Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

The biological functions and metabolic pathways of valine in swine

Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.

Biological function of resveratrol and its application in animal production:a review

With the prohibition of antibiotics in feed,plant functional substances have been widely studied as feed additives.Resveratrol,a natural stilbene,and a non-flavonoid polyphenol found in plants,possesses antioxidant,anti-inflammatory,and metabolic regulatory features.Resveratrol generated intense scientific and public interest,primarily due to its widely reported ability to prevent cancer,delay aging and alleviate related metabolic diseases.Recently,resveratrol has been studied and applied as a feed additive in animal production.This review focuses on the outline of the absorption and metabolism and biological functions of resveratrol and summarizes the application of dietary resveratrol in animal production up to the present,including pigs,poultry,and ruminants.In pigs,dietary resveratrol improved intestinal health,mitochondrial function,meat quality,and more.In poultry,studies have shown that dietary resveratrol improves growth performance and meat and egg quality and alleviates heat stress induced adverse effects.There are few studies on dietary resveratrol in ruminants;however previous studies have indicated that dietary resveratrol increases nutrient digestibility and reduces methane emissions in sheep.It is hoped that this review could provide a specific theoretical basis and research ideas for the research and application of resveratrol.

Chemical constituents,biological functions and pharmacological effects for comprehensive utilization of Eucommia ulmoides Oliver

Eucommia ulmoides Oliver is a native plant and valuable tonic Chinese medicine in China with a long history,great economic value and comprehensive development potential.Traditionally,the comprehensive utilization rate of E.ulmoides Oliv.is still very low,only bark has been used as medicine and other parts of Eucommia ulmoides Oliv.cannot be fully utilized,even the leaves have been well utilized in food products in Japan in the past decades.In order to improve the comprehensive utilization efficiency of E.ulmoides Oliv.,in this review,we summarized the varieties and contents of main active compounds,biological functions and pharmacological effects in different parts of E.ulmoides Oliv.The findings suggest that other parts of E.ulmoides Oliv.could replace the bark of E.ulmoides Oliv.to some extent besides of their respective applications.The unique and extensive physiological functions between different parts of E.ulmoides Oliv.indicate that the comprehensive utilization of E.ulmoides Oliv.has a wide space to develop,which is also an effective way to protect E.ulmoides Oliv.resources and improve its the utilization rate.

The biological function of type I receptors of bone morphogenetic protein in bone

Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.

Chemical and biological flocculation process to treat municipal sewage and analysis of biological function

The pilot scale experimental apparatus and the procedure of the chemical and biological flocculation process to verify the feasibility in treating Shanghai municipal sewage were introduced in this paper. In addition, the biological function of the process was discussed. The results of optimal running showed that in the reaction tank, the concentration of mixed liquor suspended solid(MLSS) was 2 g/L, hydraulic retention time(HRT) was 35 min, dosage of liquid polyaluminium chloride(PAC) was 60 mg/L, and the concentration of polyacrylamide(PAM) was 0 5 mg/L. The effluent average concentrations of COD Cr , TP, SS and BOD 5 were 50 mg/L, 0 62 mg/L, 18 mg/L, and 17 mg/L, respectively. These were better than the designed demand. In addition, the existence of biological degradation in this system was proven by several methods. The removal efficiencies of the chemical and biological flocculation process were 20% higher than that of the chemical flocculation process above at the same coagulant dosage. The treatment process under different situations was evaluated on a pilot scale experiment, and the results provided magnificent parameters and optimal condition for future operation of the plant.

MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells

BACKGROUND Colorectal cancer(CRC)is one of the most common malignancies worldwide.AIM To explore the expression of microRNA miR-19a-3p and Forkhead box F2(FOXF2)in patients with CRC and the relevant mechanisms.METHODS Sixty-two CRC patients admitted to the hospital were enrolled into the study group,and sixty healthy people from the same period were assigned to the control group.Elbow venous blood was sampled from the patients and healthy individuals,and blood serum was saved for later analysis.MiR-19a-3p mimics,miR-19a-3p inhibitor,miR-negative control,small interfering-FOXF2,and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells.Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells,and western blot(WB)analysis was conducted to evaluate the levels of FOXF2,glycogen synthase kinase 3 beta(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),β-catenin,p-β-catenin,α-catenin,Ncadherin,E-cadherin,and vimentin.The MTT,Transwell,and wound healing assays were applied to analyze cell proliferation,invasion,and migration,respectively,and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2.RESULTS The patients showed high serum levels of miR-19a-3p and low levels of FOXF2,and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8.MiR-19a-3p and FOXF2 were related to sex,tumor size,age,tumor-nodemetastasis staging,lymph node metastasis,and differentiation of CRC patients.Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelialmesenchymal transition,invasion,migration,and proliferation of cells.WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3β,β-catenin,N-cadherin,and vimentin;and increased the levels of GSK-3β,p-β-catenin,α-catenin,and Ecadherin.The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2.In addition,a rescue experiment revealed that there were no differences in cell proliferation,invasion,and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group.CONCLUSION Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/β-catenin signaling pathway,thereby affecting the epithelial-mesenchymal transition,proliferation,invasion,and migration of cells.Thus,miR-19a-3p is likely to be a therapeutic target in CRC.

