[Discussion on hepatic damage mechanism of Asari Radix et Rhizoma based on network pharmacology and untargeted metabolomics].

Asari Radix et Rhizoma is a common drug for relieving exterior syndrome in clinics, but its toxicity limits its use. In this study, the mechanism of hepatic damage of Asari Radix et Rhizoma was studied by network pharmacology and metabolomics. The hepatic damage-related dataset, namely GSE54257 was downloaded from the GEO database. The Limma package was used to analyze the differentially expressed genes in the dataset GSE54257. Toxic components and target genes of Asari Radix et Rhizoma were screened by TCMSP, ECTM, and TOXNET. The hepatic damage target genes of Asari Radix et Rhizoma were obtained by mapping with the differentially expressed gene of GSE54257, and a PPI network was constructed. GO and KEGG enrichment analysis of target genes were performed, and a "miRNA-target gene-signal pathway" network was drawn with upstream miRNA information. Thirty rats were divided into a blank group, a high-dose Asari Radix et Rhizoma group, and a low-dose Asari Radix et Rhizoma group, which were administered once a day. After continuous administration for 28 days, liver function indexes and liver pathological changes were detected. Five liver tissue samples were randomly collected from the blank group and high-dose Asari Radix et Rhizoma group, and small molecule metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS). The orthogonal partial least squares-discriminant analysis(OPLS-DA) method was used to screen differential metabolites, and enrichment analysis, correlation analysis, and cluster analysis were conducted for differential metabolites. Finally, the MetaboAnalyst platform was used to conduct pathway enrichment analysis for differential metabolites. It was found that there were 14 toxic components in Asari Radix et Rhizoma, corresponding to 37 target genes, and 12 genes related to liver toxicity of Asari Radix et Rhizoma were obtained by mapping to differentially expressed genes of GSE54257. The animal test results showed that Asari Radix et Rhizoma could significantly increase the liver function index, reduce the activity of the free radical scavenging enzyme, change the liver oxidative stress level, and induce lipid peroxidation damage in rats. The results of untargeted metabolomics analysis showed that compared with the blank group, nine metabolites were up-regulated, and 16 metabolites were down-regulated in the liver tissue of the Asari Radix et Rhizoma group. These 25 metabolites had strong correlations and good clustering. Pathway enrichment analysis showed that these differential metabolites and the 12 hepatotoxic target genes of Asari Radix et Rhizoma were mainly involved in purine metabolism, as well as the biosynthesis and metabolism of valine, leucine, glycine, serine, and threonine. The study confirmed that the hepatica damage effect of Asari Radix et Rhizoma was the result of multi-component, multi-target, and multi-signaling pathways, and its mechanism may be related to inhibiting nucleotide synthesis and affecting protein metabolism.

Influence of the Surface State on the Interfacial Bonding Strength of the Cold-Rolled Brass/Carbon Steel Composite.

To improve the interfacial bonding of dissimilar composites, the interaction mechanism between the surface state and severe plastic deformation to strengthen the interfacial bonding strength was revealed. In this study, the different surface states of the steel strip were designed by louver blade grinding (LBG) and diamond bowl grinding (DBG), and the cold-rolled composite method was developed to prepare the brass/carbon steel composite strips. The results show that the steel surface after DBG has a large roughness of 9.79 µm, a hard hardening layer of 6.2 GPa, and high cleanliness of 1.34 atomic % oxygen content, while that after LBG has a roughness of 1.31 µm, a hardening layer of 4.2 GPa, and an oxygen content of 2.37 atomic %. The large roughness promotes the breaking of the hardening layer; the hardening layer is beneficial to obtain sufficient interfacial stress to expose the fresh metal; and the high cleanliness reduces the barrier to the fresh metal and contributes to the bonding of the fresh metal. The interface of the cold-rolled brass/carbon steel composite strip after LBG and DBG is mechanical bonding and metallurgical bonding, respectively. In the process of the cold-rolling composite, large shear deformation occurs at the interface of brass and steel, resulting in a high concentration of vacancy and dislocation defects, which provides a channel for interdiffusion of atoms at the interface. Under the diffusion driving force provided by the cold-rolling shear deformation heat, a nanodiffusion layer with a thickness of 60 nm and high interfacial bond strength was formed.

