[Characteristics of Leontopodium leontopodioides leaf stochiometry with altitude and their relationship with soil nutrients in Qilian Mountains, Northwest China]. / ç¥è¿žå±±ä¸åŒæµ·æ‹”ç«ç»’è‰å¶ç‰‡ç”Ÿæ€åŒ–å­¦è®¡é‡ç‰¹å¾åŠå ¶ä¸ŽåœŸå£¤å »åˆ†çš„å ³ç³».

Foliar stoichiometry provides information on the biotic and abiotic changes of environment. We examined the stoichiometric characteristics of plant leaves at different altitudes to understand how plants adapt to environmental changes. Foliar stoichiometry of Leontopodium leontopodioides at various altitudes (2400, 2600, 2800, 3000 and 3200 m) were analyzed in the Qilian Mountains of China. Across the altitude gradient, mean value of leaf carbon content (LC), nitrogen content (LN), and phosphorous content (LP) of L. leontopodioides was 401.27, 23.99 and 1.22 g·kg-1, respectively. The mean value of LC:LN, LC:LP and LN:LP was 16.8, 352.5 and 20.7, respectively. LC, LC:LN, LC:LP and LN:LP initially increased with increases in altitude, rea-ching the maximum at 2600 m, then decreased, reaching the minimum at 3000 m, and finally increased again. LP exhibited the opposite trend. LN demonstrated an initial decrease with altitude, reaching the minimum at 2800 m, followed by an increase at higher altitudes. LC did not correlate with LN, but was significantly negatively correlated with LP. LN was significantly positively correlated with LP. There was no correlation between LN and any other stoichiometry ratios. LP showed a significantly negative correlation with other stoichiometry ratios. LC:LN, LC:LP, and LN:LP were positively correlated with each other. Both soil total nitrogen and total phosphorus affected LC and LN, whereas LP was significantly negatively correlated with soil total phosphorus. The results suggested that the growth of L. leontopodioides in the study region was mainly limited by P availability.

[Effects of topographic factors on leaf traits of apricot in the Loess Plateau, Northwest China]. / åœ°å½¢å› å­å¯¹é»„åœŸé«˜åŽŸå±±æå¶ç‰‡åŠŸèƒ½æ€§çŠ¶çš„å½±å“.

As important topographic factors, slope aspect and gradient affect plant growth and leaf functional traits by regulating the combination of water and heat. Exploring the response of leaf functional traits to topographic factors is helpful for understanding plant adaptation strategies. We investigated the effects of sunny slope (including half sunny slope) and shady slope (including half shady slope) and three slope gradient (15°-20°, 21°-25°, and 26°-30°) on the leaf functional traits of apricot (Prunus armeniaca L.), the main afforestation tree species on the Loess Plateau. The results showed that: 1) Slope aspect and gradient exerted significant effects on all functional traits. Except leaf water content (LWC), other leaf functional traits were not affected by the interaction of slope aspect and gradient. 2) The leaf area (LA) under the sunny slope was equivalent to that under the shady slope. Leaf dry matter content (LDMC) and LWC (0.27 g·g-1 and 67.0%, respectively) were significantly higher under the shady slope than under the sunny slope (0.24 g·g-1 and 59.6%, respectively), while specific leaf area (SLA) (163.05 cm2·g-1) was significantly lower under the former than under the latter (183.72 cm2·g-1). 3) At different slope gradients, SLA and LA reached a maximum value at 15°-20° (184.04 cm2·g-1) and 26°-30° (21.14 cm2), respectively. 4) Except no difference in soil water content (Θ) between 15°-20° and 26°-30°, it differed significantly between two slope aspects and among other slope gradients. The Θ was one of the main factors causing the differences in functional traits, especially in the 0-10 cm soil layer. 5) SLA was negatively correlated with LWC and LDW and positively correlated with LA. LDW was positively correlated with LWC and negatively correlated with LA. Θ was positively correlated with LWC but not with other leaf functional traits.

