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The detection of pathogenicity and immunogenicity in Vibrio parahaemolyticus poses a significant challenge due to its threat to human health and food safety, which is strongly correlated with lipid A. Lipid A, a critical component found in most Gram-negative bacteria, functions as a hydrophobic anchor for lipopolysaccharide. V. parahaemolyticus synthesizes multiple lipid A species with various secondary acyl chains. In this study, a secondary acyltransferase of lipid A encoded by VP_RS08405 in V. parahaemolyticus was identified. Based on sequence alignment analysis, V. parahaemolyticus VP_RS08405 has high homology to E. coli lpxL, lpxM and lpxP which encode the three secondary acyltransferases of lipid A. Therefore, V. parahaemolyticus VP_RS08405 was cloned into pBAD33, and the resulting pB08405 was introduced in E. coli mutants WHL00 in which lpxL was deleted, WHM00 in which lpxM was deleted, WHP00 in which lpxP was deleted, and WH300 in which lpxL, lpxM and lpxP were deleted. The recombinant strains WHL00/pB08405, WHM00/pB08405, WHP00/pB08405, WH300/pB08405, as well as their vector controls, were grown at normal and low temperatures. Lipid A species were isolated from the above strains and analyzed by using high-performance liquid chromatography-tandem mass spectrometry and thin-layer chromatography. After comparing the secondary acyl alterations of lipid A from different recombinant strains, it is concluded that VP_RS08405 specifically catalyzed the addition of a palmitoleate to the 2'-position of lipid A and its activity is not temperature-sensitive. In addition, to determine the dependence of VP_RS08405 on Kdo, VP_RS08405 was overexpressed in E. coli mutants WH001 in which waaA was deleted, and WH400 in which waaA, lpxL, lpxM and lpxP were deleted. Lipid A species were isolated from WH001/pB08405 and WH400/pB08405, and analyzed. The results show that the function of VP_RS08405 is Kdo-dependent. These findings provide a better understanding of the structural diversity of lipid A in V. parahaemolyticus., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Wooden breast (WB) myopathy is a common myopathy found in commercial broiler chickens worldwide. Although extensive research on WB has been conducted using transcriptomics, effectively screening and analyzing key target information remains a challenge. In this present study, 5 transcriptomic datasets obtained from the National Center for Biotechnology Information (NCBI) were used. A meta-analysis was conducted to identify meta-differentially expressed genes (meta-DEGs) involved in the response of broilers to WB myopathy. These meta-DEGs were further analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA), supplemented by protein-protein interaction (PPI) network construction to pinpoint hub genes. These analyses help to reveal key genes, pathways, and biological processes associated with WB myopathy. The results showed that 645 up-regulated and 99 down-regulated significant meta-DEGs (|log 2 FC| ≥0.6, P-Meta < 0.05, and present in at least 4 datasets) were identified. GO analysis showed that multiple fibrosis-related pathways/biological processes, such as cell adhesion, connective tissue development, and collagen-rich extracellular matrix, as well as calcium ion binding were significantly upregulated. PPI analysis identified TGFB3, COL1A1, COL1A2, and COL3A1 as central hub genes involved in the fibrotic processes. KEGG analysis revealed significant upregulation of apoptosis and lysosomal pathways, with an enrichment of Ca 2+ -related signals and lysosomal cathepsins within the apoptosis pathway. Additionally, GSEA indicated a suppression of the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (ETC) in WB myopathy, with PPI analysis also identifying specific hub genes associated with these pathways. In conclusion, our comprehensive analysis of meta-DEGs elucidated key biological processes and pathways implicated in WB myopathy, including fibrosis, apoptosis, altered calcium signaling, and metabolic disruption. The identification of specific hub genes offers avenues for further investigation into the pathogenesis of this condition, potentially guiding targeted therapeutic strategies., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The digestive characteristics of wheat starch are closely related to human health. However, the digestive mechanisms of distinct wheat starch granules are not well understood. To address this problem, A- and B-type wheat starch granules (AWS and BWS, respectively) were digested in vitro and the structural evolution of the digestive remnants was compared. After stomach-intestinal digestion of AWS, its crystallinity decreased from 12.75 % to 6.65 %, its fractal dimension decreased from 3.12 to 2.35, and the median particle size decreased from 20.613 to 10.135 μm. Additionally, the number of short chains (polymerization degree<14) and thermodynamic stability decreased after digestion. For BWS, Fourier transform infrared ratio of 1047/1022 cm -1 and 995/1022 cm -1 increased from 0.665 and 0.725 to 0.990 and 0.800, respectively. The median particle size decreased from 5.480 to 4.769 μm. An enzyme-resistant scattering peak was observed in the 1.35 nm -1 lamellar structure. Additionally, the number of B 2 and B 3 chains and the thermodynamic stability increased after digestion. Our study confirmed that BWS is more