The performance of dynamic body-feed filtration (DBF) in the removal of bulky solids produced during the manufacturing of snake antivenoms using the caprylic acid method was evaluated. For this purpose, diatomites with different filterability properties were compared in a bench-scale study to assess their effectiveness in removing the precipitated material formed after the addition of caprylic acid to equine hyperimmune plasma. C1000 diatomite at a concentration of 90 g/L of precipitated plasma showed the best performance. Then, the process was scaled up to three batches of 50 L of hyperimmune horse plasma. At this pilot scale, 108 ± 4% of the immunoglobulins present following plasma precipitation were recovered after DBF. The antivenoms generated using this procedure met quality specifications. When compared to open filtration systems commonly used at an industrial scale by many antivenom manufacturers, DBF has a similar yield and produces filtrates with comparable physicochemical characteristics. However, DBF ensures the microbiological quality of the primary clarification in a way that open systems cannot. This is because: 1) DBF is performed in a single-use closed device of depth filters which prevents microbial contamination, and 2) DBF removes bulky material in few minutes instead of the more than 24 h needed by open filtration systems, thus reducing the risk of contamination. It was concluded that DBF is a cost-effective, easily validated, and GMP-compliant alternative for primary clarification following caprylic acid precipitation of plasma in snake antivenom production.

Myocardial damage significantly impacts the prognosis of patients with cancer; however, the mechanisms of myocardial damage induced by cancer and its treatment remain unknown. We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in effect according to MCFA type. Therefore, this study investigated the role of inflammatory cytokines in cancer-induced myocardial damage and the effects of three types of MCFAs (caprylic acid [C8], capric acid [C10], and lauric acid [C12]). In a mouse model, the C8 diet showed a greater effect on improving myocardial damage compared with C10 and C12 diets. Myocardial tubes differentiated from H9C2 cardiomyoblasts demonstrated increased mitochondrial oxidative stress, decreased membrane potential and mitochondrial volume, and inhibited myocardial tube differentiation following treatment with high-mobility group box-1 (HMGB1) but not interleukin-6 and tumor necrosis factor-α cytokines. However, HMGB1 treatment combined with C8 improved HMGB1-induced mitochondrial damage, enhanced autophagy, and increased mitochondrial biogenesis and maturation. However, these effects were only partial when combined with beta-hydroxybutyrate, a C8 metabolite. Thus, HMGB1 may play an important role in cancer-related myocardial damage. C8 counteracts HMGB1\'s effects and improves cancer-related myocardial damage. Further clinical studies are required to investigate the effects of C8.

Arbuscular mycorrhizal fungi (AMF) and Chitooligosaccharide (COS) can increase the resistance of plants to disease. COS can also promote the symbiosis between AMF and plants. However, the effects of AMF & COS combined application on the rhizosphere soil microbial community of tobacco and the improvement of tobacco\'s resistance to black shank disease are poorly understood.·We treated tobacco with AMF, COS, and combined application of AMF & COS (AC), respectively. Then studied the incidence, physio-biochemical changes, root exudates, and soil microbial diversity of tobacco seedling that was inoculated with Phytophthora nicotianae. The antioxidant enzyme activity and root vigor of tobacco showed a regular of AC > AMF > COS > CK, while the severity of tobacco disease showed the opposite regular. AMF and COS enhance the resistance to black shank disease by enhancing root vigor, and antioxidant capacity, and inducing changes in the rhizosphere microecology of tobacco. We have identified key root exudates and critical soil microorganisms that can inhibit the growth of P. nicotianae. The presence of caprylic acid in root exudates and Bacillus (WdhR-2) in rhizosphere soil microorganisms is the key factor that inhibits P. nicotianae growth. AC can significantly increase the content of caprylic acid in tobacco root exudates compared to AMF and COS. Both AMF and COS can significantly increase the abundance of Bacillus in tobacco rhizosphere soil, but the abundance of Bacillus in AC is significantly higher than that in AMF and COS. This indicates that the combined application of AMF and COS is more effective than their individual use. These findings suggest that exogenous stimuli can induce changes in plant root exudates, regulate plant rhizosphere microbial community, and then inhibit the growth of pathogens, thereby improving plant resistance to diseases.

Bioconversion of CO2 into liquid fuels or chemicals, preferred medium chain carboxylic acids (caproic and caprylic acid), is an attractive CO2 utilization technology. The present study aims to investigate the effects of different ratios of H2/CO2 on regulating the distribution of C2-C8 carboxylic acid products, while the headspace pressure of 1.5 bar was set to amplify the effect of different ratios. The H2/CO2 ratio of 4:1 was more suitable for preparing acetic acid, where the highest acetic acid yield was 17.5 g/L. And the H2/CO2 ratio of 2:1 showed excellent chain elongation ability with the highest n-caprylic yield of 2.4 g/L. Additionally, the actual H2/CO2 ratios of 4:1 reactors were higher than that in 2:1 may be course chain elongation often accompanied by H2 production. The 16S rRNA genes analysis shows that the genus Terrisporobacter and Coriobacteriales may be related to acetic acid production enriched in H2/CO2 ratio 4:1 reactors, and the genus Clostridium and Paenibacillaceae may associate with the chain elongation pathway were enriched in H2/CO2 ratio 2:1 reactors.

