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BackgroundOverexpression of monopolar spindle 1 (MPS1) and histone deacetylase 8 (HDAC8) is associated with the proliferation of liver cancer cells, so simultaneous inhibition of both MPS1 and HDAC8 could offer a promising therapeutic approach for the treatment of liver cancer. Dual-targeted MPS1/HDAC8 inhibitors have not been reported.MethodsA combined approach of pharmacophore modeling and molecular docking was used to identify potent dual-target inhibitors of MPS1 and HDAC8. Enzyme inhibition assays were performed to evaluate the optimal compound with the strongest inhibitory activity against MPS1 and HDAC8. The selectivity of MPH-5 for MPS1 and HDAC8 was assessed on a panel of 68 kinases and other histone deacetylases. Subsequently, molecular dynamics (MD) simulation verified the binding stability of the optimal compound to MPS1 and HDAC8. Ultimately, in vitro cellular assays and in vivo antitumor assays evaluated the antitumor efficacy of the most promising compound for the treatment of hepatocellular carcinoma.ResultsSix dual-target compounds (MPHs 1–6) of both MPS1 and HDAC8 were identified from the database using a combined virtual screening protocol. Notably, MPH-5 showed nanomolar inhibitory effect on both MPS1 (IC50 = 4.52 ± 0.21 nM) and HDAC8 (IC50 = 6.07 ± 0.37 nM). MD simulation indicated that MPH-5 stably binds to both MPS1 and HDAC8. Importantly, cellular assays revealed that MPH-5 exhibited significant antiproliferative activity against human liver cancer cells, especially HepG2 cells. Moreover, MPH-5 exhibited low toxicity and high efficacy against tumor cells, and it overcomes drug resistance to some extent. In addition, MPH-5 may exert its antitumor effects by downregulating MPS1-driven phosphorylation of histone H3 and upregulating HDAC8-mediated K62 acetylation of PKM2. Furthermore, MPH-5 showed potent inhibition of HepG2 xenograft tumor growth in mice with no apparent toxicity and presented favorable pharmacokinetics.ConclusionThe study suggests that MPH-5 is a potent, selective, high-efficacy, and low-toxicity antitumor candidate for the treatment of hepatocellular carcinoma.

Background: Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV). Methods: One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated. Results: At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction ( P .05). Conclusions: This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival.

Current research does not fully elucidate the key compounds and their mechanisms that define the aroma profile of fresh jujube fruits. Therefore, this study conducted a comprehensive analysis of both free and glycosidically bound aroma compounds in fresh jujube fruits of ten cultivars. Utilizing gas chromatography–mass spectrometry (GC-MS), we identified 76 volatile free aroma compounds and 19 glycosidically bound volatile compounds, with esters, aldehydes, and ketones emerging as the predominant volatile compounds in the jujube fruits. Odor activity value (OAV) analysis revealed that the primary aroma profile of the jujubes is characterized by fruity and fatty odors, with β-damascenone being a key contributor to the fruity aroma, and (E)-2-oct-en-1-al and nonanal significantly influencing the fatty aroma. Moreover, the integration of sensory evaluation and partial least squares regression (PLSR) analysis pinpointed octanal, (E)-2-oct-en-1-al, nonanal, β-damascenone, and pentanal as significant contributors to the jujube’s characteristic aroma, while isoamyl acetate was identified as significantly influencing the fatty acid taste. This study not only underscores the complexity of the jujube aroma composition but also highlights the impact of environmental factors on aroma profiles, offering valuable insights into the sensory characteristics of jujube fruits.