likely than AWS to form enzyme-resistant structures during digestion. These findings provide insights into the distinct digestion mechanisms of AWS and BWS, and serve as a foundation for modifying wheat starch to increase its nutritional value., Competing Interests: Declaration of competing interest I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigates the spatial and temporal dynamics of air quality in Shandong Province from 2016 to 2022. The Air Quality Index (AQI) showed a seasonal pattern, with higher values in winter due to temperature inversions and heating emissions, and lower values in summer aided by favorable dispersion conditions. The AQI improved significantly, decreasing by approximately 39.4 % from 6.44 to 3.90. Coastal cities exhibited better air quality than inland areas, influenced by industrial activities and geographical features. For instance, Zibo's geography restricts pollutant dispersion, resulting in poor air quality. CO levels remained stable, while O 3 increased seasonally due to photochemical reactions in summer, with correlation coefficients indicating a strong positive correlation with temperature (r = 0.65). Winter saw elevated NO 2 levels linked to heating and vehicular emissions, with an observed increase in correlation with AQI (r = 0.78). PM 2.5 and PM 10 concentrations were higher in colder months due to heating and atmospheric dust, showing a significant decrease of 45 % and 40 %, respectively, over the study period. Predictive modeling forecasts continued air quality improvements, contingent on sustained policy enforcement and technological advancements. This approach provides a comprehensive framework for future air quality management and improvement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Youkenafil is a novel Phosphodiesterase type 5 inhibitor used for treating erectile dysfunction. N-desethyl compound of youkenafil (M1) is its main active metabolite. In this study, two methods were developed and validated for the simultaneous determination of youkenafil and M1 by HPLC-MS/MS in human matrices including seminal plasma and plasma, in which the multiple reaction monitoring and electrospray ionization in positive mode were adopted, and the deuterated youkenafil (youkenafil-d5) was selected as the internal standard. The collected semen sample was kept at room temperature for approximately 30 min until fully liquefied. The volume of the liquefied semen was measured and then divided into two parts. One part was centrifuged to obtain the seminal plasma for the content detection of youkenafil and M1, while the other part was used for routine semen analysis. The chromatographic separation was accomplished with the column of Poroshell 120 EC-C18 (5 × 2.1 mm, 2.7 μm, Agilent). Protein precipitation with methanol was used for the pretreatment of seminal plasma and plasma. The intra-run and inter-run precisions were less than 6.4 % (relative standard deviation) and accuracies were all within -4.7 %-6.8 % (relative error) in both matrices. All other validated bioanalytical parameters were within the acceptance criteria set by the FDA. The methods were successfully applied to different clinical studies of youkenafil. In the clinical study of the acute effect of youkenafil on semen quality in healthy males, the content of youkenafil in seminal plasma was extremely low. Concentrations of youkenafil and M1 in seminal plasma were lower than those in plasma, at 20.7 % and 4.49 % of the plasma concentration, respectively. There was no significant acute effect of youkenafil on semen quality. In the pharmacokinetic study of youkenafil after single dose-escalation administration, the exposure to youkenafil and M1 was non-linear with the dose in the range of 100-400 mg., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Soil degradation has become a major global problem owing to the rapid development of agriculture. The problems of soil drought and decreased soil fertility caused by soil degradation severely affect the development of the agricultural and forestry industries. In this study, we designed sodium alginate (SA)/sodium lignosulfonate (SLS) hydrogel based on the activation and crosslinking of inert Ca 2+ . CaCO 3 and SA were mixed, and then, inert Ca 2+ was activated to prepare a gel with a stable structure and a uniform interior and exterior. The crosslinking activated by inert Ca 2+ enhanced the stability of the hydrogel, and the optimal swelling rate of the hydrogel reached 28.91 g/g, thereby effectively improving the water-holding capacity of the soil (77.6-108.83 g/kg). SLS was degraded into humic acid (HA) and gradually released, demonstrating a positive growth-promoting effect in plant growth experiments. The SA/SLS hydrogel can be used for soil water retention and mitigation to significantly decrease the water loss rate of soil. This study will assist in addressing soil drought and fertility loss., Competing Interests: Declaration of competing interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Aims: Radiation therapy is the standard treatment for patients with nasopharyngeal carcinoma (NPC), but relapse occurs in 10% to 20% of patients. The treatment of recurrent nasopharyngeal carcinoma (rNPC) remains challenging. Chimeric antigen receptors (CAR)-T-cell therapy has achieved good outcomes in the treatment of leukemia and seems to be a promising therapeutic strategy for solid tumors. c-Met has