Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis. However, little is known about the pathogenesis and biomarkers of COVID-19. Here, we profiled host responses to COVID-19 by performing plasma proteomics of a cohort of COVID-19 patients, including non-survivors and survivors recovered from mild or severe symptoms, and uncovered numerous COVID-19-associated alterations of plasma proteins. We developed a machine-learning-based pipeline to identify 11 proteins as biomarkers and a set of biomarker combinations, which were validated by an independent cohort and accurately distinguished and predicted COVID-19 outcomes. Some of the biomarkers were further validated by enzyme-linked immunosorbent assay (ELISA) using a larger cohort. These markedly altered proteins, including the biomarkers, mediate pathophysiological pathways, such as immune or inflammatory responses, platelet degranulation and coagulation, and metabolism, that likely contribute to the pathogenesis. Our findings provide valuable knowledge about COVID-19 biomarkers and shed light on the pathogenesis and potential therapeutic targets of COVID-19.

Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry.

Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry-based high-throughput medicinal chemistry (HTMC) strategy. A combination of SuFEx- and amide-based lead molecule diversification and structure-guided design led to identification and validation of ultrapotent influenza fusion inhibitors with subnanomolar EC50 cellular antiviral activity against several influenza A group 1 strains. X-ray structures of six of these compounds with HA indicate that the appended moieties occupy additional pockets on the HA surface and increase the binding interaction, where the accumulation of several polar interactions also contributes to the improved affinity. The compounds here represent the most potent HA small-molecule inhibitors to date. Our divergent HTMC platform is therefore a powerful, rapid, and cost-effective approach to develop bioactive chemical probes and drug-like candidates against viral targets.

A potyvirus provides an efficient viral vector for gene expression and functional studies in Asteraceae plants.

Plant virus-derived vectors are rapid and cost-effective for protein expression and gene functional studies in plants, particularly for species that are difficult to genetically transform. However, few efficient viral vectors are available for functional studies in Asteraceae plants. Here, we identified a potyvirus named zinnia mild mottle virus (ZiMMV) from common zinnia (Zinnia elegans Jacq.) through next-generation sequencing. Using a yeast homologous recombination strategy, we established a full-length infectious cDNA clone of ZiMMV under the control of the cauliflower mosaic virus 35S promoter. Furthermore, we developed an efficient expression vector based on ZiMMV for the persistent and abundant expression of foreign proteins in the leaf, stem, root, and flower tissues with mild symptoms during viral infection in common zinnia. We showed that the ZiMMV-based vector can express ZeMYB9, which encodes a transcript factor inducing dark red speckles in leaves and flowers. Additionally, the expression of a gibberellic acid (GA) biosynthesis gene from the ZiMMV vector substantially accelerated plant height growth, offering a rapid and cost-effective method. In summary, our work provides a powerful tool for gene expression, functional studies, and genetic improvement of horticultural traits in Asteraceae plant hosts.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients.

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.

Switchable targeting of solid tumors by BsCAR T cells.

The development of chimeric antigen receptor (CAR) T cell therapy has become a critical milestone in modern oncotherapy. Despite the remarkable in vitro effectiveness, the problem of safety and efficacy of CAR T cell therapy against solid tumors is challenged by the lack of tumor-specific antigens required to avoid on-target off-tumor effects. Spatially separating the cytotoxic function of CAR T cells from tumor antigen recognition provided by protein mediators allows for the precise control of CAR T cell cytotoxicity. Here, the high affinity and capability of the bacterial toxin-antitoxin barnase-barstar system were adopted to guide CAR T cells to solid tumors. The complementary modules based on (1) ankyrin repeat (DARPin)-barnase proteins and (2) barstar-based CAR (BsCAR) were designed to provide switchable targeting to tumor cells. The alteration of the DARPin-barnase switches enabled the targeting of different tumor antigens with a single BsCAR. A gradual increase in cytokine release and tunable BsCAR T cell cytotoxicity was achieved by varying DARPin-barnase loads. Switchable BsCAR T cell therapy was able to eradicate the HER2+ ductal carcinoma in vivo. Guiding BsCAR T cells by DARPin-barnase switches provides a universal approach for a controlled multitargeted adoptive immunotherapy.

Electric Tuning of Vortex Ratchet Effect in NbSe2.

