Improved physicochemical stability of fish oil nanoemulsion via a dense interfacial layer formed by hyaluronic acid-poly(glyceryl)10-stearate.

This study aimed to synthesize a novel emulsifier, hyaluronic acid-poly(glyceryl)10-stearate (HA-PG10-C18), and employ it for the fabrication of nanoemulsions incorporating deep-sea fish oil to improve their apparent solubility and physicochemical stability. 1H NMR and FT-IR analyses indicated successful synthesis of HA-PG10-C18. Nanoemulsions of deep-sea fish oil loaded with HA-PG10-C18 (HA-PG10-C18@NE) were successfully fabricated by ultrasonic emulsification. The fixed aqueous layer thickness (FALT) of PG10-C18@NE and HA-PG10-C18@NE was determined and the FALT of both nanoemulsions was similar, while the surface density of HA-PG10-C18@NE (4.92 × 10-12 ng/nm2) is 60 % higher than that of PG10-C18@NE (3.07 × 10-12 ng/nm2). Notably, HA-PG10-C18@NE demonstrated an exceptional physicochemical stability when exposed to various stressed environmental conditions, especially its freeze-thaw stability. Moreover, after simulated in vitro digestion, the HA-PG10-C18@NE exhibited a comparatively greater liberation of free fatty acids (94.0 ± 1.7 %) when compared to the release observed in PG10-C18@NE (85.5 ± 2.2 %).

In-utero evaluation of the fetal umbilical-portal venous system among fetuses with persistent right umbilical vein: Two-and three-dimensional ultrasonographic study.

OBJECTIVE: The aim of this study was to describe the anatomy of the portal system in fetuses with persistent right umbilical vein (PRUV). METHODS: Prospective observational study of fetuses diagnosed with PRUV. All patients underwent a comprehensive portal system anatomy scan supplemented by two-dimensional (2D) and three-dimensional (3D) color doppler modalities. RESULTS: 29 fetuses with PRUV were studied. We perceived an identical anatomical pattern in 28 fetuses. The right umbilical vein drains to the portal sinus (future right portal vein, RPV), which has a configuration of a left portal vein (LPV) in the normal left portal system, with three emerging branches: inferior (RPVi), medial (RPVm) and superior (RPVs). The RPV then courses to the left, towards the stomach to the point of the bifurcation of the main portal vein (MPV) to become the left portal vein. The LPV has an RPV configuration in a normal portal system with anterior (LPVa) and posterior (RPVp) branches. This anatomical layout mimics a mirror image of the normal anatomy of left portal system. CONCLUSION: PRUV has unique umbilical portal venous anatomy, which is a mirror image of the normal left portal system. It can be demonstrated prenatally and serve as an additional tool for prenatal diagnosis of PRUV.

Preparation and characterization of glyceryl stearate/cassava starch composite for wax therapy.

Glyceryl stearate and cassava starch (CS) composites were prepared by an esterification process. Formulations containing starch at various concentrations were prepared, being 1, 1.5, 3, 5, 10, 15, 20, and 30 % by weight, respectively. The characteristics of pH, moisture content, FTIR, melting point, latent heat, thermal energy storage, and specific heat capacity of composites were elucidated. The optimal formulation contained 1 % w/w CS, this indicated that the composite was able to maintain its temperature for 9.4 ± 0.5 min, with a melting temperature of 51.9 ± 0.3 °C, solidification temperature of 36.1 ± 1.6 °C, latent heat of fusion of 120 ± 10 J/g, and latent heat of solidification of 126 ± 3 J/g, and specific heat capacity of 2.6 ± 0.2 J/g.K. New bonds were formed in the composite structure of glyceryl stearate and CS at these levels. The composite had a pH that was safe for contact with human skin and a moisture content that could be kept stable for a prolonged time. The innovation and the advantages of a composite materials: 1. The main components are derived from natural materials. 2. Costs effective 3. Sustainability 4. Safety, and 5. Efficacy. Therefore, composites have a high potential as are replacement for paraffin wax bath therapy.

