Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.

Construction of various lipid carriers to study the transdermal penetration mechanism of sinomenine hydrochloride.

OBJECTIVE: To investigate the transdermal mechanisms and compare the differences in transdermal delivery of Sinomenine hydrochloride (SN) between solid lipid nanoparticles (SLN), liposomes (LS), and nanoemulsions (NE). METHODS: SN-SLN, SN-LS and SN-NE were prepared by ultrasound, ethanol injection and spontaneous emulsification, respectively. FTIR, DSC, in vitro skin penetration, activation energy (Ea) analysis were used to explore the mechanism of drug penetration across the skin. RESULTS: The particle size and encapsulation efficiency were 126.60 nm, 43.23 ± 0.48%(w/w) for SN-SLN, 224.90 nm, 78.31 ± 0.75%(w/w) for SN-LS, and 83.22 nm, 89.01 ± 2.16%(w/w) for SN-LS. FTIR and DSC showed the preparations had various levels of impacts on the stratum corneum's lipid structure which was in the order of SLN > NE > LS. Ea values of SN-SLN, SN-LS, and SN-NE crossing the skin were 2.504, 1.161, and 2.510 kcal/mol, respectively. CONCLUSION: SLN had a greater degree of alteration on the skin cuticle, which allows SN to permeate skin more effectively.

An asynchronous response fluorescence sensor combines machine learning theory to qualitatively and quantitatively detect tetracyclines.

Excess use of tetracyclines poses significant health risks arising from animal-derived foods, meaning simple and sensitive methods to detect tetracyclines would be beneficial given current laboratory methods are complex and expensive. Herein, we describe an asynchronous response fluorescence sensor constructed based on Zn-based metal-organic framework and Ru(bpy)32+ (denoted as Ru@Zn-BTEC) for the qualitative and quantitative detection of tetracyclines in foods. Under excitation at 365 nm, the sensor emitted red fluorescence at 609 nm. When tetracyclines were present, these molecules aggregated in the Ru@Zn-BTEC framework, causing green fluorescence emission at 528 nm. The developed sensing system accurately distinguished the different categories of tetracyclines with a classifier accuracy of 94 %. The Ru@Zn-BTEC sensor demonstrated a detection limit of 0.012 µM and satisfactory recovery (87.81 %-113.84 %) for tetracyclines in food samples. This work provides a pathway for constructing asynchronous response fluorescence sensors for food analysis.

The in vitro intestinal cell model: different co-cultured cells create different applications.

As a vitro absorption model, the Caco-2 cells originate from a human colon adenocarcinomas and can differentiate into a cell layer with enterocyte-like features. The Caco-2 cell model is popularly applied to explore drug transport mechanisms, to evaluate the permeability of drug and to predict the absorption of drugs or bioactive substances in the gut. However, there are limitations to the application of Caco-2 cell model due to lack of a mucus layer, the long culture period and the inability to accurately simulate the intestinal environment. The most frequent way to expand the Caco-2 cell model and address its limitations is by co-culturing it with other cells or substances. This article reviews the culture methods and applications of 3D and 2D co-culture cell models established around Caco-2 cells. It also concludes with a summary of model strengths and weaknesses.

Knockdown of the Expression of Two Trehalase Genes with RNAi Disrupts the Trehalose and Chitin Metabolism Pathways in the Oriental Armyworm, Mythimna separata.

Trehalose is an important carbohydrate substance in insect hemolymph. Chitin is the main component of cuticle and peritrophic matrix in insects. Trehalase (Tre) catalyzes the decomposition of trehalose. Few studies of trehalase in lepidopteran insects have been conducted. Here, the functions of soluble Tre (Tre1) and membrane-bound Tre (Tre2) in the growth and development of Mythimna separata were investigated. We cloned and identified Tre1 and Tre2 cDNA sequences in M. separata. Analysis expression revealed that MsTre1 and MsTre2 were highly expressed in midgut and integument, respectively. The expression of MsTre1 and MsTre2 was highest in the pupal stage. We used RNA interference (RNAi) to inhibit Tre expression in M. separata larvae. Injection of dsMsTre1 or dsMsTre2 resulted in abnormal phenotypes and impeded normal molting. Silencing of MsTre1 and MsTre2 resulted in significant changes in the expression of genes in the trehalose and chitin metabolism pathways, significantly increased the trehalose and glycogen content, and significantly decreased MsTre1 and MsTre2 activity, the glucose content, and the chitin content in midgut and integument. Silencing of MsTre1 slowed larval molting, and the new cuticle was significantly thinner. These results indicate that RNAi of Tre may be useful for control strategies against M. separata.

