Evaluating the capability of soybean peptides as calcium ion carriers: a study through sequence analysis and molecular dynamics simulations.

Calcium homeostasis imbalance in the body can lead to a variety of chronic diseases. Supplement efficiency is essential. Peptide calcium chelate, a fourth-generation calcium supplement, offers easy absorption and minimal side effects. Its effectiveness relies on peptide's calcium binding capacity. However, research on amino acid sequences in peptides with high calcium binding capacity (HCBC) is limited, affecting the efficient identification of such peptides. This study used soybean peptides (SP), separated and purified by gel chromatography, to obtain HCBC peptide (137.45 µg mg-1) and normal peptide (≤95.78 µg mg-1). Mass spectrometry identified the sequences of these peptides, and an analysis of the positional distribution of characteristic amino acids followed. Two HCBC peptides with sequences GGDLVS (271.55 µg mg-1) and YEGVIL (272.54 µg mg-1) were discovered. Molecular dynamics showed that when either aspartic acid is located near the N-terminal's middle, or glutamic acid is near the end, or in cases of continuous Asp or Glu, the binding speed, probability, and strength between the peptide and calcium ions are superior compared to those at other locations. The study's goal was to clarify how the positions of characteristic amino acids in peptides affect calcium binding, aiding in developing peptide calcium chelates as a novel calcium supplement.

Conjugation of Soybean Proteins 7S/11S Isolate with Glucose/Fructose in Gels through Wet-Heating Maillard Reaction.

Conjugation with glucose (G) and fructose (F) via the Maillard reaction under the wet-heating condition is a natural and non-toxic method of improving the technological functions of 7S/11S proteins in different kinds of gels. It may be used as an affordable supply of emulsifiers and an excellent encapsulating matrix for gels. This study aimed to create a glucose/fructose-conjugated 7S/11S soy protein via the Maillard reaction. The conjugation was confirmed by determining the SDS-PAGE profile and circular dichroism spectra. In addition, these conjugates were comprehensively characterized in terms of grafting degree, browning degree, sulfhydryl content, surface hydrophobicity (H0), and differential scanning calorimetry (DSC) through various reaction times (0, 24, 48, and 72 h) to evaluate their ability to be used in food gels. The functional characteristics of the 7S/11S isolate-G/F conjugate formed at 70 °C, with a high degree of glycosylation and browning, were superior to those obtained at other reaction times. The SDS-PAGE profile indicated that the conjugation between the 7S and 11S proteins and carbohydrate sources of G and F through the Maillard reaction occurred. Secondary structural results revealed that covalent interactions with G and F affected the secondary structural components of 7S/11S proteins, leading to increased random coils. When exposed to moist heating conditions, G and F have significant potential for protein alteration through the Maillard reaction. The results of this study may provide new insights into protein modification and establish the theoretical basis for the therapeutic application of both G and F conjugation with soy proteins in different food matrixes and gels.

Social support predicted subsequent subjective well-being during the COVID-19 pandemic: a prospective study.

BACKGROUND: Subjective well-being (SWB) is associated with social support in cross-sectional studies. However, it remains unclear whether and how social support predicts SWB longitudinally, especially during the COVID-19 contingency. METHODS: By adopting a prospective design, the current work addressed this research question in a sample of 594 participants from the U.K. The data were collected via the online platform, Prolific, at two time points (June, 2020 and August, 2021) with a 14-month interval. Descriptive analysis and a moderated mediation model were conducted to test the proposed hypotheses. RESULTS: Baseline social support was a significant predictor of subjective well-being (SWB) 14 months later, even after controlling for baseline SWB and other covariates such as personality traits. Additionally, affect balance (i.e., the affective component of SWB) fully mediated the link between baseline social support and subsequent life satisfaction (i.e., the cognitive component of SWB). Moreover, household income moderated this relationship, indicating a stronger mediation for individuals with lower monthly household income. CONCLUSION: The present work sheds light on the underlying mechanism and boundary condition of the association between social support and different components of SWB during the COVID-19 pandemic.

