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Studying the seed trait–stem trait–individual spatial pattern system is helpful for understanding the developmental direction of plant dynamics and populations under grazing disturbance as well as the antagonistic relationship between animals and plants, but few systematic analyses of this spatial pattern system have been carried out. Kobresia humilis is the dominant species in alpine grasslands. We studied K. humilis seed traits and their relationship with K. humilis reproductive individuals, the relationship between reproductive and vegetative stems, and the weights and spatial patterns of reproductive and nonreproductive individuals under four grazing treatments: no grazing (control), light grazing, moderate grazing and heavy grazing. We explored the relationship among seed size and seed number with reproductive stems and vegetative stems along the grazing gradient and assessed the spatial pattern changes between reproductive and nonreproductive individuals. The results showed the following: (1) Seed size increased with increasing grazing intensity, and the coefficient of variation for seed size and seed number in the heavy grazing treatment was greater than 0.6. (2) The structural equation model showed that grazing treatment had a positive effect on seed number, seed size and reproductive stem number and a negative effect on reproductive stem weight. (3) Grazing treatment did not affect the resource allocation to reproductive stems and vegetative stems per unit length of reproductive K. humilis individuals. (4) Compared with the number of reproductive individuals in the no grazing treatment, the number in the heavy grazing treatment decreased significantly, and the negative correlation between reproductive individuals and nonreproductive individuals changed from a full-scale negative correlation to a small-scale negative correlation and a large-scale positive correlation. Our study showed that grazing could activate and change the resource allocation pattern of dominant species in a grassland and have significant positive effects on reproductive stem number, reproductive stem weight, seed number and seed size. Along a grazing intensity gradient, with the increase in distance between reproductive and nonreproductive individuals, the transformation of intraspecific relationships from a negative correlation to a positive correlation is an ecological strategy conducive to population survival.

Background: Resistance to immune checkpoint inhibitor (ICI) therapy narrows the efficacy of cancer immunotherapy. Although 4-1BB is a promising drug target as a costimulatory molecule of immune cells, no 4-1BB agonist has been given clinical approval because of severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy. Methods: HK010 was generated by antibody engineering, and the Fab/antigen complex structure was analyzed using crystallography. The affinity and activity of HK010 were detected by multiple in vitro bioassays, including enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), flow cytometry, and luciferase-reporter assays. Humanized mice bearing human PD-L1-expressing MC38 (MC38/hPDL1) or CT26 (CT26/hPDL1) tumor transplants were established to assess the in vivo antitumor activity of HK010. The pharmacokinetics (PK) and toxicity of HK010 were evaluated in cynomolgus monkeys. Results: HK010 was generated as an Fc-muted immunoglobulin (Ig)G4 PD-L1x4-1BB bispecific antibody (BsAb) with a distinguished Fab/antigen complex structure, and maintained a high affinity for human PD-L1 (KD: 2.27 nM) and low affinity for human 4-1BB (KD: 493 nM) to achieve potent PD-1/PD-L1 blockade and appropriate 4-1BB agonism. HK010 exhibited synergistic antitumor activity by blocking the PD-1/PD-L1 signaling pathway and stimulating the 4-1BB signaling pathway simultaneously, and being strictly dependent on the PD-L1 receptor in vitro and in vivo. In particular, when the dose was decreased to 0.3 mg/kg, HK010 still showed a strong antitumor effect in a humanized mouse model bearing MC38/hPDL1 tumors. Strikingly, HK010 treatment enhanced antitumor immunity and induced durable antigen-specific immune memory to prevent rechallenged tumor growth by recruiting CD8+ T cells and other lymphocytes into tumor tissue and activating tumor-infiltrating lymphocytes. Moreover, HK010 not only did not induce nonspecific production of proinflammatory cytokines but was also observed to be well tolerated in cynomolgus monkeys in 5 week repeated-dose (5, 15, or 50 mg/kg) and single-dose (75 or 150 mg/kg) toxicity studies. Conclusion: We generated an Fc-muted anti-PD-L1x4-1BB BsAb, HK010, with a distinguished structural interaction with PD-L1 and 4-1BB that exhibits a synergistic antitumor effect by blocking the PD-1/PD-L1 signaling pathway and stimulating the 4-1BB signaling pathway simultaneously. It is strictly dependent on the PD-L1 receptor with no systemic toxicity, which may offer a new option for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Studying the seed trait-stem trait-individual spatial pattern system is helpful for understanding the developmental direction of plant dynamics and populations under grazing disturbance as well as the antagonistic relationship between animals and plants, but few systematic analyses of this spatial pattern system have been carried out. Kobresia humilis is the dominant species in alpine grasslands. We studied K. humilis seed traits and their relationship with K. humilis reproductive individuals, the relationship between reproductive and vegetative stems, and the weights and spatial patterns of reproductive and nonreproductive individuals under four grazing treatments: no grazing (control), light grazing, moderate grazing and heavy grazing. We explored the relationship among seed size and seed number with reproductive stems and vegetative stems along the grazing gradient and assessed the spatial pattern changes between reproductive and nonreproductive individuals. The results showed the following: (1) Seed size increased with increasing grazing intensity, and the coefficient of variation for seed size and seed number in the heavy grazing treatment was greater than 0.6. (2) The structural equation model showed that grazing treatment had a positive effect on seed number, seed size and reproductive stem number and a negative effect on reproductive stem weight. (3) Grazing treatment did not affect the resource allocation to reproductive stems and vegetative stems per unit length of reproductive K. humilis individuals. (4) Compared with the number of reproductive individuals in the no grazing treatment, the number in the heavy grazing treatment decreased significantly, and the negative correlation between reproductive individuals and nonreproductive individuals changed from a full-scale negative correlation to a small-scale negative correlation and a large-scale positive correlation. Our study showed that grazing could activate and change the resource allocation pattern of dominant species in a grassland and have significant positive effects on reproductive stem number, reproductive stem weight, seed number and seed size. Along a grazing intensity gradient, with the increase in distance between reproductive and nonreproductive individuals, the transformation of intraspecific relationships from a negative correlation to a positive correlation is an ecological strategy conducive to population survival. [ABSTRACT FROM AUTHOR]