Solid self-microemulsifying drug delivery system (S-SMEDDS) prepared by spray drying to improve the oral bioavailability of cinnamaldehyde (CA).

The aim of this study was to prepare a solid self-microemulsifying drug delivery system (S-SMEDDS) of cinnamaldehyde (CA) by spray drying technique to improve the oral bioavailability of CA. The preparation of CA S-SMEDDS with maltodextrin as the solid carrier, a core-wall material mass ratio of 1:1, a solid content of 20% (w/v), an inlet air temperature of 150 °C, an injection speed of 5.2 mL/min, and an atomization pressure of 0.1 MPa was determined by using the encapsulation rate as the index of investigation. Differential scanning calorimetry (DSC) revealed the possibility of CA being encapsulated in S-SMEDDS in an amorphous form. The in-vitro release showed that the total amount of CA released by S-SMEDDS was approximately 1.3 times higher than that of the CA suspension. Pharmacokinetic results showed that the relative oral bioavailability of CA S-SMEDDS was also increased to 1.6-fold compared to CA suspension. Additionally, we explored the mechanism of CA uptake and transport of lipid-soluble drugs CA by S-SMEDDS in a Caco-2/HT29 cell co-culture system for the first time. The results showed that CA S-SMEDDS uptake on the co-culture model was mainly an energy-dependent endocytosis mechanism, including lattice protein-mediated endocytosis and vesicle-mediated endocytosis. Transport experiments showed that CA S-SMEDDS significantly increased the permeability of CA in this model. These findings suggested that CA S-SMEDDS is an effective oral solid dosage form for increasing the oral bioavailability of lipid-soluble drug CA.

Chinese herb couple against diabetes: integrating network pharmacology and mechanism study.

Cassia twig is a dry twig of Cinnamomum cassia Presl, a Lauraceae plant. Astragalus L is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. Chinese herb couple refers to the matching of two herbs in pairs, mostly with synergistic effects or toxicity reduction. This Chinese herb couple (Cassia twig-Astragalus) come from the classic famous book "Zhang Xichun's book on Chinese herb couple", which is widely used to treat diabetes. Moreover, both Cassia twig and Astragalus belong to the homology of medicine and food. However, its mechanism is still unclear. The study identified the effective components of Cassia twig-Astragalus by UPLC-Q-TOF-MS/MS and investigated the mechanism of Cassia twig-Astragalus in treating diabetes by virtue of network pharmacology, molecular docking and experimental verification. Firstly, based on UPLC-Q-TOF-MS/MS and network pharmacology, a total of 10 active ingredients of Astragalus and 6 active ingredients of Cassia twig were screened, and a total of 13 key targets were obtained. There were 64 targets at the intersection of Cassia twig-Astragalus with diabetes, mainly including IL-17, TNF, NF-κß, AGE-RAGE signaling pathway, etc. It mainly involves the response of cells to insulin stimulation, the response to insulin and the positive regulation of cell adhesion. Secondly, molecular docking results showed that quercetin has good binding activities with AKT1 and TNF. Calycosin has good binding activities with AKT1, TNF and CAV1. Formononetin has good binding activities with TNF and IL-6. Isorhamnetin has good binding activities with AKT1, TNF and IL-6. Finally, the animal experiments showed that Cassia twig-Astragalus could improve the body weight, blood glucose and glucose tolerance in diabetic rats. After the intervention with Cassia twig-Astragalus, the inflammatory factors (IL-10, TNF-α, IL-6) were significantly improved in diabetic rats, which also effectively reduced TG and TC.Communicated by Ramaswamy H. Sarma.

