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Cell surface heparan sulfate proteoglycan (HSPG) is a group of critical glycoproteins that mediates signal transduction. Sulfated HSPG can mediate the activation of a variety of cell growth factor signal pathway to promote the progression of gallbladder carcinoma (GBC). This study analyzed 527 clinical GBC specimens and confirmed that the HSPG sulfation level was significantly higher in GBC tissues than in gallbladder mucosa (GBM) tissues. The high HSPG sulfation level was closely associated with poor differentiation, local metastasis, and advanced clinical stage of GBC; it was also associated with the shortening of disease-free survival (DFS) and overall survival (OS) and influenced the outcome of chemotherapy or radio-chemotherapy in patients with GBC recurrence. Inhibition of HSPG sulfation on the GBC cell surface using human sulfatase 1 (hSulf-1) significantly reduced the phosphorylation levels of growth factor receptors and signaling protein kinases in GBC cells, decreased cell responses to growth factors, and inhibited cell proliferation and migration abilities. In a nude mouse model with GBC xenografts, we observed that the xenograft tumor growth was suppressed and the phosphorylation levels of signaling proteins were downregulated, together with decreased expression of Ki67 and reduced sensitivity to bFGF (basic fibroblast growth factor) induction after inhibition of HSPG sulfation. Our study demonstrated that a high HSPG sulfation endows GBC with high malignant biological behaviors and a poor prognosis. Desulfation of cell surface HSPG can inhibit the kinase activities of a variety of signaling proteins, hinder the cell response to growth factors, and effectively inhibit the malignant biological behaviors of GBC cells. [ABSTRACT FROM AUTHOR]

Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C 30 N 4 H 40 SO 5 F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo , and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment. [ABSTRACT FROM AUTHOR]

The contamination of soils by mercury (Hg) seriously threatens the local ecological environment and public health. S-functionalized amendments are common remediation technology, yet, Hg re-activation often occurs in the commonly used immobilization remediation by S-functionalized amendments, resulting in an unsatisfactory remediation effect. In this study, a novel FeS–Se functionalized biochar composite (FeS-Se-BC) amendment was prepared and applied for the efficient remediation of Hg-polluted soil. An immobilization efficiency of 99.62% and 99.22% for H 2 O-extractable Hg and TCLP solution-extractable Hg was achieved with the application of FeS-Se-BC (0.05) after 180 d. The analyses of XPS, Hg-TPD, SEM-EDS demonstrated that excellent remediation performance by FeS-Se-BC resulted from the synergistic effect of FeS and Se to form HgS and HgSe concurrently. In comparison to the treatments of biochar and FeS-functionalized biochar (FeS-BC), FeS-Se-BC promoted the transformation of exchangeable, carbonate-bound, and Fe–Mn oxides-bound Hg fractions into organic material-bound, and residual fractions, effectively reducing the risk of Hg-contaminated soil from a highly dangerous level to a low risk. Furthermore, the introduction of Se clearly inhibited the re-activation of Hg and reduced the release of Hg by 81.12% compared to FeS-BC when the ratio of S2− to Hg was 5: 1 due to the formation of extremely stable HgSe. These results suggest that FeS-Se-BC has good potential for remediation of Hg-polluted soils which provides a new inhibitory idea for Hg re-activation after immobilization. [Display omitted] • A novel sulfur-selenium modified biochar (FeS-Se-BC) was synthesized. • FeS-Se-BC mainly immobilized Hg via the formation of HgS and HgSe. • Incorporation of Se inhibit the re-activation of Hg in the case of excessive S2−. [ABSTRACT FROM AUTHOR]

The CCND1 gene is overexpressed in esophageal cancer and accelerates cell cycle progression. However, the mechanism whereby the upstream genes or factors directly regulate CCND1 expression remains unknown. By analyzing the 5′-UTR region of the CCND1 gene, we found that this region contains an octamer motif (ATTTTGCAT), which suggests that the expression of CCND1 might be directly associated with octamer-binding transcription factor 4 (OCT4). In this study, the wild-type and the octamer motif-mutanted CCND1 promoters were cloned, and their corresponding luciferase reporter vectors were then constructed to study the molecular mechanism by which OCT4 regulates the expression of CCND1 and influences the biological behaviors of esophageal cancer cells. The results indicated that suppressing the expression of CCND1 and OCT4 in esophageal cancer cells reduced cell proliferative and invasive abilities, induced cell cycle G1-phase arrest, and slowed the growth of xenografts in nude mice. Suppression of OCT4 expression significantly decreased the wild-type CCND1 promoter activity and down-regulated the expression of CCND1, but did not affect the activity of the mutant promoter. Whereas, suppression of CCND1 did not affect OCT4 expression, suggesting that OCT4 regulates CCND1 expression by activating the CCND1 promoter and subsequently promoting cell cycle progression. The results revealed and confirmed that OCT4 is the upstream factor that directly binds to the CCND1 promoter to regulate CCND1 expression, then to promote cell cycle progression and accelerate the proliferation and invasion of esophageal cancer cells. This finding may significantly contribute to elucidating the regulatory mechanism involved in the cell cycle progression of esophageal cancer cells and may aid in screening potential gene targets for the biological therapy of esophageal cancer. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cancer metastatic ability is closely related with miRNA expression. [•] miRNAs are small and easy to be secreted into extracellular microenvironments. [•] miRNAs deliver the regulatory messengers between cancer cells and stromal cells. [•] miRNAs regulate the modification and establishment of cancer metastatic microenvironment. [Copyright &y& Elsevier]