Background Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. Objectives To compare the diagnostic value of RDR and PD, by conducting leukotriene D.sub.4 (LTD.sub.4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. Methods Healthy subjects and asthmatic patients underwent LTD.sub.4-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20 % fall in forced expiratory volume in one second (PD.sub.20FEV.sub.1) and the RDR, defined as FEV.sub.1 fall (%) at the final step divided by the corresponding provocative dosage. Results Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log.sub.10RDR was positively correlated with log.sub.10PD.sub.20FEV.sub.1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD.sub.20FEV.sub.1 and higher RDR (both P < 0.05). The differences in PD.sub.20FEV.sub.1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log.sub.10PD.sub.20FEV.sub.1, the log.sub.10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤25th percentile) was associated with higher baseline FEV.sub.1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD.sub.20FEV.sub.1 led to an increased diagnostic value compared with either parameter alone. Conclusions RDR is a surrogate of PD.sub.20FEV.sub.1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants., Author(s): Wei-jie Guan[sup.1] , Jin-ping Zheng[sup.1] , Xu Shi[sup.1] , Yan-qing Xie[sup.1] , Cai-yu Jiang[sup.1] [sup.2] , Yi Gao[sup.1] , Zheng Zhu[sup.1] , Jia-ying An[sup.1] , Xin-xin Yu[sup.1] , Wen-ting [...]

A tetradentate ligand, 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene (TPPE), was adopted to construct a two-dimensional coordination polymer that incorporated valence tautomerism and luminescence, and the synergistic effect arising from energy transfer from TPPE to the semiquinone moieties was experimentally and theoretically uncovered. [ABSTRACT FROM AUTHOR]

