Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

Biological Self-Assembled Transmembrane Electron Conduits for High-Efficiency Ammonia Production in Microbial Electrosynthesis.

Usually, CymA is irreplaceable as the electron transport hub in Shewanella oneidensis MR-1 bidirectional electron transfer. In this work, biologically self-assembled FeS nanoparticles construct an artificial electron transfer route and implement electron transfer from extracellular into periplasmic space without CymA involvement, which present similar properties to type IV pili. Bacteria are wired up into a network, and more electron transfer conduits are activated by self-assembled transmembrane FeS nanoparticles (electron conduits), thereby substantially enhancing the ammonia production. In this study, we achieved an average NH4+-N production rate of 391.8 µg·h-1·L reactor-1 with the selectivity of 98.0% and cathode efficiency of 65.4%. Additionally, the amide group in the protein-like substances located in the outer membrane was first found to be able to transfer electrons from extracellular into intracellular with c-type cytochromes. Our work provides a new viewpoint that contributes to a better understanding of the interconnections between semiconductor materials and bacteria and inspires the exploration of new electron transfer chain components.

Effects of stroke on the intestinal biota in diabetic mice and type 2 diabetic patient biota.

AIMS: The intestinal biota, known for its colonization of the human intestine and its modulation of host pathophysiological responses through the immune and endocrine systems, has gained substantial interest in recent years due to its notable correlation with diabetes and stroke. METHODS: In order to examine this association, a comparative study was conducted on the intestinal biota and blood samples obtained from mouse models and type 2 diabetic patients with and without stroke complications. Advanced techniques, such as high-throughput sequencing and enzyme-linked immunosorbent assay were employed to identify the differences in the intestinal biota and blood indices of mouse models and patients. RESULTS: At the phylum level, the dominant gut bacteria identified in patients with diabetes mellitus and stroke were Firmicutes, Bacteroidetes, and Proteobacteria. It was noteworthy that the relative abundance of Bacteroides at the genus level was significantly diminished in the DB-PT group (photothrombotic diabetes mice) as compared to the DB group (diabetesmice). This result was consistent with observations in human samples. Additionally, significant variations were detected in lipid proteins, specifically APOA4, in diabetic patients with and without stroke. CONCLUSIONS: Stroke can diminish the abundance and diversity of intestinal biota, potentially correlating with lipid proteins in patients with diabetes.

Removal of ofloxacin using a porous carbon microfiltration membrane based on in-situ generated •OH.

This study investigated the removal performance of ofloxacin (OFL) by a novel electro-Fenton enhanced microfiltration membrane. The membranes used in this study consisted of metal-organic framework derived porous carbon, carbon nanotubes and Fe2+, which were able to produce hydroxyl radicals (•OH) in-situ via reducing O2 to hydrogen peroxide. Herein, membrane filtration with bias not only concentrated the pollutants to the level that could be efficiently treated by electro-Fenton but also confined/retained the toxic intermediates within the membrane to ensure a prolonged contact time with the oxidants. After validated by experiments, the applied bias of -1.0 V, pH of 3 and electrolyte concentration of 0.1 M were the relatively optimum conditions for OFL degradation. Under these conditions, the average OFL removal rate could be reach 75% with merely 5% membrane flux loss after 4 cycles operation by filtrating 1 mg/L OFL. Via decarboxylation reaction, piperazinyl ring opening, dealkylation and ipso substitution reaction, etc., OFL could be gradually and efficiently degraded to intermediate products and even to CO2 by •OH. Moreover, the oxidation reaction was preferred to following first-order reaction kinetics. This research verified a possibility for antibiotic removal by electro-enhanced microfiltration membrane.

Optimization of Covert Communication in Multi-Sensor Asymmetric Noise Systems.

