UBE2N promotes cell viability and glycolysis by promoting Axin1 ubiquitination in prostate cancer cells.

BACKGROUND: Ubiquitin-conjugating enzyme E2 N (UBE2N) is recognized in the progression of some cancers; however, little research has been conducted to describe its role in prostate cancer. The purpose of this paper is to explore the function and mechanism of UBE2N in prostate cancer cells. METHODS: UBE2N expression was detected in Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data, prostate cancer tissue microarrays, and prostate cancer cell lines, respectively. UBE2N knockdown or overexpression was used to analyze its role in cell viability and glycolysis of prostate cancer cells and tumor growth. XAV939 or Axin1 overexpression was co-treated with UBE2N overexpression to detect the involvement of the Wnt/ß-catenin signaling and Axin1 in the UBE2N function. UBE2N interacting with Axin1 was analyzed by co-immunoprecipitation assay. RESULTS: UBE2N was upregulated in prostate cancer and the UBE2N-high expression correlated with the poor prognosis of prostate cancer. UBE2N knockdown inhibited cell viability and glycolysis in prostate cancer cells and restricted tumor formation in tumor-bearing mice. Wnt/ß-catenin inhibition and Axin1 overexpression reversed the promoting viability and glycolysis function of UBE2N. UBE2N promoted Axin1 ubiquitination and decreased Axin1 protein level.

Gene therapy approaches for obesity-induced adipose neuropathy: Device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose.

Maintaining functional adipose innervation is critical for metabolic health. We found that subcutaneous white adipose tissue (scWAT) undergoes peripheral neuropathy (PN) with obesity, diabetes, and aging (reduced small-fiber innervation and nerve/synaptic/growth-cone/vesicle markers, altered nerve activity). Unlike with nerve injuries, peripheral nerves do not regenerate with PN, and therefore new therapies are needed for treatment of this condition affecting 20-30 million Americans. Here, we validated a gene therapy approach using an adipocyte-tropic adeno-associated virus (AAV; serotype Rec2) to deliver neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) directly to scWAT to improve tissue-specific PN as a proof-of-concept approach. AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN, but after longer periods of dietary obesity there was reduced efficacy, revealing a key time window for therapies. AAVRec2-NGF also increased scWAT innervation in obese mice and was more effective than BDNF, likely because Rec2 targeted adipocytes, the tissue's endogenous NGF source. AAVRec2-NGF also worked well even after 25 weeks of dietary obesity, unlike BDNF, which likely needs a vector that targets its physiological cellular source (stromal vascular fraction cells). Given the differing effects of AAVs carrying NGF versus BDNF, a combined therapy may be ideal for PN.

Selective Recovery of Cathode Materials from Spent Lithium-Ion Battery Material with a Near-Room-Temperature Separation.

Effective separation of cathode materials from the current collector is a critical step in recycling a spent lithium-ion battery (LIB). This typically necessitates the decomposition or dissolution of the organic binder, poly(vinylidene fluoride) (PVDF), to achieve efficient recovery of cathode materials. However, this process requires a high decomposition temperature, typically between 400 and 600 °C, and can lead to side reactions, such as current collector oxidation/brittleness, decomposition of cathode materials, and formation of metal fluorides. In this study, we propose that non-thermal plasma (NTP) treatment can be used to achieve an extremely high separation of cathode materials and aluminum current collector at near room temperature. Instead of relying on PVDF decomposition, which requires high temperatures, PVDF can be deactivated by partially breaking down long molecular chains with appropriate NTP conditions. With a total treatment time of around 2000 s and an environmental temperature of approximately 80 °C, minor side reactions can be avoided. The separation rate can reach up to 95.69%, and high-quality cathode materials can be obtained with only 0.02 wt % aluminum impurity content. This research could potentially offer a new approach toward minimizing recycling steps and reducing energy consumption in the recycling of spent LIBs. It could also be extended to the recovery of a broader range of electronic wastes.

Promising remedies for cardiovascular disease: Natural polyphenol ellagic acid and its metabolite urolithins.

