Prognostic value of the neutrophil-to-lymphocyte ratio and C-reactive-protein-to-prealbumin ratio in hospitalized older patients with coronavirus disease 2019.

The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-prealbumin ratio (CPAR) are novel markers of inflammation. The CPAR is an indicator of inflammation and malnutrition. We evaluated NLR and CPAR in combination as indicators of disease severity and prognosis in hospitalized older patients with coronavirus disease 2019 (COVID-19). A total of 222 hospitalized patients with COVID-19 (aged > 60 years) were divided into non-severe and severe groups. The severe group was subdivided into the surviving and deceased subgroups. We retrospectively assessed the predictive power of NLR and CPAR in combination (NLR + CPAR) to determine the prognosis of hospitalized older patients with COVID-19. The NLR and CPAR were significantly higher in the severe group than in the non-severe group (P < .001). Furthermore, the NLR and CPAR were higher in the deceased subgroup than in the surviving subgroup (P < .001). Pearson correlation analysis showed a highly significant positive correlation between NLR and CPAR (P < .001, r = 0.530). NLR + CPAR showed an area under the curve of 0.827 and sensitivity of 83.9% in the severe group; the area under the curve was larger (0.925) and sensitivity was higher (87.1%) in the deceased subgroup. The receiver operating characteristic curve of NLR + CPAR was significantly different from the receiver operating characteristic curves of either biomarker alone (P < .001). Kaplan-Meier analysis showed that patients in the severe group with elevated NLR + CPAR had a significantly lower 90-day survival rate than patients who lacked this finding (odds ratio 7.87, P < .001). NLR + CPAR may enable early diagnosis and assessment of disease severity in hospitalized older patients with COVID-19. This may also enable the identification of high-risk older patients with COVID-19 at the time of admission.

Conserved DNA sequence analysis reveals the phylogeography and evolutionary events of Akebia trifoliata in the region across the eastern edge of the Tibetan Plateau and subtropical China.

BACKGROUND: The eastern edge of the Qinghai‒Tibet Plateau (QTP) and subtropical China have various regions where plant species originate and thrive, but these regions have been the focus of very few integrative studies. Here, we elucidated the phylogeographic structure of a continuous and widespread Akebia trifoliata population across these two regions. RESULTS: Sixty-one populations consisting of 391 genotypes were examined to assess population diversity and structure via network distribution analysis, maximum likelihood phylogenetic tree reconstruction, divergence time estimation, demographic history inference, and ancestral area reconstruction of both conserved internal transcribed spacer (ITS) and chloroplast (rps16) DNA sequences. The results showed that the ITS region was more variable than the rps16 region and could be suitable for studying intraspecific phylogeography. The A. trifoliata population displayed high genetic diversity, genetic differentiation and obvious phylogeographical structure, possibly originating on the eastern QTP, expanding during the last glacial-interglacial cycle, diverging in the early Pleistocene and middle Pleistocene, and extensively migrating thereafter. The migration route from west to east along rivers could be largely responsible for the long-distance dispersal of this species, while three main refuges (Qinba Mountains, Nanling Mountains and Yunnan-Guizhou Plateau) with multiple ice shelters facilitated its wide distribution. CONCLUSIONS: Our results suggested that the from west to east long migration accompanying with the minor short reciprocal migration in the south-north direction, and the three main refuges (the Qinba Mountains, Nanling Mountains and Yunnan-Guizhou Plateau) contributed to the extant geographical distribution of A. trifoliata. In addition, this finding also strongly reduced the discrepancy between glacial contraction and postglacial expansion and the in situ survival hypothesis by simultaneously considering the existence of many similar climate-related ecological niches and migration influences.

Complete chloroplast genome of Artabotrys hexapetalus (L.f.) Bhandari 1965 (Annonaceae).

Artabotrys hexapetalus (L.f.) Bhandari, 1965, an evergreen climbing shrub of significant value, is prominent in Chinese history and culture. The whole-gene sequencing of its chloroplast genome using Illumina pair-end sequencing data is conducted during this research. The complete chloroplast genome was determined to be 178,457 bp in size, separated by a large single copy (LSC) and a small single copy (SSC) region of 90,803 and 3,066 bp, respectively. A total of 134 genes were identified, including 90 protein-coding genes, 36 tRNA, and eight rRNA genes. Phylogenetic analysis revealed a close relationship between A. hexapetalus and Artabotrys pilosus, forming a sister branch with 100% support. The study suggests that the chloroplast genome of A. hexapetalus provides valuable insights into its evolutionary history and will contribute to the conservation efforts of this species.

