Volatile flavor profiles of douchis from different origins and varieties based on GC-IMS and GC-O-QTOF/MS analysis.

The present study comprehensively characterized the flavor differences between different varieties of douchis from different origins using headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) coupled with gas chromatography-olfactometry-quadrupole time-of-flight mass spectrometry (GC-O-QTOF/MS). A total of 91 volatile organic compounds (VOCs) were identified using HS-GC-IMS and 70 VOCs were identified using GC-O-QTOF/MS, mainly including acids, aldehydes, esters and alcohols. Additionally, 23 key aroma-presenting compounds were screened in five douchi species using relative odor activity value (ROAV) and the aroma compounds that contributed the most to the aroma varied among the five douchi species. Comparative analysis of the GC-IMS and GC-O-QTOF/ MS results yielded 13 VOCs that were detected by both techniques. Nonanal, hexanal, eucalyptol, 1-octen-3-ol, isoamyl acetate, and 2-pentylfuran were identified as key VOCs in the douchi species using both methods. These findings will provide deeper insights for exploring flavor differences in douchi from different geographic sources.

Hyaluronidase overcomes the extracellular matrix barrier to enhance local drug delivery.

The stratum corneum of the skin presents the initial barrier to transdermal penetration. The dense structure of the extracellular matrix (ECM) further impedes local drug dispersion. Hyaluronidase (HAase) is a key component for the degradation of glycosidic bonding sites in hyaluronic acid (HA) within the ECM to overcome this barrier and enhance drug dispersion. HAase activity is optimal at 37-45 °C and in the pH range 4.5-5.5. Numerous FDA-approved formulations are available for the clinical treatment of extravasation and other diseases. HAase combined with various new nanoformulations can markedly improve intradermal dispersion. By degrading HA to create tiny channels that reduce the ECM density, these small nanoformulations then use these channels to deliver drugs to deeper layers of the skin. This deep penetration may increase local drug concentration or facilitate penetration into the blood or lymphatic circulation. Based on the generalization of 115 studies from 2010 to 2024, this article summarizes the most recent strategies to overcome the HAase-based ECM barrier for local drug delivery, discusses opportunities and challenges in clinical applications, and provides references for the future development of HAase. In the future, HAase-assisted topical administration is necessary to achieve systemic effects and to standardize HAase application protocols.

Effects of different curing concentrations and drying times on the microbial community structure and metabolites of dried Spanish mackerel.

Cured Spanish mackerel has a promising market owing to its nutritious nature as well as ease of transportation and preservation. However, the nutritional and flavor formation mechanism of Spanish mackerel after curing and drying is unclear. To overcome this problem, the effects of different processing conditions on the free amino acid, microbial community, and flavor of Spanish mackerel were explored. Staphylococcus and Cobetia are the main microorganisms in cured mackerel and are closely associated with the formation of their quality. Compared with fresh mackerel, cured mackerel contains increased levels of protein, fat, and chloride, contributing to its distinctive flavor. The contents of free amino acids in the BA64 group were substantially higher than those in other groups, particularly the contents of threonine, glycine, and tyrosine. These findings will contribute to the development of high-quality cured Spanish mackerel products and cured aquatic products.

Effects of curing concentration and drying time on flavor and microorganisms in dry salted Spanish mackerel.

This study investigated the quality changes of dry salted mackerel during curing and drying process and the relationship between flavor substances and microorganisms. The results showed that the thiobarbituric acid reactive substances (TBARS) values increased gradually with the increase of salt concentration and treatment time. The total volatile base nitrogen (TVB-N) values and total viable counts (TVC) values showed the same trend. Under 3% condition, the TVB-N values exceeded the standard and was not suitable for consumption. A total of 61 volatile flavor substances were identified by Gas chromatography-ion mobility spectrometry (GC-IMS), among which aldehydes contributed the most. Staphylococcus and Cobetia were the most abundant by High-throughput sequencing (HTS). There was significant correlation between TOP15 microorganisms and TOP20 flavor substances. Staphylococcus and Cobetia were positively correlated with 13 volatile flavor substances, which contributed to the formation of flavor in naturally fermented Spanish mackerel.