been found to be highly expressed in multiple cancer types, and the activation of c-Met leads to the proliferation and metastasis of cancer cells. However, the expression of c-Met in rNPC tissues and whether it can be used as a target for CAR-T therapy in rNPC remain to be investigated., Methods: We detected the expression of c-Met in 24 primary human rNPC tissues and three NPC cell lines and constructed two different antibody-derived anti-c-Met CARs, namely, Ab928z and Ab1028z. To estimate the function of these two different c-Met-targeted CAR-T cells, CD69 expression, cytotoxicity and cytokine secretion of CAR-T cells were assessed after coculture with target cells. A cell line-derived xenograft mouse model also was used to evaluate these two anti-c-Met CAR-T cells. Furthermore, we determined whether combination with an anti-EGFR antibody could promote the antitumor effect of CAR-T cells in a patient-derived xenograft mouse model., Results: High c-Met expression was detected in 23 of 24 primary human rNPC tissues by immunohistochemistry staining and in three NPC cell lines by flow cytometry. Ab928z-T cells and Ab1028z-T cells showed significantly upregulated expression of CD69 after coculture with targeted cells. However, Ab1028z-T cells showed superior cytokine secretion and antitumor activity. Furthermore, Ab1028z-T cells effectively suppressed tumor growth compared with control CAR-T cells, and the combination with nimotuzumab further enhanced the tumor-clearing ability of Ab1028z-T cells., Conclusions: We found that c-Met is highly expressed in rNPC tissues and confirmed its potential as a CAR-T target for rNPC. Our study provides a new idea for the clinical treatment of rNPC., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The incidence of wooden breast (WB) meat of commercial broiler chicken has been increasing in recent years. Histological examination found that the occurrence of WB myopathy was accompanied by the pectoralis major (PM) muscle damage. So far, the potential mechanisms are not fully understood. This study aimed to explore the underlying mechanism of the damage of WB-affected PM muscle caused by changes in mitochondrial function, mitochondrial redox status and Ca 2+ homeostasis. A total of 80 market-age Arbor Acres male broiler chickens were sampled and categorized into control (CON) and WB groups based on the evaluation of myopathic lesions. PM muscle samples were collected (n = 8 in each group) for histopathological evaluation and biochemical analyses. Ultrastructural examination and histopathological changes suggested the occurrence of PM muscle damage in broiler chickens with WB myopathy. The WB group showed an increased level of reactive oxygen species and enhanced antioxidant capacities in mitochondria of PM muscle. These changes were related to impaired mitochondria morphology and mitochondrial dysfunction. In addition, abnormal expressions of Ca 2+ channels led to substantial Ca 2+ loss in SR and cytoplasmic Ca 2+ overload, as well as Ca 2+ accumulation in mitochondria, resulting in Ca 2+ dyshomeostasis in PM muscle of broiler chickens with WB myopathy. Combined, these findings indicate that WB myopathy is related to mitochondrial dysfunction, mitochondrial redox status imbalance and Ca 2+ dyshomeostasis, leading to WB-affected PM muscle damage., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The loop B3 of glycoside hydrolase family 7 (GH7) endoglucanases is confined into long and short types. TtCel7 is a thermophilic GH7 endoglucanase from Thermothelomyces thermophilus ATCC 42464 with a long loop B3. TtCel7 was distinct for the excellent thermostability (>30 % residual activity after 1-h incubation at 90 °C). The catalytic efficiency was reduced by removing the disulfide bond in loop B3 (C220A) and truncated the loop B3 (B3 cut ). However, B3 cut exhibited improved thermostability, the remaining enzyme activity increased by 39 %-171 % compared toTtCel7 when treated at 70-90 °C for 1-h. Based on the analysis of molecular dynamics simulation, both loops B1 and A3 of B3 cut swing toward the catalytic center, which contributed to the reduced cleft-space and increased structure-rigidity. Conversely, the deletion of disulfide bond resulted in a reduction of structural rigidity in C220A. Through structure-directed enzyme modulation, this study has identified two structural elements that are related to the catalysis and thermostability of TtCel7. The loop B3 of TtCel7 possibly stretches the catalytic pocket, thereby increases the openness of the catalytic tunnel and enhancing flexibility for efficient catalysis. Additionally, the disulfide bond within loop B3 serves to enhance structural stability and maintain a heightened level of activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We provide evidence that material inducements for Covid-19 vaccination may backfire. Results from a hypothetical survey experiment in China ( N  = 1365) show incentives of 8-125 USD reduce vaccine uptake intentions compared to simply offering vaccination for free. Ours is the first Covid-19 vaccine study to separately consider and directly compare the effects of monetary and goods-based incentives, both of which have been widely employed by countries seeking to increase uptake; we demonstrate that both types backfire equally. Results are compared against the burgeoning literature on Covid-19 vaccine incentives., (© 2023 The Authors.)