Engineering piperlongumine-inspired analogs as Nrf2-dependent neuroprotectors against oxidative damage by an electrophilicity-based strategy.

Oxidative stress contributes significantly to the development of neurodegenerative diseases, thus developing nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent neuroprotectors is highly required for either prevention or treatment of these diseases. This work highlights an electrophilicity-based strategy that allows finding more active Nrf2-dependent neuroprotectors than natural piperlongumine (PL). Electrophilic modification was applied on both the exocylic and endocyclic Michael acceptors of PL, which includes placement of an electron-withdrawing trifluoromethyl group on its aromatic ring in the ortho, meta, or para position to the exocyclic olefin, and further introduction of an electron-withdrawing α-chlorine on its lactam ring. From a panel of PL analogs, we identified PLCl-4CF3, characterized by the presence of p-trifluoromethyl group and α-chlorine, to be significantly superior to the parent PL in protecting PC12 cells from oxidative damage induced by 6-hydroxydopamine hydrochloride. Mechanistic studies reveal that the increased electrophilicity of PLCl-4CF3 in its two Michael acceptors allows its ability to covalently modify Cys-151 at Keap1, facilitating inhibition against Nrf2 ubiquitination, translocation of Nrf2 into the nucleus, induction of phase 2 enzymes and final protection of PC12 cells from oxidative damage.

High-quality compressed sensing imaging with limited detector bits using sparse measurements and multiple dithers.

High-flux measurement characteristics of compressed sensing (CS) imaging causes the imaging system prone to be disturbed by quantization. To realize high-quality CS imaging with limited detector bits, an improved imaging method combining sparse measurements and multiple dithers is proposed to reduce the dynamic range of the measured signals and increase that of effective detection. Simulations and experiments show that compared with traditional CS imaging, the proposed system decreases reconstruction errors caused by quantization distortions and may reduce the required number of detector bits to 1. The effects of detector noise and system parameters are discussed to validate the feasibility and performance of this method.

Developing dietary curcumin mono-carbonyl piperidinone analogs as Nrf2-dependent cytoprotectors against oxidative damage: Structure-activity relationship and mechanisms.

Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, ß-unsaturated piperidinone. Among these, the ortho-fluorine-substituted CN-2F surfaced as a promising lead molecule, which was significantly superior to the parent curcumin in protecting HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide. Mechanically, by virtue of its Michael receptor units and ortho-substituted mode, CN-2F activated Nrf2 signaling by covalently modifying Cys-151 and Cys-288 residues at Keap1, promoting phosphorylation of JNK, ERK and p38, as well as inhibiting Nrf2 degradation. This work reveals the structural determinants and the activity mechanisms of CN-2F as an Nrf2-dependent cytoprotector, and gives useful information on how to design curcumin-inspired Nrf2 activators and cytoprotectors.

Physical activity improves outcomes of combined lenvatinib plus anti-PD-1 therapy in unresectable hepatocellular carcinoma: a retrospective study and mouse model.

