Research hotspots and frontiers of cluster headaches: a bibliometric analysis.

Background: Extensive research on cluster headaches (CHs) has been conducted worldwide; however, there is currently no bibliometric research on CHs. Therefore, this study aimed to analyze the current research hotspots and frontiers of CHs over the past decade. Methods: Raw data on CHs was obtained from the Web of Science Core Collection database from 2014 to 2023. CiteSpace V6.2 R7 (64 bit) and Microsoft Excel were used to assess the annual publication volume, authors, countries, and references. VOSviewer 1.6.19 software was used to assess the institutions, cited authors, and keywords, and co-occurrence and clustering functions were applied to draw a visual knowledge map. Results: In the past decade, the overall annual publication volume of articles related to CHs has increased year by year, showing promising development prospects. The total 1909 articles contained six types of literature, among which the proportion of original research articles was the highest (1,270 articles, 66.53%), published in 201 journals. Cephalalgia (439 articles, 23.00%) had the highest publication volume, and the Lancet was the journal with the highest impact factor (IF = 168.9). Furthermore, the United States of America was the country with the most published papers (584 articles, 30.60%), University of London was the research institution with the most published papers (142 articles, 7.44%), and Goodsby, Peter J was found to be the most prolific author (38 articles, 1.99%). Conclusion: This study may provide some direction for subsequent researcher on CHs. The hotspots and frontiers of future research on CHs are suggested as follows: in basic medicine, more attention should be paid to pathophysiology, especially on increasing research on the pathogenesis mediated by CGRP; in clinical medicine, more attention should be paid to the design of evidence-based medicine methodology, especially the strict design, including double-blind, questionnaire, and follow-up, in randomized controlled trials, using high-quality articles for meta-analyses, and recommending high-level evidence; therapeutic techniques need to be further explored, suggesting the implementation of transcranial magnetic stimulation of the cortex, and stimulation of the sphinopalatine ganglia and occipital nerve to achieve peripheral neuromodulation. Furthermore, chronic migraine and insomnia are inextricably linked to CHs.

Applying GC-MS based serum metabolomic profiling to characterize two traditional Chinese medicine subtypes of diabetic foot gangrene.

Traditional Chinese medicine (TCM) has a long history and particular advantages in the diagnosis and treatment of diabetic foot gangrene (DFG). Patients with DFG are mainly divided into two subtypes, tendon lesion with edema (GT) and ischemic lesion without edema (GI), which are suitable for different medical strategies. Metabolomics has special significance in unravelling the complexities of multifactorial and multisystemic disorders. This study acquired the serum metabolomic profiles of two traditional Chinese medicine subtypes of DFG to explore potential molecular evidence for subtype characterization, which may contribute to the personalized treatment of DFG. A total of 70 participants were recruited, including 20 with DM and 50 with DFG (20 with GI and 30 with GT). Conventional gas chromatography-mass spectrometry (GC-MS) followed by orthogonal partial least-squares discriminant analysis (OPLS-DA) were used as untargeted metabolomics approaches to explore the serum metabolomic profiles. Kyoto encyclopedia of genes and genomes (KEGG) and MetaboAnalyst were used to identify the related metabolic pathways. Compared with DM patients, the levels of 14 metabolites were altered in the DFG group, which were also belonged to the differential metabolites of GI (13) and GT (7) subtypes, respectively. Among these, urea, α-D-mannose, cadaverine, glutamine, L-asparagine, D-gluconic acid, and indole could be regarded as specific potential metabolic markers for GI, as well as L-leucine for GT. In the GI subtype, D-gluconic acid and L-asparagine are positively correlated with activated partial thromboplastin time (APTT) and fibrinogen (FIB). In the GT subtype, L-leucine is positively correlated with the inflammatory marker C-reactive protein (CRP). Arginine and proline metabolism, glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis are the most important metabolic pathways associated with GI. The main metabolic pathways related to GT include pyrimidine metabolism, glutathione metabolism, biosynthesis of valine, leucine, and isoleucine, as well as valine, serine, and isoleucine with metabolites. The results of this study indicate that patients with different DFG subtypes have distinct metabolic profiles, which reflect the pathological characteristics of each subtype respectively. These findings will help us explore therapeutic targets for DFG and develop precise treatment strategies.

