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Grain number and size are interactive agronomic traits that determine grain yield. However, the molecular mechanisms responsible for coordinating the trade-off between these traits remain elusive. Here, we characterized the rice (Oryza sativa) grain size and number1 (gsn1) mutant, which has larger grains but sparser panicles than the wild type due to disordered localized cell differentiation and proliferation. GSN1 encodes the mitogen-activated protein kinase phosphatase OsMKP1, a dual-specificity phosphatase of unknown function. Reduced expression of GSN1 resulted in larger and fewer grains, whereas increased expression resulted in more grains but reduced grain size. GSN1 directly interacts with and inactivates the mitogen-activated protein kinase OsMPK6 via dephosphorylation. Consistent with this finding, the suppression of mitogen-activated protein kinase genes OsMPK6, OsMKK4, and OsMKKK10 separately resulted in denser panicles and smaller grains, which rescued the mutant gsn1 phenotypes. Therefore, OsMKKK10-OsMKK4-OsMPK6 participates in panicle morphogenesis and acts on a common pathway in rice. We confirmed that GSN1 is a negative regulator of the OsMKKK10-OsMKK4-OsMPK6 cascade that determines panicle architecture. The GSN1-MAPK module coordinates the trade-off between grain number and grain size by integrating localized cell differentiation and proliferation. These findings provide important insights into the developmental plasticity of the panicle and a potential means to improve crop yields.

Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. Here, we characterize GSA1 , a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops. Increasing grain yield needs to be put in the context of environmental stress. Here, the authors reveal that a UDP-glucosyltransferase is associated with regulation of rice grain size, abiotic stress tolerance, flavonoid-mediated auxin signaling, and redirection of carbon flux to flavonoid glycosides synthesis.

Background Leaf morphology and spikelet number are two important traits associated with grain yield. To understand how genes coordinating with sink and sources of cereal crops is important for grain yield improvement guidance. Although many researches focus on leaf morphology or grain number in rice, the regulating molecular mechanisms are still unclear. Results In this study, we identified a prohibitin complex 2α subunit, NAL8, that contributes to multiple developmental process and is required for normal leaf width and spikelet number at the reproductive stage in rice. These results were consistent with the ubiquitous expression pattern of NAL8 gene. We used genetic complementation, CRISPR/Cas9 gene editing system, RNAi gene silenced system and overexpressing system to generate transgenic plants for confirming the fuctions of NAL8 . Mutation of NAL8 causes a reduction in the number of plastoglobules and shrunken thylakoids in chloroplasts, resulting in reduced cell division. In addition, the auxin levels in nal8 mutants are higher than in TQ, while the cytokinin levels are lower than in TQ. Moreover, RNA-sequencing and proteomics analysis shows that NAL8 is involved in multiple hormone signaling pathways as well as photosynthesis in chloroplasts and respiration in mitochondria. Conclusions Our findings provide new insights into the way that NAL8 functions as a molecular chaperone in regulating plant leaf morphology and spikelet number through its effects on mitochondria and chloroplasts associated with cell division.

研究目的：在小鼠模型中利用吲哚美辛阻断COX-1／2通路，探讨非甾体类抗炎药对肾缺血再灌注损伤的保护作用。创新要点：非甾体类抗炎药被认为具有肾毒性，本研究首次在小鼠模型中探讨非甾休类抗炎药对肾缺血再灌注损伤的保护作用。研究方法：重要结论：小鼠左侧肾蒂夹闭后，通过腹腔注射不同剂量的吲哚美辛，在肾缺血再灌注损伤24小时后，获取血液和肾脏标本。利用酶联免疫（ELISA）试剂盒测定血清肌酐和细胞因子浓度来评估肾功能，肾组织样本进行苏木精。伊红染色和免疫组化分析。腹腔注射吲哚美辛5mg／kg组的小鼠血清肌酐值与对照组相比显著降低，肾小管损伤也显著减轻（见图1和2）；腹腔注射5和7mg／kg吲哚美辛组的小鼠血清肾肿瘤坏死因子- α和白介素-6的浓度显著降低（见图3a和3b）；腹腔注射3和5mg／kg吲哚美辛组的小鼠血清血栓素B2与6-酮前列腺素F1α的比值明显降低（见图3e）；腹腔注射5mg／kg吲哚美辛组小鼠肾组织COX-1和COX-2染色较弱（见图4）。因此，吲哚美辛对小鼠肾缺血再灌注损伤的作用与其剂量相关，在某个特定的剂量范围内具有’肾保护作用。吲哚美辛对小鼠肾缺血再灌注损伤的保护作用与阻断COX-1／2有关。

Carbon nanotube （CNT）-reinforced 6061Al alloy matrix composites were prepared by chemical vapor depo- sition （CVD） combined with hot extrusion technique. During the preparation process, the 6061Al flakes obtained by ball milling of the 6061Al spherical powders were subjected to surface modification to introduce a hydrophilic polyvinyl alcohol （PVA） membrane on their surface （6061Al@PVA） to bond strongly with nickel acetate [Ni（II）]. Then the 6061Al@PVA flakes bonded with Ni（II） were calcined and reduced to Ni nanoparticles, which were then heat-treated at 580 ℃ to remove PVA for obtaining even Ni/6061Al catalyst. After that, the as-obtained Ni/6061Al catalyst was employed to synthesize CNTs on the surface of the 6061Al flakes by CVD. After hot extrusion of the CNT/6061Al composite powders, the as-obtained CNT/6061Al bulk composites with 2.26 wt% CNTs exhibited 135% increase in yield strength and 84.5% increase in tensile strength compared to pristine 6061Al matrix.