Abstract Background The altered gut microbiota is implicated in the pathogenesis of liver fibrosis. Resveratrol is a candidate for the treatment of liver fibrosis, which could ameliorate the dysregulation of gut microbiota in mice. This study aimed to clarify the role and mechanism of resveratrol in gut microbiota during liver fibrosis. Methods A mouse model of liver fibrosis induced by CCl4 was conducted to assess the effect of resveratrol on liver fibrosis. The changes of gut microbiota in liver fibrotic mice after resveratrol intervention were assessed using 16S ribosomal RNA sequencing. The mechanism of the gut microbiota dysregulation in liver fibrosis was investigated by Sirius red staining, immunohistochemical assay, bacterial translocation (BT), EUB338 fluorescence in situ hybridization, immunofluorescence, trans-epithelial electrical resistance analysis and paracellular permeability analysis. Results Resveratrol relieved CCl4-induced liver fibrosis. Besides, resveratrol restrained the gut microbiota Staphylococcus_lentus and Staphylococcus_xylosus in the liver fibrotic mice, and the Staphylococcus_xylosus and Staphylococcus_lentus facilitated the occurrence of BT and the cultures of them enhanced the permeability of intestine. The in vivo assay corroborated that the excessive Staphylococcus_xylosus and Staphylococcus_lentus canceled the protecting effect of resveratrol on liver fibrosis, and Staphylococcus_xylosus or Staphylococcus_lentus alone had a limited impact on the liver injury of normal mice. Conclusion Resveratrol ameliorated liver fibrosis by restraining the growth of Staphylococcus_xylosus and Staphylococcus_lentus.

IntroductionAccording to the principle, thymomas combined with myasthenia gravis (MG) require surgical treatment. However, patients with non-MG thymoma rarely develop MG and early- or late-onset MG after surgery is called postoperative MG (PMG). Our study used a meta-analysis to examine the incidence of PMG and risk factors.MethodsRelevant studies were searched for in the PubMed, EMBASE, Web of Science, CNKI,and Wanfang databases. Investigations that directly or indirectly analyzed the risk factors for PMG development in patients with non-MG thymoma were included in this study. Furthermore, risk ratios (RR) with 95% confidence intervals (CI) were pooled using meta-analysis, and fixed-effects or random-effects models were used depending on the heterogeneity of the included studies.ResultsThirteen cohorts containing 2,448 patients that met the inclusion criteria were included. Metaanalysis revealed that the incidence of PMG in preoperative patients with non-MG thymoma was 8%. Preoperative seropositive acetylcholine receptor antibody (AChR-Ab) (RR = 5.53, 95% CI 2.36 – 12.96, P

In this paper, a tesla-shaped emitter is proposed based on the structure of the “tesla valve” as the source of inspiration, so that the water flow in the channel would produce a variety of energy dissipation phenomena, such as diversion, hedging, and mixing, to explore the hydraulic performance and energy dissipation mechanism of the tesla-shaped emitter. The channel structure parameters were taken as factors, and 16 groups of orthogonal tests were arranged. Based on CFD technology, the pressure–flow relationship curve slope, flow ratio between the main channel and secondary channel, flow field, and head loss of the emitter were calculated and analyzed for different combinations of structural parameters. Based on a significance level α = 0.05 test, the main channel inlet section length (L3) had a significant impact on the curve slope, and the secondary channel length (L1) and main channel inlet section length (L3) had a significant impact on the flow. The multiple linear regression mathematical models between the channel structure parameters and the curve slope and the flow were constructed. The larger the ratio between the main channel and the secondary channel flow, the better the hydraulic performance of the emitter. The channel unit loss coefficient increased linearly with the increase of the emitter inlet pressure, and its value ranged from 4.5769 to 8.1716, with an excellent energy dissipation effect. The hedge mixing of the water flow was the core of the energy dissipation of the tesla-shaped emitter. By appropriately increasing the inlet size of the main channel and other elements to increase the main channel flow and optimize the flow ratio between the main channel and the secondary channel, the mixing was improved, which consequently improved the hydraulic performance of the emitter.

Bladder cancer (BC) is a common genitourinary malignancy. This study investigated the regulatory effects of an exonic circRNA, circNUDT21, in the progression of BC. The circNUDT21 level was overexpressed in BC tissues and cell lines as compared to normal controls. Overexpression and silencing of circNUDT21 promoted and inhibited, respectively, the proliferative and invasive abilities of BC cells. Mechanistical analysis showed that circNUDT21 acted as a miR-16-1-3p sponge and that MDM2 was a potential downstream target of miR-16-1-3p. We further verified that overexpression of circNUDT21 was associated with elevated MDM2 and reduced p53 expression. CircNUDT21 promoted BC progression by acting as a sponge of miR-16-1-3p to activate the miR-16-1-3p/MDM2/p53 axis. These findings suggest that circNUDT21 functions as an oncogenic circRNA and may be a potential therapy target for BC.