ß-Carotene laden antibacterial and antioxidant gelatin/polyglyceryl stearate nano-hydrogel system for burn wound healing application.

Worldwide, burn wounds are severe health issues prone to bacterial infections and challenging to treat with traditional wound dressings. Therefore, a highly desirable biological macromolecules-based wound dressing with good antioxidant, antibacterial, biocompatible, and a large surface area is required. Herein, aim to develop a biological macromolecules-based physically cross-linked gelatin/polyglyceryl stearate/graphene oxide (GPGO) hydrogel to treat burn wounds. Four sets of hydrogels were prepared by varying GO concentrations. FT-IR, FE-SEM, viscosity analysis, mechanical and thermal stability confirmed the successful preparation of hydrogels with desired properties. Further, ß-carotene (0.5 mg/mL) was encapsulated in hydrogels to enhance the antioxidant activity, and a cumulative release as well as kinetics at pH 6.4 and 7.4 was performed. With an increase in GO concentration, hydrogels showed sustained release of ß-carotene. Among all, GPGO-3 ß hydrogel showed the highest antioxidant potency (57.75 %), hemocompatible (<5 %), cytocompatible (viable with NIH 3T3 cells), cell migration, proliferation, and in vitro wound healing. Also, GPGO-3 ß hydrogel showed efficient antibacterial activity (%inhibition of 85.5 % and 80.2 % and zone of 11 mm and 9.8 mm against S. aureus and E. coli). These results demonstrated the ability of GPGO-3 ß hydrogel as a promising candidate for burn wound healing applications.

Power-Up for Mucoadhesiveness: Two Generations of Thiolated Surfactants for Enhanced Sticky Nanoemulsions.

Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity of the thiol headgroup has major influence on mucoadhesive features of the nanoemulsion. Two generations of thiolated surfactants were synthetically derived from PEG-40-stearate featuring either a free thiol group or an S-protected thiol group. The surfactants were characterized regarding critical micelle concentration (CMC), hemolytic activity, and cytotoxicity. Subsequently, they were incorporated into nanoemulsions and the resulting nanoemulsions were characterized regarding particle size, polydispersity index (PDI), zeta potential, and time-dependent stability. Afterward, mucosal interactions as well as mucoadhesion on porcine intestinal mucosa were investigated. Successful synthesis of Cysteine-PEG-40-stearate (CYS-PEG-40-stearate) and MNA-Cysteine-PEG-40-stearate (MNA-CYS-PEG-40-stearate) was confirmed by 1H NMR spectroscopy. Both chemical modifications led to slightly elevated CMC values while preserving low cytotoxicity and hemotoxicity. Incorporation into nanoemulsions had minor influence on overall physical particle characteristics, while interactions with mucus and mucoadhesiveness of the nanoemulsions were drastically improved resulting in the rank order PEG-40-stearate < CYS-PEG-40-stearate < MNA-CYS-PEG-40-stearate. Accordingly, thiolated surfactants, especially S-protected derivatives, are versatile tools to generate highly mucoadhesive nanoemulsions.

Synthesis of Thermoplastic Mixed Chitin Esters.

Mixed chitin esters, that is, chitin benzoate stearates, exhibiting thermoplasticity, were synthesized by the acylation of chitin using benzoyl and stearoyl chlorides in the presence of pyridine and N,N-dimethyl-4-aminopyridine for 1 h + 24 h at 100 °C in an ionic liquid, 1-allyl-3-methylimidazolium bromide. IR and 1H NMR spectroscopic analyses confirmed the formation of the desired chitin benzoate stearates. Powder X-ray diffraction analysis of the products indicated that the crystalline structures of the chitin main-chains and stearoyl side-chains were strongly affected by the benzoyl/stearoyl substituent ratios. Introducing a small number of benzoyl groups, in addition to a large ratio of stearoyl groups, contributed to disrupting the intrinsic chitin crystals and enabling the chitin main chains and stearoyl side chains to form regularly controlled layered and parallel arrays, respectively. The resulting products exhibited meting points, associated with regular stearoyl packings, and formed melt-pressed films during the melt-pressing process. These results suggest that chitin benzoate stearates with appropriate benzoyl/stearoyl substituent ratios exhibit thermoplasticity.