Highlights: [•] miR-21 suppresses the expression of hSulf-1 and PTEN in HCC cells. [•] Suppression of hSulf-1 or PTEN by miR-21 can activate AKT/ERK1/2 signaling. [•] Activation of AKT/ERK1/2 pathways induces EMT in HCC cells. [•] miR-21 functions to promote cancer cell proliferation and movement. [Copyright &y& Elsevier]

Abstract: Gene therapy is an important means for the comprehensive treatment of pancreatic cancer. Challenges associated with gene therapy include control of vector security and effective genetic screening. In this paper, a CEA promoter-regulated oncolytic adenovirus vector was constructed. The reporter gene assay demonstrated that the viral vector was confirmed to have tumor-specific replication features. In vitro cytology studies showed that the CEA promoter regulated the proliferation of the adenovirus vector carrying the Hsp70 gene (AdCEAp-Hsp70), which significantly increased the expression levels of Hsp70 in the CEA-positive pancreatic cancer cells, resulting in an overall reduction in the survival of cancer cells. In the human pancreatic cancer Panc-1 xenograft model in immune deficient nude mice, the CEA promoter-regulated adenovirus AdCEAp-Hsp70 significantly inhibited tumor growth. In the rat pancreatic cancer DSL-6A/C1 xenograft model in rats, the viral proliferation and high expression levels of Hsp70 promoted the interstitial infiltration of CD4+, CD8+ and gamma/delta T cells into tumors, induced host secretion of the cytokines TGF-β, INF-γ, and IL-6 and had a dual anti-tumor effects that completely inhibited the growth of pancreatic cancer. The results demonstrated that the oncolytic adenovirus under the control of CEA promoter provides additional assurances regarding the safety and efficiency of cancer gene therapy. This gene therapy model improves anti-cancer efficiency and has broad applications and developmental prospects. [Copyright &y& Elsevier]

Abstract: Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic adenovirus system validated that Survivin promoter-regulated oncolytic adenovirus had high proliferation activity and high P53 expression in Survivin-positive gallbladder cancer cells. Our in vitro cytotoxicity experiment demonstrated that AdSurp-P53 possessed a stronger cytotoxic effect against gallbladder cancer cells and hepatic cancer cells. The survival rate of EH-GB1 cells was lower than 40% after infection of AdSurp-P53 at multiplicity of infection (MOI) = 1 pfu/cell, while the rate was higher than 90% after infection of Ad-P53 at the same MOI, demonstrating that AdSurp-P53 has a potent cytotoxicity against EH-GB1 cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB1 xenografts when the total dose of AdSurp-P53 was 1 × 109 pfu, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was (33.4 ± 8.4)%. This oncolytic adenovirus system overcomes the long-standing shortcomings of gene therapy: poor transgene expression and targeting of only specific tumors, with its therapeutic effect better than the traditional Ad-P53 therapy regimen already on market; our system might be used for patients with advanced gallbladder cancer and other cancers, who are not sensitive to chemotherapy, radiotherapy, or who lost their chance for surgical treatment. [Copyright &y& Elsevier]

[Display omitted] • MXene/nZVI@FH was prepared to remove Be(II) from Be(NH 2) 2 complexing solutions. • MXene/nZVI@FH permeability (6.1 × 10−15 m2) was 301 times higher than that of MXene. • MXene/nZVI@FH exhibited a high Be sorption capacity for aqueous Be(NH 2) 2. • OH radicals generated by MXene/nZVI@FH were enhanced in acidic aerobic aqueous. • MXene/nZVI@FH had good selectivity for beryllium. Two-dimensional metal carbides or nitrides (MXenes) demonstrate various excellent properties; however, their poor permeability precludes their application in water treatment. In this study, Ti 3 C 2 T x MXene/nZVI/fungal hyphae nanofiber hybrid membranes (MXene/nZVI@FH) were prepared by chemical-intensive precipitation method for the robust capture of Be(II) from a beryllium-ammonia complexing solution. Interestingly, the MXene/nZVI@FH membrane showed favorable water permeability (6.10 × 10−15 m2), which was approximately 301 times higher than that of a pure Ti 3 C 2 T x membrane, and 99.8% Be(II) was captured from the Be(NH 2) 2 complexing solution with an extremely low concentration (19.85 ppm). Specifically, the maximum Be(II) adsorption capacity of MXene/nZVI@FH was calculated to be 95.20 mg/g from the Be(NH 2) 2 complexing solution at pH 5.0 and 35 °C. Various characterization results (e.g., SEM, FTIR, XRD, VSM and XPS) suggested that Be(II) prefers to coordinate with surface oxygen groups bonded to the MXene nanosheets by forming BeO and BeO 2 2− bidentate inner-sphere complexes. Furthermore, due to its reticular sandwiched structure, MXene/nZVI@FH could be easily activated and reused by leaching with 0.1 M HCl solution. Thus, it is a promising hybrid membrane for the removal and recovery of Be(II) from a Be(NH 2) 2 complexing solution. [ABSTRACT FROM AUTHOR]

