The potential meat flavoring derived from Maillard reaction products of rice protein isolate hydrolysate-xylose via the regulation of temperature and cysteine.

Maillard reaction products (MRPs) derived from rice protein isolate hydrolysate and D-xylose, with or without L-cysteine, were developed as a potential meat flavoring. The combined impact of temperature (80-140 °C) and cysteine on fundamental physicochemical characteristics, antioxidant activity, and flavor of MRPs were investigated through assessments of pH, color, UV-visible spectra, fluorescence spectra, free amino acids, volatile compounds, E-nose, E-tongue, and sensory evaluation. Results suggested that increasing temperature would reduce pH, deepen color, promote volatile compounds formation, and reduce the overall umami and bitterness. Cysteine addition contributed to the color inhibition, enhancement of DPPH radical-scavenging activity and reducing power, improvement in mouthfulness and continuity, reduction of bitterness, and the formation of sulfur compounds responsible for meaty flavor. Overall, MRPs prepared at 120 °C with cysteine addition could be utilized as a potential meat flavoring with the highest antioxidant activity and relatively high mouthfulness, continuity, umami, meaty aroma, and relatively low bitterness.

A novel antimicrobial peptide with broad-spectrum and exceptional stability derived from the natural peptide Brevicidine.

The global issue of antibiotic resistance is increasingly severe, highlighting the urgent necessity for the development of new antibiotics. Brevicidine, a natural cyclic lipopeptide, exhibits remarkable antimicrobial activity against Gram-negative bacteria. In this study, a comprehensive structure-activity relationship of Brevicidine was investigated through 20 newly synthesized cyclic lipopeptide analogs, resulting in the identification of an optimal linear analog 22. The sequence of analog 22 consisted of five d-amino acids and four non-natural amino acid 2,5-diaminovaleric acid (Orn) and conjugated with decanoic acid at N-terminal. Compared to Brevicidine, analog 22 was easier to synthesize, and exerted broad spectrum antimicrobial activity and excellent stability (t1/2 = 40.98 h). Additionally, analog 22 demonstrated a rapid bactericidal effect by permeating non-specifically through the bacterial membranes, thereby minimizing the likelihood of inducing resistance. Moreover, it exhibited remarkable efficacy in combating bacterial biofilms and reversing bacterial resistance to conventional antibiotics. Furthermore, it effectively suppressed the growth of bacteria in vital organs of mice infected with S. aureus ATCC 25923. In conclusion, analog 22 may represent a potential antimicrobial peptide for further optimization.

Preparation of an elderberry anthocyanin film and fresh-keeping effect of its application on fresh shrimps.

A smart packaging film was developed employing the pH-indicating activity of elderberry anthocyanins to solve the problem of refrigerated food freshness monitoring. The effect of elderberry anthocyanins on the properties of gellan gum, gelatin composite films and preservation of fresh shrimp as an indicator of freshness was investigated. The results showed that the elderberry anthocyanin-gellan gum/gelatin film had improved on film thickness (7.8×10-2 mm), TS (tensile strength) (14.57×103 MPa), WVP (water vapor permeability) (36.96×10-8 g/m·s·Pa), and a reduced EAB (elongation at break) (17.92%), and water solubility (water-soluble time of 60.5 s). SEM (scanning electron microscopy) and FTIR (infrared spectrum analysis) showed excellent compatibility between its components. Moreover, the elderberry anthocyanin film exhibited good mechanical properties and pH indication effects. Therefore, the film can be considered suitable for maintaining the quality of fresh shrimp. The results could provide a reference for research and development into new active intelligent packaging films.

IgG glycomic profiling identifies potential biomarkers for diagnosis of echinococcosis.