Glycol Stearate and Glycol Stearate SE.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982, along with updated information regarding product types and concentrations of use, and confirmed that Glycol Stearate and Glycol Stearate SE are safe as cosmetic ingredients in the practices of use and concentration as described in this report.

Hyaluronic Acid Poly(glyceryl)10-Stearate Derivatives: Novel Emulsifiers for Improving the Gastrointestinal Stability and Bioaccessibility of Coenzyme Q10 Nanoemulsions.

Fish oils are a rich source of polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid, which are reported to exhibit therapeutic effects in a variety of human diseases. However, these oils are highly susceptible to degradation due to oxidation, leading to rancidity and the formation of potentially toxic reaction products. The aim of this study was to synthesize a novel emulsifier (HA-PG10-C18) by esterifying hyaluronic acid with poly(glyceryl)10-stearate (PG10-C18). This emulsifier was then used to formulate nanoemulsion-based delivery systems to co-deliver fish oil and coenzyme Q10 (Q10). Q10-loaded fish oil-in-water nanoemulsions were fabricated, and then their physicochemical properties, digestibility, and bioaccessibility were measured. The results indicated that the environmental stability and antioxidant activity of oil droplets coated with HA-PG10-C18 surpassed those coated with PG10-C18 due to the formation of a denser interfacial layer that blocked metal ions, oxygen, and lipase. Meanwhile, the lipid digestibility and Q10 bioaccessibility of nanoemulsions formulated with HA-PG10-C18 (94.9 and 69.2%) were higher than those formulated with PG10-C18 (86.2 and 57.8%), respectively. These results demonstrated that the novel emulsifier synthesized in this study could be used to protect chemically labile fat-soluble substances from oxidative damage, while still retaining their nutritional value.

Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence.

Cellular senescence is a state of proliferative arrest, and the development of carcinoma can be suppressed by conferring tumor cell senescence. Recently, we found that carnitine palmitoyltransferase 1C (CPT1C) controls tumor cell proliferation and senescence via regulating lipid metabolism and mitochondrial function. Here, 13C-metabolic flux analysis (13C-MFA) was performed and the results revealed that CPT1C knockdown in MDA-MB-231 cells significantly induced cellular senescence accompanied by altered fatty acid metabolism. Strikingly, stearate synthesis was decreased while oleate was increased. Furthermore, stearate significantly inhibited proliferation while oleate reversed the senescent phenotype induced by silencing CPT1C in MDA-MB-231 cells as well as PANC-1 cells. A939572, an inhibitor of stearoyl-Coenzyme A desaturase 1, had the same effect as stearate to inhibit cellular proliferation. These results demonstrated that stearate and oleate are involved in CPT1C-mediated tumor cellular senescence, and the regulation of stearate/oleate rate via inhibition of SCD-1 could be an additional strategy with depletion of CPT1C for cancer therapy.

LPGAT1/LPLAT7 regulates acyl chain profiles at the sn-1 position of phospholipids in murine skeletal muscles.

