miRNA‐mediated pyroptosis play crucial effects in the development of myocardial ischaemia/reperfusion (I/R) injury (MIRI). Piperine (PIP) possesses multiple pharmacological effects especially in I/R ...condition. This study focuses on whether PIP protects MIRI from pyroptosis via miR‐383‐dependent pathway. Rat MIRI model was established by 30 minutes of LAD ligation and 4 hours of reperfusion. Myocardial enzymes, histomorphology, structure and function were detected to evaluate MIRI. Recombinant adenoviral vectors for miR‐383 overexpression or miR‐383 silencing or RP105 knockdown were constructed, respectively. Luciferase reporter analysis was used to confirm RP105 as a target of miR‐383. Pyroptosis‐related markers were measured by Western blotting assay. The results showed that I/R provoked myocardial injury, as shown by the increases of LDH/CK releases, infarcted areas and apoptosis as well as worsened function and structure. Pyroptosis‐related mediators including NLRP3, cleaved caspase‐1, cleaved IL‐1β and IL‐18 were also reinforced after MIRI. However, PIP treatment greatly ameliorated MIRI in parallel with pyroptotic repression. In mechanistic studies, MIRI‐caused elevation of miR‐383 and decrease of RP105/PI3K/AKT pathway were reverted by PIP treatment. Luciferase reporter assay confirmed RP105 as a miR‐383 target. miR‐383 knockdown ameliorated but miR‐383 overexpression facilitated pyroptosis and MIRI. Moreover, the anti‐pyroptotic effect from miR‐383 silencing was verified to be relied on the RP105/PI3K/AKT signalling pathway. Additionally, our present study further indicated the miR‐383/RP105/AKT‐dependent approach resulting from PIP administration against pyroptosis in MIRI. Therefore, PIP treatment attenuates MIRI and pyroptosis by regulating miR‐383/RP105/AKT pathway, and it may provide a therapeutic manner for the treatment of MIRI.
•The construction of deciduous broad-leaved forest having the greatest effect.•PH, soil microbial biomass carbon, and urease activity significantly increased bacterial diversity.•PH and soil ...microbial biomass carbon and nitrogen were the key driving factors of the soil bacterial community.•Sucrase activity can promote the increase of phototrophy functional bacteria.
The karst area in southwestern China is one of the largest and continuous karst landforms in the world, and its ecosystem is highly sensitive and fragile. Appropriate vegetation restoration modes are of great significance for sustaining and improving the stability of the karst ecosystem, the dominant landform type in southwest China. Bacteria, linking soil and plants, play an important role in regulating the succession and restoration of karst vegetation. However, it remains unclear how soil bacterial communities and soil biochemical properties respond to vegetation restoration practices in karst areas. In this study, a 13-year long-term trial was performed using three planting restoration modes of deciduous broad-leaved, mixed evergreen and deciduous broad-leaved forest, and evergreen broad-leaved forests, with controls of natural enclosure. We aimed to investigate the impact of different vegetation restoration modes on the structure of soil microbial communities and their driving mechanisms using 16S rDNA Illumina sequencing, combined with the determination of 11 soil indicators and statistical models. The results showed that artificial restoration can improve soil nutrient contents, enzyme activities and microbial biomass more effectively than natural closure, which is beneficial to the rapid restoration of vegetation after abandoning of farmland. Among them, the effect of deciduous broad-leaved treatment on artificial restoration mode was better than that of mixed evergreen and deciduous broad-leaved forest and evergreen broad-leaved forest. In sequencing results, artificial restoration increased the relative abundance of Proteobacteria, but decreased that of Acidobacteria. In addition, pH, soil microbial biomass carbon, and urease activity significantly increased bacterial diversity. Different vegetation restoration measures significantly changed the soil bacterial community structure. The bacterial community of deciduous broad-leaved forest was the most beneficial to the benign development of soil. Mantel test showed that pH and soil microbial biomass carbon and nitrogen were the key driving factors of the soil bacterial community. FAPROTAX analysis showed a significant positive correlation between sucrase activity and phototrophy functional bacteria. The results demonstrated that compared with natural enclosure, artificial vegetation restoration promoted rapid community succession, and construction of deciduous broad-leaved forest was the most effective way to manage karst areas, improve soil nutrients, alter its key microbial populations, promote ecosystem services, and eventually benefit the restoration of vegetation in karst areas.
