Comprehensive integration of single-cell transcriptomic data illuminates the regulatory network architecture of plant cell fate specification

Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.

A proteomic landscape of pharmacologic perturbations for functional relevance

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Protective effect of BlingLife®-berry extract on blue lightinduced eye damage and its mechanism

This study aims to investigate the protective effects of BlingLife®-berry extract on the eyes.BlingLife®-berry extract is a mixture of high-quality natural berries,including blackcurrant,aromia,bilberry and maquiberry.The main active ingredient responsible for theeye-protective effects is anthocyanins.Anthocyanins are natural water-soluble pigments belonging to the flavonoid class,and theyhave multiple benefits,including improving vision,anti-inflammatory and antibacterial properties,and antioxidant effects.Dueto the dual benefits of anthocyanins in protecting vision and eliminating free radicals,this study explores the comprehensive eye protective effects of BlingLife®-berry extract in terms of combating blue light-induced eye damage and oxidative stress-inducedvisual fatigue.The results provide robust evidence for the in vivo effects and further technological applications of BlingLife®-berry extract.

Potential application of let-7a antagomir in injured peripheral nerve regeneration

Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biological half-life,its contribution to pain response,and its inability to cross the blood-brain barrier.Considering that let-7(human miRNA)targets and regulates nerve growth factor,and that let-7 is a core regulator in peripheral nerve regeneration,we evaluated the possibilities of let-7 application in nerve repair.In this study,anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship,and functional screening.Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve,including Schwann cells,fibroblasts and macrophages.Use of hydrogel effectively achieved controlled,localized,and sustained delivery of let-7a antagomir.Finally,let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft,which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection.Our study provides an experimental basis for potential in vivo application of let-7a.

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

The proposed role of MSL-lncRNAs in causing sex lability of female poplars

Labile sex expression is frequently observed in dioecious plants,but the underlying genetic mechanism remains largely unknown.Sex plasticity is also observed in many Populus species.Here we carried out a systematic study on a maleness-promoting gene,MSL,detected in the Populus deltoides genome.Our results showed that both strands of MSL contained multiple cis-activating elements,which generated long non-coding RNAs(lncRNAs)promoting maleness.Although female P.deltoides did not have the male-specific MSL gene,a large number of partial sequences with high sequence similarity to this gene were detected in the female poplar genome.Based on sequence alignment,the MSL sequence could be divided into three partial sequences,and heterologous expression of these partial sequences in Arabidopsis confirmed that they could promote maleness.Since activation of the MSL sequences can only result in female sex lability,we propose that MSL-lncRNAs might play a role in causing sex lability of female poplars.

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.

Sex effect on growth performance and marker-aided sex discrimination of seedlings of Populus deltoides

Sex has a significant effect on various traits among dioecious plants.In this analysis of the sex effect on the radial growth and wood density of numerous 20-yearold trees of Populus deltoides growing in a common garden,male trees performed better than the females in radial growth,but sex did not significantly affect wood density.Growth rate and wood density were weakly negatively correlated.Sex selection is also critical for controlling seed-hair pollution from P.deltoides plantations.However,because the juvenile period of P.deltoides lasts for years,a reliable technique to determine the sex of juveniles has been needed.Here we developed a marker-aided technique to discriminate the sexes of P.deltoides seedlings.This study provides essential information on target traits and a highly desirable genetic toolkit for accelerate breeding programs for this important tree species.

Comprehensive regulatory networks for tomato organ development based on the genome and RNAome of MicroTom tomato

MicroTom has a short growth cycle and high transformation efficiency,and is a prospective model plant for studying organ development,metabolism,and plant–microbe interactions.Here,with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments,we constructed multiple gene co-expression networks,which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth,e.g.arbuscular mycorrhizal symbiosis and fruit development.Additionally,non-coding RNAs,including miRNAs,lncRNAs,and circRNAs were also identified,together with their potential targets.Interacting networks between different types of non-coding RNAs(miRNA-lncRNA),and non-coding RNAs and genes(miRNA-mRNA and lncRNA-mRNA)were constructed as well.Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit.Lastly,we established a database(http://eplant.njau.edu.cn/microTomBase/)with genomic and transcriptomic data,as well as details of gene co-expression and interacting networks on MicroTom,and this database should be of great value to those who want to adopt MicroTom as a model plant for research.