Distinct changes of taste quality and metabolite profile in different tomato varieties revealed by LC-MS metabolomics.

Breeding of tomato varieties based on phenotypic traits can potentially lead to a decline in taste and nutritional values, thereby impacting consumer acceptance. However, taste is an intrinsic characteristic of tomatoes. Its decoding requires the identification of crucial compounds and the associated metabolic pathways implicated in taste development and formation. In this study, the taste parameter differences of four tomato varieties were distinguished using an electronic tongue. The content of organic acids and free amino acids, which were closely associated with taste variations, was quantitatively analyzed. Several important taste metabolites and metabolic pathways were identified based on LC-MS metabolomics and enrichment analysis. Through correlation analysis, it was determined that there existed significant associations between the taste, compounds, and metabolites of tomato varieties with different phenotypes. This study could provide references and theoretical basis for tomato breeding, as well as the control and evaluation of taste and quality of tomato varieties.

Potential strategy of microneedle-based transdermal drug delivery system for effective management of skin-related immune disorders.

Skin-related immune disorders are a category of diseases that lead to the dysregulation of the body's immune response due to imbalanced immune regulation. These disorders exhibit diverse clinical manifestations and complicated pathogenesis. The long-term use of corticosteroids, anti-inflammatory drugs, and immunosuppressants as traditional treatment methods for skin-related immune disorders frequently leads to adverse reactions in patients. In addition, the effect of external preparations is not ideal in some cases due to the compacted barrier function of the stratum corneum (SC). Microneedles (MNs) are novel transdermal drug delivery systems that have theapparent advantages ofpenetrating the skin barrier, such as long-term and controlled drug delivery, less systemic exposure, and painless and minimally invasive targeted delivery. These advantages make it a good candidate formulation for the treatment of skin-related immune disorders and a hotspot for research in this field. This paper updates the classification, preparation, evaluation strategies, materials, and related applications of five types of MNs. Specific information, including the mechanical properties, dimensions, stability, and in vitro and in vivo evaluations of MNs in the treatment of skin-related immune disorders, is also discussed. This review provides an overview of the advances and applications of MNs in the effective treatment of skin-related immune disorders and their emerging trends.

Characterization of volatile flavor compounds from fish maw soaked in five different seasonings.

In this study, sensory evaluation, electronic nose, and HS-GC-IMS were used to investigate the effects of different seasonings (deionized water, onion, ginger, Sichuan pepper, and mixed seasonings) on the flavor of fish maw. The results showed that the volatile compounds of fish maw soaked in different seasonings were mainly organic sulfides and aromatic compounds. A total of 95 volatile compounds were identified, including 25 aldehydes, 23 olefins, 19 alcohols, 11 esters, 9 ketones, 3 acids, 2 sulfides, 1 furan, 1 ether and 1 ketoxime. Sichuan pepper group and mixed seasoning group had the most significant changes in volatile components, and had the most effective improvement on the flavor of fish maw compared with other groups. These findings will provide reference for producing high quality fish maw and improving its flavor quality. These findings will provide feasible theoretical support for the pretreatment and exploration of fish maw products in the future.

Antioxidant Effects of Quercetin Nanocrystals in Nanosuspension against Hydrogen Peroxide-Induced Oxidative Stress in a Zebrafish Model.

