Relations between morphological traits and body weight of shortbelly eel, Dysomma anguillare (Actinopterygii: Anguilliformes: Synaphobranchidae), from coastal waters of Zhoushan, East China Sea, determined by multivariate analyses

The shortbelly eel, Dysomma anguillare Barnard, 1923, is an essential component in the food chain of the marine ecosystem and plays an important role in nearshore fisheries and biodiversity in the East China Sea. In order to provide theoretical support for fishery resource assessment and sustainable utilization of D. anguillare, an important bycatch in the offshore area of China, the relations between morphological traits and body weight were investigated based on the measurement of 28 metric traits for the first time. The correlation analysis showed that 25 morphological traits were significantly (P < 0.05) correlated with the logarithm of body weight (lgX0), in which the correlation coefficient of the total length (X1) was the largest with the extremely high significance (P < 0.01). The optimum multiple regression equation of morphological traits was constructed after deleting redundant independent variables: lgX0 = 0.367 + 0.003X1 + 0.010X7 – 0.010X8 + 0.011X10 + 0.042X14 + 0.006X15 + 0.024X19 – 0.004X23. The total length (X1) had the highest positive direct relation with lgX0 (0.699), which was in accordance with the results of determinate coefficient analysis, while the indirect effect of body height (X7) through lower jaw length (X19) to lgX0 was the greatest. The gray correlation analysis indicated that body length (X2) and distance from snout to dorsal fin origin (X22) were the most closely related to body weight. The comprehensive comparison showed that X1, X2, and X22 should be used as the ideal morphometric traits for measuring the body weight of D. anguillare, and the conclusions obtained from this study will provide valuable references for fishery resource management of this commercial fish species

Population genetics and molecular phylogeography of Thamnaconus modestus (Tetraodontiformes, Monachanthidae) in Northwestern Pacific inferred from variation of the mtDNA control region

In order to study the genetic diversity of Thamnaconus modestus, a species of great commercial importance in Southeast Asia, the 5′-end hypervariable regions (423 bp) of the mitochondrial control region of T. modestus in nine geographical populations (248 individuals) were sequenced and analysed in this study. The target sequence fragment contained large numbers of polymorphic sites (87) involved in high levels of haplotype diversity (h = 0.97 ± 0.01) and nucleotide diversity (π = 0.0285 ± 0.0143). The genetic variations within populations (92.71%) were significantly larger than those among populations (7.29%). No significant genetic divergences were detected among the wild populations owing to their gregarious habits, strong moving ability, r-selection strategy. Significant genetic divergences were found between the cultured and wild populations, probably resulting from kin selection and aquacultural environment. Three significant phylogenetic lineages were identified, and the variation among lineages (56.90%) was greater than that among individuals within the lineages (43.10%), with the significant ΦST value (ΦST = 0.57, P = 0.0000). The results showed great and significant genetic differentiations among these three lineages, indicating that they may have independent phylogenetic dynamics. Dominant shared haplotypes that included individuals from each population and the median-joining network of haplotypes presented a star-like structure. Historic demographic analysis of each lineage showed that population expansion occurred after the Pleistocene glacial period. At the last glacial maximum, T. modestus in China seas was scattered across variable refuges, including Central South China Sea and Okinawa Trough

PHLPP Negatively Regulates Cell Motility Through Inhibition of Akt Activity and Integrin Expression in Pancreatic Cancer Cells

Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Malignant progression of pancreatic cancer depends not only on rapid proliferation of tumor cells but also on increased cell motility. In this study, we showed that increased PHLPP expression significantly reduced the rate of migration in pancreatic ductal adenocarcinoma (PDAC) cells whereas knockdown of PHLPP had the opposite effect. In addition, cell motility at the individual cell level was negatively regulated by PHLPP as determined using time-lapse imaging. Interestingly, the expression of β1 and β4 integrin proteins were decreased in PHLPP overexpressing cells and increased in PHLPP knockdown cells whereas the mRNA levels of integrin were not altered by changes in PHLPP expression. In determining the molecular mechanism underlying PHLPP-mediated regulation of integrin expression, we found that inhibition of lysosome activity rescued integrin expression in PHLPP overexpressing cells, thus suggesting that PHLPP negatively controls cell motility by inhibiting Akt activity to promote lysosome-dependent degradation of integrins. Functionally, the increased cell migration observed in PHLPP knockdown cells was effectively blocked by the neutralizing antibodies against β1 or β4 integrin. Taken together, our study identified a tumor suppressor role of PHLPP in suppressing cell motility by negatively regulating integrin expression in pancreatic cancer cells

Na/K-ATPase Y260 Phosphorylation-Mediated Src Regulation in Control of Aerobic Glycolysis and Tumor Growth

We report here the identification of α1 Na/K-ATPase as a major regulator of the proto-oncogene Src kinase and the role of this regulation in control of Warburg effect and tumor growth. Specifically, we discovered Y260 in α1 Na/K-ATPase as a Src-specific phosphorylation and binding site and that Y260 phosphorylation is required for Src-mediated signal transduction in response to a number of stimuli including EGF. As such, it enables a dynamic control of aerobic glycolysis. However, such regulation appears to be lost or attenuated in human cancers as the expression of Na/K-ATPase α1 was significantly decreased in prostate, breast and kidney cancers, and further reduced in corresponding metastatic lesions in patient samples. Consistently, knockdown of α1 Na/K-ATPase led to a further increase in lactate production and the growth of tumor xenograft. These findings suggest that α1 Na/K-ATPase works as a tumor suppressor and that a loss of Na/K-ATPase-mediated Src regulation may lead to Warburg phenotype in cancer

Neurotensin Regulates Proliferation and Stem Cell Function in the Small Intestine in a Nutrient-Dependent Manner

BACKGROUND & AIMS: Intestinal stem cells (ISCs) are sensitive to dietary alterations and nutrient availability. Neurotensin (NT), a gut peptide localized predominantly to the small bowel and released by fat ingestion, stimulates the growth of intestinal mucosa under basal conditions and during periods of nutrient deprivation, suggesting a possible role for NT on ISC function. METHODS: Leucine-rich repeat-containing G-protein coupled receptor 5-Enhanced Green Fluorescent Protein (Lgr5-EGFP) NT wild type (Nt+/+) and Lgr5-EGFP NT knockout (Nt-/-) mice were fed ad libitum or fasted for 48 hours. Small intestine tissue and crypts were examined by gene expression analyses, fluorescence-activated cell sorting, Western blot, immunohistochemistry, and crypt-derived organoid culture. Drosophila expressing NT in midgut enteroendocrine cells were fed a standard diet or low-energy diet and esg-green fluorescent protein+ ISCs were quantified via immunofluorescence. RESULTS: Loss of NT impaired crypt cell proliferation and ISC function in a manner dependent on nutrient status. Under nutrient-rich conditions, NT stimulated extracellular signal-regulated kinases 1 and 2 signaling and the expression of genes that promote cell-cycle progression, leading to crypt cell proliferation. Under conditions of nutrient depletion, NT stimulated WNT/β-catenin signaling and promoted an ISC gene signature, leading to enhanced ISC function. NT was required for the induction of WNT/β-catenin signaling and ISC-specific gene expression during nutrient depletion, and loss of NT reduced crypt cell proliferation and impaired ISC function and Lgr5 expression in the intestine during fasting. Conversely, the expression of NT in midgut enteroendocrine cells of Drosophila prevented loss of ISCs during nutrient depletion. CONCLUSIONS: Collectively, our findings establish an evolutionarily conserved role for NT in ISC maintenance during nutritional stress. GSE182828

Downregulation of SREBP Inhibits Tumor Growth and Initiation by Altering Cellular Metabolism in Colon Cancer

Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in colon cancer cells. Bioenergetic analysis revealed that silencing SREBP1 or SREBP2 expression reduced the mitochondrial respiration, glycolysis, as well as fatty acid oxidation indicating an alteration in cellular metabolism. Consequently, the rate of cell proliferation and the ability of cancer cells to form tumor spheroids in suspension culture were significantly decreased. Similar results were obtained in colon cancer cells in which the proteolytic activation of SREBP was blocked. Importantly, knockdown of either SREBP1 or SREBP2 inhibited xenograft tumor growth in vivo and decreased the expression of genes associated with cancer stem cells. Taken together, our findings establish the molecular basis of SREBP-dependent metabolic regulation and provide a rationale for targeting lipid biosynthesis as a promising approach in colon cancer treatment

Metagenomic Next-Generation Sequencing in the Diagnosis of HHV-1 Reactivation in a Critically Ill COVID-19 Patient: A Case Report

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests. Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient\u27s clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged. Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients