Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study.

Objective: To investigate the causal relationships between linoleic acid and type 2 diabetes, and between linoleic acid and glycemic traits in European populations. Methods: This study employed a two-sample Mendelian randomization approach to infer causality between linoleic acid and type 2 diabetes, as well as between linoleic acid and glycemic traits, leveraging genetic variations. Data were sourced from genome-wide association study summary datasets. Random-effects inverse-variance weighted, weighted median, and MR-Egger methods were used for the two-sample Mendelian randomization analyses. Results were presented as odds ratios with a 95% confidence interval. Multiple sensitivity analyses were conducted to assess result robustness. Results: MR findings indicated a correlation between linoleic acid levels and the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin (HbA1c), but not with fasting insulin. Specifically: type 2 diabetes (OR: 0.811, 95% CI: 0.688-0.956, P=0.013<0.05),fasting blood glucose (ß_IVW): -0.056, 95% CI: (-0.091,-0.021), P=0.002< 0.0125), glycated hemoglobin (ß_IVW: -0.032, 95% CI: (-0.048,-0.015), P=0.0002< 0.0125) and Fasting insulin (ß_IVW: -0.024, 95% CI: (-0.056,-0.008), P=0.136 >0.05).Reverse MR analyses showed a correlation between type 2 diabetes and reduced levels of linoleic acid (ß_IVW: -0.033, 95% CI: (-0.059,-0.006), P=0.014<0.05). Multiple sensitivity analyses also detected study heterogeneity but found no evidence of horizontal pleiotropy. Conclusion: High levels linoleic acid can reduce the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin, but has no significant relation with fasting insulin. Type 2 diabetes can lower linoleic acid levels; however, no significant causal relationship was observed between the three glycemic traits and reduced levels of linoleic acid.

Clearance of intracellular bacterial infections by hyaluronic acid-based ROS responsive drug delivery micelles.

Pathogenic bacteria residing inside cells could cause disruption of cellular metabolic balance. Therefore, basing on high oxidative stress response of the intracellular bacteria infected micro-environment, a novel amphipathic micelle (HATAD-TCS) was developed consisting of hyaluronic acid-derivative and reactive oxygen species (ROS) - responsive group and antibacterial agent triclosan (TCS). ROS-generating cinnamaldehyde (CA) was incorporated into ROS-cleavable linkages which are future linked to the 1-decylamine to form hydrophobicity. The cinnamaldehyde released did not just killed bacteria however, also maintained intracellular ROS levels. In this study, the HATAD-TCS micelles have been characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The HATAD-TCS micelles could release drug gradually upon exposure to endogenous ROS being caused by infected intracellular bacteria. Furthermore, the more promising therapeutic effect of the HATAD-TCS micelles was observed in a mouse pneumonia model. These results might highlight a ROS-responsive hyaluronic acid-based nanoparticle, which could effectively treat intracellular bacterial infections.

The stability and spicy taste masking effect of capsaicin loaded α-lactalbumin micelles formulated in defatted cheese.

Capsaicin (Cap) is a promising bioactive compound having many health-promoting benefits. However, it is difficult to be applied in food due to its poor aqueous solubility, low stability and bioavailability. Besides, its strong spicy taste and irritation to the gastrointestinal tract further limit the application of Cap in food. To solve this problem, Cap was loaded into a self-assembled nanocarrier formed by partial hydrolysis of α-lactalbumin (α-lac). The Cap was successfully loaded into the 21.2 nm micelles with a loading capacity of 123.4 ± 6.1 mg g-1. The aqueous solubility was greatly improved. Besides, nanomicelles also showed intestinal responsive release behavior. The in vivo bioavailability of Cap was improved by nanomicelles for 3.1 times. The Cap loaded nanomicelles in the milk system showed good colloidal stability compared to solely Cap in milk. Therefore, the Cap loaded nanocarriers were added into the de-fatted milk to prepare de-fatted cheese with an acceptable spicy flavor. The nanocarriers were clearly captured in the cheese casein network as confirmed by confocal microscopy. The sensory evaluation results showed the spicy taste of capsaicin was reduced in the nanomicelle system and further reduced in the nanomicelle-cheese systems. We postulated that it might be due to the nanomicelles reducing the contact of capsaicin with sensory neurons in the tongue thus masking the spicy taste. The cheese casein network structure further masked their contact. The above results indicated that Cap embedding via α-lac nanocarriers was feasible for masking their spicy taste and applying Cap to food systems such as milk and cheese.