BACKGROUND: Physical activity is known to have anti-cancer effects, including immunomodulatory actions. This study investigated the hypothesis that physical activity synergizes with combined lenvatinib plus anti-PD-1 therapy to enhance efficacy in patients with unresectable HCC. METHODS: The physical activity levels of patients with unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy were recorded by questionnaire. Patients were categorized according to physical activity levels (active vs. sedentary). The primary outcome was overall survival (OS). Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). A subcutaneous syngeneic HCC model was generated in C57BL/6 mice. Mice were randomized to receive placebo, combined lenvatinib plus anti-PD-1 antibodies or combination therapy plus physical activity. Tumors were measured every 3 days and harvested for immunohistochemistry analysis at 20 mm maximum diameter. RESULTS: Fifty-nine patients with unresectable HCC were categorized to active (n = 28) or sedentary (n = 31) groups. The active group had higher albumin and des-γ-carboxy prothrombin levels and lower hepatitis B virus load at baseline; other clinical and oncologic characteristics were comparable between the two groups. Patients in the active group had significantly longer OS (HR = 0.220, 95% CI 0.060-0.799) and PFS (HR = 0.158, 95% CI 0.044-0.562) and higher ORR (OR = 4.571, 95% CI 1.482-14.102) than patients in the sedentary group. Regular physical activity was independently associated with OS, PFS and ORR. The mouse model showed that physical activity significantly suppressed tumor growth and prolonged survival of tumor-bearing mice. Furthermore, physical activity inhibited Treg cell infiltration and immune checkpoint expression (including CTLA4, TIGIT and TIM3) induced by long-term combined lenvatinib plus anti-PD-1 therapy, improving efficacy. CONCLUSIONS: Regular physical activity was associated with improved outcomes in unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy. Physical activity may improve therapeutic efficacy by reprograming the tumor microenvironment from an immunosuppressive to immunostimulatory phenotype.

Prooxidative inhibition against NF-κB-mediated inflammation by pharmacological vitamin C.

Vitamin C (VC), widely found in vegetables and fruits, operates as an electron donor to perform various biological functions including anti-inflammatory activity. However, the mechanisms by which VC inhibits inflammation remain insufficiently understood. Accordingly, we performed a detail mechanistic study on anti-inflammatory activity of VC at millimolar (pharmacological) concentrations in lipopolysaccharides-stimulated RAW264.7 cells. It was found that VC and its two-electron oxidative product, dehydroascorbate (DHA) constructs an efficient redox cycle with the aid of intracellular glutathione and copper ions, thereby facilitating the generation of reactive oxygen species (ROS) and the ROS-dependent inhibition against the NF-κB-mediated inflammation.

[Protective effects of total saponins of Codonopsis on ulcerative colitis induced by TNBS in rats and its mechanism].

Objective: To study the protective effects and mechanisms of total saponins of Codonopsis (TSC) on ulcerative colitis in rats. Methods: Fifty male Wistar rats were randomly divided into 5 groups: control group, model group, salazosulfadiazine (SASP) positive control group (0.3 g/kg), TSC high- and low-dose experimental groups(1.2, 0.4 g/kg). UC rat model was established by trinitrobenzene sulfonic acid (TNBS)/ ethanol enema. After administration for 21 days, the rats' symptoms and signs, disease activity index (DAI), colonic mucosal injury index (CMDI) and colonic tissue morphology were observed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) in colon tissues were determined. Protein expression of nuclear nuclear transcription factor-κB (NF-κB) in colon tissues was detected. Finally, the effect of TCS therapy was evaluated. Results: Compared with the control group, the DAI and CMDI scores of the rats in the model group were increased significantly, meanwhile the colonic mucosa was seriously damaged, indicating that the model was successful. Compared with the model group, the TSC high and low dose groups could significantly reduce the DAI and CMDI score (P＜0.05) and improve the colonic mucosa form. TSC also could increase the SOD activity and decrease MDA content in colon tissues(P＜0.05), while inhibit the levels of IL-6 and TNF-α mRNA in the colon tissues and promote the expression of IL-10 mRNA (P＜0.01). At the same time, TSC reduced the expressions of NF-κB protein in the colon (P＜0.01). The TSC high-dose group was superior to the low-dose group (P＜0.05). Conclusion: TSC has significant protective effects on ulcerative colonic mucosal damage in UC rats, and there is a dose-dependent relationship; its mechanism may be related to anti-lipid peroxidation and inhibiting the NF-κB signaling pathway to regulate the release of inflammatory factors.