Echinococcosis caused by larval stage of the genus Echinococcus, is a serious and potentially fatal parasitic zoonosis distributed globally. The two types of the disease in human are cystic echinococcosis (CE) and alveolar echinococcosis (AE). As the biological and encysting characteristics of the parasite, early diagnosis remains to address. In the present study, we demonstrate the value of Immunoglobulin G (IgG) glycome as a potential diagnostic biomarker for echinococcosis. Serum IgG glycome profiles were analyzed by ultra-performance liquid chromatography in a cohort comprised of 127 echinococcosis patients, of them 98 were diagnosed as CE and 29 as AE. IgG N-glycome analysis in pretreatment serum of echinococcosis patients presents 25 glycans and 64 derived traits. Compared with IgG glycans of healthy control group, neutral glycans, fucosylation and agalactosylated N-glycans increased while sialylation and galactosylation decreased in echinococcosis patients. Combined with a machine-learning-based approach, we built three biomarker combinations to distinguish CE, AE and healthy controls. Meanwhile, galactosylation, sialylation and A2BG2S1 in IgG glycan profiles were evidently associated with different types of CE (from CE1 to CE5). Our findings suggest that the alterations in IgG N-glycome may be of value in CE and AE diagnosis and follow-up CE disease progress. The role of IgG N-glycans as diagnostic biomarker remains to be verified in future study.

Method for screening water physicochemical parameters to calculate water quality index based on these parameters' correlation with water microbiota.

Water quality index (WQI) plays a crucial role in guiding water resource management. However, WQI calculation methods are not uniform, especially the selection of water parameters and the weighting given to each water parameter (Pi). To optimize WQI calculation, 132 water samples from seven rivers and from Chaohu Lake (33 sampling sites in Chaohu Lake Basin) in four seasons were collected, and the water parameters and microbiota composition were analyzed using high-throughput sequencing of 16 S rDNA. The correlation coefficient R2 between water parameters and microbiota composition using redundancy analysis with the Monte Carlo method were calculated, and the water parameters that significantly correlated with the microbiota composition were selected to calculate WQImin. The results showed that TP, COD, DO, and Chl a correlated significantly with water microbiota composition. WQIb calculated by substituting R2 for Pi was more consistent with the similarity between the microbiota compositions. WQIminb calculated using TP, COD, and DO was consistent with WQIb. The results of WQIb and WQIminb were more consistent than those of WQI and WQImin. These results imply that using R2 instead of Pi could help obtain a more stable WQIb that could better reflect the biological characteristics of the Chaohu Lake Basin.

Structure-Activity Relationship Study of Antimicrobial Peptide PE2 Delivered Novel Linear Derivatives with Potential of Eradicating Biofilms and Low Incidence of Drug Resistance.

The ongoing emergence of antibiotic-resistant pathogens had been dramatically stimulating and accelerating the need for new drugs. PE2 is a kind of cyclic lipopeptide with broad-spectrum antimicrobial activity. Herein, its structure-activity relationship was systematically investigated by employing 4 cyclic analogues and 23 linear analogues for the first time. The screened linear analogues 26 and 27 bearing different fatty acyls at N-termini and a Tyr residue at the 9th position had superior potency compared to the cyclic analogues and showed equivalent antimicrobial activity compared with PE2. Notably, 26 and 27 exhibited significant ability against multidrug-resistant bacteria, favorable resistance to protease, excellent performance against biofilm, low drug resistance, and high effectiveness against the mice pneumonia model. The antibacterial mechanisms of PE2 and linear derivatives 26 and 27 were also preliminarily explored in this study. As described above, 26 and 27 are promising antimicrobial candidates for the treatment of infections associated with drug-resistant bacteria.

Influence of Different pH Values on Gels Produced from Tea Polyphenols and Low Acyl Gellan Gum.

To explore the influence of pH values on the properties of a compound system containing tea polyphenols (TPs) and low acyl gellan gum (LGG), the color, texture characteristics, rheological properties, water holding capacity (WHC), and microstructure of the compound system were measured. The results showed that the pH value noticeably affects the color and WHC of compound gels. Gels from pH 3 to 5 were yellow, gels from pH 6 to 7 were light brown, and gels from pH 8 to 9 were dark brown. The hardness decreased and the springiness increased with an increase in pH. The steady shear results showed that the viscosity of the compound gel solutions with different pH values decreased with increasing shear rates, indicating that all of the compound gel solutions were pseudoplastic fluids. The dynamic frequency results showed that the G' and G″ of the compound gel solutions gradually decreased with increasing pH and that G' was higher than G″. No phase transition occurred in the gel state under heating or cooling conditions at pH 3, indicating that the pH 3 compound gel solution was elastic. The WHC of the pH 3 compound gel was only 79.97% but the WHC of compound gels pH 6 and pH 7 was almost 100%. The network structure of the gels was dense and stable under acidic conditions. The electrostatic repulsion between the carboxyl groups was shielded by H+ with increasing acidity. The three-dimensional network structure was easily formed by an increase in the interactions of the hydrogen bonds.

