial killing efficacy attributed to the embedded HKUST‐1 MOF. In light of the recent coronavirus disease 2019 pandemic, this methodology could enable the large‐scale fabrication of essential MOF‐based personal protective wearables (e.g., clothing and masks) for use by healthcare professionals.

The larynx enables speech while regulating swallowing and respiration. Larynx function hinges on the laryngeal epithelium which originates as part of the anterior foregut and undergoes extensive remodeling to separate from the esophagus and form vocal folds that interface with the adjacent trachea. Here we find that sonic hedgehog (SHH) is essential for epithelial integrity in the mouse larynx as well as the anterior foregut. During larynx-esophageal separation, low Shh expression marks specific domains of actively remodeling epithelium that undergo an epithelial-to-mesenchymal transition (EMT) characterized by the induction of N-Cadherin and movement of cells out of the epithelial layer. Consistent with a role for SHH signaling in regulating this process, Shh mutants undergo an abnormal EMT throughout the anterior foregut and larynx, marked by a cadherin switch, movement out of the epithelial layer and cell death. Unexpectedly, Shh mutant epithelial cells are replaced by a new population of FOXA2-negative cells that likely derive from adjacent pouch tissues and form a rudimentary epithelium. These findings have important implications for interpreting the etiology of HH-dependent birth defects within the foregut. We propose that SHH signaling has a default role in maintaining epithelial identity throughout the anterior foregut and that regionalized reductions in SHH trigger epithelial remodeling.

Chidamide, a new chemically structured HDACi-like drug, has been shown to inhibit breast cancer, but its specific mechanism has not been fully elucidated. In this paper, we selected ER-positive breast cancer MCF-7 cells and used RNA-seq technique to analyze the gene expression differences of Chidamide-treated breast cancer cells to identify the drug targets of Chidamide’s anti-breast cancer effect and to lay the foundation for the development of new drugs for breast cancer treatment. The results showed that the MCF-7 CHID group expressed 320 up-regulated genes and 222 down-regulated genes compared to the control group; Gene Ontology functional enrichment analysis showed that most genes were enriched to biological processes. Subsequently, 10 hub genes for Chidamide treatment of breast cancer were identified based on high scores using CytoHubba, a plug-in for Cytoscape: TP53, JUN, CAD, ACLY, IL-6, peroxisome proliferator-activated receptor gamma, THBS1, CXCL8, IMPDH2, and YARS. Finally, a combination of the Gene Expression Profiling Interactive Analysis database and Kaplan Meier mapper to compare the expression and survival analysis of these 10 hub genes, TP53, ACLY, PPARG, and JUN were found to be potential candidate genes significantly associated with Chidamide for breast cancer treatment. Among them, TP53 may be a potential target gene for Chidamide to overcome multi-drug resistance in breast cancer. Therefore, we identified four genes central to the treatment of breast cancer with Chidamide by bioinformatics analysis, and clarified that TP53 may be a potential target gene for Chidamide to overcome multi-drug resistance in breast cancer. This study lays a solid experimental and theoretical foundation for the treatment of breast cancer at the molecular level with Chidamide and for the combination of Chidamide.

Strain sensors based on conducting polymer hydrogels are considered highly promising candidates for wearable electronic devices. However, existing conducting polymer hydrogels are susceptible to aging, damage, and failure, which can greatly deteriorate the sensing performance of strain sensors based on these substances and the accuracy of data collection under large deformation. Developing conductive polymer hydrogels with concurrent high sensing performance and self-healing capability is a critical yet challenging task to improve the stability and lifetime of strain sensors. Herein, we design a self-healable conducting polymer hydrogel by compositing poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) nanofibers and poly(vinyl alcohol) (PVA) via both physical and chemical crosslinking. This PEDOT:PSS-PVA nanocomposite hydrogel strain sensor displays an excellent strain monitoring range (>200%), low hysteresis (83.5%). Electronic skins based on such hydrogel strain sensors can perform the accurate monitoring of various physiological signals, including swallowing, finger bending, and knee bending. This work presents a novel conducting polymer hydrogel strain sensor demonstrating both high sensing performance and self-healability, which can satisfy broad application scenarios, such as wearable electronics, health monitoring, etc.