Artificial multi-verse optimisation for predicting the effect of ideological and political theory course.

Enhancing teaching sufficiency is crucial because low teaching efficiency has always been a widespread issue in ideological and political theory course. Evaluating data on the course is obtained from a freshmen class of 2022 using questionnaires. The data is organised and condensed for mining and analysis. Subsequently, an intelligent artificial multi-verse optimizer (AMVO) method s developed to predict the effect of ideological and political theory course. The proposed AMVO approach was tested against various cutting-edge algorithms to demonstrate its effectiveness and stability on the benchmark functions. The experimental results indicated that AMVO ranked first among the 23 test functions. Furthermore, the binary AMVO enhanced k-nearest neighbour classifier had excellent performance in the art ideological and political theory course in terms of error rate, accuracy, specificity and sensitivity. This model can predict the overall evaluation attitude of freshmen towards the course based on the dataset. In addition, we can further analyse the potential correlations between factors that enhance the intellectual and political content of the course. This model can further refine the evaluation of ideological and political courses by teachers and students in our school, thereby achieving the fundamental goal of moral cultivation.

Genome-wide analysis of bZIP transcription factors and their expression patterns in response to methyl jasmonate and low-temperature stresses in Platycodon grandiflorus.

Background: Platycodon grandiflorus belongs to the genus Platycodon and has many pharmacological effects, such as expectorant, antitussive, and anti-tumor properties. Among transcription factor families peculiar to eukaryotes, the basic leucine zipper (bZIP) family is one of the most important, which exists widely in plants and participates in many biological processes, such as plant growth, development, and stress responses. However, genomic analysis of the bZIP gene family and related stress response genes has not yet been reported in P. grandiflorus. Methods: P. grandiflorus bZIP (PgbZIP) genes were first identified here, and the phylogenetic relationships and conserved motifs in the PgbZIPs were also performed. Meanwhile, gene structures, conserved domains, and the possible protein subcellular localizations of these PgbZIPs were characterized. Most importantly, the cis-regulatory elements and expression patterns of selected genes exposed to two different stresses were analyzed to provide further information on PgbZIPs potential biological roles in P. grandiflorus upon exposure to environmental stresses. Conclusions: Forty-six PgbZIPs were identified in P. grandiflorus and divided into nine groups, as displayed in the phylogenetic tree. The results of the chromosomal location and the collinearity analysis showed that forty-six PgbZIP genes were distributed on eight chromosomes, with one tandem duplication event and eleven segmental duplication events identified. Most PgbZIPs in the same phylogenetic group have similar conserved motifs, domains, and gene structures. There are cis-regulatory elements related to the methyl jasmonate (MeJA) response, low-temperature response, abscisic acid response, auxin response, and gibberellin response. Ten PgbZIP genes were selected to study their expression patterns upon exposure to low-temperature and MeJA treatments, and all ten genes responded to these stresses. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that the expression levels of most PgbZIPs decreased significantly within 6 h and then gradually increased to normal or above normal levels over the 90 h following MeJA treatment. The expression levels of all PgbZIPs were significantly reduced after 3 h of the low-temperature treatment. These results reveal the characteristics of the PgbZIP family genes and provide valuable information for improving P. grandiflorus's ability to cope with environmental stresses during growth and development.

Triterpenoids from the leaves of Eleutherococcus sessiliflorus, and their antiproliferative activities in TNF-α induced HFLS-RA cells.

