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Hyperlipidemia poses significant risks for cardiovascular diseases, with emerging evidence underscoring the critical role of gut microbiota in metabolic regulation. This study explores Lactobacillus casei CAAS36, a probiotic strain with promising cholesterol-lowering capabilities, assessing its impact on hyperlipidemic hamsters. Utilizing 1H NMR-based metabolomics and 16S rRNA gene sequencing, we observed that L. casei CAAS36 treatment not only altered metabolic pathways but also reshaped gut microbiota composition. Notably, the treatment restored the balance between Firmicutes and Bacteroidetes and significantly increased the abundance of propionate-producing Muribaculaceae. Metabolically, L. casei CAAS36 administration led to the normalization of key lipid markers, including reductions in total cholesterol, LDL-C, and triglycerides (29.9%, 29.4% and 32.6%), while enhancing the protective HDL-C levels. These effects were accompanied by significant increases in beneficial metabolites such as propionate and succinate, which are known for their roles in preventing metabolic disorders. These findings highlight the dual regulatory effects of L. casei CAAS36 on the metabolic profile and gut microbiota, suggesting a substantial potential for this probiotic in the management of hyperlipidemia and possibly other metabolic diseases. Future applications may include its use as a natural therapeutic agent in clinical settings, aiming to reduce reliance on conventional pharmaceuticals and their associated side effects.

Human milk phospholipids (HMPLs) play an indispensable role in the neurodevelopment and growth of infants. In this study, a total of 37 phospholipid fatty acid (PLFA) species and 139 phospholipid molecular species were detected from human milk and other natural phospholipid sources (including 5 animal-derived species and 2 plant species). Moreover, a similarity evaluation model for HMPLs was established, including phospholipid classes, PLFAs, and phospholipid molecular species, to evaluate their natural substitutes. The closest scores for HMPL substitute in these three dimensions was 0.89, 0.72, and 0.77, which belonged to mare milk, goat milk, and camel milk, respectively. The highest comprehensive similarity score was obtained by camel milk at 0.75, while the lowest score was observed in soybean phospholipid (0.22). Therefore, these results not only monitored the stereochemical structure of HMPLs and their substitutes, but also further provided new insights for the development of infant formulae., Competing Interests: Declaration of competing interest Author Hong Zhang, Xuebing Xu, and Ruihua Guo were employed by Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

The quality issues of ultra-high-temperature (UHT) milk, such as protein hydrolysis and aging gels throughout shelf life, are caused by proteases from psychrophilic bacteria. However, existing enzyme activity detection techniques have low sensitivity and cannot accomplish the detection of product deterioration caused by low enzyme activity. In this study, an attempt was made to analyze the relationship between enzymatically cleaved peptides and product quality using peptidomics techniques. The impact of psychrophilic bacteria proteases on the quality of UHT milk was investigated based on peptidomics by exogenously adding proteases. The results indicated that the protease activity and protein hydrolysis increased significantly in UHT milk over the storage period. Through peptidomic analysis, 2479 peptides were identified, in which 32 proteins linked to the identified peptides. 17 potential marker peptides, including αS 1 -casein 143-156 , β -lactoglobulin 99-108 , and β -casein 39-66 , were screened. The correlation of all identified peptides with protease activity and protein hydrolysis was explored by the weighted gene co-expression network analysis (WGCNA) method. The peptidomics technology helps to study the release or degradation of peptides in UHT milk during storage, which can be applied to monitor the shelf life of UHT milk and predict spoilage., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The study was carried out to determine the effects of addition of Cumin (Cuminum cyminum L.), Sichuan pepper (Zanthoxylum bungeanum) or their mixture on the chemical, textural, microbial and sensory characteristics and antioxidant capacity of Camembert type cheese made from dairy goats. The chemical composition of cheese was not affected by addition of spices (Cumin, Sichuan pepper or their mixture). Addition of spices considerably affected the texture, microbial and sensory quality and antioxidant capacity of cheese. Overall acceptability score increased from 2.8 in the control cheese to 3.7, 3.2 and 3.4 in the cheeses spiced with cumin, Sichuan pepper and their mixture, respectively after 40 days of ripening. All spiced cheeses also showed higher antioxidant activity compared to the control cheese. Total phenolic content increased from 20.8 to 82.3 in the control cheese to 32.5-94.5, 46.7-118.8, 37.4-104.6 in the cheeses spiced with cumin, Sichuan pepper and their mixture, respectively during the 40 days of ripening period. Similarly, the DPPH increased from 10.4 to 60.4 in the control cheese to 16.7-73.5, 25.8-87.8, 20.3-80.7 in the cheeses spiced with cumin, Sichuan pepper and their mixture, respectively during the 40 days of ripening period. In conclusion, addition of Cumin, Sichuan pepper and their mixture produced goat milk camembert type cheese with better sensory quality and antioxidant capacity without affecting the composition of cheese., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Solomon Gebreyowhans reports equipment, drugs, or supplies was provided by Chinese Academy of Agricultural Sciences Institute of Food Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Human and animal milk contain a rich variety of milk proteins that meet the needs of their newborns. In total, 1263 skim milk proteins and 1754 MFGM proteins were identified in human milk and six types of animal milk, respectively. Both similarities and differences were observed among the species. Human milk contained more immunoglobulins involved in the adaptive immune response, playing a crucial role in mucosal defense in newborn babies. In contrast, ruminant milk contained higher amounts of antimicrobial proteins, which protect newborns from bacterial infections. The most dominant difference in MFGM proteins between human and animal milk was related to protein processing in the endoplasmic reticulum. Goat milk and camel milk were more similar to human milk in terms of skim milk and MFGM proteins compared to the other five types of animal milk. Moreover, immunoglobulins and complement and coagulation cascade proteins in goat milk were most similar to those in human milk. A higher content of immunoglobulin A was observed in donkey milk, which could be considered as a source of IgA in infant formula. These results provide more comprehensive and novel insights into protein variation among animal milk, which may support improving dairy products such as infant formula.

Lactosylation of lysines occurs during the heating of dairy products, yet how lactosylation impact the lysine release during digestion remains largely unknown. This study examines the effect of lactosylation on the digestibility of lactotransferrin using chemical analysis, proteomics, and peptidomics. Under the applied heating conditions, lactotransferrin primarily undergoes early-stage Maillard reactions, producing lactulose-lysine. Furosine content increases with heating time and temperature, with time being more influential. And 23 out of 54 lysines in lactotransferrin were lactosylated. Following in-vitro infant digestion, free lysine levels in samples heated at 130 °C for 30s decreased by 25 % compared to unheated ones, likely due to lactosylation hindering protease cleavage. Intriguingly, lactosylated lysine was absent in peptides ranging from 5 to 17 amino acids but remained in larger peptides. The formation of large lactosylated peptides from heating impeded free lysine release. Further investigation is needed to determine if the human body can utilize these lactosylated peptides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

(1) Background: This study investigated the impact of in vitro adaptations to acid and bile stress on the cholesterol-lowering activity of the probiotic Lactobacillus kefir M20. (2) Methods: Lactobacillus kefir M20 was extracted from fermented dairy products in Xinjiang, China, and isolated using MRS medium. The lactic acid bacteria were cultured for stress resistance to acid and bile salts and then gavaged into mice for animal experiments. (3) Results: The adaptation to bile stress treatment resulted in a notable enhancement of the cholesterol-lowering capacity of Lactobacillus kefir M20, with reductions of 16.5% and 33.1% in total and non-HDL cholesterol, respectively, compared to the untreated strain. Furthermore, the daily fecal total bile acid excretion was 9.2, 5.4 and 5.0 times higher in the M20-BSA group compared to the HC, M20 and M20-ASA groups, respectively. (4) Conclusions: This study suggests that targeted probiotics have the potential for application in the next generation of functional foods and probiotic formulations aimed at combating hypercholesterolemia.