This work investigates wireless covert communication in a multi-sensor asymmetric noise scenario. We adopt KL (Kullback-Leibler) divergence as the covertness constraint metric and mutual information as the transmission rate metric. To accurately approximate KL divergence and mutual information in covert communication, we employ the Taylor series expansion technique. Analytical expressions for KL divergence and mutual information in covert communication are derived, and we optimize the amplitude gain and phase angles based on these analytical expressions. Our findings underscore the importance of phase angle selection in covert communication within asymmetric noise systems. We propose an effective method for optimizing the transmission amplitude gain and phase angles in scenarios with asymmetric noise. Numerical results validate the effectiveness and superiority of our proposed method.

Epigallocatechin-3-gallate at the nanoscale: a new strategy for cancer treatment.

CONTEXT: Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways. However, its low bioavailability and rapid degradation hinder its clinical application. OBJECTIVE: This review explores the potential of nanoencapsulation to enhance the stability, bioavailability, and therapeutic efficacy of EGCG in cancer treatment. METHODS: We searched the PubMed database from 2019 to the present, using 'epigallocatechin gallate', 'EGCG', and 'nanoparticles' as search terms to identify pertinent literature. This review examines recent nano-engineering technology advancements that encapsulate EGCG within various nanocarriers. The focus was on evaluating the types of nanoparticles used, their synthesis methods, and the technologies applied to optimize drug delivery, diagnostic capabilities, and therapeutic outcomes. RESULTS: Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment. Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG. The studies highlighted include those where EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms. CONCLUSIONS: Nanoencapsulation of EGCG represents a promising approach in oncology, offering multiple therapeutic benefits over its unencapsulated form. Although the results so far are promising, further research is necessary to fully optimize the design of these nanosystems to ensure their safety, efficacy, and clinical viability.

Deep multilayer brain omics identifies the potential involvement of menopause molecular networks in Gliomas' disease progression.

The risk of high-grade gliomas is lower in young females, however, its incidence enhances after menopause, suggesting potential protective roles of female sex hormones. Hormone oscillations after menopause have received attention as a possible risk factor. Little is known about risk factors for adult gliomas. We examined the association of the aging brain after menopause, determining the risk of gliomas with proteomics and the MALDI-MSI experiment. Menopause caused low neurotransmitter levels such as GABA and ACH, high inflammatory factor levels like il-1ß, and increased lipid metabolism-related levels like triglycerides in the brain. Upregulated and downregulated proteins after menopause were correlated with differentially expressed glioma genes, such as ACTA2, CAMK2D, FNBPIL, ARL1, HEBP1, CAST, CLIC1, LPCAT4, MAST3, and DOCK9. Furthermore, differential gene expression analysis of monocytes showed that the downregulated gene LPCAT4 could be used as a marker to prevent menopausal gliomas in women. Our findings regarding the association of menopause with the risk of gliomas are consistent with several extensive cohort studies. In view of the available evidence, postmenopausal status is likely to represent a significant risk factor for gliomas.

Correlation of idiopathic benign paroxysmal positional vertigo with cerebral small vessel disease.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most prevalent form of peripheral vertigo, with vascular lesions being one of its suspected causes. The older adults are particularly vulnerable to BPPV. Cerebral small vessel disease (CSVD), on the other hand, is a clinical condition that results from damage of cerebral small vessels. Vascular involvement resulting from age-related risk factors and proinflammatory state may act as the underlying factor linking both BPPV and CSVD. AIM: The objective of this study is to explore the potential correlation between BPPV and CSVD by examining whether individuals aged 50 and older with BPPV exhibit a greater burden of CSVD. MATERIALS AND METHODS: This retrospective study included patients aged 50 years and older who had been diagnosed with BPPV. A control group consisting of patients diagnosed with idiopathic facial neuritis (IFN) during the same time period was also included. The burden of cerebral white matter hyperintensities (WMHs) was evaluated using the Fazekas scale. An ordinal regression analysis was conducted to investigate the potential correlation between BPPV and WMHs. RESULTS: The study included a total of 101 patients diagnosed with BPPV and 116 patients with IFN. Patients with BPPV were found to be significantly more likely (OR = 2.37, 95% CI 1.40-4.03, p = 0.001) to have a higher Fazekas score compared to the control group. Brain infarctions, hypertension, and age were all identified as significant predictors of white matter hyperplasia on MRI, with OR of 9.9 (95% CI 4.21-24.84, P<0.001), 2.86 (95% CI 1.67-5.0, P<0.001), and 1.18 (95% CI 1.13-1.22, P<0.001) respectively. CONCLUSION: Our findings suggest that vascular impairment caused by age-related risk factors and proinflammatory status may be contributing factors to the development of BPPV in individuals aged 50 and above, as we observed a correlation between the suffering of BPPV and the severity of WMHs.