Skeletal muscle consists of both fast- and slow-twitch fibers. Phospholipids are important structural components of cellular membranes, and the diversity of their fatty acid composition affects membrane characteristics. Although some studies have shown that acyl chain species in phospholipids differ among various muscle fiber types, the mechanisms underlying these differences are unclear. To investigate this, we analyzed phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules in the murine extensor digitorum longus (EDL; fast-twitch) and soleus (slow-twitch) muscles. In the EDL muscle, the vast majority (93.6%) of PC molecules was palmitate-containing PC (16:0-PC), whereas in the soleus muscle, in addition to 16:0-PC, 27.9% of PC molecules was stearate-containing PC (18:0-PC). Most palmitate and stearate were bound at the sn-1 position of 16:0- and 18:0-PC, respectively, and 18:0-PC was found in type I and IIa fibers. The amount of 18:0-PE was higher in the soleus than in the EDL muscle. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) increased the amount of 18:0-PC in the EDL. Lysophosphatidylglycerol acyltransferase 1 (LPGAT1) was highly expressed in the soleus compared with that in the EDL muscle and was upregulated by PGC-1α. LPGAT1 knockout decreased the incorporation of stearate into PC and PE in vitro and ex vivo and the amount of 18:0-PC and 18:0-PE in murine skeletal muscle with an increase in the level of 16:0-PC and 16:0-PE. Moreover, knocking out LPGAT1 decreased the amount of stearate-containing phosphatidylserine (18:0-PS), suggesting that LPGAT1 regulated the acyl chain profiles of phospholipids, namely, PC, PE, and PS, in the skeletal muscle.

Desaturation of sebaceous-type saturated fatty acids through the SCD1 and the FADS2 pathways impacts lipid neosynthesis and inflammatory response in sebocytes in culture.

Sebum is a lipid-rich mixture secreted by the sebaceous gland (SG) onto the skin surface. By penetrating through the epidermis, sebum may be involved in the regulation of epidermal and dermal cells in both healthy and diseased skin conditions. Saturated and monounsaturated fatty acids (FAs), found as free FAs (FFAs) and in bound form in neutral lipids, are essential constituents of sebum and key players of the inflammatory processes occurring in the pilosebaceous unit in acne-prone skin. Little is known on the interplay among uptake of saturated FFAs, their biotransformation, and induction of proinflammatory cytokines in sebocytes. In the human SG, palmitate (C16:0) is the precursor of sapienate (C16:1n-10) formed by insertion of a double bond (DB) at the Δ6 position catalysed by the fatty acid desaturase 2 (FADS2) enzyme. Conversely, palmitoleate (C16:1n-7) is formed by insertion of a DB at the Δ9 position catalysed by the stearoyl coenzyme A desaturase 1 (SCD1) enzyme. Other FFAs processed in the SG, also undergo these main desaturation pathways. We investigated lipogenesis and release of IL-6 and IL-8 pro-inflammatory cytokines in SZ95 sebocytes in vitro after treatment with saturated FFAs, that is, C16:0, margarate (C17:0), and stearate (C18:0) with or without specific inhibitors of SCD1 and FADS2 desaturase enzymes, and a drug with mixed inhibitory effects on FADS1 and FADS2 activities. C16:0 underwent extended desaturation through both SCD1 and FADS2 catalysed pathways and displayed the strongest lipoinflammatory effects. Inhibition of desaturation pathways proved to enhance lipoinflammation induced by SFAs in SZ95 sebocytes. Palmitate (C16:0), margarate (C17:0), and stearate (C18:0) are saturated fatty acids that induce different arrays of neutral lipids (triglycerides) and dissimilar grades of inflammation in sebocytes.

Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies.

The most widely used and accessible monosaccharides have a number of stereogenic centers that have been hydroxylated and are challenging to chemically separate. As a result, the task of regioselective derivatization of such structures is particularly difficult. Considering this fact and to get novel rhamnopyranoside-based esters, DMAP-catalyzed di-O-stearoylation of methyl α-l-rhamnopyranoside (3) produced a mixture of 2,3-di-O- (4) and 3,4-di-O-stearates (5) (ratio 2:3) indicating the reactivity of the hydroxylated stereogenic centers of rhamnopyranoside as 3-OH > 4-OH > 2-OH. To get novel biologically active rhamnose esters, di-O-stearates 4 and 5 were converted into six 4-O- and 2-O-esters 6-11, which were fully characterized by FT-IR, 1H, and 13C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides 6-11 with maximum lipophilic character showed better antifungal susceptibility than antibacterial activity. These experimental findings are similar to the results found from PASS analysis data. Furthermore, the pentanoyl derivative of 2,3-di-O-stearate (compound 6) showed better antifungal functionality against F. equiseti and A. flavus, which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters 4-11 was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of 10 (-7.6 kcal/mol), 9 (-7.5 kcal/mol), and 7 (-6.9 kcal/mol) were better and comparable to fluconazole (-7.3 kcal/mol), indicating the likelihood of their use as non-azole type antifungal drugs in the future.