Protective effects of sugarcane polyphenol against UV-B-induced photoaging in Balb/c mouse skin: Antioxidant, anti-inflammatory, and anti-glycosylation Effects.

Although the benefits of sugarcane polyphenol (SP) are well documented, its function in preventing photoaging has not yet been investigated. This study aimed to investigate the protective effects of SP in preventing ultraviolet (UV)-B-induced skin photoaging in Balb/c mice, as well as the underlying mechanism. Chlorogenic acid was determined to be the primary component of SP by using high-performance liquid chromatography-mass spectrometry. SP and chlorogenic acid were orally administrated to mice for 56 days, and UV-B radiation exposure was administered 14 days after SP and chlorogenic acid administration and lasted 42 days to cause photoaging. SP and chlorogenic acid administrations significantly alleviated the UV-B-induced mouse skin photoaging, as indicated by the decrease in epidermal thickness, increase in the collagen (COL) volume fraction, and elevation in type 1 and type 3 COL contents. Notably, both SP and chlorogenic acid effectively reversed the overexpression of matrix metalloproteinase induced by UV-B exposure in the mouse skin. Furthermore, SP and chlorogenic acid reduced the expression of receptor for advanced glycosylation end products in the mice; amplified the activities of antioxidant enzymes superoxide dismutase and catalase; reduced malondialdehyde levels; and decreased inflammatory cytokines interleukin 1ß, interleukin 6, and tumor necrosis factor α levels. SP could be a prospective dietary supplement for anti-photoaging applications due to its antioxidant, anti-inflammatory, and anti-glycosylation attributes, and chlorogenic acid might play a major role in these effects. PRACTICAL APPLICATION: This study can provide a scientific basis for the practical application of sugarcane polyphenols. We expect that sugarcane polyphenols can be used in food and beverage products to provide flavor while combating skin aging.

Epigenetic regulation by KDM5A mediates the effects of prenatal PM2.5 exposure on hippocampal development and synaptic integrity through the Shh signaling pathway.

Prenatal environmental exposure could be an essential health risk factor associated with neurodevelopmental disorders in offspring. However, the exact mechanisms underlying the impact of prenatal PM2.5 exposure on offspring cognition remain unclear. In our recent study using a PM2.5 exposed pregnant mouse model, we observed significant synaptic dysfunction in the hippocampi of the offspring. Concurrently, the epigenetic regulator of KDM5A and the Shh signaling pathway exhibited decreased activities. Significantly, changes in hippocampal KDM5A and Shh levels directly correlated with PM2.5 exposure intensity. Subsequent experiments revealed a marked reduction in the expression of Shh signaling and related synaptic proteins when KDM5A was silenced in cells. Notably, the effects of KDM5A deficiency were reversed significantly with the supplementation of a Shh activator. Furthermore, our findings indicate that Shh activation significantly attenuates PM2.5-induced synaptic impairments in hippocampal neurons. We further demonstrated that EGR1, a transcriptional inhibitor, plays a direct role in KDM5A's regulation of the Shh pathway under conditions of PM2.5 exposure. Our results suggest that the KDM5A's inhibitory regulation on the Shh pathway through the EGR1 gene is a crucial epigenetic mechanism underlying the synaptic dysfunction in hippocampal neurons caused by maternal PM2.5 exposure. This emphasizes the role of epigenetic regulations in neurodevelopmental disorders caused by environmental factors.

Multicomponent nickel-molybdenum-tungsten-based nanorods for stable and efficient alkaline seawater splitting.