Sulfide-driven nitrous oxide recovery during the mixotrophic denitrification process.

We propose a novel sulfide-driven process to recover N2O during the traditional denitrification process. The optimum initial sulfide concentration was 120 mg/L, and the N2O percentage in the gaseous products (N2O+N2) was up to 82.9%. Moreover, sulfide involved in denitrification processes could substitute for organic carbon as an electron donor, e.g., 1 g sulfide was equivalent to 0.5-2 g COD when sulfide was oxidized to sulfur and sulfate. The accumulation of N2O was mainly due to the inhibiting effect of sulfide on nitrous oxide reductase (N2OR), which was induced by the supply insufficiency of electrons from cytochrome c (cyt c) to N2OR. When the initial sulfide concentration was 120 mg/L, the N2OR activity was only 36.8% of its original level. According to the results of cyclic voltammetry, circular dichroism spectra and fluorescence spectra, significant changes in the conformations and protein structures of cyt c were caused by sulfide, and cyt c completely lost its electron transport capacity. This study provides a new concept for N2O recovery driven by sulfide in the denitrification process. In addition, the findings regarding the mechanism of the inhibition of N2OR activity have important implications both for reducing emissions of N2O and recovering N2O in the sulfide-driven denitrification process.

Visible-Light-Induced Photoreduction of Carborane Phosphonium Salts: Efficient Synthesis of Carborane-Oxindole-Pharmaceutical Hybrids.

Visible-light-induced photoreaction of carboranes is an effective approach to prepare carborane-containing compounds. While several methods involving boron-centered carboranyl radicals have been established, those for carbon-centered carboranyl radicals are underdeveloped, except for the UV-light-promoted photohomolysis. Herein, we describe a simple but effective approach to access carbon-centered carboranyl radicals by photoreduction of carborane phosphonium salts under blue light irradiation without using transition metals and photocatalysts. The utility of the method was demonstrated by successfully preparing a range of carborane-oxindole-pharmaceutical hybrids by radical cascade reactions. Computational and experimental studies suggest that the carbon-centered carboranyl radicals are generated by single-electron transfer of the photoactive charge-transfer complexes between the salts and the additive potassium acetate.

METTL14-mediated N6-methyladenosine modification of Pten mRNA inhibits tumour progression in clear-cell renal cell carcinoma.

BACKGROUND: Clear-cell renal-cell carcinoma (ccRCC) is one of the leading causes of tumour-related death worldwide. Methyltransferase-like 14 (METTL14) is reported to regulate m6A modification in cancers. The aim of this study is to investigate the biological function and molecular mechanism of METTL14 in the pathogenesis of ccRCC. METHODS: Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were used to detect the expression of METTL14 and Pten. METTL14 overexpression or knockdown was used in the in vitro and in vivo studies to investigate the biological functions of METTL14. m6A-RNA immunoprecipitation and RNA immunoprecipitation were used to investigate the m6A modification mediated by METTL14. RESULTS: METTL14 expression was significantly down-regulated in ccRCC tissues. Functionally, upregulation of METTL14 inhibited ccRCC cells proliferation and migration in vitro. METTL14 overexpression significantly inhibited the activation of the phosphoinositide 3 kinase (PI3K)/AKT signalling pathway. Furthermore, phosphate and tension homology deleted on chromosome ten (Pten) is a target of METTL14. Overexpression of METTL14 increased the m6A enrichment of Pten, and promoted Pten expression. METTL14-enhanced Pten mRNA stability was dependent on YTHDF1. CONCLUSIONS: METTL14-mediated m6A modification of Pten mRNA inhibited tumour progression, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for ccRCC.

