Angiotensin converting enzyme (ACE) inhibitory peptide from the tuna (Thunnus thynnus) muscle: Screening, interaction mechanism and stability.

In this study, the purpose was to screen novel angiotensin converting enzyme inhibitory peptides (ACEIPs) from tuna muscle taking two-steps enzymatic hydrolysis (Neutrase and Alkaline). Following isolation and purification by ultrafiltration, the Sephadex G-15 gel chromatography and reversed-phase high-performance liquid chromatography based on active-guide, the amino acid sequence was identified using Q-Orbitrap-MS/MS. Five peptides were chose synthesized based on the in silico screening methods. Among these, the two novel ACEIPs LTGCP and YPKP showed better inhibitory ability, and their corresponding IC50 values were 64.3 µM and 139.6 µM. Subsequently, the interaction mechanism of the best active peptide (LTGCP) against ACE was investigated by inhibitory pattern, molecular docking and molecular dynamic simulation. The result displayed that LTGCP was a mix-type inhibitor against ACE from the Lineweaver-Burk plots. LTGCP formed seven hydrogen bonds based on the molecular docking and the binding energy was -7.29 kcal/mol. LTGCP formed a stability complex with ACE based on the molecular dynamic simulation. Besides, LTGCP exhibited good stability in various temperature, pH and gastrointestinal digestion. Finally, the 0.125 mM âˆ¼ 1.0 mM LTGCP exhibited no-toxic for Caco-2 cell. In summary, these findings showed that tuna was a good material to prepare ACEIPs and LTGCP may be the good potential antihypertensive drug or nutraceuticals.

Recent Advances in Antimony Selenide Photodetectors.

Photodetectors (PDs) rapidly capture optical signals and convert them into electrical signals, making them indispensable in a variety of applications including imaging, optical communication, remote sensing, and biological detection. Recently, antimony selenide (Sb2Se3) has achieved remarkable progress due to its earth-abundant, low toxicity, low price, suitable bandgap width, high absorption coefficient, and unique structural characteristics. Sb2Se3 has been extensively studied in solar cells, but there's a lack of timely updates in the field of PDs. A literature review based on Sb2Se3 PDs is urgently warranted. This review aims to provide a concise understanding of the latest progress in Sb2Se3 PDs, with a focus on the basic characteristics and the performance optimization for Sb2Se3 photoconductive-type and photodiode-type detectors, including nanostructure regulation, process optimization, and stability improvement of flexible devices. Furthermore, the application progresses of Sb2Se3 PDs in heart rate monitoring, and monolithic-integrated matrix images are introduced. Finally, this review presents various strategies with potential and feasibility to address challenges for the rapid development and commercial application of Sb2Se3 PDs.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Spatiotemporal Changes and Influencing Factors of Hand, Foot, and Mouth Disease in Guangzhou, China, From 2013 to 2022: Retrospective Analysis.