Nuclear isoform of RAPH1 interacts with FOXQ1 to promote aggressiveness and radioresistance in breast cancer.

Radioresistance limits the efficacy of radiotherapy against breast cancer, especially the most lethal subtype of breast cancer, triple-negative breast cancer (TNBC). Epithelial-to-mesenchymal transition (EMT) is closely related to tumor radioresistance. In this work, we attempted to identify the key EMT-related transcription factor(s) that can induce radioresistance in breast cancer cells. A set of 44 EMT transcription factors were analyzed in parental and radioresistant TNBC cell lines. The function of FOXQ1, a differentially expressed transcription factor, was determined in TNBC radioresistance. FOXQ1-interacting proteins were identified by co-immunoprecipitation and mass spectrometry. Compared with parental cells, FOXQ1 was significantly upregulated in radioresistant TNBC cells. Silencing of FOXQ1 increased the radiosensitiviy of radioresistant TNBC cells both in vitro and in vivo. FOXQ1 associated with a nuclear isoform of RAPH1 (named RAPH1-i3) in radioresistant TNBC cells. Overexpression of RAPH1-i3 enhanced TNBC cell proliferation and migration, and most interestingly, induced radioresistance in parental TNBC cells when co-expressed with FOXQ1. Similar findings were observed in estrogen receptor-positive breast cancer cell lines that had co-expression of RAPH1-i3 and FOXQ1. Mechanistically, co-expression of RAPH1-i3 and FOXQ1 activated STAT3 signaling and increased the expression of CCND1, MCL1, Bcl-XL, and MMP2. Depletion of RAPH1-i3 impaired the radioresistance of radioresistant TNBC cells. Additionally, RAPH1-i3 upregulation was associated with advanced tumor stage and reduced disease-free survival in TNBC patients. These results collectively show that RAPH1-i3 interacts with FOXQ1 to promote breast cancer progression and radioresistance. RAPH1-i3 and FOXQ1 represent therapeutic targets for the treatment of breast cancer including TNBC.

Enhancing blueberry wine aroma: Insights from cultivar selection and berry sorting.

This study aimed to improve the aroma quality of blueberry wine by employing cultivar selection and precise berry sorting. We conducted a comprehensive analysis of volatile profiles in blueberry wines derived from nine cultivars commonly cultivated in the middle region of China. 'Misty' and 'V3' blueberry wines exhibited pronounced floral aromas, closely linked to elevated terpenoid and phenylacetaldehyde content. 'Legacy' and 'Star' displayed a distinct fruity aroma profile attributed to the presence of ethyl 2-methylbutyrate, ethyl phenylacetate, and diethyl succinate. 'Jewel' featured an intense buttery aroma, correlated with higher concentrations of ethyl dodecanoate, ethyl decanoate, and ethyl octanoate. Subsequently, 'Misty' and 'Star', with distinct aroma profiles, were selected to further unravel the impact of berry size on blueberry wine aroma. The findings revealed that small berries significantly enhanced 'Misty' blueberry wines, increasing higher alcohol, ester, and terpenoid content, resulting in a more intense fruity and floral aroma. Interestingly, berry size had no discernible influence on 'Star' blueberry wine aroma. This study provides valuable insights into the enhancement of blueberry wine production, shedding light on the intricate interplay of cultivar selection, berry sorting, and their impact on the aromatic attributes of the final product.

Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation.

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.

Fabrication of Co-Assembly from Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection Treatment.

