Spatiotemporal cytokinin response imaging and ISOPENTENYLTRANSFERASE 3 function in Medicago nodule development

Most legumes can establish a symbiotic association with soil rhizobia that trigger the development of root nodules. These nodules host the rhizobia and allow them to fix nitrogen efficiently. The perception of bacterial lipo-chitooligosaccharides (LCOs) in the epidermis initiates a signaling cascade that allows rhizobial intracellular infection in the root and de-differentiation and activation of cell division that gives rise to the nodule. Thus, nodule organogenesis and rhizobial infection need to be coupled in space and time for successful nodulation. The plant hormone cytokinin (CK) contributes to the coordination of this process, acting as an essential positive regulator of nodule organogenesis. However, the temporal regulation of tissue-specific CK signaling and biosynthesis in response to LCOs or Sinorhizobium meliloti inoculation in Medicago truncatula remains poorly understood. In this study, using a fluorescence-based CK sensor (pTCSn::nls:tGFP), we performed a high-resolution tissue-specific temporal characterization of the sequential activation of CK response during root infection and nodule development in M. truncatula after inoculation with S. meliloti. Loss-of-function mutants of the CK-biosynthetic gene ISOPENTENYLTRANSFERASE 3 (IPT3) showed impairment of nodulation, suggesting that IPT3 is required for nodule development in M. truncatula. Simultaneous live imaging of pIPT3::nls:tdTOMATO and the CK sensor showed that IPT3 induction in the pericycle at the base of nodule primordium contributes to CK biosynthesis, which in turn promotes expression of positive regulators of nodule organogenesis in M. truncatula.

Precise spatial and temporal characterization of cytokinin (CK) responses reveals the function of the CK biosynthesis gene ISOPENTENYLTRANSFERASE 3 during nodule development in Medicago truncatula.     

褪黑素对盐胁迫下普通菜豆芽期核酸修复的调控机制

普通菜豆(Phaseolus vulgaris)是重要的食用豆作物,然而其极易受盐胁迫危害,导致产量下降。褪黑素能提高植物耐盐能力。为探明外源褪黑素调控普通菜豆耐盐能力的机制,以普通菜豆品种奶花芸豆(GZ-YD014)为实验材料,设置水(W,对照)、盐胁迫(S)和盐胁迫+100μmol·L^–1褪黑素(M+S) 3个处理。结果发现,盐胁迫抑制了普通菜豆胚根的生长,使其长度、表面积、体积以及直径显著降低,外源褪黑素可缓解盐胁迫对普通菜豆胚根生长的抑制。外施褪黑素显著降低盐胁迫下活性氧积累和丙二醛(MDA)含量,提高保护酶(过氧化物酶、超氧化物歧化酶、过氧化氢酶以及抗坏血酸过氧化物酶)活性,增加渗透调节物质(可溶性糖和可溶性蛋白)以及生长素(IAA)、赤霉素(GA)和玉米素(ZT)的含量,降低脱落酸(ABA)含量。通过转录组分析挖掘出217个差异表达基因(DEGs),DEGs在GO富集中显著(P-value<0.05)富集到核酸相关条目上,在KEGG富集中显著(P-value<0.05)富集到核酸损伤修复(包括碱基切除修复、错配修复以及核苷酸切除修复)通路。...     

Curcumin analog HO‐3867 triggers apoptotic pathways through activating JNK1/2 signalling in human oral squamous cell carcinoma cells

Human oral squamous cell carcinoma (OSCC) is the common head and neck malignancy in the world. While surgery, radiotherapy and chemotherapy are emerging as the standard treatment for OSCC patients, the outcome is limited to the recurrence and side effects. Therefore, patients with OSCC require alternative strategies for treatment. In this study, we aimed to explore the therapeutic effect and the mode of action of the novel curcumin analog, HO‐3867, against human OSCC cells. We analysed the cytotoxicity of HO‐3867 using MTT assay. In vitro mechanic studies were performed to determine whether MAPK pathway is involved in HO‐3867 induced cell apoptosis. As the results, we found HO‐3867 suppressed OSCC cells growth effectively. The flow cytometry data indicate that HO‐3867 induce the sub‐G1 phase. Moreover, we found that HO‐3867 induced cell apoptosis by triggering formation of activated caspase 3, caspase 8, caspase 9 and PARP. After dissecting MAPK pathway, we found HO‐3867 induced cell apoptosis via the c‐Jun N‐terminal kinase (JNK)1/2 pathway. Our results suggest that HO‐3867 is an effective anticancer agent as its induction of cell apoptosis through JNK1/2 pathway in human oral cancer cells.     