ROS-responsive hyaluronic acid hydrogel for targeted delivery of probiotics to relieve colitis.

Probiotics are generally used as therapeutic intervention in inflammatory bowel disease. However, the low survival rate in harsh gastrointestinal environment and limited retention in intestine greatly restrict their health benefits. To address this problem, a ROS-responsive hydrogel based on hyaluronic acid (HA) was developed for encapsulation and targeted delivery of probiotics. The hydrogel was prepared facilely by physiological crosslink with methacrylated HA and thiolated thioketal. As a model probiotic, Lactobacillu reuteri showed a significantly increased survival rate in simulated digestive conditions after encapsulated in hydrogel. The negative properties conferred the hydrogel preferential adhesions to inflammation sites. Meanwhile, the excess reactive oxygen species (ROS) produced by inflamed colon tissues selectively cleaved thioketal linkages resulted in hydrogel degradation and local probiotics release. Furthermore, the hydrogel exerted an appropriate ROS-scavenge capacity and protected HT-29 cells from oxidative damage. Animal experiments indicated that hydrogel-encapsulated L. reuteri could remarkably alleviate the symptoms and improve the survival rate of mice with dextran sulfate sodium (DSS)-induced colitis. These results suggested that the biocompatible hydrogel may be a delivery platform to target inflamed intestines and expand the application of probiotics as pharmaceuticals.

The In Vitro Antimicrobial and Antibiofilm Activities of Lysozyme against Gram-Positive Bacteria.

Objective: To analyze the in vitro antibacterial and antibiofilm activities of lysozyme (LYS) and its combination with various drugs against Gram-positive bacteria (GPB, n = 9), thus to provide an exploration direction for drug development. Methods: The minimum inhibitory concentrations (MICs) of linezolid (LZD), amikacin (AMK), ceftriaxone/sulbactam (CRO/SBT), cefotaxime/sulbactam (CTX/SBT), piperacillin/sulbactam (PIP/SBT), doxycycline (DOX), levofloxacin (LVX), amoxicillin/clavulanate potassium (7 : 1, AK71), imipenem (IPM), azithromycin (AZM), and their combinations with LYS were determined with tuber twice dilution. The antimicrobial and antibiofilm activities of LYS, AZM, LVX, and their combinations with others were evaluated through MTT and crystal violet assay. Results: High-dose LYS (30 µg/mL) combined with PIP/SBT and AK71, respectively, showed synergistic antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), while it showed no synergistic activities when combined with other drugs. LYS and AZM inhibited the biofilm formation of one MRSA strain, but they and LVX had no similar activities against methicillin-resistant Staphylococcus epidermidis (MRSE) or vancomycin-resistant Enterococcus faecium (VREF). Particularly, LYS increased the permeability of biofilms of MRSA 33 and exhibited antibiofilm activities against MRSA 31 (inhibition rate = 38.1%) and MRSE 61 (inhibition rate = 46.6%). The combinations of PIP/SBT+LYS, AMK+LYS, and LZD+LYS showed stronger antibiofilm activities against MRSA 62, MRSE 62, MRSE 63, and VREF 11. Conclusion: The antimicrobial and antibiofilm activities of LYS against MRSA were better than AZM, while that of LYS against MRSE and VREF, respectively, was similar with AZM and LVX.

Development of responsive chitosan-based hydrogels for the treatment of pathogen-induced skin infections.