• A cost-effective strategy to develop low-cost biomass-based carbon materials were prepared. • The highest surface area of hierarchical porous carbon is up to 3936 m2 g−1. • The porous carbon exhibits record-high acetone and methanol adsorption capacity at 25 °C. • The oxygen groups can enhance the acetone and methanol uptake at relatively low pressure. • The narrow micropore determines the acetone/methanol selectivity at relatively low pressure. In this study, biomass-based hierarchical porous carbons (HPCs) were synthesized by developing a cost-effective strategy that combines pyrolysis with KOH activation. The highest surface area of HPCs is up to 3936 m2 g−1, which presents record-high acetone (26.1 mmol g−1 at 18 kPa) and methanol (46.9 mmol·g−1 at 15 kPa) adsorption capacity at 25 °C. Based on experiments and molecular simulations, the total pore volume mainly determines adsorption amount of acetone and methanol at relatively high pressure. However, the oxygen groups can provide adsorption sites for acetone and methanol at relatively low pressure, which is attributed to electrostatic interaction between gas molecules and carbon frameworks. Additionally, the narrow micropore determines the acetone/methanol selectivity at relatively low pressure, and the oxygen groups have no benefit effect on acetone/methanol selectivity. Therefore, this work provides theoretical and experimental support for the design, preparation, and application of VOCs adsorbents. [ABSTRACT FROM AUTHOR]

[Display omitted] • The synergistic effects of surface functional groups and pore sizes were elucidated. • The capture property of CO 2 at low pressures and high pressures was investigated. • The intrinsic enhancement mechanism in adsorption capacity was clarified. • Provide an alternative strategy in preparation and synthesis of carbon materials. In this work, the capture property of CO 2 molecules on M-doped (M = N, P, S, and O) functionalized-graphite surfaces with different pore sizes (0.8–5.0 nm) were investigated by using grand canonical Monte Carlo simulation (GCMC) and density functional theory (DFT). The synergistic effects of surface functional groups and pore sizes on the adsorption behavior of CO 2 on functionalized surfaces were elucidated. At low pressures, the surface functional groups presented a significant enhancement on CO 2 adsorption performance, regardless of the pore size. At high pressures, for pore size being larger than 1.0 nm, the surface functional groups made an important contribution on the saturated CO 2 adsorption capacity. Among all the surface functional groups, the P-doped functionalized-graphite surfaces had a prominent influence on CO 2 uptake owning to the strong electron-gaining/donating capacity and high adsorption energies. At low pressures, G-CO─PO(OH) 2 exhibited a superior CO 2 capture performance (6.0 mmol/cm3 for 1.0 nm pore) at 16 kPa. At high pressures, G-C 3 ─P has the maximum CO 2 uptake (15.3 mmol/cm3 for 1.0 nm pore) at 300 kPa. Based on the comprehensive research of various polar functional groups and pore sizes, this study clarified the intrinsic enhancement mechanism in adsorption capacity of functionalized-graphite surfaces, which would pave an alternative way in the design and synthesis of carbon materials for gas capture. [ABSTRACT FROM AUTHOR]

The structurally ordered low-Pt compounds (PtNi 3 -C and PtFe 3 -C) were synthesized via the chemical reduction method and the toluene catalytic oxidation experiments were conducted to test their catalytic performance. And the reaction kinetics and catalytic mechanism are investigated based on the MVK model. • The low-Pt catalysts were synthesized via the chemical reduction method. • High toluene catalytic activity and stability were obtained. • The reaction kinetic parameters from the MVK model were calculated. • The MVK mechanism and the in-situ DRIFT was used to study the reaction pathway. • The accessibility of toluene to bimetal catalysts was explored by DFT simulation. The low-Pt bimetal compounds (PtNi 3 -C and PtFe 3 -C) were synthesized via the chemical reduction method and the toluene catalytic oxidation experiments were conducted to test their catalytic performance. The sample of PtFe 3 -C (T 100 = 255 ℃) possessed a better low-temperature catalytic activity than PtNi 3 -C (T 100 = 288 ℃) due to a higher content of Pt (0), while both two catalysts had a desirable catalytic stability (⁓100 % within 72 h). The reaction kinetic parameters were acquired from the Mars-van Krevelen (MVK) model, and the MVK mechanism combined with the in-situ DRIFT was used to investigate the reaction pathway. Moreover, the theoretical calculations based on DFT was applied to study the accessibility of toluene to the surface of metal atoms doping. Herein, this study not only can provide a promising catalyst with the superior low-temperature catalytic activity and stability, but also can give a comprehensive understanding on the toluene catalytic oxidation mechanism over bimetal catalysts. [ABSTRACT FROM AUTHOR]

Optical projection tomography (OPT) is an imaging technology that employs light to reconstruct 3D models of objects. Recent advancements in neural radiance field (NeRF) have improved 3D biomedical imaging, yet they perform suboptimally with low signal-to-noise ratio (SNR) data in low-cost setups and are not directly applicable to OPT systems. Here, we introduce neural optical projection tomography (NeOPT), leveraging a low-cost OPT imaging setup combined with a pose-robust neural-based 3D reconstruction method to achieve high-quality OPT results. NeOPT incorporates discrete wavelet transform (DWT) to reduce imaging noise under low-SNR conditions. Experiments demonstrate that NeOPT significantly outperforms traditional OPT techniques.

Rhenium represents an irreplaceable metal resource, which finds extensive applications in diverse fields, particularly in the aerospace and petrochemical industry. However, its remarkably low natural abundance and the lack of independent ore deposits pose significant challenges to its extraction and recovery processes. In this study, we present the highly efficient adsorption of perrhenate by a cationic polymeric nanotrap material, namely CPN-3VIm. The maximum adsorption capacity of CPN-3VIm-Cl for ReO 4 - attains an impressive value of 1220 mg ⋅ g -1 . Notably, even in the low-concentration ReO 4 - solution of 8.5 ppm, the removal rate could still exceed 99 %. The recycling performance of CPN-3VIm-Cl also shows exceptional results, with both ReO 4 - removal and recovery rates surpassing 90 % throughout five adsorption-desorption cycles. Furthermore, CPN-3VIm-Cl exhibits nearly 100 % extraction efficiency for ReO 4 - within a broad pH range of 4-10 and demonstrates remarkable structural stability under extreme conditions, such as 3 M sulfuric acid or 3 M nitric acid. Additionally, a comprehensive investigation into the interaction mechanism between CPN-3VIm-Cl and perrhenate was carried out using SEM-EDS mapping, Raman, FT-IR, and XPS analysis., (© 2025 Wiley-VCH GmbH.)