Background: In the past 10 years, the number of hand, foot, and mouth disease (HFMD) cases reported in Guangzhou, China, has averaged about 60,000 per year. It is necessary to conduct an in-depth analysis to understand the epidemiological pattern and related influencing factors of HFMD in this region. Objective: This study aims to describe the epidemiological characteristics and spatiotemporal distribution of HFMD cases in Guangzhou from 2013 to 2022 and explore the relationship between sociodemographic factors and HFMD incidence. Methods: The data of HFMD cases in Guangzhou come from the Infectious Disease Information Management System of the Guangzhou Center for Disease Control and Prevention. Spatial analysis and space-time scan statistics were used to visualize the spatiotemporal distribution of HFMD cases. Multifactor ordinary minimum regression model, geographically weighted regression, and geographically and temporally weighted regression were used to analyze the influencing factors, including population, economy, education, and medical care. Results: From 2013 to 2022, a total of 599,353 HFMD cases were reported in Guangzhou, with an average annual incidence rate of 403.62/100,000. Children aged 5 years and younger accounted for 93.64% (561,218/599,353) of all cases. HFMD cases showed obvious bimodal distribution characteristics, with the peak period from May to July and the secondary peak period from August to October. HFMDs in Guangzhou exhibited a spatial aggregation trend, with the central urban area showing a pattern of low-low aggregation and the peripheral urban area demonstrating high-high aggregation. High-risk areas showed a dynamic trend of shifting from the west to the east of peripheral urban areas, with coverage first increasing and then decreasing. The geographically and temporally weighted regression model results indicated that population density (ß=-0.016) and average annual income of employees (ß=-0.007) were protective factors for HFMD incidence, while the average number of students in each primary school (ß=1.416) and kindergarten (ß=0.412) was a risk factor. Conclusions: HFMD cases in Guangzhou were mainly infants and young children, and there were obvious differences in time and space. HFMD is highly prevalent in summer and autumn, and peripheral urban areas were identified as high-risk areas. Improving the economic level of peripheral urban areas and reducing the number of students in preschool education institutions are key strategies to controlling HFMD.

Ancestral Origins and Admixture History of Kazakhs.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin, genomic makeup, and genetic interaction with surrounding populations are not well understood. To decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from 4 ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from the Uyghurs in terms of their overall genomic makeup, although the 2 populations were closely related in genetics, and both showed a substantial admixture of western and eastern peoples. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those living or along the old Silk Road.

Fluorogenic Peptide Sensor Array Derived from Angiotensin-Converting Enzyme 2 Classifies Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.

Petal-Shaped Graphene Porous Films with Enhanced Absorption-Dominated Electromagnetic Shielding Performance and Mechanical Properties.

The absorption-dominated graphene porous materials, considered ideal for mitigating electromagnetic pollution, encounter challenges related to intricate structural design. Herein, petal-like graphene porous films with dendritic-like and honeycomb-like pores are prepared by controlling the phase inversion process. The theoretical simulation and experimental results show that PVP K30 modified on the graphene surface via van der Waals interactions promotes graphene to be uniformly enriched on the pore walls. Benefiting from the regulation of graphene distribution and the construction of honeycomb pore structure, when 15 wt % graphene is added, the porous film exhibits absorption-dominated electromagnetic shielding performance, compared with the absence of PVP K30 modification. The total electromagnetic shielding effectiveness is 24.1 dB, an increase of 170%; the electromagnetic reflection coefficient reduces to 2.82 dB; The thermal conductivity reaches 1.1 W/(m K), representing a 104% increase. In addition, the porous film exhibits improved mechanical properties, the tensile strength increases to 6.9 MPa, and the elongation at break increases by 131%. The method adopted in this paper to control the enrichment of graphene in the pore walls during the preparation of honeycomb porous films by the phase inversion method can avoid the agglomeration of graphene and improve the overall performance of the porous graphene porous films.

Synergy between nanoplastics and benzo[a]pyrene promotes senescence by aggravating ferroptosis and impairing mitochondria integrity in Caenorhabditis elegans.

Micro-nano plastics have been reported as important carriers of polycyclic aromatic hydrocarbons (PAHs) for long-distance migration in the environment. However, the combined toxicity from long-term chronic exposure beyond the vehicle-release mechanism remains elusive. In this study, we investigated the synergistic action of Benzo[a]pyrene (BaP) and Polystyrene nanoparticles (PS) in Caenorhabditis elegans (C. elegans) as a combined exposure model with environmental concentrations. We found that the combined exposure to BaP and PS, as opposed to single exposures at low concentrations, significantly shortened the lifespan of C. elegans, leading to the occurrence of multiple senescence phenotypes. Multi-omics data indicated that the combined exposure to BaP and PS is associated with the disruption of glutathione homeostasis. Consequently, the accumulated reactive oxygen species (ROS) cannot be effectively cleared, which is highly correlated with mitochondrial dysfunction. Moreover, the increase in ROS promoted lipid peroxidation in C. elegans and downregulated Ferritin-1 (Ftn-1), resulting in ferroptosis and ultimately accelerating the aging process of C. elegans. Collectively, our study provides a new perspective to explain the long-term compound toxicity caused by BaP and PS at real-world exposure concentrations.