Effect of ultrasound treatment on interactions of whey protein isolate with rutin.

Rutin is a biologically active polyphenol, but its poor water solubility and low bioavailability limit its application to the food industry. We investigated the effect of ultrasound treatment on the properties of rutin (R) and whey protein isolate (WPI) using spectral and physicochemical analysis. The results revealed that there was covalent interaction between whey protein isolate with rutin, and the binding degree of whey isolate protein with rutin increased with ultrasound treatment. Additionally, solubility and surface hydrophobicity of WPI-R complex improved with ultrasonic treatment, and a maximum solubility of 81.9 % at 300 W ultrasonic power. The ultrasound treatment caused the complex to develop a more ordered secondary structure, resulting in a three-dimensional network structure with small and uniform pore sizes. This research could provide a theoretical reference for studying protein-polyphenol interactions and their applications in food delivery systems.

Effect of pH on the thermal gel properties of whey protein isolate-high acyl gellan gum.

BACKGROUND: Protein-polysaccharide gels have significant and unique properties in food formulations. However, they are susceptible to environmental influences like heat and pH. The present work investigated the effects of acid and alkali treatments on the gel properties and microstructural changes of whey protein isolate (WPI) high acyl gellan gum (HG). RESULTS: The results showed that the pH had a strong effect on the gel hardness, water-holding capacity (WHC), free sulfhydryl groups (-SH), and other properties of the composite gel. The hardness reached a maximum level of 282.50 g and the best WHC was 98.33% at pH 7, indicating that a suitable pH could promote this cross-linking between the WPI and HG molecules. The rheological analysis demonstrated that the pH affected the gel formation time. Meanwhile, the gel formation time reached a maximum at pH 7, and the gel's storage modulus G' value was the largest in the final state. Fourier transform infrared spectroscopy (FTIR) results showed that pH affected the interaction between WPI and HG. Scanning electron microscopy (SEM) analysis also indicated that the composite gel formed a three-dimensional network structure at pH 7-9. CONCLUSION: These results could broaden the application of protein-polysaccharide gels in food and delivery systems. © 2023 Society of Chemical Industry.

Rational design of HJH antimicrobial peptides to improve antimicrobial activity.

Antimicrobial peptides (AMPs) have attracted considerable interest in the past decade due to their advantages for tackling antibiotic resistance. They exhibit potential antimicrobial activity through unique cell membrane destruction mechanism based on their net charge, hydrophobic properties, and α-helix. In this work, a series of HJH peptides was rationally designed and synthesized. The antimicrobial activity and cytotoxicity assays indicated that HJH-5 and HJH-6 containing hydrophobic residues and helices displayed prominent antimicrobial activity and mild cytotoxicity, respectively. These peptides may be developed for combatting microbial infections.

Short, mirror-symmetric antimicrobial peptides centered on "RRR" have broad-spectrum antibacterial activity with low drug resistance and toxicity.

