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Simple Summary: Pancreatic cancer (PC) is one of the most lethal malignancies across the world. More than 80% patients are diagnosed at an advanced stage with limited treatment options. PC has the highest frequency of developing cancer cachexia (CC)–sarcopenia (SC) syndrome, but there is no optimal efficient intervention for CC or SC targeting their complicated biological and irreversible processes. As a result, identifying the clinicopathological features and patient characteristics in each advanced PC patient with CC and/or SC is urgently needed to distinguish different wasting phenotypes or body composition and thus support precision medicine and achieve optimal outcomes. We performed a retrospective cohort study of 232 advanced PC patients to determine the differential clinical characteristics of CC and SC and the overlap of CC- or SC-related factors in each patient. The impacts of CC, SC, and their relevant factors on the outcomes of PC patients were also evaluated. Pancreatic cancer (PC) has the highest frequency of developing cancer cachexia (CC)–sarcopenia (SC) syndrome, which negatively influences patients' outcome, quality of life, and tolerance/response to treatments. However, the clinical impacts of CC, SC, and their associated factors on outcomes for advanced PC has yet to be fully investigated. A total of 232 patients were enrolled in this study for the retrospective review of their clinical information and the measurement of skeletal muscle areas at the third lumber vertebra by computed tomography scan to identify CC or SC. The association and concurrent occurrence of clinicopathological features in each patient, prevalence rates, and prognosis with the CC or SC were calculated. CC and SC were observed in 83.6% (n = 194) and 49.1% (n = 114) of PC patients, respectively. Low hemoglobin levels more often occurred in CC patients than in non-CC patients (p = 0.014). Older age (p = 0.000), female gender (p = 0.024), low body mass index (BMI) values (p = 0.004), low hemoglobin levels (p = 0.036), and low albumin levels (p = 0.001) were more often found in SC patients than in non-SC patients. Univariate and multivariate analyses showed that CC was an independent poor prognostic factor of overall survival (OS) and progression-free survival for all patients, the chemotherapy (C/T) subgroup, and the high BMI subgroup. Meanwhile, SC was an independent predictor of poor OS for the subgroups of C/T or high BMI but not for all patients. These findings reveal the clinical differences for CC and SC and provide useful information for predicting the prognosis of advanced PC patients and conducting personalized medicine. [ABSTRACT FROM AUTHOR]

Species of Cystolepiota are known as diminutive lepiotaceous fungi with a worldwide distribution. Previous studies revealed that Cystolepiota is not monophyletic and preliminary DNA sequence data from recent collections suggested that several new species exist. Based on multi-locus DNA sequence data (the nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2, ITS; the D1–D2 domains of nuc 28S rDNA, LSU; the most variable region of the second-largest subunit of RNA polymerase II, rpb2 and a portion of the translation–elongation factor 1-α. tef1), C. sect. Pulverolepiota forms a distinct clade separating from Cystolepiota. Therefore, the genus Pulverolepiota was resurrected and two combinations, P. oliveirae and P. petasiformis were proposed. With the integration of morphological characteristics, multi-locus phylogeny, and information on geography and habitat, two new species, viz. C. pseudoseminuda and C. pyramidosquamulosa, are described and C. seminuda was revealed to be a species complex containing at least three species, viz. C. seminuda, C. pseudoseminuda, and Melanophyllum eryei. In addition, C. seminuda was re-circumscribed and neo-typified based on recent collections. [ABSTRACT FROM AUTHOR]

A laminated Pd-Cu alloy/C/Nafion multilayer was prepared to sense O2 atmosphere in a metal-air structure. As a matrix, palladium was doped with various amounts of copper to conduct a preliminary test with optimum response, and four compositions, Pd, Pd8Cu2, Pd6Cu4, and Pd5Cu5, were selected as the candidate electrodes. It was found that the Pd6Cu4/C electrode showed higher sensitivity for all the electrodes. According to the phase identification of X-ray diffraction and X-ray photoelectron spectroscopy tests, the high sensitivity was attributed to the doped Cu, which was merged into the Pd matrix to repel the Pd out of the matrix as a Pd-skin layer on the surface. In the Pd-Cu alloy, the Cu site served as a template reaction site to break the O-O bond and reduce the interaction force of adsorbated oxygen on the Pd site. During the oxygen reduction reaction, not only did the decomposition of O2 molecules occur on the electrode, but the electrode itself proceeded with a phase transformation to high valance of oxide, PdO3. The sensing potential for O2 sensing was determined by polarization curves in which the flat region resulting from a diffusion-control was adopted. Chronoamperometric measurements were employed to construct calibration curves for the selected electrodes. A successive response was measured to test the endurance, which showed appreciable sensitivity decay. We also tested the selectivity by introducing a series of disturbance gases, CO, SO2, and NO2, in which the Pd6Cu4 electrode prevailed over the other electrodes. [ABSTRACT FROM AUTHOR]

