The Coordination of Centromere Replication, Spindle Formation, and Kinetochore–Microtubule Interaction in Budding Yeast

The kinetochore is a protein complex that assembles on centromeric DNA to mediate chromosome–microtubule interaction. Most eukaryotic cells form the spindle and establish kinetochore–microtubule interaction during mitosis, but budding yeast cells finish these processes in S-phase. It has long been noticed that the S-phase spindle in budding yeast is shorter than that in metaphase, but the biological significance of this short S-phase spindle structure remains unclear. We addressed this issue by using ask1-3, a temperature-sensitive kinetochore mutant that exhibits partially elongated spindles at permissive temperature in the presence of hydroxyurea (HU), a DNA synthesis inhibitor. After exposure to and removal of HU, ask1-3 cells show a delayed anaphase entry. This delay depends on the spindle checkpoint, which monitors kinetochore–microtubule interaction defects. Overproduction of microtubule-associated protein Ase1 or Cin8 also induces spindle elongation in HU-arrested cells. The spindle checkpoint-dependent anaphase entry delay is also observed after ASE1 or CIN8 overexpression in HU-arrested cells. Therefore, the shorter spindle in S-phase cells is likely to facilitate proper chromosome–microtubule interaction

Recent Advance in Tumor Microenvironment-Based Stimuli-Responsive Nanoscale Drug Delivery and Imaging Platform

The tumor microenvironment (TME) plays an important role in the development, progression, and metastasis of cancer, and the extremely crucial feature is hypoxic and acidic. Cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), mesenchymal cells, blood vessels, and interstitial fluid are widely recognized as fundamentally crucial hallmarks for TME. As nanotechnology briskly boomed, the nanoscale drug delivery and imaging platform (NDDIP) emerged and has attracted intensive attention. Based on main characteristics of TME, NDDIP can be classified into pH-sensitive delivery and imaging platforms, enzyme-sensitive delivery and imaging platforms, thermo-sensitive delivery and imaging platforms, redox-sensitive delivery and imaging platforms, and light-sensitive delivery and imaging platforms. Furthermore, imageology is one of the significant procedures for disease detection, image-guided drug delivery, and efficacy assessment, including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), and fluorescence imaging. Therefore, the stimuli-responsive NDDIP will be a versatile and practicable tumor disease diagnostic procedure and efficacy evaluation tool. In this review article, we mainly introduce the characteristics of TME and summarize the progress of multitudinous NDDIP as well as their applications

Adsorbate-Induced Structural Evolution of Pd Catalyst for Selective Hydrogenation of Acetylene

ACKNOWLEDGMENT: This work was financially supported by National Natural Science Foundation of China (21908002), project funded by China Postdoctoral Science Foundation (2019M660416, 2020T130045) and the Fundamental Research Funds for the Central Universities (buctrc201921, JD2004, XK1802-6). We would like to thank the UK catalysis Hub for help collecting the XAS.Peer reviewedPostprin

Environmental filtering, spatial processes and biotic interactions jointly shape different traits communities of stream macroinvertebrates

The metacommunity concept has been widely used to explain the biodiversity patterns at various scales. It considers the influences of both local (e.g., environmental filtering and biotic interactions) and regional processes (e.g., dispersal limitation) in shaping community structures. Compared to environmental filtering and spatial processes, the influence of biotic interactions on biodiversity patterns in streams has received limited attention. We investigated the relative importance of three ecological processes, namely environmental filtering (including local environmental and geo-climatic factors), spatial processes and biotic interactions (represented by interactions of macroinvertebrates and diatom), in shaping different traits of macroinvertebrate communities in subtropical streams, Eastern China. We applied variance partitioning to uncover the pure and shared effects of different ecological processes in explaining community variation. The results showed that environmental filtering, spatial processes, and biotic interactions jointly determined taxonomic and trait compositions of stream macroinvertebrates. Spatial processes showed a stronger influence in shaping stream macroinvertebrate communities than environmental filtering. The contribution of biotic interactions to explain variables was, albeit significant, rather small, which was likely a result of insufficient representation (by diatom traits) of trophic interactions associated with macroinvertebrates. Moreover, the impact of three ecological processes on macroinvertebrate communities depends on different traits, especially in terms of environmental filtering and spatial processes. For example, spatial processes and environmental filtering have the strongest effect on strong dispersal ability groups; spatial processes have a greater effect on scrapers than other functional feeding groups. Overall, our results showed that the integration of metacommunity theory and functional traits provides a valuable framework for understanding the drivers of community structuring in streams, which will facilitate the development of effective bioassessment and management strategies.Peer Reviewe

Metal-free base-mediated oxidative annulation cascades to 3-substituted-3-hydroxyoxindole and its 3-spirocyclic derivative

A simple and efficient method was developed for the construction of the medicinally important 3-substituted-3-hydroxyoxindoleand its 3-spirocyclic derivativeswith readily available aniline derivatives as starting materials. Thishighly atom-and step-economical one-pot protocolwas carried out undermetal-freebase-mediated conditions througha novel oxidative annulationstrategywith oxygen as the oxidant.The key intermediates were isolated and confirmed.A reasonablereaction pathway was proposed and supported by both the preliminary experiments and computational studies

Environmental filtering, spatial processes and biotic interactions jointly shape different traits communities of stream macroinvertebrates