BACKGROUND: Cardiovascular disease (CVD) is a significant worldwide factor contributing to human fatality and morbidity. With the increase of incidence rates, it is of concern that there is a lack of current therapeutic alternatives because of multiple side effects. Ellagic acid (EA), the natural polyphenol (C14H6O8), is abundant in pomegranates, berries, and nuts. EA and its intestinal microflora metabolite, urolithins, have recently attracted much attention as a potential novel "medicine" because of their wide pharmacological properties. PURPOSE: This study aimed to critically analyze available literature to summarize the beneficial effects of EA and urolithins, and highlights their druggability and therapeutic potential in various CVDs. METHODS: We systematically studied research and review articles between 1984 and 2022 available on various databases to obtain the data on EA and urolithins with no language restriction. Their cardiovascular protective activities, underlying mechanism, and druggability were highlighted and discussed comprehensively. RESULTS: We found that EA and urolithins may exert preventive and curative effects on CVD with negligible side effects and possibly regulate lipid metabolism imbalance, pro-inflammatory factor production, vascular smooth muscle cell proliferation, cardiomyocyte apoptosis, endothelial cell dysfunction, and Ca2+ intake and release. Potentially, this may lead to the prevention and amelioration of atherosclerosis, hypertension, myocardial infarction, cardiac fibrosis, cardiomyopathy, cardiac arrhythmias, and cardiotoxicities in vivo. Several molecules and signaling pathways are associated with their therapeutic actions, including phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, NF-κB, nuclear factor erythroid-2 related factor 2, sirtuin1, miRNA, and extracellular signal-regulated kinase 1/2. CONCLUSION: In vitro and in vivo studies shows that EA and urolithins could be used as valid candidates for early prevention and effective therapeutic strategies for various CVDs.

A sustainable process for selective recovery of metals from gallium-bearing waste generated from LED industry.

With the rapid development of the LED industry, gallium (Ga)-bearing waste generated is regarded as one of the most hazardous as it typically contains heavy metals and combustible organics. Traditional technologies are characterized by long processing routes, complex metal separation processes and significant secondary pollution emission. In this study, we proposed an innovative and green strategy to selectively recovery Ga from Ga-bearing waste by using a quantitative phase-controlling transition process. In the phase-controlling transition process, the gallium nitride (GaN) and indium (In) are converted to alkali-soluble gallium (III) oxide (Ga2O3) and alkali-insoluble indium oxides (In2O3) by oxidation calcination, while nitrogen is converted into diatomic nitrogen gas instead of ammonia/ammonium (NH3/NH4+). By selective leaching with NaOH solution, nearly 92.65% of Ga can be recycled with a leaching selectivity of 99.3%, while little emissions of NH3/NH4+. Ga2O3 with a purity of 99.97% was obtained from the leachate which is also economy promising by economic assessment. Therefore, the proposed methodology compared to the conventional acid and alkali leaching methods is potentially greener and more efficient process for extracting valuable metals from nitrogen-bearing solid waste.

The Biomimetics of Mg2+-Concentration-Resolved Microenvironment for Bone and Cartilage Repairing Materials Design.

With the increase in population aging, the tendency of osteochondral injury will be accelerated, and repairing materials are increasingly needed for the optimization of the regenerative processes in bone and cartilage recovery. The local environment of the injury sites and the deficiency of Mg2+ retards the repairing period via inhibiting the progenitor osteogenesis and chondrogenesis cells' recruitment, proliferation, and differentiation, which results in the sluggish progress in the osteochondral repairing materials design. In this article, we elucidate the Mg2+-concentration specified effect on the cell proliferation, osteochondral gene expression, and differentiation of modeling chondrocytes (extracted from New Zealand white rabbit) and osteoblasts (MC3T3-E1). The concentration of Mg2+ in the culture medium affects the proliferation, chondrogenesis, and osteogenesis: (i) Appropriate concentrations of Mg2+ promote the proliferation of chondrocytes (1.25−10.0 mM) and MC3T3-E1 cells (2.5−30.0 mM); (ii) the optimal concentration of Mg2+ that promotes the gene expression of noncalcified cartilage is 15 mM, calcified cartilage 10 mM, and subchondral bone 5 mM, respectively; (iii) overdosed Mg2+ leads to the inhibition of cell activity for either chondrocytes (>20 mM) or osteoblasts (>30 mM). The biomimetic elucidation for orchestrating the allocation of gradient concentration of Mg2+ in accordance of the physiological condition is crucial for designing the accurate microenvironment in osteochondral injury defects for optimization of bone and cartilage repairing materials in the future.