Available vaccine-based immunity may at high risk of being evaded due to substantial mutations in the variant Omicron. The main protease (Mpro) of SARS-CoV-2 and human neuropilin-1 (NRP1), two less mutable proteins, have been reported to be crucial for SARS-CoV-2 replication and entry into host cells, respectively. Their dual blockade may avoid vaccine failure caused by continuous mutations of the SARS-CoV-2 genome and exert synergistic antiviral efficacy. Herein, four cyclic peptides non-covalently targeting both Mpro and NRP1 were identified using virtual screening. Among them, MN-2 showed highly potent affinity to Mpro (Kd = 18.2 ± 1.9 nM) and NRP1 (Kd = 12.3 ± 1.2 nM), which was about 3,478-fold and 74-fold stronger than that of the positive inhibitors Peptide-21 and EG3287. Furthermore, MN-2 exhibited significant inhibitory activity against Mpro and remarkable anti-infective activity against the pseudotyped variant Omicron BA.2.75 without obvious cytotoxicity. These data demonstrated that MN-2, a novel non-covalent cyclic peptide, is a promising agent against Omicron BA.2.75.

BackgroundCuproptosis is a type of programmed cell death that is involved in multiple physiological and pathological processes, including cancer. We constructed a prognostic cuproptosis-related long non-coding RNA (lncRNA) signature for acute myeloid leukemia (AML).MethodsRNA-seq and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) database. The cuproptosis-related prognostic lncRNAs were identified by co-expression and univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) was performed to construct a cuproptosis-related lncRNA signature, after which the AML patients were classified into two risk groups based on the risk model. Kaplan-Meier, ROC, univariate and multivariate Cox regression, nomogram, and calibration curves analyses were used to evaluate the prognostic value of the model. Then, expression levels of the lncRNAs in the signature were investigated in AML samples by quantitative polymerase chain reaction (qPCR). KEGG functional analysis, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. The sensitivities for potential therapeutic drugs for AML were also investigated.ResultsFive hundred and three lncRNAs related to 19 CRGs in AML samples from the TCGA database were obtained, and 21 differentially expressed lncRNAs were identified based on the 2-year overall survival (OS) outcomes of AML patients. A 4-cuproptosis-related lncRNA signature for survival was constructed by LASSO Cox regression. High-risk AML patients exhibited worse outcomes. Univariate and multivariate Cox regression analyses demonstrated the independent prognostic value of the model. ROC, nomogram, and calibration curves analyses revealed the predictive power of the signature. KEGG pathway and ssGSEA analyses showed that the high-risk group had higher immune activities. Lastly, AML patients from different risk groups showed differential responses to various agents.ConclusionA cuproptosis-related lncRNA signature was established to predict the prognosis and inform on potential therapeutic strategies for AML patients.

Restoration is the natural and intervention-assisted set of processes designed to promote and facilitate the recovery of an ecosystem that has been degraded, damaged, or destroyed. However, it can also have an adverse effect on the environment. Thus, assessing an ecological restoration project’s impact is crucial to determining its success and optimum management strategies. We performed a meta-analysis concerning the environmental outcomes during the years 2000–2015 resulting from the “Grain for Green” Project (GFGP) implementation in the Loess Plateau (LP). Data were gathered from 40 peer-reviewed English-language articles chosen from a pool of 332 articles. The results showed that, on average, GFGP increased forest coverage by 35.7% (95% CI [24.15–47.52%]), and grassland by 1.05% (95% CI [0.8–1.28%]). At the same time, GFGP has a positive impact on soil carbon (C) sequestration, net ecosystem production (NEP), and net primary production (NPP), from the years 2000 to 2015 by an average of 36% (95% CI [28.96–43.18%]), 22.7% (95% CI [9.10–36.79%]), and 13.5% (95% CI [9.44–17.354%]), respectively. Soil erosion, sediment load, runoff coefficient, and water yield were reduced by 13.3% (95% CI [0.27–25.76%]), 21.5% (95% CI [1.50–39.99%]), 22.4% (95% CI [5.28–40.45%]) and 43.3% (95% CI [27.03–82.86%]), respectively, from the years 2000 to 2015. Our results indicate that water supply decreased with the increase of vegetation coverage. Therefore, to balance the needs for green space, GFGP policies and strategies should recover, enhance, and sustain more resilient ecosystems.

