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Due to the effect of climate changes and human activities, groundwater over-exploitation and aquifer depletion have become global issues of concern. Artificial recharge of groundwater through a river has been paid more attention among a variety of artificial intervention measures. It is found that not all rivers or river reaches are suitable for artificial recharge of groundwater owing to the limitations of recharge potential by infiltration and storage capacity of the vadose zone. At present, there is still a lack of widely accepted suitability assessment methods. In this study, the Yongding River in the Beijing Plain section and the underlying aquifer are taken as the study area and the case study is carried out. Moreover, the measured data are used to verify the results. The suitability assessment model (LMBGITSC model) constructed by the index system method includes eight indexes: land use types of riverbed, sediment types of riverbed, channel width, channel topographic slope, medium types of the vadose zone, thickness of the vadose zone, specific yield of the vadose zone and horizontal permeability of the vadose zone. The results show that the suitability of groundwater recharge in the Yongding River changes from good degree to medium degree along the river flow direction (except the reaches carried out anti-seepage engineering), presenting a "step-type" evolution law. The proposed method is of good applicability and can also provide reference for similar regions.

Due to extensive water exchanges and abundant active biochemical compositions, active and complex hydrogeochemical processes often exist in riverbank filtration (RBF). The distribution of microbes is considered to be profoundly affected by these processes and is considered to impact the hydrogeochemical processes and the migration and transformation of water pollutants in turn and then impact the water quality. The distribution of microbes and their response to the physiochemical properties along a vertical RBF profile perpendicular to the Songhua River in Northeast China was explored by using 16 S rRNA and redundancy analysis (RDA). The results showed that various microbes were found in the vertical riparian filter (RBF) curve, including Actinobacteria, Proteobacteria, Acidobacteria, Chloroflexi, and Firmicutes. With increasing depth (vertical) and distance from the river (lateral), the microbial community and diversity in the RBF sediment profile decreased. Nitrospirota, Pseudomonas, Gammaproteobacteria, Ochrobactrum, Acinetobacter and Desulfobacterota of the RBF core taxa were also significantly correlated with the biotransformation behavior of typical groundwater pollutants (ammonia, Fe, Mn and S). The amount of As in the RBF is too low to sustain microbial survival. Some microbes in RBF can also degrade natural organic pollutants. This study not only revealed the spatial distribution of geological microbes under the impact of hydrological processes but also lays a foundation for the further study of the hydrobiogeochemical processes of active biochemical compositions in groundwater and water quality evolution, which is of positive significance to ensure the quality safety of the drinking water supplied by RBFs.

As one of the most widespread pollutants worldwide, nitrogen has long been a concern in the environment, including groundwater. However, due to the limitations of investigations and study progress, there is still a poor understanding of groundwater nitrogen pollution and its potential effects on human health in many areas, particularly in developing countries. The spatiotemporal evolution of groundwater nitrate nitrogen levels and potential human health risks in the Songnen Plain, Northeast China were comprehensively studied based on both our own test data and available published data that were collected by us over a study period from 1995 to 2015. Groundwater nitrate nitrogen concentrations exhibited significant temporal and spatial differences: there was an increasing trend with time; and the distribution of high concentration areas expanded from the central and western areas to the east with time. The similar pattern existed in the potential health risks posed to the residents considering the two exposure pathways including drinking water and dermal contact. The effects of groundwater nitrate nitrogen on human health depend on the nitrate concentration but there were also age differences, namely, in the order of infants > children > adult females ≈ adult males, according to the hazard quotient (HQ) used in the human health risk assessment (HHRA) model. The spatiotemporal evolution of groundwater nitrate nitrogen levels and potential human health risks indicate that the issue of nitrogen pollution in groundwater in the study area is worsening and needs further attention. The drivers that increased nitrate nitrogen concentrations in the groundwater of the study area were the increased fertilizer use due to the increased cultivated land area and implementation of a land fertility policy by the local government. It should be acknowledged that the results have uncertainties that not only come from the layout of sampling points and selection of spatial interpolation methods but also come from the parameter settings in the assessment model and assumptions of drinking water scenarios. However, the conclusions still have important reference value for groundwater pollution control and management and human health risk supervision and early warning.