Background: Skin flap transplantation is used to effectively reconstruct defects of the hand and foot skin and soft tissues. We here investigated the effect of the PF127/bleomycin (BLM) hydrogel on the extracellular matrix (ECM) remodeling of skin flaps and the underlying mechanism, thereby providing a new reference point for personalized flap modification and overcoming abrasion resistance- and stability-associated difficulties., Methods: The appropriate PF127/BLM concentration was selected based on the gelation time and drug release curve. Migration assays, scratch assays, and live/dead staining were conducted to verify the effect of PF127/BLM on human skin fibroblasts (HSFs). The effects of PF127/BLM on the ECM were assessed through hematoxylin and eosin and Masson staining. Additionally, we examined the expression of ECM remodeling-related genes and proteins involved in their associated signaling pathway. Finally, the effects of PF127/BLM on organ fibrosis and toxicity to liver and kidney functions were assessed in mice., Results: A 25% PF127/BLM hydrogel was selected as the study concentration. PF127/BLM augmented HSF chemotaxis and proliferation. Furthermore, PF127/BLM promoted subcutaneous ECM remodeling and fibrosis, increased the flap dermis thickness, and reduced the toxic side effects of BLM on liver/lung fibrosis and liver/kidney function. Additional studies confirmed that the PF127/BLM-mediated regulation of ECM remodeling in skin flaps was associated with TGFβ-Col signaling pathway activation., Conclusion: The PF127/BLM hydrogel promoted subcutaneous ECM remodeling and fibrosis, which aided the construction of personalized flaps through the TGFβ-Col signaling pathway, with decreased hepatic, pulmonary, and renal toxicities.

Milk is an ideal environment for the growth of microorganisms, especially psychrotrophic bacteria, which can survive under cold conditions and produce heat-resistant enzymes. Psychrotrophic bacteria create the great problem of spoiling milk quality and safety. Several ways that milk might get contaminated by psychrotrophic bacteria include animal health, cowshed hygiene, water quality, feeding strategy, as well as milk collection, processing, etc. Maintaining the quality of raw milk is critically essential in dairy processing, and the dairy sector is still affected by the premature milk deterioration of market-processed products. This review focused on the recent detection and control strategies of psychrotrophic bacteria and emphasizes the significance of advanced sensing methods for early detection. It highlights the ongoing challenges in the dairy industry caused by these microorganisms and discusses future perspectives in enhancing milk quality through innovative rapid detection methods and stringent processing controls. This review advocates for a shift towards more sophisticated on-farm detection technologies and improved control practices to prevent spoilage and economic losses in the dairy sector.

FMS-like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase, which is an important target for anti-cancer therapy. In this work, we conducted a structure-activity relationship (SAR) study on 3867 FLT3 inhibitors we collected. MACCS fingerprints, ECFP4 fingerprints, and TT fingerprints were used to represent the inhibitors in the dataset. A total of 36 classification models were built based on support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGBoost), and deep neural networks (DNN) algorithms. Model 3D_3 built by deep neural networks (DNN) and TT fingerprints performed best on the test set with the highest prediction accuracy of 85.83% and Matthews correlation coefficient (MCC) of 0.72 and also performed well on the external test set. In addition, we clustered 3867 inhibitors into 11 subsets by the K-Means algorithm to figure out the structural characteristics of the reported FLT3 inhibitors. Finally, we analyzed the SAR of FLT3 inhibitors by RF algorithm based on ECFP4 fingerprints. The results showed that 2-aminopyrimidine, 1-ethylpiperidine,2,4-bis(methylamino)pyrimidine, amino-aromatic heterocycle, [(2E)-but-2-enyl]dimethylamine, but-2-enyl, and alkynyl were typical fragments among highly active inhibitors. Besides, three scaffolds in Subset_A (Subset 4), Subset_B, and Subset_C showed a significant relationship to inhibition activity targeting FLT3., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this study, we built classification models using machine learning techniques to predict the bioactivity of non-covalent inhibitors of Bruton's tyrosine kinase (BTK) and to provide interpretable and transparent explanations for these predictions. To achieve this, we gathered data on BTK inhibitors from the Reaxys and ChEMBL databases, removing compounds with covalent bonds and duplicates to obtain a dataset of 3895 inhibitors of non-covalent. These inhibitors were characterized using MACCS fingerprints and Morgan fingerprints, and four traditional machine learning algorithms (decision trees (DT), random forests (RF), support vector machines (SVM), and extreme gradient boosting (XGBoost)) were used to build 16 classification models. In addition, four deep learning models were developed using deep neural networks (DNN). The best model, Model D_4, which was built using XGBoost and MACCS fingerprints, achieved an accuracy of 94.1% and a Matthews correlation coefficient (MCC) of 0.75 on the test set. To provide interpretable explanations, we employed the SHAP method to decompose the predicted values into the contributions of each feature. We also used K-means dimensionality reduction and hierarchical clustering to visualize the clustering effects of molecular structures of the inhibitors. The results of this study were validated using crystal structures, and we found that the interaction between the BTK amino acid residue and the important features of clustered scaffold was consistent with the known properties of the complex crystal structures. Overall, our models demonstrated high predictive ability and a qualitative model can be converted to a quantitative model to some extent by SHAP, making them valuable for guiding the design of new BTK inhibitors with desired activity., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Management of large irregular wounds in children had been confusing plastic and reconstructive surgeons. Herein, this study was aimed to propose a new treatment method based on the principle of adapting different recipient zones to overcome the intractable wounds, simplifying and programing the design process of targeted flaps for covering large irregular soft-tissue defects., Patients and Methods: From January 2009 to December 2020, 31 children (9 girls and 22 boys) aged 3-16 years (mean 9.8 years) underwent multiple modular flaps with edge to edge splicing reconstruction of the lower extremities. All the wounds were large with non-adjacent defects and with or without a dead space. Several variants of flaps were harvested according to the needs and reconstruction requirements of patients., Results: A total of 71 flaps were harvested from 31 patients and all flaps donor sites received primary closure. Nine patients underwent split-thickness skin grafting, and three cases of flaps survived from vascular crisis by rebuilding the vessels and the rest accepting LD flap transplants. And five partial necrosis of the distal epidermis flaps recovered using skin grafting and dressing change. No major complication was encountered in other patients and donor sites, except one heel ulcer. During the follow-up (ranging from 16 to 38 months, mean 27.7 months), aesthetic and functional results of reconstructed limbs were satisfactory in all patients., Conclusions: The Individualized design program of multiple flaps for adapting different recipient zones is an alternative for repairing large irregular soft-tissue defects in children, beneficial for plastic and reconstructive surgeons to simplify and program the process of designing and perform multiple flaps to achieve this goal., Level of Evidence: III, Retrospective., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

We aimed to obtain the optimal formula for human milk fat substitute (HMFS) through a combination of software and an evaluation model and further verify its practicability through an animal experiment. The results showed that a total of 33 fatty acid (FA) and 63 triglyceride (TAG) molecular species were detected in vegetable oils. Palmitic acid, oleic acid, linoleic acid, 18:1/16:0/18:1, 18:2/16:0/18:2, 18:1/18:1/18:1 and 18:1/18:2/18:1, were the main molecular species among the FAs and TAGs in the vegetable oils. Based on the HMFS evaluation model, the optimal mixed vegetable oil formula was blended with 21.3% palm oil, 2.8% linseed oil, 2.6% soybean oil, 29.9% rapeseed oil and 43.4% maize oil, with the highest score of 83.146. Moreover, there was no difference in the weight, blood routine indices or calcium and magnesium concentrations in the feces of the mice between the homemade mixed vegetable oil (HMVO) group and the commercial mixed vegetable oil (CMVO) group, while nervonic acid (C24:1) and octanoic acid (C8:0) were absorbed easily in the HMVO group. Therefore, these results demonstrate that the mixing of the different vegetable oils was feasible via a combination of computer software and an evaluation model and provided a new way to produce HMFS.