Nitrate removal by anammox biomass with intracellular carbon source as electron donors via DNRA pathway.

In this work, a novel nitrate (NO3-) reduction pathway by anaerobic ammonium oxidation (anammox) biomass was firstly discovered with the intracellular carbon sources as the only electron donors. And the possible reaction mechanism was deduced to be intracellular dissimilatory nitrate reduction to ammonium (DNRA) pathway according to the experimental results. In batch experiments, without any external electron donors, NO3--N (about 50 mg/L) was reduced to N2 within 48 h, and a small amount of NO2--N was detected (the maximum of 2 mg/L) with the anammox biomass concentration of 4400 mg/L. Acetylene (4.46 mmol/L) addition resulted in obvious NH4+ accumulation during NO3- degradation by anammox biomass, since acetylene mainly interfered in hydrazine (N2H4) generation from NH4+ and NO. Without HCO3- addition, the NO3--N degradation rate was slower than that with HCO3- addition. Simultaneously, glycogen contents inside anammox biomass decreased to 133.22 ± 1.21 mg/g VSS and 129.79 ± 1.21 mg/g VSS with and without HCO3-, respectively, from 142.20 ± 0.61 mg/g VSS. In the long-term experiment, anammox biomass stably degraded NO3--N without external electron donors addition, and the maximum removal efficiency of NO3--N reached 55.4%. The above results indicated the anammox bacteria utilized the DNRA pathway to reduce NO3- to NO2- and further NH4+, then normal anammox metabolism would continue to convert the produced NO2- and NH4+ to N2. The intracellular stored carbon sources (e.g., glycogen) were supposed to be electron donors for NO3- degradation. This capability would enhance the viability and living space of anammox bacteria in different natural ecosystems, and make it plausible that complete nitrogen removal could be implemented only by the anammox process.

Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury.

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4-/- mice with deficiency of the hepatobiliary phospholipid transporter. METHODS: Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4-/- (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group). A total of 58 human subjects were recruited into the study, including patients with alcohol-associated liver disease (AALD; n = 31) and healthy controls (n = 27). The hepatic and ileal expressions of genes involved in bile acid metabolism, plasma FGF levels, and bile acid and its precursors 7α- and 27-hydroxycholesterol (7α- and 27-OHC) concentrations were determined. Primary mouse hepatocytes were isolated for cell culture experiments. RESULTS: Alcohol feeding significantly induced plasma FGF21 and decreased hepatic Cyp7a1 levels. Hepatic expression levels of Fibroblast growth factor receptor 1 (Fgfr1), Fgfr4, Farnesoid X-activated receptor (Fxr), and Small heterodimer partner (Shp) and plasma FGF15/FGF19 levels did not differ with alcohol challenge. Exogenous FGF21 treatment suppressed Cyp7a1 in a dose-dependent manner in vitro. AALD patients showed markedly higher FGF21 and lower 7α-OHC plasma levels while FGF19 did not differ. CONCLUSIONS: The simultaneous upregulation of FGF21 and downregulation of Cyp7a1 expressions upon chronic plus binge alcohol feeding together with the invariant plasma FGF15 and hepatic Shp and Fxr levels suggest the presence of a direct regulatory mechanism of FGF21 on bile acid homeostasis through inhibition of CYP7A1 by an FGF15-independent pathway in this ACLI model. Lay Summary: Alcohol challenge results in the upregulation of FGF21 and repression of Cyp7a1 expressions while circulating FGF15 and hepatic Shp and Fxr levels remain constant both in healthy and pre-injured livers, suggesting the presence of an alternative FGF15-independent regulatory mechanism of FGF21 on bile acid homeostasis through the inhibition of Cyp7a1.