Inversion symmetry breaking has played an important role in recent discoveries of nonreciprocal charge transport. Niobium diselenide, for example, lacks an inversion center in the monolayer form and can host prominent nonreciprocal transport property. Here, however, we observe a nonreciprocal transport signal in the second-harmonic channel of bulk-like NbSe2, in which inversion symmetry of the lattice seems preserved. The second-harmonic signal occurs along different in-plane current orientations and appears not only in the vortex-liquid regime but also even in the superconducting fluctuation regime without an applied magnetic field. By adding a direct current (DC) bias, we quantify the symmetry breaking effect in the vortex-liquid regime. The DC bias also suggests that the rectification effect at the contacts may account for the seemingly nonreciprocal transport at zero magnetic field. Our results demonstrate that DC biasing is a useful knob for addressing nonreciprocal charge transport in a wide range of materials.

Unveiling the Anomalous Hall Response of the Magnetic Structure Changes in the Epitaxial MnBi2Te4 Films.

Recently discovered as an intrinsic antiferromagnetic topological insulator, MnBi2Te4 has attracted tremendous research interest, as it provides an ideal platform to explore the interplay between topological and magnetic orders. MnBi2Te4 displays distinct exotic topological phases that are inextricably linked to the different magnetic structures of the material. In this study, we conducted electrical transport measurements and systematically investigated the anomalous Hall response of epitaxial MnBi2Te4 films when subjected to an external magnetic field sweep, revealing the different magnetic structures stemming from the interplay of applied fields and the material's intrinsic antiferromagnetic (AFM) ordering. Our results demonstrate that the nonsquare anomalous Hall loop is a consequence of the distinct reversal processes within individual septuple layers. These findings shed light on the intricate magnetic structures in MnBi2Te4 and related materials, offering insights into understanding their transport properties and facilitating the implementation of AFM topological electronics.

Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.

Integrated Catalyst-Substrate Electrodes for Electrochemical Water Splitting: A Review on Dimensional Engineering Strategy.

Water splitting (or, water electrolysis) is considered as a promising approach to produce green hydrogen and relieve the ever-increasing energy consumption as well as the accompanied environmental impact. Development of high-efficiency, low-cost practical water-splitting systems demands elegant design and fabrication of catalyst-loaded electrodes with both high activity and long-life time. To this end, dimensional engineering strategies, which effectively tune the microstructure and activity of electrodes as well as the electrochemical kinetics, play an important role and have been extensively reported over the past years. Here, a type of most investigated electrode configurations is reviewed, combining particulate catalysts with 3D porous substrates (aerogels, metal foams, hydrogels, etc.), which offer special advantages in the field of water splitting. It is analyzed the design principles, structural and interfacial characteristics, and performance of particle-3D substrate electrode systems including overpotential, cycle life, and the underlying mechanism toward improved catalytic properties. In particular, it is also categorized the catalysts as different dimensional particles, and show the importance of building hybrid composite electrodes by dimensional control and engineering. Finally, present challenges and possible research directions toward low-cost high-efficiency water splitting and hydrogen production is discussed.

A distributed data processing scheme based on Hadoop for synchrotron radiation experiments.

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

Aquaporin-4 Antibody Dynamics and Relapse Risk in Seropositive Neuromyelitis Optica Spectrum Disorder Treated with Immunosuppressants.

OBJECTIVE: To investigate aquaporin-4 antibody (AQP4-IgG) dynamics and relapse risk in patients with seropositive neuromyelitis optica spectrum disorder treated with immunosuppressants. METHODS: This observational cohort study with prospectively collected data included 400 neuromyelitis optica spectrum disorder patients seropositive for AQP4-IgG and treated with immunosuppressants. Serum AQP4-IgG was detected by fixed cell-based assay every 6 months. RESULTS: After treatment with immunosuppressants, 128 patients became AQP4-IgG seronegative. The median time to become seronegative for 400 patients was 76.4 months (61.4 months, NA). Among those patients with negative change of AQP4-IgG, the mean annualized relapse rate significantly decreased after patients became seronegative (0.20 vs 0.77, p < 0.001), and a positive correlation was observed between time to become seronegative and relapse (OR 1.018, 95% CI 1.001-1.035, p < 0.05). Independent risk factors for AQP4-IgG becoming seronegative were older age at onset, initiation of immunosuppressants at onset, and shorter disease duration before maintenance therapy. Independent risk factors for relapse included younger age (≤46.4 years) at onset, poly-system involvement in the first attack, and unchanged or increased AQP4-IgG titer. The relapse risk was not associated with sex, combination with connective tissue disease, seropositivity for systemic autoimmune antibodies, or incomplete recovery from the first attack. INTERPRETATION: Patients with younger age at onset, poly-system involvement in the first attack, and unchanged or increased titer of AQP4-IgG are most likely to experience relapse under treatment with immunosuppressants. Time to AQP4-IgG becoming seronegative and change of AQP4-IgG titer may become the surrogate efficacy biomarkers in clinical trials. ANN NEUROL 2023;93:1069-1081.