Aminoacylation of tRNA generates an aminoacyl-tRNA (aa-tRNA) that is active for protein synthesis on the ribosome. Quantification of aminoacylation of tRNA is critical to understand the mechanism of specificity and the flux of the aa-tRNA into the protein synthesis machinery, which determines the rate of cell growth. Traditional assays for the quantification of tRNA aminoacylation involve radioactivity, either with a radioactive amino acid or with a [3′-32P]-labeled tRNA. We describe here a label-free assay that monitors aminoacylation by biotinylation-streptavidin (SA) conjugation to the α-amine or the α-imine of the aminoacyl group on the aa-tRNA. The conjugated aa-tRNA product is readily separated from the unreacted tRNA by a denaturing polyacrylamide gel, allowing for quantitative measurement of aminoacylation. This label-free assay is applicable to a wide range of amino acids and tRNA sequences and to both classes of aminoacylation. It is more sensitive and robust than the assay with a radioactive amino acid and has the potential to explore a wider range of tRNA than the assay with a [3′-32P]-labeled tRNA. This label-free assay reports kinetic parameters of aminoacylation quantitatively similar to those reported by using a radioactive amino acid, suggesting its broad applicability to research relevant to human health and disease. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effects to evade immune system recognition. However, the clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, high infiltration of CD8+ T cells could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion. [ABSTRACT FROM AUTHOR]

Cancer cachexia (CC), characterized by body weight loss and sarcopenia, contributes to over 20% of all cancer-related death. Approximately 80% of pancreatic cancer (PC) patients develop CC during disease progression. Pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, have been correlated with CC; however, its prognostic significance remains unclear. In this study, serum levels of the CC-related cytokines were determined in normal donors and PC patients. IL-8 expression was assessed in PC tissue microarrays. The correlation of levels of each cytokine with disease progression, weight loss, and sarcopenia was calculated. The relationships among the baseline variables, CC, and IL-8 expression with disease progression were examined using univariate and multivariate analyses. Of these mentioned cytokines, only serum IL-8 level was elevated in the locally advanced group (n = 55) compared with the normal (n = 17) and resected groups (n = 55). Serum IL-8 level was positively correlated with CC status, weight loss, sarcopenia, but was negatively correlated with total psoas area (TPA). IL-8 expression in tissue samples was also positively associated with weight loss. Furthermore, serum IL-8 level was an independent predictor of survival. In conclusion, elevated serum IL-8 level significantly correlates with CC and sarcopenia and can be used as a prognostic indicator in PC. [ABSTRACT FROM AUTHOR]