The increasingly severe bacterial resistance worldwide pushes people to discover and design potential antibacterial drugs unavoidably. In this work, a series of short, mirror-symmetric peptides were designed and successfully synthesized, centered on "RRR" and labeled with hydrophobic amino acids at both ends. Based on the structure-activity relationship analysis, LWWR (LWWRRRWWL-NH2) was screened as a desirable mirror-symmetric peptide for further study. As expected, LWWR displayed broad-spectrum antibacterial activity against the standard bacteria and antibiotic-resistant strains. Undoubtedly, the high stability of LWWR in a complex physiological environment was an essential guarantee to maximizing its antibacterial activity. Indeed, LWWR also exhibited a rapid bactericidal speed and a low tendency to develop bacterial resistance, based on the multiple actions of non-receptor-mediated membrane actions and intra-cellular mechanisms. Surprisingly, although LWWR showed similar in vivo antibacterial activity compared with Polymyxin B and Melittin, the in vivo safety of LWWR was far higher than that of them, so LWWR had better therapeutic potential. In summary, the desirable mirror-symmetric peptide LWWR was promised as a potential antibacterial agent to confront the antibiotics resistance crisis. STATEMENT OF SIGNIFICANCE: Witnessing the growing problem of antibiotic resistance, a series of short, mirror-symmetric peptides based on the symmetric center "RRR" and hydrophobic terminals were designed and synthesized in this study. Among, LWWR (LWWRRRWWL-NH2) presented broad-spectrum antibacterial activity both in vitro and in vivo due to its multiple mechanisms and good stability. Meanwhile, the low drug resistance and toxicity of LWWR also suggested its potential for clinical application. The findings of this study will provide some inspiration for the design and development of potential antibacterial agents, and contribute to the elimination of bacterial infections worldwide as soon as possible.

Improving the Antimicrobial Performance of Amphiphilic Cationic Antimicrobial Peptides Using Glutamic Acid Full-Scan and Positive Charge Compensation Strategies.

Nonselective toxicity of antimicrobial peptides (AMPs) needs to be solved urgently for their application. Temporin-PE (T-PE, FLPIVAKLLSGLL-NH2), an AMP extracted from skin secretions of frogs, has high toxicity and specific antimicrobial activity against Gram-positive bacteria. To improve the antimicrobial performance of T-PE, a series of T-PE analogues were designed and synthesized by glutamic acid full-scan, and then their key positions were replaced with lysine. Finally, E11K4K10, the highest therapeutic indicial AMP, was screened out. E11K4K10 was not easy to induce and produce drug-resistant bacteria when used alone, as well as it could also inhibit the development of the drug resistance of traditional antibiotics when it was used in combination with the traditional antibiotics. In addition, E11K4K10 had an excellent therapeutic effect on a mouse model of pulmonary bacterial infection. Taken together, this study provides a new approach for the further improvement of new antimicrobial peptides against the antimicrobial-resistance crisis.

Sortase A-mediated cyclization of novel polycyclic RGD peptides for ανß3 integrin targeting.

Cyclic arginine-glycine-aspartic (RGD) peptides that specifically bind to integrin ανß3 have been developed for drug delivery, tracers, and imaging for tumor diagnosis and treatment. Herein, a series of polycyclic RGD peptides containing dual, tri, and tetra rings were designed and synthesized through sortase A-mediated ligation. An in vitro test on cell adhesion inhibition indicated that the RGD peptide containing tricylic structure exhibited outstanding potency and selectivity for ανß3 integrin.

Application and Evaluation of the Flipped Classroom Based on Micro-Video Class in Pharmacology Teaching.

With the continuous development of information technology, new teaching resources "micro-video class" and teaching model "flipped classroom" have gradually attracted the attention of teachers. Whether and how they can be applied in pharmacology teaching has already become the focus of medical education research in recent years. This paper explores the application and evaluation of the flipped classroom based on micro-video class in pharmacology teaching in our college. Students in Class 1 and Class 2 majoring in clinical medicine of 2018 in Chengdu Medical College were randomly divided into experimental group and control group. The teaching model of flipped classroom based on micro-video class was used in the experimental group, while the traditional teaching model was used in the control group. Theory tests and questionnaires were carried out at the end of the course. The average scores of theoretical knowledge in experimental group were significantly higher than those in control group (P < 0.05). In addition, the results of the feedback questionnaire showed that the overall satisfaction of students participating in flipped classroom based on micro-video class was higher (P < 0.05), and students thought that their learning enthusiasm, learning efficiency, and abilities of autonomous learning and problem-solving were greatly improved compared with those of students taught applying the traditional teaching model. Flipped classroom based on micro-video class model successfully improved the outcome of pharmacology teaching. It is supposed to provide reference for the reform of pharmacology teaching in medical college.