Light and voltage dual-modulated volatile resistive switching in single ZnO nanowires.

A single ZnO nanowire device with volatile resistive switching behavior has been prepared. Different from traditional resistive switching devices, such ZnO nanowire devices do not exhibit resistive switching behaviors under a single bias voltage, and appear resistive switching behavior under the combined action of light stimuli and bias voltage. Through the demonstration of the time-dependent hysteresis curve and atmosphere-dependent hysteresis loop of the resistive switching devices, it is believed that under the resistive switching process, ultraviolet illumination can increase the carrier concentration and modulate the barrier depletion structure, and external bias voltage can ionize the surface state. They work together to modulate the switching process of the devices. Such light stimuli and bias voltage dual-modulated resistive switching device enables optical control and may thus be considered for sensory applications or optically tunable memories.

The functions of triple gene block proteins and coat protein of apple stem pitting virus in viral cell-to-cell movement.

Apple stem pitting virus is a species in the genus Foveavirus in the family Betaflexiviridae. Apple stem pitting virus (ASPV) commonly infects apple and pear plants grown worldwide. In this study, by integrating bimolecular fluorescence complementation, split-ubiquitin-based membrane yeast two-hybrid, and Agrobacterium-mediated expression assays, the interaction relationships and the subcellular locations of ASPV proteins TGBp1-3 and CP in Nicotiana benthamiana leaf cells were determined. Proteins CP, TGBp1, TGBp2, and TGBp3 were self-interactable, and TGBp2 played a role in the formation of perinuclear viroplasm and enhanced the colocalization of TGBp3 with CP and TGBp1. We found that the plant microfilament and endoplasmic reticulum structures were involved in the production of TGBp3 and TGBp2 vesicles, and their disruption decreased the virus accumulation level in the systemic leaves. The TGBp3 motile vesicles functioned in delivering the viral ribonucleoprotein complexes to the plasma membrane. Two cysteine residues at sites 35 and 49 of the TGBp3 sorting signal were necessary for the diffusion of TGBp3-marked vesicles. Furthermore, our results revealed that TGBp1, TGBp2, and CP could increase plasmodesmal permeability and move to the adjacent cells. This study demonstrates an interaction network and a subcellular location map of four ASPV proteins and for the first time provides insight into the functions of these proteins in the movement of a foveavirus.

Global Analysis of the WOX Transcription Factor Family in Akebia trifoliata.

Akebia trifoliata is an economically important, self-incompatible fruit tree in the Lardizabalaceae family. Asexual propagation is the main strategy used to maintain excellent agronomic traits. However, the generation of adventitious roots during asexual propagation is very difficult. To study the important role of the WUSCHEL-related homeobox (WOX) transcription factor in adventitious root growth and development, we characterized this transcription factor family in the whole genome of A. trifoliata. A total of 10 AktWOXs were identified, with the following characteristics: length (657~11,328 bp), exon number (2~5), isoelectric point (5.65~9.03), amino acid number (176~361 AA) and molecular weight (20.500~40.173 kDa), and their corresponding expression sequence could also be detectable in the public transcriptomic data for A. trifoliata fruit. A total of 10 AktWOXs were classified into modern (6), intermediate (2) and ancient clades (2) and all AktWOXs had undergone strong purifying selection during evolution. The expression profile of AktWOXs during A. trifoliata adventitious root formation indicated that AktWOXs play an important role in the regulation of adventitious root development. Overall, this is the first study to identify and characterize the WOX family in A. trifoliata and will be helpful for further research on A. trifoliata adventitious root formation.

Association of the TGFß gene family with microenvironmental features of gastric cancer and prediction of response to immunotherapy.