As a key component of a drip irrigation system, the performance of drip irrigation emitters is determined by the flow channel structures and parameters. In this paper, a novel Y-shaped labyrinth-channel emitter was proposed, and the influence of the hydraulic performance was researched under different waist-arc angles (α) and ratios of crown height to chord length (a:b). The flow characteristics and energy dissipation mechanisms of water in the emitter were analyzed by using fluid dynamics software. The analysis showed that, keeping the ratio of crown height to chord length unchanged and with an increase in the waist-arc angle from 90° to 180°, the pressure-drop ratio before and after the water flow through the vortex area increased, and the hydraulic performance of the emitter was improved, specifically: the design flow could be reduced by 6.02–26.7%, and the slope of the curve could be reduced by 9.83–28.1%. The smaller the ratio of crown height to chord length, the weaker the influence of waist-arc angle was on the design flow and hydraulic performance. Keeping the waist-arc angle unchanged, there was a decrease in the ratio of crown height to chord length from 6:30 to 1:30, the vortex strength inside the emitter channel increased, and the hydraulic performance was improved: the design flow could be reduced by 7.56–23.5%, and the slope of the curve could be reduced by 5.43–20.5%. The bigger the waist-arc angle, the weaker the influence of the ratio of crown height to chord length was on the design flow and the hydraulic performance, even to the point of having no effect. When the Y-shaped emitter was close to the pressure-flow curve slope of the commonly-used triangular-channel emitter, the hydraulic performance of the two was similar, and the former could increase the channel width by 25%, as compared to the latter, or shorten the channel length by 44.3%. The results showed that the Y-shaped emitter had better hydraulic performance compared with the triangular-flow-channel emitter commonly used today. Therefore, the Y-shaped emitter has broad application prospects in water-saving irrigation.

Abstracts Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

The opposed-power reciprocating pump has the characteristics of high pressure, large flow, and high efficiency and energy saving. However, due to the special structure of the opposed-power reciprocating pump, existing theoretical methods cannot analyze its dynamic performance. Therefore, this paper proposes a method of analyzing the power end of the opposed-power reciprocating pump. Firstly, according to the working principle and structural characteristics of the traditional plunger pump, the novel and complex structure of the opposed-power reciprocating pump is analyzed by analogy, and the force analysis model of the crankshaft is established. The dynamic analysis model of the Matlab program is used to solve the dynamic load and section stress in the working process, and the variation law of crankshaft load is obtained. The 25 most critical working conditions are selected for analysis, and the most critical station and section of the crankshaft are obtained. With the connection between ANSYS Workbench and Solidworks, the model is imported into ANSYS Workbench, the load on the crank pin is loaded by APDL command flow, and the static analysis of the crankshaft is carried out to obtain the stress and strain of the crankshaft. Finally, the static and fatigue strength of the dangerous section is checked, and it is proven that the strength and stiffness of the crankshaft meet the design requirements. The results show that the dynamic analysis results of the crankshaft under critical working conditions are consistent with the finite element analysis, verifying the rationality of the method and providing a reference for the improvement and optimized design of the crankshaft of the opposed-power reciprocating pump.

Lactate has been observed to fuel TCA cycle and is associated with cancer progression in human lung cancer, the leading cause of cancer deaths worldwide, but the effect of lactate on lung cancer metabolism is rarely reported. In this study, disordered metabolism in non-small cell lung cancer was demonstrated by increased G6PD and SDHA protein levels via immunofluorescence, and up-regulated lactate dehydrogenase was found to be associated with poor prognosis. Then flow cytometry and Seahorse XFe analyzer were utilized to detect the effect of lactate on glycolysis and mitochondrial function in non-small cell lung cancer cells. The results show that in non-small cell lung cancer cells lactate attenuates glucose uptake and glycolysis while maintaining mitochondrial homeostasis as indicated by improved mitochondrial membrane potential. Further exploration found that mRNA levels of glycolytic enzymes (HK-1, PKM) and TCA cycle enzymes (SDHA, IDH3G) are respectively down-regulated and up-regulated by lactate, and increased histone lactylation was observed in promoters of HK-1 and IDH3G via chromatin immunoprecipitation assay. Taken together, the above results indicate that lactate modulates cellular metabolism at least in part through histone lactylation-mediated gene expression in non-small cell lung cancer.