In this study, Senescence Accelerated Mice (SAMP8) were supplemented with exogenous DHA milk, endogenous DHA milk, normal milk, or 0.9 % saline solution. Enzyme-linked immunosorbent assay (ELISA), gas chromatography (GC), ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI MS/MS), and Morris water maze were used to characterize the effects of diet on oxidative stress and cognition in SAMP8 mice. Supplementation endogenous DHA milk or exogenous DHA milk can enhance the antioxidant capacity of mice organs. Endogenous DHA milk increased the superoxide dismutase (SOD) activity of mice brain and serum than normal milk and 0.9 % saline solution (P ≤ 0.05), as well as increased SOD activity of mice liver and glutathione peroxidase (GSH-Px) activity of mice brain than normal milk (P ≤ 0.05). Exogenous DHA milk increased SOD activity of mice brain than normal milk and 0.9 % saline solution, as well as increased SOD activity of mice serum than 0.9 % saline solution (P ≤ 0.05). Several polar lipid relative content, such as 18:0/18:2 PS, 17:0 Ceramide, and 20:4 LPC in mice brain was affected by dietary supplementation with DHA-containing milk. Lipid oxidation metabolites in mice brain were not affected by DHA-containing milk. Endogenous DHA milk increased the number of platform location crossing times of mice in the Morris water maze test, compared with Exogenous DHA milk, normal milk, and 0.9 % saline solution (P ≤ 0.05)., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: A new spray adhesive (KYNA-PF127) was established through the combination of thermosensitive hydrogel (Pluronic F127) and KYNA, aimed to investigate the effect of KYNA-PF127 on multi-territory perforator flaps and its possible molecular mechanism., Materials and Methods: 36 SD male rats with 250-300 g were randomly divided into 3 groups (n = 12): control group, blank glue group and KYNA-PF127 group. KYNA-PF127 hydrogel was prepared and characterized for its morphology and properties using scanning electron microscopy. CCK-8 assay, scratch wound assay, transwell assay, tube formation assay and Ki67 staining were used to study the effect of KYNA-PF127 on the proliferation, migration, and tube formation of HUVECs. VEGF and FGF2 were measured by qPCR to evaluate the angiogenesis capacity of HUVECs in vitro. In vivo, the effect of each group on the survival area of the cross-zone perforator flap was evaluated, and angiogenesis was evaluated by HE and immunofluorescence (CD31 and MMP-9). The effect of inflammation on skin collagen fibers was assessed by Masson. Immunohistochemistry (SOD1, IL-1β, TNF-α) was used to evaluate the effects of oxidative stress and inflammatory factors on multi-territory flaps., Results: KYNA-PF127 has good sustained release and biocompatibility at 25% concentration. KYNA-PF127 promoted the proliferation, migration, and angiogenesis of HUVECs in vitro. In vivo, the survival area of multi-territory perforator flaps and angiogenic capability have increased after KYNA-PF127 intervention. KYNA-PF127 could effectively reduce the oxidative stress and inflammation of multi-territory perforator flaps., Conclusion: KYNA-PF127 promotes angiogenesis through its antioxidant stress and anti-inflammatory effects, and shows potential clinical value in promoting the survival viability and drug delivery of multi-territory perforator flaps., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The study aims to analyze the composition of the gut microbiota in Chinese individuals using metagenomic sequencing technology, with a particular focus on the abundance of Akkermansia muciniphila (Akk). To improve the efficiency of Akk isolation and identification accuracy, modifications were made to the enrichment culture medium and 16S rRNA universal primers. Additionally, potential growth-promoting factors that stimulate Akk growth were explored through in vitro screening. The research results revealed that the abundance of Akk in Chinese fecal samples ranged from 0.004% to 0.4%. During optimization, a type of animal protein peptide significantly enhanced the enrichment efficiency of Akk, resulting in the isolation of three Akk strains from 14 fecal samples. Furthermore, 17 different growth-promoting factors were compared, and four factors, including galactose, sialic acid, lactose, and chitosan, were identified as significantly promoting Akk growth. Through orthogonal experiments, the optimal ratio of these four growth-promoting factors was determined to be 1:1:2:1. After adding 1.25% of this growth-promoting factor combination to the standard culture medium, Akk was cultivated at 37° for 36 h, achieving an OD 600nm value of 1.169, thus realizing efficient proliferation and optimized cultivation of Akk. This study provides important clues for a deeper understanding of the gut microbiota composition in Chinese individuals, while also offering effective methods for the isolation and cultivation of Akk, laying the groundwork for its functional and application research in the human body.

Milk samples were collected from 3625 Chinese Holstein cows to assess the effects of κ-casein (κ-CN) and β-lactoglobulin (β-LG) genetic variants on its milk coagulation properties. The results show that Chinese Holstein cows have a higher frequency of the κ-CN AA and AB variants, and β-LG of the AB and AA variants. Of these, κ-CN B variants, the β-LG AA and BB variants were more frequent in milk showing good coagulation. The effects of the genetic variants on milk composition, milk proteome, and protein phosphorylation sites were studied. The results showed that higher concentrations of protein and dry matter were found in κ-CN BE variant. Moreover, large variations in milk proteome among different κ-CN and β-LG variants were observed. Highly phosphorylated for κ-CN, especially Ser 97 , was observed in cows with the κ-CN BE variant, but no effect of β-LG variants on phosphorylation site was found. Of the various factors examined, variation of κ-CN phosphorylation sites Ser 97 may be the most important in affecting casein structure and milk coagulation ability. Some milk protein contents were found to be negative factors for milk coagulation. In summary, this study showed that κ-CN genetic variants contained different milk compositions and phosphorylation site Ser 97 influenced milk coagulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

