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Digital transformation has pass through aspects of social livelihood and manufacture services, and digital finance has become a new motor for progress with quality as the main goal of China’s financial condition. Here first elaborates on the connotation of progress with quality as the main goal, selects 20 indicators from five aspects of progress with quality as the main goal, necessity and progression productiveness, and measures the indicator weights using principal component analysis. Secondly, spatial panel information originate 30 all regions in China are used to study the coordinated action condition among mathematical finance and the progress with quality as the main goal regional financial condition using the spatial face-plate pattern. Finally, the coordinated action test and enclosure correlation are applied to verify coordinated action mathematical financial condition progression on capital situation in different regions high-quality development and the internal system of action. The empirical results show that the capital situation in different regions progression in China exhibits 86.67% more significant spatial autocorrelation, and the Moran I index values of the mathematical financial condition progression level and progress with quality as the main goal from 2010 to 2021 are both greater than 0, and both are important at the 1% magnitude, directive that the continuous create and progression of mathematical treasury supply important positive contribution to progress with quality as the main goal economic development. The research in here provides a acknowledge basis for strengthening the construction of mathematical infrastructure, improving the capital market and related policies, and expedite the digital reform transversion finance.

Carbon nanotubes were prepared with commercial resin by a simple method to explore the effects of different calcination temperatures.

High-throughput sequencing technology has been facilitated the development of new methodologies and approaches for studying the origin and evolution of plant genomes and subgenomes, population domestication, and functional genomics. Orchids have tens of thousands of members in nature. Many of them have promising application potential in the extension and conservation of the ecological chain, the horticultural use of ornamental blossoms, and the utilization of botanical medicines. However, a large-scale gene knockout mutant library and a sophisticated genetic transformation system are still lacking in the improvement of orchid germplasm resources. New gene editing tools, such as the favored CRISPR-Cas9 or some base editors, have not yet been widely applied in orchids. In addition to a large variety of orchid cultivars, the high-precision, high-throughput genome sequencing technology is also required for the mining of trait-related functional genes. Nowadays, the focus of orchid genomics research has been directed to the origin and classification of species, genome evolution and deletion, gene duplication and chromosomal polyploidy, and flower morphogenesis-related regulation. Here, the progressing achieved in orchid molecular biology and genomics over the past few decades have been discussed, including the evolution of genome size and polyploidization. The frequent incorporation of LTR retrotransposons play important role in the expansion and structural variation of the orchid genome. The large-scale gene duplication event of the nuclear genome generated plenty of recently tandem duplicated genes, which drove the evolution and functional divergency of new genes. The evolution and loss of the plastid genome, which mostly affected genes related to photosynthesis and autotrophy, demonstrated that orchids have experienced more separate transitions to heterotrophy than any other terrestrial plant. Moreover, large-scale resequencing provide useful SNP markers for constructing genetic maps, which will facilitate the breeding of novel orchid varieties. The significance of high-throughput sequencing and gene editing technologies in the identification and molecular breeding of the trait-related genes in orchids provides us with a representative trait-improving gene as well as some mechanisms worthy of further investigation. In addition, gene editing has promise for the improvement of orchid genetic transformation and the investigation of gene function. This knowledge may provide a scientific reference and theoretical basis for orchid genome studies.

High-mobility group box-1 (HMGB1) is a nuclear protein associated with early inflammatory changes upon extracellular secretion expressed in various cells, including neurons and microglia. With the progress of research, neuroinflammation is believed to be involved in the pathogenesis of neurological diseases such as Parkinson's, epilepsy, and autism. As a key promoter of neuroinflammation, HMGB1 is thought to be involved in the pathogenesis of Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, and amyotrophic lateral sclerosis. However, in the clinic, HMGB1 has not been described as a biomarker for the above-mentioned diseases. However, the current preclinical research results show that HMGB1 antagonists have positive significance in the treatment of Parkinson's disease, stroke, traumatic brain injury, epilepsy, and other diseases. This review discusses the possible mechanisms by which HMGB1 mediates Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, amyotrophic lateral sclerosis, and the potential of HMGB1 as a biomarker for these diseases. Future research needs to further explore the underlying molecular mechanisms and clinical translation.

Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration of the lower motor neurons. There are currently 29 reported causative genes and 4 disease loci implicated in dHMN. Despite the high genetic heterogeneity, mutations in the known genes account for less than 20% of dHMN cases with the mutations identified predominantly being point mutations or indels. We have expanded the spectrum of dHMN mutations with the identification of a 1.35 Mb complex structural variation (SV) causing a form of autosomal dominant dHMN (DHMN1 OMIM %182906). Given the complex nature of SV mutations and the importance of studying pathogenic mechanisms in a neuronal setting, we generated a patient-derived DHMN1 motor neuron model harbouring the 1.35 Mb complex insertion. The DHMN1 complex insertion creates a duplicated copy of the first 10 exons of the ubiquitin-protein E3 ligase gene (UBE3C) and forms a novel gene-intergenic fusion sense transcript by incorporating a terminal pseudo-exon from intergenic sequence within the DHMN1 locus. The UBE3C intergenic fusion (UBE3C-IF) transcript does not undergo nonsense-mediated decay and results in a significant reduction of wild type full length UBE3C (UBE3C-WT) protein levels in DHMN1 iPSC-derived motor neurons. An engineered transgenic C. elegans model expressing the UBE3C-IF transcript in GABA-ergic motor neurons shows neuronal synaptic transmission deficits. Furthermore, the transgenic animals are susceptible to heat stress which may implicate defective protein homeostasis underlying DHMN1 pathogenesis. Identification of the novel UBE3C-IF gene-intergenic fusion transcript in motor neurons highlights a potential new disease mechanism underlying axonal and motor neuron degeneration. These complementary models serve as a powerful paradigm for studying the DHMN1 complex SV and an invaluable tool for defining therapeutic targets for DHMN1.

Distal hereditary motor neuropathies (dHMNs) are a group of inherited diseases involving the progressive, length-dependent axonal degeneration of the lower motor neurons. There are currently 29 reported causative genes and four disease loci implicated in dHMN. Despite the high genetic heterogeneity, mutations in the known genes account for less than 20% of dHMN cases, with the mutations identified predominantly being point mutations or indels. We have expanded the spectrum of dHMN mutations with the identification of a 1.35 Mb complex structural variation (SV) causing a form of autosomal dominant dHMN (DHMN1 OMIM %182906). Given the complex nature of SV mutations and the importance of studying pathogenic mechanisms in a neuronal setting, we generated a patient-derived DHMN1 motor neuron model harbouring the 1.35 Mb complex insertion. The DHMN1 complex insertion creates a duplicated copy of the first 10 exons of the ubiquitin-protein E3 ligase gene (UBE3C) and forms a novel gene–intergenic fusion sense transcript by incorporating a terminal pseudo-exon from intergenic sequence within the DHMN1 locus. The UBE3C intergenic fusion (UBE3C-IF) transcript does not undergo nonsense-mediated decay and results in a significant reduction of wild-type full-length UBE3C (UBE3C-WT) protein levels in DHMN1 iPSC-derived motor neurons. An engineered transgenic Caenorhabditis elegans model expressing the UBE3C-IF transcript in GABA-ergic motor neurons shows neuronal synaptic transmission deficits. Furthermore, the transgenic animals are susceptible to heat stress, which may implicate defective protein homeostasis underlying DHMN1 pathogenesis. Identification of the novel UBE3C-IF gene–intergenic fusion transcript in motor neurons highlights a potential new disease mechanism underlying axonal and motor neuron degeneration. These complementary models serve as a powerful paradigm for studying the DHMN1 complex SV and an invaluable tool for defining therapeutic targets for DHMN1.

The study aims to investigate how the internet has affected China’s financial inclusion from the standpoint of developing internet technologies. Firstly, using the coefficient of variation method and the principal component analysis method, the financial inclusion index (IFI) and the internet development index (INT) were built from multiple dimensions based on the 2006–2016 provincial panel data of China. Then, the fixed-effect panel threshold model, the fixed-effect estimate, and the 2SLS estimate were used to empirically test the impact of internet development on inclusive finance in China. We found that China’s financial inclusion was significantly and positively affected by internet development. Additionally, this effect was nonlinear, and there was a threshold effect on the proportion of internet users. The development of the internet had a significant positive effect on financial inclusion when the internet user proportion (ISP) was higher than 19%, and the effect on IFI became stronger when ISP rose above 53%. This study complements earlier research, in which internet finance is usually perceived as a composite notion, by thoroughly examining the effects of internet information technology on the growth of financial inclusion. Based on our findings, we further put forward policy recommendations for the sustainable development of inclusive finance in terms of the intelligent integration and collaboration of internet communication technologies. Financial inclusion is critical for achieving sustainability because it provides access to affordable financial services to underserved individuals and businesses, and brings them into the formal financial sector, thereby improving their livelihoods while reducing poverty and inequality.

Using the Kullback-Leibler distance between two density functions about a matrix T distribution and a matrix normal distribution, we obtain a Berry-Esseen boundary for the T distribution. Further, we give the condition under which a matrix T is uniformly asymptotically matrix normal distribution, and point out the convergence rate.