Long-term antibiotic use induces drug resistance in bacteria. This has given rise to the challenge of refractory infections, which have become a global health threat. Berberine (BBR) and tannic acid (TA) from plants exhibit promising antibacterial activities and may overcome antibiotic resistance. However, poor solubility and/or low penetration capability have limited their application. Carrier-free co-assembled nanocomposites composed entirely of BBR and TA exhibit improved or new properties and produce improved efficacy. Herein, we demonstrated that an ordered nanostructure could be spontaneously co-assembled by the solvent evaporation method using the two natural products. These co-assembled berberine-tannic acid nanoparticles (BBR-TA NPs) exhibited the best antibacterial effect compared with the corresponding physical mixture, pristine BBR, and some first-line antibiotics (benzylpenicillin potassium-BP and ciprofloxacin-Cip) against Staphylococcus aureus (S. aureus) and multidrug-resistant Staphylococcus aureus (MRSA). Even if the concentration of BBR-TA NPs was as low as 15.63 µg/mL, the antibacterial rate against S. aureus and MRSA was more than 80%. In addition to the synergistic effect of the two compounds, the antibacterial mechanism underlying the nanostructures was that they strongly adhered to the surface of the bacterial cell wall, thereby inducing cell membrane damage and intracellular ATP leakage. Furthermore, the in vivo wound healing effect of BBR-TA NPs was verified using an MRSA wound infection mouse model. The BBR-TA NPs achieved the best efficacy compared with BP and Cip. Moreover, cytotoxic and histopathological evaluations of mice revealed that the nanodrug had good biological safety. This facile and green co-assembly strategy for preparing nanoparticles provides a feasible reference for the clinical treatment of bacterial infection.

Aroma enhancement of blueberry wine by postharvest partial dehydration of blueberries.

Blueberries with 20%, 30%, and 40% weight loss were used for winemaking, aiming to explore the feasibility of applying postharvest dehydration for improving blueberry wine aroma. Postharvest dehydration decreased the titratable acidity of blueberries and their resultant wines. Total anthocyanins and phenols in blueberries with 30% weight loss were increased by 25.9% and 16.1%, respectively, due to concentration effects, while further dehydration resulted in a decline. Similar trends were observed in blueberry wines. Moderate postharvest dehydration increased total terpenes, benzeneacetaldehyde and phenylethyl alcohol, ethyl butanoate, methyl salicylate, 1-hexanol, and γ-nonalactone content in blueberries and wines, which could enhance the floral, fruity, and sweet notes of blueberry wines. Wines made from blueberries under severe dehydration (40% weight loss) had the lowest overall aroma score, which was related to the higher content of 4-ethyl-phenol and 4-ethylguaiacol. In conclusion, moderate postharvest dehydration benefited the aroma enhancement of blueberry wine.

Association between self-esteem and fear of cancer recurrence in cancer survivors: A cross-sectional study.

PURPOSE: There may be a correlation between self-esteem as an important psychological resource for individuals and Fear of cancer recurrence (FCR), but the relationship between the two is unclear. The aim of our investigation was to evaluate the association of FCR and self-esteem in cancer survivors. METHODS: Cross-sectional sampling was used to select cancer survivors. The study instruments used included: General information questionnaire, Rosenberg Self-Esteem Scale, Perceived Social Support Scale, Fear of Cancer Recurrence Inventory- Shorter Form. We used logistic regression, where models were adjusted considering confounding variables to determine odds ratios (ORs) with 95% confidence intervals (CIs) for the association of FCR with self-esteem. RESULTS: Between February 2022 to July 2022, we screened 380 participants for eligibility, of whom 348 were included in the study. The percentage of cancer survivors who experienced clinical level of FCR was 73.9% and the self-esteem score was 27.73 ± 3.67 at a moderate level. The Pearson' s correlation coefficient indicated a significant inverse relationship between FCR and self-esteem (p < 0.001; r = -0.375). In a multivariable logistic regression model, FCR still has a negative correlation with self-esteem (OR, 0.812; 95%CI, 0.734-0.898). Subgroup analysis indicated that the correlation between FCR and self-esteem in cancer survivors was nearly the same in various strata, demonstrating its soundness and stability. CONCLUSIONS: This study confirms that elevated self-esteem in individuals surviving cancer may be a protective factor for FCR. Improving the level of self-esteem in cancer survivors can be one of the important directions of clinical interventions for FCR.

Co-assembled nanocomplexes comprising epigallocatechin gallate and berberine for enhanced antibacterial activity against multidrug resistant Staphylococcus aureus.