Abstract Background Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. Methods To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund’s adjuvant (CFA) in rats. Results Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models. Conclusions Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG.

Abstract As a royal temple, the Fengguo Temple has profound historical, artistic, scientific and social values. With a thousand-year history, it is one of the three existing temples of the Liao Dynasty in China. Now there remains the Main Hall with delicate wall paintings and vivid painted sculptures. The research subject of this paper is the painted Bodhisattva sculptures in the Main Hall. The study target is to reveal the craftsmanship and materials of the painted Bodhisattva sculptures. X-ray detection and the ground-penetrating radar were employed to explore the internal structure of the painted sculptures reasonably. Through microscope analysis, X-ray fluorescence spectrometer, X-ray diffractometer, scanning electron microscopy and infrared spectroscopic analysis, the chemical constituents and hierarchical structure of the pigment layer were detected and analyzed. The grain composition and chemical composition of the base layer were presented as well. The research results offer detailed documents for subsequent restoration and pave the way for preventive conservation. Finally, this paper summarized the craftsmanship and materials of painted sculpture works in different periods, so as to explore the development history of the painted sculptures culture.

Breast cancer is one of the leading threats to the health of women. It has the highest incidence and mortality in women worldwide. Although progress has been made in the development and application of anti-breast cancer drugs such as Chidamide and others, the occurrence of drug resistance limits the effective application of chemotherapies. The purpose of this study is to explore the role of LncRNA in the pharmacological effect of Chidamide in breast cancer therapy. The human breast cancer MCF-7 or MDA-MB-231 cells were used as the research cell models. The RNA library screening and high-throughput sequencing comparative analysis was conducted. The binding of LncRNA and its downstream target genes in RNA and protein levels was tested. The results showed that the expression of LncRNA ENST869 in cells treated with Chidamide increased significantly, as demonstrated by real-time PCR and cell viability assay. RNAplex analysis showed that LncRNA ENST869 and Nestin mRNA may interact. RNA interference and Western blot analysis indicated that LncRNA ENST869 could target and regulate the expression of Nestin. Luciferase assay and RNA-protein pulldown showed that LncRNA ENST869 affected Nestin transcription. There might be a highly active binding region of LncRNA ENST869 in regulating Nestin transcriptional activity within the site of 250 bp upstream of the transcription starting point of Nestin. In addition, LncRNA ENST869 did not directly interact with Nestin protein to affect its activity. In conclusion, our results demonstrated that LncRNA ENST869 could affect the function of Nestin in breast cancer cells treated with Chidamide. Nestin is a key player in influencing the pharmacological activity of Chidamide and an essential factor in drug resistance of breast cancer cells.

Polyindole (PIn) has attracted extensive interest as promising energy storage materials owing to fairly good thermal stability, high redox activity and stability, however, it is challenging to prepare high-quality PIn in neutral solvents by electrochemical method. Herein, a simple route, based on MoS2 nanosheets as electrolytes, has been developed for the electrochemical preparation of PIn/MoS2 nanocomposite in acetonitrile solution. Due to the coordination interaction between indole and MoS2, the onset oxidation potential of indole in this medium was reduced to 0.5 V from 0.75 V determined in acetonitrile/LiClO4. The morphologies and structures of as-obtained PIn/MoS2 nanocomposite were characterized using SEM, TEM, XRD, Raman and XPS. The results of thermal analysis indicated that the PIn/MoS2 nanocomposite had an improved thermal stability relative to PIn and MoS2 nanosheets. Moreover, the specific capacitance of PIn/MoS2 nanocomposite was 8.3 times higher than that of PIn prepared acetonitrile/LiClO4. To the best of our knowledge, this is the first report on the high-efficiency electrodeposition of PIn/MoS2 nanocomposite in MoS2-based acetonitrile solution, which will be a promising candidate as a high efficient electrode material in the application of supercapacitors.