Five undescribed elesesterpenes L-U, along with nine known 3,4-seco-lupane-type triterpenoids were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Elesesterpene L-S, and U were lupane-type triterpenoids, whereas elesesterpene T was an oleanane-type triterpenoid, probably artifact, as suggested by LC-MS analysis. Out of the nine known compounds, five were initially identified in E. sessiliflorus. Moreover, their structures were definitively determined using spectroscopic analyses, and the absolute configurations of elesesterpenes L-M and sachunogenin 3-O-glucoside were clarified using X-ray crystallographic techniques. The absolute configuration of elesesterpene T was determined by measuring and calculating its ECD. In addition, all compounds were tested to examine their ability to inhibit the proliferation of HFLS-RA cells induced by TNF-α in vitro. Elesesterpene M, chiisanogenin, chiisanoside, and 3-methylisochiisanoside significantly inhibited HFLS-RA proliferation.

Natural products reverse cancer multidrug resistance.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

A broadband multi-frequency microwave combined biological exposure setup.

With the rapid popularization of wireless electronic devices, there has been an increasing concern about the impacts of the electromagnetic environment on health. However, most research reports on the biological effects of microwaves have focused on a single frequency point. In reality, people are exposed to complex electromagnetic environments that consist of multiple frequency microwave signals in their daily lives. It is important to investigate whether multi-frequency combined microwave energies have different biological effects compared with single frequency microwave energy. Unfortunately, there are limited reports on this topic due to the lack of suitable platforms for research on multi-frequency microwave energy combined with biological exposure. To address this issue, this study presents a setup that has a very wide working frequency bandwidth and can be compatible with single frequency and multi-frequency microwave combined exposure. Moreover, it can achieve relatively equal exposure to multiple biological samples at any frequency point in the working frequency range, which is crucial for electromagnetic biology research. The experimental results are in good agreement with the simulation results, confirming its capability to facilitate the study of complex electromagnetic environment effects on organisms.

Networks of Nerve Fibers, and Blood and Lymphatic Vessels in the Mouse Auricle: The Structural Basis of Ear Acupuncture.

Objective: Ear acupuncture, as a system for treating and preventing diseases through stimulation of points on the auricle, has been systematically introduced during the last 60 years. Although the auricular cartography was described somatotopically as an inverted fetus by Paul Nogier, MD, the underlying mechanism of auricular stimulation remains unclear. The aim of this research was to gain an understanding of the structural basis of auricular stimulation, as well as showing the distribution of the nerve fibers, and the blood and lymphatic vessels. Materials and Methods: The distribution of nerve fibers, and blood and lymphatic vessels was examined in whole-mount auricular skins of mice by combining the biomarkers protein gene product 9.5, cluster of differentiation 31, and lymphatic-vessel endothelial hyaluronan receptor-1 following tissue-clearing treatment with multiple immunofluorescent staining. Results: The labeled nerve fibers, and the blood and lymphatic vessels were distributed extensively in the inner and outer parts of the auricular skin. Auricular nerves aligning with blood vessels ran from the basal region to the peripheral region and crossed over lymphatic vessels, thus forming the neural, vascular, and lymphatic networks. Conclusions: As these are important tissue components of auricular skin, this result implies that the auricular nerve fibers, and blood and lymphatic vessels may coordinate with each other to respond directly to auricular stimulation.

Deep learning automatically assesses 2-µm laser-induced skin damage OCT images.

The present study proposed a noninvasive, automated, in vivo assessment method based on optical coherence tomography (OCT) and deep learning techniques to qualitatively and quantitatively analyze the biological effects of 2-µm laser-induced skin damage at different irradiation doses. Different doses of 2-µm laser irradiation established a mouse skin damage model, after which the skin-damaged tissues were imaged non-invasively in vivo using OCT. The acquired images were preprocessed to construct the dataset required for deep learning. The deep learning models used were U-Net, DeepLabV3+, PSP-Net, and HR-Net, and the trained models were used to segment the damage images and further quantify the damage volume of mouse skin under different irradiation doses. The comparison of the qualitative and quantitative results of the four network models showed that HR-Net had the best performance, the highest agreement between the segmentation results and real values, and the smallest error in the quantitative assessment of the damage volume. Based on HR-Net to segment the damage image and quantify the damage volume, the irradiation doses 5.41, 9.55, 13.05, 20.85, 32.71, 52.92, 76.71, and 97.24 J/cm² corresponded to a damage volume of 4.58, 12.56, 16.74, 20.88, 24.52, 30.75, 34.13, and 37.32 mm³. The damage volume increased in a radiation dose-dependent manner.