Objective To evaluate the optimal Kryptor threshold for sFlt-1/PlGF on PE among the hypertensive pregnant women. Design A single centre prospective study. Setting Guangzhou Women and Children’s Medical Care Center. Population or Sample 565 singleton pregnant women with hypertension from January 2018 to June 2021. Methods PlGF/sFlt-1 and perinatal data were collected and logistic regression was used to explore the cutoffs of sFlt-1/PlGF for PE from different hypertension types in HDP. Main outcome measures PlGF/sFlt-1 cutoff of PE and chrHBP with PE in HDP . Results: The sFlt-1 /PlGF ratio in PE and chrHBP with PE were significantly higher than GH & chrHBP, in which early-onset were higher. For gestatioanl hypertension, sFlt-1 /PlGF ratio> 36.44 could rule in PE occurence(AUC=76.17% - 78.39%) in 1-4week with PPV 0.91-0.94 & NPV 0.67 before 34 weeks, while sFlt-1 /PlGF ratio< 51.52 could rule out PE occurrence (AUC=75.29% - 78.39%) in 1-4 weeks with NPV 0.91-0.96 & PPV 0.62-0.73 after 34 weeks. For chronic hypertension, sFlt-1 /PlGF ratio> 47.78 could rule in PE occurrence (AUC=82.5% - 86.36%) in 1-4 weeks with PPV 0.9-0.96 & NPV 1.0 before 34 weeks, while sFlt-1 /PlGF ratio< 28.61 could rule out PE occurence(AUC=72.41% - 73.03%) in 1-4 weeks with NPV 0.88 & PPV 0.43-0.79 after 34 weeks. Conclusion: Lower sFlt-1/PlGF had high positive potential to identify the patients to develop early onset PE from gestational and chronic hypertension, which could complement the strategy to hypertensive disorders in pregnany. Funinding Guangzhou science and technology Program Project (202102010163) .

Context Leukocyte telomere length (LTL) is a biomarker of biological aging and is associated with metabolic diseases such as type 2 diabetes. Insufficient maternal vitamin D was associated with increased risk for many diseases and adverse later life outcomes. Objective This study investigates the relationship between vitamin D levels and offspring LTL at early life. Methods This observational, longitudinal, hospital-based cohort study included eligible mother-child pairs from the HAPO Hong Kong Field Centre, with 853 offspring at age 6.96 ± 0.44 (mean ± SD) years. LTL was measured using real-time polymerase chain reaction while serum vitamin D metabolites 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3 were measured in maternal blood (at gestation 24-32 weeks) and cord blood by liquid chromatography–mass spectrometry. Results LTL at follow-up was significantly shorter in boys compared with girls (P Conclusion Our findings suggest 25(OH)D3 and 3-epi-25(OH)D3 in utero may impact on childhood LTLs, highlighting a potential link between maternal vitamin D and biological aging.

Combinational utilization of intravenous non-steroidal anti-inflammatory drugs (NSAIDs) with opium analgesic is an effective alternative modality for pain control after surgery. This regimen is known for reducing the risk of addiction induced by opium analgesic. However, current intravenous NSAIDs have solubility problems, limiting their clinical applications. Although loxoprofen exhibits strong anti-inflammatory and analgesic activities with relatively low ulcerogenicity, its relatively low bioavailability makes it not an ideal drug candidate for intravenous injection. We selected the bioactive metabolite (6) of loxoprofen as a candidate and developed a new intravenous NSAID, HR1405-01. This metabolite exhibited significantly stronger anti-inflammatory and analgesic activities than parecoxib sodium injection or ibuprofen injection. The excellent potency and solubility of HR1405-01 allowed the avoidance of utilization of cosolvent in the formulation, resulting in fewer side effects and a better safety profile. Therefore, HR1405-01 might be a promising candidate for the development of a new intravenous NSAID.

IgG4-related sialadenitis (IgG4-RS) is a chronic fibroinflammatory disease characterized by glandular fibrosis and hyposalivation. This study was undertaken to explore the role of cellular senescence in the pathogenesis of IgG4-RS-related fibrosis.The expression of senescence markers and proinflammatory cytokines in the submandibular glands (SMGs) of IgG4-RS patients (n = 18) and controls (n = 14) was determined by proteomics, real-time polymerase chain reaction, Western blotting, and immunohistochemistry. After interleukin-4 (IL-4) treatment, high-throughput RNA sequencing was performed to identify the differentially expressed genes in SMG-C6 cells. A glandular fibrosis model was established by the intraglandular injection of IL-4 into mouse SMGs (n = 8 per group).Salivary acinar and ductal epithelial cells underwent senescence in IgG4-RS patients, as indicated by the elevated activity of senescence-associated β-galactosidase, lipofuscin accumulation, enhanced expression of senescence markers (p53 and p16The cellular senescence induced by IL-4 through the ROS/p38 MAPK-p16