Vancomycin (Van) remains one of the first-line drugs for the treatment of wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the unsatisfactory bioavailability of vancomycin alone has greatly limited its potential health benefits. Here a responsive chitosan-based hydrogel was developed as the delivery system which not only would reduce this side effect but also increase efficacy of vancomycin. The hydrogel was prepared by grafting chitosan and cinnamaldehyde-based thioacetal (CTA) together with ginipin (G) as the crosslinker. Upon exposure to reactive oxygen species which were enriched in the bacterial wound, the hydrogel can locally degrade and sustainably release the loaded vancomycin near the lesion to compete with the troubling MRSA. Compared with vancomycin alone, the chitosan-based hydrogel loaded with vancomycin demonstrated accelerated acute wound healing. This achievement reveals that this multi-functional hydrogel may be a promising drug-delivery device for improving the efficacy of local antibiotic therapy.

Carboxymethyl chitosan-based multifunctional hydrogels incorporated with photothermal therapy against drug-resistant bacterial wound infection.

Wound infection especially that induced by drug resistant bacteria has been considered an increasing medical crisis. Herein a biocompatible wound dressing is conveniently constructed by incorporating (Sr0.6Bi0.305)2Bi2O7 (denoted as SBO) with excellent photothermal performance into a facile antibacterial hydrogel (gel) obtained from multiple physical crosslinks among Ag+, carboxymethyl chitosan and polyacrylic acid. The prepared SBO gel features excellent bactericidal activities, hemostasis, adequate mechanical properties, adhesiveness and adsorption capacities to bacterial cells and toxin. The gel can disperse SBO homogeneously in the network and SBO effectively convert visible light energy into localized heat for synergistic sterilization. In vitro assays confirm the potent broad-spectrum bactericidal activities of SBO gel to some common pathogens and drug resistant strains such as MRSA and CAPA. Mice model of MRSA-induced wound infections verified the practical efficacy of SBO gel in combating bacterial infections and accelerating wound healing. Moreover, this is the first report of SBO as a photothermal agent applied in anti-infection treatment. All of these results highlight the potential application of SBO gel in drug-resistant bacteria associated wound management.

Stable Indium Pyridylcarboxylate Framework with Highly Selective Adsorption of Cationic Dyes and Effective Nitenpyram Detection.

On the basis of an undeveloped asymmetrical pyridylcarboxylate ligand, 2-(2-carboxypyridin-4-yl)terephthalic acid (H3CPTA), an indium pyridylcarboxylate framework, [(Me)2NH2]1.5[In1.5(CPTA)2]·5.5NMF·6H2O (1), is synthesized under solvent thermal conditions. 1 displays a 3D anionic framework with a large void space, which contains open square channels with a cross section of 14.6 Å and a pore surface decorated with carboxylic oxygen atoms. Depending on the anionic skeleton and high water stability, 1 exhibits high adsorption selectivity and capacity for cationic dyes in aqueous solution. Furthermore, the luminescence performance illustrates that 1 has selectivity and sensitivity to nitenpyram with good recyclability.

Construction of a Three-Dimensional Interpenetrating Network Sponge for High-Efficiency and Cavity-Enhanced Solar-Driven Wastewater Treatment.

It is well known that the photothermal conversion performance of solar-driven interfacial water evaporation systems is known to have a stronger photothermal conversion performance than suspended water evaporation systems due to their relatively strong ability to suppress overall heat loss. Natural polymer chitosan and gelatin can form a three-dimensional interpenetrating network (IPN) sponge to provide an interface for water evaporation due to strong hydrogen bonding and electrostatic attraction interaction. However, the lack of effective light absorption, the intrinsic short lifetime, and the poor photothermal conversion greatly compromise their steam generation performance. Here, we fabricated a chitosan/gelatin-based IPN sponge incorporated with melanin-coated titania hollow nanospheres (CG@MPT-h) as a solar thermal converter, which is designed to exhibit a unique cavity structure and vertical channels. The cavity structure of melanin-coated titania acts as a solar thermal transducer, while the chitosan/gelatin-based IPN sponge acts as a single-pass water pump. A water hyacinth-inspired evaporation system shows outstanding steam generation performance, and the highest steam generation rate was 3.17 kg m-2 h-1 under a 2.5 sun illumination because of the cavity enhancement effect, far above TiO2 particles and reported photo-thermal conversion materials. More importantly, the embedding of MPT-h nanoparticles in the IPN sponge effectively inhibits the growth of bacteria in the vertical channels, resulting in an antibacterial solar-driven water evaporator. This advanced sponge provides a cost-effective and practical sustainable energy technique for solar-driven wastewater treatment.