The electrolysis of seawater for hydrogen production holds promise as a sustainable technology for energy generation. Developing water-splitting catalysts with low overpotential and stable operation in seawater is essential. In this study, we employed a hydrothermal method to synthesize NiMoWOX microrods (NiMoWOX@NF). Subsequently, an annealing process yielded a composite N-doped carbon-coated Ni3N/MoO2/WO2 nanorods (NC@Ni3N/MoO2/WO2@NF), preserving the ultrahigh-specific surface area of the original structure. A two-electrode electrolytic cell was assembled using NC@Ni3N/MoO2/WO2@NF as the cathode and NiMoWOX@NF as the anode, demonstrating exceptional performance in seawater splitting. The cell operated at a voltage of 1.51 V with a current density of 100 mA·cm-2 in an alkaline seawater solution. Furthermore, the NC@Ni3N/MoO2/WO2@NF || NiMoWOX@NF electrolytic cell exhibited remarkable stability, running continuously for over 120 h at a current of 1100 mA·cm-2 without any observable delay. These experimental results are corroborated by density functional theory calculations. The NC@Ni3N/MoO2/WO2@NF || NiMoWOX@NF electrolyzer emerges as a promising option for industrial-scale hydrogen production through seawater electrolysis.

Reconstructing Complex Shaped Clothing from a Single Image with Feature Stable Unsigned Distance Fields.

Single-view clothing reconstruction usually relies on topologically fixed clothing templates to reduce the problem complexity, but this strategy also makes the reconstructed clothing shape contours simple and lack diversity. In this paper, we propose a novel clothing reconstruction method to generate complex shape contours and open clothing mesh from a single image. At the heart of our work is an implicit unsigned distance field condition on clothing-oriented and pose-stable spatial shape features to represent the clothing from the image. This feature can provide spatially aligned clothing shape priors to improve the pose robustness. It is based on a type-generic clothing template derived from the mainstream clothing generative model to avoid tedious template design and switching. To output open clothing mesh results from noisy clothing unsigned distance fields, we develop a two-stage clothing mesh extraction method. It takes the point clouds as an intermediate representation and produces smooth, plausible and editable clothing mesh results. To provide effective supervision, we construct a pose-rich and shape-complete clothing scan dataset by enhancing clothing pose diversity and complementing missing clothing geometry caused by occlusion. Extensive experiments demonstrate that our method achieves state-of-the-art levels. More importantly, we provide a simple but effective, and low-cost way to reconstruct complex shape contours clothing from a single image.

The Effect of N-Carbamylglutamate Supplementation during the Last Third of Gestation on the Growth and Development of Fetuses Born to Nutrient-Restricted Twin-Bearing Ewes.

N-carbamylglutamate (NCG) is postulated to improve fetal growth in nutrient-restricted gestations when supplemented from day 35 to 110 of gestation, but the effects of supplementation from 100 days of gestation to birth have not been evaluated. The aim of this study was to evaluate the effect of oral NCG supplementation from 100 days of gestation (dga) to term in naturally nutrient-restricted grazing twin-bearing ewes, on the maternal body weight (BW), body condition score (BCS), placental morphology, fetal body and organ weights and blood biochemistry and antioxidant status in the ewe and fetuses. Eighteen twin-bearing ewes maintained under grazing management were randomly allocated to either a treatment group (NCG; n = 10), orally dosed once daily with 60 mg/kg of NCG from day 100 until 140 dga, or an unsupplemented control group (CON; n = 8). At 140 dga, blood gases, redox status, maternal and fetal plasma and fetal biometrics were obtained after caesarian section. The serum concentration of NCG was increased 15-fold in the NCG ewes compared to the CON. No major effects on dam or fetal body weight nor on blood biochemistry or antioxidant parameters were observed. These results indicate that NCG supplementation in mid-to-late gestation to grazing ewes was unable to rescue the negative production effects of severe natural nutritional restriction on both the dam and fetuses.

Investigating the antibacterial mode of Limosilactobacillus reuteri LR08 regulated by soybean proteins and peptides.