Berberine (BBR), a major alkaloid in Coptis chinensis, and (-)-epigallocatechin-3-gallate (EGCG), a major catechin in green tea, are two common phytochemicals with numerous health benefits, including antibacterial efficacy. However, the limited bioavailability restricts their application. Advancement in the co-assembly technology to form nanocomposite nanoparticles precisely controls the morphology, electrical charge, and functionalities of the nanomaterials. Here, we have reported a simple one-step method for preparing a novel nanocomposite BBR-EGCG nanoparticles (BBR-EGCG NPs). These BBR-EGCG NPs exhibit improved biocompatibility and greater antibacterial effects both in vitro and in vivo relative to free-BBR and first-line antibiotics (i.e., benzylpenicillin potassium and ciprofloxacin). Furthermore, we demonstrated a synergistic bactericidal effect for BBR when combined with EGCG. We also evaluated the antibacterial activity of BBR and the possible synergism with EGCG in MRSA-infected wounds. A potential mechanism for synergism between S. aureus and MRSA was also explored through ATP determination, the interaction between nanoparticles and bacteria, and, then, transcription analysis. Furthermore, our experiments on S. aureus and MRSA confirmed the biofilm-scavenging effect of BBR-EGCG NPs. More importantly, toxicity analysis revealed that the BBR-EGCG NPs had no toxic effects on the major organs of mice. Finally, we proposed a green method for the fabrication of BBR-EGCG combinations, which may provide an alternative approach to treating infections with MRSA without using antibiotics.

The intestinal mucosal barrier - A key player in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a recurrent chronic autoimmune disease, which is not only difficult to treat, but also has a great adverse impact on the physical and mental health of patients. The intestinal mucosa barrier has some relationship with RA and it consists of mechanical barrier, chemical barrier, immune barrier, and microflora barrier. It is a dynamic system that contributes to the stability of the intestinal environment by regulating the absorption of relevant substances from the lumen into the circulation, while limiting the passage of harmful substances. This article summarizes the connection between the intestinal mucosa barrier and RA, and proposes the role of relevant Chinese medicines on RA from the point of improving barriers, to provide new perspectives on the pathogenesis and therapeutic strategies of RA.

[Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics].

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1ß(IL-1ß), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Trehalose-6-phosphate synthase regulates chitin synthesis in Mythimna separata.

Trehalose is a substrate for the chitin synthesis pathway in insects. Thus, it directly affects chitin synthesis and metabolism. Trehalose-6-phosphate synthase (TPS) is a crucial enzyme in the trehalose synthesis pathway in insects, but its functions in Mythimna separata remain unclear. In this study, a TPS-encoding sequence in M. separata (MsTPS) was cloned and characterized. Its expression patterns at different developmental stages and in diverse tissues were investigated. The results indicated that MsTPS was expressed at all analyzed developmental stages, with peak expression levels in the pupal stage. Moreover, MsTPS was expressed in the foregut, midgut, hindgut, fat body, salivary gland, Malpighian tubules, and integument, with the highest expression levels in the fat body. The inhibition of MsTPS expression via RNA interference (RNAi) resulted in significant decreases in the trehalose content and TPS activity. It also resulted in significant changes in Chitin synthase (MsCHSA and MsCHSB) expression, and significantly decrease the chitin content in the midgut and integument of M. separata. Additionally, the silencing of MsTPS was associated with a significant decrease in M. separata weight, larval feed intake, and ability to utilize food. It also induced abnormal phenotypic changes and increased the M. separata mortality and malformation rates. Hence, MsTPS is important for M. separata chitin synthesis. The results of this study also suggest RNAi technology may be useful for enhancing the methods used to control M. separata infestations.

Effects of Torulaspora delbrueckii co-fermented with Saccharomyces cerevisiae on physicochemical and aromatic profiles of blueberry fermented beverage.