PCSK9 promotes tumor growth by inhibiting tumor cell apoptosis in hepatocellular carcinoma.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis. RESULTS: High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway. CONCLUSIONS: PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.

[Qualitative analysis of Gynostemma longipes for medicinal usage].

The Qinling-Daba Mountains area is the main producing areas of Gynostemma longipes for medicinal usage, and samples of wild whole plants in Pingli, Shaanxi Province and Qingchuan, Sichuan Province were collected. The ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS~E) was used to profile the chemical compositions and analyze the similarities and differences of G. longipes samples in these areas. Based on the accurate molecular weight and fragment information obtained from Q-TOF-MS~E, the structures of the main components were identified by combining with the mass spectra, chromatographic behaviors of reference standards and related literatures. The results showed that the components of wild G. longipes from different places among Qinling-Daba Mountains area were similar. Forty-five chemical components were identified in the whole plant of G. longipes from Pingli, Shaanxi Province, including 43 triterpenoid saponins and 2 flavonoids which contain all main peaks in its fingerprint. The main components are dammarane-type triterpenoid saponins, such asgypenoside ⅩLⅨ, gypenoside A and its malonylated product of glycosyl.

Irbesartan inhibits metastasis by interrupting the adherence of tumor cell to endothelial cell induced by angiotensin II in hepatocellular carcinoma.

BACKGROUND: The use of angiotensin II inhibitors is associated with a low risk of recurrence and metastasis in hepatocellular carcinoma (HCC) patients. Vascular cell adhesion molecule-1 (VCAM-1) is a key factor in tumor metastasis. METHODS: The effects of angiotensin II and irbesartan (an angiotensin II inhibitor) on HCC were explored with a xenograft model, microarray analysis and cell adhesion experiments. The relationship between the expression of VCAM-1 in HCC tissues and prognosis was analyzed with public and our institutional clinical databases. The effects of angiotensin II, irbesartan and VCAM-1 on adhesion and metastasis in HCC were explored with a xenograft model and cell adhesion experiments. The regulatory mechanisms were analyzed by Western blot analysis. RESULTS: Angiotensin II type 1 receptor and VCAM-1 were expressed in HCC tissues. Irbesartan inhibited HCC growth and metastasis in vivo and weakened the adhesion of HCC cells to endothelial cells, an effect that was enhanced by angiotensin II. VCAM-1 was found to be an independent risk factor for recurrence and survival in HCC patients with microvascular invasion. Angiotensin II upregulated VCAM-1 expression, and this upregulation was inhibited by irbesartan. Angiotensin II enhanced adhesion mainly by promoting the expression of VCAM-1 in HCC cells. Irbesartan inhibited the expression of VCAM-1 by reducing p38/MAPK phosphorylation activated by angiotensin II in HCC cells. CONCLUSIONS: Irbesartan attenuates metastasis by inhibiting angiotensin II-activated VCAM-1 via the p38/MAPK pathway in HCC.

Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial.

OBJECTIVE: The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. METHODS: Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. RESULTS: A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DISCUSSION: Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02430259.

Prognostic nomograms and risk classifications of outcomes in very early-stage hepatocellular carcinoma patients after hepatectomy.