Background: The decision for household cooking fuel choice is a complex and multi-dimensional process. This study aims to: 1) examine the trend of cooking fuel types during past decades; and 2) examine the association between switching from polluting to clean fuels for cooking and mortality risk., Methods: This analysis included data on 39,359 participants from 9 waves of the China Health and Nutrition Survey (CHNS) (1991-2015). Participants with consistent polluting fuel use and with the polluting-to-clean transition were identified. Generalized estimating equations were used to examine the trend of clean fuel use from 1991 to 2015. Propensity score matching was used to address the data imbalance and confounding factors and Cox proportional hazards models were used to estimate the association., Results: We found an increasing trend of clean fuel use after adjusting for potential confounders in the full sample (OR = 56.89, 95 % CI: 48.17, 67.19), which appeared to be more pronounced for those in rural areas and with low socioeconomic status. Switching from polluting to clean fuels was associated with a 75 % lower risk of mortality (HR = 0.25, 95 % CI: 0.11, 0.54). These associations became more pronounced during the lag period from 9 to 15 years., Conclusions: The transition from polluting to clean cooking fuels reduced excess deaths in China, particularly over a long period. Our findings support the increasing implementation of clean fuels and call for more efforts to improve its universal service, especially in rural and low socioeconomic status areas, to minimize health inequality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

In this study, to improve the soil amendment performance of film materials, composite films with the adjustable number of layers and controlled slow-release time were prepared using sodium alginate (SA), chitosan (CS) and activated charcoal (AC) as raw materials. The prepared multilayer films exhibited a wide pH response range and excellent slow-release time. The cumulative release of humic acid (HA) increased from 19.87 ± 0.98% to 66.72 ± 1.06% with increasing the pH from 4.0 to 10.0 after 700 h of slow-release. In addition, after 50 d of remediation in red soil, plantation soil, and saline soil, the NH 4 + -N, Olsen-P, Olsen-K, and organic matter contents in the three soils were increased by 2.91-28.62 mg/kg, 46.97-70.43 mg/kg, 55.89-77.01 mg/kg, and 12.47-22.52 g/kg, respectively, and were able to provide sustained crop growth promotion effect. This study demonstrates the promising application of multilayer film in soil remediation and agricultural production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this study, three high-performance porous biochars were synthesized by the cocarbonization of Pistia stratiotes-derived precursors (raw biomass, hydrochar and pyrochar) with potassium hydroxide and utilized for the sorption of diethyl phthalate from aqueous solution. The developed pore structure, surface functional groups, high hydrophobicity characteristic and graphene structure of porous biochars contributed to the excellent sorption quantity of up to 813 mg g -1 (C e , 25 mg L -1 ). Among the three precursors, hydrochar-derived porous biochar showed better properties in terms of its specific surface area and hydrophobicity, and it displayed the highest sorption capacity. The sorption kinetics and isotherm experiments confirmed that pore filling and partitioning dominated the sorption capacity while the mass transfer, hydrogen bonding and π-π stacking in the hydrochar limited the sorption rate. This finding helped to propose a feasible method for the efficient utilization of invasive aquatic plants and provided novel insight into the selection of precursors for preparing porous biochars., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Direct biomimetic modification of nanoparticles (NPs) with endogenous surfactants is helpful to improve the biocompatibility of NPs and avoid damage to the physiological function of the lung. Therefore, the objective of this study is to investigate the influence of biomimetic endogenous pulmonary