To investigate the effects of mixed fermentation with T. delbrueckii on aroma profiles of blueberry fermented beverage, five fermentations were conducted: monoculture of T. delbrueckii and S. cerevisiae, respectively; co-inoculation of two strains; sequential inoculation of two strains at time intervals of 24 h and 48 h, respectively. Compared with pure S. cerevisiae fermentation, ethanol level was decreased by up to 1.1% vol., while total anthocyanins were increased by 27.7%-85.0% in mixed fermentations. Marker aroma compounds in different fermentations with relative odor activity values higher than 1were identified. T. delbrueckii significantly decreased volatile acid content (especially acetic acid) by 22.2%-83.3%. Ethyl 3-methylbutanoate, ethyl hexanoate and ethyl octanoate, in pure T. delbrueckii fermentation were significantly decreased, while their concentrations were increased by 1.6-4.4 folds in sequential fermentations. Besides, linalool, rose oxide, benzeneacetaldehyde were significantly increased by sequential fermentation, which was associated with the enhancement of fruity and sweet notes.

A Shape-Adaptive Gallic Acid Driven Multifunctional Adhesive Hydrogel Loaded with Scolopin2 for Wound Repair.

Wound healing is one of the major challenges in the biomedical fields. The conventional single drug treatment has unsatisfactory efficacy, and the drug delivery effectiveness is restricted by the short retention on the wound. Herein, we develop a multifunctional adhesive hydrogel that can realize robust adhesion, transdermal delivery, and combination therapy for wound healing. Multifunctional hydrogels (CS-GA-S) are mixed with chitosan-gallic acid (CS-GA), sodium periodate, and centipede peptide-scolopin2, which slowly releases scolopin2 in the layer of the dermis. The released scolopin2 induces the pro-angiogenesis of skin wounds and enables excellent antibacterial effects. Separately, GA as a natural reactive-oxygen-species-scavenger promotes antioxidation, and further enables excellent antibacterial effects and wet tissue adhesion due to a Schiff base and Michael addition reaction for accelerating wound healing. Once adhered to the wound, the precursor solution becomes both a physically and covalently cross-linked network hydrogel, which has potential advantages for wound healing with ease of use, external environment-isolating, and minimal tissue damage. The therapeutic effects of CS-GA-S on wound healing are demonstrated with the full thickness cutaneous wounds of a mouse model. The significant improvement of wound healing is achieved for mice treated with CS-GA-S. This preparation reduces wound system exposure, prolongs local drug residence time, and improves efficacy. Accordingly, with the incorporation of scolopin2 into the shape-adaptive CS-GA hydrogel, the composite hydrogel possesses multi-functions of mechanical adhesion, drug therapy, and skin wound healing. Overall, such an injectable or sprayable hydrogel plays an effective role in emergency wound treatment with the advantage of convenience and portability.

Axillary management for early invasive breast cancer patients: Who will truly benefit?

Background: The implementation of sentinel lymph node biopsy (SLNB) and further completion axillary lymph node dissection (cALND) after positive sentinel lymph nodes (SLNs) on early invasive breast cancer patients should be cautiously tailored. Identifying predictors for SLN and non-sentinel lymph node (nSLN) metastases can help surgeons make better surgical decisions. Methods: A retrospective case-control study was designed and a total of 560 eligible patients were enrolled consecutively. They were all diagnosed in our center and received appropriate medical care. According to the metastasis of SLN and nSLN, they were divided into metastatic and non-metastatic groups on two successive occasions to investigate the relationship between clinical factors, pathological factors, hematological factors and lymph node metastasis. Results: In total, 101 (18.04%) patients developed SLN metastases, including 98 patients with macro-metastases and 3 patients with micro-metastases. Out of 97 patients receiving further cALND, 20 patients (20.62%) developed nSLN metastases. Multivariate analysis revealed that "high expression of Ki-67" and "lymphatic invasion" predicted a higher risk of SLN metastasis; and "increased number of positive SLNs" and "increased systemic inflammation index (SII)" predicted a higher risk of nSLN metastasis. Conclusion: Surgery for early invasive breast cancer patients should be more customized and precise. Appropriate axillary management is necessary for patients with the associated predictors.