Perineural Invasion is a Better Prognostic Indicator than Lymphovascular Invasion and a Potential Adjuvant Therapy Indicator for pN0M0 Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) at pN0M0 can be more locally aggressive and disseminated than those with lymph node and distant metastasis. Perineural invasion (PNI) is reported as a poor prognostic factor in cancer and is thought to be related to regional tumor spread and metastasis. However, its clinicopathological role and meaning for treatment in pN0M0 ESCC are unknown. PATIENTS AND METHODS: We applied scoring methods of PNI and lymphatic and vascular invasion (LI, VI) based on immunohistochemistry staining on tumor tissues of pN0M0 ESCC patients. ROC analyses, Kaplan-Meier analyses, Cox regression, and χ2 test were performed for survival analysis, comparison of PNI with LI and VI, and exploration of the relevance between PNI and other clinicopathological features. RESULTS: Presence of PNI was significantly associated with poor survival in pN0M0 patients, whereas LI and VI were not predictive of outcome (P > 0.05). Neural invasion index (NII), defined as the ratio of the number of tumor-invaded nerves to the total number of nerves per tumor microsection, was the most consistent measure of PNI (P = 0.006, HR = 6.892, 1.731-27.428). Postoperative radiotherapy significantly improved survival in high-NII patients (P = 0.035, HR = 0.390, 0.163-0.936). CONCLUSIONS: PNI is an important risk factor for the outcome of pN0M0 ESCC patients. NII can be used for risk assessment and to tailor adjuvant radiotherapy in this population.

Genome sequence of the potato pathogenic fungus Alternaria solani HWC-168 reveals clues for its conidiation and virulence.

BACKGROUND: Alternaria solani is a known air-born deuteromycete fungus with a polycyclic life cycle and is the causal agent of early blight that causes significant yield losses of potato worldwide. However, the molecular mechanisms underlying the conidiation and pathogenicity remain largely unknown. RESULTS: We produced a high-quality genome assembly of A. solani HWC-168 that was isolated from a major potato-producing region of Northern China, which facilitated a comprehensive gene annotation, the accurate prediction of genes encoding secreted proteins and identification of conidiation-related genes. The assembled genome of A. solani HWC-168 has a genome size 32.8 Mb and encodes 10,358 predicted genes that are highly similar with related Alternaria species including Alternaria arborescens and Alternaria brassicicola. We identified conidiation-related genes in the genome of A. solani HWC-168 by searching for sporulation-related homologues identified from Aspergillus nidulans. A total of 975 secreted protein-encoding genes, which might act as virulence factors, were identified in the genome of A. solani HWC-168. The predicted secretome of A. solani HWC-168 possesses 261 carbohydrate-active enzymes (CAZy), 119 proteins containing RxLx[EDQ] motif and 27 secreted proteins unique to A. solani. CONCLUSIONS: Our findings will facilitate the identification of conidiation- and virulence-related genes in the genome of A. solani. This will permit new insights into understanding the molecular mechanisms underlying the A. solani-potato pathosystem and will add value to the global fungal genome database.

Evaluation of the influence of salt processing on pharmacokinetics of psoralen and isopsoralen in Psoralea corylifolia L.

A sensitive, specific and rapid ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed to investigate pharmacokinetic properties of psoralen and isopsoralen, two compounds isolated from raw/salt-processed fruit of Psoralea corylifolia L. UHPLC-MS/MS was used with positive ion electrospray. The mobile phase was composed of acetonitrile and 0.1% formic acid aqueous solution and a gradient elution program at flow rate of 0.3 mL/min was applied. Multiple reaction monitoring mode was used for the quantification of psoralen, isopsoralen ([M + H](+) m/z 187.0 → m/z 131.0) and scoparone (m/z 207.0 → m/z 151.1). Scoparone served as an internal standard. The method was fully validated for its sensitivity, selectivity, stability, matrix effect and extraction recovery. The obtained results showed that salt-processed Buguzhi significantly promoted the absorption of psoralen and isopsoralen, and increased the bioavailability of these compounds.

[Anti-tumor effect of brucine-loaded chitosan nanoparticles in vitro].

We designed two novel polymer materials N-glycyrrhetinic acid-polyethylene glycol-chitosan derivatives (NGPC) and N-quaternary ammonium-chitosan derivatives (NQC). We prepared three kinds of drug loaded chitosan nanoparticles (brucine/NGPC-NPs, brucine/NQC-NPs, brucine/MNPs) by ionic crosslinking method with brucine as a model drug and chitosan nanoparticles（brucine/NGPC-NPs, brucine/NQC-NPs） as the reference formulation. Using high content analysis, flow cytometry, immunofluorescence, transmission electron microscopy and other advanced technology, we tested the effect of 20 µg·mL(-1) concentration of brucine solution and brucine/ chitosan nanoparticles（brucine/CTS-NPs） in hepatocarcinoma (HEpG2) cells and evaluated the apoptosis induced by the treatment. The results suggested that brucine-CTS/NPs had a strongest activity in killing tumor cells, and increased the total cell apoptosis rate with a significant formation of "crescent-shaped" body, swelling mitochondria, mitochondria cristae missing, decreased mitochondrial membrane potential and release of cytochrome C. The activity was enhanced by multifunctional nanocomposite particles that increased the cumulative amount of drug in the mitochondria for the anti-tumor effect.