Encapsulation of Lactobacillus rhamnosus in Hyaluronic Acid-Based Hydrogel for Pathogen-Targeted Delivery to Ameliorate Enteritis.

Probiotics were found to be effective in ameliorating the microbial dysbiosis and inflammation caused by intestinal pathogens. However, biological challenges encountered during oral delivery have greatly limited their potential health benefits. Here, a model probiotic (Lactobacillus rhamnosus) was encapsulated in an intestinal-targeted hydrogel to alleviate bacterial enteritis in a novel mode. The hydrogel was prepared simply by the self-cross-linking of thiolated hyaluronic acid. Upon exposure to H2S which were excreted by surrounding intestinal pathogens, the hydrogel can locally degrade and rapidly release cargos to compete with source pathogens in turn for binding to the host. The mechanical properties of hydrogel were studied by rheological analysis, and the ideal stability was achieved at a polymer concentration of 4% (w/v). The morphology of the optimal encapsulation system was further measured by a scanning electron microscope, exhibiting uniform payload of probiotics. Endurance experiments indicated that the encapsulation of L. rhamnosus significantly enhanced their viability under gastrointestinal tract insults. Compared with free cells, encapsulated L. rhamnosus exerted better therapeutic effect against Salmonella-induced enteritis with negligible toxicity in vivo. These results demonstrate that this redox-responsive hydrogel may be a promising encapsulation and delivery system for improving the efficacy of orally administered probiotics.

Improved viability of Akkermansia muciniphila by encapsulation in spray dried succinate-grafted alginate doped with epigallocatechin-3-gallate.

We explored the possibility of improving the viability of Akkermansia muciniphila by encapsulating it in succinate-grafted alginate doped with epigallocatechin-3-gallate (EGCG). In this study, the determined surface properties of microcapsules and modified materials and the measured viability of probiotics after spray drying showed that the modified sodium alginate made the surfaces of microcapsules smoother and denser during the spray drying, thus preventing damages. EGCG enhanced the antioxidant capacity of probiotics by filling the pores inside microgels. Moreover, we analyzed the long-term storage vitality changes, oxidation resistance, uniformity, particle size and Zeta potential of microcapsules and found that spray-dried modified sodium alginate microcapsules with EGCG showed the better storability and stability. In addition, we experimentally analyzed the resistances of different microcapsules to the gastrointestinal fluid and found that EGCG-modified sodium alginate microcapsules better protected the probiotic activity from gastrointestinal fluid. This study provides a slimming product with industrial application potential.

Gentamicin decorated phosphatidylcholine-chitosan nanoparticles against biofilms and intracellular bacteria.

Biofilms and intracellular bacteria often cause a series of overwhelming public health issues due to their strong drug resistance. Hence, chitosan nanoparticles (CS NPs), phosphatidylcholine and gentamicin were used to synthesize a novel nanodrug delivery system (GPC NPs). Dynamic light scattering (DLS) demonstrated that the surface zeta-potential of GPC NPs was -19.5 mV. The morphology of GPC NPs was observed by scanning electron microscopy (SEM). The gentamicin adsorption and release behaviors of GPC NPs were also investigated. The GPC NPs could effectively damage and remove the biofilm formed by pathogens through permeation of the antibiotic into the biofilm. In addition, the nanoparticles were readily engulfed by macrophages which facilitated the killing of intracellular bacteria and had neglectable cytotoxicity. Our study indicated that GPC NPs could be used as a promising nanoantibacterial agent against biofilms and intracellular bacteria.