Soybean proteins (pro) and soybean peptides (pep) are beneficial to the growth and metabolism of Limosilactobacillus reuteri (L. reuteri). However, whether they could assist L. reuteri in inhibiting intestinal pathogens and the inhibition mode of them is still unclear. In this study, a co-culture experiment of L. reuteri LR08 with Escherichia coli JCM 1649 (E. coli) was performed. It showed that pro and pep could still favour the growth of L. reuteri over E. coli under their competition. The inhibition zone experiment showed the digested soybean proteins (dpro) could improve its antibacterial activity by increasing the secretion of organic acids from L. reuteri. Furthermore, digested soybean peptides (dpep) could enhance nitrogen utilization capacity of L. reuteri over E. coli. These results explained the patterns of dpro and dpep assisting L. reuteri in inhibiting the growth of E. coli by regulating its organic acid secretion and the ability of nitrogen utilization.

Quality, Thermo-Rheology, and Microstructure Characteristics of Cubic Fat Substituted Pork Patties with Composite Emulsion Gel Composed of Konjac Glucomannan and Soy Protein Isolate.

Composite emulsion gel can effectively mimic animal adipose tissue. In this study, composite emulsion gels composed of soy protein isolates and konjac glucomannan (KGM) were prepared as plant-based cubic fat substitutes (CFS). The effects of CFS on the quality and structure of pork patties were investigated in terms of the proximate composition, lipid oxidation stability, technological characteristics, color, sensory attributes, texture, thermo-rheological behavior, and microstructure. CFS samples composed of various ratios of KGM were added to lean meat patties to ascertain the optimal CFS composition for its potential replacement of pork back fat in patties. The addition of CFS containing 7.0% KGM was found to decrease the hardness of the lean meat patties by 71.98% while simultaneously improving their sensory quality. The replacement of pork back fat with CFS also reduced the fat content of the patties to as little as 3.65%. Furthermore, the addition of CFS enhanced the technological characteristics, lipid oxidation stability, and surface color of the fat-replaced patties, with no significant impact on their overall acceptability. The gel network of the patties was shown to be fine and remained compact as the fat replacement ratio increased to 75%, while the texture parameters, storage modulus, and fractal dimension all increased. Quality and structure improvements may allow the composite emulsion gels to replace fat in pork patties to support a healthy diet. This study may be beneficial for the application and development of plant-based cubic fat substitutes.

Learning Pose Controllable Human Reconstruction with Dynamic Implicit Fields from a Single Image.

Recovering a user-special and controllable human model from a single RGB image is a nontrivial challenge. Existing methods usually generate static results with an image consistent subject's pose. Our work aspires to achieve pose-controllable human reconstruction from a single image by learning a dynamic (multi-pose) implicit field. We first construct a feature-embedded human model (FEHM) as a bridge to propagate image features to different pose spaces. Based on FEHM, we then encode three pose-decoupled features. Global image features represent user-specific shapes in images and replace widely used pixel-aligned ways to avoid unwanted shape-pose entanglement. Spatial color features propagate FEHM-embedded image cues into 3D pose space to provide spatial high-frequency guidance. Spatial geometry features improve reconstruction robustness by using the surface shape of the FEHM as the prior. Finally, new implicit functions are designed to predict the dynamic human implicit fields. For effective supervision, a realistic human avatar dataset, SimuSCAN, with 1000+ models is constructed using a low-cost hierarchical mesh registration method. Extensive experiments demonstrate that our method achieves the state-of-the-art reconstruction level.

Association of asthma and lung cancer risk: A pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Over the past 2 decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these 2 conditions remain poorly understood. METHODS: We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until May 04, 2023. Only articles published in English were included in our study. We performed a meta-analysis using random-effects models to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses were conducted based on study design, gender, and histologic types. We also conducted a 2-sample Mendelian randomization (MR) using the genome-wide association study pooled data (408,422 people) published by the UK Biobank to explore further the potential causal relationship between asthma and lung cancer. RESULTS: Our meta-analysis reviewed 24 population-based cohort studies involving 1072,502 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19-1.38) in all individuals. Subgroup analysis showed a significantly higher risk of lung cancer in females with asthma (OR = 1.23, 95% CI 1.01-1.49). We found no significant association between asthma and lung adenocarcinoma (LUAD) (OR = 0.76, 95% CI 0.54-1.05), lung squamous carcinomas (LUSC) (OR = 1.09, 95% CI 0.79-1.50), or small-cell lung cancer (SCLC) (OR = 1.00, 95% CI 0.68-1.49). Interestingly, our MR analysis supported an increasing causality between asthma and lung cancer (OR = 1.11, 95% CI 1.04-1.17, P = .0008), specifically in those who ever smoker (OR = 1.09, 95% CI 1.01-1.16, P = .0173) and LUSC pathological type (OR = 1.15, 95% CI 1.05-1.26, P = .0038). CONCLUSION: Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study further support an increasing causal relationship between asthma and the risk of lung cancer, particularly in smokers and LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.