Groundwater is an essential source of drinking and irrigation water. However, elevated Fe and Mn concentrations in groundwater have been found in recent decades, which can adversely affect human health and decrease crop quality and yields. The roles of hydrogeochemical changes and groundwater pollution (exogenous reductive material inputs) in this have not been studied adequately. We determined the distribution of Fe and Mn concentrations in groundwater in the Songnen Plain, northeast China, which is known for elevated Fe and Mn concentrations, and investigated the factors and mechanisms involved in causing the elevated concentrations. Chemical and statistical analyses indicated that the Fe and Mn concentrations in groundwater significantly correlated with climate parameters (precipitation and temperature), surface features (altitude, distance from a river, soil type, soil texture, and land use type) and hydrogeochemical characteristics (chemical oxygen demand and NH4+, NO3−, and P concentrations). In particular, the Fe and Mn concentrations in groundwater are higher in areas containing paddy fields and water bodies than other land use type areas. Areas with groundwater containing ultra-high Fe and Mn concentrations have almost all of the favorable factors. The main reasons for the elevated Fe and Mn concentrations in groundwater in the study area are the Fe/Mn mineral-rich strata and soil with abundant organic matter acting as sources of Fe and Mn to the groundwater and the reductive environment in the lower terrain and areas containing water bodies favoring Fe and Mn dissolution in the groundwater. Inputs of pollutants from agricultural activities have caused the Fe and Mn concentrations in groundwater to increase. Future studies should be performed to study interactions between pollutants from agricultural activities and Fe and Mn in groundwater and develop environmental management strategies for preventing future increases in Fe and Mn concentrations and promoting sustainable development of agriculture.

Abstract Background Lung cancer is one of the most frequent cancers and the leading cause of cancer-related deaths worldwide with poor prognosis. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is crucial in the regulation of the extracellular matrix (ECM), impacting its formation, homeostasis and remodeling, and has been linked to cancer progression. However, the specific involvement of ADAMTS4 in the development of lung cancer remains unclear. Methods ADAMTS4 expression was identified in human lung cancer samples by immunohistochemical (IHC) staining and the correlation of ADAMTS4 with clinical outcome was determined. The functional impact of ADAMTS4 on malignant phenotypes of lung cancer cells was explored both in vitro and in vivo. The mechanisms underlying ADAMTS4-mediated lung cancer progression were explored by ubiquitination-related assays. Results Our study revealed a significant upregulation of ADAMTS4 at the protein level in lung cancer tissues compared to para-carcinoma normal tissues. High ADAMTS4 expression inversely correlated with the prognosis of lung cancer patients. Knockdown of ADAMTS4 inhibited the proliferation and migration of lung cancer cells, as well as the tubule formation of HUVECs, while ADAMTS4 overexpression exerted opposite effects. Mechanistically, we found that ADAMTS4 stabilized c-Myc by inhibiting its ubiquitination, thereby promoting the in vitro and in vivo growth of lung cancer cells and inducing HUVECs tubule formation in lung cancer. In addition, our results suggested that ADAMTS4 overexpression activated MAPK signaling pathway. Conclusions We highlighted the promoting role of ADAMTS4 in lung cancer progression and proposed ADAMTS4 as a promising therapeutic target for lung cancer patients.