Computed tomography (CT) with its remarkable capability for three-dimensional imaging from multiple projections, enjoys a broad range of applications in clinical diagnosis, scientific observation, and industrial detection. Neural adaptive tomography (NeAT) is a recently proposed 3D rendering method based on neural radiance field for CT, and it demonstrates superior performance compared to traditional methods. However, it still faces challenges when dealing with the substantial perturbations and pose shifts encountered in CT scanning processes. Here, we propose a neural rendering method for CT reconstruction, named iterative neural adaptive tomography (INeAT), which incorporates iterative posture optimization to effectively counteract the influence of posture perturbations in data, particularly in cases involving significant posture variations. Through the implementation of a posture feedback optimization strategy, INeAT iteratively refines the posture corresponding to the input images based on the reconstructed 3D volume. We demonstrate that INeAT achieves artifact-suppressed and resolution-enhanced reconstruction in scenarios with significant pose disturbances. Furthermore, we show that our INeAT maintains comparable reconstruction performance to stable-state acquisitions even using data from unstable-state acquisitions, which significantly reduces the time required for CT scanning and relaxes the stringent requirements on imaging hardware systems, underscoring its immense potential for applications in short-time and low-cost CT technology.

A Gram-stain-negative, strictly aerobic, non-motile, catalase- and oxidase-positive, pink and rod-shaped strain, designated RY-2 T , was isolated from sediment of Fuyang River located in Wuqiang County, Hengshui City, Hebei Province, PR China. The strain grew at 25-45 °C (optimum, 37 °C), pH 7.0-8.0 (optimum, pH 7.0) and in the presence of 0-1.5 % (w/v) NaCl (optimum, 1 %). From the phylogenetic analysis of the 16S rRNA gene sequence, strain RY-2 T was affiliated to the genus Mariniradius , and had the highest 16S rRNA gene sequence similarity to Mariniradius saccharolyticus JCM 17389 T (98.3 %) and the similarity values between strain RY-2 T and other type strains was all below 89.3 %. The genome size of strain RY-2 T was 4.75 Mb and the DNA G+C content was 46.6 %. Values of digital DNA-DNA hybridization and average nucleotide identity between strain RY-2 T and the reference strain were 63.2 and 95.5 %, respectively. The major fatty acids (≥5.0 %) were iso-C 15 : 0 (37.9 %), summed feature 9 (8.4 %, iso-C 17 : 1 ω 9 c and/or C 16 : 0 10-methyl), anteiso-C 15 : 0 (8.2 %), iso-C 17 : 0 3-OH (7.6 %) and summed feature 4 (5.2 %, iso-C 17 : 1 I and/or anteiso-C 17 : 1 B) and its sole menaquinone was MK-7. The polar lipids consisted of phosphatidylethanolamine, an unknown phosphoglycolipid, an unidentified phospholipid, two unidentified aminolipids, three unidentified glycolipids and nine unidentified lipids. Based on the results of biochemical, physiological, phylogenomic and chemotaxonomic analyses, strain RY-2 T is considered to represent a novel species of the genus Mariniradius within the family Cyclobacteriaceae , for which the name Mariniradius sediminis sp. nov. is proposed. The type strain is RY-2 T (=GDMCC 1.2781 T =JCM 35631 T ).

Matrine , one of the active ingredients of Sophora flavescens Ait. , has a protective effect in animal models on acute liver injury and liver fibrosis. However, since the protective effects are short-lived, a structural modification of matrine is needed to improve its anti-fibrotic effects. In the previous study we obtained a stable, highly active new matrine derivative, WM130, and explored its anti-fibrotic effects on the human hepatic stellate cell line, LX-2. CCK-8, wound healing, and transwell assays were used to investigate cell proliferation and migration, while 3D mimic study was used to determine the target of WM130. Western blots investigated the levels of α-SMA, cofilin 1, p-cofilin 1, F-actin, PI3K, p-Akt, Akt, and PTEN in LX-2 cells treated with MW130. The results revealed that WM130 can significantly inhibit the proliferation of LX-2 cells at an IC 50 of 60 μg/ml. At 30 µg/ml, matrine or WM130 significantly inhibited the migration of LX-2 cells. Moreover, WM130 significantly reduced the expression of α-SMA, cofilin 1, F-actin, PI3K, and p-Akt, and increased PTEN levels. In conclusion, WM130 inhibits the proliferation, activation, and migration of human hepatic stellate LX-2 cells by targeting cofilin 1., Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00548-w., Competing Interests: Competing interestsThe authors declare no competing interests.Conflict of interestNone., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Oncolytic virotherapy has become an important strategy in cancer immunotherapy. Oncolytic virus (OV) can reshape the tumor microenvironment (TME) through its replication-mediated oncolysis and transgene-produced anticancer effect, inducing an antitumor immune response and creating favorable conditions for the combination of other therapeutic measures. Extensive preclinical and clinical data have suggested that OV-based combination therapy has definite efficacy and promising prospects. Recently, several clinical trials of oncolytic virotherapy combined with immunotherapy have made breakthroughs. This review comprehensively elaborates the OV types and their targeting mechanisms, the selection of anticancer genes armed in OVs, and the therapeutic modes of action and strategies of OVs to provide a theoretical basis for the better design and construction of OVs and the optimization of OV-based therapeutic strategies., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022. Published by Elsevier Inc.)