Quercetin, a flavonoid compound rich in hydroxyl groups, possesses antioxidant properties, whereas its poor water solubility limits its bioavailability. In pursuit of addressing the water solubility of quercetin and comprehending the impact of nanocrystal particle size on antioxidant efficacy, we prepared three different-sized quercetin nanocrystals, namely small (50 nm), medium (140 nm), and large (360 nm), using a nanosuspension method in this study. Within the in vitro setting, assessments employing solubility and radical scavenging assays revealed that quercetin nanocrystals displayed superior solubility (26, 21, and 13 fold corresponding to small, medium, and large particle sizes) and antioxidant performance compared to the coarse quercetin. Furthermore, quercetin nanocrystals of three particle sizes all demonstrated significant protection effects on the survival rate of H2O2-treated zebrafish at 72 h (77.78%, 73.33%, and 66.67% for small, medium, and large particle sizes, respectively), while the coarse quercetin group exhibited a low survival rate (53.3%) similar to the H2O2-treated group (47.8%). Moreover, all quercetin nanocrystals exhibited potent antioxidant capacity on both the antioxidants and enzymatic antioxidant system in H2O2-treated zebrafish to restore zebrafish to a normal state under oxidative stress. For instance, the levels of reactive oxygen species were reduced to 101.10%, 108.83%, and 109.77% of the normal levels for small, medium, and large particle-sized quercetin nanocrystals, respectively. In conclusion, quercetin nanocrystals demonstrated enhanced solubility, robust antioxidant capacity, and protective effects in zebrafish compared to coarse quercetin.

Dissolving microneedles for alopecia treatment.

Alopecia is a treatable benign disease, however, approximately 15-30% of women and 50% of men suffer from alopecia, which greatly affects patient's self-esteem and quality of life. Currently, commercial products for alopecia treatment include topical minoxidil solution, oral finasteride tablets and oral baricitinib tablets. However, the barrier of stratum corneum, systemic adverse effects and poor cure rate limit the application of commercial products. Therefore, researchers investigated the mechanism of alopecia, and developed new drugs that could target lactate dehydrogenase-related pathways, remove excessive reactive oxygen in hair follicles, and reduce the escape of hair follicle stem cells, thus injecting new strength into the treatment of alopecia. Moreover, starting from improving drug stratum corneum penetration and reducing side effects, researchers have developed hair loss treatment strategies based on dissolved microneedles (MNs), such as drug powders/microparticles, nanoparticles, biomimetic cell membranes, phototherapy and magnetically responsive soluble microneedles, which show exciting alopecia treatment effects. However, there are still some challenges in the practical application of the current alopecia treatment strategy with soluble microneedles, and further studies are needed to accelerate its clinical translation.

Nanocrystals in cosmetics and cosmeceuticals by topical delivery.

The main issues with local delivery of cosmetics are their high sensitivity and limited drug loading of active pharmaceutical ingredient. Nanocrystal technology offers consumers cutting-edge and effective products and exhibits enormous development potential in the beauty business as a new delivery method to address the issue of low solubility and low permeability of sensitive chemicals. In this review, we described the processes for making NCs, along with the impacts of loading and the uses of different carriers. Among them, nanocrystalline loaded gel and emulsion are widely used and may further improve the stability of the system. Then, we introduced the beauty efficacy of drug NCs from five aspects: anti-inflammation and acne, anti-bacterial, lightening and freckle removal, anti-aging as well as UV protection. Following that, we presented the current scenario about stability and safety. Finally, the challenges and vacancy were discussed along with the potential uses of NCs in the cosmetics industry. This review serves as a resource for the advancement of nanocrystal technology in the cosmetics sector.

Antioxidant and antibacterial activity of Apis laboriosa honey against Salmonella enterica serovar Typhimurium.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common food-borne pathogen that commonly causes gastroenteritis in humans and animals. Apis laboriosa honey (ALH) harvested in China has significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. We hypothesize that ALH has antibacterial activity against S. Typhimurium. The physicochemical parameters, minimum inhibitory and bactericidal concentrations (MIC and MBC) and the possible mechanism were determined. The results showed that there were significantly different physicochemical parameters, including 73 phenolic compounds, among ALH samples harvested at different times and from different regions. Their antioxidant activity was affected by their components, especially total phenol and flavonoid contents (TPC, TFC), which had a high correlation with antioxidant activities except for the O2- assay. The MIC and MBC of ALH against S. Typhimurium were 20-30% and 25-40%, respectively, which were close to those of UMF5+ manuka honey. The proteomic experiment revealed the possible antibacterial mechanism of ALH1 at IC50 (2.97%, w/v), whose antioxidant activity reduced the bacterial reduction reaction and energy supply, mainly by inhibiting the citrate cycle (TCA cycle), amino acid metabolism pathways and enhancing the glycolysis pathway. The results provide a theoretical basis for the development of bacteriostatic agents and application of ALH.