Abstract Functional coatings, including organic and inorganic coatings, play a vital role in various industries by providing a protective layer and introducing unique functionalities. However, its design often involves time‐consuming experimentation with multiple materials and processing parameters. To overcome these limitations, data‐driven approaches are gaining traction in materials science. In this paper, recent advances in data‐driven materials research and development (R&D) for functional coatings, highlighting the importance, data sources, working processes, and applications of this paradigm are summarized. It is begun by discussing the challenges of traditional methods, then introduce typical data‐driven processes. It is demonstrated how data‐driven approaches enable the identification of correlations between input parameters and coating performance, thus allowing for efficient prediction and design. Furthermore, carefully selected case studies are presented across diverse industries that exemplify the effectiveness of data‐driven methods in accelerating the discovery of new functional coatings with tailored properties. Finally, the emerging research directions, involving integrating advanced techniques and data from different sources, are addressed. Overall, this review provides an overview of data‐driven materials R&D for functional coatings, shedding light on its potential and future developments.

ObjectiveTo explore the relationship between the deep medullary vein (DMV) score and atrophy in patients with cerebral small vessel disease (CSVD).MethodsImaging and clinical data from 125 patients with CSVD from January to December 2022 were reviewed. Normalized gray matter volume (GM_N) was calculated by dividing the gray matter volume by the whole brain volume. DMV scoring is conducted using susceptibility-weighted magnetic resonance imaging, wherein the DMV area is partitioned into six distinct regions: bilateral frontal, parietal, and occipital regions. Each region undergoes assessment based on the clarity and consistency of DMV visibility. Subsequently, the scores from these six regions are summed, resulting in a score ranging from 0 to 18 points.ResultsDMV score was associated with GM_N (r = −0.376, p

Abstract Background Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC. However, the expression and biological function of OTUD5 in HCC are still controversial. Results We determined that the expression of OTUD5 was significantly upregulated in HCC tissues. High levels of OTUD5 were also detected in most HCC cell lines. TCGA data analysis demonstrated that high OTUD5 expression indicated poorer overall survival in HCC patients. OTUD5 silencing prominently suppressed HCC cell proliferation, while its overexpression markedly enhanced the proliferation of HCC cells. Mass spectrometry analysis revealed solute carrier family 38 member 1 (SLC38A1) as a candidate downstream target protein of OTUD5. Coimmunoprecipitation analysis confirmed the interaction between OTUD5 and SLC38A1. OTUD5 knockdown reduced and OTUD5 overexpression increased SLC38A1 protein levels in HCC cells. However, OTUD5 alteration had no effect on SLC38A1 mRNA expression. OTUD5 maintained SLC38A1 stability by preventing its ubiquitin-mediated proteasomal degradation. SLC38A1 silencing prominently attenuated the OTUD5-induced increase in HCC cell proliferation. Finally, OTUD5 knockdown markedly suppressed the growth of HCC cells in vivo. Conclusions OTUD5 is an oncogene in HCC. OTUD5 contributes to HCC cell proliferation by deubiquitinating and stabilizing SLC38A1. These results may provide a theoretical basis for the development of new anti-HCC drugs.

Abstract Ferroptosis is closely associated with inflammatory diseases, including acute pancreatitis (AP); however, the involvement of ferroptosis in hypertriglyceridemic pancreatitis (HTGP) remains unclear. In the present study, we aimed to explore the relationship between lipid metabolism and ferroptosis in HTGP and the alleviating effect of liproxstatin-1 (Lip-1) in vivo. This study represents the first exploration of lipid metabolism and endoplasmic reticulum stress (ERS) in HTGP, targeting ferroptosis as a key factor in HTGP. Hypertriglyceridemia (HTG) was induced under high-fat diet conditions. Cerulein was then injected to establish AP and HTGP models. Lip-1, a specific ferroptosis inhibitor, was administered before the induction of AP and HTGP in rats, respectively. Serum triglyceride, amylase, inflammatory factors, pathological and ultrastructural structures, lipid peroxidation, and iron overload indicators related to ferroptosis were tested. Moreover, the interaction between ferroptosis and ERS was assessed. We found HTG can exacerbate the development of AP, with an increased inflammatory response and intensified ferroptosis process. Lip-1 treatment can attenuate pancreatic injury by inhibiting ferroptosis through lipid metabolism and further resisting activations of ERS-related proteins. Totally, our results proved lipid metabolism can promote ferroptosis in HTGP by regulating ACSL4/LPCAT3 protein levels. Additionally, ERS may participate in ferroptosis via the Bip/p-EIF2α/CHOP pathway, followed by the alleviating effect of Lip-1 in the rat model.