Myoinositol and methyl stearate increases rifampicin susceptibility among drug-resistant Mycobacterium tuberculosis expressing Rv1819c.

The alarming increase in multidrug resistance, which includes Bedaquiline and Delamanid, stumbles success in Tuberculosis treatment outcome. Mycobacterium tuberculosis gains resistance to rifampicin, which is one of the less toxic and potent anti-TB drugs, through genetic mutations predominantly besides efflux pump mediated drug resistance. In recent decades, scientific interventions are being carried out to overcome this hurdle using novel approaches to save this drug by combining it with other drugs/molecules or by use of high dose rifampicin. This study reports five small molecules namely Ellagic acid, Methyl Stearate, Myoinositol, Rutin, and Shikimic acid that exhibit synergistic inhibitory activity with rifampicin against resistant TB isolates. In-silico examinations revealed possible blocking of Rv1819c-an ABC transporter efflux pump that was known to confer resistance in M. tuberculosis to rifampicin. The synergistic anti-TB activity was assessed using a drug combination checkerboard assay. Efflux pump inhibition activity of ellagic acid, myoinositol, and methyl stearate was observed through ethidium bromide accumulation assay in the drug-resistant M. tuberculosis clinical strains and recombinant Mycobacterium smegmatis expressing Rv1819c in coherence with the significant reduction in the minimum inhibitory concentration of rifampicin. Cytotoxicity of the active efflux inhibitors was tested using in silico and ex vivo methods. Myoinositol and methyl stearate were completely non-toxic to the hematological and epithelial cells of different organs under ex vivo conditions. Based on these findings, these molecules can be considered for adjunct TB therapy; however, their impact on other drugs of anti-TB regimen needs to be tested.

Enzymatic production of wax esters by esterification using lipase immobilized via physical adsorption on functionalized rice husk silica as biocatalyst.

The present study consists of developing an enzymatic process for the production of wax esters (lauryl stearate and cetyl stearate) by esterification in a heptane medium. Lipase from Thermomyces lanuginosus (TLL) immobilized via interfacial activation on silica particles from rice husks functionalized with triethoxy(octyl)silane (TLL-Octyl-SiO2 ) was used as biocatalyst. Maximum immobilized protein loading of around 22 mg g-1 (that corresponds to an immobilization yield of ≈55%) of support was observed using an initial protein loading of 40 mg g-1 of Octyl-SiO2 . Its hydrolytic activity (olive oil emulsion hydrolysis) was of 620 U g-1 of biocatalyst. The effect of certain factors on the cetyl estearate production was evaluated using a central composite rotatable design (CCDR). Under optimal conditions (64°C, 21% of mass of biocatalyst per volume of reaction mixture, 170 rpm, and stoichiometric acid:alcohol molar ratio 1 mol L-1 of each reactant), maximum acid conversion percentage of 91% was observed after 60 min of reaction. Lauryl stearate was also produced under such conditions, and an acid conversion of 93% after 60 min of reaction was also achieved. Free lipase exhibited acid conversion of only 15%-20% for both reaction mixtures. After nine successive esterification batches, TLL-Octyl-SiO2 retained 85%-90% of its original activity. These results show the promising use of the prepared biocatalyst in wax esters production due to its high catalytic activity and reusability.

Stearate-derived very long-chain fatty acids are indispensable to tumor growth.

Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains unclear. While previous studies have focused on involvement of long-chain fatty acids (LCFAs) including palmitate in cancer, little attention has been paid to the role of very long-chain fatty acids (VLCFAs). Here, we show that depletion of acetyl-CoA carboxylase (ACC1), a critical enzyme involved in the biosynthesis of fatty acids, inhibits both de novo synthesis and elongation of VLCFAs in human cancer cells. ACC1 depletion markedly reduces cellular VLCFA but only marginally influences LCFA levels, including palmitate that can be nutritionally available. Therefore, tumor growth is specifically susceptible to regulation of VLCFAs. We further demonstrate that VLCFA deficiency results in a significant decrease in ceramides as well as downstream glucosylceramides and sphingomyelins, which impairs mitochondrial morphology and renders cancer cells sensitive to oxidative stress and cell death. Taken together, our study highlights that VLCFAs are selectively required for cancer cell survival and reveals a potential strategy to suppress tumor growth.

Transformation of Hydrophilic Drug into Oil-Miscible Ionic Liquids for Transdermal Drug Delivery.

The transdermal delivery of hydrophilic drugs remains challenging owing to their poor ability to permeate the skin; formulation with oil media is difficult without adding chemical permeation enhancers or co-solvents. Herein, we synthesized 12 oil-miscible ionic liquid (IL) drugs comprising lidocaine-, imipramine-, and levamisole (Lev)-hydrochloride with fatty acid permeation enhancers, i.e., laurate, oleate, linoleate, and stearate as counterions. A set of in vitro and in vivo studies was performed to investigate the potency and deliverability of the transdermal drug formulations. All of the synthesized compounds were freely miscible with pharmaceutically acceptable solvents/agents (i.e., ethanol, N-methyl pyrrolidone, Tween 20, and isopropyl myristate (IPM)). In vitro permeation studies revealed that the oleate-based Lev formulation had 2.6-fold higher skin permeation capability than the Lev salts and also superior ability compared with the laurate-, linoleate-, and stearate-containing samples. Upon in vivo transdermal administration to mice, the peak plasma concentration, elimination half-life, and area under the plasma concentration curve values of Lev-IL were 4.6-, 2.9-, and 5.4-fold higher, respectively, than those of the Lev salt. Furthermore, in vitro skin irritation and in vivo histological studies have demonstrated that Lev-IL has excellent biocompatibility compared with a conventional ionic liquid-based carrier. The results indicate that oil-miscible IL-based drugs provide a simple and scalable strategy for the design of effective transdermal drug delivery systems.

Elemental, fatty acid, and protein composition of appendicoliths.

Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we investigated the composition of appendicoliths using laser ablation inductively coupled plasma mass spectroscopy, gas chromatography, polarized light microscopy, X-ray crystallography and protein mass spectroscopy. Forty-eight elements, 32 fatty acids and 109 human proteins were identified within the appendicoliths. The most common elements found in appendicoliths are calcium and phosphorus, 11.0 ± 6.0 and 8.2 ± 4.2% weight, respectively. Palmitic acid (29.7%) and stearate (21.3%) are the most common fatty acids. Some stearate is found in crystalline form-identifiable by polarized light microscopy and confirmable by X-ray crystallography. Appendicoliths have an increased ratio of omega-6 to omega-3 fatty acids (ratio 22:1). Analysis of 16 proteins common to the appendicoliths analyzed showed antioxidant activity and neutrophil functions (e.g. activation and degranulation) to be the most highly enriched pathways. Considered together, these preliminary findings suggest oxidative stress may have a role in appendicolith formation. Further research is needed to determine how dietary factors such as omega-6 fatty acids and food additives, redox-active metals and the intestinal microbiome interact with genetic factors to predispose to appendicolith formation.

Prioritization of micropollutants in municipal wastewater and the joint inhibitory effects of priority organic pollutants on Vibrio qinghaiensis sp.-Q67.