Genome-Wide Analysis of AGC Kinases Reveals that MoFpk1 Is Required for Development, Lipid Metabolism, and Autophagy in Hyperosmotic Stress of the Rice Blast Fungus Magnaporthe oryzae.

During eukaryotic evolution, the TOR-AGC kinase signaling module is involved in the coordinated regulation of cell growth and survival. However, the AGC kinases in plant-pathogenic fungi remain poorly understood. In this study, we have identified 20 members of the AGC family of protein kinases. Evolutionary and biological studies have revealed that AGC kinases are highly conserved and involved in the growth (8 genes), conidiation (13 genes), conidial germination (9 genes), appressorium formation (9 genes), and pathogenicity (5 genes) of Magnaporthe oryzae, in which a subfamily protein of the AGC kinases, MoFpk1, the activator of flippase, specifically exhibited diverse roles. Two kinase sites were screened and found to be critical for MoFpk1: 230K and 326D. Moreover, MoFpk1 is involved in cell wall integrity through the negative regulation of MoMps1 phosphorylation. The deletion of MoFpk1 resulted in defective phosphatidylacetamide (PE) and phosphatidylserine (PS) turnover and a series of lipid metabolism disorders. Under hyperosmotic stress, since the ΔMofpk1 mutant is unable to maintain membrane asymmetry, MoYpk1 phosphorylation and MoTor activity were downregulated, thus enhancing autophagy. Our results provide insights into the evolutionary and biological relationships of AGC kinases and new insight into plasma membrane (PM) homeostasis, i.e., responses to membrane stress and autophagy through lipid asymmetry maintenance. IMPORTANCE Our identification and analysis of evolutionary and biological relationships provide us with an unprecedented high-resolution view of the flexible and conserved roles of the AGC family in the topmost fungal pathogens that infect rice, wheat, barley, and millet. Guided by these insights, an AGC member, MoFpk1, was found to be indispensable for M. oryzae development. Our study defined a novel mechanism of plasma membrane homeostasis, i.e., adaptation to stress through the asymmetric distribution of phospholipids. Furthermore, defects in the asymmetric distribution of phospholipids in the membrane enhanced autophagy under hyperosmotic stress. This study provides a new mechanism for the internal linkage between lipid metabolism and autophagy, which may help new fungicide target development for controlling this devastating disease.

Synthesis and Applications of SAPO-34 Molecular Sieves.

Silicoaluminophosphate zeolite (SAPO-34) has been attracting increasing attention due to its excellent form selection and controllability in the chemical industry, as well as being one of the best industrial catalysts for methanol-to-olefin (MTO) reaction conversion. However, as a microporous molecular sieve, SAPO-34 easily generates carbon deposition and rapidly becomes inactivated. Therefore, it is necessary to reduce the crystal size of the zeolite or to introduce secondary macropores into the zeolite crystal to form a hierarchical structure in order to improve the catalytic effect. In this review, the synthesis methods of conventional SAPO-34 molecular sieves, hierarchical SAPO-34 molecular sieves and nanosized SAPO-34 molecular sieves are introduced, and the properties of the synthesized SAPO-34 molecular sieves are described, including the phase, morphology, pore structure, acid source, and catalytic performance, in particular with respect to the synthesis of hierarchical SAPO-34 molecular sieves. We hope that the review can provide guidance to the preparation of the SAPO-34 catalysts, and stimulate the future development of high-performance hierarchical SAPO-34 catalysts to meet the growing demands of the material and chemical industries.

Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris.

BACKGROUND: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive. PURPOSE: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms. METHODS: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis. RESULTS: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/ß-catenin signaling via alleviating the overexpression of ß-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis. CONCLUSION: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.

Dietary intake of mixture coarse cereals prevents obesity by altering the gut microbiota in high-fat diet fed mice.

Functional components including ß-glucan, dietary fiber, resistant starch and polyphenols extracted from various coarse cereals have been reported to prevent high-fat diet (HFD) induced obesity via modulating gut microbiota. In this study, millet, maize, oat, soybean, and purple potato were ultrafine comminuted, mixed, and then extruded for the preparation of puffed mixture coarse cereals. HFD was used to investigate the effects of mixture coarse cereals on obesity and gut microbiota in mice. The results showed that dietary intake of mixture coarse cereals could decrease body weight gain and fat accumulation, improve the blood glucose tolerance and serum lipids levels, reduce the systemic inflammation, and down-regulate the expression of hepatic lipogenic genes. In addition, the levels of SCFAs and the composition of gut microbiota were investigated. The results indicated that mixture coarse cereals could promote the release of SCFAs, enhance the diversity of gut microbiota, and increase the relative abundance of Lactobacillus and Bifidobacterium, which might contribute to the anti-obesity activity. Present work suggested that the mixture coarse cereals could be developed as a nutraceutical for the prevention of HFD-induced obesity.

Comprehensive characterization on Ga (In)-bearing dust generated from semiconductor industry for effective recovery of critical metals.

Gallium (indium)-bearing dust generated from semiconductor industry is an important secondary resource for critical metal recycling. However, the diverse and distinct physicochemical natures of such waste material have made its recycling less effective, e.g. low extraction rate and complex treatment procedures. This research is devoted to gaining in-depth knowledge of the physical and chemical properties of such waste, including the chemical composition, physical phases, particle size distribution and chemical-thermal properties with a series of technologies. As a consequence, the occurrence and distribution of GaN and metallic indium phases are found to be crucial to efficient metal recycling. The thermal-chemical behavior shows that continuous oxidation occurred in the air atmosphere, indicating that heat-treatment followed by acid leaching is feasible to improve their recycling efficiencies. This process is able to leach 80.35% of gallium and 95.78% of indium with one-step operation. Furthermore, different treatment strategies for the waste material are preliminarily evaluated and discussed for the aim of metal recovery. The results show that gallium can be selectively recycled with recycling rate of 89.59% using alkaline leaching. With this research, the understanding on the recyclability of different metals and possibilities of selective recovery can be improved. It provides guidelines during the stage of decision-making for critical metal recycling in order to achieve efficient resource circulation.

Relationship of phenolic composition of selected purple maize (Zea mays L.) genotypes with their anti-inflammatory, anti-adipogenic and anti-diabetic potential.

This study aimed to investigate the associations between phenolic composition of selected purple maize genotypes and their anti-inflammatory, anti-adipogenic and anti-diabetic properties in vitro. Anthocyanin-rich water extracts (PMWs) from 20 purple maize genotypes were evaluated in RAW 264.7 macrophages and 3T3-L1 adipocytes under different conditions. Cyanidin-3-O-glucoside (C3G), pelargonidin-3-O-glucoside (Pr3G), peonidin-3-O-glucoside (P3G) and corresponding acylated forms were major anthocyanins in PMW, accompanied by ten tentatively identified non-anthocyanin phenolics. Correlation studies showed that C3G, P3G, and derivatives, but not Pr3G and its acylated form contributed to the biological properties of PMW. Besides anthocyanins, quercetin, luteolin, and rutin were the dominant anti-inflammatory and anti-diabetic components, in terms of down-regulating pro-inflammatory mediator production in inflamed macrophages and adipocytes, modulating diabetes-related key enzymes and improving insulin sensitivity in insulin-resistant adipocytes. Quercetin and phenolic acids, especially vanillic acid and protocatechuic acid, were closely associated with anti-adipogenic properties of PMW via inhibition of the preadipocyte-adipocyte transition.