Hyaluronidase Promote Transdermal Diffusion of Small Sized Curcumin Nanocrystal by Dissolving Microneedles Delivery.

Hyaluronidase is clinically used in treating many skin diseases due to its good permeability-promoting effect, which may motivate the diffusion and absorption of drugs. To verify the penetration osmotic effect of hyaluronidase in microneedles, 55 nm-size curcumin nanocrystals were fabricated and loaded into microneedles containing hyaluronidase in the tip. Microneedles with bullet shape and backing layer of 20% PVA + 20% PVP K30 (w/v) showed excellent performance. The microneedles were able to pierce the skin effectively with a skin insert rate of 90% and demonstrated good mechanical strength. In the in vitro permeation assay, with the increase of hyaluronidase concentration at the tip of the needle, the cumulative release of curcumin increased, as well as the skin retention decreased. In addition, compared with the microneedles without hyaluronidase, the microneedles containing hyaluronidase in the tip exhibited a larger drug diffusion area and deeper diffusion depth. In conclusion, hyaluronidase could effectively promote the transdermal diffusion and absorption of the drug.

Characterization of non-volatile and volatile flavor profiles of Coregonus peled meat cooked by different methods.

This study investigated the effects of different cooking methods on non-volatile flavor (free amino acids, 5'-nucleotides, and organic acids, etc.) of Coregonus peled meat. The volatile flavor characteristics were also analyzed by electric nose and gas chromatography-ion migration spectrometry (GC-IMS). The results indicated that the content of flavor substances in C. peled meat varied significantly. The electronic tongue results indicated that the richness and umami aftertaste of roasting were significantly greater. The content of sweet free amino acids, 5'-nucleotides, and organic acids was also higher in roasting group. Electronic nose principal component analysis can distinguish C. peled meat cooked (the first two components accounted for 98.50% and 0.97%, respectively). A total of 36 volatile flavor compounds were identified among different groups, including 16 aldehydes, 7 olefine aldehydes, 6 alcohols, 4 ketones, and 3 furans. In general, roasting was recommended and gave more flavor substances in C. peled meat.

Skin permeation of curcumin nanocrystals: Effect of particle size, delivery vehicles, and permeation enhancer.

Nanocrystals are characterized by high drug loading, low carrier toxicity, and great structural stability. Therefore, they are a promising and versatile strategy for enhancing the local delivery of insoluble drugs. They achieve this by improving skin adhesion, concentration gradients, and hair follicle accumulation, as well as generating corona diffusion (which forms through the overlap of dissolved drug molecules around a nanocrystal). The development of suitable formulations for enhancing the passive diffusion and/or follicular targeting of nanocrystals is of great importance to clinical practice. We sought to elucidate the influence of particle size, a penetration enhancer, and delivery vehicles on the follicular accumulation and passive dermal permeation of nanocrystals. For this purpose, curcumin nanocrystals (particle size: 60, 120, and 480 nm) were incorporated into xanthan gum gels (delivery vehicles) with propylene glycol (penetration enhancer). This evaluation was performed in a porcine skin model. The results showed that xanthan gum reduced the follicular penetration and passive skin accumulation of curcumin nanocrystals. The propylene glycol enhanced the skin penetration and retention of curcumin nanocrystals in vitro for 24 h. The curcumin nanocrystals of smaller particle size (i.e., 60 and 120 nm) displayed higher passive skin penetration versus those with larger particle size (i.e., 480 nm); however, the latter type showed deeper follicular accumulation. In conclusion, the delivery vehicles, penetration enhancer, and particle sizes examined in this study affect the dermal penetration and accumulation of curcumin nanocrystals. Hence, their effects should be adequately considered when designing formulations of such nanocrystals.