Background: HBeAg-positive chronic infection is a unique phase of chronic hepatitis B virus (HBV) infection. Current guidelines advise against starting antiviral treatment for HBeAg-positive chronic hepatitis B virus (HBV) infection patients, some data suggest treating such patients may reduce the risk of hepatocellular carcinoma. We aimed to explore whether these patients can have evident histological liver injury (EHLI), and develop a non-invasive model for identifying EHLI in such patients. Method: We assessed whether HBeAg-positive chronic HBV infection patients can have EHLI defined by Ishak fibrosis stage ≥3 and/or histologic activity index ≥ 9 in a prospective multicenter study. Logistic and Lasso regression was used to select the optimal predictors. We used Akaike information criterion, discrimination improvement, net reclassification improvement to develop and validate models predicting EHLI risk in training cohort and two external validation cohorts. Findings: Of these 336 patients met the inclusion criteria, 181(54%) were HBeAg-positive chronic HBV infection, of whom 60 patients (33%) had EHLI, the proportion of significant fibrosis was higher than that of significant inflammation (33% vs. 8%, P

After leukemia, tumors of the brain and spine are the second most common form of cancer in children. Despite advances in treatment, brain tumors remain a leading cause of death in pediatric cancer patients and survivors often suffer from life-long consequences of side effects of therapy. The 5-year survival rates, however, vary widely by tumor type, ranging from over 90% in more benign tumors to as low as 20% in the most aggressive forms such as glioblastoma. Even within historically defined tumor types such as medulloblastoma, molecular analysis identified biologically heterogeneous subgroups each with different genetic alterations, age of onset and prognosis. Besides molecularly driven patient stratification to tailor disease risk to therapy intensity, such a diversity demonstrates the need for more precise and disease-relevant pediatric brain cancer models for research and drug development. Here we give an overview of currently available in vitro and in vivo pediatric brain tumor models and discuss the opportunities that new technologies such as 3D cultures and organoids that can bridge limitations posed by the simplicity of monolayer cultures and the complexity of in vivo models, bring to accommodate better precision in drug development for pediatric brain tumors.

Abstract Background CircRNA myosin light chain kinase (circRNA MYLK) has been shown to promote the progression of various tumor diseases. The purpose of this study was to explore the potential molecular mechanism of circMYLK in hepatocellular carcinoma (HCC). Methods The quantitative Real-Time PCR (qRT-PCR) was used to measure the expressions of circMYLK, miR-362-3p and Rab23 in HCC tissues and cell lines. Huh7 and Hep3B cells were selected to explore the role of circMYLK in proliferation, invasion and migration of HCC cells in vitro. The interaction among circMYLK, miR-362-3p and Rab23 was investigated by biological information and dual luciferase gene reporter assay. The effect of circMYLK on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. Results CircMYLK was highly expressed in HCC tissues and cell lines, which was associated with poor prognosis in HCC patients. In addition, knockdown of circMYLK remarkably inhibited the proliferation, invasion, and migration of Huh7 and Hep3B cells. MiR-362-3p was a direct target of circMYLK, and Rab23 was a direct target gene of miR-362-3p. Meanwhile, circMYLK was negatively correlated with the expression of miR-362-3p and positively correlated with Rab23 expression. Moreover, either overexpressed miR-362-3p or silencing Rab23 could observably suppress the enhanced proliferation, invasion, and migration induced by circMYLK in Huh7 and Hep3B cells. Finally, knockdown of circMYLK and overexpressed miR-362-3p could suppress the expression of Rab23, thus inhibiting the growth and proliferation of Hep3B cells in vivo. Conclusion circMYLK promotes the occurrence and development of HCC by regulating the miR-362-3p/Rab23 axis, which provides a novel direction and theoretical basis for the early diagnosis and treatment of HCC.