Alterations in the sequence and bioactivity of food-derived oligopeptides during simulated gastrointestinal digestion and absorption: a review.

Food-derived oligopeptides (FOPs) exhibit various bioactivities. However, little was known about their sequence changes in the gastrointestinal tract and the effect of changes on bioactivities. FOPs' sequence features, changes and effects on bioactivities have been summarised. The sequence length of FOPs decreases with increased exposure of hydrophobic and basic amino acids at the terminal during simulated gastrointestinal digestion. A decrease in bioactivities after simulated intestinal absorption has correlated with a decrease of Leu, Ile, Arg, Tyr, Gln and Pro. The sequence of FOPs that pass readily through the intestinal epithelium corresponds to transport modes, and FOPs whose sequences remain unchanged after transport are the most bioactive. These include mainly dipeptides to tetrapeptides, consisting of numerous hydrophobic and basic amino acids, found mostly at the end of the peptide chain, especially at the C-terminal. This review aims to provide a foundation for applications of FOPs in nutritional supplements and functional foods.

The investigation of soybean protein isolates and soybean peptides assisting Lactobacillus plantarum K25 to inhibit Escherichia coli.

Soybean protein isolates and their hydrolysates are considered as one of the most high-quality proteins among plant proteins, and current research has shown that they have potential probiotic functions. The purpose of this study was to investigate the effects of digested soybean protein isolates (dSPI) and digested soybean peptides (dPEP) on L. plantarum K25 alone and the two bacteria when co-cultured with E. coli. It showed that dSPI and dPEP promoted the growth and metabolism of L. plantarum K25, and dSPI had a better effect. Besides, dSPI and dPEP still promoted the growth and organic acid secretion of L. plantarum K25 when co-cultured with E. coli, and the dPEP treatment was more effective than dSPI. Moreover, dSPI and dPEP reduced the survival rate of E. coli when co-cultured with L. plantarum K25. These results to some extent explained the cooperation of dSPI and dPEP with L. plantarum K25 to produce acid thereby weaken the growth of E. coli.

MiRNA-100 ameliorates diabetes mellitus-induced erectile dysfunction by modulating autophagy, anti-inflammatory, and antifibrotic effects.

BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) has become a common disease in adult men that can seriously reduce the quality of life of patients, and new therapies are urgently needed. miRNA-100 has many targets and can induce autophagy and reduce fibrosis by inhibiting the mTOR pathway and the TGF-ß pathway. However, no research has been conducted with miR-100 in the field of DMED, and the specific mechanism of action is still unclear. OBJECTIVES: To ascertain the effects of miR-100 on corpus cavernosum tissue of DMED rats and vascular endothelial cells in a high glucose environment and to elucidate the relevant mechanisms in autophagy, fibrosis and inflammation to find a new approach for the DMED therapy. METHODS: Thirty rats were divided into three groups: the control group, the DMED group, and the DMED + miR-100 group. Using intraperitoneal injections of streptozotocin, all rats except the control group were modeled with diabetes mellitus, which was verified using the apomorphine (APO) test. For rats in the DMED + miR-100 group, rno-miR-100-5p agomir (50 nmol/kg, every 2 days, 6 times in total) was injected via the tail vein. After 13 weeks, the erectile function of each rat was assessed using cavernous manometry, and the corpus cavernosum tissue was harvested for subsequent experiments. For cellular experiments, human coronary microartery endothelial cells (HCMEC) were divided into four groups: the control group, the high-glucose (HG, 40 mM) group, the HG + mimic group, and the HG + inhibitor group. The cells were cultured for 6 days and collected for subsequent experiments 2 days after transfection. RESULTS: Diabetic modeling impaired the erectile function in rats, and miR-100 reversed this effect. By measuring autophagy-related proteins such as mTOR/Raptor/Beclin1/p62/LC3B, we found that miR-100 could suppress the expression of mTOR and induce autophagy. The analysis of the eNOS/NO/cGMP axis function indicated that impaired endothelial function was improved by miR-100. By evaluating the TGF-ß1/CTGF/Smad2/3 and NF-κB/TNF-α pathways, we found that miR-100 could lower the level of inflammation and fibrosis, which contributed to the improvement of the erectile function. Cellular experiments can be used as supporting evidence for these findings. CONCLUSION: MiR-100 can improve the erectile function by inhibiting mTOR and thus inducing autophagy, improving the endothelial function through the eNOS/NO/cGMP axis, and exerting antifibrotic and anti-inflammatory effects, which may provide new ideas and directions for the treatment of DMED.

