Ratiometric fluorescent detection of Cu2+ based on dual‐emission ZIF‐8@rhodamine‐B nanocomposites

Zeolitic imidazolate framework‐8 (ZIF‐8) loading rhodamine‐B (ZIF‐8@rhodamine‐B) nanocomposites was proposed and used as ratiometric fluorescent sensor to detect copper(II) ion (Cu²⁺). Scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray powder diffraction, nitrogen adsorption/desorption isotherms and fluorescence emission spectroscopy were employed to characterize the ZIF‐8@rhodamine‐B nanocomposites. The results showed the rhodamine‐B was successfully assembled on ZIF‐8 based on the π‐π interaction and the hydrogen bond between the nitrogen atom of ZIF‐8 and –COOH of rhodamine‐B. The as‐obtained ZIF‐8@rhodamine‐B nanocomposites were octahedron with size about 150–200 nm, had good water dispersion, and exhibited the characteristic fluorescence emission of ZIF‐8 at 335 nm and rhodamine‐B at 575 nm. The Cu²⁺ could quench fluorescence of ZIF‐8 rather than rhodamine‐B. The ZIF‐8 not only acted as the template to assemble rhodamine‐B, but also was employed as the signal fluorescence together with the fluorescence of rhodamine‐B as the reference to construct a novel ratiometric fluorescent sensor to detect Cu²⁺. The resulted ZIF‐8@rhodamine‐B nanocomposite fluorescence probe showed good linear range (68.4 nM to 125 μM) with a low detection limit (22.8 nM) for Cu²⁺ combined with good sensitivity and selectivity. The work also provides a better way to design ratiometric fluorescent sensors from ZIF‐8 and other fluorescent molecules.     

Microbial community responses reduce soil carbon loss in Tibetan alpine grasslands under short‐term warming

Changes in labile carbon (LC) pools and microbial communities are the primary factors controlling soil heterotrophic respiration (R_h) in warming experiments. Warming is expected to initially increase R_h but studies show this increase may not be continuous or sustained. Specifically, LC and soil microbiome have been shown to contribute to the effect of extended warming on R_h. However, their relative contribution is unclear and this gap in knowledge causes considerable uncertainty in the prediction of carbon cycle feedbacks to climate change. In this study, we used a two‐step incubation approach to reveal the relative contribution of LC limitation and soil microbial community responses in attenuating the effect that extended warming has on R_h. Soil samples from three Tibetan ecosystems—an alpine meadow (AM), alpine steppe (AS), and desert steppe (DS)—were exposed to a temperature gradient of 5–25°C. After an initial incubation period, soils were processed in one of two methods: (a) soils were sterilized then inoculated with parent soil microbes to assess the LC limitation effects, while controlling for microbial community responses; or (b) soil microbes from the incubations were used to inoculate sterilized parent soils to assess the microbial community effects, while controlling for LC limitation. We found both LC limitation and microbial community responses led to significant declines in R_h by 37% and 30%, respectively, but their relative contributions were ecosystem specific. LC limitation alone caused a greater R_h decrease for DS soils than AMs or ASs. Our study demonstrates that soil carbon loss due to R_h in Tibetan alpine soils—especially in copiotrophic soils—will be weakened by microbial community responses under short‐term warming.     

Discovery of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups as potential PTP1B inhibitors

Two series of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups were identified as competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors. Among the compounds studied, IIIv was found to have the best in vitro inhibition activity against PTP1B (IC₅₀?=?0.67?±?0.09?µM) and the best selectivity (9-fold) between PTP1B and T-cell protein tyrosine phosphatase (TCPTP). Molecular docking studies demonstrated that compounds IIIm, IIIv and IVg could occupy simultaneously at both the catalytic site and the adjacent pTyr binding site. These results provide novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.     

Design,synthesis and biological evaluation of hypolipidemic compounds based on BRD4 inhibitor RVX-208

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.     

IgA1 isolated from Henoch‐Schönlein purpura children promotes proliferation of human mesangial cells in vitro

Previous studies show that the proliferation of human mesangial cells (HMCs) played a significant part in the pathogenesis of Henoch‐Schönlein purpura nephritis (HSPN). The aim of this study was to explore the proliferation of HMCs induced by IgA1 isolated from the sera of HSP patients. HMCs were cultured in three different types of media, including IgA1 from patients with HSP (HSP IgA1 group), healthy children (healthy IgA1 group) and medium (control group). The proliferation of HMCs incubated with IgA1 was determined by cell counting kit‐8 assay and bromodeoxyuridine incorporation. The expression of ERK1/2 and phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of the rapamycin (PI3K/AKt/mTOR) signals and transferrin receptor (TfR/CD71) was detected with the methods of immunoblotting. The results indicated that the proliferation of HMCs significantly increased in the HSP IgA1 group compared with that in the control group or the healthy IgA1 group (P < 0.001). Moreover, we found that IgA1 isolated from HSP patients activated ERK and PI3K/AKt/mTOR signals, and markedly increased TfR/CD71 expression in HMCs. These effects induced by IgA1 isolated from patients with HSP were inhibited by human TfR polyclonal antibody (hTfR pAb) and soluble human transferrin receptor (sTfR), indicating that IgA1‐induced HMC proliferation and ERK1/2 and PI3K/AKt/mTOR activation were dependent on TfR/CD71 engagement. Altogether, these data suggested that TfR/CD71 overexpression and ERK1/2 and PI3K/AKt/mTOR activation were engaged in HMC proliferation induced by IgA1 from HSP patients, which might be related to the mesangial injury of HSPN.     

LncDACH1 promotes mitochondrial oxidative stress of cardiomyocytes by interacting with sirtuin3 and aggravates diabetic cardiomyopathy

Science China Life Sciences - Diabetic cardiomyopathy (DCM) is a common complication in diabetic patients. The molecular mechanisms of DCM remain to be fully elucidated. The intronic long noncoding...     

The persistence of parasitic plasmids

The conditions under which plasmids are predicted to persist remain controversial. Here, we reevaluate the ordinary differential equations used previously to model plasmid persistence and conclude that the parameter space required for maintenance is far less stringent than has been supposed. Strikingly, our model demonstrates that purely parasitic plasmids may persist, even in the absence of heterogeneity in the host population, and that this persistence is expressed by oscillations or damped oscillations between the plasmid-bearing and the plasmid-free class.     

Single protein production (SPP) system in Escherichia coli

Here, we provide a detailed protocol for the single protein production (SPP) system, which is designed to produce only a single protein of interest in living Escherichia coli cells. Induction of MazF, an mRNA interferase that cleaves RNA at ACA nucleotide sequences, results in complete cell growth arrest. However, if mRNA encoding a protein of interest is engineered to be devoid of ACA base triplets and is induced at 15 degrees C using pCold vectors in MazF-expressing cells, only the protein from this mRNA is produced at a yield of 20-30% of total cellular protein; other cellular protein synthesis is almost completely absent. In theory, any protein can be produced by the SPP system. Protein yields are typically unaffected even if the culture is condensed up to 40-fold, reducing the cost of protein production by up to 97.5%. The SPP system has a number of key features important for protein production, including high-yield and prolonged production of isotope-labeled protein at a very high signal-to-noise ratio. The procedure can be completed in 7 d after cloning of an ACA-less target gene into the expression system.     

雌激素受体β基因CA重复序列多态性与绝经后骨质疏松症的关联性研究

绝经后骨质疏松症(PMO)是一种多基因调控的遗传性疾病。雌激素受体β亚型基因是骨质疏松症的重要侯选基因。此文采用病例对照设计(78名股骨颈PMO病人和122名对照以及108名腰椎PMO病人和92名对照)研究中国人(汉族)雌激素受体β基因(ESR2)第5内含子CA重复序列多态性与PMO的相关性。以CA重复序列平均数22次为界将重复序列基因分为短基因(<22)和长基因(≥22),分别以S和L表示。股骨颈及腰椎(L2-4)部位,病例组中LL基因型和L等位基因者频率显著高于对照组(P<0.01),SL、LL及SL LL基因型者较SS基因型者患PMO风险显著增高(P<0.05);调整年龄、绝经时间、绝经年龄及体质指数后,Logistic回归分析显示ESR2(CA)n多态性仍然与股骨颈(OR4.923,95%CI1.986～12.203,P=0.001)及L2-4(OR2.267,95%CI1.121～4.598,P=0.023)PMO显著相关。结果显示:ESR2基因CA重复序列多态性与股骨颈和L2-4部位PMO独立关联,L等位基因显性影响PMO的发病风险。