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Probiotics are commonly used as nutritional supplements and antibiotic substitutes and thus are of great commercial interest. The present study was performed to demonstrate the probiotic potential of Exiguobacterium acetylicum G1–33 isolated from the gut of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) by integrating genomics and phenotypic traits. In silico genome analysis confirmed its identity as E. acetylicum. Functional annotation of the genome revealed the existence of molecular markers responsible for the functional properties of potential probiotics, such as resistance to the host’s harsh gastrointestinal environment, adhesion and colonization of the intestinal mucosa, competition and inhibition of pathogens, responses to oxidative stress, and biosynthesis of essential amino acids and vitamins. The genomic analysis was validated by in vitro experiments. Effective toxin-encoding genes were not identified in the G1–33 genome, and the safety of the strain was confirmed by in vitro experiments. These results indicate that E. acetylicum G1–33 exhibits excellent probiotic properties and can become a probiotic with high application value in aquaculture.

This study aims to examine the effects of the mixture of Bacillus cereus G1–11 and Exiguobacterium acetylicum G1–33, isolated from the gut of hybrid groupers (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂), on the host. The hybrid groupers were divided into a control (C, without any probiotics), B. cereus (BC, 1010 cfu/g), E. acetylicum (EA, 108 cfu/g), compound (mix, a 1:1 mixture of B. cereus and E. acetylicum), and positive reference group (P, Lactobacillus acidophilus, 5 × 108 cfu/L). Each group had four replicates, with 30 fish per replicate (53.30 ± 0.50 g), and were fed for 60 days. The results showed that adding probiotics to the feed significantly improved the weight gain, weight growth rate, specific growth rate, and digestive enzyme activities of hybrid groupers compared to the C group. The compound group was the most significant. In addition, composite probiotics added to feed significantly upregulated the expression levels of several growth-related genes in the liver and muscles. The activities of alkaline phosphatase, catalase, glutathione peroxidase, glutathione transferase, lysozyme, and total antioxidant capacity in the serum and liver were significantly influenced through mixed probiotic feeding. Moreover, the expression levels of several immune-related genes in the liver, spleen, and head kidney were significantly enhanced by adding single and mixed probiotics to feed, with the synergy of mixed probiotics being the best. An analysis of the gut microbiota showed that adding composite bacteria enhanced the richness and diversity of the gut microbiota, significantly increasing the relative abundance of potential probiotics (Cetobacterium and Microbacterium) while decreasing the presence of potential pathogens (Mycoplasma). Overall, our findings highlighted the efficacy of mixed probiotics (B. cereus and E. acetylicum) in enhancing growth performance, nutritional value of hybrid grouper feed, antioxidant capacity, immune response, and intestinal health, in finding the best combination of functional feed additives.

Excessive lipid accumulation promotes the occurrence and progression of hepatocellular carcinoma (HCC), accompanied by high levels of fatty acid synthetase (FASN) and more active lipogenesis. Heat shock protein 90 (Hsp90) acts as a chaperone to maintain the stability and activity of the client proteins. Studies have revealed that Hsp90 regulates the lipid metabolism of HCC, but the effect of Hsp90 on FASN still remains unknown. This study aims to discover the mechanism of Hsp90 inhibition on lipid accumulation and investigate the different effects of Hsp90 N-terminal domain inhibitor STA9090 and C-terminal domain inhibitor novobiocin on FASN protein stability and transcription pathway in HCC. We found that HCC cells tended to store lipids, which could be disrupted by Hsp90 inhibitors in vivo and in vitro. High levels of Hsp90α and FASN in tumor tissue had correlation with poor prognosis of HCC patients, and Hsp90α interacted with FASN to maintain its protein stability. Furthermore, N-terminal domain of Hsp90α was essential for process of sterol regulatory element binding protein 1 to activate FASN transcription and Hsp90α prevented proteasomal degradation of liver X receptor α to upregulate FASN transcription via liver X receptor α/sterol regulatory element binding protein 1 axis. Our data reveal that Hsp90α promotes lipid accumulation by increasing the protein stability and FASN mRNA transcription, and can be alleviated by Hsp90 inhibitors, which provides a theoretical basis for Hsp90-targeted therapy on lipid metabolism in HCC.

Voltage-dependent anion-selective channel protein 1 (VDAC1) is the most abundant protein in the mitochondrial outer membrane and plays a crucial role in the control of hepatocellular carcinoma (HCC) progress. Our previous research found that cytosolic molecular chaperone heat shock protein 90 (Hsp90) interacted with VDAC1, but the effect of the C-terminal and N-terminal domains of Hsp90 on the formation of VDAC1 oligomers is unclear. In this study, we focused on the effect of the C-terminal domain of Hsp90 on VDAC1 oligomerization, ubiquitination, and VDAC1 channel activity. We found that Hsp90 C-terminal domain inhibitor Novobiocin promoted VDAC1 oligomerization, release of cytochrome c, and activated mitochondrial apoptosis pathway. Atomic coarse particle modeling simulation revealed C-terminal domain of Hsp90α stabilized VDAC1 monomers. The purified VDAC1 was reconstituted into a planar lipid bilayer, and electrophysiology experiments of patch clamp showed that the Hsp90 C-terminal inhibitor Novobiocin increased VDAC1 channel conductance via promoting VDAC1 oligomerization. The mitochondrial ubiquitination proteomics results showed that VDAC1 K274 mono-ubiquitination was significantly decreased upon Novobiocin treatment. Site-directed mutation of VDAC1 (K274R) weakened Hsp90α-VDAC1 interaction and increased VDAC1 oligomerization. Taken together, our results reveal that Hsp90 C-terminal domain inhibition promotes VDAC1 oligomerization and VDAC1 channel conductance by decreasing VDAC1 K274 mono- ubiquitination, which provides a new perspective for mitochondria-targeted therapy of HCC.

