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The autonomic nerve system (ANS) innervates organs and tissues throughout the body and maintains functional balance among various systems. Further investigations have shown that excessive activation of ANS not only causes disruption of homeostasis, but also may promote tumor formation. In addition, the dynamic interaction between nerve and tumor cells in the tumor microenvironment also regulate tumor progression. On the one hand, nerves are passively invaded by tumor cells, that is, perineural invasion (PNI). On the other hand, compared with normal tissues, tumor tissues are subject to more abundant innervation, and nerves can influence tumor progression through regulating tumor proliferation, metastasis and drug resistance. A large number of studies have shown that nerve-tumor crosstalk, including PNI and innervation, is closely related to the prognosis of patients, and contributes to the formation of cancer pain, which significantly deteriorates the quality of life for patients. These findings suggest that nerve-tumor crosstalk represents a potential target for anti-tumor therapies and the management of cancer pain in the future. In this review, we systematically describe the mechanism by which nerve-tumor crosstalk regulates tumorigenesis and progression., 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, Aspergillus sydowii FJH-1 isolated from soil was verified to be a novel triphenyl phosphate (TPhP) degrader. Biodegradation efficiency of TPhP by Aspergillus sydowii FJH-1 exceeded 90% within 6 days under the optimal conditions (pH 4-9, 30 ℃, initial concentration less than 20 mg/L). Proteomics analysis uncovered the proteins perhaps involved in hydrolysis, hydroxylation, methylation and sulfonation of TPhP and the primary intracellular adaptive responses of Aspergillus sydowii FJH-1 to TPhP stress. The expression of carboxylic ester hydrolase along with several thioredoxin- and glutathione-dependent oxidoreductases were induced to withstand the toxicity of TPhP. The presence of TPhP also caused obvious upregulation of proteins concerned with glycolysis, pentose phosphate pathway and tricarboxylic acid cycle. Data from toxicological tests confirmed that the cytotoxicity and phytotoxicity of TPhP was effectively decreased after treatment with Aspergillus sydowii FJH-1. Additionally, bioaugmentation with Aspergillus sydowii FJH-1 was available for promoting TPhP removal in real water and water-sediment system. Collectively, the present study offered a deeper insight into the biodegradation mechanism and pathway of TPhP by a newly screened fungal strain Aspergillus sydowii FJH-1 and validated the feasibility of applying this novel degrader in the bioremediation of TPhP-polluted matrices., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel kind of phosphonate functionalized polythiophene microsphere was designed and fabricated via Friedel-Crafts reaction. Diethyl (thiophen-2-ylmethyl) phosphonate (DTYP) and thiophene were co-polymerized by Fe (III) catalysis, without any surfactant, stabilizer and initiator. Functional phosphonate group was directly introduced into the microsphere without redundant modification steps. The adsorption amount of the as-synthesized microsphere, Ti-poly(Th-co-DTYP), was as high as 66.7 mg/g, which was higher than that of commercial Ti 4+ -IMAC microsphere (49.7 mg/g). The microsphere was explored on the specific capture of phosphopeptides from either tryptic digests of milk or HeLa cell protein. As a result, 88 of unique phosphopeptides mapping to 21 phosphoproteins were identified from 150 μg of milk tryptic digest after enrichment, and a total of 2534 unique phosphopeptides mapping to 1087 phosphoproteins was identified from HeLa cell. It is expected that such a robust and facile approach will be explored in other functional microspheres to be commercialized in the future., 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 © 2021 Elsevier B.V. All rights reserved.)

Microplastics (< 5 mm diameter) are one of most important environmental pollutants and contaminants worldwide. However, how microplastics affect liver immune microenvironment in not well understood. Microplastics (0.5 µm) were administered orally to C57BL/6J mice for 4 consecutive weeks at the rate of 0.5 mg/day. Non-parenchymal cells were isolated from of the mice through fractionation of fresh hepatic tissues. The immune landscape for four cell populations of B cells, T cells, NK cells and macrophages in the liver tissues was then evaluated using flow cytometry. The secretion level of inflammatory cytokines and associated signaling pathway were investigated using quantitative real-time polymerase chain reaction and western blot. Oral ingestion of microplastics increases liver weight, general liver index as well as expression of serum, liver function-related indicators. Microplastics also increased the infiltration of natural killer cells and macrophages to non-parenchymal liver cells, but reduced that of B cells to the same tissues. However, microplastics had no effect on the infiltration of T cell to non-parenchymal liver cells. Ingestion of MPs also up-regulated the expression of IFN-γ, TNF-α, IL-1β, IL-6 and IL-33 mRNA, but down-regulated that of IL-4, IL-5, IL-10, IL-18 and TGF-β1. Overall, the aforementioned processes were regulated via the NF-κB pathway in the hepatic non-parenchymal cells. Microplastics disrupts inflammatory process in liver tissues via the NF-κB signaling pathway. These findings provide a strong foundation on immune processes in hepatic tissues following prolonged ingestion of microplastics., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