Antitumor Effects of Poplar Propolis on DLBCL SU-DHL-2 Cells.

Propolis is resinous natural product produced by Western honeybees using beeswax and plant and bud exudates, which has a wide range of biological activities, including antioxidation, antibacterial, anti-inflammation, immune regulation, antitumor, and so on. Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer, and accounts for about 30% of all lymphomas. The effect of poplar propolis on DLBCL has not been reported. The IC50 of propolis on the proliferation of DLBCL SU-DHL-2 cell line and its proteins and gene expressions were detected by CCK-8 kit, label-free proteomic, and RT-PCR. The results showed that the IC50 of propolis at the 5 × l05/mL cell for 24 h was 5.729 µg/mL. Label-free-based proteomics analysis showed that there were 115 differentially expressed proteins (61 up-regulated and 54 down-regulated proteins) between IC50 dose-treated and solvent control groups. There were 32.47% differential proteins located in the nucleus, 20.78% in the cytoplasm, and 14.29% in mitochondria. The most significant different pathway (p = 0.0016) of protein enrichment was ferroptosis (including glutamate-cysteine ligase regulatory subunit, ferritin, and heme oxygenase). The relative expression trend of 17 of the total 22 genes selected according to proteomics results was in line with their encoded protein. The highest protein-protein interaction was serine/threonine-protein kinase PLK, which interacted with 16 differential proteins. In conclusion, poplar propolis inhibited SU-DHL-2 cells via ferroptosis pathway, accelerating cell death and down-regulated serine/threonine-protein kinase PLK1, affecting apoptosis of cell. This result provides a theoretical basis for the treatment of DLBCL using propolis.

Dual Antimelanogenic Effect of Nicotinamide-Stabilized Phloretin Nanocrystals in Larval Zebrafish.

Melanin is a kind of dark insoluble pigment that can cause pigmentation and free-radical clearance, inducing melasma, freckles, and chloasma, affecting the quality of life of patients. Due to poor water solubility and low safety, the absorption of poorly water-soluble drugs is limited by the hinderance of a skin barrier. Therefore, it is necessary to develop new, safe, and highly efficient drugs to improve their transdermal absorption efficiency and thus to inhibit the production of melanin. To address these issues, we developed a new nicotinamide (NIC)-stabilized phloretin nanocrystals (PHL-NCs). First, NC technology significantly increased the solubility of PHL. The in vitro release results indicated that at 6 h, the dissolution of the PHL-NIC-NCs was 101.39% ± 2.40% and of the PHL-NCs was 84.92% ± 4.30%, while that of the physical mixture of the two drugs was only 64.43% ± 0.02%. Second, NIC acted not only as a stabilizer to enlarge the storage time of PHL-NIC-NCs (improved to 10-day in vitro stability) but also as a melanin transfer inhibitor to inhibit melanin production. Finally, we verified the melanin inhibition effect of PHL-NIC-NCs evaluated by the zebrafish model. It showed that 0.38 mM/L PHL-NIC-NCs have a lower tyrosinase activity at 62.97% ± 0.52% and have less melanin at 36.57% ± 0.44%. The inhibition effect of PHL-NCs and PHL-NIC-NCs was stronger compared to the positive control arbutin. In conclusion, the combination of NIC and PHL achieves better inhibition of tyrosinase and inhibition of melanin production through synergism. This will provide a direction to the subsequent development of melanin-inhibiting drugs and the combined use of pharmaceutical agents.

Strategies and Mechanism in Reversing Intestinal Drug Efflux in Oral Drug Delivery.