Based on the volume of fluid algorithm and user-defined function, the flow and heat transfer of falling film on an elliptical transverse tube with different axis ratios was numerically studied. Simulation results are discussed based on the velocity, pressure, and temperature distribution of the liquid. According to the results, the liquid film pattern, heat and mass transfer of the liquid film are affected by the axis ratios: the liquid flow rate of the film outside the elliptical tube was faster compared with a circular tube; the simulated wall pressure gradually decreased along the flow direction and then rapidly recovered, and the position of the minimum pressure moved backwards with the increase of the axis ratio. Also, the distribution of local Nu along the wall was similar to the pressure distribution with the minimum value of X = 0.90. In general, the heat transfer of an elliptical tube performs best when the axis ratio is e = 1.65. The simulated Nu number distribution and film thickness were compared with published experimental data, which showed acceptable consistency. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 (Hsp90) has been an important therapeutic target for cancer therapy for decades. Unexpectedly, the monotherapy of N-terminal Hsp90 inhibitor STA9090 related clinical trials halted in phase III, and metastases were reported in animal models with the treatment of N-terminal Hsp90 inhibitors. Vacuolar protein sorting-associated protein 35 (VPS35) plays a vital role in endosome-derived EV (extracellular vesicle) traffic in neurodegeneration diseases, but no vps35 related EV were reported in tumors till now. Since tumor derived EVs contributes to metastasis and VPS35 is recently found to be involved in the invasion and metastasis of hepatocellular carcinoma (HCC), whether N-terminal Hsp90 inhibitor STA9090 induced EVs generation and the role of VPS35 in it were explored in this study. We found that N-terminal Hsp90 inhibitor STA9090 upregulated Bclaf1 and VPS35 levels, increased the secretion of EVs, and STA9090-induced-EVs promoted the invasion of HepG2 cells. As the clinical data suggested that the increased Bclaf1 and VPS35 levels correlated with increased metastasis and poorer prognosis in HCC, we focused on the Bclaf1-VPS35-EVs axis to further explore the mechanism of VPS35-related metastasis. The results demonstrated that Bclaf1 facilitated the transcription of VPS35 via bZIP domain, and knockdown of Bclaf1 or VPS35 alleviated pro-metastatic capability of STA9090-induced-EVs. All the results revealed the role of Bclaf1-VPS35-EVs axis on metastasis of HCC, and VPS35 knockdown decreased Hsp90 Inhibitor STA9090 induced extracellular vesicle release and metastasis, which provided a new combination therapeutic strategy to inhibit the metastasis of HCC caused by N-terminal Hsp90 inhibitor induced extracellular vesicles.

In this paper, firstly, a new intuitionistic fuzzy (IF) entropy has been put forward, which considered both the uncertainty and the hesitancy degree of IF sets. Through comparing with other entropy measures, the advantage of the new entropy measure is obvious. Secondly, based on the new entropy measure, a new decision making method of a multi-attribute decision making problem was subsequently put forward, in which attribute values are expressed with IF values. In the cases of attribute weights, completely unknown and attribute weights are partially known. Two methods were constructed to determine them. One method is an extension of the ordinary entropy weight method, and the other method is a construction the optimal model according to the minimum entropy principle. Finally, two practical examples are given to illustrate the effectiveness and practicability of the proposed method.

As a new extension of Pythagorean fuzzy set (also called Atanassov’s intuitionistic fuzzy set of second type), interval-valued Pythagorean fuzzy set which is parallel to Atanassov’s interval-valued intuitionistic fuzzy set has recently been developed to model imprecise and ambiguous information in practical group decision making problems. The aim of this paper is to put forward a novel decision making method for handling multiple criteria group decision making problems within interval-valued Pythagorean fuzzy environment based on interval-valued Pythagorean fuzzy numbers (IVPFNs). There are three key issues being addressed in this approach. The first is to introduce an interval-valued Pythagorean fuzzy weighted arithmetic averaging (IVPF-WAA) operator to aggregate the decision data in order to get the overall preference values of alternatives. Some desirable properties of the IVPF-WAA operator are also investigated. Based on the idea of the maximizing deviation method, the second is to establish an optimization model for determining the weights of criteria for each expert. The third is to construct a minimizing consistency optimal model to derive the weights of criteria for the group. Finally, an illustrating example is given to verify the proposed approach.