Seroprevalence of IgM and IgG Antibodies against SARS-CoV-2 in Asymptomatic People in Wuhan: Data from a General Hospital Near South China Seafood Wholesale Market during March to April in 2020.

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test, t-test, and Mann-Whitney test were used to compare the standardized seroprevalence of IgG and IgM for age and gender between different groups. The results indicated the standardized seroprevalence of IgG and IgM showed a downward trend and was significantly higher among females than males. Besides, different geographic areas and workplaces had different seroprevalence of IgG among asymptomatic people, and the number of abnormalities in CT imaging were higher in IgG antibody-positive cases than IgG-negative cases. We hope these findings can provide references for herd immunity investigation and provide basis for vaccine development.

A redox modulated fluorescence nanoplatform for the detection of alkaline phosphatase activity with fluorescent polydopamine nanoparticles.

Herein, we simply synthesized intrinsic fluorescent polydopamine nanoparticles (PDA NPs) in sodium hydroxide solution (NaOH, pH 11), and constructed a new fluorescence nanoplatform for the detection of alkaline phosphatase (ALP) using PDA NPs as an effective signal reporter. The nanoplatform was constructed by the combination of enzymatic hydrolysis of ALP to the substrate l-ascorbic acid-2-phosphate (AA2P) and the chemical redox reaction between l-ascorbic acid (AA) and mercury ion (Hg2+). The fluorescence of PDA NPs could be effectively quenched by Hg2+ through the coordination effect between Hg2+ and the functional groups on the surface of PDA NPs. However, the quenching effect was greatly inhibited by the addition of AA into the solution. Based on this point, the activity of ALP could be monitored by hydrolysis of the substrate AA2P to AA and the fluorescence output of PDA NPs. The nanoplatform exhibited high sensitivity and desirable selectivity for ALP detection. With a wide linear range of 0 to 18 U L-1, a detection limit of 0.4 U L-1 was achieved using the developed nanosensor. The proposed method could not only be used to screen the inhibitor of ALP but also be used to detect ALP activity in human serum samples successfully. Moreover, the strategy can easily be expanded to determining other kinds of enzymes participating in AA-generation reactions.

Inhibition of pre-B cell colony-enhancing factor attenuates inflammation induced by hyperoxia in EA.hy926 cells.

The aim of this study was to investigate the role of pre-B cell colony-enhancing factor (PBEF) in the pathogenesis of bronchopulmonary dysplasia (BPD) using an established cell model of BPD. For this purpose, EA.hy926 cell cultures were divided into 4 groups as follows: the air group as the blank control, the hyperoxia group, the hyperoxia plus PBEF siRNA group and the hyperoxia plus scramble siRNA group. Cell viability and the generation of reactive oxygen species (ROS) were determined using respective kits. Moreover, the protein and mRNA expression levels of PBEF, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) were also detected by corresponding methods. Compared with the hyperoxia group, the ROS levels in the hyperoxia plus PBEF siRNA group were significantly reduced (P<0.01). The silencing of PBEF increased cell viability compared with the hyperoxia group. The protein and mRNA expression levels of PBEF, IL-8 and TNF-α were all decreased in the hyperoxia plus PBEF siRNA group compared with the hyperoxia group (P<0.01). Our study thus demonstrates that the inhibition of PBEF attenuates oxidative stress and inflammation induced by hyperoxia in EA.hy926 cells, suggesting that PBEF may be a potential diagnostic and therapeutic target, which may be used for the development of novel treatment strategies for BPD.

Mitochondria-targeted drug delivery system for cancer treatment.

Mitochondria are one type of the major organelles in the cell, participating in a variety of important physiological and biochemical processes, such as tricarboxylic acid cycle, fatty acid metabolism and oxidative phosphorylation. Meanwhile, it also happens to be the key regulator of apoptosis by triggering the complex cell-death processes through a variety of mechanisms. Since it plays a pivotal role in cell-death, a mitochondria-targeted treatment strategy could be promising for cancer therapy. In this comprehensive review, we focused on the mechanisms of mitochondrial targeting and a variety of strategies to realize the purpose of mitochondrial targeting, including that based on the use of lipophilic cations, and mitochondrial targeting signal peptides (MTS) as well as cell-penetrating peptides (CPPs). Then on this basis we present some several developed strategies for multifunctional mitochondria-targeted agents so as to achieve the good anti-cancer therapeutic effects.