surfactant phospholipid modification on the in vivo fate of NPs after lung delivery. Here, two neutral phospholipids (dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylamine (DPPE)) and two negatively charged phospholipids (dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylserine (DPPS)) were selected to modify paclitaxel (PTX)-loaded PLGA NPs with different molar ratio. DPPC, DPPE, and DPPG improved mucoadhesion, in contrast, DPPS improved the mucus permeability of the NPs. Neutral DPPC and DPPE reduced, but negatively charged DPPS and DPPG increased the uptake by alveolar macrophages, all types of phospholipid increased the uptake by lung epithelial cells and increased PTX retention in the whole lung. Whereas, DPPC, DPPE, and DPPG promoted PTX retention in bronchoalveolar lavage fluid (BALF), while DPPS promoted PTX absorption in the lung tissue. Only DPPS-PLGA (1:1) NPs remarkably increased PTX systemic exposure. A good correlation between PTX percentage in the supernatant of BALF and PTX concentration in plasma was established, implying PTX entered the system circulation mainly in molecular form. Phospholipid modification had no effect on extrapulmonary organ distribution of PTX. Taken together, our study disclosed that different phospholipid modification can endow the NPs mucoadhesive or mucus penetration and cellular uptake properties, with tunable retention in BALF and absorption in the lung tissue, providing the scientific background for translational nanocarrier design for inhalation as required. STATEMENT OF SIGNIFICANCE: Inhaled nanomedicines will inevitably interact with pulmonary surfactant and form "surfactant corona". However, the contribution of individual pulmonary surfactant phospholipid on the in vivo fate of nanomedicines is still unclear. In this regard, the most abundant pulmonary surfactant phospholipid dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylamine, and dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylserine were selected to modify the paclitaxel loaded PLGA nanoparticles and the effect of these pulmonary surfactant phospholipids on their in vivo fate was investigated. It was demonstrated that different phospholipid modification can endow the nanoparticles mucoadhesive or mucus penetration properties, with tunable retention in bronchoalveolar lavage fluid, alveolar macrophages uptake and absorption in the lung tissue. The present study provided a comprehensive understanding for the role of pulmonary surfactant phospholipid on inhaled nanomedicines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

As the sixth most prevalent cancer, liver cancer has been reported as the second cause of cancer-induced deaths globally. Lysionotin, a flavonoid compound widely distributed in Lysionotus pauciflorus Maxim, has attracted considerable attention due to its multiple biological activities. The present study analyzes the anti-liver cancer effects of lysionotin in cells and mouse models. In HepG2 and SMMC-7721 cells, lysionotin significantly reduced the viability of cells, inhibited cell proliferation and migration, enhanced cell apoptosis, promoted the increase of intracellular reactive oxygen species (ROS) levels, decreased mitochondrial membrane potential (MMP), and alternated the content of apoptosis-related proteins. In HepG2-and SMMC-7721-xenograft tumor mouse models, lysionotin inhibited tumor growth, reduced the expression levels of anti-apoptotic proteins and enhanced the expression levels of pro-apoptotic proteins in tumor tissues. Additionally, the pre-treatment of Ac-DEVD-CHO, an inhibitor of caspase-3, strongly restored the low cell viability, the enhanced apoptosis rate, the dissipation of MMP caused by lysionotin exposure, as well as prevented the lysionotin-caused enhancement on expressions of apoptosis related proteins, especially cleaved poly (ADP-ribose) polymerase (PARP), Fas Ligand (FasL), cleaved caspase-3 and Bax in both HepG2 and SMMC-7721 cells. Altogether, lysionotin showed significant anti-liver cancer effects related to caspase-3 mediated mitochondrial apoptosis., (Copyright © 2021. Published by Elsevier B.V.)