Three-Dimensional (3D)-Printed Zero-Order Released Platform: a Novel Method of Personalized Dosage Form Design and Manufacturing.

In 2017, there are 451 million people with diabetes worldwide. These figures were expected to increase to 693 million by 2045. The research and development of hypoglycemic drugs has become a top priority. Among them, sulfonylurea hypoglycemic drugs such as glipizide are commonly used in non-insulin-dependent type II diabetes. In order to adapt to the wide range of hypoglycemic drugs and the different individual needs of patients, this topic used glipizide as a model drug, and prepared glipizide preparations with 3D printing technology. The purpose of this study was to investigate the prescription applicability and control-release behavior of structure and explore the application prospects of 3D printing personalized drug delivery formulations. This article aims to establish a production process for personalized preparations based on 3D printing technology. The process is easy to obtain excipients, universal prescriptions, flexible dosages, exclusive customization, and integrated automation. In this paper, the UV method was used to determine the in vitro release and content analysis method of glipizide; the physical and chemical properties of the glipizide were investigated. The established analysis method was inspected and evaluated, and the experimental results met the methodological requirements. Glipizide controlled-release tablets were prepared by the semisolid extrusion (SSE) method using traditional pharmaceutical excipients combined with 3D printing technology. The formulation composition, in vitro release, and printing process parameters of the preparation were investigated, and the final prescription and process parameters (traveling speed 6.0-7.7 mm/s and extruding speed 0.0060-0.0077 mm/s) were selected through comprehensive analysis. The routine analysis results of the preparation showed that the performance of the preparation meets the requirements. In order for 3D printing technology to play a better role in community medicine and telemedicine, this article further explored the universality of the above prescription and determined the scope of application of prescription drugs and dosages. Glipizide, gliclazide, lornoxicam, puerarin, and theophylline were used as model drugs, and the range of drug loading percentage was investigated. The results showed when the solubility of the drug is 9.45 -8.34 mg/mL, and the drug loading is 3-43%; the release behavior is similar.

Sensitivity of pituitary gonadotropes to hyperglycemia leads to epigenetic aberrations and reduced follicle-stimulating hormone levels.

The connection between metabolism and reproductive function is well recognized, and we hypothesized that the pituitary gonadotropes, which produce luteinizing hormone and follicle-stimulating hormone (FSH), mediate some of the effects directly via insulin-independent glucose transporters, which allow continued glucose metabolism during hyperglycemia. We found that glucose transporter 1 is the predominant glucose transporter in primary gonadotropes and a gonadotrope precursor-derived cell line, and both are responsive to culture in high glucose; moreover, metabolite levels were altered in the cell line. Several of the affected metabolites are cofactors for chromatin-modifying enzymes, and in the gonadotrope precursor-derived cell line, we recorded global changes in histone acetylation and methylation, decreased DNA methylation, and increased hydroxymethylation, some of which did not revert to basal levels after cells were returned to normal glucose. Despite this weakening of epigenetic-mediated repression seen in the model cell line, FSH ß-subunit ( Fshb) mRNA levels in primary gonadotropes were significantly reduced, apparently due in part to increased autocrine/paracrine effects of inhibin. However, unlike thioredoxin interacting protein and inhibin subunit α, Fshb mRNA levels did not recover after the return of cells to normal glucose. The effect on Fshb expression was also seen in 2 hyperglycemic mouse models, and levels of circulating FSH, required for follicle growth and development, were reduced. Thus, hyperglycemia seems to target the pituitary gonadotropes directly, and the likely extensive epigenetic changes are sensed acutely by Fshb. This scenario would explain clinical findings in which, even after restoration of optimal blood glucose levels, fertility often remains adversely affected. However, the relative accessibility of the pituitary provides a possible target for treatment, particularly crucial in the young in which hyperglycemia is increasingly common and fertility most relevant.-Feldman, A., Saleh, A., Pnueli, L., Qiao, S., Shlomi, T., Boehm, U., Melamed, P. Sensitivity of pituitary gonadotropes to hyperglycemia leads to epigenetic aberrations and reduced follicle-stimulating hormone levels.