Surface Activity, Wettability, and Aggregation Behavior of Ecofriendly Fluorocarbon Surfactant Based on Double Perfluorinated Branched Short Chains.

This article reports the synthesis of a novel sulfonated fluorocarbon surfactant (SFDC) containing double C6 perfluorinated branched short chains and compares its surface properties with a similar structured compound (SFDC-L) in solutions. The critical micelle concentration (CMC) and the corresponding surface tension (γCMC) of SFDC aqueous solution are 9.77 × 10-3 mmol/L and 22.15 mN/m, respectively, indicating that SFDC has excellent surface properties. Besides, the addition of n-hexyltrimethylammonium bromide (HTAB) could further enhance the surface properties of SFDC. Meanwhile, the micellization, aggregation behavior, wettability, and adsorption at the air-water interface of SFDC and SFDC/HTAB mixture aqueous solutions are systematically investigated. Both SFDC and SFDC/HTAB show excellent wettability at low concentrations. The aggregation of SFDC and SFDC/HTAB mixtures in aqueous solution could be clearly seen as vesicles and rod-like micelles on TEM micrographs.

Brigatinib combined with cetuximab in the fifth-line treatment of non-small cell lung cancer with EGFR p.C797S mutation in critically ill patients: a report of two cases and literature review.

For critically ill patients with non-small cell lung cancer (NSCLC) in need of life-saving treatment, there is currently no reported evidence regarding the use of medication specifically targeting epidermal growth factor receptor ( EGFR ) p.C797S mutation, which is known to cause resistance to third-generation tyrosine kinase inhibitors (TKIs). Our report aims to investigate and explore treatment strategies to overcome resistance associated with EGFR p.C797S mutation in order to provide potential therapeutic options for these patients. Here, we reported two cases with NSCLC who initially harbored an EGFR -sensitive mutation and were both treated with osimertinib, a third-generation TKI. Next-generation sequencing tests conducted prior to the initiation of fifth-line therapy in critically ill patients revealed the presence of EGFR p.C797S mutations in both patients, suggesting acquired resistance. In the course of fifth-line therapy, the administration of a combination of brigatinib and cetuximab proved vital in saving critically ill patients, moderately extending their overall survival period. Our findings suggested that a combined regimen of brigatinib and cetuximab could serve as a potentially life-saving therapeutic strategy for critically ill patients with NSCLC, particularly those demonstrating EGFR p.C797S-mediated resistance. Further studies, however, are required to validate and expand upon these promising findings.

Associations of pyrethroid exposure with bone mineral density and osteopenia in adults.

INTRODUCTION: This study was to investigate the correlations between pyrethroid exposure and bone mineral density (BMD) and osteopenia. MATERIALS AND METHODS: This cross-sectional study included 1389 participants over 50 years of age drawn from the 2007-2010 and 2013-2014 National Health and Nutrition Examination Survey (NHANES). Three pyrethroid metabolites, 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid (trans-DCCA), and 4-fluoro-3-phenoxybenzoic acid (4-F-3PBA) were used as indicators of pyrethroid exposure. Low BMD was defined as T-score < - 1.0, including osteopenia. Weighted multivariable linear regression analysis or logistic regression analysis was utilized to evaluate the correlation between pyrethroid exposure and BMD and low BMD. Bayesian kernel machine regression (BKMR) model was utilized to analyze the correlation between pyrethroids mixed exposure and low BMD. RESULTS: There were 648 (48.41%) patients with low BMD. In individual pyrethroid metabolite analysis, both tertile 2 and tertile 3 of trans-DCCA were negatively related to total femur, femur neck, and total spine BMD [coefficient (ß) = - 0.041 to - 0.028; all P < 0.05]. Both tertile 2 and tertile 3 of 4-F-3PBA were negatively related to total femur BMD (P < 0.05). Only tertile 2 [odds ratio (OR) = 1.63; 95% CI = 1.07, 2.48] and tertile 3 (OR = 1.65; 95% CI = 1.10, 2.50) of trans-DCCA was correlated with an increased risk of low BMD. The BKMR analysis indicated that there was a positive tendency between mixed pyrethroids exposure and low BMD. CONCLUSION: In conclusion, pyrethroids exposure was negatively correlated with BMD levels, and the associations of pyrethroids with BMD and low BMD varied by specific pyrethroids, pyrethroid concentrations, and bone sites.