So far, no information about the biodegradability of TPhP by white rot fungi has previously been made available, herein, Pycnoporus sanguineus was used as the representative to investigate the potential of white rot fungi in TPhP bioremediation. The results suggested that the biodegradation efficiency of 5 mg/L TPhP by P. sanguineus was 62.84% when pH was adjusted to 6 and initial glucose concentration was 5 g/L. Seven biodegradation products were identified, indicating that TPhP was biotransformed through oxidative cleavage, hydroxylation and methylation. The proteomic analysis revealed that cytochrome P450s, aromatic compound dioxygenase, oxidizing species-generating enzymes, methyltransferases and MFS general substrate transporters might occupy important roles in TPhP biotransformation. Carboxylesterase and glutathione S-transferase were induced to resist TPhP stress. The biotreatment by P. sanguineus contributed to a remarkable decrease of TPhP biotoxicity. Bioaugmentation with P. sanguineus could efficiently promote TPhP biodegradation in the water-sediment system due to the cooperation between P. sanguineus and some putative indigenous degraders, including Sphingobium, Burkholderia, Mycobacterium and Methylobacterium. Overall, this study provided the first insights into the degradation pathway, mechanism and security risk assessment of TPhP biodegradation by P. sanguineus and verified the feasibility of utilizing this fungus for TPhP bioremediation applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this work, to check the effect of the transposition of the rings in typical patterns, a series of pyrazoline derivatives 3a-3t bearing the characteristic 3,4,5-trimethoxy phenyl and thiophene moieties were synthesized and evaluated as tubulin polymerization inhibitors. Basically, as the concise output of our design, a majority of the synthesized compounds showed potency in inhibiting the tubulin polymerization. The top hit, 3q, exhibited potent anti-proliferation activity on cancer cell lines. It was comparable on tubulin-polymerization inhibition with the positive control Colchicine but lower toxic. The VEGFR2 inhibitory potency was introduced occasionally. The flow cytometry assay confirmed the apoptotic procedure and the confocal imaging revealed the tubulin-microtubule dynamics pattern. The anti-cancer mechanism of 3q was similar to Colchicine but not exactly the same on forming multi-polar spindles. The docking simulation visualized the possible binding patterns of 3q into tubulin and VEGFR2, respectively. The results inferred that further investigations on the transposition of the rings might lead to the improvement of tubulin polymerization inhibitory activity and the steadily introduction of the VEGFR2 inhibition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The pretreatment of complicated biological samples to eliminate the interference of nonglycopeptides and improve the efficiency of glycopeptides detection is crucial in glycoproteomics research. Hydrophilic interaction chromatography (HILIC) has been adopted for enrichment of glycosylated peptides following identification with mass spectrometry, but it is still urgent to develop novel hydrophilic materials to save cost and improve enrichment efficiency. Scientists are pursuing to fabricate freestanding intelligent artificial materials. One promising approach is to use biomimic material. In our case, "one-pot" strategy was developed to prepare bioinspired nano-core-shell silica microspheres (CSSMs), employing tetrapropylorthosilicate as the silicon source and phenolic resin as the soft template. The pore structure of the obtained microspheres diverged from the center to the outside with diameter ranged from 150 to 340 nm, and shell layer ranged from 25 to 83 nm by adjusting the preparation parameters. Some of them showed dandelion-like morphology. After hydrophilic modification, these CSSMs exhibited great hydrophilicity and could be used as sorbents for enriching N-glycopeptides from complicated biological samples in HILIC. Up to 594 unique N-glycopeptides and 367 N-glycosylation sites from 182 N-glycoproteins were unambiguously identified from 2 μL of human serum, which was superior to the enrichment performance of many HILIC materials in reported papers, demonstrating great potential advantages in proteomic application., 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 © 2021 Elsevier B.V. All rights reserved.)

Background: It has been shown that circulating tumor cells in peripheral blood can be used to predict survival in patients with breast, prostate and other epithelial tumors. In the present study, we performed a meta-analysis to evaluate the prognostic role of circulating tumor cells (CTCs) in patients with pancreatic cancer., Methods: A systematic literature search of the databases was conducted from the inception to Jul 20, 2019. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated under a fixed or random effect model., Results: A total of 19 studies with 1320 confirmed individuals were included. Our meta-analysis showed that patients in the CTC-positive group had a significantly shorter overall survival (OS) (RR = 0.47, 95%CI = 0.33-0.61, P < 0.001) and progression-free survival (PFS) (P = 0.003) than CTC-negative patients. Moreover, subgroup analysis by ethnicity indicated that CTC-positive patients had a significantly shorter OS in both Asian and Western populations. Further subgroup analysis by detection methods, treatments, and Tumor Node Metastasis (TNM) stages also indicated that CTC-positive patients were associated with significant decreases in both OS and PFS  in most subgroups., Conclusion: Our meta-analysis indicates that CTC-positive patients have a worse OS and PFS than CTC-negative patients, which suggests that CTCs may act as predictive biomarkers for pancreatic cancer patients before treatment., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to facilely develop biomimetic amino modified mesoporous silica xerogel (AMSX) and study how AMSX regulated loading and in vitro sustained delivery of carboxyl-containing drug levorotary ofloxacin (LOFL). Characteristics of AMSX, including morphology, porous structure, elements and crystalline state were investigated and pharmaceutical performance of AMSX for the delivery of LOFL was studied. The result showed that AMSX was accumulational spherical nanoparticles with mesoporous structure. Hydrogen bonding force was formed between carboxylic groups of LOFL and amino groups grafted on the surface of AMSX. Furthermore, a three-level three-factorial Box-Behnken experimental design was applied to optimize the amount of major agent for synthesizing AMSX with expected drug loading capacity and also to figure out how AMSX regulated in vitro delivery of LOFL. It is believed that the present work will provide novel insights for designing mesoporous silica as drug carrier and favored the development of sustained release system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Several studies have noted that the discriminatory ability and stratification performance of the AJCC 8th edition staging system is not entirely satisfactory. We aimed to improve the American Joint Committee on Cancer (AJCC) 8th edition staging system for intrahepatic cholangiocarcinoma (ICC)., Methods: A multicentric database from three Chinese mainland centers (n = 1601 patients) was used to modify the 8th edition staging system. This modified TNM (mTNM) staging system was then validated using the SEER database (n = 761 patients). A new TNM staging system, by incorporating serum tumor markers (TNMIS) into the mTNM staging system was then proposed., Results: The 8th edition staging system did not provide an adequate stratification of prognosis in the Chinese multicentric cohort. The mTNM staging system offered a better discriminatory capacity in the multicentric cohort than the original 8th edition. External validation in the SEER cohort showed that the mTNM staging system also had a good stratification performance. After further incorporating a serum marker stage into the mTNM staging, the TNMIS staging system was able to stratify prognosis even better., Conclusion: The proposed mTNM staging system resulted in better stratification performance and the TNMIS staging system provided even more accurate prognostic classification than the conventional TNM system., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Spontaneous tumor rupture (STR) of hepatocellular carcinoma (HCC) is a life-threatening condition. This study investigates the influences of STR on the observed survival and conditional survival of patients received hepatectomy., Methods: A retrospective cohort of patients who underwent hepatectomy from 2009 to 2013 was divided into tumor rupture group and non-rupture group. Propensity score matching (PSM) was used for comparison of the observed survival and conditional survival probabilities between these two groups., Results: 89 pairs of patients who had comparable background and tumor characteristics were created using PSM analysis. There was significant association between STR and increased risk of OS no matter when before or after PSM (p < 0.01). STR was significantly associated with increased risks of PFS before, while not after PSM. Multivariate Cox regression analyses demonstrated that STR was an independent risk factor associated with OS. There were significant differences in two groups for conditional probabilities of OS and PFS for an additional 6 months and 1 year before PSM, while not after PSM., Conclusions: This study identified STR but not PFS as an independent risk factor influencing OS, in patients with HCC following hepatectomy. In selected patients with STRHCC, hepatectomy should be performed with acceptable outcomes., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The primary purpose of this research was to explore the potential chiral recognition functions induced by two kinds of novel concealed body mesoporous silica nanoparticles (Cb-D-MSN and Cb-L-MSN) with the entrapment of indometacin (IMC). The as-synthesized Cb-D-MSN and Cb-L-MSN were successfully fabricated through grafting molecular functional groups. The TEM result showed that Cb-D-MSN and Cb-L-MSN were regular spheres with concealed pore channels. Nitrogen adsorption/desorption analysis confirmed mesoporous structure of Cb-D-MSN and Cb-L-MSN. In vitro drug release study indicated that both Cb-D-MSN and Cb-L-MSN significantly improved IMC dissolution compared with Naked-MSN (N-MSN). Interestingly, the results of anti-inflammation pharmacodynamics and pharmacokinetics indicated that Cb-D-MSN and Cb-L-MSN exerted different chiral recognition functions, which Cb-D-MSN can deliver more IMC evidenced by molecular simulations. It is expected that the herein favorable carriers with unique advantages in triggering chiral biological environment can be promising for constructing drug delivery system., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Intrahepatic recurrence is a significant problem for patients who have undergone a hepatic resection for hepatocellular carcinoma (HCC). The objective of the present study was to identify risk factors and evaluate the management of early and late recurrence of solitary HCC after curative resection., Methods: Included in this study were 816 patients with solitary HCC who underwent a curative partial hepatectomy. Intrahepatic recurrence in these patients was followed up retrospectively. Prognosis and therapy for the recurrence were investigated and analysed., Results: Early and late intrahepatic recurrence occurred in 423 patients and 199 patients, respectively. Multivariate analysis showed that a tumour diameter >5 cm, the absence of a tumour capsule and the presence of microvascular invasion were correlated with early recurrence, whereas cirrhosis and alpha-fetal protein >400 μg/l were independent risk factors contributing to late recurrence. The 5-year survival of HCC patients with early recurrence was significantly lower than that of patients with late recurrence. Further curative treatment for intrahepatic recurrence offered a 5-year overall survival of 56.0%, which was better than alternative management., Conclusion: Early and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence., (© 2014 International Hepato-Pancreato-Biliary Association.)