BACKGROUND: Numerous clinical models have been proposed to evaluate and predict recurrence and survival of hepatocellular carcinoma (HCC) patients in different stages after resection, but no model for very early-stage HCC. METHODS: The data of 661 very early-stage HCC patients after curative resection in our hospital were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyze recurrence and survival. The risk classifications for recurrence and survival were established by using classification and regression tree analysis. The nomograms were constructed and validated using bootstrap resampling and an independent 186-patient validation cohort from the same institution. RESULTS: According to the results of multivariate analysis for prognosis after resection, decision trees and 3-stratification classifications that satisfactorily determined the risk of recurrence and survival were established. Based on these two risk classifications, a six-factor nomogram for predicting recurrence and a six-factor nomogram for predicting survival were created. The concordance indexes were 0.64 for recurrence nomogram, with a 95% confidence interval of 0.60-0.67, and 0.76 for survival nomogram, with a 95% confidence interval of 0.70-0.82. The calibration curves showed good agreement between the predictions made by the nomograms and the actual survival outcomes. These predicting results for recurrence and survival were better than three common classical HCC stages and were confirmed in the independent validation cohort. CONCLUSIONS: The 3-stratification classifications enabled satisfactory risk evaluations of recurrence and survival, and the nomograms showed considerably accurate predictions of the risk of recurrence and survival in very early-stage HCC patients after curative resection.

Insight into role and mechanism of Li on the key aspects of biodegradable ZnLi alloys: Microstructure evolution, mechanical properties, corrosion behavior and cytotoxicity.

ZnLi based alloys have been proved as desirable candidates for biodegradable materials accounting for its high mechanical performance and great biocompatibility. However, effects of Li on microstructure and comprehensive properties of Zn alloys are seldom investigated and need to be addressed. Herein, Zn-(0.1-1.4 wt%)Li alloys are fabricated and systematically analyzed. Lath-like Zn precipitates are observed in the primary ß-LiZn4 (ß) phase of Zn-(0.5-1.4 wt%)Li alloys, leading to the formation of dense ß/Zn lamellar structure with an inter-spacing of 0.8 µm. Mechanical tests show that the strengths of the ZnLi alloys have at least tripled due to the formation of dense ß/Zn lamellar structure. Early degradation behaviors of the ZnLi alloys in simulated body fluid (SBF) reveal a competitive releasing of Li+ and Zn2+. As the priority of Li+ releasing becomes more obvious with increasing Li content in the alloys, aqueous insoluble Li-rich corrosion products containing LiOH and Li2CO3 form a passivation film on Zn-(0.5-1.4 wt%)Li alloys. Consequently, corrosion rate decreases significantly from 45.76 µm/y of pure Zn to 14.26 µm/y of Zn-1.4Li alloy. Importantly, observations of white light interferometer microscope and transmission electron microscope demonstrate that ß phase degrades prior to Zn in the alloys, suggesting that biomedical implants made of ZnLi alloys are likely to degrade completely in human body. Cytotoxicity tests of the alloys exhibit no cytotoxicity in 10% extracts. The most tolerated Zn2+/Li+ concentrations of the alloy extracts to L-929 cells are calculated, which provides guidance for future design of Zn alloys containing Li.

Enhancement in mechanical and corrosion resistance properties of a biodegradable Zn-Fe alloy through second phase refinement.

Biodegradable Zn alloys containing Fe suffer from a common problem that FeZn13 second phase particles are coarse. This problem roots thermodynamically from the negligible solid solubility of Fe in Zn and priority of FeZn13 solidification over Zn. In this paper, bottom circulating water-cooled casting method is successfully developed to significantly refine FeZn13 particles in Zn-0.3Fe alloy, owing to its cooling speed about 8 times of that of conventional casting. The second phase refinement alleviates brittleness of the alloy, increases the ultimate tensile strength by about 62%, and decreases electrochemical corrosion rate (CR) by about 19%, but immersion CR by only about 4% due to barrier effect of corrosion products. Viability of human umbilical vein endothelial cells maintains at a high level over 95% in 25-100% extracts. A great potential is shown for improving comprehensive properties of biodegradable Zn alloys without changing its chemical compositions through such a physical method.

NT5DC2 promotes tumor cell proliferation by stabilizing EGFR in hepatocellular carcinoma.