In the complex tumor microenvironment, TGFß is a pleiotropic cytokine involved in regulating cellular processes such as cancer cell proliferation, apoptosis and metastasis. TGFß defines three subtypes (TGFß1, TGFß2, and TGFß3), of which TGFß is highly expressed in many cancers, especially those showing high dissemination potential. In addition, increased expression of TGFß in multiple cancers is usually positively correlated with epithelial mesenchymal transition (EMT) and coordinated with the expression of genes driving EMT-related genes. TGFß signaling in the tumor microenvironment inhibits the antitumor function of multiple immune cell populations, including T cells and natural killer cells, and the resulting immunosuppression severely limits the efficacy of immune checkpoint inhibitors and other immunotherapeutic approaches. As a major pathway to enhance the efficacy of cancer immunotherapy effects, the role of TGFß signaling inhibitors have been evaluated in many clinical trials. However, the potential functions and mechanisms of TGFß1, TGFß2 and TGFß3 in gastric cancer progression and tumor immunology are unclear. In this study, we comprehensively analyzed TGFß1, TGFß2 and TGFß3 and gastric cancer microenvironmental features, including immune cell infiltration, EMT, hypoxia, mutation, immunotherapy and drug treatment, based on HMUCH sequencing data (GSE184336) and public databases. We also validated the protein expression levels of TGFß in gastric cancer tissues as well as the role of TGFß factor in cytology experiments. This report reveals the important role of the TGFß gene family in gastric cancer and provides possible relationships and potential mechanisms of TGFß in gastric cancer.

A Secreted Lignin Peroxidase Required for Fungal Growth and Virulence and Related to Plant Immune Response.

Botryosphaeria spp. are important phytopathogenic fungi that infect a wide range of woody plants, resulting in big losses worldwide each year. However, their pathogenetic mechanisms and the related virulence factors are rarely addressed. In this study, seven lignin peroxidase (LiP) paralogs were detected in Botryosphaeria kuwatsukai, named BkLiP1 to BkLiP7, respectively, while only BkLiP1 was identified as responsible for the vegetative growth and virulence of B. kuwatsukai as assessed in combination with knock-out, complementation, and overexpression approaches. Moreover, BkLiP1, with the aid of a signal peptide (SP), is translocated onto the cell wall of B. kuwatsukai and secreted into the apoplast space of plant cells as expressed in the leaves of Nicotiana benthamiana, which can behave as a microbe-associated molecular pattern (MAMP) to trigger the defense response of plants, including cell death, reactive oxygen species (ROS) burst, callose deposition, and immunity-related genes up-regulated. It supports the conclusion that BkLiP1 plays an important role in the virulence and vegetative growth of B. kuwatsukai and alternatively behaves as an MAMP to induce plant cell death used for the fungal version, which contributes to a better understanding of the pathogenetic mechanism of Botryosphaeria fungi.

TGFß2 is a Prognostic Biomarker for Gastric Cancer and is Associated With Methylation and Immunotherapy Responses.

TGFß signaling plays a key role in cancer progression and by shaping tumor architecture and inhibiting the anti-tumor activity of immune cells. It was reported that high expression of TGFß can promote the invasion and metastasis of cancer cells in a variety of tumors. However, there are few studies on TGFß2 and its methylation in gastric cancer. We analyzed the Harbin Medical University Cancer Hospital (HMUCH) sequencing data and used public data to explore the potential function and prognostic value of TGFß2 and its methylation in gastric cancer. In this study, we used the ssGSEA algorithm to quantify 23 methylation sites related to TGFß2. Survival analysis showed that high expression of TGFß2 and hypomethylation levels of TGFß2 were negative factors in the prognosis of gastric cancer. Functional enrichment analysis of methylation revealed that methylation of different TGFß2 methylation scores was mainly involved in energy metabolism, extracellular matrix formation and cell cycle regulation. In the gastric cancer microenvironment TGFß2 was associated with high levels of multiple immune cell infiltration and cytokine expression, and high TGFß2 expression was significantly and positively correlated with stemness markers, stromalscore and EMT. Gene set enrichment analysis also revealed an important role of TGFß2 in promoting EMT. In addition, we discussed the relationship between TGFß2 and immunotherapy. The expression of PD-1, PD-L1 and CTLA-4 was elevated in the TGFß2 high expression group. Also when TGFß2 was highly expressed, the responsiveness of immune checkpoint blockade (ICB) was significantly enhanced. This indicates that TGFß2 may become an indicator for predicting the efficacy of immunosuppressive agents and a potential target for immunotherapy.

Active-ion-gated room temperature acetone gas sensing of ZnO nanowires array.