Based on the uncommon Kramers ions CeIII, SmIII and YbIII, complexes [Ce(dppbO2)2Cl3] (1, dppbO2 = 1,2-bis(diphenylphosphino)benzene dioxide), [Sm(dppbO2)2Cl3] (2) and [Yb(dppbO2)2Cl2]Cl (3) toward single-ion magnets were obtained and fully characterized. Complexes 1 and 2 are isostructural seven-coordinate with distorted geometries between a capped trigonal prism and a capped octahedron, while 3 is six-coordinate with an octahedral geometry. Dynamic magnetic property measurements reveal their field induced slow magnetic relaxation behaviours. Fits to the temperature dependent relaxation time (τ) result in effective barriers of 38(2), 11.7(2) and 20.2(6) cm−1 for 1, 2 and 3, respectively, as well as relatively low Raman exponents (3.4(2) for 1 and 2.1(1) for 3). Ab initio calculations were then performed and they indicated that the first excited Kramers doublets (KDs) for 1, 2 and 3 lie at ca. 291, 63.5 and 137 cm−1, respectively, which are much higher than the fitting results. Combining the significant transverse magnetic moments between the ground state KDs and the first excited KDs, we thus attribute the dominant relaxation pathway of the three compounds to a Raman process, while quantum tunnelling of magnetization and direct relaxation processes may coexist. In this case, the obtained effective barriers in a high temperature region for 1 and 3 are actually the energies of the vibrational modes, which lead to second-order Raman processes with exponential temperature dependence. [ABSTRACT FROM AUTHOR]

With the growth of the global population and the increasing frequency of natural disasters, crop yields must be steadily increased to enhance human adaptability to risks. Pre-harvest sprouting (PHS), a term mainly used to describe the phenomenon in which grains germinate on the mother plant directly before harvest, is a serious global problem for agricultural production. After domestication, the dormancy level of cultivated crops was generally lower than that of their wild ancestors. Although the shortened dormancy period likely improved the industrial performance of cereals such as wheat, barley, rice, and maize, the excessive germination rate has caused frequent PHS in areas with higher rainfall, resulting in great economic losses. Here, we systematically review the causes of PHS and its consequences, the major indicators and methods for PHS assessment, and emphasize the biological significance of PHS in crop production. Wheat quantitative trait loci functioning in the control of PHS are also comprehensively summarized in a meta-analysis. Finally, we use Arabidopsis as a model plant to develop more complete PHS regulatory networks for wheat. The integration of this information is conducive to the development of custom-made cultivated lines suitable for different demands and regions, and is of great significance for improving crop yields and economic benefits. [ABSTRACT FROM AUTHOR]

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The construction of active sites with excellent water oxidation activity is of great significance in the design of OER electrocatalysts. Herein, we propose an anion regulation strategy, in which N-doped carbon nanotubes play a protective role by coating the Ni3Fe alloy particles and two non-metallic elements S and Se are introduced to adjust the electronic structure, this can further help construct a heterogeneous surface, improve the valence state, and increase the hydrophilicity of the catalysts. The two as-prepared catalysts N-CNTs@NiS2/Fe7S8 (overpotential of 330 mV to achieve 50 mA cm−2 and Tafel slope of 51.49 mV dec−1) and N-CNTs@NiSe2/Fe3Se4 (360 mV and 72.32 mV dec−1, respectively) exhibited considerably high OER activity in 1.0 M KOH solutions. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) signaling and nicotinamide adenine dinucleotide (NAD) signaling are two basic signal regulation pathways in organisms, playing crucial roles in signal transduction, energy metabolism, stress tolerance, and various developmental processes. Notably, calmodulins (CaMs) and NAD kinases (NADKs) are important hubs for connecting these two types of signaling networks, where CaMs are the unique activators of NADKs. NADK is a key enzyme for NADP (including NADP+ and NADPH) biosynthesis by phosphorylating NAD (including NAD+ and NADH) and therefore, maintains the balance between NAD pool and NADP pool through an allosteric regulation mode. In addition, the two respective derivatives from NAD+ (substrate of NADK) and NADP+ (product of NADK), cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), have been considered to be the important messengers for intracellular Ca2+ homeostasis which could finally influence the combination between CaM and NADK, forming a feedback regulation mechanism. In this review article, we briefly summarized the major research advances related to the feedback regulation pathway, which is activated by the interaction of CaM and NADK during plant development and signaling. The theories and fact will lay a solid foundation for further studies related to CaM and NADK and their regulatory mechanisms as well as the NADK-mediated NAD signaling behavior in plant development and response to stress. [ABSTRACT FROM AUTHOR]