Over-expression of LRIG1 Suppresses Biological Function of Pituitary Adenoma via Attenuation of PI3K/AKT and Ras/Raf/ERK Pathways In Vivo and In Vitro

Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor（EGFR） can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1（ LRIG1）, a negative mediated gene of Erb B receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.

Biological Function of REE in Plants & Microbes

Rare earth elements （REE） and their compounds years. The bioinorganic chemical research of REE during the are widely applied in agronomic and medical fields for many past few years indicates that REE play important roles in the promotion of photosynthetic rate as well as root absorption, regulation of hormone and nitrogen metabolism, and suppression of microbes, etc. The metallic or non-metallic targets of key biomolecule in various physiological processes can be chosen by REE for the chelation or replacement, which enables REE to regulate the biological functions or behaviors of those biomolecule and consequently leads to significant embodiment of biological function of REE in plants and microbes. Overdose of REE, however, shows an inhibitory effect on living organisms. Therefore, this paper proposes two suggestions that will be available in the extension of full use of REE＇s biological function. One is to obey the dose law of REE and control REE concentrations within a safe range. The other is to further test the bioaccumulation and long-period influence of REE on organisms.

Effect of microRNA-143-3p-mediated CTNND1 on the biological function of lung cancer cells

Lung cancer poses a serious threat to human life with high incidence and miRNA is an important biomarkerin tumors. This study aimed to explore the effect of miR-143-3p on the biological function of lung cancer cells and theunderlying mechanism. Eighty-seven samples of lung cancer tissues and 81 samples of tumor-adjacent tissues from patients undergoing radical lung cancer surgery in our hospital were collected. The lung cancer cells and lung fibroblastcells (HFL-1) were purchased, and then miR-143-3p-mimics, miR-NC, si-CTNND1, and NC were transfected into A549 and PC-9 cells to establish cell models. MiR-143-3p and CTNND1 expression levels were measured by the qRT-PCR, Bax, Bcl-2, and CTNND1 expression levels by the Western Blot (WB), and cell proliferation, invasion, and apoptosis by the MTT assay, Transwell assay, and flow cytometry. Dual luciferase report assay was used to determinethe relationship between miR-143-3p and CTNND1. In this study, miR-143-3p was lowly expressed in lung cancer and CTNND1 was highly expressed in lung cancer. The overexpression of miR-143-3p inhibited cell proliferation and invasion, promoted cell apoptosis, significantly increased Bax protein expression, and decreased Bcl-2 protein expression. The inhibition of CTNND1 led to opposite biological characteristic in cells. The dual luciferase reporter assay demonstrated that miR-143-3p was a target region of CTNND1. Such results suggest that miR-143-3p can inhibitthe proliferation and invasion of lung cancer cells by regulating the expression of CTNND1 and promote the apoptosisof lung cancer cells, sott is expected to be a potential target for lung cancer.

Biological Function Research Progress of FABP5

The intracellular Fatty Acid Binding Proteins （FABPs） are a well-conserved family which functions as lipid chaperones. Recent findings also reveal that they are crucial mediators of lipid metabolism, cell growth and differentiation, cellular signaling and gene transcription. Ongoing studies are identifying the mechanistic complexity and vast biological diversity of different isoforms of FABPs. This paper introduced the biological function of FABP5 in inflammatory, metabolic diseases and milk fat synthesis.