Reducing the high operation temperature of gas sensor to room temperature (RT) have attracted intense interests for its distinct preponderances, including energy-saving and super stability, which presents great prospects in commercial application. The exciting strategies for RT gas sensing, such as unique materials with activated surface or light activation, do not directly modulate the active ions for gas sensing, limiting the RT gas sensing performances. Here, an active-ion-gated strategy has been proposed for RT gas sensing with high performance and low power consumption, in which gas ions in triboelectric plasma are introduced into metal oxide semiconductor (MOS) film to act as both floating gate and active sensing ions. The active-ion-gated ZnO nanowires (NWs) array shows a sensitivity of 38.3% to 10 ppm acetone gas at RT, and the maximum power consumption is only 4.5 mW. At the same time, the gas sensor exhibits excellent selectivity to acetone. More importantly, the response (recovery) time of this sensor is as low as 11 s (25 s). It is found that OH-(H2O)4 ions in plasma are the key for realizing RT gas sensing ability, and an accompanied resistive switch is also observed. It is considered that the electron transfer between OH-(H2O)4 and ZnO NWs will forms a hydroxyl-like intermediate state (OH*) on the top of Zn2+, leading to the band bending of ZnO and activating the reactive O2 - ions on the oxygen vacancies. The active-ion-gated strategy proposed here present a novel exploration to achieving RT gas sensing performance of MOS by activating sensing properties at the scale of ions or atoms.

ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood.

Numerous studies have reported that a variety of long noncoding RNAs (lncRNAs) can promote the proliferation, invasion, and migration of different tumor cells. However, different lncRNAs regulate cell functions in various forms, and the exact mechanisms are not clear. Here, we investigated the effect of the lncRNA ELF3-AS1 on gastric cancer (GC) cell function and explored the exact mechanism. Quantitative real-time polymerase chain reaction was used to detect the expression of ELF3-AS1 in GC tissues and adjacent nontumor tissues. Knockdown and overexpression of ELF3-AS1 was used to detect the effect of ELF3-AS1 on cell function. Potential downstream target genes were identified using RNA transcriptome sequencing, while RNA immunoprecipitation, chromatin immunoprecipitation, and Western blotting were performed to explore the tumor promotion mechanisms of ELF3-AS1. We observed that ELF3-AS1 was highly expressed in GC tissues, and high ELF3-AS1 expression predicted poor prognosis. The knockdown of ELF3-AS1 significantly inhibited cell proliferation, migration, and epithelial-mesenchymal transition and promoted apoptosis. Mechanistic investigations revealed that ELF3-AS1 may regulate the downstream target gene, C-C motif chemokine 20, by binding with the RNA-binding protein hnRNPK. Additionally, we found that high ELF3-AS1 expression was associated with thrombocytosis. Interleukin-6 and thrombopoietin may be involved in ELF3-AS1-induced paraneoplastic thrombocytosis. Together, our results demonstrate that aberrantly expressed ELF3-AS1 in GC may play important roles in oncogenesis and progression and is expected to become a new target for the diagnosis and treatment of GC.

A novel Actinidia cytorhabdovirus characterized using genomic and viral protein interaction features.

A novel cytorhabdovirus, tentatively named Actinidia virus D (AcVD), was identified from kiwifruit (Actinidia chinensis) in China using high-throughput sequencing technology. The genome of AcVD consists of 13,589 nucleotides and is organized into seven open reading frames (ORFs) in its antisense strand, coding for proteins in the order N-P-P3-M-G-P6-L. The ORFs were flanked by a 3' leader sequence and a 5' trailer sequence and are separated by conserved intergenic junctions. The genome sequence of AcVD was 44.6%-51.5% identical to those of reported cytorhabdoviruses. The proteins encoded by AcVD shared the highest sequence identities, ranging from 27.3% (P6) to 44.5% (L), with the respective proteins encoded by reported cytorhabdoviruses. Phylogenetic analysis revealed that AcVD clustered together with the cytorhabdovirus Wuhan insect virus 4. The subcellular locations of the viral proteins N, P, P3, M, G, and P6 in epidermal cells of Nicotiana benthamiana leaves were determined. The M protein of AcVD uniquely formed filament structures and was associated with microtubules. Bimolecular fluorescence complementation assays showed that three proteins, N, P, and M, self-interact, protein N plays a role in the formation of cytoplasm viroplasm, and protein M recruits N, P, P3, and G to microtubules. In addition, numerous paired proteins interact in the nucleus. This study presents the first evidence of a cytorhabdovirus infecting kiwifruit plants and full location and interaction maps to gain insight into viral protein functions.