Sodium is one of the most promising anode candidates for the beyond-lithium-ion batteries. The development of Na metal batteries with a high energy density, high safety, and low cost is desirable to meet the requirements of both portable and stationary electrical energy storage. However, several problems caused by the unstable Na metal anode and the unsafe liquid electrolyte severely hinder their practical applications. Herein, we report a facile but effective methodology to construct an in situ polymer electrolyte and Na-rich artificial solid-electrolyte interface (SEI) layer concurrently. The obtained integrated Na metal batteries display long cycling life and admirable dynamic performance with total inhibition of dendrites, excellent contact of the cathode/polymer electrolyte, and reduction of side reactions during cycling. The modified Na metal electrode with the in situ polymer electrolyte is stable and dendrite-free in repeated plating/stripping processes with a life span of above 1000 h. Moreover, this method is compatible with different cathodes that demonstrate outstanding electrochemical performance in full cells. We believe that this approach provides a practical solution to solid-state Na metal batteries.

Background: Oncolytic virotherapy has become an important branch of cancer immunotherapy. This study investigated the efficacy of an oncolytic adenovirus (OAV), OncoViron, with synergistic mechanisms in the treatment of multiple solid tumors., Methods: An OAV, OncoViron, was constructed and investigated by cytological experiments and implanted tumor models of multiple solid tumor cell lines to certify its anticancer efficacy, the synergistic effects of viral oncolysis and transgene anticancer activity of OncoViron, as well as oncolytic virotherapy combined with immunotherapy, were also verified., Results: The selective replication of OncoViron mediated high expression of anticancer factors, specifically targeted a variety of solid tumors and significantly inhibited cancer cell proliferation. On a variety of implanted solid tumor models in immunodeficient mice, immunocompetent mice, and humanized mice, OncoViron showed great anticancer effects on its own and in combination with programmed death 1 (PD-1) antibody and chimeric antigen receptor (CAR) T cells. Pathological examination, single-cell sequencing, and spatial transcriptome analysis of animal implanted tumor specimens confirmed that OncoViron significantly altered the gene expression profile of infected cancer cells, not only recruiting a large number of lymphocytes, natural killer cells, and mononuclear macrophages into tumor microenvironment (TME) and activated immune cells, especially T cells but also inducing M1 polarization of macrophages and promoting the release of more immune cytokines, thereby remodeling the TME for coordinating PD-1 antibody or CAR T therapy., Conclusions: The chimeric OncoViron is a novel broad-spectrum anticancer product with multiple mechanisms of synergistic and potentiated immunotherapy, creating a good opportunity for combined immunotherapy against solid tumors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Much evidence suggested that cholesterol, eicosanoid and phospholipid metabolism plays crucial roles in inflammation, atherosclerosis, carcinogenesis, etc. Therefore, fast and accurate quantification of the metabolites in these metabolic pathways is necessary for discovering the molecular mechanisms and biomarkers of related diseases. In this assay, ultra-high performance liquid chromatography combined with triple quadrupole mass spectrometry platform (UPLC-QqQ-MS) based protocols were developed to simultaneously quantify a total of 104 key metabolites including 32 phospholipids (PLs), 44 eicosanoids (EAs), 28 oxysterols and bile acids (BAs), within 15 minutes. Validation results showed that this method is stable, sensitive and accurate for analyzing different matrix samples. Next, this method was used to characterize the metabolic phenotype of a CCl4-induced liver injury model. The results showed that polyunsaturated fatty acids (PUFA) and PUFA acyl-phospholipids (PFA-PLs) were down-regulated and the levels of saturated fatty acyl-phospholipids (SFA-PLs) and EAs were up-regulated in both the liver tissue and plasma of the CCl4-injury group. BAs were up-regulated in plasma, but down-regulated in the liver tissue of the CCl4-injury group. Immunohistochemistry assay demonstrated that the expression levels of cytosolic phospholipase A2 (cPLA2), phosphorylated cytosolic phospholipase A2 (p-cPLA2), secreted phospholipase A2-IIA (sPLA2-IIA) and lysophosphatidylcholine acyltransferase 1 (LPCAT1) were all up-regulated. According to our results, we drew a diagram of the CCl4-induced acute liver injury molecular mechanism. Moreover, we found that the area under the receiver operating characteristic curve (AUC) of 7α-hydroxycholesterol and 7β-hydroxycholesterol was 1.0, which indicates that the two metabolites have significant potential for the diagnosis of acute liver injury. The outstanding performance of this analytical method proves its further usefulness for mechanism studies and biomarker screening of related diseases.

The capture and separation properties of surface-functionalized activated carbons (AC-Rs, R= -COOH, -OH, -NH 2 , and -SO 3 H) for the methanol-acetone mixture were investigated for the first time by grand canonical Monte Carlo simulation (GCMC) and density functional theory (DFT). The effects of surface functional groups and structural characteristics of AC-Rs on the adsorption and separation behaviors of methanol and acetone were clarified. The surface functional group with strong electron-donating or electron-accepting capacity (i.e., -NH 2 , -OH, and -SO 3 H) was a crucial factor for the methanol-acetone capture and separation performance at the lower pressure range, and the accessible surface area was found to be another determinative factor. AC-NH 2 with the relatively large accessible surface area (4497 m 2 /g) exhibited an efficient capture performance for the single component (15.7 mol/kg for methanol and 6.7 mol/kg for acetone) and the highest methanol/acetone selectivity (∼23) at 0.02 kPa. At high pressures, the surface functionalization and available pore volume of AC-Rs played pivotal roles in the adsorptive separation process. This study provided mechanistic insights on how the surface functional groups affected the capture and separation properties of ACs, which would further provide a rational alternative strategy in the preparation and synthesis of ACs for the effective gas mixture separation.