Fibroblast growth factor 21 reverses high‐fat diet‐induced impairment of vascular function via the anti‐oxidative pathway in ApoE knockout mice

Circulating endothelial progenitor cells (EPCs), which function in vascular repair, are the markers of endothelial dysfunction and vascular health. Fibroblast growth factor 21 (FGF21), a liver‐secreted protein, plays a crucial role in glucose homeostasis and lipid metabolism. FGF21 has been reported to attenuate the progression of atherosclerosis, but its impact on EPCs under high oxidative stress conditions remains unclear. In vitro studies showed that the β‐klotho protein was expressed in cultured EPCs and that its expression was upregulated by FGF21 treatment. Hydrogen peroxide (H₂O₂)‐induced oxidative stress impaired EPC function, including cell viability, migration and tube formation. Pretreatment with FGF21 restored the functions of EPCs after the exposure to H₂O₂. Administration of N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME), an inhibitor of nitric oxide synthase, inhibited the effects of FGF21 in alleviating oxidative injury by suppressing endothelial nitric oxide synthase (eNOS). In an in vivo study, the administration of FGF21 significantly reduced total cholesterol (TC) and blood glucose levels in apolipoprotein E (ApoE)‐deficient mice that were fed a high‐fat diet (HFD). Endothelial function, as reflected by acetylcholine‐stimulated aortic relaxation, was improved after FGF21 treatment in ApoE‐deficient mice. Analysis of mRNA levels in the aorta indicated that FGF21 increased the mRNA expression of eNOS and upregulated the expression of the antioxidant genes superoxide dismutase (SOD)1 and SOD2 in ApoE‐deficient mice. These data suggest that FGF21 improves EPC functions via the Akt/eNOS/nitric oxide (NO) pathway and reverses endothelial dysfunction under oxidative stress. Therefore, administration of FGF21 may ameliorate a HFD‐induced vascular injury in ApoE‐deficient mice.     

Chromosome‐level genome assembly for the horned‐gall aphid provides insights into interactions between gall‐making insect and its host plant

The aphid Schlechtendalia chinensis is an economically important insect that can induce horned galls, which are valuable for the medicinal and chemical industries. Up to now, more than twenty aphid genomes have been reported. Most of the sequenced genomes are derived from free‐living aphids. Here, we generated a high‐quality genome assembly from a galling aphid. The final genome assembly is 271.52 Mb, representing one of the smallest sequenced genomes of aphids. The genome assembly is based on contig and scaffold N50 values of the genome sequence are 3.77 Mb and 20.41 Mb, respectively. Nine‐seven percent of the assembled sequences was anchored onto 13 chromosomes. Based on BUSCO analysis, the assembly involved 96.9% of conserved arthropod and 98.5% of the conserved Hemiptera single‐copy orthologous genes. A total of 14,089 protein‐coding genes were predicted. Phylogenetic analysis revealed that S. chinensis diverged from the common ancestor of Eriosoma lanigerum approximately 57 million years ago (MYA). In addition, 35 genes encoding salivary gland proteins showed differentially when S. chinensis forms a gall, suggesting they have potential roles in gall formation and plant defense suppression. Taken together, this high‐quality S. chinensis genome assembly and annotation provide a solid genetic foundation for future research to reveal the mechanism of gall formation and to explore the interaction between aphids and their host plants.     