Efflux transporters distributed at the apical side of human intestinal epithelial cells actively transport drugs from the enterocytes to the intestinal lumen, which could lead to extremely poor absorption of drugs by oral administration. Typical intestinal efflux transporters involved in oral drug absorption process mainly include P-glycoprotein (P-gp), multidrug resistance proteins (MRPs) and breast cancer resistance protein (BCRP). Drug efflux is one of the most important factors resulting in poor absorption of oral drugs. Caco-2 monolayer and everted gut sac are sued to accurately measure drug efflux in vitro. To reverse intestinal drug efflux and improve absorption of oral drugs, a great deal of functional amphiphilic excipients and inhibitors with the function of suppressing efflux transporters activity are generalized in this review. In addition, different strategies of reducing intestinal drugs efflux such as silencing transporters and the application of excipients and inhibitors are introduced. Ultimately, various nano-formulations of improving oral drug absorption by inhibiting intestinal drug efflux are discussed. In conclusion, this review has significant reference for overcoming intestinal drug efflux and improving oral drug absorption.

Polysaccharide-Based Transdermal Drug Delivery.

Materials derived from natural plants and animals have great potential for transdermal drug delivery. Polysaccharides are widely derived from marine, herbal, and microbial sources. Compared with synthetic polymers, polysaccharides have the advantages of non-toxicity and biodegradability, ease of modification, biocompatibility, targeting, and antibacterial properties. Currently, polysaccharide-based transdermal drug delivery vehicles, such as hydrogel, film, microneedle (MN), and tissue scaffolds are being developed. The addition of polysaccharides allows these vehicles to exhibit better-swelling properties, mechanical strength, tensile strength, etc. Due to the stratum corneum's resistance, the transdermal drug delivery system cannot deliver drugs as efficiently as desired. The charge and hydration of polysaccharides allow them to react with the skin and promote drug penetration. In addition, polysaccharide-based nanotechnology enhances drug utilization efficiency. Various diseases are currently treated by polysaccharide-based transdermal drug delivery devices and exhibit promising futures. The most current knowledge on these excellent materials will be thoroughly discussed by reviewing polysaccharide-based transdermal drug delivery strategies.

Particle Size Effect of Curcumin Nanocrystals on Transdermal and Transfollicular Penetration by Hyaluronic Acid-Dissolving Microneedle Delivery.

Microneedles are one promising penetration enhancement vehicle to overcome the stratum corneum skin barrier, which hampers the penetration of drug nanocrystals by transdermal delivery. In order to clarify the particle size effect of nanocrystals on transdermal delivery, 60 nm, 120 nm, and 480 nm curcumin nanocrystals were fabricated and incorporated into dissolving hyaluronic acid polysaccharide microneedles. The microneedles showed good mechanical strength with 1.4 N/needle, possessing the ability to insert into the skin. The passive permeation results showed that the smaller particle size of 60 nm curcumin nanocrystals diffused faster and deeper than the larger 120 nm and 480 nm curcumin nanocrystals with size-dependent diffusion behaviors. Thereafter, higher concentration gradients and overlap diffusional coronas also formed in the skin layers by the smaller-particle-size nanocrystals. Furthermore, the diffusion rate of the smaller particle size of curcumin nanocrystals to the hair follicle was also higher than that of the larger curcumin nanocrystals. In conclusion, the particle sizes of curcumin nanocrystals influenced the transdermal and transfollicular penetration in deeper skin layers.

A Nanocrystals-Based Topical Drug Delivery System with Improved Dermal Penetration and Enhanced Treatment of Skin Diseases.

Topical drug delivery methods are important in the treatment of skin diseases. Drug nanocrystals, which are nanometersized particles of active pharmaceutical ingredients, offer efficient topical delivery with high stability, high drug loading capacity, steady dissolution, and sustained drug release profiles. The use of nanocrystals for the topical delivery of skin disease therapies is currently being evaluated; this review focuses on how nanocrystals facilitate active pharmaceutical ingredient transport across skin barriers, exploring the underlying transportation mechanisms of the nanocrystals and active pharmaceutical ingredient molecules to the dermal and epidermal skin cells. In topical delivery, previous skin treatments, choice of excipients and vehicles, and penetration enhancement strategies critically influence the topical delivery of drug nanocrystals. Various research and applications of drug nanocrystals in skin disease therapy are highlighted in this review, and intellectual property protection for drug nanocrystal formulations, clinical trial data, and products with commercial potential are also discussed.