Abstract Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscapes in single cells. Single-cell ATAC-seq data are sparse and noisy, and analyzing such data is challenging. Existing computational methods cannot accurately reconstruct activities of individual cis-regulatory elements (CREs) in individual cells or rare cell subpopulations. We present a new statistical framework, SCATE, that adaptively integrates information from co-activated CREs, similar cells, and publicly available regulome data to substantially increase the accuracy for estimating activities of individual CREs. We demonstrate that SCATE can be used to better reconstruct the regulatory landscape of a heterogeneous sample.

The next generation IP network is a new type of public network.It integrates wire and wireless,broad-band and narrow-band,transmit and receive,passive and active,which leads to the diverse and complex service scenarios.However,different scenario has different needs and standards,and there remains gaps with the current techniques,protocols and standards.In order to ensure the completeness and security of all kinds of techniques and facilities in the new application scenarios,and the upcoming new characteristics in the process of network development,a comprehensive test system framework needs to be established.The next generation IP network test framework based on micro services architecture was proposed,combined with different new application characteristics,which provided support for the development of network technology.

Abstract Background Pain is a subjective experience derived from complex interactions among biological, environmental, and psychosocial pathways. Sex differences in pain sensitivity and chronic pain prevalence are well established. However, the molecular basis underlying these sex dimorphisms are poorly understood particularly with regard to the role of the peripheral nervous system. Here we sought to identify shared and distinct gene networks functioning in the peripheral nervous systems that may contribute to sex differences of pain in rats after nerve injury. Results We performed RNA-seq on dorsal root ganglia following chronic constriction injury of the sciatic nerve in male and female rats. Analysis from paired naive and injured tissues showed that 1513 genes were differentially expressed between sexes. Genes which facilitated synaptic transmission in naïve and injured females did not show increased expression in males. Conclusions Appreciating sex-related gene expression differences and similarities in neuropathic pain models may help to improve the translational relevance to clinical populations and efficacy of clinical trials of this major health issue.

The molecular mechanisms by which uterine leiomyoma (UL) cells proliferate are unclear. Long noncoding RNA (lncRNA) is reported to participate in the occurrence and development of gynecological cancers. We investigated the molecular mechanisms that lncRNA uses in UL. We found that lncRNA Alu-mediated p21 transcriptional regulator (APTR) showed higher expression in UL tumor tissues compared with that in normal uterine tissues. APTR induced cell proliferation and colony formation both in vitro and in vivo. The JASPAR database showed that APTR was likely interacted with ERα, and these molecules were identified via laser scanning confocal microscopy and RNA immunoprecipitation analysis. To verify the correlation between APTR and ERα, we overexpressed and underexpressed APTR and simultaneously expressed ERα. The results showed that APTR function was suppressed. APTR increased the expressions of the proteins in the Wnt pathway, and inhibiting ERα eliminated these responses. In conclusion, our data suggest that APTR promoted leiomyoma cell proliferation through the Wnt pathway by targeting ERα, suggesting a new role of APTR in the Wnt signaling pathway in UL.

Abstract The low specific capacitance and energy density of carbon electrode has extremely limited the wide application of supercapacitors. For developing a high‐performance carbon electrode using a simple and effective method, a fishnet‐like, N‐doped porous carbon (FNPC) film is prepared by calcining the KOH‐activated polyindole precoated on carbon cloths. The FNPC film is tightly anchored on carbon cloths without any binder. The FNPC film with 3.8 at% N content exhibits a fairly high specific capacitance of 416 F g−1 at 1.0 A g−1. Moreover, the assembled button‐type cell with two FNPC film electrodes shows a high energy density of 16.4 Wh kg−1, a high power density of 67.4 kW kg−1, and long‐term cyclic stability of 92% of the initial capacitance after 10 000 cycles at 10 A g−1. The high performances mainly came from the integration of pseudocapacitance and electrical double‐layer capacitance behavior, wettability, fishnet‐like nanostructure, as well as the low interfacial resistivity. This strategy provides a practical, uncomplicated, and low‐cost design of binder‐free flexible carbon materials electrode for high‐performance supercapacitors.