Semaphorins (SEMAs) are axon guidance factors that participate in axonal connections and nerve system development. However, the functional roles of SEMAs in tumorigenesis are still largely uncovered. By using in silico data analysis, we found that SEMA6C was downregulated in pancreatic cancer, and its reduction was correlated with worse survival rates. RNA sequencing revealed that cell cycle-related genes, especially cyclin D1, were significantly altered after blockage of SEMA6C by neutralizing antibodies or ectopic expressions of SEMA6C. Mechanistic investigation demonstrated that SEMA6C acts as a tumor suppressor in pancreatic cancer by inhibiting the AKT/GSK3 signaling axis, resulting in a decrease in cyclin D1 expression and cellular proliferation. The enhancement of cyclin D1 expression and cyclin-dependent kinase activation in SEMA6C-low cancer created a druggable target of CDK4/6 inhibitors. We also elucidated the mechanism underlying SEMA6C downregulation in pancreatic cancer and demonstrated a novel regulatory role of miR-124-3p in suppressing SEMA6C. This study provides new insights of SEMA6C-mediated anti-cancer action and suggests the treatment of SEMA6C-downregulated cancer by CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: According to a report from International Diabetes Federation, in 2020 approximately 463 million adults (20–79 years) were living with diabetes, the principles of medical nutrition therapy are to decrease the risk of diabetes by encouraging healthy food choices and physical activity. Djulis is a unique traditional pseudo-cereal crop native to Taiwan. The hull of djulis, which is usually considered to be agricultural waste, is disposed of in landfills and causes some environmental problems. In recent years, many studies have investigated the functional properties of djulis hull. The focus has been on the byproducts of djulis, a waste utilization approach, to further develop enriched functional foods. Djulis hull contained dietary fibre 75.21 ± 0.17% dry weight, and insoluble dietary fibre (IDF) reached 71.54 ± 0.27% dry weight. The IDF postponed the adsorption of glucose and reduced the activity of α-amylase. We found that it is a good source of valuable ingredients that contain a high amount of dietary fibre. Furthermore, for patients with T2DM, consuming djulis hull 30 and 60 min before a meal significantly reduced blood glucose content as compared with patients at the same postprandial times who did not consume it. Djulis (Chenopodium formosanum Koidz.) is a species of cereal grain native to Taiwan. It is rich in dietary fibre and antioxidants and therefore reputed to relieve constipation, suppress inflammation, and lower blood glucose. The aim of this study was to investigate the composition and physicochemical properties of dietary fibre from djulis hull. Meanwhile, determination of the in vivo antidiabetic effect on patients with type 2 diabetes mellitus (T2DM) after consuming the djulis hull powder. Djulis hull contained dietary fibre 75.21 ± 0.17% dry weight, and insoluble dietary fibre (IDF) reached 71.54 ± 0.27% dry weight. The IDF postponed the adsorption of glucose and reduced the activity of α-amylase. Postprandial blood glucose levels in patients with T2DM showed three different tendencies. First, the area under the glucose curve was significantly lower after ingesting 10 or 5 g djulis hull powder, which then postponed the adsorption of glucose, but the area under the glucose curve was similar with the two doses. After consuming 10 g djulis hull before 75 g glucose 30 and 60 min after the meal, patients with T2DM had blood glucose values that were significantly lower at the same postprandial times than those of patients who did not consume djulis hull. In short, patients who consumed djulis hull prior to glucose administration had decreased blood glucose level compared with those who did not. Djulis hull may have benefits for patients with T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is the third most commonly diagnosed cancer in the world, and surgical resection is the commonly used curative management of early-stage disease. However, the recurrence rate is high after resection, and liver fibrosis has been thought to increase the risk of recurrence. Conventional histological staging of fibrosis is highly subjective to observer variations. To overcome this limitation, we used a fully quantitative fibrosis assessment tool, qFibrosis (utilizing second harmonic generation and two-photon excitation fluorescence microscopy), with multi-dimensional artificial intelligence analysis to establish a fully-quantitative, accurate fibrotic score called a "combined index", which can predict early recurrence of HCC after curative intent resection. Therefore, we can pay more attention on the patients with high risk of early recurrence. Background: Liver fibrosis is thought to be associated with early recurrence of hepatocellular carcinoma (HCC) after resection. To recognize HCC patients with higher risk of early recurrence, we used a second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) microscopy to create a fully quantitative fibrosis score which is able to predict early recurrence. Methods: The study included 81 HCC patients receiving curative intent hepatectomy. Detailed fibrotic features of resected hepatic tissues were obtained by SHG/TPEF microscopy, and we used multi-dimensional artificial intelligence analysis to create a recurrence prediction model "combined index" according to the morphological collagen features of each patient's non-tumor hepatic tissues. Results: Our results showed that the "combined index" can better predict early recurrence (area under the curve = 0.917, sensitivity = 81.8%, specificity = 90.5%), compared to alpha fetoprotein level (area under the curve = 0.595, sensitivity = 68.2%, specificity = 47.6%). Using a Cox proportional hazards analysis, a higher "combined index" is also a poor prognostic factor of disease-free survival and overall survival. Conclusions: By integrating multi-dimensional artificial intelligence and SHG/TPEF microscopy, we may locate patients with a higher risk of recurrence, follow these patients more carefully, and conduct further management if needed. [ABSTRACT FROM AUTHOR]

Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial–mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-β) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-β-induced EMT pathway. [ABSTRACT FROM AUTHOR]

Flavonoids and isoflavonoids are polyphenolic secondary metabolites usually produced by plants adapting to changing ecological environments over a long period of time. Therefore, their biosynthesis pathways are considered as the most distinctive natural product pathway in plants. Seemingly, the flavonoids and isoflavones from fungi and actinomycetes have been relatively overlooked. In this review, we summarized and classified the isoflavones and flavonoids derived from fungi and actinomycetes and described their biological activities. Increasing attention has been paid to bioactive substances derived from microorganism whole-cell biotransformation. Additionally, we described the utilization of isoflavones and flavonoids as substrates by fungi and actinomycetes for biotransformation through hydroxylation, methylation, halogenation, glycosylation, dehydrogenation, cyclisation, and hydrogenation reactions to obtain rare and highly active biofunctional derivatives. Overall, among all microorganisms, actinomycetes are the main producers of flavonoids. In our review, we also summarized the functional genes involved in flavonoid biosynthesis. [ABSTRACT FROM AUTHOR]