The role of prolactin/vasoinhibins in cardiovascular diseases

Prolactin(PRL)is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary.There are two main isoforms of PRL:23-kDa PRL(named full-l ength PRL)and vasoinhibins(including 5.6–18 kDa fragments).Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization,including endothelial cell proliferation and migration,protease production,and apoptosis.However,their effects on vascular function and cardiovascular diseases are different or even contrary.In addition to the structure,secretion regulation,and signal transduction of PRL/vasoinhibins,this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

Overexpression of miR390b promotes stem elongation and height growth in Populus

MicroRNA390(miR390)is involved in plant growth and development by down-regulating the expression of the downstream genes trans-acting short interfering RNA3(TAS3)and AUXIN RESPONSE FACTORs(ARFs).There is a scarcity of research on the involvement of the miR390-TAS3-ARFs pathway in the stem development of Populus.Here,differentially expressedmiRNAs during poplar stem development were screened by small RNA sequencing analysis,and a novel function of miR390b in stem development was revealed.Overexpression of miR390b(OE-miR390b)resulted in a large increase in the number of xylem fiber cells and a slight decrease in the cell length at the longitudinal axis.Overall increases in stem elongation and plant height were observed in the OE-miR390b plants.According to transcriptome sequencing results and transient co-expression analysis,TAS3.1 and TAS3.2 were identified as the target genes of miR390 in poplar and were negatively regulated by miR390 in the apex.The transcription levels of ARF3.2 and ARF4 were significantly repressed in OE-miR390b plants and strongly negatively correlatedwith the number of xylem fiber cells along the longitudinal axis.These findings indicate that the conserved miR390-TAS3-ARFs pathway in poplar is involved in stem elongation and plant height growth.

Circular RNAs in pulmonary hypertension:Emerging biological concepts and potential mechanism

Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circRNAs have been identified and further functional studies have been performed.It is known that circRNAs act as potential biomarkers,sponges for microRNAs(miRNAs)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circRNAs are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circRNAs are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circRNAs in the pathogenesis of PH.

Superconvergence Study of the Direct Discontinuous Galerkin Method and Its Variations for Diffusion Equations

In this paper,we apply the Fourier analysis technique to investigate superconvergence properties of the direct disontinuous Galerkin(DDG)method(Liu and Yan in SIAM J Numer Anal 47(1):475-698,2009),the DDG method with the interface correction(DDGIC)(Liu and Yan in Commun Comput Phys 8(3):541-564,2010),the symmetric DDG method(Vidden and Yan in Comput Math 31(6):638-662,2013),and the nonsymmetric DDG method(Yan in J Sci Comput 54(2):663-683,2013).We also include the study of the interior penalty DG(IPDG)method,due to its close relation to DDG methods.Error estimates are carried out for both P2 and P3 polynomial approximations.By investigating the quantitative errors at the Lobatto points,we show that the DDGIC and symmetric DDG methods are superior,in the sense of obtaining(k+2)th superconvergence orders for both P2 and P3 approximations.Superconvergence order of(k+2)is also observed for the IPDG method with P3 polynomial approximations.The errors are sensitive to the choice of the numerical flux coefficient for even degree P2 approximations,but are not for odd degree P3 approxi-mations.Numerical experiments are carried out at the same time and the numerical errors match well with the analytically estimated errors.

Heavy metals potentially drive co-selection of antibiotic resistance genes by shifting soil bacterial communities in paddy soils along the middle and lower Yangtze River

Heavy metals(HMs)and antibiotic resistance have become serious environmental problems affecting soil and human health.Soil microorganisms play key roles in pollutant degradation and biogeochemical cycling processes;however,the interactions among HMs,soil microbial communities,and antibiotic resistance genes(ARGs)in agricultural soils remain unclear.Using quantitative real-time polymerase chain reaction and NovaSeq sequencing,we evaluated heavy metal contents,abundances of ARGs,soil bacterial community structure and functions,and their correlations in paddy soils at 43 sampling sites along the middle and lower reaches of the Yangtze River,central and eastern China.Our results showed the co-occurrence of HMs,ARGs,and HM resistance genes across all paddy soils.Additionally,significant positive associations were detected between HMs and resistance genes.Cadmium,czcA,and int1 were positively correlated with bacterial community diversity.The Mantel test showed that bacterial community composition and functions were significantly associated with HMs and resistance genes,such as Cd,Cr,Zn,copA,czcA,int1,and sul1.Moreover,HMs and ARGs were the major factors shaping soil bacterial communities;thus,HMs triggered proliferation of HM and antibiotic resistances by influencing the mobile genetic element(int1)and soil microbial communities.Our study revealed that HMs potentially drive the co-selection of ARGs by shifting soil bacterial community structure and functions,thereby increasing the potential risks to human health as well as ecological environment in the paddy soils along the middle and lower reaches of the Yangtze River.

