No abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. As a branch of glucose metabolism, hexosamine biosynthesis pathway (HBP) has been reported to play a critical role in the insulin resistance and progression of cancer. Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting enzyme of the HBP; nevertheless, the prognostic value of GFAT1 in HCC remains elusive. In this study, we found that high expression of GFAT1 was significantly associated with serum alpha-fetoprotein (AFP), serum alanine aminotransferase (ALT), tumor size, tumor encapsulation, T stage and TNM stage. High GFAT1 expression was identified as an independent prognostic factor which predicted poor overall survival (OS) and recurrence-free survival (RFS) in HCC patients. Incorporation of GFAT1 expression could improve the prognostic accuracy of traditional TNM stage system. Integration of GFAT1 expression with other independent prognosticators generated a predictive nomogram, which showed better prognostic efficiency for OS and RFS in HCC patients. In vitro studies also revealed that GFAT1 promoted the proliferation, cell cycle progression, migration and invasion of HCC cells. In conclusion, GFAT1 is a potential prognostic biomarker for overall survival and recurrence-free survival of HCC patients after surgery.

Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwise inert monocytes responsive to IL-7. Active IL-7 signaling engaged epigenetically coupled, STAT5-coordinated transcriptional programs to restrain inflammatory gene expression, resulting in inverse correlation between CD127 expression and inflammatory phenotypes in a seemingly homogeneous monocyte population. In COVID-19 and rheumatoid arthritis, CD127 marked a subset of monocytes/macrophages that retained hypoinflammatory phenotypes within the highly inflammatory tissue environments. Furthermore, generation of an integrated expression atlas revealed unified features of human inflammatory monocytes across different diseases and different tissues, exemplified by those of the CD127high subset. Overall, we phenotypically and molecularly characterized CD127-imprinted functional heterogeneity of human inflammatory monocytes with direct relevance for inflammatory diseases.

Lasioderma serricorne , also known as cigarette beetle, can exploit a wide variety of stored materials as foods, but it is particularly common on tobacco and herbs. This beetle is a dominant pest species of stored Chinese medicinal materials (CMMs) causing high economic damages, making effective control strategies urgently needed. Behavioural manipulation is an important component of Integrated Pest Management. To the best of our knowledge, plant-borne volatile organic compounds (VOCs) have never been explored to develop lures for managing L . serricorne . In this study, the behavioural responses of L . serricorne to VOCs from four selected CMMs ( Euphorbia kansui , Aconitum carmichaelii , Eucommia ulmoides and Pinellia ternata ) were studied and their components analysed. Then, the olfactory responses of L . serricorne to the most abundant VOC identified in the preferred CMM, i.e., paeonal, was tested. L . serricorne showed significant differences in its preferences for the VOCs from the four CMMs, i.e, E . kansui > A . carmichaelii > E . ulmoides > P . ternata . From the VOCs of E . kansui , A . carmichaelii , E . ulmoides , and P . ternata , 77, 74, 56, and 81 molecules, were identified, respectively. Paeonal (23.5%), junipene (17.2%), hexanal (17.1%), and benzeneacetonitrile (14.0%) were the most abundant, respectively. Since paeonal dominated the VOC spectrum of the most preferred CMM, this compound was selected for further studies. L . serricorne showed significant positive responses to paeonal tested at various doses, with the most attractive ones being 100 μg and 500 μg. Our findings shed light on the olfactory cues routing the food searching behaviour in the cigarette beetle, providing important information on how L . serricorne targets particular CMMs. The high attractiveness of paeonal at low doses tested here may be exploited further to develop novel monitoring and control tools (e.g., lure-and-kill strategies) against this important stored product pest.