High-Performance Up-Conversion Photodetectors with Zero-Barrier Interconnection via Self-Assembled Surface Dipoles.

The performance of lead sulfide (PbS) quantum-dot-based up-conversion photodetectors is greatly limited owing to a large potential barrier at the interconnection layer between the photodetecting (PD) unit and light-emitting (LED) unit. Thus, very high driving voltage is required, rendering high energy consumption and poor working stability. By introducing azetidinium iodide (AzI) at the PD/LED interface, zero-barrier interconnection was achieved for the PbS-based infrared up-conversion photodetectors. The turn-on voltage under infrared illumination was greatly reduced to 1.2 V and a high photon-to-photon conversion efficiency (ηpp) of ∼3% was obtained at 3 V, showing a 10-fold enhancement compared to those previously reported devices. The mechanism for the regulation of interface energy level alignments was related to the self-assembly of the AzI dipole molecules, resulting from the van der Waals force between the S atoms in the ligands of PbS and the protonated H atoms around N atoms in AzI.

Decoding the research landscape of drug resistance and therapeutic approaches in head and neck cancer: a bibliometric analysis from 2000 to 2023.

Introduction: Head and neck cancer is one of the most common tumors worldwide. However, drug resistance in its treatment has become a major factor limiting the efficacy. This study aims to comprehensively understand the current status of research in this field. Methods: The study analyzes papers related to therapeutic resistance in head and neck cancer published between 2000 and 2023 in the Web of Science Core Collection To achieve the research objectives, we searched the WoSCC for research and review papers on therapeutic resistance in head and neck cancer from 2000 to 2023, screened the English literature, and analyzed the research hotspots, academic collaborations, and trends in detail using tools such as Citespace, SCImago Graphica, and VOS viewer. Results: This study summarizes 787 head and neck cancer treatment resistance publications from WoSCC. The analysis showed that China and the United States are the major contributors in this field, and Grandis Jennifer R and Yang Jai-Sing are the key scholars. Keyword analysis showed that "cisplatin resistance" is a continuing focus of attention, while "Metastasis" and "Ferroptosis" may be emerging research hotspots. Literature clustering analysis pointed out that "Ferroptosis", "Immunotherapy" and "ERK signaling" were the recent hotspots that received extensive attention and citations. Finally, we discuss the current status and challenges in drug-resistant therapies for head and neck cancer. Conclusion: This study is the first comprehensive bibliometric analysis of drug resistance in head and neck cancer. Reveals current trends and helps researchers grasp cutting-edge hotspots in the field.

Dithiophosphinylation of Allenyl Acetates: Access to 1,2-Bis(diphenylphosphino)ethane-Type Bidentate Ligands.

1,2-Bis(diphenylphosphino)ethanes (DPPEs) are versatile and immensely important ligands in transition metal catalysts. Here we report the dithiophosphinylation of readily available allenyl acetates to give DPPEs in high yields and regioselectivity. This protocol features a broad substrate scope and mild conditions, avoiding the use of transition metals and air-sensitive sources of phosphorus. Mechanism studies indicate that the reaction was accomplished via an SN2'-type addition-elimination followed by a 1,4-addition step.

[Integrated Analysis of Soil Organic Matter Molecular Composition Changes Under Different Land Uses].

The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.

Association of Neutrophil-to-Lymphocyte Ratio With All-Cause Mortality in the Elderly Population in China: A Retrospective Cohort Study.