Hyaluronic acid-coated ZIF-8 for the treatment of pneumonia caused by methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of hospital infection. Here, we showed that hyaluronic acid modified organic metal framework material ZIF-8 could be a Trojan horse of vancomycin (Van) for effective treatment of MRSA infections. The Van-loaded nanoparticles were readily up-taken by macrophages via a CD44-mediated process and collapsed in the acidic condition of endosome/lysosome, as a consequence, it could eradicate MRSA with high efficiency in macrophages. This drug delivery system with negligible toxicity could resolve MRSA infections in a well-established mouse pneumonia model.

Hyaluronic acid-based levofloxacin nanomicelles for nitric oxide-triggered drug delivery to treat bacterial infections.

Antibiotics are powerful weapons to fight against bacterial infections, while most of them lack of selective targeting towards pathological site which could restrict their antibacterial efficacy. To overcome this challenge, an antimicrobial levofloxacin(LF)was conjugated onto hyaluronic acid (HA) moieties via an o-phenylenediamine linker to prepare a NO-sensitive nanosystem (HA-NO-LF) in this study. The HA-NO-LF nanomicelles could enter host cells via a CD44 mediated endocytosis and release drug gradually upon exposure to endogenous NO. Furthermore, the more promising therapeutic effect of the nanomicelles in ameliorating inflammatory levels was observed in a mouse pneumonia model than that of LF. These results suggest that the HA-NO-LF nanomicelles may exert potent curative effect in infectious diseases.

One water-soluble polysaccharide from Ginkgo biloba leaves with antidepressant activities via modulation of the gut microbiome.

Depression, a mental illness characterized by persistent feeling of sadness and loss of interest, has been a serious health problem worldwide. Manipulation of the microbiota by probiotics and prebiotics represents a novel emerging strategy for the treatment of various psychiatric disorders such as major depressive disorders. Here, we show that one water-soluble polysaccharide from Ginkgo biloba leaves (GPS) reduced stress-induced depression and reversed gut dysbiosis. Similar to the antidepressant paroxetine, GPS significantly reduced the immobility times in the tail suspension test (TST) and forced swimming test (FST) and anxiety-like behavior in the open field test (OFT). Consistent with the improvement of depression-like behavior above, GPS mice had elevated serotonin and dopamine levels in multiple brain regions including the hippocampus, cerebral cortex and olfactory bulb, relative to unpredictable chronic mild stress (UCMS) treatment mice. GPS treatment could alleviate the stress-induced reduction in the density of serotonin-positive and dopamine-positive cells. Fecal microbiome transplant (FMT) combined with antibiotic treatment showed that the anti-depressant activity of GPS had a causal relationship with intestinal microbes. By performing a pyrosequencing-based analysis of bacterial 16S rRNA (V3 + V4 region) in fecal of the mice, the results showed that GPS reversed depression-associated gut dysbiosis and increased the richness of Lactobacillus species which has been proven to be a path to relieve depression. Our results demonstrated that the polysaccharide from Ginkgo biloba leaves might be a promising pharmacotherapeutic candidate for treating depression.

Screening of aroma-producing lactic acid bacteria and their application in improving the aromatic profile of yogurt.