Morphology, surface characteristics and tribological properties of whey protein/chitosan composite particles and their fat replacing effect in O/W emulsion.

Whey protein isolate (WPI) and chitosan were used to fabricate WPI/chitosan composite particles at temperatures of 75 °C (WPI/chitosan-75) and 95 °C (WPI/chitosan-95). The morphologic structure, surface properties, and the resulting tribological characteristics of the particles were investigated. The composite particles showed larger particle size than pure WPI particles (WPI-75) (~ 509 nm), with WPI/chitosan-95 the largest (932 nm). WPI/chitosan-75 showed complete core-shell structure from microstructure results. The dispersion of WPI/chitosan-75 exhibited higher surface hydrophobicity but lower viscosity compared to WPI/chitosan-95. Tribological analysis revealed that WPI/chitosan composite particles showed dramatically lower friction coefficient (µ) than pure WPI particles at sliding speed <10 mm/s and WPI/chitosan-75 demonstrated superior lubrication effects. With the presence of artificial saliva, the µ of WPI-75 was greatly lowered at sliding speed <16 mm/s, while the values of WPI/chitosan-75 only showed a slight decrease at sliding speed <1 mm/s. Chitosan might have played the similar role as artificial saliva in lubricating on the hydrophobic surface. Moreover, the incorporation of 0.5 % WPI/chitosan-75 in the low-fat (5 %) oil-in-water emulsion led to even lower µ than full-fat (20 %) emulsion at sliding speed <10 mm/s. Hence, WPI/chitosan-75 exhibited promising potential as a fat replacement and biolubricant.

Statistical Characterization of Food-Derived α-Amylase Inhibitory Peptides: Computer Simulation and Partial Least Squares Regression Analysis.

α-Amylase inhibitory peptides are used to treat diabetes, but few studies have statistically characterized their interaction with α-amylase. This study performed the molecular docking of α-amylase with inhibitory peptides from published papers. The key sites, side chain chargeability, and hydrogen bond distribution characteristics were analyzed. Molecular dynamics simulated the role of key sites in complex stability. Moreover, partial least squares regression (PLSR) was used to analyze the contribution of different amino acids in the peptides to inhibition. The results showed that, for the α-amylase molecule, His201 and Gln63, with the highest interaction numbers (INs, 15, 15) and hydrogen bond values (HBVs, 11.50, 10.33), are the key sites on α-amylase, and amino acids with positively charged side chains were important for inhibitory activity. For the inhibitory peptides, Asp and Arg had the highest HBVs, and amino acids with charged side chains were more likely to form hydrogen bonds and exert inhibitory activity. In molecular dynamics simulations, peptides involving key binding sites formed more stable complexes with α-amylase than α-amylase alone, suggesting enhanced inhibitory effects. Further, PLSR results showed that amino acids close to the N-terminus of the inhibitory peptide, located in the third and fifth positions, were significantly correlated with its inhibitory activity. In conclusion, this study provides a new approach to developing and screening α-amylase inhibitors.