Polylactic acid nano- and microchamber arrays for encapsulation of small hydrophilic molecules featuring drug release via high intensity focused ultrasound.

Long term encapsulation combined with spatiotemporal release for a precisely defined quantity of small hydrophilic molecules on demand remains a challenge in various fields ranging from medical drug delivery, controlled release of catalysts to industrial anti-corrosion systems. Free-standing individually sealed polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip-coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient conditions. The wall thickness of these hydrophobic nano-microchambers is tunable from 150 nm to 7 µm by varying the PLA solution concentration. Furthermore, small hydrophilic molecules were successfully in situ precipitated within individual microchambers in the course of solvent evaporation after sonicating the PLA@PDMS stamp to remove air-bubbles and to load the active substance containing solvent. The cargo capacity of single chambers was determined to be in the range of several picograms, while it amounts to several micrograms per cm2. Two different methods for sealing chambers were compared: microcontact printing versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for entrapment of micro-air-bubbles enabling microchambers with both ultrasound responsiveness and reduced permeability. Cargo release triggered by external high intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and compared with numerical simulations.

Maripseudobacter aurantiacus gen. nov., sp. nov., a novel member of the family Flavobacteriaceae isolated from a sedimentation basin.

A Gram-stain negative, orange-pigmented, aerobic, non-motile and ovoid- to rod-shaped bacterial strain, designated CDA4T, was isolated from a sediment sample collected from the sedimentation basin of a mariculture farm in Zhejiang province, China. The temperature range for growth of strain CDA4T was 15-40 °C, wirrth an optimum at 35 °C. The pH range for growth was 6.0-8.5, with an optimum around pH 7.5. NaCl was required for growth at the concentration range 0.5-5.0 % (w/v), with an optimum at 2.0 % (w/v). Chemotaxonomic analysis indicated that the main respiratory quinone was menaquinone 6 (MK-6), the predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G, unknown ECL 13.565 and iso-C17 : 0 3-OH, and the major polar lipids were phosphatidylethanolamine, two unidentified lipids, two unidentified phospholipids and four unidentified aminolipids. The genomic DNA G+C content of strain CDA4T was 38.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CDA4T formed a distinct lineage in the clade of the family Flavobacteriaceae. Based on the polyphasic taxonomic characterization, strain CDA4T is considered to represent a novel species of a new genus, for which the name Maripseudobacter aurantiacus gen. nov., sp. nov. is proposed. The type strain of the type species is CDA4T (=KCTC 52409T=MCCC 1K03210T).

Marinibaculum pumilum gen. nov., sp. nov., isolated from seawater.

A Gram-stain-negative, facultatively anaerobic, motile and rod-shaped strain, designed H2T, was isolated from the Western Pacific Ocean, and subjected to a taxonomic investigation using a polyphasic approach. Strain H2T grew at 15-40 °C and pH 6.0-9.0 (optimum 37 °C and pH 6.5), and with 1-10 % (w/v) NaCl (optimum 2 %). The predominant respiratory quinone was ubiquinone-10 (Q-10) and the major fatty acids identified were C19 : 0 cyclo ω8c, C18 : 1ω7c, C18 : 0 and 11-methyl-C18 : 1ω7c. The polar lipids of strain H2T consisted of phosphatidylglycerol, one unknown phospholipid, one unknown glycolipid and three unidentified aminolipids. The DNA G+C content was 75.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain H2T formed a distinct clade belong to the family Rhodospirillaceae within the Alphaproteobacteria. On the basis of morphological, physiological and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain H2T represents a novel species in a new genus in the family Rhodospirillaceae, for which the name Marinibaculumpumilum gen. nov., sp. nov. is proposed. The type strain of the type species is H2T(=MCCC 1K02279T=KCTC 42964T).