Mitigating Membrane Fouling Based on In Situ •OH Generation in a Novel Electro-Fenton Membrane Bioreactor.

A novel electro-Fenton membrane bioreactor was constructed to investigate the effect of electro-Fenton on mitigating membrane fouling. Herein, porous carbon (PC), carbon nanotubes (CNTs) and Fe2+ were spun into hollow fiber membranes (Fe-PC-CHFM), then served as cathode and filtration core simultaneously. The H2O2 can be in situ produced by O2 reduction with electro-assistance, and further induce hydroxyl radicals (•OH) generation with loaded Fe2+ on the surface of Fe-PC-CHFM. In addition, Fe3+/Fe2+ cycle can be realized effectively by the electro-assistance, avoiding ferrous iron addition. During over 100-day operation, the electro-Fenton membrane bioreactor achieved 93% of COD and 88% of NH4+-N removal at a HRT of 8 h. At the end of operation, the membranes in electro-Fenton membrane bioreactor still exhibited obviously mesh-like structure similarly to initial level. Importantly, merely 15 min with an operation voltage of -0.8 V was sufficient to completely recover permeate flux of the fouled Fe-PC-CHFM. The energy consumption used for membrane fouling control was barely 8.64 × 10-5 kW·h/m3. Therefore, this novel energy-saved electro-Fenton membrane bioreactor process could provide an envisaging prospective and promising method for practice wastewater membrane treatment.

An epigenetic switch repressing Tet1 in gonadotropes activates the reproductive axis.

The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, but Tet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function. We find that all three TET enzymes are expressed in gonadotrope-precursor cells, but Tet1 mRNA levels decrease markedly with completion of cell differentiation, corresponding with an increase in expression of the luteinizing hormone gene, Lhb We demonstrate that poorly differentiated gonadotropes express a TET1 isoform lacking the N-terminal CXXC-domain, which represses Lhb gene expression directly and does not catalyze 5hmC at the gene promoter. We show that this isoform is also expressed in other differentiated tissues, and that it is regulated by an alternative promoter whose activity is repressed by the liganded estrogen and androgen receptors, and by the hypothalamic gonadotropin-releasing hormone through activation of PKA. Its expression is also regulated by DNA methylation, including at an upstream enhancer that is protected by TET2, to allow Tet1 expression. The down-regulation of TET1 relieves its repression of the methylated Lhb gene promoter, which is then hydroxymethylated and activated by TET2 for full reproductive competence.

Enhanced Oral Delivery of Curcumin via Vitamin E TPGS Modified Nanodiamonds: a Comparative Study on the Efficacy of Non-covalent and Covalent Conjugated Strategies.

Despite that either non-covalent or covalent attachment of hydrophilic polymers or surfactants onto nanodiamonds (NDs) could overcome the shortcomings of being a drug delivery system, it is hard to draw a definite conclusion which strategy is more effective. Hence, with the purpose of comparing the influence of different coating approach of NDs on the oral delivery efficiency of water-insoluble model drug curcumin (CUR), NDs were firstly modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via non-covalent or covalent conjugation method, and then loaded with CUR (CUR@NDs-COOH/TPGS or CUR@NDs-TPGS). In comparison with the core-shell-structured CUR@NDs-COOH/TPGS, CUR@NDs-TPGS were irregular in shape with dense TPGS film, and exhibited smaller size, more negatively potential, and higher drug loading efficiency. The covalent connection group also showed higher anti-cancer activity, cellular uptake, and permeability through the Caco-2 cell monolayers, as well as favorable distribution, penetration, and retention in rat intestines. The oral bioavailability study in rats demonstrated that CUR@NDs-TPGS showed significantly greater Cmax and AUC0-t in contrast with CUR suspension and the TPGS-coated ones, respectively. The findings illustrated that covalent grafting TPGS onto the surface of NDs possesses better efficacy and biocompatibility on oral delivery of poorly soluble drug CUR than pristine and non-covalent coated nanoparticles.