Sulfur-doped activated carbons (SACs) with high sulfur content and large specific surface area were synthesized from polythiophene for acetone removal. The sulfur content of carbons (3.10-8.43 at.%) could be tunable by adjusting the activation temperature. The BET surface area and pore volume of the obtained samples were 916-2020 m 2  g -1 and 0.678-1.100 cm 3  g -1 , with a significant proportion of microporosity (up to 84% and 72% for BET surface area and pore volume, respectively). The resulting SACs show a superior acetone adsorption capacity (i.e., 716.4 mg g -1 at 15 °C and 705 mg g -1 at 25 °C for SAC700). In terms of the adsorption behavior of acetone on the activated carbons, compared to the Langmuir model, the Langmuir-Freundlich model showed better agreement with the adsorption amount. The results reveal that the surface area and micropore volume are the key factors for acetone adsorption, while the sulfur-doped functional groups, especially oxidized sulfur functional groups, can enhance the acetone adsorption capacity at a certain low pressure. Temperature programmed desorption (TPD) experiments were performed to get desorption activation energy of acetone on SAC samples, and the results ranged from 23.54 to 38.71 kJ mol -1 . The results of the molecular simulation show that the introduction of sulfur element can increase the binding energy between acetone molecule and carbon surface, and the tri-oxidized sulfur (sulfonic acid) functional group has the highest binding energy of - 0.4765 eV. Graphical abstract.

Background: Cell division cycle 20 (CDC20) is frequently overexpressed in malignant tumours and involved in the differentiation process of hematopoietic stem cells. However, the role of CDC20 in prostate cancer stem-like cells (CSCs) remains poorly understood., Methods: The expression of CDC20, CD44, β-catenin were examined in prostate cancer specimens by immunohistochemistry assay, the role of CDC20 on the stem-like properties of prostate CSCs was accessed by real-time quantitive PCR, spheroid formation, in vitro and in vivo limiting dilution assay., Finding: CDC20 was associated with malignant progression of prostate cancer, the patients with both high expression CDC20 and CD44 or β-catenin were associated with more aggressive clinicopathological features and poor prognosis. CDC20 was usually enriched in CD44 + prostate CSCs. Knockdown of CDC20 could inhibit the expression of stemness-related genes, self-renewal ability, chemo-resistance, invasion capability and tumorigenicity of CD44 + prostate CSCs. Mechanistically, CDC20 promoted degradation of Axin1, the core member of β-catenin destruction complex, sequentially reduced the phosphorylation of β-catenin, promoting the latter into the nucleus, thereby enhancing the self-renewal capacity of CD44 + prostate CSCs., Interpretation: Our results indicated that CDC20 maintains the self-renewal ability of CD44 + prostate CSCs by promoting nuclear translocation and trans-activation of β-catenin. In addition, CDC20 combined with CD44 or β-catenin can serve as an important indicator for prognosis of patients with prostate cancer., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer., Competing Interests: The authors declare no conflict of interest.

Survivin is an anti-apoptotic protein belonging to the inhibitor of apoptosis protein (IAP) family. It is involved in the regulation of important physiological and pathological processes in cells and functions to inhibit cell apoptosis and promote cell proliferation. Normally and terminally differentiated tissues are nearly negative for survivin. In contrast, survivin is highly expressed in most human tumor tissues, including hepatocellular carcinoma (HCC). The abnormal overexpression of survivin is closely related to the malignant biological behaviors of tumors. During the development and progression of HCC, the high level of survivin expression promotes cancer cell proliferation, inhibits cancer cell apoptosis, induces tumor stromal angiogenesis, reduces the sensitivity of cancer cells to radiotherapy and chemotherapy, and ultimately affects the prognosis of patients with HCC. Survivin expression is regulated by a large number of factors. The latest discovery indicated that the transcription factor octamer-binding transcription factor 4 (OCT4) enhances the expression of survivin though cyclin D1 (CCND1), which, in part, accounts for tumor cell proliferation, recurrence and metastasis. Survivin plays key roles in HCC, which renders it an ideal target for the treatment of HCC. The present article reviews the research progress on the relationship between survivin and HCC and on the HCC treatment strategies targeting survivin., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The patient-derived tumor xenograft (PDTX) models can reproduce a similar natural genetic background and similar biological behaviors to tumor cells in patients, which is conducive to the assessment of personalized cancer treatment. In this study, to verify the targeting and effectiveness of the therapeutic strategy using a Survivin promoter-regulated oncolytic adenovirus expressing Hsp70, the PDTX models of hepatocellular carcinoma (HCC) were established in nude mice and the cytokine-induced killer (CIK) cells were intravenously infused into mice to partially reconstruct the mouse immune function. The results demonstrated that, either the immune anti-tumor effect caused by CIK cell infusion or the oncolytic effect generated by oncolytic adenovirus replication was very limited. However, the synergistic tumor inhibitory effect was significantly enhanced after treatments with oncolytic adenovirus expressing Hsp70 combined with CIK cells. Oncolytic adenovirus mediated the specific expression of Hsp70 in cancer tissues allowed the CIK chemotaxis, and induce the infiltration of CD3+ T cells in tumor stroma, thereby exhibiting anti-tumor activity. The anti-tumor effect was more effective for the highly malignant tumor xenografts with highly Survivin expression. This strategy can synergistically activate multiple anti-tumor mechanisms and exert effective anti-tumor activities that have a significant inhibitory effect against the growth of HCC xenografts.