Methylation reactions at dopaminergic nerve endings, serving as biological off-switches in managing dopaminergic functions

The mechanisms for the regulation of synaptic dopamine （DA） include its release from presynaptic vesicles, its interaction with post-synaptic and pre-synaptic DA receptors, the reuptake of DA, via dopamine transporter （DAT）, the diffusion of DA and its metabolism by mono-amine oxidase （MAO） and cate- chol-O-methyl transferase （COMT）. DA controls complex and specialized functions including, movements, behavior, mood, perception, reward, and more recently, neurogenesis （Popolo et al., 2004; Reimer et al., 2013） and neuroregeneration （Hoglinger et al., 2004; Yang et al., 2008）. These functions are varied and of high fidelity. Movement, as an example, requires regulatory mechanisms for initiating, stopping, slowing-down speed- ing-up, changing directions, for governing the relentless urges to move in the young and sedentariness in the old as well as in motor-freezing, catalepsy, tremor and stereotypy.

Proteomic and Functional Analyses of Outer Membrane Vesicles Secreted by Vibrio splendidus

Vibrio splendidus is an important opportunistic pathogen ubiquitously present in the marine environment,exhibiting virulence to a variety of cultured animals.The extracellular products secreted by V.splendidus are crucial to bacterial survival and virulence.In this study,the secretion of outer membrane vesicles(OMVs)by V.splendidus was determined,purified,and morphologically characterized.The protein composition of OMVs was analyzed by proteomic analysis.The results showed that approximately 120 proteins were contained in these OMVs,including outer membrane proteins,flagellins,ABC transporters,protease,and iron regulation proteins,etc.,which were involved in bacterial motility,formation of biofilms and the cell membrane components,and cellular localization based on their structural molecule activity,passive transmembrane transporter activity,channel activity,neurotransmitter receptor activity,extracellular ligand-gated ion channel activity,glutamate receptor activity,ligand-gated ion channel activity,and transmembrane signaling receptor activity.To explore the biological functions of OMVs in V.splendidus,the effects of OMVs on the bacterial adaption to iron limitation,antibiotic,and the coelomic fluid of the Apostichopus japonicus were confirmed.This study is the first time to show that V.splendidus secretes OMVs,and OMVs carry functional proteins that enhance bacterial survival under various stresses.

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

Recent Advances in Deciphering the Mechanisms and Biological Functions of DNA Demethylation

5-Methylcytosine (5mC) is a dynamic and reversible epigenetic modification in genomic DNA of higher eukaryotes.It has been well-established that the demethylation of 5mC occurs through the ten-eleven translocation (TET)-mediated oxidation of 5mC followed by thymine DNA glycosylase (TDG)-initiated base excision repair (BER).Recent findings also have identified an alternative pathway of DNA demethylation.In this pathway,TET enzymes directly oxidize 5mC to form 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC).These modified bases can undergo direct deformylation or decarboxylation,respectively.Additionally,DNA demethylation can also occur through the deamination of 5mC and 5hmC,resulting in the production of thymine and 5-hydroxymethyluracil (5hmU),respectively.Various DNA demethylation pathways possess critical functional implications and roles in biological processes.This Recent Advances article will focus on the studies of mechanisms and biological functions of DNA demethylation,shedding light on the reversible nature of the epigenetic modification of 5mC.

EjGASA6 promotes flowering and root elongation by enhancing gibberellin biosynthesis

The Gibberellic Acid-stimulated Arabidopsis(GASA)gene family is involved in the regulation of gene expression and plant growth,development,and stress responses.To investigate the function of loquat GASA genes in the growth and developmental regulation of plants,a loquat EjGASA6 gene homologous to Arabidopsis AtGASA6 was cloned.EjGASA6 expression was induced by gibberellin,and ectopic transgenic plants containing this gene exhibited earlier bloom and longer primary roots since these phenotypic characteristics are related to higher gibberellin content.Transcriptome analysis and qRT-PCR results showed that the expression levels of GA3ox1 and GA20ox1,which encode key enzymes in gibberellin biosynthesis,were significantly increased.Furthermore,we confirmed that EjGASA6 could promote the expression of GA20ox1 via the luciferase reporter system.Overall,our results suggest that EjGASA6 promotes blooming and main-root elongation by positively regulating gibberellin biosynthesis.These findings broaden our understanding of the role of GASAs in plant development and growth,and lay the groundwork for future research into the functions of EjGASA6 in regulating loquat growth and development.