Valuing water is difficult and contentious owing to water’s physical, political, and economic characteristics. Combining household-level and county-level data at the county level could clarify the responsibilities of both the government and users. In the Thousand Island Lake Water Distribution Project (TILWDP), the upstream ecosystem services provider, Chunan County, is assumed to sustain a tremendous opportunity cost due to the extremely strict environmental protection requirements of the project. To estimate the opportunity cost of supplying fresh water that meets the standards of the National Primary Drinking Water Regulations, a synthetic control model is introduced, and county-level macroeconomic data are used. A funding gap was estimated in the current government-financed situation. Meanwhile, willingness to pay is calculated based on household-level data collected in the downstream area. The estimate indicates that the combination of ecological compensation payments from governments and downstream stakeholders’ willingness to pay for water services could completely cover the upstream service provider’s opportunity cost. Specifically, the related central and downstream governments would need to take on approximately 1/3 of the total cost, while the users from the downstream area would take on the rest. The proposed policies include adopting government–user joint-financing payment for ecosystem services (PES) schemes for regional ecological and environmental cooperation in China, implementing diversified payment vehicles, launching additional environmental education projects, etc.

Background Little is known about the presence of 3-epi-25 hydroxyvitamin D in maternal and neonatal circulation, the extent of its contribution to total 25 hydroxyvitamin D, or factors influencing its levels. Methods A total of 1502 and 1321 archived maternal and umbilical cord serum samples from the Hyperglycemia and Adverse Pregnancy Outcome Study cohort from Hong Kong were assayed for 25(OH)D2, 25(OH)D3, and isomeric form of 25(OH)D3 (3-epi-25(OH)D3) by a liquid chromatography-tandem mass spectrometry method. Results Vitamin D deficiency (total serum 25(OH)D level < 50 nmol/L) and severe vitamin D deficiency (total serum 25(OH)D level < 25 nmol/L) occurred in 590 (39.3%) and 25 (1.7%) mothers, respectively. 3-epi-25(OH)D3 could be detected in 94.5% of maternal and 92.1% of neonatal umbilical sera, with the highest 3-epi-25(OH)D3 levels contributing to 19.9% and 15.3% of the maternal and umbilical cord sera 25(OH)D3 levels, respectively. Pregnancy with a male fetus, ambient solar radiation, and maternal glycemia and 25(OH)D3 levels were independent factors associated with maternal 3-epi-25(OH)D3 level. Advanced maternal age, multiparity, maternal gestational weight gain below the Institute of Medicine recommendation, maternal glycemic status, and earlier gestational age at delivery were significantly associated with higher umbilical cord serum 3-epi-25(OH)D3. Conclusions 3-epi-25(OH)D3 accounted for a significant portion of total 25(OH)D in maternal and neonatal circulations. Further study is needed to determine the possible mechanism underlying this observation.

Leukocyte telomere length (LTL) is a biomarker of biological aging, and has been associated with metabolic diseases such as type 2 diabetes (T2DM). Insufficient maternal vitamin D (25(OH)D) has also been associated with increased disease risk for many diseases and adverse later life outcomes. The association between maternal and cord blood total 25(OH)D and LTL was examined in mother-child pairs from the HAPO Hong Kong Field Centre, including 815 offspring at age (mean±SD) 6.96 ± 0.44 years. LTL was measured using real-time polymerase chain reaction and serum 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 were measured in maternal blood (at gestation 24-32 weeks) and cord blood by liquid chromatography-mass spectrometry. Children LTL at follow-up was significantly shorter in boys compared to girls (p Disclosure K. Wong: None. B. E. Metzger: None. W. Lowe: None. W. H. Tam: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. F. Cheng: None. D. Mao: None. C. K. P. Lim: Stock/Shareholder; Self; GemVCare Ltd. R. Wang: None. C. H. Tam: None. M. A. Joglekar: None. A. A. Hardikar: None. A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V.

M-QAM is very favorable in high speed communication systems, because it could enhance the frequency spectrum utilization. In this paper, we propose an improved simplified soft demodulation algorithm for 64QAM signal through fundamental principle and simulation analysis. The new algorithm optimizes the decision calculation rules, which greatly reduces the amounts of calculation with almost no system performance loss, and it has high practical value.