Anticancer IrIII -Aspirin Conjugates for Enhanced Metabolic Immuno-Modulation and Mitochondrial Lifetime Imaging.

The chemo-anti-inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated IrIII complexes Ir2 and Ir3 formed by conjugation of Ir1 with two antiphlogistics (aspirin and salicylic acid) have been designed. Ir2 and Ir3 exhibit higher antitumor and anti-inflammatory potencies than a mixture of Ir1 and aspirin/salicylic acid. We show that they can be hydrolyzed, accumulate in mitochondria, and induce mitochondrial dysfunction. Due to their intense long-lived phosphorescence, Ir2 and Ir3 can track mitochondrial morphological changes. Phosphorescence lifetime imaging shows that Ir2 and Ir3 can aggregate during mitochondrial dysfunction. As expected, Ir2 and Ir3 exhibit immunomodulatory properties by regulating the activity of immune factors. Both Ir2 and Ir3 can induce caspase-dependent apoptosis and caspase-independent paraptosis and inhibit several events related to metastasis. Moreover, Ir2 and Ir3 show potent tumor growth inhibition in vivo. Our study demonstrates that the combination of mitochondrial-targeting and immunomodulatory activities is feasible to develop multifunctional metal-based anticancer agents.

Anticancer Cyclometalated Iridium(III) Complexes with Planar Ligands: Mitochondrial DNA Damage and Metabolism Disturbance.

Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity than cisplatin and they can effectively localize to mitochondria. Among them, complexes Ir3 and Ir4 with dipyrido[3,2- a:2',3'- c]phenazine (dppz) ligands can bind to DNA tightly in vitro, intercalate to mtDNA in situ, and induce mtDNA damage. Ir3- and Ir4-impaired mitochondria exhibit decline of mitochondrial membrane potential, disability of adenosine triphosphate generation, disruption of mitochondrial energetic and metabolic status, which subsequently cause protective mitophagy, G0/G1 phase cell cycle arrest, and apoptosis. In vivo antitumor evaluations also show that Ir4 can inhibit tumor xenograft growth effectively. Overall, our work proves that targeting the mitochondrial genome may present an effective strategy to develop metal-based anticancer agents to overcome cisplatin resistance.

Elevational variations of leaf stochiometry in Leontopodium leontopodioides on the Qinghai-Tibetan Plateau, China.

Topography has major impacts on the trade-off of plant survival strategies. Exploring the differential pattern of leaf ecological stoichiometry along the elevation gradient contributes to a better understanding of plant's response to environmental changes and its ecological adaptability. We investigated leaf C, N, and P concentrations and stoichiometric ratios of Leontopodium leontopodioides at three elevations, including from 4400 m to 4700 m, from 4701 m to 5000 m, and from 5001 m to 5300 m, on the northeastern margin of the Qinghai-Tibetan Plateau in China. The results showed that the concentrations of leaf C, N, and P of L. leontopodioides were 405.36 g·kg-1, 18.42 g·kg-1 and 0.94 g·kg-1, respectively. Leaf C/N, C/P, and N/P were 22.67, 467.61 and 20.30, respectively. The concentrations of leaf N and P of L. leontopodioides consistently increased with the increases of elevation. The coefficient of variations for leaf C, N and P concentrations and ratios of L. leontopodioides were all less than 30%, with an order of P (30%) > C/P (29%) > C/N (18%) > N (17%) > N/P (15%) > C (3%). The growth of L. leontopodioides on the Qinghai-Tibetan Plateau was mainly limited by P availability.

Photodamaging of Mitochondrial DNA to Overcome Cisplatin Resistance by a RuII -PtII Bimetallic Complex.