ZW10 interacting kinetochore protein (ZWINT), an essential part of the kinetochore complex, plays a crucial role in maintaining genome stability by correcting improper attachments between the kinetochore and microtubules. An initial analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed that ZWINT is significantly expressed across a diverse range of tumor types. We subsequently investigated the influence of ZWINT on clinical outcomes and potential signaling pathways. A multidimensional analysis of ZWINT revealed significant statistical associations between ZWINT expression and clinical outcomes, as well as the E2F1 oncogenic signature. Experimental validation confirmed the increased expression of ZWINT in both pancreatic cancer cell lines and pancreatic adenocarcinoma tissues. Furthermore, our findings indicate that ZWINT promotes the proliferation of PANC-1 cells through cell cycle regulation. This comprehensive analysis of ZWINT suggests a strong correlation between its expression and various types of tumors, especially pancreatic adenocarcinoma (PAAD), indicating its potential oncogenic role. These findings enhance our understanding of the function of ZWINT in carcinogenesis., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Polydatin has shown considerable pharmacological activities in ischemia-reperfusion injuries of various organs. However, its effects and mechanisms in spinal cord ischemia-reperfusion injury have not been fully established. In this study, the mechanisms of polydatin against spinal cord ischemia-reperfusion injury were investigated via network pharmacology, molecular docking and molecular dynamics simulation., Methods: Spinal cord ischemia-reperfusion injury-related targets were obtained from the GeneCards database, while polydatin-related action targets were obtained from the CTD and SwissTarget databases. A protein-protein interaction network of potential targets was constructed using the String platform. After selecting the potential key targets, GO functional enrichment and KEGG pathway enrichment analyses were performed via the Metascape database, and a network map of "drug-target-pathway-disease" constructed. The relationships between polydatin and various key targets were assessed via molecular docking. Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking., Results: Topological analysis of the PPI network revealed 14 core targets. GO functional enrichment analysis revealed that 435 biological processes, 12 cell components and 29 molecular functions were enriched while KEGG pathway enrichment analysis revealed 91 enriched signaling pathways. Molecular docking showed that polydatin had the highest binding affinity for MAPK3, suggesting that MAPK3 is a key target of polydatin against spinal cord ischemia-reperfusion injury. Molecular dynamics simulations revealed good binding abilities between polydatin and MAPK3., Conclusions: Polydatin exerts its effects on spinal cord ischemia-reperfusion injury through multiple targets and pathways. MAPK3 may be a key target of polydatin in spinal cord ischemia-reperfusion injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, we aimed to detect the physicochemical properties of distilled products (residue and distillate) obtained from anhydrous milk fat (AMF) and its dry fractionation products (liquid and solid fractions at 25°C [25 L and 25 S]). The results showed that the saturated fatty acids and low- and medium molecular-weight triglycerides were easily accumulated in the distillate, and the percentage of unsaturated fatty acid and high molecular-weight triglycerides in the residue were higher, and these components in 25 S and 25 L were influenced more significantly than those in the AMF. In addition, the distillate had larger melting ranges in comparison with the distilled substrate, while the melting ranges of residue was smaller. The triglycerides were presented as the mixture crystal forms (α, β', and β crystal) in 25 S, AMF, and their distilling products, and it was transformed gradually to a single form as the increasing of distilling temperature. Moreover, the accumulated pattern of triglycerides was double chain length in 25 S, AMF, and their distilling products. These results provide a new approach to obtain the milk fat fractions with different properties, and the findings of this study enrich the theoretical basis of milk fat separation in practical production., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This study aims to explore the effect of the Maillard reaction (MR) on flavour development of cheese protein hydrolysates. In addition, the effects of proteolysis, lipolysis, and the degreasing process on the MR have been explored. Cheese protein hydrolysates subjected to different treatments were heated with glucose and xylose, and their amino reactant components, colour parameters, and volatile compounds were determined. The results showed that the MR significantly affected the content of free amino acids, peptides, and volatile flavours of cheese protein hydrolysates. Peptides below 1500 Da and most of the free amino acids were the important amino reactants during the MR. 3-Ethyl-2,5-dimethylpyrazine, 2,5-dimethylpyrazine, 2-undecanone and 2-heptanone were the key volatile components of the MR products. The results also indicated that N-terminal amino acids of the peptide chain were easier to be reacted than C-terminal amino acids and thus produce a pyrazine-like flavour in the MR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Macrophages play an important role in regulating the course of spinal tuberculosis within the bone microenvironment. This study aimed to investigate the differential expression of miRNA in macrophage-derived exosomes within the tuberculosis-infected bone microenvironment, to identify miRNAs that hold potential as diagnostic markers and therapeutic targets., Methods: We established study cohorts for spinal tuberculosis, collected bone marrow blood samples, isolated macrophage exosomes, and performed exosome miRNA sequencing. A miRNA-mRNA co-expression network was constructed using WGCNA analysis. Gene GO analysis and KEGG pathway enrichment analysis were performed using KOBAS software. Target miRNAs were selected based on fold change, P -value, and false discovery rate, and their validation was carried out using qRT-PCR and ROC curve studies. Subsequently, we constructed a target gene network for these miRNAs and performed KEGG pathway enrichment analysis to explore the potential signaling mechanisms involved in regulating the disease course of spinal tuberculosis., Results: Our findings revealed that macrophages from the tuberculosis-infected bone microenvironment exhibited an M1 phenotype. The successful extraction of exosomes from macrophage supernatants was confirmed through electron microscopy, particle size analysis, and protein blot analysis. Exosome miRNA-seq demonstrated that 28 miRNAs were up-regulated, while 34 miRNAs were down-regulated in individuals with spinal tuberculosis. GO analysis and KEGG pathway enrichment analysis indicated that the differentially expressed miRNAs were involved in various biological processes, cell components, molecular functions, and signaling pathways, which collectively contribute to the regulation of the disease course of spinal tuberculosis. Notably, miRNA-125b-5p was successfully selected based on fold change, p -value, and false discovery rate. qRT-PCR validation further confirmed the significant up-regulation of miRNA-125b-5p in spinal tuberculosis. The ROC curve revealed that miR-125b-5p is a potential diagnostic biomarker for spinal tuberculosis. Moreover, construction of the miRNA-125b-5p target gene network and subsequent KEGG enrichment analysis highlighted the importance of MAPK, TNF, Ras, Rap1, and the PI3K-Akt signaling pathways in the regulation of the disease course of spinal tuberculosis., Conclusion: Our study demonstrates differential expression of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment. Specifically, MiRNA-125b-5p is significantly up-regulated in spinal tuberculosis and shows potential as a diagnostic biomarker for spinal tuberculosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Pang, Wang and Zeng.)

Thermal-denatured whey protein-milk fat emulsion gels with different degrees of pre-emulsification were prepared by pre-emulsifying milk fat with thermal-denatured whey protein and used in the preparation of reduced-sodium processed cheeses. The effect of the thermal-denatured whey protein pre-emulsification process on the texture and microstructure of reduced-sodium processed cheeses was evaluated by studying the composition, color, texture, functional properties, microstructure and sensory analysis of the processed cheeses. The results showed that compared with cheese without pre-emulsified fat (1.5% ES control), the moisture content of cheese with pre-emulsified 100% fat (1.5% ES100) increased by 5.81%, the L* values increased by 7.61%, the hardness increased by 43.24%, and the free oil release decreased by 38%. The microstructure showed that the particle size of fat was significantly reduced, and the distribution was more uniform. In addition, compared with the cheese added with 3% emulsifying salt (3% ES control), the amount of emulsifying salt in the 1.5% ES100 decreased by 50%, but the fat distribution of the two kinds of cheese tended to be consistent, and there was no obvious change in texture characteristics and meltability. Sensory scores increased with the increase in pre-emulsification degree. Overall, the pre-emulsification of milk fat with thermal-denatured whey protein can reduce the sodium content of processed cheese and improve its quality.