Stainless steel (SS) has been widely applied as one of the most efficient implant metal materials, although corrosion and infection in body environment are still challenging. Herein, an antibacterial passivation method was employed to enhance the antibacterial performance and corrosion resistance of the medical 316L SS. The result proved that the antibacterial-passivated 316L SS exhibited stable antibacterial activity and effectively inhibited the formation of bacterial biofilm. Electrochemical measurements combined with X-ray photoelectron spectroscopy technique were used to study the corrosion resistance and semiconductor behavior of passivated 316L SS immersed in simulated physiological environment. The results indicated that the 316L SS after antibacterial passivation treatment for 1 h, soaking in the medium for 10 days, showed satisfactory corrosion resistance attributing to proper Cu deposition in the passive film. The anodic stripping voltammetry measurement further confirmed that the Cu-bearing passive film could continuously release Cu ions into medium. The zebrafish test demonstrated an excellent in vivo biocompatibility for the 316L SS with antibacterial passivation for 0.5 and 1 h, respectively. In addition, changes of surface roughness, contact angle and chemical composition after antibacterial passivation played an important role in explaining the antibacterial mechanism, which could be clearly divided into contact killing and ionic release killing. Hence, the antibacterial passivation treatment was preliminarily proved as a potential way for enhancing the persistent antibacterial activity and corrosion resistance of 316L SS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A facile method of assembling oxindole and phthalide units through a Lewis based catalyzed allylic alkylation reaction of Morita-Baylis-Hillman carbonates of isatins and 3-cyanophthalides was recently developed. The method efficiently delivers a hybrid of 3,3'-disubstituted oxindole with a valuable phthalide pharmacophore. In the present study, we proved the deleterious effects of 5h2c, a screened synthesis compound, against hepatocellular carcinoma (HCC) in both in vitro and in vivo models. 5h2c strongly decreased cell viability, caused over-release of lactate dehydrogenase, inhibited cell migration, and enhanced the apoptosis rate in HepG2 and PLC/PRF/5 cells. 5h2c led to an increase in intracellular reactive oxygen species levels and a decrease in mitochondrial membrane potential. In HepG2-and PLC/PRF/5-xenograft tumor mouse models, treatment with 5h2c inhibited tumor growth without affecting the animals' bodyweight or organ functions. Proteome profiling of tumor tissues after 24-h exposure to 5h2c showed significantly enhanced expression levels of Bcl-2 associated X protein, cleaved caspase -3, -8, and -9, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), heme oxygenase-2, paraoxonase 2, catalase, and factor associated suicide ligand, and reduced the expression levels of B-cell lymphoma-2, B-cell lymphoma-extra large, heat shock protein 27, heat shock protein 60, and heat shock protein 70 in HepG2 and PLC/PRF/5 cells. All of our data confirmed that oxidative stress-mediated mitochondrial apoptosis (especially the Nrf-2/HO-1 pathway) is responsible for 5h2c-induced HCC damage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: PTK6 is involved in cell proliferation, invasion and migration. Patients with lower PTK6 expression predicts poor prognosis of LSCC. However, the mechanism of PTK6 in LSCC progression remains unclear. We investigated the role of PTK6 in the pathogenesis of LSCC., Methods: Human LSCC tissues and paired adjacent non-tumor tissues were obtained to evaluate PTK6 expression. The biological function of PTK6 in LSCC was determined by overexpression of PTK6 in Hep-2 cells in vitro and in nude mice. The potential PTK6 target factors and signaling pathways were identified by Western blotting assay and immunohistochemical staining., Results: PTK6 was downregulated in tissues of human LSCC. Biological function investigation of PTK6 demonstrated that overexpression of PTK6 significantly decreased cell growth, clonogenicity, invasion and migration capacity in vitro and suppressed xenograft tumor growth as well as lung metastasis in vivo. PTK6 suppresses LSCC proliferation mainly by inhibiting c-myc and cyclinD1 expression. In addition, PTK6 promotes cell apoptosis in LSCC. Moreover, PTK6 mitigated LSCC invasion and migration through regulating EMT and MMP-9., Conclusion: PTK6 plays a tumor suppressor role in LSCC by regulating c-myc and cyclinD1 expression, cell apoptosis, EMT and MMP-9., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Carnosic acid (CA), an important bioactive phenolic diterpene mainly found in labiate plants, exerts various biological functions, including antioxidant, anti-inflammatory, antitumor, and neuroprotective activities. In the present study, we proved the deleterious effects of CA against hepatocellular carcinoma (HCC) in both in vitro and in vivo models. In vitro, CA significantly decreased cell