Apoptosis is the major cause of cardiomyocyte death in myocardial ischemia/reperfusion injury (MI/RI). Increasing evidence suggests that microRNAs (miRNAs) can contribute to the regulation of ...cardiomyocytes apoptosis by posttranscriptional modulation of gene expression networks. However, the effects of miR‐327 in regulating MI/RI‐induced cardiomyocytes apoptosis have not been extensively investigated. This study was performed to test whether miR‐327 participate in cardiomyocytes apoptosis both in vitro and in vivo, and reveal the potential molecular mechanism of miR‐327 regulated MI/RI through targeting apoptosis repressor with caspase recruitment domain (ARC). Sprague–Dawley (SD) rats were subjected to MI/RI by left anterior descending coronary artery occlusion for 30 min and reperfusion for 3 hr. H9c2 cells were exposed to hypoxia for 4 hr and reoxygenation for 12 hr to mimic I/R injury. miRNA‐327 recombinant adenovirus vectors were transfected into H9c2 cells for 48 hr and rats for 72 hr before H/R and MI/RI treatment, respectively. The apoptosis rate, downstream molecules of apoptotic pathway, and the target reaction between miRNA‐327 and ARC were evaluated. Our results showed that miR‐327 was upregulated and ARC was downregulated in the myocardial tissues of MI/RI rats and in H9c2 cells with H/R treatment. Inhibition of miR‐327 decreased the expression levels of proapoptotic proteins Fas, FasL, caspase‐8, Bax, cleaved caspase‐9, cleaved caspase‐3, and the release of cytochrome‐C, as well as increasing the expression levels of antiapoptotic protein Bcl‐2 via negative regulation of ARC both in vivo or vitro. In contrast, overexpression miR‐327 showed the reverse effect. Moreover, the results of luciferase reporter assay indicated miR‐327 targets ARC directly at the posttranscriptional level. Taken together, inhibition of miR‐327 could attenuate cardiomyocyte apoptosis and alleviate I/R‐induced myocardial injury via targeting ARC, which offers a new therapeutic strategy for MI/RI.
In summary, inhibition of miR‐327 may alleviate I/R‐induced myocardial injury and suppress both extrinsic and intrinsic apoptotic cascades after myocardial ischemia/reperfusion injury (MI/RI) by targeting ARC. The manipulation of miR‐327‐mediated ARC stability may offer a new therapeutic strategy for MI/RI.
Warming temperatures caused by climate change are predicted to vary temporally and spatially. For mid‐ and high‐latitude reptiles, the seasonal variation in warming temperatures experienced by ...embryos and hatchlings may determine offspring fitness, yet this has remained largely unexplored.
To evaluate the independent and interactive influence of seasonal variation in warming temperatures on embryonic and hatchling development, we incubated eggs and reared hatchlings of a cold‐climate oviparous ectothermic species, the Heilongjiang grass lizard (Takydromus amurensis), following a 2 × 2 factorial design (present climate versus warming climate for embryos × present climate versus warming climate for hatchlings). We then evaluated embryonic and hatchling development, including hatching success, incubation period, initial hatchling body size, hatchling metabolic rate, growth rate and survival in the mesocosms.
We found that warming temperatures shortened the incubation period and produced hatchlings with higher survival rates than those incubated under the present climate conditions. Similarly, hatchlings reared under a warming climate had similar growth rates and resting metabolic rates, but higher survival rates than those reared under the present climate. Hatchlings that experienced both warming incubation and warming growth conditions had the highest survival rates.