Cryo-EM structure of the heptameric calcium homeostasis modulator 1 channel

Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca²⁺-gated ATP channel that plays an important role in neuronal signaling. However, as the previously reported CALHM structures are all in the ATP-conducting state, the gating mechanism of ATP permeation is still elusive. Here, we report cryo-EM reconstructions of two Danio rerio CALHM1 heptamers with ordered or flexible long C-terminal helices at resolutions of 3.2 Å and 2.9 Å, respectively, and one D. rerio CALHM1 octamer with flexible long C-terminal helices at a resolution of 3.5 Å. Structural analysis shows that the heptameric CALHM1s are in an ATP-nonconducting state with a central pore diameter of approximately 6.6 Å. Compared with those inside the octameric CALHM1, the N-helix inside the heptameric CALHM1 is in the “down” position to avoid steric clashing with the adjacent TM1 helix. Molecular dynamics simulations show that as the N-helix moves from the “down” position to the “up” position, the pore size of ATP molecule permeation increases significantly. Our results provide important information for elucidating the mechanism of ATP molecule permeation in the CALHM1 channel.     

650 nm激光穴位照射与针刺治疗良性前列腺增生症的疗效对比观察

目的:观察、评估650 nm激光照射穴位治疗良性前列腺增生症(中医辨证为肾阳虚)的临床疗效。方法:对30例良性前列腺增生症患者,采用650 nm激光,照射会阴、关元、肾俞,并随机选取30例,用针刺治疗作临床对比观察,针刺肾俞、秩边、关元、命门、足三里、脾俞、三阴交、次髎等穴。结果:激光照射穴位与针刺治疗均对良性前列腺增生症有较好的疗效,两组治疗前后症状评分、尿动力学均有显著的改变(P<0.05),但两者的临床疗效差异无统计学意义(P>0.05)。结论:650 nm激光穴位照射是临床治疗良性前列腺增生症(肾阳虚型)的有效治疗方法之一,值得深入研究。     

TNFAIP8 protein functions as a tumor suppressor in inflammation-associated colorectal tumorigenesis

Tumor necrosis factor-α-induced protein 8 (TNFAIP8 or TIPE) is a member of the TNFAIP8 family. While TIPE was broadly considered to be pro-cancerous, its precise roles in carcinogenesis especially those of the intestinal tract are not clear. Here, we show that genetic deletion of TIPE in mice exacerbated chemical-induced colitis and colitis-associated colon cancer. Loss of TIPE exacerbated inflammatory responses and inflammation-associated dysbiosis, leading to the activation of NF-κB and STAT3, and it also accelerated dysplasia, DNA damage and proliferation of intestinal epithelial cells. We further show that colon microbiota were essential for increased tumor growth and progression in Tipe^−/− mice. The tumor suppressive function of TIPE originated primarily from the non-hematopoietic compartment. Importantly, TIPE was downregulated in human colorectal cancers, and patients with low levels of Tipe mRNA were associated with reduced survival. These results indicate that TIPE serves as an important modulator of colitis and colitis-associated colon cancer.Subject terms: Cancer microenvironment, Chronic inflammation     

High-performance liquid chromatographic method for the determination of a novel thymidylate synthase inhibitor, AG 331, in human serum

AG 331 is a novel thymidylate synthase inhibitor currently in Phase I clinical trial. To determine the pharmacokinetic parameters of AG 331 in human subjects, a suitable analytical method was developed using high-performance liquid chromatography. Serum and urine samples were prepared using both solid-phase extraction and solvent extraction. Either 4,4′-diaminodiphenyl sulfone or benz[cd]indole-2(1H)-one were used as internal standards for the method. A reversed-phase C₁₈ analytical column completely resolved the drug and internal standard peaks from non-specific substances present in biological matrix. The method was validated for precision, accuracy, and reproducibility in serum and was linear over a concentration range of 50–2000 ng/ml, with a limit of detection of 20.0 ng/ml and a quantifiable limit of 50 ng/ml.     

基于AnyBodyTM技术的人体运动建模方法

人体运动的建模与仿真是当今运动生物力学研究的一个热点.利用数值模型研究人体的运动规律,是人体运动研究的一个重要手段和有效工具.其关键技术在于应用逆向运动学方法求解人体运动,并获取人体运动中各个肌肉力学上技术参数.文中主要探讨基于AnyBodyTM System软件人体运动仿真的建模方法来研究人体运动力学规律,结合The AnyBodyTM system对人体运动具体应用,说明The AnyBodyTM system技术在人体运动仿真领域的优势.