Long non-coding RNA SNHG1 mediates neuronal damage in Parkinson's disease model cells by regulating miR-216a-3p/Bcl-2-associated X protein.

BACKGROUND: Parkinson's disease (PD) is a common central nervous system degenerative disease in middle-aged and elderly people. Our study aimed to illuminate the relationship and mechanism of long-chain non-coding RNA SNHG1 and miRNA (miR)-216a-3p in PD. METHODS: Human neuroblastoma cell lines were treated with MPP+ to construct a PD model. Real-time fluorescent quantitative PCR was used to detect the cellular expression of SNHG1. Neuronal cell activity and apoptosis were compared before and after SNHG1 knock-down, as was neuronal miR-216a-3p expression. Further, a luciferase reporter gene experiment was performed to verify BAX as the target of miR-216a-3p. Anti-miR-216a-3p and BAX were co-transfected into PD model cells, and neuronal cellular activity and apoptosis were observed. Finally, the potential regulatory network of SNHG1/miR-216a-3p/BAX in PD was investigated. RESULTS: The expression of miR-216a-3p was decreased in the PD model cells, and re-expression reversed the high apoptotic rate and cell vitality inhibition in PD model cells. SNHG1 interacted with miR-216a-3p and negatively regulated its upstream molecules, while miR-216a-3p attenuated the effect of SNHG1 knock-down on neurons. The overexpression of BAX in the PD cell model blocked the damage by miR-216a-3p to neurons. At the same time, SNHG1 acted as a coordinator, mediating the regulation of BAX via miR-216a-3p, thereby affecting the activity and apoptotic rate of neurons in the PD model. CONCLUSIONS: SNHG1 interacts with miR-216a-3p to regulate the expression of BAX. This SNHG1/miR-216a-3p/BAX molecular regulatory network is implicated in the pathogenesis of PD.

The p23 of Citrus Tristeza Virus Interacts with Host FKBP-Type Peptidyl-Prolylcis-Trans Isomerase 17-2 and Is Involved in the Intracellular Movement of the Viral Coat Protein.

Citrus tristeza virus is a member of the genus Closterovirus in the family Closteroviridae. The p23 of citrus tristeza virus (CTV) is a multifunctional protein and RNA silencing suppressor. In this study, we identified a p23 interacting partner, FK506-binding protein (FKBP) 17-2, from Citrus aurantifolia (CaFKBP17-2), a susceptible host, and Nicotiana benthamiana (NbFKBP17-2), an experimental host for CTV. The interaction of p23 with CaFKBP17-2 and NbFKBP17-2 were individually confirmed by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Subcellular localization tests showed that the viral p23 translocated FKBP17-2 from chloroplasts to the plasmodesmata of epidermal cells of N. benthamiana leaves. The knocked-down expression level of NbFKBP17-2 mRNA resulted in a decreased CTV titer in N. benthamiana plants. Further, BiFC and Y2H assays showed that NbFKBP17-2 also interacted with the coat protein (CP) of CTV, and the complexes of CP/NbFKBP17-2 rapidly moved in the cytoplasm. Moreover, p23 guided the CP/NbFKBP17-2 complexes to move along the cell wall. To the best of our knowledge, this is the first report of viral proteins interacting with FKBP17-2 encoded by plants. Our results provide insights for further revealing the mechanism of the CTV CP protein movement.

Diagnostic Sensitivity of NLR and PLR in Early Diagnosis of Gastric Cancer.

The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are markers of systemic inflammation. However, there is little evidence of the value of inflammation in the early diagnosis of gastric cancer (GC). A total of 2,606 patients diagnosed with GC in the past three years and 3,219 healthy controls over the same period were included in this study. Peripheral blood samples were obtained to analyze the NLR, PLR, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). The optimal cutoff levels for the NLR and PLR were defined by receiver operating characteristic (ROC) curve analysis (NLR = 2.258, PLR = 147.368). The value of different biomarkers for diagnosing GC was compared by the area under the curve (AUC). The NLR and PLR showed diagnostic sensitivity in GC (AUC = 0.715, AUC = 0.707). Using the Bonferroni correction, the NLR and PLR were superior to CEA and CA19-9 in the diagnosis of GC (P < 0.0001). The systemic inflammatory markers were significantly higher in the early stage of GC than tumor markers. After grouping patients and healthy controls by gender, we found that the diagnostic significance of combined NLR and PLR for GC was greater in male patients than in female patients (P < 0.0001). The diagnostic value of the NLR and PLR in GC is higher than that of the traditional tumor markers CEA and CA19-9. Systemic markers of inflammation are more valuable in male than female patients.