Emerging studies have shown that mitochondrial DNA (mtDNA) is an attractive target for anticancer therapeutics. Herein, a heterobimetallic complex [Ru(dip)2 (µ-bpm)PtCl2 ]Cl2 (RuPt; dip=4,7-diphenyl-1,10-phenanthroline; bpm=2,2'-bipyrimidine) and the corresponding mononuclear complex [Ru(dip)2 (bpm)]Cl2 (Ru) have been designed and synthesized. RuPt can bind to mtDNA and damage it both in the dark and upon visible light irradiation. By using a variety of methods, it was demonstrated that RuPt can interfere with the function of mtDNA by decreasing the amplification and copy number of mtDNA, and affecting the transcriptional level of mitochondria-encoded genes. Furthermore, RuPt can disturb the physiological processes of mitochondria and induce caspase-dependent apoptosis in the presence of light. In addition, RuPt shows low systemic toxicity and potent in vivo anticancer potency upon light irradiation. This study provides strong evidence that mtDNA is an important molecular target of RuPt, and photodamaging mtDNA is an effective strategy to overcome cisplatin resistance.

[Effects of grassland management on soil nutrients and their spatial distribution on the Qinghai-Tibetan Plateau, China]. / é’è—é«˜åŽŸè‰åœ°ç®¡ç†æ–¹å¼å¯¹åœŸå£¤å »åˆ†åŠå ¶ç©ºé—´åˆ†å¸ƒçš„å½±å“.

After grasslands were contracted to individual households on the Qinghai-Tibetan Pla-teau, two grassland management patterns were formed, i.e., the single-household management pattern (SMP) and the multi-household management pattern (MMP). The soil nutrients and their spatial distributions under those two patterns were compared in the Nagchu Prefecture of Tibet. The results showed that the soil organic carbon, total nitrogen, and total phosphorus under the MMP (84.31, 6.87 and 0.59 g·kg-1) were all significantly higher than those under the SMP (73.57, 6.07 and 0.54 g·kg-1). On the vertical dimension, the variation coefficient of soil total phosphorous between 0-15 cm layer and 15-30 cm layer under SMP had no significant difference, while that of soil pH, soil organic carbon and total nitrogen in 15-30 cm layer were all higher than 0-15 cm layer under both patterns. On the horizontal dimension, the variation coefficients of soil organic carbon and total nitrogen under SMP were significantly higher than those under MMP, with the estimated values for the former being 25.7% and 23.5%, and for the latter being 19.3% and 18.6%, respectively. Compared with the MMP, the uneven distribution of nutrients could easily lead to soil nutrient loss under the SMP.

Cyclometalated iridium(iii) complexes induce mitochondria-derived paraptotic cell death and inhibit tumor growth in vivo.

The development of iridium complexes as potent anticancer agents has received increasing attention in recent years. In this study, four cyclometalated Ir(iii) complexes with good photophysical properties and potent anticancer activity have been synthesized and characterized. They are taken up by human lung adenocarcinoma A549 cells very quickly and specifically target mitochondria. Mechanism studies reveal that one of them, namely IrM2, induces paraptosis accompanied by excessive mitochondria-derived cytoplasmic vacuoles. Meanwhile, IrM2 affects the ubiquitin-proteasome system (UPS) and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, IrM2 rapidly induces a series of mitochondria-related dysfunctional events, including the loss of mitochondrial membrane potential, cellular ATP depletion, mitochondrial respiration inhibition and reactive oxygen species (ROS) elevation. The rapid loss of mitochondrial functions, elevation of ROS and impairment of the UPS induced by IrM2 lead to the collapse of mitochondria and the subsequent cytoplasmic vacuolation before the cells are ready to start the mechanisms of apoptosis and/or autophagy. Among the ROS, superoxide anion radicals play a critical role in IrM2-mediated cell death. In vivo studies reveal that IrM2 can significantly inhibit tumor growth in a mouse model. This work gives useful insights into the design and anticancer mechanisms of new metal-based anticancer agents.

Iridium(iii) complexes with five-membered heterocyclic ligands for combined photodynamic therapy and photoactivated chemotherapy.