This paper is to explore the impact of entrepreneurial psychological capital and capital heterogeneity on venture capital behavior, and further analyze the effect of venture capital on the innovation activities of enterprises. Based on the existing research results, this paper proposed hypotheses on the relationship between venture capital and technological innovation. According to the data samples of growth enterprises market (GEM) listed companies from 2010 to 2016, the main research variables were defined and a theoretical analysis model was constructed. The theory and empirical research clarify the relationship between venture capital and technological innovation. (1) According to the regression results of venture capital participation as well as innovation input and innovation output, the regression coefficients of venture capital participation are 0.609 and 0.203, which are significant at the levels of 10 and 1%, respectively. It indicates that venture capital participation has a positive impact on the innovation input and output of enterprises. (2) The coefficient of venture capital participation is positive, and the coefficient of HHI×VC¯ is significantly negative. Therefore, the degree of product market competition has a significant moderating effect on the relationship between venture capital participation and technological innovation. Venture capital provides funding support for technological innovation in startups. At the same time, because it holds a certain percentage of shares, it participates in enterprise innovation activities and provides guidance for companies to maintain profitable growth, thereby improving their innovation awareness and level. This research makes up for the shortcomings of the previous research model that uses a single dimension to measure technological innovation. As a result, this study comprehensively investigates the impact of venture capital on the innovation input and output of enterprises, enhancing the integrity and reliability of previous research conclusions.

Charcot-Marie-Tooth (CMT) is a group of inherited diseases clinically and genetically heterogenous, characterised by length dependent degeneration of axons of the peripheral nervous system. A missense mutation (p.R158H) in the pyruvate dehydrogenase kinase 3 gene (PDK3) has been identified as the genetic cause for an X-linked form of CMT (CMTX6) in two unrelated families. PDK3 is one of four PDK isoenzymes that regulate the activity of the pyruvate dehydrogenase complex (PDC). The balance between kinases (PDKs) and phosphatases (PDPs) determines the extend of oxidative decarboxylation of pyruvate to generate acetyl CoA, critically linking glycolysis and the energy producing Krebs cycle. We had shown the p.R158H mutation causes hyperactivity of PDK3 and CMTX6 fibroblasts show hyperphosphorylation of PDC, leading to reduced PDC activity and ATP production. In this manuscript we have generated induced pluripotent stem cells (iPSCs) by re-programming CMTX6 fibroblasts (iPSCCMTX6). We also have engineered an isogenic control (iPSCisogenic) and demonstrated that genetic correction of the p.R158H mutation reverses the CMTX6 phenotype. Patient-derived motor neurons (MNCMTX6) show increased phosphorylation of the PDC, energy metabolism defects and mitochondrial abnormalities, including reduced velocity of trafficking mitochondria in the affected axons. Treatment of the MNCMTX6 with a PDK inhibitor reverses PDC hyperphosphorylation and the associated functional deficits founds in the patient motor neurons, demonstrating that the MNCMTX6 and MNisogenic motor neurons provide an excellent neuronal system for compound screening approaches to identify drugs for the treatment of CMTX6.

The herb dwarf lilyturf tuber (Maidong, Ophiopogonis Radix) is widely used in Chinese traditional medicine to manage diabetes and its complications. However, the role of Maidong polysaccharide extract (MPE) in pancreatic β-cell function is unclear. Here, we investigated whether MPE protects β-cell function and studied the underlying mechanisms. We treated db/db and high-fat diet (HFD)-induced obese mice with 800 or 400 mg/kg MPE or water for 4 weeks, followed by an oral glucose tolerance test. Pancreas and blood were collected for molecular analyses, and clonal MIN6 β-cells and primary islets from HFD-induced obese mice and normal chow diet–fed mice were used in additional analyses. In vivo, MPE both increased insulin secretion and reduced blood glucose in the db/db mice but increased only insulin secretion in the HFD-induced obese mice. MPE substantially increased the β-cell area in both models (3-fold and 2-fold, p < 0.01, for db/db and HFD mice, respectively). We observed reduced nuclear translocation of the p65 subunit of NF-κB in islets of MPE-treated db/db mice, coinciding with enhanced glucose-stimulated insulin secretion (GSIS). In vitro, MPE potentiated GSIS and decreased interleukin 1β (IL-1β) secretion in MIN6 β-cells. Incubation of MIN6 cells with tumor necrosis factor α (TNFα), interferon-γ, and IL-1β amplified IL-1β secretion and inhibited GSIS. These effects were partially reversed with MPE or the IκB kinase β inhibitor PS1145, coinciding with reduced activation of p65 and p-IκB in the NF-κB pathway. We conclude that MPE may have potential for therapeutic development for β-cell protection.