The application ofstereotactic technique is rapidly growing. For instance, deep brain stimulation （DBS）, an important neurostimulation technique in the treatment of Parkinson＇s disease, dystonia, essential tremor, and other diseases, uses the stereotactic method to implant electrodes.

Aim： To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms. Methods： Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferation was examined using MTT assay. Cell cycle distribution and sub-G1 fraction were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry. Cell death was measured based on the release of lactate dehydrogenase （LDH）. The expression levels of p53 and p21WAF1/cipl as well as caspase activation were examined using Western blot analysis. Results： Treatment of the 3 types of cancer cells with crocetin （60-240 μmol/L） for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin （240 pmol/L） significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21WAF1/Cipl induction. Crocetin （120-240μmol/L） caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner. In the 3 types of cancer cells, crocetin （60 μmol/L） significantly enhanced the cytotoxicity induced by vincristine （1 μmol/L）. Furthermore, this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR. Conclusion： Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine.

This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate （AA） and enzalutamide （Enz） for metastatic castration-resistant prostate cancer （mCRPC）. A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA （active comparator） and Enz （true placebo） randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings （HR. 0.90, 95% CI, 0.73-1.11; HR： 0.85, 95% CI, 0.68-1.07）. Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons： time to prostate-specific antigen （PSA） progression （HR. 0.34, 95% CI, 0.28-0.42; HR： 0.40, 95% CI, 0.30-0.53）, radiographic progression-free survival （HR： 0.37, 95% CI, 0.28-0.48; HR： 0.61, 95% CI, 0.50-0.74）, and PSA response rate （OR： 18.29, 95% CI, 11.20-29.88; OR： 10.69, 95% CI, 3.92-29.20）. With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

Parasitic wasps produce several factors including venom, polydnaviruses (PDVs) and specialized wasp cells named teratocytes that benefit the survival of offspring by altering the physiology of hosts. However, the underlying molecular mechanisms for the alterations remain unclear. Here we find that the teratocytes of Cotesia vestalis , an endoparasitoid of the diamondback moth Plutella xylostella , and its associated bracovirus (CvBV) can produce miRNAs and deliver the products into the host via different ways. Certain miRNAs in the parasitized host are mainly produced by teratocytes, while the expression level of miRNAs encoded by CvBV can be 100-fold greater in parasitized hosts than non-parasitized ones. We further show that one teratocyte-produced miRNA (Cve-miR-281-3p) and one CvBV-produced miRNA (Cve-miR-novel22-5p-1) arrest host growth by modulating expression of the host ecdysone receptor ( EcR ). Altogether, our results show the first evidence of cross-species regulation by miRNAs in animal parasitism and their possible function in the alteration of host physiology during parasitism. The moth Plutella xylostella during its larval stage is the host of the endoparasitic wasp Cotesia vestalis . Here the authors show that the parasitoids deliver microRNAs to their hosts through their symbiotic virus and specialized cells leading to induced developmental delay.

BackgroundImmunotherapy against solid tumors has long been hampered by the development of immunosuppressive tumor microenvironment, and the lack of a specific tumor-associated antigen that could be targeted in different kinds of solid tumors. Human leukocyte antigen G (HLA-G) is an immune checkpoint protein (ICP) that is neoexpressed in most tumor cells as a way to evade immune attack and has been recently demonstrated as a useful target for chimeric antigen receptor (CAR)-T therapy of leukemia by in vitro studies. Here, we design and test for targeting HLA-G in solid tumors using a CAR strategy.MethodsWe developed a novel CAR strategy using natural killer (NK) cell as effector cells, featuring enhanced cytolytic effect via DAP12-based intracellular signal amplification. A single-chain variable fragment (scFv) against HLA-G is designed as the targeting moiety, and the construct is tested both in vitro and in vivo on four different solid tumor models. We also evaluated the synergy of this anti-HLA-G CAR-NK strategy with low-dose chemotherapy as combination therapy.ResultsHLA-G CAR-transduced NK cells present effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro, as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models. In tumor coculture assays, the anti-HLA-G scFv moiety promotes Syk/Zap70 activation of NK cells, suggesting reversal of the HLA-G-mediated immunosuppression and hence restoration of native NK cytolytic functions. Tumor expression of HLA-G can be further induced using low-dose chemotherapy, which when combined with anti-HLA-G CAR-NK results in extensive tumor ablation both in vitro and in vivo. This upregulation of tumor HLA-G involves inhibition of DNMT1 and demethylation of transporter associated with antigen processing 1 promoter.ConclusionsOur novel CAR-NK strategy exploits the dual nature of HLA-G as both a tumor-associated neoantigen and an ICP to counteract tumor spread. Further ablation of tumors can be boosted when combined with administration of chemotherapeutic agents in clinical use. The readiness of this novel strategy envisions a wide applicability in treating solid tumors.