Abstract Background Kinesin family member 26B (KIF26B) is unveiled acted as important role in many solid tumors, however, the function of KIF26B in hepatocellular carcinoma (HCC) is unclear. Methods The expression of KIF26B in HCC tissues and cell lines were measured with immunochemistry, real-time PCR and western blotting. The correlation between KIF26B expression and clinicopathological characteristics were analyzed by SPSS19.0. Functional experiments of KIF26B was conducted by CCK-8, transwell, EDU, colony formation in vitro and tumorigenesis in vivo. The gene set enrichment analysis was used to search the downstream pathway, luciferase reporter experiment was used to find the upstream regulatory factor of KIF26B. Results In this study, we found that KIF26B was overexpressed both in HCC tissues and cell lines. High expression of KIF26B was associated with poor overall survival (OS), late TNM stage and poor differentiation. Loss of function experiments showed that suppression of KIF26B could inhibit cell viability, proliferation rate and invasion ability of HCC cells. KEGG and GO analysis showed that expression of KIF26B was highly relevant with PI3K/AKT signal pathway, and suppression of KIF26B could decrease the expression of m-TOR, p-PI3K and p-AKT. Further study demonstrated that expression of KIF26B was negative correlated with miR-450b-5p level in HCC tissues, and miR-450b-5p could inhibit cell viability, proliferation rate and invasion ability of HCC cells via targeted inhibiting KIF26B. Conclusion Our study demonstrated that miR-450-5p/KIF26B/AKT axis is critical for progression of HCC, and might provide novel prognostic biomarker and therapeutic target for HCC.

In this paper, a split-flow channel layout with one (group) inlet and two (group) outlets is adopted, based on computational fluid dynamics technology, and compared with the current commonly used channel with one (group) inlet and one (group) outlet emitter. On the premise of the same outlet spacing, the pressure–flow relationship curve and slope of the split-flow emitter were analyzed under the three channel layouts of non-return, single-sided re-entry, and bilateral re-entry, with different channel widths and lengths. When exploring the influence of the channel layout and size on the hydraulic performance of split-flow emitters, the results showed that when the split-flow emitter with a non-return channel is adopted and the hydraulic performance is not reduced, the single-side channel length is half that of the one-in-one-out emitter, meaning the channel width needs to be reduced by 15%. When the channel layout is a single-sided channel re-entry, the hydraulic performance is better than that of the one-in-one-out emitter; if the hydraulic performance of the two remains unchanged, the channel width can be increased by 10% or the single-sided channel length can be reduced by 20%. When the channel layout is a bilateral channel re-entry, the channel width can be increased by nearly 30% if the hydraulic performance of the 2 is consistent, and the single-side channel length is increased by about 50%. When the split-flow emitter adopts a non-return channel layout, the channel width needs to be reduced to ensure the hydraulic performance is consistent. If the layout of single-sided channel re-entry or bilateral channel re-entry is adopted, the hydraulic performance is better than that of the one-in-one-out emitter and the hydraulic performance of the two is consistent. Thus, the channel length can be reduced or the channel width increased, which is beneficial for improving the anti-clogging performance of the emitter.

Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis.

PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.

The maximum gasification rate of corn stalk char (CSC) appeared at high conversion range, and its quite different gasification behaviors from other carbonaceous materials are all derived from the catalytic effect of alkali and alkali earth metals (AAEMs), so it is necessary to study the effect of AAEMs and gasification kinetics of such biomass char. However, there are few systematic discussions about this effect and kinetic modeling. Thus, in this study, CSC samples were prepared in a fast pyrolysis fixed-bed reactor, and its gasification experiments were conducted on a pressurized magnetic suspension balance at various total pressures (0.1–0.7 MPa), steam concentrations (10–70 vol.%) and temperatures (725–900 °C). Moreover, a water-leached CSC (H2O-CSC) was also prepared to evaluate the impact of AAEMs on the gasification performance of CSC, and some well-known models were adopted to describe the gasification behaviors. On the basis of these results, the effect of primary AAEMs on the gasification behaviors of CSC and gasification kinetic modeling were obtained. Results showed total pressure had no obvious influence on the gasification rate of CSC, and the reaction order varied at 0.43–0.55 with respect to steam partial pressures. In addition, the modified random pore model (MRPM) and Langmuir–Hinshelwood (L-H) model were satisfactorily applied to predict the gasification behaviors of CSC. The catalytic effect of AAEMs on CSC gasification was weakened due to water-leaching treatment. A random pore model (RPM) could describe the gasification behavior of H2O-CSC well, followed by grain model (GM) and volumetric model (VM).