CD66b+ neutrophils and α-SMA+ fibroblasts predict clinical outcomes and benefits from postoperative chemotherapy in gastric adenocarcinoma.

BACKGROUND: Emerging evidence indicates that the tumor microenvironment (TME) influences tumor progression through the various cells it contains. Tumor-associated neutrophils (TANs) and cancer-associated fibroblasts (CAFs) are prominent constituents of diverse malignant solid tumors and are crucial in the TME and cancer evolution. However, the relationships and combined prognostic value of these two cell types are not known in gastric adenocarcinoma (GAC). MATERIALS AND METHODS: In total, 215 GAC patients who underwent curative surgery were enrolled. TANs were assessed by immunohistochemical staining for CD66b, and CAFs were evaluated by immunohistochemical staining for α-smooth muscle actin (α-SMA). RESULTS: The percentages of patients with high-density TANs and CAFs in GAC tissue were 47.9% (103/215) and 43.3% (93/215), respectively. The densities of TANs and CAFs in GAC tissue samples were markedly elevated and independently correlated with GAC clinical outcomes. A strong correlation (R = .348, P < .001) was detected between TANs and CAFs in GAC. The combination of TANs and CAFs produced a more exact outcome than either factor alone. Patients with an α-SMAlow CD66bhigh (hazard ratio [HR] = 1.791; 95% CI: 1.062-3.021; P = .029), α-SMAhigh CD66blow (HR = 2.402; 95% CI: 1.379-4.183; P = .002), or α-SMAhigh CD66bhigh (HR = 3.599; 95% CI: 2.330-5.560; P < .001) phenotype were gradually correlated with poorer disease-free survival than the subset of patients with an α-SMAlow CD66blow phenotype. The same results were observed for disease-specific survival in the subgroups. Noticeably, in stage II-III patients with the α-SMAlow CD66blow phenotype, an advantage was obtained with postoperative chemotherapeutics, and the risk of a poor prognosis was reduced compared with stage II-III patients with the α-SMAlow CD66bhigh , α-SMAhigh CD66blow or α-SMAhigh CD66bhigh phenotype (HR: 0.260, 95% CI: 0.124-0.542, P < .001 for disease-free survival; and HR: 0.258, 95% CI: 124-0.538, P < .001 for disease-specific survival). CONCLUSION: Overall, we concluded that the combination of CD66b+ TANs and α-SMA+ CAFs could be used as an independent factor for patient outcomes and to identify GAC patients who might benefit from the administration of postoperative chemotherapeutics.

Estrogen facilitates gastric cancer cell proliferation and invasion through promoting the secretion of interleukin-6 by cancer-associated fibroblasts.

As a common disease, gastric cancer (GC) has influenced over 1 million people worldwide. Despite of prevention and optimal treatments, GC still has a high mortality. The role of cancer-associated fibroblasts (CAFs) in tumor progression has recently attracted attention, yet few studies have focused on GC. Estrogen has been reported to relate to the poor prognosis of GC. Therefore, we investigated whether estrogen can stimulate CAFs to produce tumor promoting factors in this study. Gastric CAFs were isolated from GC tissues and treated with estrogen. ELISA results suggested that CAFs produced interleukin-6 (IL-6) after estrogen treatment in a dose-dependent manner. The cell culture supernatant for estrogen-treated CAFs was collected and used as conditioned medium (CM) for GC cells. After cultured in CM, increased cell proliferation and alteration of cell cycle were detected by CCK-8 assay, BrdU assay, and flow cytometry. Western blot and gelatin zymography were used to determine cancer invasion-associated proteins. Results indicated that the expression of matrix metalloproteinase 2 (MMP2) and MMP9 were enhanced by Estrogen-CAFs-CM. Additional transwell assay showed that cell invasion and migration were promoted after cultured in CM. Lastly, western blot and immunofluorescence results demonstrated that the level of phosphorylated signal transducer and activator of transcription 3 (STAT3) in GC cells increased after cultured in CM. The effect was neutralized by IL-6 neutralizing antibody and STAT3 siRNA. Conclusively speaking, estrogen can activate CAFs to produce IL-6, ending up with promotion of GC cell proliferation and invasion. This result may suggest a new therapeutic target for GC.