Milk samples were collected from 10 cows, in the colostrum (3-4 days) and mature (90 days) lactation stage, to assess the differential expression of all whey proteins and N -glycoproteins. In total, 240 whey proteins and 315 N -glycosylation sites on 214 glycoproteins were quantified. GO annotations, KEGG pathway analysis, and protein classification were performed to understand the similarities and differences of the biological functions of whey proteins and N -glycoproteins among different lactation stages in bovine milk. Furthermore, differential expression of whey proteins and whey N -glycosylated proteins was found between different lactation stages. The related changes of biological functions in differentially expressed proteins were discussed. For example, the increased frequency of glycosylation on lactoferrin and folate receptor alpha occurring in bovine colostrum may provide protection and stimulate development of the newborn calf. Our study thereby improves understanding of variations of glycosylation sites on milk glycoproteins among lactation stages.

Introduction: Glycosylation is one of the essential post-translational modifications that influences the function of milk proteins., Methods: In the present study, 998 proteins and 764 glycosylated sites from 402 glycoproteins were identified in human milk by TMT labeling proteomics. Compared to human milk proteins, the glycoproteins were mainly enriched in cell adhesion, proteolysis, and defense/immune process., Results: The abundance of 353 glycosylated sites and their 179 parent proteins was quantified. After normalization to their parent protein's abundance, 78 glycosylated sites in 56 glycoproteins and 10 glycosylated sites in 10 glycoproteins were significantly higher in colostrum and mature milk, respectively. These changed glycoproteins were mainly related to host defense. Intriguingly, one glycosylated site (Asp144) in IgA and two glycosylated sites (Asp38 and Asp1079) in tenascin are significantly upregulated even though their protein abundance was downregulated during lactation., Discussion: This study helps us figure out the critical glycosylated sites in proteins that might influence their biological function in an unbiased way., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Zhang, Ma, Pang, Dai, Zhu, Liu, Xing, Zhang and Lv.)

Equol is the most potent soy isoflavone metabolite and is produced by specific intestinal microorganisms of mammals. It has promising application possibilities for preventing chronic diseases such as cardiovascular disease, breast cancer, and prostate cancer due to its high antioxidant activity and hormone-like activity. Thus, it is of great significance to systematically study the efficient preparation method of equol and its functional activity. This paper elaborates on the metabolic mechanism of equol in humans; focuses on the biological characteristics, synthesis methods, and the currently isolated equol-producing bacteria; and looks forward to its future development and application direction, aiming to provide guidance for the application and promotion of equol in the field of food and health products.

This study aimed to determine chemical composition and assess exposure in flavored milk among Chinese residents, based on risk assessment methodologies of acceptable daily intake (ADI) and toxicological concern threshold (TTC). Esters (32.17%), alcohols (11.19%), olefins (9.09%), aldehydes (8.39%), and ketones (7.34%) comprised the majority of the flavoring samples. Methyl palmitate (90.91%), ethyl butyrate (81.82%), and dipentene (81.82%) had the highest detection rates in flavor samples. This study screened fifteen flavor components of concern and discovered that 2,3,5-trimethylpyrazine, furfural, benzaldehyde, and benzenemethanol were detected in 100% of flavored milk samples. Benzenemethanol was found in the highest concentration (14,995.44 μg kg -1 ). The risk assessment results revealed that there was no risk for Chinese residents in consuming flavored milk, and the maximum per capita daily consumption of 2,3,5-trimethylpyrazine, furfural, and benzenemethanol were 226.208 g, 140.610 g, and 120.036 g, respectively. This study could provide guidelines for amounts of flavor additive ingredients in milk.

Background: Surgical intervention is necessary for resolving the symptoms of the spinal cord and nerve compression caused by symptomatic metastatic epidural spinal cord compression. However, surgeons are constantly seeking ways to improve surgical efficiency and safety. This study aims to evaluate the efficacy of 3D simulation/printing-assisted surgery for symptomatic metastatic epidural spinal cord compression of the posterior column., Methods: We retrospectively analyzed the clinical data of patients who underwent surgical treatment for symptomatic metastatic epidural spinal cord compression of the posterior column in our hospital from January 2015 to January 2020. The simulated group underwent a 3D digital simulation of the lesion area using imaging data before surgery. Twelve patients in the simulated group also received 3D printing, while the direct surgery group did not receive any 3D simulation or printing. All patients were followed up for at least 2 years. We collected clinical data, including operation time, intraoperative blood loss, pedicle screw adjustment rate, intraoperative fluoroscopy times, the incidence of dural injury and cerebrospinal fluid leakage, VAS score, postoperative neurological function improvement, and tumor recurrence. Statistical analysis was performed using SPSS23.0, and P  < 0.05 was considered statistically significant., Results: A total of 46 patients were included in this study, with 20 in the simulated group and 26 in the non-simulated group. The simulated group had better operation time, intraoperative blood loss, screw adjustment rate, fluoroscopy times, and incidence of dural injury/cerebrospinal fluid leakage compared to the non-simulated group. The VAS scores of the two groups improved significantly after the operation and at the last follow-up compared to before the operation. However, there was no statistically significant difference between the two groups. There was also no statistically significant difference in neurological function improvement between the two groups. In the simulated group, 25% of patients relapsed, while in the non-simulated group, 34.61% of patients relapsed. However, there was no statistical difference between the two groups., Conclusion: Preoperative 3D simulation/printing-assisted surgery is a practical and feasible approach for treating symptomatic metastatic epidural spinal cord compression of the posterior column., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sun, Jia, Wang and Pang.)

Heat shock protein family A member 5 (HSPA5) plays a pivotal role in the endoplasmic reticulum (ER) stress response and unfolded protein response (UPR), both of which are crucial for protein folding, assembly, and quality control within cells. In response to ER stress, HSPA5 becomes overexpressed to preserve cellular homeostasis. A previous study revealed a robust association between HSPA5 expression and various cancers. However, the prognostic function of HSPA5 and its involvement in tumor formation remain largely unknown. In this study, we integrated HSPA5 expression data from databases such as the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) to conduct a comprehensive pan-cancer analysis of HSPA5. Our findings revealed that HSPA5 is overexpressed in various tumor types and is significantly associated with poor prognosis. Additionally, HSPA5 expression is significantly correlated with immune checkpoints, stromal infiltration, and consequent alterations in the immune landscape. Verification was conducted on samples from patients with various tumor types, including breast and liver cancers. Additionally, we also performed verification in vitro. In conclusion, HSPA5 may offer a potential target for cancer treatment., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Vascular malformations are common but complicated types of disease in infants, with unclear causes and lack of effective prevention. The symptoms usually do not disappear and tend to progress without medical intervention. It is extremely necessary to choose correct treatment options for different types of vascular malformations. A large number of studies have confirmed that sclerotherapy has a tendency to become the first-line treatment in near future, but it is also associated with mild or severe complications. Furthermore, to our knowledge, the serious adverse event of progressive limb necrosis has not been systematically analyzed and reported in the literature., Case Presentation: Three cases (two females and one male) were presented who were all diagnosed as vascular malformations and were treated by several sessions of interventional sclerotherapy. Their previous medical records showed the use of several sclerosants in different sessions including Polidocanol and Bleomycin. The sign of limb necrosis did not occur during the first sclerotherapy, but after the second and third sessions. Furthermore, the short-term symptomatic treatment could improve the necrosis syndrome, but could not change the outcome of amputation., Conclusion: Sclerotherapy undoubtedly tends to be the first-line treatment in near future, but the adverse reactions still remain major challenges. Awareness of progressive limb necrosis after sclerotherapy and timely management by experts in centers of experience of this complication can avoid amputation., (© 2023. The Author(s).)