Total dissolved gas (TDG) supersaturation, which can be caused by flood discharge, results in gas bubble disease (GBD) in fish and threatens their survival downstream of dams. TDG supersaturation has become a serious environmental problem in the Yangtze River. Few studies have evaluated the effect of TDG supersaturation on fish in natural rivers during periods of flood discharge. To estimate fish tolerance to TDG supersaturation under natural conditions, juvenile Myxocyprinus asiaticus and juvenile Procypris rabaudi were exposed to TDG-supersaturated water for 96 h at various depths (0–0.3 m, 0.3–1.3 m, 1.3–2.3 m and 0–2.3 m) during periods of flood discharge of Dagangshan hydropower station. The results showed that juvenile Procypris rabaudi and juvenile Myxocyprinus asiaticus exhibited obvious GBD signs. An increase in exposure time decreased survival probability of the two species. Deeper water depths can increase the tolerance of juvenile Procypris rabaudi to TDG supersaturation in natural rivers during periods of flood discharge while it cannot improve the survival of juvenile Myxocyprinus asiaticus. Compared with juvenile Myxocyprinus asiaticus, juvenile Procypris rabaudi showed weaker tolerance of TDG supersaturation in shallow water, and juvenile Procypris rabaudi were more vulnerable to TDG supersaturation than juvenile Myxocyprinus asiaticus even if the TDG level (116%) was low.

The rectangular labyrinth emitter is taken as the study object in this article, as we added internal teeth to vortex-free and vortex areas in its lateral channel or lengthened the vertical channel, to change the channel structure. Using the computational fluid dynamics (CFD) method simulates the water flow field, to get the relationship between flow rate and pressure, and the vortexes distribution in channel. The aim of this study is to explore the reasons for the influence of structural change on hydraulic performance of the emitter through the analysis of vortex intensity and its distribution from the perspective of the vortex. The results show that the relative error of simulated results and experimental data was 1.02–2.11%. Adding internal teeth to vortex-free areas in lateral channel can improve hydraulic performance of the emitter; adding them to vortex areas can reduce it. The increase in vortex number and intensity in flow field is the internal reason for the improvement of the emitter’s hydraulic performance. The channel structure changes promote the formation of a larger velocity gradient, and the increase in the velocity gradient in flow field exacerbates vortex formation. Changing channel structure to improve the emitter’s hydraulic performance can promote an increase in the number and intensity of vortexes in the channel.

Recent studies have shown that long noncoding RNAs (lncRNAs) play pivotal roles in the initiation and progression of cancer, including esophageal squamous cell carcinoma (ESCC). The lncRNA HOX transcript antisense RNA (HOTAIR) was reported to be dysregulated and correlated with the progression of ESCC. However, the biological role and the underlying mechanism of HOTAIR in the development of ESCC remain unclear. Herein, we found that HOTAIR was aberrantly upregulated in ESCC cells and that HOTAIR depletion inhibited proliferation and led to G1 cell cycle arrest in ESCC cells. Besides, we found that HOTAIR acted as an endogenous sponge to downregulate miR-1 expression by directly binding to miR-1. Furthermore, HOTAIR overturned the effect of miR-1 on the proliferation and cell cycle profile in ESCC cells, which involved the derepression of cyclin D1 (CCND1) expression, a target of miR-1. Taken together, our study elucidated a novel HOTAIR /miR-1/CCND1 regulatory axis in which HOTAIR acted as a competing endogenous RNA by sponging miR-1 and upregulated CCND1 expression, thereby facilitating the tumorigenesis of ESCC. Investigation of this lncRNA/miRNA/mRNA pathway may contribute to a better understanding of ESCC pathogenesis and facilitate the development of lncRNA-directed therapy against this disease.