viability, inhibited cell proliferation and migration, enhanced apoptosis, and increased caspase-3, -8, and -9 activities in HepG2 and SMMC-7721 cells. Specifically, CA led to a decreased mitochondrial membrane potential (MMP) and increases in intracellular reactive oxygen species (ROS) levels and apoptosis-related protein expression. Pre-incubation of HCC cells with N-Acetyl-l-cysteine (NAC), a ROS inhibitor, strongly suppressed CA-induced apoptotic phenomena, including reduced cell viability, excessive ROS levels, MMP decreases, and abnormal protein expression, suggesting an association of CA-induced apoptosis with oxidative stress-mediated mitochondrial pathways. In HepG2-and SMMC-7721-xenograft tumor mouse models, treatment with CA inhibited tumor growth and modulated apoptosis-related protein expression, confirming the anti-HCC effects of this chemical. Moreover, the CA-mediated anti-HCC effects associated with oxidative stress provide experimental evidence to support the potential use of CA as a drug therapy for HCC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Apolipoprotein B mRNA-editing catalytic polypeptide (APOBEC) 3 proteins have been identified as potent viral DNA mutators and have broad antiviral activity. In this study, we demonstrated that apolipoprotein B mRNA-editing catalytic polypeptide 3A (A3A) and A3G expression levels were significantly upregulated in human papillomavirus (HPV)-infected cell lines and tissues. Heat treatment resulted in elevated expression of A3A and A3G in a temperature-dependent manner in HPV-infected cells. Correspondingly, HPV-infected cells heat-treated at 44 °C showed accumulated G-to-A or C-to-T mutation in HPV E2 gene. Knockdown of A3A or A3G could promote cell viability, along with the lower frequency of A/T in HPV E2 gene. In addition, regressing genital viral warts also harbored high G-to-A or C-to-T mutation in HPV E2 gene. Taken together, we demonstrate that apolipoprotein B mRNA-editing catalytic polypeptide 3 expression and editing function was heat sensitive to a certain degree, partly explaining the mechanism of action of local hyperthermia to treat viral warts., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Substance use by youth living with HIV (YLWH) is a concern, given potential interactions with virus-associated immune suppression and adverse effects on risk behaviors, neurocognition, and adherence. Self-report substance use measures provide efficient cost-effective assessments. Analyses describe self-reported substance use among YLWH and examine agreement with toxicology assays., Methods: Seventy-eight youth age 18-24 years (87% male, 71% African-American) with behaviorally acquired HIV-1 infection and 55 uninfected youth completed the Alcohol, Smoking, and Substance Involvement Screening Test to assess drug use frequency, including tobacco, marijuana, cocaine, and alcohol, over the prior three months. Elisa-based toxicology assays were used to detect 27 substances in plasma. Chi-square tests compared substance use between YLWH and uninfected youth; Kappa statistics compared agreement between self-report and toxicology., Results: YLWH reported marijuana (49%), tobacco (56%), and alcohol (87%) use, with 20%, 28% and 3% reporting daily use of each substance, respectively; other substance use was uncommon. Uninfected youth reported less tobacco use but otherwise similar substance use. All youth who reported daily use of marijuana or tobacco had positive plasma toxicology results, while concordance decreased with less frequent self-reported use. Among youth reporting no substance use, few tested positive (4% YLWH, 2% uninfected youth for cannabis; 8%YLWH for tobacco)., Conclusions: Youth report high rates of marijuana, tobacco, and alcohol use. Concordance between self-report and toxicology for marijuana and tobacco use, particularly for daily users, supports self-report as a valid indicator of substance use in research studies of youth with or without HIV-1 infection., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Augmenter of liver regeneration (ALR) has been shown to protect hepatocytes from various toxins. The aim of this study was to investigate the effects of ALR gene therapy on liver injury and fibrosis induced by CCl(4) in rats and further explore the underlying mechanisms. Human ALR expression plasmid was delivered via the tail vein. ALR gene therapy might protect the liver from CCl(4)-induced injury and fibrogenesis by attenuating the mitochondrial dysfunction, suppressing oxidative stress, and inhibiting activation of HSCs. This report demonstrated that ALR gene therapy protected against the ATP loss, increased the activity of ATPase, decreased intrahepatic reactive oxygen species level, and down-regulated transforming growth factor-β1, platelet-derived growth factor-BB, and α-smooth muscle actin expression. Following gene transfer liver function tests were significantly improved. In brief, ALR gene therapy might be an effective therapeutic reagent for liver fibrosis with potential clinical applications., (Copyright © 2011 Elsevier Inc. All rights reserved.)