Novel Anaerobic Electrochemical Membrane Bioreactor with a CNTs Hollow Fiber Membrane Cathode to Mitigate Membrane Fouling and Enhance Energy Recovery.

A novel anaerobic treatment system that combines the impact of applied voltage with membrane filtration over carbon nanotubes hollow fiber membranes (CNTs-HFMs) was developed at low temperature (15-20 °C) to mitigate membrane fouling, treat wastewater, and recover energy (CH4). Herein, electro-assisted CNTs-HFMs served a dual function as the cathode and membrane filtration. In contrast with other two anaerobic membrane bioreactors (AnMBRs; polyvinylidene fluoride hollow fiber membranes and CNTs-HFMs without electro-assistance), the CNTs-HFMs with electro-assistance (-1.2 V applied voltage) had slower transmembrane pressure (TMP) increasing rates and better TMP recovery with a more than 95% effluent chemical oxygen demand (COD) removal rate during an almost 100-day operation period. This result can be attributed to the presence of an electrostatic repulsion force pushing pollutants (mainly extracellular polymeric substances, EPS) away from the membrane surface, thereby hindering the formation of a gel layer and mitigating membrane pore blocking in the anaerobic electro-assisted membrane bioreactor (AnEMBR). Due to the almost two-times higher Methanomicrobia content and more H2-utilizing methanogens than the other two AnMBRs, approximately more than 111.12 mL/gVSS d of CH4 was obtained in the AnEMBR with electro-assistance. This work provides an efficient strategy for mitigating membrane fouling, improving water quality, and enhancing CH4 yield.

Synthesis, Formulation, and Characterization of Doxorubicin-Loaded Laponite/Oligomeric Hyaluronic Acid-Aminophenylboronic Acid Nanohybrids and Cytological Evaluation against MCF-7 Breast Cancer Cells.

As a synthetic clay material, laponite RDS (LR) was investigated as an effective drug carrier as a result of the special nanodisk structure together with the negative-charged surface to achieve enhanced cellular uptake and targeted delivery. In this research work, the synthesized oligomeric hyaluronic acid-aminophenylboronic acid (oHA-APBA) was entangled onto LR nanodisks to fabricate a valid targeted platform for breast cancer therapy. Briefly, through the formation of amide bonds, 3-APBA was connected to the chain of oHA with a substituted ratio of 4.0 ± 0.2% to synthesize oHA-APBA copolymer. Thereafter, doxorubicin (DOX) was inserted into the interlayer space of LR by the way of the ion exchange process, followed by an assembly with oHA-APBA as a targeted protection layer. The satisfactory drug encapsulation efficiency (> 80%) and narrow size distribution were achieved. The in vitro drug release study demonstrated the release of DOX from DOX@LR/oHA-APBA was sustained and acid dependent. In addition, after fitting the drug cumulative release of DOX@LR/oHA-APBA under different pH conditions with several kinetic models, it was identified that drug release from DOX@LR/oHA-APBA nanohybrids at pH 5.0 was mainly dependent on both diffusion and ion exchange effects. However, under the condition of pH 7.4, the drug was most efficiently released by diffusion effect. Importantly, DOX@LR/oHA-APBA showed remarkable cellular uptake and intracellular drug distribution in MCF-7 cells, which were consistent with inhibitory ability against MCF-7 cells. Hence, the high DOX loading capacity and enhanced cellular tracking can enlighten LR/oHA-APBA as an effective drug delivery carrier for breast cancer therapy.