Associations Between Internet-Specific Parenting, General Parenting, and Adolescents' Online Behaviors: A Cross-Lagged Panel Network Analysis.

Parents play a crucial role in adolescents' Internet use. Both general parenting (i.e., autonomy-supportive and controlling parenting) and Internet-specific parenting (i.e., restrictive mediation, active mediation, and parental encouragement) are related to adolescents' online behaviors. However, existing studies have focused either on an Internet-specific parenting or general parenting strategy and have neglected their interaction, failing to capture the intricate nature of the parenting context of youth's online behaviors. Few studies have examined parental encouragement or acknowledged the bidirectional influence of parenting on adolescents' online behaviors. To address this gap, this study employed a cross-lagged panel network model to examine the associations among restrictive and active mediation, parental encouragement, and autonomy-supportive and controlling parenting, as well as the interplay of all five parenting strategies with adolescents' online behaviors. A total of 564 Chinese students (51.1% male; mean age = 14.54, SD = 0.7) completed the survey at two time points. The results indicate that in most cases, previous online behaviors are significant and strong predictors of subsequent parenting strategies and not vice versa, corroborating the child effect. The parent and reciprocal effects were observed in the problematic smartphone-use domain, suggesting that the effects may differ for distinct behavioral domains. The effects of parental mediation extend beyond parental encouragement, implying that risk-prevention-related parenting is an effective means of guiding adolescents' online behaviors. Autonomy-relevant general parenting is closely related to active mediation and parental encouragement, while restrictive general parenting is closely related to restrictive mediation, suggesting a consistency between Internet-specific and general parenting strategies.

Electrocatalysis Boosts the Methanol Thermocatalytic Dehydrogenation for High-Purity H2 and CO Production.

Hydrogen production from methanol represents an energy-sustainable way to produce ethanol, but it normally results in heavy CO2 emissions. The selective conversion of methanol into H2 and valuable chemical feedstocks offers a promising strategy; however, it is limited by the harsh operating conditions and low conversion efficiency. Herein, we realize efficient high-purity H2 and CO production from methanol by coupling the thermocatalytic methanol dehydrogenation with electrocatalytic hydrogen oxidation on a bifunctional Ru/C catalyst. Electrocatalysis enables the acceleration of C-H cleavage and reduces the partial pressure of hydrogen at the anode, which drives the chemical equilibrium and significantly enhances methanol dehydrogenation. Furthermore, a bilayer Ru/C + Pd/C electrode is designed to mitigate CO poisoning and facilitate hydrogen oxidation. As a result, a high yield of H2 (558.54 mmol h-1 g-1) with high purity (99.9%) was achieved by integrating an applied cell voltage of 0.4 V at 200 °C, superior to the conventional thermal and electrocatalytic processes, and CO is the main product at the anode. This work presents a new avenue for efficient H2 production together with valuable chemical synthesis from methanol.

Multimode ultrasonic-assisted decontamination of fruits and vegetables: A review.

Fruits and vegetables (F&V) are a significant part of our diet consumption. Microbial and pesticide residues are the predominant safety hazards of F&V consumption. Ordinary water washing has a very limited effect on removing microorganisms and pesticide residues and requires high water usage. Ultrasound, as an environmentally friendly technology, shows excellent potential for reducing microbial contamination and pesticide residue. This paper summarizes the research on ultrasound application in F&V washing, including the removal of microbial and pesticide residues and the comprehensive effect on their physicochemical characteristics. Furthermore, multimode ultrasonic-assisted techniques like multi-frequency and sequential ultrasound, combined with novel and conventional methods, can enhance the ultrasound-based effect and be more effective and sustainable in preventing F&V from microbial contamination. Overall, this work explicitly establishes the background on the potential for ultrasound cleaning and disinfection in the food industry as a green, effective, and ultimate method of preventing foodborne illnesses.