The metacommunity concept has been widely used to explain the biodiversity patterns at various scales. It considers the influences of both local (e.g., environmental filtering and biotic interactions) and regional processes (e.g., dispersal limitation) in shaping community structures. Compared to environmental filtering and spatial processes, the influence of biotic interactions on biodiversity patterns in streams has received limited attention. We investigated the relative importance of three ecological processes, namely environmental filtering (including local environmental and geo-climatic factors), spatial processes and biotic interactions (represented by interactions of macroinvertebrates and diatom), in shaping different traits of macroinvertebrate communities in subtropical streams, Eastern China. We applied variance partitioning to uncover the pure and shared effects of different ecological processes in explaining community variation. The results showed that environmental filtering, spatial processes, and biotic interactions jointly determined taxonomic and trait compositions of stream macroinvertebrates. Spatial processes showed a stronger influence in shaping stream macroinvertebrate communities than environmental filtering. The contribution of biotic interactions to explain variables was, albeit significant, rather small, which was likely a result of insufficient representation (by diatom traits) of trophic interactions associated with macroinvertebrates. Moreover, the impact of three ecological processes on macroinvertebrate communities depends on different traits, especially in terms of environmental filtering and spatial processes. For example, spatial processes and environmental filtering have the strongest effect on strong dispersal ability groups; spatial processes have a greater effect on scrapers than other functional feeding groups. Overall, our results showed that the integration of metacommunity theory and functional traits provides a valuable framework for understanding the drivers of community structuring in streams, which will facilitate the development of effective bioassessment and management strategies

Clinical characteristics and prognosis of 272 postterm choriocarcinoma patients at Peking Union Medical College Hospital: a retrospective cohort study

BACKGROUND: The objective of our study was to investigate the clinical characteristics and prognosis of postterm choriocarcinoma patients at Peking Union Medical College Hospital within the past 30 years. METHODS: The clinical characteristics and pertinent follow-up data of 272 patients with postterm choriocarcinoma diagnosed from December 1985 through December 2014 in our hospital were reviewed. The clinical characteristics of two cohorts cut off at 2006 were compared using χ(2) tests. Risk factors of prognosis were estimated by multivariate Cox proportional regression analysis. RESULTS: The most common initial symptom was abnormal uterine bleeding. After individualized treatment 239 patients (87.9 %) achieved complete remission, including 140 patients received initial treatment of 5-fluorouracil-based multidrug chemotherapy. There were almost no statistically significant differences in the clinical characteristics and survival rates between the two cohorts. The results of the multivariate analysis showed that history of resistance to multidrug chemotherapy, liver metastasis and FIGO score greater than 12 were independent risk factors of prognosis. CONCLUSIONS: Postterm choriocarcinoma patients were usually accompanied by several high-risk factors that should received combined chemotherapy to prevent delay in adequate treatment. 5-fluorouracil-based multidrug chemotherapy, which has been applied at PUMCH for several decades, can be an effective initial treatment for postterm choriocarcinoma patients. More emphasis should be placed on those who have history of resistance to multidrug chemotherapy, liver metastasis or a FIGO score greater than 12. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2383-1) contains supplementary material, which is available to authorized users

Highly branched poly(β-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells

Current therapies for most neurodegenerative disorders are only symptomatic in nature and do not change the course of the disease. Gene therapy plays an important role in disease modifying therapeutic strategies. Herein, we have designed and optimized a series of highly branched poly(β-amino ester)s (HPAEs) containing biodegradable disulfide units in the HPAE backbone (HPAESS) and guanidine moieties (HPAESG) at the extremities. The optimized polymers are used to deliver minicircle DNA to multipotent adipose derived stem cells (ADSCs) and astrocytes, and high transfection efficiency is achieved (77% in human ADSCs and 52% in primary astrocytes) whilst preserving over 90% cell viability. Furthermore, the top-performing candidate mediates high levels of nerve growth factor (NGF) secretion from astrocytes, causing neurite outgrowth from a model neuron cell line. This synergistic gene delivery system provides a viable method for highly efficient non-viral transfection of ADSCs and astrocytes

Pre-Treatment with Melatonin Enhances Therapeutic Efficacy of Cardiac Progenitor Cells for Myocardial Infarction

Background/Aims: Melatonin possesses many biological activities such as antioxidant and anti-aging. Cardiac progenitor cells (CPCs) have emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the low survival of transplanted CPCs in infarcted myocardium limits the successful use in treating MI. In the present study, we aimed to investigate if melatonin protects against oxidative stress-induced CPCs damage and enhances its therapeutic efficacy for MI. Methods: TUNEL assay and EdU assay were used to detect the effects of melatonin and miR-98 on H2O2-induced apoptosis and proliferation. MI model was used to evaluate the potential cardioprotective effects of melatonin and miR-98. Results: Melatonin attenuated H2O2-induced the proliferation reduction and apoptosis of c-kit+ CPCs in vitro, and CPCs which pretreated with melatonin significantly improved the functions of post-infarct hearts compared with CPCs alone in vivo. Melatonin was capable to inhibit the increase of miR-98 level by H2O2 in CPCs. The proliferation reduction and apoptosis of CPCs induced by H2O2 was aggravated by miR-98. In vivo, transplantation of CPCs with miR-98 silencing caused the more significant improvement of cardiac functions in MI than CPCs. MiR-98 targets at the signal transducer and activator of the transcription 3 (STAT3), and thus aggravated H2O2-induced the reduction of Bcl-2 protein. Conclusions: Pre-treatment with melatonin protects c-kit+ CPCs against oxidative stress-induced damage via downregulation of miR-98 and thereby increasing STAT3, representing a potentially new strategy to improve CPC-based therapy for MI