Treatment of wastewater in municipal wastewater treatment plants has become a major barrier to organic pollutants entering the aquatic environment. In this study, qualitative screening of organic micropollutants was conducted in a typical municipal wastewater treatment plant (MWWTP) using gas chromatography-mass spectrometry (GC-MS). The identified compounds were prioritized according to their comprehensive scores ranked by detection frequency, semi-quantitative concentration, bioaccumulation, ecotoxicity, and biodegradability. The results showed dibutyl phthalate, antioxidant 2246, methyl stearate, 2,4,6-tri­tert-butylphenol, and dioctyl phthalate had the top five scores and were ranked as priority organic pollutants in the municipal wastewater. The individual and joint toxicity determinations of the five compounds were carried out by a bioluminescence inhibition assay using Vibrio qinghaiensis sp.-Q67 (V. qinghaiensis). The individual toxicity assay results of these pollutants on V. qinghaiensis demonstrated that the order of the acute toxicity of the five priority organic pollutants was as follows: dioctyl phthalate> dibutyl phthalate> methyl stearate> antioxidant 2246> 2,4,6-tri­tert-butylphenol. The joint toxicity showed partial addition or antagonism among these pollutants. The prediction results of the mixed toxicity were compared between the concentration addition model and the independent action model, indicating that a single traditional prediction model could not accurately predict the mixed toxicity of different types of organic pollutants, and that a comprehensive application of model prediction could improve the accuracy of mixed toxicity prediction. This method could provide a theoretical basis for systematic screening and toxicity prediction of pollutants in wastewater.

FASN inhibitor TVB-3166 prevents S-acylation of the spike protein of human coronaviruses.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses mediates host cell entry and is S-acylated on multiple phylogenetically conserved cysteine residues. Multiple protein acyltransferase enzymes have been reported to post-translationally modify spike proteins; however, strategies to exploit this modification are lacking. Using resin-assisted capture MS, we demonstrate that the spike protein is S-acylated in SARS-CoV-2-infected human and monkey epithelial cells. We further show that increased abundance of the acyltransferase ZDHHC5 associates with increased S-acylation of the spike protein, whereas ZDHHC5 knockout cells had a 40% reduction in the incorporation of an alkynyl-palmitate using click chemistry detection. We also found that the S-acylation of the spike protein is not limited to palmitate, as clickable versions of myristate and stearate were also labelled the protein. Yet, we observed that ZDHHC5 was only modified when incubated with alkyne-palmitate, suggesting it has specificity for this acyl-CoA, and that other ZDHHC enzymes may use additional fatty acids to modify the spike protein. Since multiple ZDHHC isoforms may modify the spike protein, we also examined the ability of the FASN inhibitor TVB-3166 to prevent S-acylation of the spike proteins of SARS-CoV-2 and human CoV-229E. We show that treating cells with TVB-3166 inhibited S-acylation of expressed spike proteins and attenuated the ability of SARS-CoV-2 and human CoV-229E to spread in vitro. Our findings further substantiate the necessity of CoV spike protein S-acylation and demonstrate that de novo fatty acid synthesis is critical for the proper S-acylation of the spike protein.

Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation.

Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also negatively affect the critical quality attributes of pharmaceutical products. Therefore, we provided a rather comprehensive evaluation of another two FDA-approved metallic stearates, sodium stearate (NaSt) and calcium stearate (CaSt), as alternative tablet lubricants. The primary objective of the present study is to comparatively evaluate the physicochemical properties and lubrication efficiency of the three metallic stearates. In addition, it was also aimed to specify the most influential factor for ranking and differentiating the lubricity of various lubricants using principal component analysis. Unit ejection force could be used herein as a simple and the most powerful parameter to evaluate the lubrication performance instead of the friction coefficient. The results suggested that CaSt, MgSt, and NaSt had similar impacts on the mechanical strength of tablets. However, CaSt exhibited insufficient lubrication effects as the formulations containing CaSt showed low pressure transmission ratios, high unit ejection forces, and high friction coefficients. In contrast, both MgSt and NaSt displayed satisfactory lubrication efficiency without negatively impacting tabletability. Notably, the lubrication performance of the formulation containing 0.5 wt% NaSt was almost identical to that of the formulation with 1 wt% MgSt, indicating that NaSt had a remarkable lubrication capability probably due to its high specific surface area. In summary, the findings of this investigation should provide practical information and feasible methodologies to readily determine the lubricity and to sensibly select alternative lubricants for pharmaceutical tablet formulations.