Biological roles and potential clinical values of circular RNAs in gastrointestinal malignancies

Circular RNAs(circ RNAs),a class of endogenous RNA molecules,are produced by alternative splicing of precursor RNA and are covalently linked at the 5′and 3′ends.Recent studies have revealed that dysregulated circ RNAs are closely related to the occurrence and progression of gastrointestinal malignancies.Accumulating evidence indicates that circ RNAs,including circ PVT1,circ LARP4,circ-SFMBT2,cir-ITCH,circ RNA_100782,circ_100395,circ-DONSON,hsa_circ_0001368,circ NRIP1,circ FAT1(e2),circ CCDC66,circ SMARCA5,circ-ZNF652,and circ_0030235 play important roles in the proliferation,differentiation,invasion,and metastasis of cancer cells through a variety of mechanisms,such as acting as micro RNA sponges,interacting with RNA-binding proteins,regulating gene transcription and alternative splicing,and being translated into proteins.With the characteristics of high abundance,high stability,extensive functions,and certain tissue-,time-and diseasespecific expressions,circ RNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.

The diversity and potential function of endophytic bacteria isolated from Kobreasia capillifolia at alpine grasslands on the Tibetan Plateau, China

A total of 50 endophytic bacterial isolates were obtained from Kobreasia capillifolia at alpine grasslands in the Eastern Qilian Mountains on the Tibetan Plateau in China. Based on the sequencing and phylogenetic analysis of 16 S r DNA genes, all isolates phylogenetically related closely to Bacillus, Acinetobacter, Stenotrophomonas, Brevundimonas, Arthrobacter, Curtobacterium, Paenibacillus, Plantibacter, Promicromonospora, Serratia, and Microbacterium, among which Bacillus was the predominant genus（47.8% of the total number of endophytic isolates）. These isolates possessed different biological functions. In 50 endophytic bacteria, 42 isolates produced indole acetic acid（IAA） on King medium. There were seven isolates showing potency of mineral phosphate solubilization in Pikovaskaia＇s（PKO） liquid medium. Seven isolates exhibited antagonistic effect against Fusarium avenaceum, Colletotrichum coccodes and Phoma foveata. This was the first report on diversity and plant growth promotion of endophytic bacteria from K. capillifolia on alpine grassland in the Eastern Qilian Mountains, Chain. It is essential for revealing the relationship among plant, microorganism, and the special environment because the potential function of endophytic bacteria made a contribution to the interactions of plants and endophytic bacteria.

Structure and Function Analysis of Canine ZP3 Protein

To further study the biological function and mechanism of ZP3 in domestic canine （ CaMs lupu familiaris） , the coding sequence （CDS） of ZP3 gene was searched from NCBI database using bioinformatics method, and further transformed into protein sequence via MAGE software. The primary, secondary and terti- ary structure of protein was predicted with ExPASy, BLAST and DNA Star bioinformatics online software and program; the evolution and selected sites of ZP3 pro- tein extracted from 11 species were analyzed using PAML software; the conservation of ZP3 protein gene was analyzed with Predictprotein and Weblogo program; the tertiary structure of protein was edited by Python and PyMOL. The results showed that canine ZP3 gene encoded 426 amino acids, and the encoding product was a hydrophilic transmembrane protein with signal peptide; the 1 -23ra amino acids were signal peptide areas, and transmembrane domain distributed in the （x-helix area of the 386th -408th amino acids; four loci were affected by phosphorylation, and these phosphorylation sites might be associated with signal transduction ; there were nine protein binding sites on ZP domain; a high variation region was found in 325 -385 section of ZP3, and most of phosphorylation and selected amino acid sites were distributed in this area. This indicated that the area had experienced rapid evolution, suggesting that ZP domain and the high variation area might be in- volved in interaction of sperm and egg.

Exposure to Hyaluronan and Radon-Containing Water during the Treatment of Periodontal Pockets

Hyaluronic acid (HA) preparations have emerged as pivotal components in contemporary dentistry, gaining widespread recognition for their multifaceted roles in various biological functions. Extensive literature underscores the significance of HA in maintaining tissue water balance, fostering cell proliferation, promoting rapid cell migration, influencing cell differentiation during organism development, and facilitating tissue regeneration. Notably, HA’s interactions with cell surface receptors contribute to the viscosity of synovial fluid, activate the immune system, and enhance cartilage elasticity. Beyond these established functions, HA has also been investigated for its potential involvement in determining and studying the hormetic effects of radon water, adding a novel dimension to its applications in dental research. A thorough exploration of existing studies reveals a nuanced understanding of how HA interventions impact the outcomes of dental procedures. The comprehensive scope of these investigations allows for a more accurate assessment of the potential effectiveness of specific interventions and provides valuable insights into post-procedural prognoses for individual patients. This synthesis of literature serves as the foundation for elucidating the intricate interplay between HA, radon exposure, and their relevance in modern dental practices.