One- and Two-Photon Photophysical Properties, Ultrafast Dynamics, and DFT Study of Three Modified Zinc Phthalocyanines.

As two-photon absorption (TPA) materials, phthalocyanine molecules have promising application prospects due to their large TPA absorption cross-section, high third-order nonlinear optical susceptibility, and ultrafast response characteristics. In this work, optical properties and the ultrafast response of three modified zinc phthalocyanine molecules (P-HPcZn, Pc-P-Pc, and (DR1)4PcZn) were analyzed. No obvious side-shoulder absorption peaks in the Q-band can be observed from the steady-state absorption spectra of the three molecules, confirming the lack of aggregation products in the solutions of our measurement. Open-aperture Z-scan results show relatively large TPA cross-section values of 136.4 and 55.3 GM for Pc-P-Pc and (DR1)4PcZn, respectively. The nonlinear optical results show that the absorption process observed under the excitation of femtosecond pulses is a reverse saturable absorption (RSA) mechanism. Up-conversion fluorescence spectra of (DR1)4PcZn in THF solution indicate that the fluorescence emission mechanism is TPA. In the study of ultrafast dynamics, the transient absorption spectra were investigated and the decay lifetime of the dynamic traces corresponding to some representative probe wavelengths was obtained through data fitting with a multi-exponential function. Finally, the charge transfer and excited state properties of the modified zinc phthalocyanine molecules were discussed in depth by the DFT method. The energy gaps of P-HPcZn, Pc-P-Pc, and (DR1)4PcZn are 2.16, 1.39, and 2.13 eV, respectively. The results indicate that the Pc-P-Pc of donor-acceptor-donor (D-A-D) structure has the smallest energy gap as well as the best charge transfer properties.

CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification.

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

Comprehensive Analysis and Experimental Validation of the Parkinson's Disease Lysosomal Gene ACP2 and Pan-cancer.

The pivotal role of lysosomal function in preserving neuronal homeostasis is recognized, with its dysfunction being implicated in neurodegenerative processes, notably in Parkinson's disease (PD). Yet, the molecular underpinnings of lysosome-related genes (LRGs) in the context of PD remain partially elucidated. We collected RNA-seq data from the brain substantia nigra of 30 PD patients and 20 normal subjects from the GEO database. We obtained molecular classification clusters from the screened lysosomal expression patterns. The lysosome-related diagnostic model of Parkinson's disease was constructed by XGBoost and Random Forest. And we validated the expression patterns of signature LRGs in the diagnostic model by constructing a PD rat model. Finally, the linkage between PD and cancer through signature genes was explored. The expression patterns of the 33 LRGs screened can be divided into two groups of PD samples, enabling exploration of the variance in biological processes and immune elements. Cluster A had a higher disease severity. Subsequently, critical genes were sieved through the application of machine learning methodologies culminating in the identification of two intersecting feature genes (ACP2 and LRP2). A PD risk prediction model was constructed grounded on these signature genes. The model's validity was assessed through nomogram evaluation, which demonstrated robust confidence validity. Then we analyzed the correlation analysis, immune in-filtration, biological function, and rat expression validation of the two genes with common pathogenic genes in Parkinson's disease, indicating that these two genes play an important role in the pathogenesis of PD. We then selected ACP2, which had a significant immune infiltration correlation, as the entry gene for the pan-cancer analysis. The pan-cancer analysis revealed that ACP2 has profound associations with prognostic indicators, immune infiltration, and tumor-related regulatory processes across various neoplasms, suggesting its potential as a therapeutic target in a range of human diseases, including PD and cancers. Our study comprehensively analyzed the molecular grouping of LRGs expression patterns in Parkinson's disease, and the disease progression was more severe in cluster A. And the PD diagnosis model related to LRGs is constructed. Finally, ACP2 is a potential target for the relationship between Parkinson's disease and tumor.

Molecular cloning and functional characterization of mitochondrial RNA splicing 2 in fish Megalobrama amblycephala, and its potential roles in magnesium homeostasis and mitochondrial function.

Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg2+) channel located in the inner mitochondrial membrane, thereby mediating the Mg2+ influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.

The health benefits of dietary polyphenols on pediatric intestinal diseases: Mechanism of action, clinical evidence and future research progress.

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.