Multi-Field Synergy Process for Polymer Plasticization: A Novel Design Concept for Screw to Facilitate Phase-to-Phase Thermal and Molecular Mobility

A novel concept of screw design has been proposed considering the multi-field synergy principle to facilitate phase-to-phase thermal and molecular mobility; subsequently, a torsion element has been designed. This new screw design allows an innovative and effective way to resolve a growing challenge in polymer process engineering, especially for nanocomposites or biopolymers, that is, an inadequate control of mass transfer and thermal management for multicomponent melt flows through narrow channels during extrusion or injection. The adaption of torsion element in the screw facilitated the plasticization mixing and thermal distribution in polymer melts, and the torsional flow induced by the torsion elements shows a synergistic effect on the melt-phase mass flow and the thermal flow field. The latter effect enhances the mass and heat transfer of heterogeneous polymer systems and realizes effective heat management to achieve properly uniform temperature field

Contribution of CRISPRable DNA to human complex traits

CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes’ protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits

Protective Effects of Armillaria mellea Polysaccharides against Ethanol-Induced Vascular Endothelial Cell Injury in Rats

The aim of this study is to evaluate the protective effect of Armillaria mellea polysaccharides (AMP) against ethanol-induced vascular endothelial cell injury in rats. Altogether 40 SD rats were randomly divided into 4 groups: normal control, injury, low- and high-dose AMP. The rats from all groups except the normal control group were gavaged with 40% ethanol at 10 mL/kg mb to induce endothelial cell injury. The rats in the low- and high-dose groups were gavaged with AMP at 100 and 400 mg/kg mb, respectively, while the remaining groups were given an equal volume of physiological saline. The administration period lasted for 4 weeks. The histopathological changes of carotid arteries were observed by hematoxylin-eosin (HE) staining. Serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nitric oxide (NO), endothelin 1 (ET-1), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected. In addition, the effects of different doses (100 and 400 μg/mL) of AMP on the levels of reactive oxygen species (ROS), mitochondrial transmembrane potential, apoptosis, and the expression of apoptosis-associated proteins such as B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), and caspase-3 in human umbilical vein endothelial cell injured by 600 μmol/mL ethanol were investigated. Results: AMP attenuated ethanol-induced endothelial cell injury, decreased T-CHO, TG, LDL-C, iNOS, NO, ET-1, and MDA levels, and increased HDL-C and SOD activity. In vitro, AMP reduced cellular ROS levels, inhibited the ethanol-induced decrease in mitochondrial transmembrane potential and apoptosis, increased Bcl-2/Bax ratio and down-regulated the expression of cleaved caspase-3. Conclusion: AMP have a protective effect against ethanol-induced endothelial cell injury in rats, and the mechanism may be related to their lipid-lowering, antioxidant, and anti-apoptotic effects

KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.

Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma

Dural arteriovenous fistula and sinus thrombosis presenting as parkinsonism and dementia: a case report with literature review

IntroductionDural arteriovenous fistula (DAVF) is an uncommon malformation involving an abnormal connection between dural arteries, or the pachymeningeal branches of cerebral arteries, and dural veins. Its exact pathogenesis remains elusive. Known potential triggers for DAVF include cerebral venous sinus thrombosis (CVST), trauma, ear infections, and cranial surgeries. Due to its rarity and diverse clinical presentations, diagnosing DAVF can be a challenge.Case descriptionWe present a case of DAVF associated with CVST, manifesting as rapidly advancing parkinsonism accompanied by dementia over a month. Brain magnetic resonance imaging (MRI) revealed bilateral symmetric T2 hyperintensities in the basal ganglia and brain stem. Cerebral angiography further confirmed a fistula between the torcular herophili and the transverse-sigmoid sinuses. Despite strong recommendations for transvenous embolization of the fistula, the patient declined the procedure. The anticoagulant therapy and symptomatic treatments administered did not yield any improvement in the patient’s condition. Additionally, we reviewed 27 DAVF-derived parkinsonism and dementia cases.ConclusionDAVF must be considered in the differential diagnosis of cases of rapidly progressive parkinsonism with concurrent dementia. Given its potential for treatment and reversibility, timely diagnosis and intervention for DAVF are paramount

NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations. Knockdown of NMI promoted CSCs traits while its overexpression inhibited CSCs traits, including the expression of CSC-related markers, the number of CD44+CD24- cell populations and the ability of mammospheres formation. We also found that NMI-mediated regulation of BCSCs traits was at least partially realized through the modulation of hTERT signaling. NMI knockdown upregulated hTERT expression while its overexpression downregulated hTERT in breast cancer cells, and the changes in CSCs traits and cell invasion ability mediated by NMI were rescued by hTERT. The in vivo study also validated that NMI knockdown promoted breast cancer growth by upregulating hTERT signaling in a mouse model. Moreover, further analyses for the clinical samples demonstrated that NMI expression was negatively correlated with hTERT expression and the low NMI/high hTERT expression was associated with the worse status of clinical TNM stages in breast cancer patients. Furthermore, we demonstrated that the interaction of YY1 protein with NMI and its involvement in NMI-mediated transcriptional regulation of hTERT in breast cancer cells. Collectively, our results provide new insights into understanding the regulatory mechanism of CSCs and suggest that the NMI-YY1-hTERT signaling axis may be a potential therapeutic target for breast cancers

ChIP-Hub provides an integrative platform for exploring plant regulome

Plant genomes encode a complex and evolutionary diverse regulatory grammar that forms the basis for most life on earth. A wealth of regulome and epigenome data have been generated in various plant species, but no common, standardized resource is available so far for biologists. Here, we present ChIP-Hub, an integrative web-based platform in the ENCODE standards that bundles >10,000 publicly available datasets reanalyzed from >40 plant species, allowing visualization and meta-analysis. We manually curate the datasets through assessing ~540 original publications and comprehensively evaluate their data quality. As a proof of concept, we extensively survey the co-association of different regulators and construct a hierarchical regulatory network under a broad developmental context. Furthermore, we show how our annotation allows to investigate the dynamic activity of tissue-specific regulatory elements (promoters and enhancers) and their underlying sequence grammar. Finally, we analyze the function and conservation of tissue-specific promoters, enhancers and chromatin states using comparative genomics approaches. Taken together, the ChIP-Hub platform and the analysis results provide rich resources for deep exploration of plant ENCODE. ChIP-Hub is available at https://biobigdata.nju.edu.cn/ChIPHub/.Peer Reviewe