Novel synovial targeting peptide-sinomenine conjugates as a potential strategy for the treatment of rheumatoid arthritis.

Sinomenine (SIN) is an effective anti-inflammatory agent, but its therapeutic efficacy is limited by its short half-life and the high dosage required. Tissue-specific strategies have the potential to overcome these limitations. The synovial homing peptide (CKSTHDRLC) was identified to have high synovial endothelium targeting affinity. In this work, two peptide-drug conjugates (PDCs), conjugate (L) and conjugate (C), were synthesized, in which SIN was covalently connected to the linear and cyclic synovial homing peptide, respectively, via a 6-aminocaproic acid linker. An evaluation of biostability showed that conjugate (C) was more stable in mouse serum and inflammatory joint homogenate than conjugate (L). The two conjugates gradually released free SIN. Interestingly, conjugate (L) self-cyclized via a disulfide bridge in a biological environment, which significantly impacted its biostability. It had an almost equipotent half-life in serum but faster degradation in the inflammatory joint than conjugate (C). Therefore, conjugate (C) exhibited better therapeutic efficacy and tissue targeting. All the results indicated that PDCs particularly in its cyclic form might be more efficient for targeted deliver and represent a potential strategy for the treatment of rheumatoid arthritis.

Novel ß-Hairpin Antimicrobial Peptides Containing the ß-Turn Sequence of -RRRF- Having High Cell Selectivity and Low Incidence of Drug Resistance.

The emergence of multidrug-resistant bacteria has dramatically increased the lethality, level of resistance, and difficulty of treatment. In this study, a series of new antimicrobial peptides (AMPs) based on the ß-hairpin structure with the template (XY)2RRRF(YX)2-NH2 (X: hydrophobic amino acids; Y: cationic amino acids) were synthesized; surprisingly, almost all of the new peptides have strong antibacterial activity and negligible hemolytic toxicity. Particularly, the therapeutic index (TI) values of F(RI)2R and F(KW)2K reached up to 115.9 and 70.7, respectively. In addition, they did not show induced drug resistance and inhibited the development of antibiotic resistance when combined and used with traditional antibiotics. In addition, their antibacterial mechanism was preliminarily studied. Moreover, the new peptides F(RI)2R and F(KW)2K showed excellent performance in the pulmonary bacterial infection model and low toxicity in mice. In conclusion, F(RI)2R and F(KW)2K are considered new antimicrobial alternatives to address the antimicrobial-resistance crisis.

Optimization of the decolorization conditions of Rose Bengal by using Aspergillus niger TF05 and a decolorization mechanism.

Aspergillus niger TF05 was applied to decolorize Rose Bengal dye. The effects of carbon source, nitrogen source, metal ion and spore concentration on Rose Bengal treatment with A. niger TF05 were studied. A Plackett-Burman design (PBD) and a uniform design (UD) were used to optimize the decolorization conditions of A. niger TF05 and enhance its decolorization effect. The mechanism of Rose Bengal decolorization by A. niger TF05 was examined by analysing degradation products via UV-visible light spectroscopy, IR spectroscopy and GC-MS. The best decolorization effect was achieved in the single factor test with glucose and ammonium chloride as carbon and nitrogen sources, respectively. Mg2+ was an essential ion that could improve the mould ball state and adsorption efficiency if the spore concentration was maintained at 106 spores ml-1. The optimal decolorization conditions obtained using the PBD and UD methods were 11.5 g l-1 glucose, 6.5 g l-1 ammonium chloride, 0.4 g l-1 magnesium sulphate, pH 5.8, 28 °C, 140 r.p.m. rotational speed, 0.18 g l-1 dye concentration, 0.5 ml of inocula and 120 h decolorization time. Under these conditions, the maximum decolorization rate was 106%. Spectral analysis suggested that the absorption peak of the product changed clearly after decolorization; GC-MS analysis revealed that the intermediate product tetrachlorophthalic anhydride formed after decolorization. The combined use of the PBD and UD methods can optimize multi-factor experiments. A. niger TF05 decolorized Rose Bengal during intracellular enzymatic degradation after adsorption.