Transcriptomic and Metatranscriptomic Analyses Provide New Insights into the Response of the Pea Aphid Acyrthosiphon pisum (Hemiptera: Aphididae) to Acetamiprid.

Acetamiprid is a broad-spectrum neonicotinoid insecticide used in agriculture to control aphids. While recent studies have documented resistance to acetamiprid in several aphid species, the underlying mechanisms are still not fully understood. In this study, we analyzed the transcriptome and metatranscriptome of a laboratory strain of the pea aphid, Acyrthosiphon pisum (Harris, 1776), with reduced susceptibility to acetamiprid after nine generations of exposure to identify candidate genes and the microbiome involved in the adaptation process. Sequencing of the transcriptome of both selected (RS) and non-selected (SS) strains allowed the identification of 14,858 genes and 4938 new transcripts. Most of the differentially expressed genes were associated with catalytic activities and metabolic pathways involving carbon and fatty acids. Specifically, alcohol-forming fatty acyl-CoA reductase (FAR) and acyl-CoA synthetase (ACSF2), both involved in the synthesis of epidermal wax layer components, were significantly upregulated in RS, suggesting that adaptation to acetamiprid involves the synthesis of a thicker protective layer. Metatranscriptomic analyses revealed subtle shifts in the microbiome of RS. These results contribute to a deeper understanding of acetamiprid adaptation by the pea aphid and provide new insights for aphid control strategies.

Clinical characteristics of persistent or recurrent pneumonia combined with airway malacia in children.

OBJECTIVE: The aim of this study is to investigate the clinical characteristics and pathogens involved in persistent or recurrent pneumonia combined with airway malacia in children. METHODS: We retrospectively reviewed the information of children hospitalised with persistent or recurrent pneumonia, including clinical presentations, laboratory examination results and pathogens. RESULTS: A total of 554 patients were admitted, 285 (51.44%) of whom were found to have airway malacia. There were 78 (27.37%), 166 (58.25%) and 41 (14.39%) patients with mild, moderate and severe malacia, respectively. Patients with airway malacia were younger than those without malacia (6.0 vs. 12.0 months, p < 0.01) and were more likely to present with wheezing (75.07%), fever (34.39%), dyspnoea (28.77%), cyanosis (13.68%) and wheezing in the lungs (78.95%). The incidence of preterm delivery, oxygen therapy, paediatric intensive care unit (PICU) admission and mechanical ventilation was higher, and the hospital stay (11.0 vs. 10.0 days, p = 0.04) was longer in these patients than in those without malacia. Patients with severe airway malacia were more likely to undergo oxygen therapy, PICU admission, mechanical ventilation and have multiple malacia than were those with mild or moderate malacia. Mycoplasma pneumoniae (30.18%) was the most common pathogen. CONCLUSION: Severe airway malacia likely aggravates conditions combined with pneumonia. The proportion of multisite malacia was greater in severe airway malacia patients.

Regulating the Chiroptical Expression of Aggregated Solvophobic Core by Solvophilic Segments.

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

Environmental antibiotics exposure and childhood obesity: A cross-sectional case-control study.

Children's exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09-1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1-2.05). Comparing none (

Association between hyperuricemia and ultrasound-detected hand synovitis.