Objectives: CD4+Foxp3+ regulatory T-cells (Treg) are known to accumulate under certain pathological conditions. This study was conducted to evaluate the characteristics of and dynamic changes in Treg cells in chronic hepatitis C (CHC) patients during antiviral therapy. Methods: One hundred and forty-five subjects were enrolled in this study, including 105 CHC patients and 40 healthy donors. The phenotypes and functions of Treg cells were analyzed by flow cytometry. Results: A significant elevation in Treg cells was observed in the peripheral blood of CHC patients compared with healthy donors. Interestingly, compared with non-suppressive Treg (non-Treg) and resting Treg (rTreg) cells, activated Treg (aTreg) cells expressed higher levels of ectonucleotidase, CD39, and CD73. After treatment with interferon alpha (IFN-α) and ribavirin (RBV) in vitro, the frequencies of total Treg cells and aTreg cells in peripheral blood mononuclear cells (PBMC), as well as the levels of transforming growth factor beta (TGF-β) secreted by aTreg and non-Treg cells, were significantly decreased. Importantly, it was found that levels of aTreg cells in patients with a sustained virological response (SVR) were lower than in relapsed patients, suggesting that a high frequency of aTreg cells might be associated with a poor clinical outcome in HCV infection. Conclusion: These results demonstrate a decreasing trend in aTreg cells, which express higher levels of CD39, CD73, and TGF-β, in SVR patients during antiviral therapy.

The full N,N-methylation of 4,4′-methylenedianiline (MDA) with dimethyl carbonate (DMC) was investigated. The yield of the major product 4,4′-methylene bis(N,N-dimethylaniline) (MBDMA) reached as high as 97% over NaY catalyst at 190°C for 6 h. The catalyst could be used for two more times with acceptable MBDMA yields higher than 90%. The main by-products were identified as three N-methylated derivatives. Surprisingly, the formation of the N-methoxycarbonylation product was extremely restrained, which could be produced in high yields of 98% on zinc acetate catalyst. Furthermore, the reaction pathway to the major product MBDMA was proposed. Finally, a feasible synthetic route of 4,4′-methylene bis(N,N-dimethylaniline) (MBDMA) was established, featuring a high yield, mild reaction conditions, and simple operations.

In modern clinical medicine, lung cancer is one of the most common types of cancer, and the brain is a routine organ of metastasis. Recently, researchers have evaluated hematologic indicators, such as the neutrophil-tolymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and confirmed that they are valid indices for predicting the outcome of patients with lung cancer. However, their prognostic significance for patients with lung cancer who have progressed to brain metastasis (BM) has not been clarified. Our study performed and reported a meta-analysis focusing on the association of pretreatment NLR, PLR, and overall survival (OS) in lung cancer patients with BM. We searched the PubMed, Embase, and China National Knowledge Infrastructure databases using the PRISMA strategy. Meta-analyses of OS were performed using random-effects models because of the significant heterogeneity. We included 11 articles to evaluate NLR and PLR in 1,977 eligible patients. The NLR group consisted of 11 studies whose meta-analysis showed that OS was significantly shorter in patients with high NLR than in those with low NLR (pooled HR=1.84 (95% CI: 1.47–2.31). Five studies were included in the PLR group, and the results suggested that OS was significantly shorter in patients with high PLR than in those with low PLR (pooled HR=1.53 (95% CI: 1.07–2.20). Our metaanalysis showed a statistically significant association between NLR, PLR, and OS. Lower pre-treatment NLR and PLR predicted a better OS. [ABSTRACT FROM AUTHOR]

Lung cancer is currently the leading cause of cancer mortality and morbidity worldwide and greatly burdens humanity. Therefore, the prevention and treatment of lung cancer remains a serious global problem. The Wnt/β-catenin signaling pathway also regulates tumor cell growth and invasion through epithelial-mesenchymal transition and tumor stem cells. In this review, we first summarise the role of the Wnt/β-catenin signaling pathway in lung cancer, focusing on the reported links in the Wnt/β-catenin signaling pathway that are relevant to lung cancer cell line growth, cell survival, and patient prognosis. Then describe the advances in the Wnt/β-catenin signaling pathway in lung cancer therapy, the precise regulation of the Wnt/β-catenin signaling pathway, that precise regulation of the Wnt/β-catenin signaling pathway should be used to balance anti-tumor effects and adverse events. [ABSTRACT FROM AUTHOR]