Neutrophil-to-lymphocyte ratio (NLR) is an emerging systemic inflammation marker associated with disease progression and mortality in patients. However, there is limited research on the predictive value of NLR in the general population. This study aimed to investigate the relationship between NLR and all-cause mortality in an elderly Chinese population. A retrospective cohort study was conducted based on health examination in a community in Shanghai, China, between 2015 and 2020. Among 6364 participants (aged ≥ 55 years), a total of 169 (2.66%) participants died during a median follow-up period of 5.37 years. The median NLR was 1.63. Multivariate analysis revealed that the upper 2 quartiles of NLR were positively associated with all-cause mortality (Q3 vs Q1: hazard ratio [HR] = 1.82; Q4 vs Q1: HR = 2.22). The stratified and interaction analyses showed that age, sex, body mass index (BMI), history of diabetes, or history of hypertension did not significantly modify the association between NLR and all-cause mortality. Elevated NLR was independently associated with an increased risk of all-cause mortality in the elderly Chinese population.

Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway.

Colorectal cancer (CRC) is the third most common tumor, with an increasing number of deaths worldwide each year. Tremendous advances in the diagnosis and treatment of CRC have significantly improved the outcomes for CRC patients. Additionally, accumulating evidence has hinted the relationship between acidic nuclear phosphoprotein 32 family member E (ANP32E) and cancer progression. But the role of ANP32E in CRC remains unclear. In our study, through TCGA database, it was demonstrated that the expression of ANP32E was enhanced in COAD tissues (n = 286). In addition, the mRNA and protein expression of ANP32E was also confirmed to be upregulated in CRC cell lines. Further investigation uncovered that knockdown of ANP32E suppressed cell proliferation and glycolysis, and facilitated cell apoptosis in CRC. Moreover, inhibition of ANP32E inhibited the AKT/mTOR pathway. Through rescue assays, we discovered that the reduced cell proliferation, glycolysis and the enhanced cell apoptosis mediated by ANP32E repression was reversed by SC79 treatment. In summary, ANP32E aggravated the growth and glycolysis of CRC cells by stimulating the AKT/mTOR pathway. This finding suggested that the ANP32E has the potential to be explored as a novel biomarker for CRC treatment.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Electrochemical biosensing platform based on AuNWs/rGO-CMC-PEDOT:PSS composite for the detection of superoxide anion released from living cells.

Detection of superoxide anion (O2·-) levels holds significant importance for the diagnosis and even clinical treatments of oxidative stress-related diseases. Herein, we prepared a composite electrode material to encapsulate copper-zinc superoxide dismutase (SOD1) for biosensing of O2·-. The sensing material consists of gold nanowires (AuNWs), reduced graphene oxide (rGO), carboxymethyl cellulose (CMC) and PEDOT:PSS. CMC provides abundant -COOH to bind SOD1, with a high adsorption coverage of 1.499 × 10-9 mol cm-2 on the sensor surface. rGO and PEDOT endow the composite with significant conductivity, whereas PSS has antifouling capability. Moreover, AuNWs exhibit excellent electrical conductivity and a high aspect ratio, which promotes electron transfer, and ultimately enhances the catalytic performance of the enzyme. Meanwhile, SOD1(Cu2+) catalyzes the dismutation of O2·- to O2 and H2O2, and H2O2 is then electrochemically oxidized to generate amperometric signals for determination of O2·-. The sensor demonstrates outstanding detection performance for O2·- with a low detection limit of 2.52 nM, and two dynamic ranges (14.30 nM-1.34 µM and 1.34 µM-42.97 µM) with corresponding sensitivity of 0.479 and 0.052 µA µM-1cm-2, respectively. Additionally, the calculated apparent Michaelis constant (Kmapp) of 1.804 µM for SOD1 demonstrates the outstanding catalytic activity and the surface-immobilized enzyme's substrate affinity. Furthermore, the sensor shows the capability to dynamically detect the level of O2·- released from living HepG2 cells. This study provides an inovative design to obtain a biocompatible electrochemical sensing platform with plenty of immobilization sites for biomolecules, large surface area, high conductivity and flexibility.