The development of yogurt flavor is a complicated and dynamic biochemical process. In addition to traditional starter cultures, adjunct cultures could also make significant contributions to the flavor profiles of yogurt. In the current study, two Lactobacillus plantarum strains (1-33 and 1-34) were isolated based on their abilities to produce acetaldehyde and diacetyl. In co-fermentation with traditional starters, these isolated strains were able to maintain viability without affecting the yogurt's acidification profiles. Furthermore, they positively influenced the aroma quality of the yogurt samples. They promoted the formation of volatile metabolites, especially acetaldehyde, diacetyl, and acetoin, which are recognized as characteristic compounds. The results of this work provide novel knowledge about the contributions of isolated strains on the flavor profiles of yogurt, which will help to improve the organoleptic properties of the final products. PRACTICAL APPLICATIONS: Using lactic acid bacteria (LAB) as adjunct cultures co-fermented with traditional yogurt starter cultures can increase the quantities of flavor compounds in yogurt. This study enriches our understanding of the effects of adjunct cultures on yogurt flavor. Researchers and manufacturers that specialize in yogurt making can use the results of this study to improve the aromatic profile and organoleptic quality of yogurt.

Pathogen-targeting glycovesicles as a therapy for salmonellosis.

Antibiotic therapy is usually not recommended for salmonellosis, as it is associated with prolonged fecal carriage without reducing symptom duration or severity. Here we show that antibiotics encapsulated in hydrogen sulfide (H2S)-responsive glycovesicles may be potentially useful for the treatment of salmonellosis. The antibiotics are released in the presence of Salmonella, which is known to produce H2S. This approach prevents the quick absorption of antibiotics into the bloodstream, allows localized targeting of the pathogen in the gut, and alleviates disease symptoms in a mouse infection model. In addition, it reduces antibiotic-induced changes in the gut microbiota, and increases the abundance of potentially beneficial lactobacilli due to the release of prebiotic xylooligosaccharide analogs.

Versatile Chlorin e6-based magnetic polydopamine nanoparticles for effectively capturing and killing MRSA.

Bacterial infections are a growing global challenge for public health as antibiotic resistance could cause the failure of anti-infective treatment eventually. So, it is urgent to develop new potential antibacterial materials. Herein, a multifunctional chitosan (CS) functionalized magnetic Chlorin e6 (CS-MP-Ce6) was constructed to combat methicillin-resistant Staphylococcus aureus (MRSA) infection by integrating bacterial conjugation and enrichment, and near-infrared (NIR)-triggered photodynamic sterilization. CS-MP-Ce6 could efficiently capture bacteria due to positively charged property of CS, and Ce6 acted as an effective photodynamic killer to convert NIR light into local energy to enhance antibacterial activity. Specifically, after being trapped together with MRSA, CS-MP-Ce6 showed an excellent in vitro photodynamic sterilization ability. In vivo MRSA-induced abscess treatment studies showed faster healing when CS-MP-Ce6 was used as subcutaneous nano-localized energy sources with the assistance of external magnet to concentrate CS-MP-Ce6-bacteria conjugate. This work provides a promising framework for constructing a new system for efficiently combating MRSA.

Preparation and biological activities of an extracellular polysaccharide from Rhodopseudomonas palustris.

The photosynthetic bacterium, Rhodopseudomonas palustris has been widely used as probiotics in aquaculture, while the molecular basis underlying the probiotic properties of this organism remains largely unknown. In this study, a novel extracellular polysaccharides (RPEPS-30) extracted from the fermentation of Rhodopseudomonas palustris was characterized. Results illustrated that RPEPS-30 was an α-mannan with a molecular weight of 46.82 kDa, which possessed a backbone consisted of 1, 2-linked and 1, 4-linked mannose residues, with side chains composed of 1 → 6 linked and 1 → 2,6 linked mannose residues and substitution at O-6. The in vitro immunomodulatory tests revealed that RPEPS-30 could enhance phagocytic capacity, NO release and mRNA expression of cytokines in macrophages. In addition, RPEPS-30 was shown to promote the growth of resident beneficial gut microbiotasuch as Lactobacillus reuteri, Bacteroides thetaiotaomicron and Akkermansia muciniphila. These findings might help us to partially understand the molecular mechanism concerning the probiotic properties of Rhodopseudomonas palustris, in which the extracellular polysaccharide RPEPS-30 stimulated host immune response and favored the growth of specific benificial micriobiota in the gut.