Drug Release from Disulfide-Linked Prodrugs: Role of Thiol Agents.

The disulfide bond (SS) has been widely used in prodrugs for the redox-responsive drug release, but its drug release mechanism and rate were seldom compared in different thiol agents. Herein, self-assembling nanoaggregates (NAs) formed by camptothecin (CPT)-oleic acid (OA) prodrugs linked by two frequently used SS linkers (ETCSS and ACSS) were used for such comparative investigation. It is found that the cleavage of ETCSS was directly coupled with CPT release, whereas the breakage of ACSS resulted in the generation of CPT intermediates, the chemical stability of which determined CPT release. In both cases, the redox-responsive drug release was highly dependent on the reactivity between SS and thiol agents, with an order of dithiothreitol > cysteine ≈ glutathione. Moreover, the presence of SS significantly accelerated the extracellular CPT release, which was around 3-4 fold higher than intracellular CPT release. Therefore, the in vitro cytotoxicity of SS-linked CPT-OA NAs could not be ascribed to the glutathione-trigged intracellular drug release but rather to the SS-accelerated extracellular CPT release. The above results would effectively guide the rational design and evaluation of SS-linked prodrug NAs for efficient drug delivery.

New Antimicrobial Peptides with Repeating Unit against Multidrug-Resistant Bacteria.

With the aim of tackling the increasingly serious antimicrobial resistance and improving the clinical potential of AMPs, a facile de novo strategy was adopted in this study, and a series of new peptides comprising repeating unit (WRX)n (X represents I, L, F, W, and K; n = 2, 3, 4, or 5) and amidation at C-terminus were designed. Most of the newly designed peptides exhibited a broad range of excellent antimicrobial activities against various bacteria, especially difficult-to-kill multidrug-resistant bacteria clinical isolates. Among (WRK)4 and (WRK)5, with n = 4 and n = 5 of repeating unit WRK, the highest selectivity for anionic bacterial membranes over a zwitterionic mammalian cell membrane is presented with strong antimicrobial potential and low toxicity. Additionally, both (WRK)4 and (WRK)5 emerged with fast killing speed and low tendency of resistance in sharp contrast to the conventional antibiotics ciprofloxacin, gentamicin, and imipenem, as well as having antimicrobial activity through multiple mechanisms including a membrane-disruptive mechanism and an intramolecular mechanism (nucleic acid leakage, DNA binding and ROS generation) characterized by a series of assays. Furthermore, (WRK)4 exerted impressive therapeutic effects in vivo similarly to polymyxin B but displayed much lower toxicity in vivo than polymyxin B. Taken together, the newly designed peptides (WRK)4 and (WRK)5 presented tremendous potential as novel antimicrobial candidates in response to the growing antimicrobial resistance.

Antimicrobial peptides with symmetric structures against multidrug-resistant bacteria while alleviating antimicrobial resistance.

In response to the dramatically increasing antimicrobial resistance, a series of new symmetric peptides were designed and synthesized in this study by a "WWW" motif as the symmetric center, arginine as the positive charge amino acid and the terminus symmetrically tagged with hydrophobic amino acids. Amongst the new symmetric peptide FRRW (FRRWWWRRF-NH2) presented the highest cell selectivity for bacteria over mammalian cell and exerted excellent antimicrobial potential against a broad of bacteria, especially difficult-to-kill multidrug-resistant strains clinical isolates. FRRW also displayed perfect stability in physiological salt ions and rapid killing speed as well as acted on multiple mechanisms including non-receptor mediated membrane and intra-molecular mechanisms. Importantly, FRRW emerged a low tendency of resistance in contrast to traditional antibiotics ciprofloxacin and gentamicin. What's more, FRRW could resist or alleviate or even reverse the ciprofloxacin- and gentamicin-resistance by changing the permeability of bacterial membrane and inhibiting the efflux pumps of bacteria. Furthermore, FRRW exhibited remarkable effectiveness and higher safety in vivo than polymyxin B. In summary, the new symmetric peptide FRRW was promised to be as a new antimicrobial candidate for overcoming the increasing bacterial resistance.