Organometallic iridium complexes have emerged as potent anticancer agents in recent years. In this work, three cyclometalated iridium(iii) complexes Ir1-Ir3 containing monodentate five-membered heterocyclic ligands have been synthesized and characterized. Upon visible light (425 nm) irradiation, the five-membered heterocyclic ligands will dissociate from the metal centre. Moreover, Ir1-Ir3 can also act as effective singlet oxygen photosensitizers. Thus, Ir1-Ir3 can exert their light-mediated activation of anticancer effects by dual modes including ligand exchange reactions and generation of singlet oxygen (1O2) upon visible light irradiation. Notably, Ir1 displays a high phototoxicity index of 61.7 against human cancer cells. Further studies show that light-mediated anticancer properties exerted by Ir1-Ir3 occur through reactive oxygen species (ROS) generation, caspase activation, and eventually apoptosis induction. Our study demonstrates that these complexes can act as novel dual-mode light-mediated anticancer agents.

Valproic Acid-Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents.

Valproic acid (VPA) is a short-chain, fatty acid type histone deacetylase inhibitor (HDACi), which can cause growth arrest and induce differentiation of transformed cells. Phosphorescent cyclometalated IrIII complexes have emerged as potential anticancer agents. By conjugation of VPA to IrIII complexes through an ester bond, VPA-functionalized cyclometalated iridium(III) complexes 1 a-3 a were designed and synthesized. These complexes display excellent two-photon properties, which are favorable for live-cell imaging. The ester bonds in 1 a-3 a can be hydrolyzed quickly by esterase and display similar inhibition of HDAC activity to VPA. Notably, 1 a-3 a can overcome cisplatin resistance effectively and are about 54.5-89.7 times more cytotoxic than cisplatin against cisplatin-resistant human lung carcinoma (A549R) cells. Mechanistic studies indicate that 1 a-3 a can penetrate into human cervical carcinoma (HeLa) cells quickly and efficiently, accumulate in mitochondria, and induce a series of cell-death-related events mediated by mitochondria. This study gives insights into the design and anticancer mechanisms of multifunctional anticancer agents.

Light-Up Mitophagy in Live Cells with Dual-Functional Theranostic Phosphorescent Iridium(III) Complexes.

Phosphorescent Ir(III) complexes are expected to be new multifunctional theranostic platforms that enable the integration of imaging capabilities and anticancer properties. Mitophagy is an important selective autophagic process that degrades dysfunctional mitochondria. Until now, the regulation of mitophagy is still poorly understood. Herein, we present two phosphorescent cyclometalated iridium(III) complexes (Ir1 and Ir2) that can accumulate in mitochondria and induce mitophagy. Because of their intrinsic phosphorescence, they can specially image mitochondria and track mitochondrial morphological alterations. Mechanism studies show that Ir1 and Ir2 induce mitophagy by depolarization of mitochondrial membrane potential, depletion of cellular ATP, perturbation in mitochondrial metabolic status, and induction of oxidative stress. Moreover, no sign of apoptosis is observed in Ir1- and Ir2-treated cells under the same conditions that an obvious mitophagic response is initiated. We demonstrate that Ir1 is a promising theranostic agent that can induce mitophagy and visualize changes in mitochondrial morphology simultaneously.

Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes.

Cancer cell metabolism is reprogrammed to sustain the high metabolic demands of cell proliferation. Recently, emerging studies have shown that mitochondrial metabolism is a potential target for cancer therapy. Herein, four mitochondria-targeted phosphorescent cyclometalated iridium(iii) complexes have been designed and synthesized. Complexes 2 and 4, containing reactive chloromethyl groups for mitochondrial fixation, show much higher cytotoxicity than complexes 1 and 3 without mitochondria-immobilization properties against the cancer cells screened. Further studies show that complexes 2 and 4 induce caspase-dependent apoptosis through mitochondrial damage, cellular ATP depletion, mitochondrial respiration inhibition and reactive oxygen species (ROS) elevation. The phosphorescence of complexes 2 and 4 can be utilized to monitor the perinuclear clustering of mitochondria in real time, which provides a reliable and convenient method for in situ monitoring of the therapeutic effect and gives hints for the investigation of anticancer mechanisms. Genome-wide transcriptional analysis shows that complex 2 exerts its anticancer activity through metabolism repression and multiple cell death signalling pathways. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of phosphorescent iridium complexes.