Chain-like ZSM-5 zeolite with long b-axis length and mesoporosity has been synthesized rapidly and efficiently in supercritical CO2. X-ray diffraction (XRD) patterns and scanning electron microscopy (SEM) images demonstrate that chain-like ZSM-5 zeolite has good crystallinity and chain-like morphology. N2 sorption isotherm indicates that chain-like ZSM-5 has mesopores. The formation of p-xylene from m-xylene isomerization has been tested in catalytic paltform, showing that chain-like ZSM-5 has higher conversion of m-xylene and selectivity of p-xylene, due to the combination of the long b-axis length and the mesoporosity in the chain-like ZSM-5 sample, compared with conventional ZSM-5 zeolite.

A major hurdle in stem cell therapy is the tumorigenic risk of residual undifferentiated stem cells. This report describes the design and evaluation of synthetic hybrid molecules that efficiently reduce the number of human induced pluripotent stem cells (hiPSCs) in cell mixtures. The design takes advantage of Kyoto probe 1 (KP-1), a fluorescent chemical probe for hiPSCs, and clinically used anticancer drugs. Among the KP-1-drug conjugates we synthesized, we found an exceptionally selective, chemically tractable molecule that induced the death of hiPSCs. Mechanistic analysis suggested that the high selectivity originates from the synergistic combination of transporter-mediated efflux and the cytotoxicity mode of action. The present study offers a chemical and mechanistic rationale for designing selective, safe, and simple reagents for the preparation of non-tumorigenic clinical samples.

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1β) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1β and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.

Pharmacophore-focused chemical libraries are continuously being created in drug discovery programs, yet screening assays to maximize the usage of such libraries are not fully explored. Here, we report a chemical proteomics approach to reutilizing a focused chemical library of 1,800 indole-containing molecules for discovering uncharacterized ligand-protein pairs. Gel-based protein profiling of the library using a photo-affinity indole probe 1 enabled us to find new ligands for glyoxalase 1 (Glo1), an enzyme involved in the detoxification of methylglyoxal. Structure optimization of the ligands yielded an inhibitor for Glo1 (9). Molecule 9 increased the cellular methylglyoxal levels in human cells and suppressed the osteoclast formation of mouse bone marrow-derived macrophages. X-ray structure analyses revealed that the molecule lies at a site abutting the substrate binding site, which is consistent with the enzyme kinetic profile of 9. Overall, this study exemplifies how chemical proteomics can be used to exploit existing focused chemical libraries.

Pinopode and Mucin 1 (MUC1) have both been proposed as morphological and molecular markers of endometrial receptivity for implantation. However, their spatial relationship in luminal epithelium and its association with reproductive failure are still unclear. This was a prospective cohort study conducted at a university assisted reproductive unit including 9 receptive control women, 18 infertile women, and 22 women with recurrent implantation failure (RIF) and 22 women with recurrent miscarriage (RM). Endometrial tissues were obtained at 7 days after luteinizing hormone surge during implantation window. Luminal epithelium was examined by scanning electron microscopy (SEM). MUC1 localization in luminal epithelium was detected by scanning immunoelectron microscopy (SIM) and compared by modified double immunofluorescence (mIF) staining without antigen retrieval. SEM did not show any significant difference in percentage of secretory cells, any stage of pinopodes, and ciliated cells between control, infertility, RIF and RM groups. SIM identified MUC1 was mainly localized on surface of ciliated cells and at the bottom of cilia, not secretory cells and pinopodes, and its specific localization was validated by mIF staining. MUC1 expression in ciliated cells in control women was significantly higher than those women with reproductive failure, but there was no significant difference between RIF and RM. In conclusion, MUC1 is mainly expressed in ciliated cells, not secretory cells and pinopodes, of the endometrial luminal epithelium during implantation window. The specific expression of MUC1 in the ciliated cells in receptive control women is higher than that of women with reproductive failure during implantation window.

ATP7A encodes a copper-transporting P-type ATPase and is one of 23 genes in which mutations produce distal hereditary motor neuropathy (dHMN), a group of diseases characterized by length-dependent axonal degeneration of motor neurons. We have generated induced pluripotent stem cell (iPSC)-derived motor neurons from a patient with the p.T994I ATP7A gene mutation as an in vitro model for X-linked dHMN (dHMNX). Patient motor neurons show a marked reduction of ATP7A protein levels in the soma when compared to control motor neurons and failed to upregulate expression of ATP7A under copper-loading conditions. These results recapitulate previous findings obtained in dHMNX patient fibroblasts and in primary cells from a rodent model of dHMNX, indicating that patient iPSC-derived motor neurons will be an important resource for studying the role of copper in the pathogenic processes that lead to axonal degeneration in dHMNX., Summary: The authors describe a neuronal model to investigate how mutations in the copper transporter ATP7A cause axonal degeneration in the peripheral nervous system.