Purpose: Eosinophils are proven to play a role in the prognosis of some malignant-tumors. The prognostic value of eosinophils in glioma patients is, however, scarcely reported. The authors of this article have designed a novel prognostic indicator based on eosinophils and the neutrophil-to-lymphocyte ratio (NLR), named ENS, to predict the survival of patients with glioma. Methods: A retrospective study was conducted on 217 glioma patients. The cutoff values for eosinophil, NLR, and other clinical variables were determined by the receiver operating characteristic (ROC) curve analysis. Patients with both low eosinophil count (<0.08 ×10 9 /L) and high NLR (≥1.70) were given a score of 2. Those with one or neither got a score of 1 or 0, respectively. The nomogram was based on ENS and several other clinical variables, its performance was determined by the concordance index (c-index). Results: Our results showed that ENS is an independent prognostic indicator for overall survival (OS). The three-year OS rates for low-grade glioma patients (LGGs) were 84.0%, 69.0%, and 46.4% for ENS=0, ENS=1, and ENS=2, respectively (P=0.014). The three-year OS incidence for LGGs stratified into eosinophils count ≥0.08×109/L and<0.08×109/L subgroups were 88.1% and 80.0%, respectively (P=0.043). ENS was positively correlated with glioma grade (r=0.311, P<0.001). The c-index for OS prognosis was 0.80 using this nomogram in LGGs. Conclusion: Preoperative ENS can predict OS to some extent for LGGs and can increase prognostic accuracy for individual OS in LGGs postoperatively when incorporating other clinical variables compose a nomogram.

Activation of transforming growth factor-β (TGF-β) signaling has been used to enhance healing of meniscal degeneration in several models. However, the exact role and molecular mechanism of TGF-β signaling in meniscus maintenance and degeneration are still not understood due to the absence of in vivo evidence. In this study, we found that the expression of activin receptor-like kinases 5 (ALK5) in the meniscus was decreased with the progression of age and/or osteoarthritis induced meniscal degeneration. Col2α1 positive cells were found to be specifically distributed in the superficial and inner zones of the anterior horn, as well as the inner zone of the posterior horn in mice, indicating that Col2α1-CreER mice can be a used for studying gene function in menisci. Furthermore, we deleted Alk5 in Col2α1 positive cells in meniscus by administering tamoxifen. Alterations in the menisci structure were evaluated histologically. The expression levels of genes and proteins associated with meniscus homeostasis and TGF-β signaling were analyzed by quantitative real-time PCR analysis (qRT-PCR) and immunohistochemistry (IHC). Our results revealed severe and progressive meniscal degeneration phenotype in 3- and 6-month-old Alk5 cKO mice compared with Cre-negative control, including aberrantly increased hypertrophic meniscal cells, severe fibrillation, and structure disruption of meniscus. qRT-PCR and IHC results showed that disruption of anabolic and catabolic homeostasis of chondrocytes may contribute to the meniscal degeneration phenotype observed in Alk5 cKO mice. Thus, TGF-β/ALK5 signaling plays a chondro-protective role in menisci homeostasis, in part, by inhibiting matrix degradation and maintaining extracellular matrix proteins levels in meniscal tissues.

SK protects against TAC-induced renal injury.

Calpain-4 belongs to the calpain family of calcium-dependent cysteine proteases, and functions as a small regulatory subunit of the calpains. Recent evidence indicates that calpain-4 plays critical roles in tumor migration and invasion. However, the roles of calpain-4 in gastric tumorigenesis remain poorly understood. Herein, we examined calpain-4 expression by immunohistochemical staining on tissue microarrays containing tumor samples of 174 gastric cancer patients between 2004 and 2008 at a single center. The Kaplan-Meier method was used to compare survival curves, and expression levels were correlated to clinicopathological factors and overall survival. Our data demonstrated that calpain-4 was generally increased in gastric cancer cell lines and primary tumor tissues. High expression of calpain-4 was positively associated with vessel invasion, lymph node metastasis, and advanced TNM (Tumor Node Metastasis) stage. Multivariate analysis identified calpain-4 as an independent prognostic factor for poor prognosis. A predictive nomogram integrating calpain-4 expression with other independent prognosticators was constructed, which generated a better prognostic value for overall survival of gastric cancer patients than a TNM staging system. In conclusion, calpain-4 could be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer.