Comparative Effects of Microalgal Species on Growth, Feeding, and Metabolism of Pearl Oysters, Pinctada fucata martensii and Pinctada maxima

Pinctada fucata martensii and P. maxima are two main traditional pearl oyster species that can produce seawater pearls. Our previous study showed a higher clearance rate (CR) and growth performance in P. f. martensii than in P. maxima fed with Isochrysis galbana. In this study, the P. f. martensii and P. maxima juveniles of two sizes (large and small) were fed with six different microalgae diets [I. galbana (I), Platymonas subcordiformis (P), Chaetoceros muelleri I, I+P, I+C, and P+C] to evaluate the differences in growth, feeding, and metabolism between two pearl oyster species. After 60 d of the rearing period, P. f. martensii and P. maxima fed with mixed microalgae showed a significantly higher relative growth rate (RGR) than those fed with single microalgae (P< 0.05). The RGRs were significantly higher in P. f. martensii than those in P. maxima fed with the same diets (P< 0.05). The RGRs showed a decreasing tendency with the growth in both pearl oyster species. The CRs of pearl oysters fed with mixed microalgae were significantly higher than those fed with single microalgae (P< 0.05), and the CRs of P. f. martensii were significantly higher than those of P. maxima fed with the same diets (P< 0.05). Significantly lower respiration rates (RRs) were observed in small-size P. f. martensii groups fed with I, P, and I+P diets and all large P. f. martensii groups compared to P. maxima fed with the same diets (P< 0.05). Higher activities of amylase, cellulase, lipase, and pepsin in P. f. martensiiwere observed compared to P. maxima fed with the same diets at two sizes. The pepsin activities in P. maxima decreased with the growth, while there were no consistent pepsin activities of P. f. martensii with the growth. The carbonic anhydrase activities in P. maxima were significantly higher than those in P. f. martensii fed with the same diets (P< 0.05). The carbonic anhydrase activities were highest in the I+C diet group, followed by C+P and I+P, I, C, and P groups. Significant differences were observed among different diet groups in the same pearl oyster species (P< 0.05). Our results suggest that the lower CR and activities of digestive enzymes and higher RRs and activities of carbonic anhydrase may cause a lower growth rate of P. maxima compared to P. f. martensii

Icariin Protects Bone Marrow Mesenchymal Stem Cells Against Iron Overload Induced Dysfunction Through Mitochondrial Fusion and Fission, PI3K/AKT/mTOR and MAPK Pathways

Iron overload has been reported to contribute to bone marrow mesenchymal stem cells (BMSCs) damage, but the precise mechanism still remains elusive. Icariin, a major bioactive monomer belonging to flavonoid glucosides isolated from Herba Epimedii, has been shown to protect cells from oxidative stress induced apoptosis. The aim of this study was to investigate whether icariin protected against iron overload induced dysfunction of BMSCs and its underlying mechanism. In this study, we found that iron overload induced by 100 μM ferric ammonium citrate (FAC) caused apoptosis of BMSCs, promoted cleaved caspase-3 and BAX protein expressions while inhibited Bcl-2 protein expression, which effects were significantly attenuated by icariin treatment. In addition, iron overload induced significant depolarization of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and inhibition of mitochondrial fusion/fission, which effects were also attenuated by icariin treatment. Meanwhile, we found that iron overload induced by 100 μM FAC significantly inhibited mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, inhibited DRP1 and Cytochrome C protein translocation from the cytoplasm to mitochondria. Icariin at concentration of 1 μM was able to promote mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, and increase DRP1 and cytochrome C protein translocation from the cytoplasm to mitochondria. Further, osteogenic differentiation and proliferation of BMSCs was significantly inhibited by iron overload, but icariin treatment rescued both osteogenic differentiation and proliferation of BMSCs. Further studies showed that icariin attenuated iron overload induced inactivation of the PI3K/AKT/mTOR pathway and activation of the ERK1/2 and JNK pathways. In summary, our study indicated that icariin was able to protect against iron overload induced dysfunction of BMSCs. These effects were potentially related to the modulation of mitochondrial fusion and fission, activation of the PI3K/AKT/mTOR pathway and inhibition of ERK1/2 and JNK pathways

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Preoperative albumin-to-fibrinogen ratio predicts chemotherapy resistance and prognosis in patients with advanced epithelial ovarian cancer

Abstract Background Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery. Methods A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan–Meier method using log-rank test. Results The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan–Meier method by log-rank test (P < 0.001). Conclusions A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery

Scientific Machine Learning of 2D Perovskite Nanosheet Formation

We apply a scientific machine learning framework to aid the prediction and understanding of nanomaterial formation processes via a joint spectral-kinetic model. We apply this framework to study nucleation and growth of 2D perovskite nanosheets. Colloidal nanomaterials have size-dependent optical properties, and can be observed in situ, all of which make them a good model for understanding the complex processes of nucleation, growth and phase transformation of 2D perovskites. Our results demonstrate that this model nanomaterial can form through two processes at the nanoscale: either via a layer-by-layer chemical exfoliation process from lead bromide nanocrystals or via direct nucleation from precursors. We utilize a phenomenological kinetic analysis to study the exfoliation process and scientific machine learning to study the direct nucleation and growth, and discuss the circumstances under which it is more appropriate to use phenomenological or more complex machine learning models. Data for both analysis techniques are collected through in-situ spectroscopy in a stopped flow chamber, incorporating over 500,000 spectra taken under more than 100 different conditions. More broadly, our research shows that the ability to utilize and integrate traditional kinetics and machine learning methods will greatly assist the understanding of complex chemical systems

Efficacy of vigabatrin in the treatment of infantile epileptic spasms syndrome: A systematic review and meta‐analysis

Abstract This systematic review and meta‐analysis aimed to evaluate the efficacy of vigabatrin (VGB) in treating infantile epileptic spasms syndrome (IESS). Databases of PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library were systematically searched. All the relevant randomized controlled trials (RCTs) and observational studies (OSs) of VGB for IESS were included and analyzed separately. The primary outcome was the cessation of epileptic spasms (ES). Five RCTs and nine OSs compared the efficacy of VGB vs hormonal monotherapy for IESS. Meta‐analysis of the five RCTs showed that hormonal monotherapy was significantly better than VGB monotherapy (OR = 0.37, 95% CI = 0.20‐0.67) for patients with new‐onset IESS. Meta‐analysis of the nine OSs agrees with the result from RCTs (OR = 0.61, 95% CI = 0.43‐0.85). VGB was more effective in patients with TSC than in those with other etiologies (five OSs, OR = 5.59, 95% CI = 2.17‐14.41). There was no significant difference in the efficiency of VGB combined with hormonal therapy vs hormonal monotherapy for IESS (two RCTs, OR = 0.75, 95% CI = 0.09‐6.45). Hormonal monotherapy is better than VGB monotherapy for non‐TSC‐associated IESS. But for patients with IESS due to TSC, VGB is the first choice. VGB combined with hormone therapy does not definitely increase ES control rates compared with that of hormonal monotherapy

Protein Phosphatase 6 Interacts with the DNA-Dependent Protein Kinase Catalytic Subunit and Dephosphorylates γ-H2AX▿ †

The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) plays a major role in the repair of DNA double-strand breaks (DSBs) by nonhomologous end joining (NHEJ). We have previously shown that DNA-PKcs is autophosphorylated in response to ionizing radiation (IR) and that dephosphorylation by a protein phosphatase 2A (PP2A)-like protein phosphatase (PP2A, PP4, or PP6) regulates the protein kinase activity of DNA-PKcs. Here we report that DNA-PKcs interacts with the catalytic subunits of PP6 (PP6c) and PP2A (PP2Ac), as well as with the PP6 regulatory subunits PP6R1, PP6R2, and PP6R3. Consistent with a role in the DNA damage response, silencing of PP6c by small interfering RNA (siRNA) induced sensitivity to IR and delayed release from the G2/M checkpoint. Furthermore, siRNA silencing of either PP6c or PP6R1 led to sustained phosphorylation of histone H2AX on serine 139 (γ-H2AX) after IR. In contrast, silencing of PP6c did not affect the autophosphorylation of DNA-PKcs on serine 2056 or that of the ataxia-telangiectasia mutated (ATM) protein on serine 1981. We propose that a novel function of DNA-PKcs is to recruit PP6 to sites of DNA damage and that PP6 contributes to the dephosphorylation of γ-H2AX, the dissolution of IR-induced foci, and release from the G2/M checkpoint in vivo