This study revealed that moderate warming temperatures (Representative Concentration Pathway, RCP 4.5, 1.1–2.6°C) experienced by embryos and hatchlings interact to benefit hatchling fitness in cold‐climate oviparous ectotherms. Our study also highlighted the importance of integrating seasonal variation in warming temperatures when evaluating the responses to climate warming in multiple developmental stages in oviparous ectotherms.
摘要
气候变暖导致的温度升高存在着时空变异。对于中高纬度的爬行动物而言, 胚胎发育和后代生长经历的变暖温度可能存在季节间差异。而此种季节间差异的变暖温度如何影响后代的适合度, 目前仍然知之甚少。
为了评估季节间差异的变暖温度对胚胎发育和后代发育的独立或交互的影响, 我们以一种寒冷气候区分布的卵生外温物种黑龙江草蜥 (Takydromus amurensis) 为研究对象, 利用2 × 2因子控制的实验方案开展胚胎孵化和幼体饲养等工作 (当前气候与变暖气候胚胎孵化 × 当前气候与变暖气候幼体饲养)。并且, 我们检测了胚胎和幼体发育的指标, 包括孵化成功率、孵化期和幼体初始体长和体重、幼体代谢率、生长率和存活率等。
我们发现, 模拟气候变暖的孵化环境缩短了胚胎的孵化期, 并且孵出的幼体具有更高的存活率。此外, 尽管与当前气候下饲养的幼体在生长率和代谢率上并无差异, 但是在模拟变暖气候下饲养的幼体的存活率得到了显著地提升。从胚胎发育到后代生长阶段均经历变暖温度的幼体, 具有最高的存活率。
本研究揭示了胚胎和幼体均经历中等程度的气候变暖 (RCP 4.5, 1.1–2.6°C) 交互地提升了幼体的适合度, 证明了中等程度的气候变暖可能有益于寒冷气候的卵生外温动物。不仅如此, 本研究也强调了在评估具有多生活史阶段的卵生外温动物对气候变暖的响应时, 考虑季节间温度变暖差异的重要性。
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Read the free Plain Language Summary for this article on the Journal blog.
We explore the semileptonic and nonleptonic decays of doubly heavy baryons
(
Ω
cc
(
∗
)
+
,
Ω
bb
(
∗
)
0
,
Ω
bc
(
∗
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-
,
Ω
bc
′
0
)
induced by the
s
→
u
transition. Hadronic form factors are ...parametrized by transition matrix elements and are calculated in the light front quark model. With the form factors, we make use of helicity amplitudes and analyze semileptonic and nonleptonic decay modes of doubly heavy baryons. Benchmark results for partial decay widths, branching fractions, forward–backward asymmetries and other phenomenological observables are derived. We find that typical branching fractions for semileptonic decays into
ℓ
ν
¯
are at the order
10
-
7
-
10
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8
and the ones for nonleptonic decays are at the order
10
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5
, which are likely detectable such as in LHCb experiment. With the potential data accumulated in future, our results may help to shape our understanding of the decay mechanism in the presence of two heavy quarks.
2D semiconducting metal phosphorus trichalcogenides, particularly the bulk crystals of MPS3 (M = Fe, Mn, Ni, Cd and Zn) sulfides and MPSe3 (M = Fe and Mn) selenides, have been synthesized, ...crystallized and exfoliated into monolayers. The Raman spectra of monolayer FePS3 and 3-layer FePSe3 show the strong intralayer vibrations and structural stability of the atomically thin layers under ambient condition. The band gaps can be adjusted by element choices in the range of 1.3–3.5 eV. The wide-range band gaps suggest their optoelectronic applications in a broad wavelength range. The calculated cleavage energies of MPS3 are smaller than that of graphite. Therefore, the monolayers used for building of heterostructures by van der Waals stacking could be considered as the candidates for artificial 2D materials with unusual ferroelectric and magnetic properties.