Most hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage; however, the effect of systemic therapy on advanced HCC remains undetermined. Therefore, new treatment targets must be identified. We analyzed Gene Expression Omnibus datasets from two HCC patient cohorts and found that NT5DC2 was associated with vascular invasion and poor survival. In two hepatoma cell lines, NT5DC2 overexpression promoted HCC cell proliferation and clone formation in vitro and promoted tumor growth in vivo. Coimmunoprecipitation assays and liquid chromatography with tandem mass spectrometry analysis revealed that NT5DC2 bound directly to epidermal growth factor receptor (EGFR). NT5DC2 upregulated EGFR expression by downregulating EGFR ubiquitination and preventing its degradation via the ubiquitin-proteasome pathway but did not upregulate its transcription. EGFR upregulation activated downstream signal transduction, which played a critical role in the protumor effects of NT5DC2. Erlotinib, a small-molecule inhibitor of EGFR, blocked the effect of NT5DC2 in promoting HCC cell proliferation. In a cohort of 79 patients who underwent curative resection for HCC, NT5DC2 expression in the tumors was associated with larger tumors and microvascular invasion. NT5DC2 expression was also independently associated with recurrence-free survival. The present study demonstrated for the first time that NT5DC2 promotes tumor cell proliferation in HCC and may serve as a potential molecular target for treating HCC. EGFR blockage could be used to treat selected patients with NT5DC2 upregulation.

In vitro antifungal activity and possible mechanisms of action of chelerythrine.

Chelerythrine (CHE) possesses broad pharmacological activities. In this study, the extract of Chelidonium majus L. were characterized by high performance liquid chromatography (HPLC), infrared radiation (IR) spectroscopy and nuclear magnetic resonance (NMR). It was proved that the extract was CHE. The antifungal activity of CHE against five fungal pathogens of rice was researched in vitro, revealing that CHE inhibited Ustilaginoidea virens (U. virens) and Cochliobolus miyabeanus (C. miyabeanus) with 50% effective concentrations (EC50) of 6.53 × 10-3 mg/mL and 5.62 × 10-3 mg/mL, respectively. When the concentration of CHE was 7.5 × 10-3 mg/mL, the inhibition rate of U. virens reached 56.1%. Moreover, CHE (4 × 10-3 mg/mL) exhibited the greatest efficacy in inhibiting spore of U. virens growth with an inhibition rate as high as 86.7%. CHE displayed the best inhibitory activity against U. virens at the concentration of 7.5 × 10-3 mg/mL, compared with the other two isoquinoline alkaloids and commercial fungicide validamycin. After treating U. virens mycelia with CHE, twisted and atrophied mycelia were observed by optical microscopy. SEM results demonstrated narrow and locally fractured mycelium. TEM observations showed that the cell wall had become thin and broken, and most organelles were difficult to recognize. Furthermore, membrane of mycelia was destroyed and reactive oxygen species (ROS) of spores was accumulated, which induced apoptosis of pathogenic fungi. From these results, our understanding of the mechanisms of antifungal activity of CHE against U. virens was enriched and this research is relevant for developing novel pesticides.

Design biodegradable Zn alloys: Second phases and their significant influences on alloy properties.

Alloying combined with plastic deformation processing is widely used to improve mechanical properties of pure Zn. As-cast Zn and its alloys are brittle. Beside plastic deformation processing, no effective method has yet been found to eliminate the brittleness and even endow room temperature super-ductility. Second phase, induced by alloying, not only largely determines the ability of plastic deformation, but also influences strength, corrosion rate and cytotoxicity. Controlling second phase is important for designing biodegradable Zn alloys. In this review, knowledge related to second phases in biodegradable Zn alloys has been analyzed and summarized, including characteristics of binary phase diagrams, volume fraction of second phase in function of atomic percentage of an alloying element, and so on. Controversies about second phases in Zn-Li, Zn-Cu and Zn-Fe systems have been settled down, which benefits future studies. The effects of alloying elements and second phases on microstructure, strength, ductility, corrosion rate and cytotoxicity have been neatly summarized. Mg, Mn, Li, Cu and Ag are recommended as the major alloying elements, owing to their prominent beneficial effects on at least one of the above properties. In future, synergistic effects of these elements should be more thoroughly investigated. For other nutritional elements, such as Fe and Ca, refining second phase is a matter of vital concern.