Objectives: Paracolic gutter exudation (PGE) may influence the severity of acute pancreatitis, but no study has explored it extensively. The objective of this study was to evaluate PGE for assessing the severity of disease. Methods: We performed a retrospective analysis of 488 patients from three tertiary hospitals in Guangxi, China. General clinical information, severity, and clinical courses were recorded. The PGE score were classified as follows: 0 for no exudation, 1 for unilateral exudation, and 2 for bilateral exudation. We used ROC curves to assess the predictive value of the PGE score, and logistic regression analysis to determine risk factors associated with death, ICU admission, and the occurrence of MODS. Results: This study included 352 patients with moderately severe acute pancreatitis (MSAP) and 136 patients with severe acute pancreatitis (SAP). Patients who had PGE experienced higher total hospitalization costs, longer hospital stays, a higher incidence of SAP, higher mortality rates, higher ICU admission rates, a higher incidence of MODS, and higher incidence of infections than those without (P 1 is an independent risk factor for ICU admission and MODS occurrence. (P

ABSTRACT: Although vaccines play a major role in the prevention of infectious bronchitis (IB), Anti-IB drugs still have great potential in poultry production. Radix Isatidis polysaccharide (RIP) is a crude extract of Banlangen with antioxidant, antibacterial, antiviral, and multiple immunomodulatory functions. The aim of this study was to explore the innate immune mechanisms responsible for RIP-mediated alleviation of infectious bronchitis virus (IBV)-induced kidney lesions in chickens. Specific-pathogen-free (SPF) chicken and chicken embryo kidney (CEK) cells cultures were pretreated with RIP and then infected with the QX-type IBV strain, Sczy3. Morbidity, mortality, and tissue mean lesion scores were calculated for IBV-infected chickens, and the viral loads, inflammatory factor gene mRNA expression levels, and innate immune pathway gene mRNA expression levels in infected chickens and CEK cell cultures were determined. The results show that RIP could alleviate IBV-induced kidney damage, decrease CEK cells susceptibility to IBV infection, and reduce viral loads. Additionally, RIP reduced the mRNA expression levels of the inflammatory factors IL-6, IL-8, and IL-1β by decreasing the mRNA expression level of NF-κB. Conversely, the expression levels of MDA5, TLR3, STING, Myd88, IRF7, and IFN-β were increased, indicating that RIP conferred resistance to QX-type IBV infection via the MDA5, TLR3, IRF7 signaling pathway. These results provide a reference for both further research into the antiviral mechanisms of RIP and the development of preventative and therapeutic drugs for IB.

The S2 subunit serves a crucial role in infectious bronchitis virus (IBV) infection, particularly in facilitating membrane fusion. Using reverse genetic techniques, mutant strains of the S2 locus exhibited substantially different syncytium-forming abilities in chick embryonic kidney cells. To determine the precise formation mechanism of syncytium, we demonstrated the co-ordinated role of Abl2 and its mediated cytoskeletal regulatory pathway within the S2 subunit. Using a combination of fluorescence quantification, RNA silencing, and protein profiling techniques, the functional role of S2 subunits in IBV-infected cells was exhaustively determined. Our findings imply that Abl2 is not the primary cytoskeletal regulator, the viral S2 component is involved in indirect regulation, and the three different viral strains activate various cytoskeletal regulatory pathways through Abl2. CRK, CRKL, ABI1, NCKAP1, and ENAH also play a role in cytoskeleton regulation. Our research provides a point of reference for the development of an intracellular regulatory network for the S2 subunit and a foundation for the rational design of antiviral drug targets against Abl2.