Camel milk has unique compositional, functional and therapeutic properties compared to cow's milk and also contains many protective proteins with anti-cancer, anti-diabetic and anti-bacterial properties. In this experiment, fresh camel milk was heat-treated at different temperatures and times, and the changes in Millard reaction products were analyzed. Meanwhile, headspace-gas chromatography-ion migration spectrometry (HS-GC-IMS), electronic nose and electronic tongue were used to analyze the changes of volatile components in camel milk after different heat treatments. The results showed that the Maillard reaction was more severe with the increase of heat treatment, and the contents of furosine and 5-hydroxymethylfurfural increased significantly when the heat treatment temperature was higher than 120°C. HS-GC-IMS results showed that the contents of aldehydes and ketones increased obviously with the increase of heat treatment degree. The study clarifies the effects of different heat treatment degrees on Maillard reaction degree and flavor of camel milk, which has practical production guidance significance for the research and industrialization of liquid camel milk products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Guo, Zhang, Pang, Wang, Lv and Zhang.)

Objective: Vascularized composite allografts (VCAs) refer to the transplantation of multiple types of tissues during plastic and reconstructive surgery. Several publications have emerged in the field of VCA. However, there are no bibliometric studies on this topic. The aim was to multidimensionally analyze the knowledge base and hotspots in this subject., Methods: We retrieved all publications related to VCA from the Web of Science Core Collection (WoSCC), published from 2002 to 2021. Next, scientometric analysis of different items was performed using various bibliometrics software to explore knowledge base, research hotspots, and advancement trends in this field., Results: We included a total of 3,190 English articles from 2002 to 2021. The number of publications increased steadily annually. The United States produced the highest number of publications, followed by China. Most publications were from Harvard University, followed by Johns Hopkins University. The most authoritative academic journal was Plastic and Reconstructive Surgery. Transplantation occupied the first rank of co-cited journal list. Maria Z Siemionow may have the highest influence in the VCA field with the highest number of citations (n = 88) and co-cited references (n = 1252). Clinical studies on different allografts, immunosuppression, and tissue engineering were both the knowledge base and recent topics in VCA research., Conclusions: The first bibliometric study comprehensively summarized the trends and development of VCA research with steady growth over the past two decades. Currently, the most active topics are the clinical application of multiple allografts, immunosuppression strategies/therapies, and translation of tissue engineering to clinical practice., Competing Interests: None., (AJTR Copyright © 2023.)

Human milk oligosaccharides (HMOs) act as a vital role in the development of infant's gut microbiome and immune function. This study aimed to measure 12 oligosaccharides in milk from Chinese donors (n = 203), and evaluated the influences of multiple factors on the HMOs profiles. The results indicated that concentrations of 6'-sialyllactose were the highest among 12 oligosaccharides (2.31 ± 0.81 g/L). HMOs concentrations varied depending on geographical location. Latitude was observed to be related to concentrations of Lacto-N-neohexaose, lacto-N-fucopentaose III, 3'-sialyllactose (r = -0.67, r = +0.63 and r = +0.50, respectively). Environmental factors like seasons correlated with lacto-N-difucohexaose Ⅱ, Lacto-N-neohexaose and 2'-fucosyllactose (r = -0.47, r = -0.4, r = -0.35, respectively). Several HMOs concentrations were correlated with maternal diet. As a consequence, the HMOs profiles measured were influenced by geographical, environmental, maternal anthropometric as well as dietary factors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Kinesin family member 2C (KIF2C) is the best-characterized member of the kinesin-13 family and is involved in accurately fine-tuned dynamics of mitotic spindles. As KIF2C is involved in both spindle formation and regulation of DNA double-strand breaks, precise regulation of KIF2C is essential to prevent malignant transformation associated with gains and losses of DNA content. In the present study, we initially reviewed The Cancer Genome Atlas database and observed that KIF2C is abundantly expressed in most tumor types. We then analyzed the gene alteration profile, protein expression, prognosis, and immune reactivities of KIF2C in more than 10,000 samples from several well-established databases. In addition, we conducted a gene enrichment set analysis to investigate the potential mechanisms underlying the role of KIF2C in tumorigenesis. Multi-omics analysis of KIF2C demonstrated significant statistical correlations between KIF2C expression and clinical prognosis, oncogenic signature gene sets, myeloid-derived suppressor cell infiltration, ImmunoScore, immune checkpoints, microsatellite instability, and tumor mutational burden across multiple tumors. Single-cell data showed that KIF2C is abundantly expressed in malignant cells. The experimental validation demonstrated that KIF2C is highly expressed in gastric cancer cell lines, gastric adenocarcinoma, and hepatocelluar carcinoma. The findings of this study provide important insight for understanding the role and mechanisms of KIF2C in tumorigenesis and immunotherapy in a variety of cancers., Competing Interests: None., (AJCR Copyright © 2022.)

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated proteins) system is an efficient and precise gene editing tool. The development of this technology has promoted genome editing into a rapid development stage. The most widely used Cas9 protein is SpyCas9 from Streptococcus pyogenes . As a "gene scissors", the SpyCas9 protein is widely used in eukaryotes including mammals and plants. However, the application of this protein in some lactic acid bacteria (LAB) is still hampered by many factors. It has been identified that LAB genomes possess many types of CRISPR system and are rich in uncharacterized Cas proteins. Genome editing of LAB is possible by repurposing the endogenous CRISPR-Cas systems in LAB combined with exogenous single guide RNA (sgRNA) and homologous recombination template. This method employs its endogenous CRISPR-Cas system for gene editing, which has the advantages including easiness for transformation due to the relatively small targeting vector, and no concern about the toxicity of heterologous Cas9 to host cells. Compared to CRISPR-SpyCas9, the endogenous CRISPR-Cas system is more suitable for genome editing of LAB, and it may become the main genome editing tool for some LAB in the future. This article summarizes the advances in this field.

The objective of this study was to detect the influence of dietary Schizochytrium microalgae on milk composition, milk fatty acids, and milk sn-2 fatty acids in goat's milk. Firstly, we could see that the fat content increased in low microalgae supplementation goat's milk (LM, 15 g/day) and the lactose content decreased in medium microalgae supplementation goat's milk (MM, 25 g/day) compared with control goat's milk (C, 0 g/day). Moreover, the absolute concentration of the docosahexaenoic acid (DHA) of LM, MM, and high microalgae supplementation (HM, 35 g/day) goat's milk was 29.485, 32.351, and 24.817 mg/100 g raw milk, respectively, which were all higher than that in the control goat's milk with 4.668 mg/100 g raw milk. In addition, the sn-2 DHA content increased in MM and HM goat's milk. However, the decreasing trend of the sn-2 DHA content was observed in LM goat's milk. As for other fatty acids, the oleic acid (C18:1n9c) and linolenic acid (C18:3n3) content decreased and increased, respectively, in all experimental goat milk. Finally, an interesting phenomenon was found, which was that docosanoic acid (C22:0) and tetracosenic acid (C24:1) were only detected in test goat's milk. Consequently, the phenomena of this study demonstrated that dietary Schizochytrium microalgae have an obvious effect on the fatty acid and sn-2 fatty acid profile of goat's milk, and they provide an effective method to improve the content of goat's milk DHA in practical production.