A prospective study of the effect of terlipressin on portal vein pressure and clinical outcomes after hepatectomy: A pilot study.

BACKGROUND: Portal hypertension after hepatectomy is associated with impaired postoperative recovery. Terlipressin decreased portal vein pressure in patients with variceal bleeding and improved patient survival, but the role of postoperative terlipressin treatment for patients who underwent liver resection is not clear. METHODS: We determined the effect of terlipressin on portal vein pressure in patients with portal vein pressure >12 mmHg after hepatectomy. If portal vein pressure was decreased (ie, Responders), a continuous infusion of terlipressin at 2 mg/day for 4 days was given. The incidence of posthepatectomy liver failure, abdominal drainage, acute kidney injury, operative complications, and side-effects of terlipressin in the Responders were compared with those whose portal vein pressure did not decrease (ie, non-Responders) and patients whose portal vein pressure was ≤12 mmHg after hepatectomy (low portal vein pressure group). RESULTS: We recruited 110 patients, 65 of whom were eligible for terlipressin administration. Portal vein pressure decreased in 46 patients (71%) with the mean portal vein pressure decreasing from 15.8 ± 2.6 mmHg to 14.3 ± 2.9 mmHg (P < .001). The median [interquartile range] postoperative abdominal drainage for the first 3 postoperative days was less in the Responders than in the non-Responders (350 mL [228-573] vs 730 mL [330-980]; P = .004). Incidence of posthepatectomy liver failure in the Responders was less than the non-Responders (26% vs 53%, P = .04). Acute kidney injury, operative complications, and side-effects of terlipressin were not different between groups. CONCLUSION: Terlipressin decreased posthepatectomy portal vein pressure and may decrease the incidence of posthepatectomy liver failure and postoperative abdominal drainage (NCT03352349).

[Effects of Biejia Yugan Granule on rat with ethanol-induced hepatic fibrosis].

Objective: To investigate the prevention and treatment effect of Biejia Yugan Granule (BYG) on ethanol-induced hepatic fibrosis (EHF) rats. Methods: SD rats were randomly divided into blank control group, model group, BYG group, colchicine group and BYG low and BYG high dose groups (n=8). The EHF rat model was established by intragastric edible ethanol with a gradually increased dose. Briefly, the rats of model group, colchicine group and BYG low and high dose groups were given gavage of 5 g/(kg·d) ethanol at week 1～4, 7 g/(kg·d) ethanol at week 5～8, 9 g/(kg·d) ethanol at week 9～12 and 9.5 g/(kg·d) ethanol at week 13～24. And the other two groups were treated with equal volume water. At the same time, the corresponding drugs were administrated daily: BYG group was treated with Biejia Yugan Granules 5.55 g/kg, colchicine group was treated with colchicine 0.1 mg/kg, BYG low-dose and high-group were treated with Biejia Yugan Granules 1.85 and 5.55 g/kg respectively. The blank control group and model control group were given the same amount of purified water. On the 169th day of the experiment, the effects of BYG on the macroscopic changes of rat liver organs, the water content of liver tissue and the pathological changes of fibrosis, the content of hydroxy proline (Hyp) in liver tissue and the expression levels of α-SMA and CREB were observed. Results: BYG at the doses of 1.85 and 5.55 g/kg could significantly improve the macroscopic changes of liver and pathological changes of liver tissue fibrosis in rats with EHF, reduce the contents of water and Hyp in liver tissue, and down-regulate the expressions of α-SMA and CREB. Conclusion: BYG has obvious effect on inhibiting EHF and one of its mechanisms is down-regulate the content of CREB.