Characterization of microRNAs in serum： a novel class of biomarkers for diagnosis of cancer and other diseases

在各种各样的纸巾的 microRNAs (miRNAs ) 的 Dysregulated 表示与许多疾病被联系了，包括癌症。这里，我们证明 miRNAs 在象老鼠，老鼠，牛的胎儿，小牛，和马那样的人和另外的动物的浆液和血浆是在场的。在浆液的 miRNAs 的层次在一样的种类的个人之中稳定、可再现、一致。采用 Solexa，我们定序健康中国题目的所有浆液 miRNAs 并且分别地在男、女的题目发现超过 100 和 91 浆液 miRNAs。我们也为肺癌症， colorectal 癌症，和糖尿病识别了浆液 miRNAs 的特定的表示模式，提供证据那浆液 miRNAs 为各种各样的疾病包含指纹。癌症特定的浆液 miRNAs 由 Solexa 获得了的二个非小的房间肺进一步在 75 个健康施主和 152 个癌症病人的独立审判被验证，用量的反向的抄写聚合酶链反应试金。通过这些分析，我们断定浆液 miRNAs 能为各种各样的癌症和另外的疾病的察觉用作潜在的 biomarkers。

Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products

最近的婴儿的公式奶粉污染事件证明了在牛奶质量控制的经典标记或标准在识别鈥渕a nipulated 鈥 ? 是不够的差质量的牛奶。在现在的学习，我们第一次证明奶牛牛奶包含大量 microRNAs ( miRNAs )并且牛奶特定的 miRNAs 的唯一的表示侧面能为未加工的牛奶和牛奶相关的商业产品的质量控制用作新奇指示物和可能的新标准，例如液体牛奶和粉状的公式牛奶。用定序的 Solexa，首先，我们系统地在未加工的牛奶屏蔽了 miRNA 表示并且在未加工的牛奶识别了 245 miRNAs 的一个总数。不同于层次在哺乳的不同时期是其表达式将近相同的另外的经典 biomarkers，单个 miRNAs 能显著地在哺乳过程期间被改变，含有那 miRNAs 可以是更精确的指示物反映牛奶的优秀改变。第二，使用 TaqMan 基于探查的 miRNA 量的 RT-PCR ，我们进一步识别了七 miRNAs 重要地在整个哺乳过程，和更多有相对一致的表情，这七牛奶特定的 miRNAs 的表示侧面能为区别用作理想的 biomarker 差质量或从纯未加工的牛奶的 鈥渕a nipulated 鈥?牛奶，象为商业乳制品的质量控制一样，例如液体，牛奶和粉状的公式挤。一起，我们的调查结果为为决定未加工的牛奶或牛奶相关的商业产品的质量理解牛奶 miRNAs 和一个新潜在的标准的生理的角色提供一个基础。

Phylogenetic diversity and specificity of bacteria associated with Microcystis aeruginosa and other cyanobacteria

Interactions between bacteria and cyanobacteria have been suggested to have a potential to influence harmful algal bloom dynamics; however, little information on these interactions has been reported. In this study, the bacterial communities associated with five strains of Microcystis aeruginosa, three species of other Microcystis spp., and four representative species of non-Microcystis cyanobacteria were compared. Bacterial 16S rDNA fragments were amplified and separated by denaturing gradient gel electrophoresis （DGGE） followed by DNA sequence analysis. The similarities among bacterial communities associated with these cyanobacteria were compared to the digitized DGGE profiles using the cluster analyses. The bacterial community structure of all cyanobacterial cultures differed. Cluster analysis showed that the similarity values among M. aeruginosa cultures were higher than those of other cyanobacterial cultures. Sequence analysis of DGGE fragments indicated the presence of bacteria including, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Bacteroidetes and Actinobacteria in the cyanobacterial cultures. Members of the Sphingomonadales were the prevalent group among the Microcystis-associated bacteria. The results provided further evidence for species-specific associations between cyanoabcteria and heterotrophic bacteria, which are useful for understanding interactions between Microcystis and their associated bacteria.