Transcriptional repression needs to be rapidly reversible during embryonic development. This extends to the Hedgehog pathway, which primarily serves to counter GLI repression by processing GLI proteins into transcriptional activators. In investigating the mechanisms underlying GLI repression, we find that a subset of GLI binding regions, termed HH-responsive enhancers, specifically loses acetylation in the absence of HH signaling. These regions are highly enriched around HH target genes and primarily drive HH-specific transcriptional activity in the mouse limb bud. They also retain H3K27ac enrichment in limb buds devoid of GLI activator and repressor, indicating that their activity is primarily regulated by GLI repression. Furthermore, the Polycomb repression complex is not active at most of these regions, suggesting it is not a major mechanism of GLI repression. We propose a model for tissue-specific enhancer activity in which an HDAC-associated GLI repression complex regulates target genes by altering the acetylation status at enhancers.

A map of the activities of all genomic regulatory elements across cell types and conditions would be a tremendous resource. The computational method introduced here predicts genome-wide accessible sites from gene expression data and allows the authors to build a database of regulatory element activities using publicly available transcriptome data.

ABSTRACT IMPACT: Our improved understanding of the changes in chromatin accessibility that occur in persistent pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG. OBJECTIVES/GOALS: Efforts to understand genetic variability involved in an individual’s susceptibility to persistent pain support a role for upstream regulation by epigenetic mechanisms. Our objective was to examine the transcriptomic and epigenetic basis of persistent pain following nerve injury. METHODS/STUDY POPULATION: We used a multiomic approach to identify novel molecular pathways associated with nerve injury-induced pain hypersensitivity. Adult Sprague Dawley rats were randomized to Chronic Constriction Injury (CCI) to the sciatic nerve or no treatment (naive). The ipsilateral L4-L6 dorsal root ganglia (DRG)s were removed on Day 14 and used for ChIP-seq for H3K4me1, ATAC-seq, and RNA-seq. We assessed for differential chromatin accessibility, transcription factor motifs, and enrichment for biological processes in chromatin accessible regions associated with cis-regulatory regions identified by ATAC-seq and H3K4me1 enrichment. Luciferase assays determined the functional significance of these sequences. RESULTS/ANTICIPATED RESULTS: We identified 58,446 genomic regions where H3K4me1 enrichment overlapped with chromatin accessibility. Differential analysis identified 2145 of these 58,446 regions that had changes in accessibility after CCI. The majority of these regions were located in introns or intergenic regions. Functional annotation of the differentially accessible regions identified disparate molecular functions enriched following nerve injury which suggests that altered chromatin structure plays a role in the development of mechanical hypersensitivity. Motif analysis identified specific transcription factor families whose binding sequences were enriched in regions of increased or decreased accessibility. Luciferase assays showed significant enhancement or repression of gene transcription. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our data provides a comprehensive map of chromatin accessibility changes in the DRG after CCI and emphasizes the importance of chromatin structure in the development and maintenance of chronic pain.

The isomers of conducting polymers usually have different properties, however, there are still few studies on the isomeric effect of conducting polymers in supercapacitors field. In this work, four isomers (4-nitroindole, 5-nitroindole, 6-nitroindole, and 7-nitroindole) were selected as the research objects to study the positional isomeric effect of nitro group substituted indoles on the electropolymerization and the capacitance performances of their polymers. The results show that the prepared poly(5-nitroindole) (5-PNI) and poly(6-nitroindole) (6-PNI) are in nanowires structure, poly(7-nitroindole) (7-PNI) is in dense structure, while poly(4-nitroindole) (4-PNI) fails to be prepared. In addition, the as-prepared 5-PNI, 6-PNI nanowires and dense 7-PNI exhibit very different electrochemical properties and capacitance performances. Taking into account the specific capacitance (364 F g-1 at 5 mV s-1), rate capability (58.5%) and cyclic stability (94% capacitance retention after 1000 cycles test), it can be concluded that 5-PNI is the most suitable electrode material in the field of supercapacitors. [ABSTRACT FROM AUTHOR]