In order to improve the flavor and taste of Camembert cheese, the use of Monascus as an adjunct starter for the production of Camembert-type cheese was studied to investigate its effect on the proteolysis, lipolysis, and volatile compounds during ripening for 40 days. The Camembert cheese without Monascus was used as a control. The results showed that proteolytic and lipolytic activities increased to a certain extent. The addition of Monascus promoted primary and secondary proteolysis, due to the release of some proteases by Monascus. Aspartic, Threonine, Glutamic, Glycine, Methione, Isoleucine, Phenyalanine, and Lysine contents in experimental group (R) cheese were significantly higher than those in control group (W) cheeses. In addition, the free amino acid and fatty acid contents were also affected. The identification of flavor components using gas-mass spectrometry (GC-MS) showed that 2-undecone, 2-tridecanone, phenylethyl alcohol, butanediol (responsible for the production of flowery and honey-like aroma), ethyl hexanoate, ethyl octanoate, and ethyl citrate (fruit-like aroma) were significantly higher (p < 0.05) in the experimental cheeses than in the control. The contents of 2-nonanone, 2-octanone and 2-decanone (showing milky flavor), and 1-octene-3 alcohol with typical mushroom-like flavor were lower than the control.

This research investigated the effect of ultrasound (US) pretreatment prior to spray drying on the powder flow and moisture sorption behaviour of micellar casein concentrate (MCC). MCC produced from skim milk microfiltration was sonicated at energy intensity of 0 (control), 47 J/mL (S-2000), 62 J/mL (S-3000) and 76 J/mL (S-4000). The results revealed that US pretreatment significantly increased the average particle size (D50) from 82.46 μm to 100.73 μm and reduced the surface fat content from 19.2% to 13.8%, resulting in decreased basic flow energy, cake energy and cohesion. Besides, the US treated samples showed relatively poor ability to acquire the moisture from the atmosphere than the control. Protein structure analysis showed that α-helix decreased with enhanced US power, while β-sheet and surface hydrophobicity increased, implying hydrophobic groups were exposed and water sorption rate was impeded. As a result, US pretreatment can improve the powder flow and potentially reduce the negative effect of cake formation at high humidity., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Multi-territory perforator flaps are a reconstructive measure for repairing large soft tissue defects caused by tumors or trauma. However, the use of these flaps in clinical practice has been restricted due to the uncertain blood supply. Therefore, promoting the survival of the multi-territory perforator flap is critical for clinical repair and reconstruction. In our study, we explored the effects of melatonin (MLT) on multi-territory perforator flaps and the possible molecular mechanisms. Materials and Methods: Seventy-two Sprague-Dawley rats (250-300 g) were randomly divided into 3 groups ( n = 24): Control, MLT and MLT + ML385 groups. First, we assessed the survival area of the flap, followed by the micro-vessel density and CD31-positive vessel expression. Apoptosis of the skin flap under immunofluorescence and expression of the apoptosis-related proteins Bcl-2, Bax and Caspase3 were measured. Additionally, angiogenesis of the skin flaps was shown by angiography, and NRF2 and FUNDC1 mRNA and protein expression was detected by real-time PCR and western blotting. Results: The results showed that MLT increased the survival area of the multi-territory perforator flap, which was related to increased angiogenesis and decreased apoptosis. We also found that mRNA and protein of NRF2 and FUNDC1 levels were significantly increased after MLT treatment, and an NRF2 inhibitor reversed the ability of MLT to enhance multi-territory perforator flap survival, promote angiogenesis and inhibit apoptosis and reduced FUNDC1 protein expression. Conclusion: MLT promoted angiogenesis and inhibited apoptosis to promote the survival of multi-territory perforator flaps, which may be regulated via the NRF2/FUNDC1 axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Qing, Pang, Fu, Xiao, Tang and Wu.)

Neural precursor cells (NPCs) tend to aggregate and develop into three-dimensional (3D) spheres, which in turn help maintain the stemness of the cells. This close relationship between spherical environments and cell stemness direct us to assume that 3D spheres of astrocytes (ASTs) may facilitate the acquisition of stem cell-like features and generate sufficient seed cells for the regeneration of neurons. In vitro results confirmed that mouse ASTs cultured on agarose surfaces spontaneously formed cell spheres and exhibited molecular features similar to stem cells, particularly capable of further differentiating into neurons and forming functional synaptic networks with synchronous burst activities. RNA-sequencing results revealed the similarity between AST-derived stem cells (A-iSCs) and NPCs in global gene expression profiles. The potency of A-iSCs in repairing neural injuries was evaluated in a mouse model of middle cerebral artery occlusion. It was observed that the transplanted A-iSCs expressed a series of markers related to neural differentiation, such as NeuN, Tuj1, and Map2, indicating the conversion of the transplanted A-iSCs into neurons in the scenario. We also found that the injured mice injected with A-iSCs exhibited significant improvements in sensorimotor functions after 8 weeks compared with the sham and control mice. Taken together, mouse ASTs form cell spheres on agarose surfaces and acquire stem cell-associated features; meanwhile, the derived A-iSCs possess the capacity to differentiate into neurons and facilitate the regeneration of damaged nerves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Cao, Pang, Jiang, Li, Zhang, Tian, Tu, Wu and Nie.)

(1) Background: to date, a clear description of the impact of specific enzymes on the enzyme-modified cheese (EMC) flavor is lacking. Moreover, comparative studies on the aroma compounds' intensity of EMC have been rarely investigated. Therefore, this study was done to determine the influence of incubating substrates with proteases and different lipases on cheese ripening index and aroma compounds. (2) Methods: two-stage processing was adopted; proteolysis followed by lipolysis. (3) Results: results showed that the usage of Flavourzyme may improve the value of pH 4.6-WSN/TN%. Butanoic acid and hexanoic acid have a significant influence on the overall flavor of EMCs. In particular, the ethenyl acetate compound was detected in all products and was perceived as a fruity and sweet aroma, which has not been reported in previous literature. The concentration of short-chain fatty acids of EMCs made by Lipase MER was higher than EMCs made by Palatase, while the total content of medium and long-chain fatty acids of EMCs made by Lipase MER was lower than EMCs made by Palatase. The percentage of esters compounds in EMCs made by Lipase AY 30G was higher than the other two lipases, except EMC1. (4) Conclusions: Flavourzyme may be used to speed up the ripening of cheeses that need extensive proteolysis. The ability of Lipase MER to hydrolyze short-chain fatty acids was stronger than that of Palatase, while the ability of Lipase MER to hydrolyze medium and long-chain fatty acids was weaker than that of Palatase. The use of Lipase AY 30G was accompanied by the production of some other flavor esters, which made the final hydrolysates more fragrant and may be a good choice to produce fruity cheese flavor EMC. While Lipase MER may barely contain ester activity. This study may provide a reference for the selection of incubated enzymes for specific flavor EMC.

Micellar casein concentrate (MCC) is a novel dairy ingredient with high protein content. However, its poor functional properties impair its potential for further application, highlighting the importance of using innovative processing methods to produce modified MCC, such as ultrasound (US). This work investigated the impact of US on the physical and functional properties of MCC under temperature-controlled and -uncontrolled conditions for different time intervals. Under temperature-controlled ultrasound (TC-US) treatment, a reduction was found in the supernatant particle size of casein micelles. Soluble calcium content and hydrophobicity increased following ultrasound treatment at 20 °C, resulting in a remarkable improvement in emulsification. However, long-time ultrasonication led to an unstable state, causing the MCC solutions to show shear thinning behavior (pseudoplastic fluid). Compared with 50 °C temperature-controlled ultrasonication, ultrasonication at 20 °C had a greater influence on particle size, viscosity and hydrophobicity. These findings indicate that 20 °C TC-US could be a promising technology for the modification of MCC.