Treatment of simulated wastewater containing Reactive Red 195 by zero-valent iron/activated carbon combined with microwave discharge electrodeless lamp/sodium hypochlorite

A comparative study of treatment of simulated wastewater containing Reactive Red 195 using zero-valent iron/activated carbon （ZVI/AC）, microwave discharge electrodeless lamp/sodium hypochlorite （MDEL/NaCIO） and the combination of ZVI/AC- MDEL/NaCIO was conducted. The preliminary results showed the two steps method of ZVI/AC-MDEL/NaCIO had much higher degradation efficiency than both single steps. The final color removal percentage was nearly up to 100% and the chemical oxygen demand reduction percentage was up to approximately 82%. The effects of operational parameters, including initial pH value of simulated wastewater, ZVI/AC ratio and particle size of ZVI were also investigated. In addition, from the discussion of synergistic effect between ZVI/AC and MEDL/NaCIO, we found that in the ZVI/AC-MEDL/NaCIO process, ZVI/AC could break the azo bond firstly and then MEDLfNaCIO degraded the aromatic amine products effectively. Reversing the order would reduce the degradation efficiency.

Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells

AIM:To investigate the effects of tectorigenin on human hepatocellular carcinoma(HCC)HepG2 cells.METHODS:Tectorigenin,one of the main components of rhizome of Iris tectorum,was prepared by simple methods,such as extraction,filtration,concentration,precipitation and recrystallization.HepG2 cells were incubated with tectorigenin at different concentrations,and their viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was detected by morphological observation of nuclear change,agarose gel electrophoresis of DNA ladder,and flow cytometry with Hoechst 33342,Annexin V-EGFP and propidium iodide staining.Generation of reactive oxygen species was quantified using DCFH-DA.Intracellular Ca2+was monitored by Fura 2-AM.Mitochondrial membrane potential was monitored using Rhodamine 123.Release of cytochrome c from mitochondria to cytosol was detected by Western blotting.Activities of caspase-3,-8 and-9 were investigated by Caspase Activity Assay Kit.RESULTS:The viability of HepG2 cells treated by tectorigenin decreased in a concentration-and timedependent manner.The concentration that reduced the number of viable HepG2 cells by 50%(IC50)after 12,24 and 48 h of incubation was 35.72 mg/L,21.19 mg/L and 11.06 mg/L,respectively.However,treatment with tectorigenin at 20 mg/L resulted in a very slight cytotoxicity to L02 cells after incubation for 12,24 or 48 h.Tectorigenin at a concentration of 20 mg/L greatly inhibited the viability of HepG2 cells and induced the condensation of chromatin and fragmentation of nuclei.Tectorigenin induced apoptosis of HepG2 cells in a time-and dose-dependent manner.Compared with the viability rate,induction of apoptosis was the main mechanism of the anti-proliferation effect of tectorigenin in HepG2 cells.Furthermore,tectorigenininduced apoptosis of HepG2 cells was associated with the generation of reactive oxygen species,increased intracellular[Ca2+]i,loss of mitochondrial membrane potential,translocation of cytochrome c,and activation of caspase-9 and-3.CONCLUSION:Tectorigenin induces apoptosis of HepG2 cells mainly via mitochondrial-mediated pathway,and produces a slight cytotoxicity to L02 cells.