OBJECTIVE: Although hand synovitis is prevalent in the older population, the aetiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population-based sample. METHODS: We performed a cross-sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate >420 µmol/L in men and >360 µmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both grey-scale synovitis and Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0-3). We evaluated the association of hyperuricemia with hand grey-scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex and body mass index. RESULTS: All required assessments for analysis were available on 3,286 participants. The prevalence of hand grey-scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI]:1.00-1.62). Participants with hyperuricemia also had higher prevalence of PDS (aOR=2.36, 95% CI:1.15-4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with presence of grey-scale synovitis (aOR=1.27, 95% CI:1.00-1.60, and adjusted prevalence ratio [aPR]=1.26, 95% CI:1.10-1.44, respectively), and PDS (aOR=2.35, 95% CI:1.15-4.79, and aPR=2.34, 95% CI:1.28-4.30, respectively). CONCLUSION: This population-based study provides more evidences for a positive association between hyperuricemia and prevalent hand synovitis.

Hyposalinity stress reduces mussel byssus secretion but does not cause detachment.

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.

Cucurbit[8]uril Mediated Supramolecular and Photocrosslinked Interpenetrating Network Hydrogel Matrices for 3D-Bioprinting.

Printing of biologically functional constructs is significant for applications in tissue engineering and regenerative medicine. Designing bioinks remains remarkably challenging due to the multifaceted requirements in terms of the physical, chemical, and biochemical properties of the three-dimensional matrix, such as cytocompatibility, printability, and shape fidelity. In order to promote matrix and materials stiffness, while not sacrificing stress relaxation mechanisms which support cell spreading, migration, and differentiation, this work reports an interpenetrating network (IPN) bioink design. The approach makes use of a chemically defined network, combining physical and chemical crosslinking units with a tunable composition and network density, as well as spatiotemporal control over post-assembly material stiffening. To this end, star-shaped poly(ethylene glycol)s functionalized with Phe-Gly-Gly tripeptide or photoactive stilbazolium are synthesized, and used to prepare three-dimensional networks with cucurbit[8]uril (CB[8]) through supramolecular host-guest complexation. The hydrogel obtained shows fast relaxation and thus supports the proliferation and differentiation of cells. Upon irradiation, the mechanical properties of the hydrogel can be rapidly adapted via selective photochemical dimerization of stilbazolium within CB[8], leading to IPNs with increased form stability while retaining the dynamic nature of the hydrogels. This modular approach opens new design opportunities for extrudable and cell-friendly dynamic biomaterials for applications in 3D-bioprinting.

Identification, rapid screening, docking mechanism and in vitro digestion stability of novel DPP-4 inhibitory peptides from wheat gluten with ginger protease.

To better understand the hypoglycemic potential of wheat gluten (WG), we screened dipeptidyl peptidase IV (DPP-4) inhibitory active peptides from WG hydrolysates. WG hydrolysates prepared by ginger protease were found to have the highest DPP-4 inhibitory activity among the five enzymatic hydrolysates, from which a 1-3 kDa fraction was isolated by ultrafiltration. Further characterization of the fraction with nano-HPLC-MS/MS revealed 1133 peptides. Among them, peptides with P'2 (the second position of the N-terminal) and P2 (the second position of the C-terminal) as proline residues (Pro) accounted for 12.44% and 43.69%, respectively. The peptides including Pro-Pro-Phe-Ser (PPFS), Ala-Pro-Phe-Gly-Leu (APFGL), and Pro-Pro-Phe-Trp (PPFW) exhibited the most potent DPP-4 inhibitory activity with IC50 values of 56.63, 79.45, and 199.82 µM, respectively. The high inhibitory activity of PPFS, APFGL, and PPFW could be mainly attributed to their interaction with the S2 pocket (Glu205 and Glu206) and the catalytic triad (Ser630 and His740) of DPP-4, which adopted competitive, mixed, and mixed inhibitory modes, respectively. After comparative analysis of PPFS, PPFW, and PPF, Ser was found to be more conducive to enhancing the DPP-4 inhibitory activity. Interestingly, peptides with P2 as Pro also exhibited good DPP-4 inhibitory activity. Meanwhile, DPP-4 inhibitory peptides from WG showed excellent stability, suggesting a potential application in type 2 diabetes (T2DM) therapy or in the food industry as functional components.