Cervical cancer (CC) is one of the most common female malignancies in the world. Although paclitaxel (PTX) is a critical chemotherapy agent for the treatment of CC, its treatment outcome is limited by the development of drug resistance. The present study aims to define the role of long non-coding RNA (lncRNA) LINC00511 in the progression of CC with the involvement of cell proliferation, apoptosis and resistance to PTX in Hela/PTX cells. CC and adjacent normal tissue samples were collected from 84 patients with CC, and used to determine LINC0051 expression. PTX-resistant Hela/PTX cell line was constructed, in which LINC0051 was overexpressed or silenced to further investigate the effect of LINC00511 on PTX-resistant Hela/PTX cell viability, proliferation, migration, invasion, cell cycle, apoptosis and resistance of CC cells to PTX. The expression of Bcl-2, Bax, cleaved-caspase-3, matrix metalloproteinase (MMP)-2, MMP-9, multidrug resistance protein 1 (MRP1) and P-glycoprotein (P-GP) was also assessed. High-expression of LINC00511 was found in CC with its close association with the tumor stage, tumor size and lymph node metastasis. After silencing LINC00511 expression, the expression of MRP1, P-GP, Bcl-2, MMP-2 and MMP-9 was decreased, while Bax and cleaved-caspase-3 increased with more CC cells arrested at G1 phase. Furthermore, silencing of LINC00511 could suppress cell resistance to PTX, cell viability, cell proliferation, migration and invasion yet promoted cell apoptosis in PTX-resistant Hela/PTX cells. Collectively, our findings demonstrate that silencing of LINC00511 could inhibit CC cell resistance to PTX, cell proliferation, migration and invasion, and promote cell apoptosis in CC. Silencing of LINC00511 provides a novel therapeutic target for CC.

Cervical cancer (CC) is one of the most common female malignancies in the world. Although paclitaxel (PTX) is a critical chemotherapy agent for the treatment of CC, its treatment outcome is limited by the development of drug resistance. The present study aims to define the role of long non-coding RNA (lncRNA) LINC00511 in the progression of CC with the involvement of cell proliferation, apoptosis and resistance to PTX in Hela/PTX cells. CC and adjacent normal tissue samples were collected from 84 patients with CC, and used to determine LINC0051 expression. PTX-resistant Hela/PTX cell line was constructed, in which LINC0051 was overexpressed or silenced to further investigate the effect of LINC00511 on PTX-resistant Hela/PTX cell viability, proliferation, migration, invasion, cell cycle, apoptosis and resistance of CC cells to PTX. The expression of Bcl-2, Bax, cleaved-caspase-3, matrix metalloproteinase (MMP)-2, MMP-9, multidrug resistance protein 1 (MRP1) and P-glycoprotein (P-GP) was also assessed. High-expression of LINC00511 was found in CC with its close association with the tumor stage, tumor size and lymph node metastasis. After silencing LINC00511 expression, the expression of MRP1, P-GP, Bcl-2, MMP-2 and MMP-9 was decreased, while Bax and cleaved-caspase-3 increased with more CC cells arrested at G1 phase. Furthermore, silencing of LINC00511 could suppress cell resistance to PTX, cell viability, cell proliferation, migration and invasion yet promoted cell apoptosis in PTX-resistant Hela/PTX cells. Collectively, our findings demonstrate that silencing of LINC00511 could inhibit CC cell resistance to PTX, cell proliferation, migration and invasion, and promote cell apoptosis in CC. Silencing of LINC00511 provides a novel therapeutic target for CC.

Shell is aquatic product processing industry waste, shrimp, crab and shellfish contain heavy metal, cause this kind of waste water deposits, the pollution caused by the Marine area, but the shell and shrimp shell contains rich off acetyl chitosan, chitosan degradation into shell oligosaccharides have many function effect, from the perspective of environmental protection is to deal with some of the pollution, and the preparation of the beneficial shell oligosaccharides. This paper introduces the extraction of chitosan from shrimp shells and the preparation of sunscreen by using physical degradation method to extract chitosan oligosaccharide from chitosan. In this paper, natural chito-oligosaccharides were extracted from shellfish waste and used as ingredients to make natural sunscreen, which was an exploration of chito-oligosaccharides in the field of daily use in fine chemical industry.