An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza.

Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a standalone vaccine, intranasal immunization with AdC68-HATRBD induced comprehensive and potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, and memory T cells, which protected the mice from BA.5.2 and pandemic H1N1 infections. When used as a heterologous booster, AdC68-HATRBD markedly improved the protective immune response of the licensed SARS-CoV-2 or influenza vaccine. Therefore, whether administered intranasally as a standalone or booster vaccine, this combination vaccine is a valuable strategy to enhance the overall vaccine efficacy by inducing robust systemic and mucosal immune responses, thereby conferring dual lines of immunological defenses for these two viruses.

Cytoskeletal Protein 4.1R in Health and Diseases.

The protein 4.1R is an essential component of the erythrocyte membrane skeleton, serving as a key structural element and contributing to the regulation of the membrane's physical properties, including mechanical stability and deformability, through its interaction with spectrin-actin. Recent research has uncovered additional roles of 4.1R beyond its function as a linker between the plasma membrane and the membrane skeleton. It has been found to play a crucial role in various biological processes, such as cell fate determination, cell cycle regulation, cell proliferation, and cell motility. Additionally, 4.1R has been implicated in cancer, with numerous studies demonstrating its potential as a diagnostic and prognostic biomarker for tumors. In this review, we provide an updated overview of the gene and protein structure of 4.1R, as well as its cellular functions in both physiological and pathological contexts.

Protein 4.1R regulates M1 macrophages polarization via glycolysis, alleviating sepsis-induced liver injury in mice.

Acute liver injury (ALI) is a common clinical disease caused by sepsis, metabolic syndrome, hepatitis virus. Macrophage plays an important role in the development of ALI, which is characterized by polarization and inflammatory regulation. The polarization process of macrophages is related to membrane binding proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in cell activation and cytokine secretion. However, whether protein 4.1R is involved in regulating macrophage polarization and inflammation-induced liver injury remains unknown. In this study, protein 4.1R is identified with the special effect on macrophage M1 polarization. And it is further demonstrated that protein 4.1R deficiency significantly enhance glycolytic metabolism. Mechanistically, the regulation of protein 4.1R on pyruvate kinase M2 (PKM2) plays a key role in glycolysis metabolism. In addition, we found that protein 4.1R directly interacts with toll-like receptor 4 (TLR4), inhibits the activation of the AKT/HIF-1α signaling pathway. In conclusion, protein 4.1R targets HIF-1α mediated glycolysis regulates M1 macrophage polarization, indicating that protein 4.1R is a candidate for regulating macrophage mediated inflammatory response. In conclusion, we have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy. We have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy.

Insight into the Mechanism Underlying the Reduction of Digestibility and IgG/IgE Binding Ability in Ovalbumin during Different High-Temperature Conduction Modes-Induced Glycation.

Effects of different high-temperature conduction modes [high-temperature air conduction (HAC), high-temperature contact conduction (HCC), high-temperature steam conduction (HSC)]-induced glycation on the digestibility and IgG/IgE-binding ability of ovalbumin (OVA) were studied and the mechanisms were investigated. The conformation in OVA-HSC showed minimal structural changes based on circular dichroism, fluorescence, and ultraviolet spectroscopy. The degree of hydrolysis analysis indicated that glycated OVA was more resistant to digestive enzymes. Liquid chromatography-Orbitrap mass spectrometry identified 11, 14, and 15 glycation sites in OVA-HAC, OVA-HCC, and OVA-HSC, respectively. The IgG/IgE-binding ability of OVA was reduced during glycation and digestion, and the interactions among glycation, allergenicity, and digestibility were further investigated. Glycation sites masked the IgG/IgE epitopes resulting in a reduction in allergenicity. Digestion enzymes destroyed the IgG/IgE epitopes thus reducing allergenicity. Meanwhile, the glycation site in proximity to the digestion site of pepsin was observed to cause a reduction in digestibility.