As the key producers of reactive oxygen species (ROS), NADPH oxidases (NOXs), also known as respiratory burst oxidase homologs (RBOHs), play crucial roles in various biological processes in plants with considerable evolutionary selection and functional diversity in the entire terrestrial plant kingdom. However, only limited resources are available on the phylogenesis and functions of this gene family in wheat. Here, a total of 46 NOX family genes were identified in the wheat genome, and these NOXs could be classified into three subgroups: typical TaNOXs, TaNOX-likes, and ferric reduction oxidases (TaFROs). Phylogenetic analysis indicated that the typical TaNOXs might originate from TaFROs during evolution, and the TaFROs located on Chr 2 might be the most ancient forms of TaNOXs. TaNOXs are highly expressed in wheat with distinct tissue or organ-specificity and stress-inducible diversity. A large-scale expression and/or coexpression analysis demonstrated that TaNOXs can be divided into four functional groups with different expression patterns under a broad range of environmental stresses. Different TaNOXs are coexpressed with different sets of other genes, which widely participate in several important intracellular processes such as cell wall biosynthesis, defence response, and signal transduction, suggesting their vital but diversity of roles in plant growth regulation and stress responses of wheat. [ABSTRACT FROM AUTHOR]

NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of fundamental biological processes by acting as reducing power and maintaining the intracellular redox balance of all life kingdoms. As the only enzymes that catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in many essential metabolic reactions, redox sensitive regulation, photosynthetic performance and also reactive oxygen species (ROS) homeostasis of cells and therefore, play crucial roles in both development and stress responses of plants. NADKs are highly conserved enzymes in amino acid sequences but have multiple subcellular localization and diverse functions. They may function as monomers, dimers or multimers in cells but the enzymatic properties in plants are not well elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are expressed in almost all tissues and developmental stages of plants with specificity for different members. Their transcripts can be greatly stimulated by a number of environmental factors such as pathogenic attack, irritant applications and abiotic stress treatments. Using transgenic approaches, several studies have shown that NADKs are involved in chlorophyll synthesis, photosynthetic efficiency, oxidative stress protection, hormonemetabolismand signaling regulation, and therefore contribute to the growth regulation and stress tolerance of plants. In this review, the enzymatic properties and functional mechanisms of plant NADKs are thoroughly investigated based on literature and databases. The results obtained here are greatly advantageous for further exploration of NADK function in plants. [ABSTRACT FROM AUTHOR]

Leaf rolling is considered as one of the most important agronomic traits in rice breeding. It has been previously reported that SEMI- ROLLED LEAF 1 ( SRL1) modulates leaf rolling by regulating the formation of bulliform cells in rice (Oryza sativa); however, the regulatory mechanism underlying SRL1 has yet to be further elucidated. Here, we report the functional characterization of a novel leaf-rolling mutant, curled leaf and dwarf 1 ( cld1), with multiple morphological defects. Map-based cloning revealed that CLD1 is allelic with SRL1, and loses function in cld1 through DNA methylation. CLD1/ SRL1 encodes a glycophosphatidylinositol ( GPI)-anchored membrane protein that modulates leaf rolling and other aspects of rice growth and development. The cld1 mutant exhibits significant decreases in cellulose and lignin contents in secondary cell walls of leaves, indicating that the loss of function of CLD1/ SRL1 affects cell wall formation. Furthermore, the loss of CLD1/ SRL1 function leads to defective leaf epidermis such as bulliform-like epidermal cells. The defects in leaf epidermis decrease the water-retaining capacity and lead to water deficits in cld1 leaves, which contribute to the main cause of leaf rolling. As a result of the more rapid water loss and lower water content in leaves, cld1 exhibits reduced drought tolerance. Accordingly, the loss of CLD1/ SRL1 function causes abnormal expression of genes and proteins associated with cell wall formation, cuticle development and water stress. Taken together, these findings suggest that the functional roles of CLD1/ SRL1 in leaf-rolling regulation are closely related to the maintenance of cell wall formation, epidermal integrity and water homeostasis. [ABSTRACT FROM AUTHOR]

Herein, two photosensitive platinum(II)-based tripods were designed and synthesized. Notably, complex 1 ({[Pt(dien)]3 L}(NO3)6, L=tri(4-pyridylphenyl)amine and dien=diethylenetriamine), which mainly accumulated in the cell nucleus, exhibited very low cytotoxicity in the absence of light irradiation, but displayed a remarkable increase in cytotoxicity upon visible light irradiation. Mechanistic investigations revealed that the tripod interacted with DNA in the nucleus, induced ROS generation upon light irradiation, and consequently elicited rapid DNA damage response; thereby triggering cancer cell apoptosis. [ABSTRACT FROM AUTHOR]