Uncoupling protein 2 (UCP2), located in the mitochondrial inner membrane, is a predominant isoform of UCP that expressed in the heart and other tissues of human and rodent tissues. Nevertheless, its ...functional role during myocardial ischemia/reperfusion (I/R) is not entirely understood. Ischemic preconditioning (IPC) remarkably improved postischemic functional recovery followed by reduced lactate dehydrogenase (LDH) release with simultaneous upregulation of UCP2 in perfused myocardium. We then investigated the role of UCP2 in IPC‐afforded cardioprotective effects on myocardial I/R injury with adenovirus‐mediated in vivo UCP2 overexpression (AdUCP2) and knockdown (AdshUCP2). IPC‐induced protective effects were mimicked by UCP2 overexpression, while which were abolished with silencing UCP2. Mechanistically, UCP2 overexpression significantly reinforced I/R‐induced mitochondrial autophagy (mitophagy), as measured by biochemical hallmarks of mitochondrial autophagy. Moreover, primary cardiomyocytes infected with AdUCP2 increased simulated ischemia/reperfusion (sI/R)‐induced mitophagy and therefore reversed impaired mitochondrial function. Finally, suppression of mitophagy with mdivi‐1 in cultured cardiomyocytes abolished UCP2‐afforded protective effect on sI/R‐induced mitochondrial dysfunction and cell death. Our data identify a critical role for UCP2 against myocardial I/R injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.
Our data identify a critical role for uncoupling protein 2 (UCP2) against myocardial ischemia/reperfusion (I/R) injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.
A metal-free photocatalytic protocol for efficient construction of difluoro-containing dibenzazepines is developed. The transformation is redox-neutral and environmentally benign, has a wide range of ...substrate scope, proceeds at room temperature under irradiation of visible light, and furnishes dibenzazepine derivatives in mild to excellent yield.
In the genus Macleaya, Macleaya cordata and Macleaya microcarpa have been recognized as traditional herbs that are primarily distributed in China, North America, and Europe and have a long history of ...medicinal usage. These herbs have been long valued and studied for detumescence, detoxification, and insecticidal effect. This review aims to provide comprehensive information on botanical, phytochemical, pharmacological, and toxicological studies on plants in the genus Macleaya. Plants from the genus of Macleaya provide a source of bioactive compounds, primarily alkaloids, with remarkable diversity and complex architectures, thereby having attracted attention from researchers. To date, 291 constituents have been identified and/or isolated from this group. These purified compounds and/or crude extract possess antitumor, anti‐inflammatory, insecticidal, and antibacterial activities in addition to certain potential toxicities. Macleaya species hold potential for medicinal applications. However, despite the pharmacological studies on these plants, the mechanisms underlying the biological activities of active ingredients derived from Macleaya have not been thoroughly elucidated to date. Additionally, there is a need for research focusing on in vivo medical effects of Macleaya compounds and, eventually, for clinical trials.
Trifluoromethyl cationic carbyne (CF3C+:) possessing dual carbene‐carbocation behavior emulated as trifluoromethyl metal‐carbynoid (CF3C+=M) has not been explored yet, and its reaction ...characteristics are unknown. Herein, a novel α‐diazotrifluoroethyl sulfonium salt was prepared and used in Rh‐catalyzed three‐component 2+1+2 cycloadditions for the first time with commercially available N‐fused heteroarenes and nitriles, yielding a series of imidazo1,5‐a N‐heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh‐carbynoid (CF3C+=Rh) into C=N bonds of N‐fused heteroarenes was involved. This strategy demonstrates synthetic applications in late‐stage modification of pharmaceuticals, construction of CD3‐containing N‐heterocycles, gram‐scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo1,5‐a N‐heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.
A novel α‐diazotrifluoroethyl sulfonium salt was prepared, and it was applied in Rh‐catalyzed three‐component 2+1+2 cycloadditions for the first time, affording various imidazo1,5‐a N‐heterocycles under mild conditions. This strategy involved a unique trifluoromethyl Rh‐carbynoid (CF3C+=Rh), wherein three new chemical bonds were forged at the α‐carbon of trifluoromethyl in a single step.