The S2 subunit of infectious bronchitis virus (IBV) plays a critical role in the process of IBV infection. A comparison between the S2 subunit sequence of chicken embryo kidney cell (CEK) adapted virulent QX-like IBV strain SczyC30 (hereafter referred to as zy30) and its CEK-attenuated strain, SczyC100, revealed an N1038S substitution in S2 subunit and a 1154EQTRPKKSV1162 residue deletion in the C-terminus of the S2 subunit. In order to explore whether these two mutations are related to changes in the biological characteristics of IBV, we firstly constructed an infectious clone of zy30 using a bacterial artificial chromosome (BAC), which combines the transcription of infectious IBV genomic RNA in non-susceptible BHK-21 cells with the amplification of rescued virus rzy30 in CEK cells. Then, three recombinant viruses, including an rzy30S2-N1038S strain that contained the N1038S substitution, an rzy30S2-CT9△ strain that contained the 1154EQTRPKKSV1162 deletion, and an rzy30S2-N1038S-CT9△ strain that contained both mutations, were constructed using rescued virus rzy30 as the backbone. The results showed that each mutation did not significantly affect the replication titer in CEK cells but reduced pathogenicity in chickens, while in combination, the N1038S substitution and 1154EQTRPKKSV1162 deletion improved the proliferation efficiency in CEK cells and reduced pathogenicity, compared to rzy30 strain. The contribution made by the 1154EQTRPKKSV1162 deletion in reducing pathogenicity was higher than that of N1038S substitution. Our results revealed that the N1038S substitution and 1154EQTRPKKSV1162 deletion in S2 subunit were deeply involved in the replication efficiency of IBV and contributed to reduction of viral pathogenicity.

Background: The potential functions of Thrombospondin 2 (THBS2) in the progression and immune infiltration of gastric cancer (GC) remain unclear. The purpose of this study was to clarify the role of THBS2 in GC prognosis and the relationship between THBS2 and GC immune cell infiltration.Material and Methods: The differential expression levels of THBS2 in the GC and cancer-adjacent tissues were identified using the TCGA databases and verified using real-time polymerase chain reaction (PCR), immunohistochemical staining and two datasets from Gene Expression Omnibus (GEO). THBS2 related differential expressed genes (DEGs) were identified and used for further functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Furthermore, a THBS2-related immune infiltration analysis was also performed. Kaplan-Meier and Cox regression analyses were utilized to illustrate the effects of THBS2 on the prognosis and clinical variables of GC. Finally, a nomogram was constructed to predict the survival probability of patients with GC.Results: The THBS2 expression in GC was significantly higher than that in cancer-adjacent tissues (p < 0.001), which was verified using real-time PCR, immunohistochemical staining and datasets from GEO. The 599 identified DEGs were primarily enriched in pathways related to tumorigenesis and tumor progression, including the focal adhesion pathway, signaling by vascular endothelial growth factor, and Wnt signaling. THBS2 expression was positively correlated with the enrichment of the macrophages (r = 0.590, p < 0.001), which was also confirmed by immunohistochemistry; however, negatively correlated with the enrichment of Th17 cells (r = 0.260, p < 0.001). The high expression of THBS2 was significantly correlated with the pathological grade (p < 0.01), histological grade (p < 0.05), histological type (p < 0.05), T stage (p < 0.001), and poor overall survival (OS) (P = 0.003) of GC. The constructed nomogram can well predict the 1-, 3-, and 5-years OS probability of patients with GC (C-index [95% confidence interval] = 0.725 [0.701–0.750]).Conclusion: THBS2 is closely related to the poor prognosis and immune infiltration of gastric cancer.