The XRCC1 Arg194Trp and Arg280His polymorphisms are likely to be implicated with the development of head and neck cancer. However, studies of association have been inconsistent. This meta-analysis of the available literature was performed to make a more precise estimation of the risk associated with these polymorphisms. A comprehensive literature search was conducted to identify all case-control studies of the XRCC1 Arg194Trp and Arg280His polymorphisms in head and neck cancer. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 20 eligible studies were selected for this meta-analysis, including 3,362 cases and 5,796 controls for the XRCC1 Arg194Trp polymorphism and 1,932 cases and 2,757 controls for the XRCC1 Arg280His polymorphism. Overall, no significant associations were found in all genetic models when the studies were pooled into the meta-analysis for the Arg194Trp and Arg280His polymorphisms. When stratified by ethnicity, significant associations were found for Arg194Trp polymorphism in CT vs CC (OR = 1.26, 95% CI = 1.05-1.52) and the recessive model (OR = 1.28, 95% CI = 1.07-1.53) in Asian population, and no significant associations were found in non-Asian population in all genetic models. This meta-analysis suggests that the XRCC1 Arg194Trp polymorphism is a risk factor for head and neck cancer in Asian populations.

The effect of purified Cry1Ca insecticidal protein on the growth of Chlorella pyrenoidosa was studied in a three-generation toxicity test. The C. pyrenoidosa medium with a density of 5.4 × 10(5) cells/mL was subcultured for three generations with added Cry1Ca at 0, 10, 100, and 1000 µg/L, and cell numbers were determined daily. To explore the distribution of Cry1Ca in C. pyrenoidosa and the culture medium, Cry1Ca was added at 1000 µg/L to algae with a high density of 4.8 × 10(6) cells/mL, and Cry1Ca content was determined daily in C. pyrenoidosa and the culture medium by enzyme-linked immunosorbent assays. Our results showed that the growth curves of C. pyrenoidosa exposed to 10, 100, and 1000 µg/L of Cry1Ca almost overlapped with that of the blank control, and there were no statistically significant differences among the four treatments from day 0 to day 7, regardless of generation. Moreover, the Cry1Ca content in the culture medium and in C. pyrenoidosa sharply decreased under exposure of 1000 µg/L Cry1Ca with high initial C. pyrenoidosa cell density. The above results demonstrate that Cry1Ca in water can be rapidly adsorbed and degraded by C. pyrenoidosa, but it has no suppressive or stimulative effect on algae growth., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Gene therapy is a promising adjuvant therapeutic strategy for cancer treatment. To overcome the limitations of current gene therapy, such as poor transfection efficiency of vectors, low levels of transgene expression and lack of tumor targeting, the Survivin promoter was used to regulate the selective replication of oncolytic adenovirus in tumor cells, and the heat shock protein 70 (Hsp70) gene was loaded as the anticancer transgene to generate an AdSurp-Hsp70 viral therapy system. The efficacy of this targeted immunotherapy was examined in gastric cancer. The experiments showed that the oncolytic adenovirus can selectively replicate in and lyse the Survivin-positive gastric cancer cells, without significant toxicity to normal cells. AdSurp-Hsp70 reduced viability of cancer cells and inhibited tumor growth of gastric cancer xenografts in immuno-deficient and immuno-reconstruction mouse models. AdSurp-Hsp70 produced dual antitumor effects due to viral replication and high Hsp70 expression. This therapeutic system used the Survivin promoter-regulated oncolytic adenovirus vector to mediate targeted expression of the Hsp70 gene and ensure safety and efficacy for subsequent gene therapy programs against a variety of cancers.

Gene therapy and antibody approaches are crucial auxiliary strategies for hepatocellular carcinoma (HCC) treatment. Previously, we established a survivin promoter-regulated oncolytic adenovirus that has inhibitory effect on HCC growth. The human sulfatase-1 (hSulf-1) gene can suppress the growth factor signaling pathways, then inhibit the proliferation of cancer cells and enhance cellular sensitivity to radiotherapy and chemotherapy. I(131)-metuximab (I(131)-mab) is a monoclonal anti-HCC antibody that conjugated to I(131) and specifically recognizes the HAb18G/CD147 antigen on HCC cells. To integrate the oncolytic adenovirus-based gene therapy and the I(131)-mab-based radioimmunotherapy, this study combined the CArG element of early growth response-l (Egr-l) gene with the survivin promoter to construct a radiation-inducible enhanced promoter, which was used to recombine a radiation-inducible oncolytic adenovirus as hSulf-1 gene vector. When I(131)-mab was incorporated into the treatment regimen, not only could the antibody produce radioimmunotherapeutic effect, but the I(131) radiation was able to further boost adenoviral proliferation. We demonstrated that the CArG-enhanced survivin promoter markedly improved the proliferative activity of the oncolytic adenovirus in HCC cells, thereby augmenting hSulf-1 expression and inducing cancer cell apoptosis. This novel strategy that involved multiple, synergistic mechanisms, including oncolytic therapy, gene therapy and radioimmunotherapy, was demonstrated to exert an excellent anti-cancer outcome, which will be a promising approach in HCC treatment., (Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Oncolytic adenoviruses are modified based on adenovirus serotype 5 (Ad5), which belongs to subgroup C and depends on Coxsackie-adenovirus receptor (CAR) to recognize target cells. However, expression of CAR is generally low or lost in certain tumors including hepatocellular carcinoma (HCC). By contrast, CD46 is highly expressed in various types of malignant tumor cells. Therefore, we constructed an adenovirus vector expressing the human RANTES/CCL5 gene regulated by oxygen-dependent degradation domain (ODD) and analyzed its antitumor effects in vitro and in vivo. The human RANTES/CCL5 gene was fused with ODD by PCR and the recombinant oncolytic adenovirus containing RANTES-ODD, SG511-CCL5-ODD, was constructed by the Gateway system, which infected cells by binding CD46. Viral replication experiments were performed to evaluate the selective replication ability of SG511-CCL5-ODD. RANTES expression was determined by ELISA. The chemotactic test was used to analyze the ability of the expressed RANTES to recruit NK92 cells. The antitumor effects of SG511-CCL5-ODD were examined in HCC xenografts in nude mice. A chimeric oncolytic adenovirus, SG511-CCL5-ODD, was constructed successfully. Cells infected with the recombinant virus were able to express RANTES selectively in different environments controlled by ODD and the expressed RANTES was able to recruit NK92 cells by its chemotactic effect in vitro and improve the anticancer immune response in HCC xenografts in nude mice. The chimeric adenovirus SG511-CCL5-ODD highly expressed the RANTES-ODD fusion gene in the hypoxia of HCC under the control of the ODD and effectively attracted NK92 cells and a high number of immunocytes. These factors had complementary advantages and, in combination, exerted enhanced antitumor efficacy.