Genipin attenuates dextran sulfate sodium-induced colitis via suppressing inflammatory and oxidative responses.

Genipin is one of the major component in Gardenis fruit, which has long been used in the treatment of many chronic diseases, such as colitis. In the present study, we investigated the protective effects and mechanism of genipin on dextran sodium sulfate (DSS)-induced colitis in mice. Colitis was induced by giving 2.5% (wt/vol) DSS for 7 days. As the results show, DSS-induced body weight loss and colonic histological changes were inhibited by the treatment of genipin. DSS-induced MPO activity, MDA level, TNF-α, and IL-1ß production in colonic tissues were also suppressed by genipin. To investigate the mechanism of genipin on DSS-induced colitis, the NF-κB and Nrf2 signaling pathways were detected. The results showed genipin significantly attenuated DSS-induced NF-κB activation and increased the expression of Nrf2 and HO-1 in a dose-dependent manner. The results of the present study indicated that genipin protected mice against colitis through inhibiting inflammatory and oxidative effects.

The combination of preoperative fibrinogen and neutrophil-lymphocyte ratio is a predictive prognostic factor in esophagogastric junction and upper gastric cancer.

Objective: Cancer-associated systemic inflammation response and hyperfibrinogenemia play crucial roles in cancer progression and prognosis. In this study, we assessed the clinical value of the preoperative fibrinogen and the neutrophil-lymphocyte ratio (NLR) in patients with adenocarcinoma of the esophagogastric junction (AEG) and upper gastric cancer (UGC). Methods: Patients with AEG or UGC who underwent curative surgery were divided into a training set (n=161) and a validation set (n=195). Univariate and multivariate Cox analyses were performed to evaluate the prognostic indicators for overall survival (OS). The optimization cut-off values for fibrinogen and the NLR were 3.09g/L and 1.84, respectively. The combination of fibrinogen and NLR (F-NLR) was 2 for patients with high fibrinogen (≥3.09g/L) and elevated NLR (≥1.84), whereas those with one or neither were indexed as 1 or 0, respectively. Results: F-NLR was identified as an independent prognostic indicator for OS in the training set (P=0.007) which was confirmed in the validation set (P=0.003). In the subgroup analyses, the prognostic significance of F-NLR was still maintained for stages I-II (P = 0.030 in the training set; and P =0.020 in the validation set) and III (P = 0.001 in the training set; and P <0.001 in the validation set).Notably, among patients with F-NLR 2 could benefit from adjuvant chemotherapy compared with those with F-NLR 0-1 (P = 0.020 in the training set; and P =0.005 in the validation set). Conclusions: The preoperative F-NLR score is an independent prognosis indicator for patients with AEG and UGC. And it may help clinicians to identify those patients who at high prognostic risk and will benefit from planning individualized treatment strategies.

Ubiquitin­specific protease 7 promotes osteosarcoma cell metastasis by inducing epithelial­mesenchymal transition.

Osteosarcoma (OS) is the most common primary malignant bone tumour among adolescents and young adults; however, its molecular pathogenesis has not been completely elucidated. Ubiquitin­specific protease 7 (USP7), a member of the deubiquitinating enzyme family, plays a role in the malignancy process of various cancer types by targeting the key oncoprotein; however, its biological function and mechanism in OS have not been elucidated. The present study demonstrated that USP7 expression in OS tumour tissues was markedly higher than that in the paired surrounding tissues, and high USP7 expression was positively correlated with the TNM stage and metastasis in patients with OS. Next, biological function assays demonstrated that USP7 knockdown markedly inhibited OS cell migration and invasion, whereas USP7 overexpression enhanced it. Notably, USP7 can directly bind with ß­catenin to activate the Wnt/ß­catenin signalling pathway and induce epithelial­mesenchymal transition (EMT) of OS cells. Overall, USP7 overexpression could promote OS cell metastasis by activating the Wnt/ß­catenin signalling pathway by inducing EMT, suggesting that USP7 is a potential therapeutic target for OS.