BackgroundIn the early days of COVID-19 outbreak, the normally orderly health system was severely challenged by large numbers of feverish patients and shortage of healthcare workers. The outbreak played a harmful role in the mental health of these healthcare workers.ObjectiveWe aim to assess the prevalence of moderate or severe anxiety and depression symptoms (ADSs) of healthcare workers in different regions during COVID-19 disaster and identify the potential risk factors.MethodsWe did a cross-sectional study on ADS of healthcare workers in epicenter-Hubei province and regions in lower epidemic-other provinces by questionnaire online. The data of ADS, the demographic characteristics, occupational exposure, physical condition, family situation, and coping styles were collected and analyzed.ResultsA total of 24.68% of the respondents had experienced moderate or severe ADS. Moderate or severe ADSs were in a higher prevalence in Hubei (32.39%) than other provinces (18.22%). Suspicious symptoms on their own and in family members were independent risk factors of moderate or severe ADS of all health workers. Working on the frontline was the independent risk factor for participants in Hubei province, whereas quarantine was the independent risk factor for those in other provinces. Moreover, among all participants, those with negative coping style were more than four times more likely to have moderate or severe ADS than those with positive coping style.ConclusionModerate or severe ADSs were in a higher prevalence in healthcare workers of Hubei province during COVID-19 outbreak. The coping style may have major impact on ADS in such situation.

Background: Biglycan (BGN) plays a role in the occurrence and progression of several malignant tumors, though its role in gastric cancer (GC) remains unclear. The objective of this study was to investigate BGN expression, its role in GC prognosis, and immune infiltration.Material and Methods: Gene expression data and corresponding clinical information were downloaded from TCGA and GTEx, respectively. We compared the expression of BGN in GC and normal tissues and verified the differential expression via Real-Time PCR and immunohistochemistry. BGN-related differentially expressed genes (DEGs) were identified. Additionally, the relationships between BGN gene expression and clinicopathological variables and survival in patients with GC were also investigated through univariate and multivariate Cox regression analyses. Finally, we established a predictive model that could well predict the probability of 1-, 3-, and 5-years survival in GC.Results: We found a significantly higher expression of BGN in GC than that in normal tissues (p < 0.001), which was verified by Real-Time PCR (p < 0.01) and immunohistochemistry (p < 0.001). The 492 identified DEGs were primarily enriched in pathways related to tumor genesis and metastasis, including extracellular matrix (ECM)-receptor interaction, focal adhesion pathway, Wnt signaling, and signaling by VEGF. BGN expression was positively correlated with the enrichment of the NK cells (r = 0.620, p < 0.001) and macrophages (r = 0.550, p < 0.001), but negatively correlated with the enrichment of Th17 cells (r = 0.250, p < 0.001). BGN expression was also significantly correlated with histologic grade (GI&G2 vs. G3, p < 0.001), histologic type (Diffuse type vs. Tubular type, p < 0.001), histologic stage (stage I vs. stage II and stage I vs. stage III, p < 0.001), T stage (T1 vs. T2, T1 vs. T3, and T1 vs. T4, p < 0.001) and Helicobacter pylori (HP) infection (yes vs. no, p < 0.05) in GC. High BGN expression showed significant association with poor overall survival (OS) in GC patients (HR = 1.53 (1.09–2.14), p = 0.013). The constructed nomogram can well predict the 1-, 3-, and 5-years overall survival probability of GC patients (C-index = 0.728).Conclusion: BGN plays an important role in the occurrence and progression of GC and is a potential biomarker for the diagnosis and treatment of GC.