Syntheses and Crystal Structures of 3,5-Diiodo-salicylalidehyde and 3,5-Diiodo-salicylalidene-4-nitroaniline

The title compounds, C7H4I2O2 1 and C13H7I2N2O3 2, have been synthesized and characterized by single-crystal X-ray diffraction. Compound 1 crystallizes in monoclinic, space group P21/c with a = 9.802（2）, b = 13.867（3）, c = 7.364（2） A, β = 109.74（3）°, V= 942.1（3） A^3, Dc= 2.636 g/cm^3, C7H4I2O2, Mr= 373.90, F（000） = 672, μ = 6.627 mm^-1, Z = 4, R = 0.0459 and wR = 0.1018 for 1805 observed reflections （I 〉 2 σ（I））. Compound 2 belongs to the monoclinic system, space group P21/n with a = 9.015（2）, b = 12.024（2）, c = 14.072（3） A, β = 103.91（3）°, V = 1480.6（5） A^3, Dc= 2.216 g/cm^3, C13H7I2N2O3, Mr= 494.01, F（000） = 920, p = 4.255 mm^-1, Z = 4, R = 0.0777 and wR = 0.1757 for 2896 observed reflections （I 〉 2σ（I））. Compounds 1 and 2 were assayed for antibacterial activities against three Gram positive bacterial strains （B. subtilis, S. aureus and S. faecalis） and three Gram negative bacterial strains （E. coli, P. aeruginosa and E. cloacae） by MTr method. Fortunately, compound 2 is found to show potent antibacterial activity against these six bacterial strains.

Extraction and Characterization of Antioxidant Compositions From Fermented Fruit Juice of Morinda citrifolia (Noni)

Extraction and characterization of antioxidative compositions from the extracts of fermented Xisha Noni （Morinda citrifolia L.） juice were studied. The antioxidative constituents of 184.6 g freeze-dried extracts of naturally fermented Xisha Noni juice were isolated successfully by petroleum ether, EtOAc and n-BuOH solvents, and the antioxidative effects were measured according to scavenging activity against hydroxyl generated in Fenton reaction system and superoxide anion radicals in pyrogallol autoxidation system. The EtOAc extract exhibited most significantly higher （P 〈 0.01） antioxidative activity than mannitol or vitamin C, while the petroleum ether and n-BuOH extracts showed lower activities compared to mannitol. Three antioxidant phenolic compounds, isoscopoletin, aesculetin and 3,3＇,4＇,5,7-pentahydroxyflavone （quercetin） were isolated from the EtOAc extract by several chromatography techniques for the first time. The results suggest that several compounds, in particular, the phenolic compounds, contribute separately or synergistically to the antioxidative activity of fermented Noni fruit juice.

Enzymatic Synthesis of Agmatine by Immobilized Escherichia coli Cells with Arginine Decarboxylase Activity

A new method for the enzymatic synthesis of agmatine by immobilized Escherichia coli cells with arginine decarboxylase（ADC） activity was established and a series of optimal reaction conditions was set down. The arginine decarboxylase showed the maximum activity when the pyridoxal phosphate（PLP） concentration was 50 mmol/L, pH=7 and 45 °C. The arginine decarboxylase exhibited the maximum production efficiency when the substrate concentration was 100 mmol/L and the reaction time was 15 h. It was also observed that the appropriate concentration of Mg2＋, especially at 0.5 mmol/L promoted the arginine decarboxylase activity; Mn2＋ had little effect on the arginine decarboxylase activity. The inhibition of Cu2＋ and Zn2＋ to the arginine decarboxylase activity was significant. The immobilized cells were continuously used 6 times and the average conversion rate during the six-time usage was 55.6%. The immobilized cells exhibited favourable operational stability. After optimization, the maximally cumulative amount of agmatine could be up to 20 g/L. In addition, this method can also catalyze D,L-arginine to agmatine, leaving the pure optically D-arginine simultaneously. The method has a very important guiding significance to the enzymatic preparation of agmatine.