Submerged combustion vaporizer (SCV) is widely equipped in liquefied natural gas (LNG) gasification plants and receiving terminals as the emergency or peaking regasification facility. This paper constructs an energy balance-based numerical model to predict the thermal behavior of SCV operating at subcritical pressures. The heat transfer coupling between the ice formation at the water bath-side and the flow boiling at the LNG-side is considered in the numerical model for the first time, and numerous correlations are utilized to estimate the convective heat transfer rate at both the water bath and LNG sides. The thermal behavior of a typical SCV in the presence of ice layer is studied numerically after validating against the field operating data. The predicted results indicate that the SCV can vaporize cryogenic LNG to a near-normal atmospheric temperature under low water bath temperatures, although an ice layer, having negative effects on heat transfer, is formed on the lower part of the heat transfer tube. Both the operating parameters and heat transfer enhancement measures have significant impacts on the thermal behavior.

This report describes the design and evaluation of phosphorylated 7-ethyl-10-hydroxycamptothecin (SN38-P), which selectively eliminates tumor-forming proliferative stem cells, including human induced pluripotent stem cells (hiPSCs) and neural stem cells, from iPSC-derived neural cell mixtures. Results of the present study demonstrate that simple phosphorylation of an anticancer drug can provide a safe, cost-effective, and chemically-defined tool for decontaminating hiPSC-derived neuron.

In this paper, the performance bound has been analyzed on Hamming-Weight-Analysis (HWA) algorithm. We first introduce the description of the linear block code and the theoretical analysis of the HWA algorithm. According to the theoretical analysis, we build simulation model and analyze the performance of HWA algorithm. HWA algorithm has a good recognition performance under the condition of low code rate and high BER. Finally, the performance bound of HWA algorithm is given based on the simulation results. The results in this paper have been validated through simulation on MATLAB.

Cell replacement therapy for diabetes mellitus requires cost-effective generation of high-quality, insulin-producing, pancreatic β cells from pluripotent stem cells. Development of this technique has been hampered by a lack of knowledge of the molecular mechanisms underlying β-cell differentiation. The present study identified reserpine and tetrabenazine (TBZ), both vesicular monoamine transporter 2 (VMAT2) inhibitors, as promoters of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Neurog3 (referred to henceforth as Ngn3)-positive endocrine precursors. VMAT2-controlled monoamines, such as dopamine, histamine and serotonin, negatively regulated β-cell differentiation. Reserpine or TBZ acted additively with dibutyryl adenosine 3',5'-cyclic AMP, a cell-permeable cAMP analog, to potentiate differentiation of embryonic stem (ES) cells into β cells that exhibited glucose-stimulated insulin secretion. When ES cell-derived β cells were transplanted into AKITA diabetic mice, the cells reversed hyperglycemia. Our protocol provides a basis for the understanding of β-cell differentiation and its application to a cost-effective production of functional β cells for cell therapy.

Marine litter poses numerous threats to the global environment. To estimate the social costs of marine litter in China, two stated preference methods, namely the contingent valuation model (CVM) and the choice experiment model (CEM), were used in this research. This paper conducted surveys at ten different beaches along the East China Sea in Zhejiang province in October 2017. The results indicate that approximately 74.1% of the interviewees are willing to volunteer to participate in clean-up programmes and are willing to spend 1.5 days per month on average in their daily lives, which equates to a potential loss of income of USD 1.08 per day. The willingness to pay for the removal of the main types of litter ranges from USD 0.12&ndash, 0.20 per visitor across the four sample cities, which is mainly determined by the degree of the removal, the crowdedness of the beach and the visitor&rsquo, s perception. The social costs are USD 1.08&ndash, 1.40 per visitor when the contingent valuation method is applied and USD 1.00&ndash, 1.07 per visitor when the choice experiment method is adopted, which accounts for 8&ndash, 14% of the beach entrance fee. The analysis of the social costs of marine litter yielded some useful implications regarding future coastal management policy, including extra entrance fee, the quality-oriented environmental strategy and more incentives to volunteers.

The value of wasteheat utilization in large general hospitals is a critical problem that can not be ignored with social development. To make use of this source means to establish a system of wasteheat utilization, and two priorities are determining the weigh of different wasteheat utilization point properly and determine the best path for waste heat utilization. In this paper, based on Analytic Hierarchy Process (AHP) and Information Entropy of wasteheat utilization point distribution model, we find the way to determine the weights. At the same time, the Minimum Spanning Tree Model based on Kruskal's algorithm helps to find the new method of optimal path in using wasteheat. Both models will be used in the heat research of a hospital, and we identify both clear wasteheat utilization point weights distribution and minimum cost of the best path which really paves the way for the further system construction of wasteheat utilization in large general hospital with further research and application value.