Objectives: The polyfoliate anterolateral thigh perforator flap needs to dissect two or more perforators, which is an ideal choice for repairing wide and irregular wounds. However, the uncertainty of perforating vessels restricts the development of this operation. This study discusses the feasibility and clinical efficacy of the polyfoliate anterolateral thigh perforator flap with single-perforator., Methods: Fifteen patients with skin and soft tissue defects in extremities, were treated with polyfoliate anterolateral thigh perforator flap with single-perforator. Based on the perforator detected by Doppler ultrasound or color Doppler ultrasonography before operation, a polyfoliate anterolateral thigh perforator flap with single-perforator was designed. The perforating point of perforator was near the boundary of the skin paddle. Following the perforating vessels and vascular pedicles free, the vessels in the deep layer of the superficial fascia were meticulously free under the microscope. After obtaining the appropriate length, the skinpaddles were separated and recombined. After confirming the blood supply of flap, the vascular pedicle was ligated and transplanted to the recipient area., Results: In 15 cases, the area of the flap was 8.0 cm×5.0 cm+6.0 cm×5.5 cm to 16.0 cm× 9.5 cm+24.0 cm×9.0 cm. All flaps survived well without necrosis and had a satisfactory appearance. The donor area was closed directly. The patients were followed up for 3 to 12 months, with an average of 6 months. The skin flaps were normal in color and good in texture., Conclusions: It's a better method to repair the skin and soft tissue defects in extremities by the polyfoliate anterolateral thigh perforator flap with single-perforator because only one perforator needs to be dissected, a group of blood vessels need to be anastomosed, and only one donor area needs to be sacrificed.

Human milk (HM) is the golden standard of infant nutrition that can protect immature body function and enhance nutrition metabolism to ensure infant growth. Region specificity and lactation period could change the protein composition in HM. In this research, proteomics analysis was used to compare proteomes across eight cities, namely Harbin, Lanzhou, Guangzhou, Chengdu, Jinhua, Weihai, Zhengzhou, and Beijing, which represented the northeast, northwest, southeast, southwest, east, and north and central regions of China,. Proteins varied significantly among the cities. These different proteins were mainly involved in the process of platelet degranulation, innate immune response, and triglyceride metabolic process, which might be due to different living environments. These differences also lead to variation in protection and fat metabolism from mothers to infants in different cities. Four proteins were expressed differently during 6 months of lactation, namely Dipeptidyl peptidase 1, Lysozyme C, Carbonic anhydrase 6, and Chordin-like protein 2. The changes in these proteins might be because of the change of growth needs of the infants. The findings from our results might help to improve the understanding of HM as well as to design infant formula., Competing Interests: JP, YL, and SJ were employed by the company Heilongjiang Feihe Dairy Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sari, Pan, Zhang, Li, Zhu, Pang, Zhang, Jiang, Lu and Lv.)

Background: A high incidence of osteonecrosis of the femoral head (ONFH), a commonly seen and intractable disease, has been reported. This retrospective study aims to compare the reconstructive outcomes by free vascularized iliac bone flap (FVIBF) with those by vascularized pedicled iliac bone flap (PIBF) to determine which one is better for ONFH patients., Methods: From January 2010 to December 2017, 35 patients (40 hips) were treated by PIBF grafting, and 32 patients (36 hips) were treated by FVIBF grafting. The two groups were then compared in terms of the preoperative baseline conditions, intraoperative data, and postoperative Harris hip score (HHS)., Results: In the PIBF group, the operating time was significantly longer than the FVIBF group (195.5 ± 26.4 vs 147.2 ± 17.7 min, respectively), and the intra-operative blood loss was significantly heavier (330.0 ± 63.9 vs 240.3 ± 37.5 ml, respectively). Meanwhile, the recipient site morbidity rate in the PIBF group outnumbered that in the FVIBF group (27.5% vs 8.3%, respectively), and a higher rate of lateral femoral cutaneous nerve (LFCN) injury was observed in the PIBF group than in the FVIBF group (27.5% vs 8.3%, respectively). No difference was found in postoperative HHS score between the two groups. In both groups, the recovery effect of the patients in stage II was better than that in stage III., Conclusion: While maintaining a similar clinical effect, the FVIBF grafting exhibited a distinct advantage over the PIBF grafting, in terms of shorter operative time, less blood loss, and lower risk of LFCN injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest and sources of funding: None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this article. This publication was funded in part by the Hunan Natural Science Foundation (2018JJ2640).

Kestoses, the smallest fructooligosaccharides, are trisaccharides composed of a fructose molecule and a sucrose molecule linked by either β -(2,1) or β -(2,6) linkage. 1-kestose, 6-kestose and neokestose are the three types of kestoses occurring in nature. As the main kind of fructooligosaccharide, kestoses share similar physiological effects with other fructooligosaccharides, and they have recently been determined to show more notable effects in promoting the growth of probiotics including Faecalibacterium prausnitzii and Bifidobacterium than those of other fructooligosaccharides. Kestoses exist in many plants, but the relatively low content and the isolation and purification are the main barriers limiting their industrial application. The production of kestoses by enzymatic biosynthesis and microbial fermentation has the potential to facilitate its production and industrial use. In this article, the recent advances in the research of kestoses were overviewed, including those studying their functions and production. Kestose-producing enzymes were introduced in detail, and microbial production and fermentation optimization techniques for enhancing the yield of kestoses were addressed. β -Fructofuranosidase is the main one used to produce kestoses because of the extensive range of microbial sources. Therefore, the production of kestoses by microorganisms containing β -fructofuranosidase has also been reviewed. However, few molecular modification studies have attempted to change the production profile of some enzymes and improve the yield of kestoses, which is a topic that should garner more attention. Additionally, the production of kestoses using food-grade microorganisms may be beneficial to their application in the food industry.

Recently, we have proposed that quinoa yoghurt (QY) has the anti-diabetic properties based on an in vitro study. Here, its antidiabetic activity was further validated by investigating its hypoglycemic and hypolipidemic influence in high fat diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) mice. The results showed that QY increased the body weights of and reduced the fasting blood glucose levels in T2DM mice. QY significantly (p < 0.05) reduced the serum levels of total cholesterol, triglyceride and LDL-C, while it increased the HDL-C level. In addition, the hepatic glycogen content, and superoxide dismutase, catalase, and glutathione peroxidase activities were significantly (p < 0.05) increased, while lipid peroxidation was remarkably reduced. Sprouted QY had the highest influence on serum oxidation when compared with non-germinated QY. The level of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) were significantly (p < 0.05) decreased, while the level of anti-inflammatory cytokine IL-10 was increased. Histopathological studies showed that QY protected the tissue structure of the liver of T2DM mice. Immunohistochemistry showed that QY increased AKT-2 and AMPK-α2 expressions, while it suppressed p85. The qRT-PCR analysis indicated that QY exerted its hypoglycemic and anti-hyperlipidemic effects through the AKT/AMPK/PI3K signaling pathway. Germination significantly (p < 0.05) influenced the glucose and lipid homeostasis in T2DM mice in such a way that sprouted QY showed the highest hypoglycemic and cholesterol-lowering effects when compared with non-germinated QY.