Abstract Background Chemo-resistance in hepatocellular carcinoma (HCC) is a major problem, and acquired drug resistance prevents cancer therapies from achieving complete responses. Molecular targeting therapy presents an opportunity to impede tumor through combination or sequential therapy, while the accurate effect is vague. Methods The efficacy of combinations between oxaliplatin and anti-cancer molecular targeting drugs was screened. Strangely, the combined chemotherapy with oxaliplatin and saracatinib induced significantly antagonistic effects. Then the antitumor effects of combined treatment with saracatinib and oxaliplatin were confirmed in wide type HCC as well as in saracatinib- and oxaliplatin-resistant HCC. RNA sequencing was used to explore the resistance mechanism, and the roles of ATP-binding cassette transporter G1 (ABCG1) and Wnt signaling in oxaliplatin resistance were confirmed. Results Chemotherapy with oxaliplatin and saracatinib individually induced strong anti-HCC effects, while combined or sequential treatment of HCC cells with these two drugs exhibited reduced efficacy compared to treatment with the single drugs. And it was saracatinib treatment caused oxaliplatin resistance. RNA sequencing revealed 458 genes that were altered by treatment with saracatinib and oxaliplatin. Of these, the gene encoding ABCG1 and Wnt-associated genes were significantly upregulated. Upregulation of ABCG1 and oxaliplatin resistance were associated with activation of Wnt signaling. Interference with ABCG1 expression or inhibition of Wnt signaling resulted in reversal of the saracatinib-induced oxaliplatin resistance in HCC. Conclusions These studies demonstrated that combined or sequential chemotherapy with oxaliplatin and saracatinib reduced antitumor efficacy, and this antagonism was attributed to the activation of Wnt signaling and upregulation of ABCG1 by saracatinib.

Abstract Background Hepatic stellate cells (HSCs) have a key role in fibrogenesis and in the filtrates of the hepatocellular carcinoma (HCC) stroma, in which they are remodeled and play a critical role in HCC progression. However, the precise role of HSCs trending, infiltration and paracrine in orchestrating the stroma-derived oxaliplatin-resistance in HCC is still vague. Methods The chemo-resistant models were established to explore the correlation between HSC cells and the condition of chemoresistance. The HCC clinical samples were collected to confirm this phenomenon. Then, the relationship between secretory CCN3 from oxaliplatin-resistant HCC and the infiltration of HSCs in associated HCC microenvironment was evaluated. Finally, the role and mechanism of HSCs remodeling in the orchestration of oxaliplatin-resistant HCC were explored. Results The increased infiltration of HSCs and collagen accumulation were found in the microenvironment of oxaliplatin-resistant HCC. The cDNA profiles of the oxaliplatin-resistant HCC was reanalyzed, and CCN3 was one of the significantly increased genes. In HCC clinical samples, the levels of CCN3 and α-SMA are positively correlated, and high expression of CCN3 and α-SMA are positively associated with malignant phenotype and poor prognosis. Then the enhanced abilities of migration and proliferation of HSCs, and elevation of the cytokines paracrine from HSCs relating to HCC malignancy were proved in vitro and in vivo, and which were related to CCN3-ERK signaling pathway activation. Conclusions HSCs remodeling are positively related to CCN3 paracrine in hepatocellular carcinoma, which orchestrated the stroma-derived resistance to chemotherapy in HCC.

ABSTRACT: Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1β, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1β, IL-5, IL-6, TGF-β, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway.

Poly (lactic acid) (PLA) is a renewable and biodegradable polymer with high modulus, high strength but low toughness. Blending PLA with plant fiber has been believed an available strategy to improve the toughness of PLA. PLA/Flax composites were fabricated by extrusion and injection molding processes. The flax fiber surfaces were modified before blending to improve the compatibility, and the chemical structures of both untreated and treated fiber were characterized by Fourier transform infrared spectroscopy. Results of mechanical test showed that the impact strength and elongation at break of PLA/Flax composites were remarkably higher than PLA. The impact fractures of PLA/Flax composites were also observed by scanning electron microscope. The results showed uniform dispersion of fibers in PLA matrix and good compatibility between treated fibers and PLA matrix. Moreover, it can be observed that crazing propagation was hindered by fibers and transcrystalline developed along fibers by polarized optical microscope. Differential scanning calorimetry analysis was carried out to study the crystallinity of PLA and it was found that incorporation of fiber improved the crystallinity of PLA. The toughening mechanism of PLA/Flax composites was discussed according to the results. [ABSTRACT FROM AUTHOR]