The haplotype-resolved genome assembly of autotetraploid rhubarb Rheum officinale provides insights into its genome evolution and massive accumulation of anthraquinones

Rheum officinale,a member of the Polygonaceae family,is an important medicinal plant that is widely used in traditional Chinese medicine.Here,we report a 7.68-Gb chromosome-scale assembly of R.officinale with a contig N50 of 3.47 Mb,which was clustered into 44 chromosomes across four homologous groups.Comparative genomics analysis revealed that transposable elements have made a significant contribution to its genome evolution,gene copy number variation,and gene regulation and expression,particularly of genes involved in metabolite biosynthesis,stress resistance,and root development.We placed the recent autotetraploidization of R.officinale at~0.58 mya and analyzed the genomic features of its homol-ogous chromosomes.Although no dominant monoploid genomes were observed at the overall expression level,numerous allele-differentially-expressed genes were identified,mainly with different transposable element insertions in their regulatory regions,suggesting that they functionally diverged after polyploidization.Combining genomics,transcriptomics,and metabolomics,we explored the contributions of gene family amplification and tetraploidization to the abundant anthraquinone production of R.officinale,as well as gene expression patterns and differences in anthraquinone content among tissues.Our report of-fers unprecedented genomic resources for fundamental research on the autopolyploid herb R.officinale and guidance for polyploid breeding of herbs.

High-quality Fagopyrum esculentum genome provides insights into the flavonoid accumulation among different tissues and self-incompatibility

Common buckwheat(Fagopyrum esculentum)and Tartary buckwheat(Fagopyrum tataricum),the two most widely cultivated buckwheat species,differ greatly in flavonoid content and reproductive mode.Here,we report the first high-quality and chromosome-level genome assembly of common buckwheat with 1.2 Gb.Comparative genomic analysis revealed that common buckwheat underwent a burst of long terminal repeat retrotransposons insertion accompanied by numerous large chromosome rearrangements after divergence from Tartary buckwheat.Moreover,multiple gene families involved in stress tolerance and flavonoid biosynthesis such as multidrug and toxic compound extrusion(MATE)and chalcone synthase(CHS)underwent significant expansion in buckwheat,especially in common buckwheat.Integrated multi-omics analysis identified high expression of catechin biosynthesis-related genes in flower and seed in common buckwheat and high expression of rutin biosynthesis-related genes in seed in Tartary buckwheat as being important for the differences in flavonoid type and content between these buckwheat species.We also identified a candidate key rutindegrading enzyme gene(Ft8.2377)that was highly expressed in Tartary buckwheat seed.In addition,we identified a haplotype-resolved candidate locus containing many genes reportedly associated with the development of flower and pollen,which was potentially related to self-incompatibility in common buckwheat.Our study provides important resources facilitating future functional genomics-related research of flavonoid biosynthesis and selfincompatibility in buckwheat.

Bistratal Au@Bi2S3 nanobones for excellent NIR-triggered/multimodal imaging-guided synergistic therapy for liver cancer

To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal(PT)conversion efficiency,remarkable photoacoustic(PA)imaging and high computed tomography(CT)performance;these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging.Subsequently,poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs(Au@Bi2S3-PVP NBs)were successfully loaded with the anticancer drug doxorubicin(DOX),and a satisfactory pH sensitive release profile was achieved,thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells.Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy,including extremely low toxicity,good biocompatibility,high drug loading ability,precise tumor targeting and effective accumulation.Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy(PTT).As both a contrast enhancement probe and therapeutic agent,Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia

The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement.Zinc ions have been reported to stimulate angiogenesis,but application was limited to the toxicity concerns.We hypothesized that zinc based metal-EGCG capsule(EGCG/Zn Ps)can achieve sustained release Zn2+resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG.The surface morphology,zeta potential,infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured.In vitro,EGCG/Zn showed significantly antioxidant,antiinflammatory and induced cell migration effect.In addition,EGCG/Zn Ps enabled the sustained release of zinc ions,which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor(VEGF)in vitro and in vivo.In mouse models of limb ischemia,EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues.Moreover,EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score,limb temperature and blood flow than other groups.In conclusion,EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+and EGCG,thus enabling the direct application to limb ischemia.