The transcriptional factor Oct-4 and Survivin are the key regulatory factors in cancer cell proliferation and mitosis. A dual cancer-specific shRNA adenovirus vector, Ad5-Dual-shRNA, targeting Oct-4 and Survivin genes was constructed by molecular cloning and recombination. After cells were infected with virus, hepatocellular carcinoma cell line EHBH-H1 was used for detecting the expression of Oct-4 and Survivin proteins by Western blotting. The viral cytotoxic effect on cancer cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay in vitro, and the inhibition effect on tumor xenografts was observed in nude mice. The results showed that the expression of Oct-4 and Survivin in cancer cell line EHBH-H1 could be silenced markedly by Ad5-Dual-shRNA. In MTT and animal experiments, Ad5-Dual-shRNA also represented much stronger anti-tumor effect on tumor growth than Ad5-Surv-shRNA and Ad5-Oct4-shRNA. From this research we can draw a conclusion that the cancer-specific adenovirus vector expressing dual-shRNA targeting Oct-4 and Survivin genes may provide us a more effective, specific and convenient gene therapy method.

Background: Hepatitis B virus infection is a major problem in liver transplantation. In this study, we examined the potential efficay of a recombinant adenovirus expressing an antibody against the HBV preS2 antigen (Ab-H-HBV-S2) in preventing HBV recurrent infection after liver transplantation., Methods: A gene for humanized antibody against the HBV preS2 antigen was cloned into pDC315, a type 5 adenoviral shuttle plasmid. Recombinant virus was obtained by homologous recombination in the 293 packaging cells. The virus containing the Ab-H-HBV-S2 gene was transduced into the rat liver graft during cold preservation. The recombinant virus produced antibody and showed protective effects on human hepatocytes from hepatitis B virus infection in vitro., Results: The recombinant virus titer determined by TCID50 analysis was 5.1x10(10) PFU/mL. The concentration of preS2 antibody in BALB/C nude mice was 16.7 +/- 10.5 microg/mL on day 3,30.9 +/- 13.6 pg/mL on day 7, and lasted for 5 weeks after the injection. At a concentration of 0.5 microg/mL or above, the preS2 antibody protected cultured human hepatocytes from hepatitis B virus., Conclusions: Adenovirus-mediated gene transduction of anti-preS2 antibody in the transplanted liver may be a useful approach to prevent hepatitis B infection after liver transplantation.

The regulation of a target gene expression is very important in gene therapy. However, constitutive or inappropriate expression of the genes with traditional expression system may interfere with the effect of the gene therapy, even may lead to lethal side effect. We constructed an RU486 inducible eukaryotic vector carrying DsRed protein and evaluated its regulatable effect in vitro. The single vector named PDC-RURED was constructed with molecular biological methods, which contained DsRed gene, promoter and RU486-inducible system. To minimize any potential interference, we spaced the two transcriptional elements with a 1.6 kb insulator. The vector was identified by different enzyme restrictions, sequencing analysis and PCR assay. We demonstrated the regulatable expression of this vector after transfection in HEK293 cells by fluorescence microscopy and flow cytometry. In the absence of RU486, no significant DsRed protein activation was observed, whereas in the presence of RU486 up to 40 fold activation of the DsRed protein was observed in cultured cells. The data show that the novel eukaryotic expression plasmid vector can be used to regulate the expression level of genes of interest in appropriate time under the control of RU486. This inducible expression vector provides a powerful tool for the research of gene regulation and gene therapy.

Objective: To study the status of CDKN2/p16 gene point mutation in lung cancer., Methods: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing were used to detect the point mutation of CDKN2/p16 gene exon 2 in 89 cases of lung cancer., Results: In 69 cases of the lung cancer without deletion of CDKN2/p16 gene exon 2, 16 cases were found to have suspicious abnormality of CDKN2/p16 gene exon 2 by PCR-SSCP, and in these 16 cases, 9 were found to harbor point mutations of CDKN2/p16 gene exon 2 by automated sequencing analysis., Conclusion: The point mutation is one of the mechanisms for CDKN2/p16 gene inactivation, but it is not the chief mechanism. The inactivation of CDKN2/p16 gene aroused by point mutation plays a role to some extent in the genesis and progression of lung cancer.