The polysaccharide of Atractylodes macrocephala Koidz (PAMK) is recognized as an immune enhancer, with anti-cancer, anti-tumour, lymphocyte-activating and lymphocytes proliferation-inducing effects. For investigating the mechanism that PAMK alleviates the decline in T cell activation induced by CTX, 24 6-week-old BALB/c female mice were randomly divided into four groups (C, PAMK, CTX, PAMK + CTX). The spleen index, splenocytes morphology and death, cytokine concentration, T cell activating factors (CD25, CD69, CD71), mRNA expression levels related to the CD28 signal pathway were detected. Furthermore, the lymphocytes of mice was isolated and cultured, and then the Th1/Th2 ratio, activating factors, mRNA levels related to the CD28 signal pathway were detected. The results showed that PAMK significantly improved the spleen index, alleviated abnormal splenocytes morphology and death, maintained the balance of Th1/Th2 cells, increased the levels of IL-2, IL-6, TNF-α, and IFN-γ, and increased the mRNA levels of CD28, PLCγ-1, IP3R, NFAT, and AP-1. In conclusion, PAMK increased cytokines levels and alleviated the decline in activation level of lymphocytes induced by CTX through CD28/IP3R/PLCγ-1/AP-1/NFAT signal pathway.

Proton exchange membrane fuel cells (PEMFC) are considered a promising solution for renewable energy application. To meet industrial requirements, the power source consisting of PEMFC is required to be power regulator to generate a stable and desired current and/or voltage under various working conditions. In this article, the adaptive sliding mode control integrating with the radial basis function neural network (RBFNN) approach for DC/DC buck converter-based PEMFC is presented to address perturbations from inner parameters as well as external disturbances in terms of power conditioning. Sliding mode control (SMC) and backstepping schemes are integrated to tackle the nonlinear and coupled outputs resulting in large control errors and slow response caused by PEMFC characteristics. To accurately estimate the parametric uncertainties and disturbance injections, such as buck converter parameter varying and PEMFC operation point changing, the RBFNN adaptive law is developed according to the defined Lyapunov and Gaussian functions overcoming the limitations of non-/linear parameter estimating. Simulations and experiments on the PEMFC power supply prototype governed by the DS1104 board are carried out. The comparative results indicate that the proposed RBFNN estimation associated with the backstepping SMC can reduce up to 7.5% overshoot and smooth PEMFC voltage and inductor current when disturbance changes in a voltage regulation experiment. Thus, the proposed method can regulate the current or voltage of a PEMFC power supply with robustness, adaptivity, and no chattering phenomenon.

Abstract SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and neuron‐specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression‐free survival (PFS) were analyzed. Serum SP70 levels were significantly decreased after chemotherapy in the partial remission (PR) group (P

Across the disciplines and levels of education, team projects are becoming an increasingly important tool for assessment. However, it is often difficult to make sure that work is fairly distributed, that a reasonable schedule is formed which does not leave everything for the last minute, and that individual students are fairly rewarded/penalized for their respective contributions. To solve these problems, we can model a project using events, rules, and workflows. Depending on the nature of an event, an appropriate rule can be triggered, which can subsequently initiate a workflow that will assign specific tasks to specific roles within the team. Events that occur over the course of the project, fired from a variety of sources, can lead to the derivation of new knowledge, and potentially alter the flow of the team’s activities. An integration of mobile devices into the system can insure that students are always aware of the current state of the system and their roles within it. At the conclusion and at all prior points in the project lifecycle, a comprehensive log of each student’s activities will be available and will greatly simplify the task of assigning fair and accurate grades. The result will be a more educational, more equitable, and far more engaging learning experience.

There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients.We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles.The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377-3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147-4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178-3.337, P