We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.

Ion pair is an effective chemical approach to promoting drug transdermal permeation, and the traditional interpretation for its enhanced permeation effect is mainly attributed to counterions altering the physicochemical properties of the drug (lipophilicity, melting point, etc.). In this work, guanfacine (GFC), a non-stimulant for anti-attention deficit and hyperactivity disorder (ADHD), was used as a model drug, and several organic or inorganic acids were designed thereby successfully constructing ion pairs. The transdermal permeation ability of ion pairs through isolated porcine skin was observed and ranked as follows: guanfacine caprylate (GFC-CA) > GFC > guanfacine laurate (GFC-LA) > guanfacine fumarate (GFC-FA) > guanfacine hydrochloride (GFC-HA) > guanfacine palmitate (GFC-PA). The effect of key physicochemical properties (octanol-water partition coefficient, molecular volume, melting point) on the transdermal permeation rate of the model drug was analyzed in detail. In addition, GFC-CA was observed to alter the lipid structure of the skin, suggesting the traditional explanation of the action of ion pair may be inadequate and underrated, and ion pair may also enhance permeation by disrupting skin structure. The intriguing phenomenon is expected to provide a novel approach to achieving precise transdermal drug delivery.

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Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid-aminoacid1-amonoacid2-aspartate amphiphiles (Cn acid-AA1-AA2-D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear magnetic resonance spectroscopy. Of them, 13 conjugates formed hydrogels at low concentrations (≥0.25% w/v), but C8 acid-ILD-NH2 showed the best hydrogelation and was investigated further. Scanning electron microscopy revealed that C8 acid-ILD-NH2 formed fibrous network structures and rapidly formed hydrogels that were stable in phosphate-buffered saline (pH 2-8, 37 °C), a typical pathophysiological condition. Injection and rheological studies revealed that the hydrogels manifested important wound treatment properties, including injectability, shear thinning, rapid re-gelation, and wound-compatible mechanics (e.g., moduli G″ and G\', ~0.5-15 kPa). The C8 acid-ILD-NH2(2) hydrogel markedly accelerated the healing of third-degree burn wounds on C57BL/6J mice. Taken together, our findings demonstrated the potential of the Cn fatty acid-AA1-AA2-D molecular template to form hydrogels capable of promoting the wound healing of third-degree burns.

Physicochemical properties of the binary mixtures based on Caprylic acid: Quaternary ammonium salts (QAS) (7:3 mol ratio) are investigated using MD simulations. Considering the hydrophobic character of eutectic solvents based on long-chain fatty acids, the stability of the binary mixtures was investigated in the adjacent water. In order to investigate the effect of water on intermolecular interactions in binary mixtures, the structural properties of the binary mixtures in the pure state and adjacent to water were investigated at 310 K. Assessed structural properties include the combined distribution functions (CDFs), the radial distribution functions (RDFs), the angular distribution functions (ADFs), and the Hydrogen bonding network between HBA and HBD and Spatial distribution functions (SDF). We aimed to represent the structural stability of eutectic solvents based on Caprylic acid and Quaternary ammonium salts (QAS) as a function of the alkyl chain length of cations, the evidence was found for the interaction between the chloride anion leads to the transition of HBA to the water-rich phase. The alkyl chain length of cations of Quaternary ammonium salts shows the stability of eutectic solvents in the adjacent water.

Medium-chain fatty acids (MCFAs) can rapidly cross the blood-brain barrier and provide an alternative energy source for the brain. This study aims to determine 1) whether plasma caprylic acid (C8:0) is associated with risk of incident mild cognitive impairment (MCI) among baseline cognitively normal (CN) participants, and incident Alzheimer\'s Disease (AD) among baseline MCI participants; and 2) whether these associations differ by sex, comorbidity of cardiometabolic diseases, apolipoprotein E (APOE) ε4 alleles, and ADAS-Cog 13.
Within the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) cohort, plasma C8:0 was measured at baseline in 618 AD-free participants aged 55 to 91. Logistic regression models were used to estimate odds ratios (ORs) and 95% CIs with incident MCI and AD as dependent variables, separately.
The inverse association between circulating C8:0 and risk of incident MCI was of borderline significance. The inverse association between circulating levels of C8:0 and risk of incident MCI was significant among CN participants with ≥1 cardiometabolic diseases [OR (95% CI): 0.75 (0.58-0.98) (P=0.03)], those with one copy of APOE ε4 alleles [OR (95% CI): 0.43 (0.21-0.89) (P=0.02)], female [OR (95% CI): 0.60 (0.38-0.94) (P=0.02)], and ADAS-Cog 13 above the median [OR (95%CI): 0.69 (0.50-0.97)(P=0.03)] after adjusting for all covariates.
The inverse associations were present only among subgroups of CN participants, including female individuals, those with one or more cardiometabolic diseases, or one APOE ε4 allele, or higher ADAS-Cog 13 scores. If confirmed, this finding will facilitate precision prevention of MCI, in turn, AD among CN older adults.