Effect of extrusion on the protein structure and digestibility of extruded soybean protein.

BACKGROUND: Extrusion is the main method for the preparation of plant-based meat. Current studies have focused on the effect of different extrusion parameters on the texture and quality of plant-based meat, but there has been less research on their digestibility. This study determined the textural properties of extruded soybean protein (ESPro) for different extrusion parameters and the digestibility after in vitro simulated digestion experiments. The effect of extrusion on the structure and digestibility of ESPro and the relationship between them were elucidated. RESULTS: The results demonstrated a significant improvement in the digestibility of ESPro through extrusion, with the highest values for cohesiveness, springiness, chewiness, fibrous degree, digestibility, and proportion of digested peptides with <1 kDa molecular weight at an extrusion temperature of 160 °C and a screw speed of 30 rpm (ESPro1). In addition, ß-sheet content in the secondary structure of the ESPro showed a significant negative association with ESPro digestibility. CONCLUSION: In this study, extrusion could improve the digestibility of ESPro by altering the protein structure. This advancement holds the potential for more effective applications in plant-based meats. © 2023 Society of Chemical Industry.

HIV-1 p17 matrix protein enhances type I interferon responses through the p17-OLA1-STING axis.

Stimulator of IFN genes (STING; also known as STING1) is an important adaptor protein for detecting cytosolic double-stranded DNA, which can come from HIV infection. Several HIV proteins, such as p6, Vpx and Vif, can influence STING-mediated innate immunity, but the function of p17 is still unknown. In this study, we find that HIV-1 p17, but not HIV-2 p17 or SIV p17, promotes STING signaling induced by cyclic GMP-AMP (cGAMP) treatment. Mechanistically, HIV-1 p17 binds to Obg-like ATPase 1 (OLA1) and inhibits the regulation of STING by OLA1. Here, OLA1 interacts with STING and inhibits the translocation and phosphorylation of STING upon cGAMP stimulation. Furthermore, compared with HIV-2 and SIV, the ATPase and GTPase activities of OLA1 are only promoted by HIV-1 p17. Our study shows that the p17 of HIV-1, but not HIV-2 or SIV, promotes STING-mediated innate immunity by interfering the interaction between OLA1 and STING, thus providing a new clue for specific immune activation of HIV-1.

Spinal interleukin-16 mediates inflammatory pain via promoting glial activation.

Proinflammatory cytokines are crucial contributors to neuroinflammation in the development of chronic pain. Here, we identified il16, which encodes interleukin-16 (IL-16), as a differentially expressed gene in spinal dorsal horn of a complete Freund's Adjuvant (CFA) inflammatory pain model in mice by RNA sequencing. We further investigated whether and how IL-16 regulates pain transmission in the spinal cord and contributes to the development of inflammatory pain hypersensitivity. RNA sequencing and bioinformatics analysis revealed elevated IL-16 transcript levels in the spinal dorsal horn after CFA injection. This increase was further confirmed by qPCR, immunofluorescence, and western blotting. Knockdown of IL-16 by intrathecal injection of IL-16 siRNA not only attenuated CFA-induced mechanical and thermal pain hypersensitivity, but also inhibited enhanced c-fos expression and glial activation in the spinal dorsal horn in male mice injected with CFA. Moreover, exogenous IL-16 induced nociceptive responses and increased c-fos expression and glial activation in spinal dorsal horn. This effect was largely impaired when CD4, the binding receptor for IL-16, was inhibited. In addition, CD4 expression was upregulated in the spinal dorsal horn after CFA injection and CD4 was present in microglia and in contact with astrocytes and activated spinal neurons. Taken together, these results suggest that enhanced IL-16-CD4 signaling triggers pain and activates microglia and astrocytes in the spinal dorsal horn, thus contributing to inflammatory pain. IL-16 may serve as a promising target for the treatment of inflammatory pain.