Functionalization of bismuth sulfide nanomaterials for their application in cancer theranostics

Multifunctional bismuth sulfide(Bi_(2)S_(3))nanomate rials exhibit significant potential as na no medicines for the diagnosis and treatment of cancer.These nanomaterials act as excellent photothermal agents and radiation sensitizers for the treatment of tumors,and they can also act as contrast agents for computed tomography(CT)imaging,photoacoustic imaging(PA),and other forms of imaging to provide real-time tumor monitoring and testing guidance.Compared with other nanomaterials,Bi2S3 nanomaterials can readily adapt to different applications by virtue of the fact that they can be easily functionalized.However,these nanomaterials have some limitations that cannot be ignored and need to be addressed,such as poor biocompatibility,toxicity,and low chemical stability.It is widely believed that appropriate functionalization of Bi_(2)S_(3) nanomaterials could remedy such defects and significantly improve performance.This review summarizes the ways in which Bi_(2)S_(3) nanomaterials can be functionalized and discusses their applications in cancer theranostics over the last few years,focusing particularly on imaging and therapy.We also discuss issues relating to how Bi_(2)S_(3) nanomaterials can be analyzed,including how we might be able to use these systems to inhibit and treat tumors and how current limitations might be ove rcome to improve treatment efficacy.Finally,we hope to provide inspiration and guidance as to how we might create a mo re optimized multifunctio nal nano-system for the diagnosis and treatment of tumors.

Mild hyperthermia synergized chemotherapy by Bi_(2)Se_(3)/MoSe_(2)nanosaucers for cancer treatment with negligible thermal resistance

Harsh photothermal temperatures(>50℃)caused heating damage to the normal tissues and induced thermal resistance in cancer cells,which significantly limited the safety and efficacy of photothermal therapy(PTT)in cancer treatment.Mild hyperthermia(<42℃)combined with chemotherapy might solve this issue.Herein,a novel transition metal dichalcogenides nanostructure,namely,Bi_(2)Se_(3)/MoSe_(2)nanosaucers(BMNSs),was designed to produce mild photo-hyperthermia(mPTT)and combined with chemotherapy to improve the overall antitumor efficacy.The BMNSs were constituted by Bi_(2)Se_(3)hexagonal nanoplates and enclosed with MoSe_(2)nanosheets evenly.While the MoSe_(2)moiety endowed the nanoplatform with excellent photothermal efficacy,the Bi_(2)Se_(3)substrates provided large specific surface area to anchor more doxorubicin(DOX)molecules as chemotherapeutic agent.Under the stimuli of mPTT/tumor acidic microenvironment,the tumor-specific drug release and the enhanced chemotherapy could be realized,showing impressive therapeutic outcomes against 4T1 cells.The synergetic therapeutic mechanism might be attributed to the mPTT induced cell membrane permeability,and interestingly,the expression of heat shock proteins 70 was not elevated obviously after the synergetic therapy,thus to avoid the tumor thermal resistance and further improve the therapeutic effect.The in vivo anti-tumoral performance of the BMNSs was further studied and complete tumor eradication was achieved without any recurrence and biotoxicity.Not only demonstrating a paradigm of high therapeutic efficacy of mild hyperthermia and synergistic chemotherapy for precise cancer therapy,our findings proved that the cancer therapeutic effect can be improved with minimal side effects through exquisite designing of the microstructures and the physiochemical properties of the nanoplatform.

Synthesis of cobalt vanadium nanomaterials for efficient electrocatalysis of oxygen evolution

A low-cost and high-activity catalyst for oxygen evolution reaction （OER） is the key to the water splitting technology for hydrogen generation. Here we report the use of three solvents, DMF, ethanol and glycol, in the solvothermal synthesis of three nano-catalysts, Co3（VO4）2-I, Co3（VO4）2-II, and Co3（VO4）2-III, respec- tively. Transmission electron microscope shows Co3（VO4）2-I, II, and III exist as ultrafine nanosheets, ultrathin nanofilms, and ultrafine nanosheet-comprised microspheres, respectively. These Co3（VO4）2 catalysts exhibit OER electrocatalysis, among which the Co3（VO4）2-II shows the lowest onset overpotential of 310 mV and only requires a small overpotential of 330 mV to drive current density of 10 mA/cm^2. Due to their high surface free energy, the ultmthin nanofilms of Co3（VO4）2- II exhibits a good immobilization effect with the high electrocatalytic activity for OER.