Tumor-targeted supramolecular nanoparticles self-assembled from a ruthenium-ß-cyclodextrin complex and an adamantane-functionalized peptide.

We report here a supramolecular strategy to assemble a cyclodextrin-functionalized anticancer Ru(ii) complex with an adamantane-appended tumor-targeting peptide into discrete and stable phosphorescent nanostructures that can induce cell death in integrin αvß3-rich tumor cells with high selectivity. This strategy presents new opportunities for the construction of tumor-targeting metallo-anticancer therapeutics.

Cyclometalated iridium(iii) complexes as lysosome-targeted photodynamic anticancer and real-time tracking agents.

Stimuli-activatable photosensitizers (PSs) are highly desirable for photodynamic therapy (PDT) to selectively demolish tumor cells. On the other hand, lysosomes are emerging as attractive anticancer targets. Herein, four cyclometalated iridium(iii)-ß-carboline complexes with pH-responsive singlet oxygen (1O2) production and lysosome-specific imaging properties have been designed and synthesized. Upon visible light (425 nm) irradiation, they show highly selective phototoxicities against cancer cells. Notably, complex 2 ([Ir(N^C)2(N^N)](PF6) in which N^C = 2-phenylpyridine and N^N = 1-(2-benzimidazolyl)-ß-carboline) displays a remarkably high phototoxicity index (PI = IC50 in the dark/IC50 in light) of >833 against human lung carcinoma A549 cells. Further studies show that 2-mediated PDT induces caspase-dependent apoptosis through lysosomal damage. The pH-responsive phosphorescence of complex 2 can be utilized to monitor the lysosomal integrity upon PDT, which provides a reliable and convenient method for in situ monitoring of therapeutic effect and real-time assessment of treatment outcome. Our work provides a strategy for the construction of highly effective multifunctional subcellular targeted photodynamic anticancer agents through rational structural modification of phosphorescent metal complexes.

[Ecological sensitivity of Shanghai City based on GIS spatial analysis].

In this paper, five sensitivity factors affecting the eco-environment of Shanghai City, i.e., rivers and lakes, historical relics and forest parks, geological disasters, soil pollution, and land use, were selected, and their weights were determined by analytic hierarchy process. Combining with GIS spatial analysis technique, the sensitivities of these factors were classified into four grades, i.e., highly sensitive, moderately sensitive, low sensitive, and insensitive, and the spatial distribution of the ecological sensitivity of Shanghai City was figured out. There existed a significant spatial differentiation in the ecological sensitivity of the City, and the insensitive, low sensitive, moderately sensitive, and highly sensitive areas occupied 37.07%, 5.94%, 38.16%, and 18.83%, respectively. Some suggestions on the City's zoning protection and construction were proposed. This study could provide scientific references for the City's environmental protection and economic development.

[Study on difference of biological characteristics and resistance to powdery mildew of different Astragalus populations].

OBJECTIVE: To study difference among populations which belong to Astragalus membranaceus and A. membranaceus var. mongholicus on morphology, habit, characteristics of physiology and resistance to powdery mildew, and classify them in order to provide theoretical basis for breeding and improving varieties. METHOD: Morphology, habits, isozyme and soluble protein electrophoretograms were compared among the populations. They were categorized by cluster analysis based on those electrophoretograms. Different ability of resistance to powdery mildew was also studied through comparing disease indices among six populations. RESULT: The results showed A. membranaceus var. mongholicus was distinctly different from A. membranaceus. There was a special type in colonies of A. membranaceus, which showed hairy upper epidermis of leaflets and later florescence. CONCLUSION: Astragalus for medicine could be categorized in three types A. membranaceus var. mongholicus, A. membranaceus early florescence type and A. membranaceus late florescence type. Among them A. membranaceus var. mongholicus is most resistant to powdery mildew, while A. membranaceus is easily infected, and the early florescence type is even more easily infected.