中国河北省卢龙县儿童轮状病毒腹泻研究

轮状病毒是我国儿童重症腹泻的主要病原。按照WHO轮状病毒监测方案,于1999年7月至2003年6月,在河北省卢龙县开展了医院和社区为基础<5岁儿童轮状病毒腹泻的监测。结果表明:卢龙县<5岁儿童腹泻的发病率为1 3次/人/年。4年中全县共有2350名<5岁急性腹泻患儿住院,占所有住院儿童的38%(2350/6213)。住院的腹泻患儿每年有两个高峰,一个是夏季(6～8月),占全年腹泻住院病例的22%;另一个在冬季(12月至次年2月),占58%。住院的轮状病毒腹泻只有一个高峰,是在冬季(12月至次年2月),高峰期的轮状病毒腹泻住院患儿数占全年轮状病毒腹泻患儿住院数的86%。按全年统计,轮状病毒腹泻占住院腹泻患儿的46%,轮状病毒腹泻的住院率为11/1000儿童/年。在门诊腹泻患儿中轮状病毒腹泻患儿占28%,在社区腹泻患儿中轮状病毒腹泻占10%。轮状病毒毒株的分布,G3型(45%)最常见,其次为G1型(35%)、G2型(8%)、G4型(3%)、G9型(0 6%),混合感染较少(1%)。还有8%的毒株未能分出型别。在轮状病毒腹泻患者中,9～11月龄的儿童检出率最高(53%),其次是12～17月龄(51%)、18～23月龄(36%)和6～8月龄(30%)。在4年研究期间共有5～10名1～59月龄儿童可能因为轮状病毒腹泻死亡,其中有1例确诊为P[8]G1型毒株感染。初步估计,该县1～59月龄儿童轮状病毒腹泻的死     

Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation

Background  

Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem, ranging from deterministic to non-deterministic and systemic to stochastic ones. In this work, we described an efficient conformation sampling method named Cyndi, which is based on multi-objective evolution algorithm.     

Dispersal among local communities does not reduce historical contingencies during metacommunity assembly

Ample evidence suggests that ecological communities can exhibit historical contingencies. However, few studies have explored whether differences in assembly history can generate alternative local community states in metacommunities in which local communities are linked by dispersal. In a protist microcosm experiment, we examined the influence of species colonization history on metacommunity assembly under homogeneous environmental conditions, by manipulating both the sequence of species colonization into local communities and the rate of dispersal among local communities. Whereas the role of dispersal in structuring local communities decreased over time and became non‐significant towards the end of the experiment, species colonization history significantly influenced local communities throughout the experiment. Local communities, regardless of the rate of dispersal among them, exhibited two alternative states characterized by the dominance of different species. The alternative community states, however, emerged in the absence of priority effects that were often associated with alternative community states found in other assembly studies. Rather, they were driven by variation in species interaction strength among local communities with different assembly histories. These results suggest that dispersal among local communities may not necessarily reduce the role of species colonization history in shaping metacommunity assembly, and that differences in species colonization history need to be explicitly considered as an important factor in causing heterogeneous community states in metacommunities.     

Splicing function of mitotic regulators links R-loop–mediated DNA damage to tumor cell killing

Although studies suggest that perturbing mitotic progression leads to DNA damage and p53 activation, which in turn lead to either cell apoptosis or senescence, it remains unclear how mitotic defects trigger p53 activation. We show that BuGZ and Bub3, which are two mitotic regulators localized in the interphase nucleus, interact with the splicing machinery and are required for pre-mRNA splicing. Similar to inhibition of RNA splicing by pladienolide B, depletion of either BuGZ or Bub3 led to increased formation of RNA–DNA hybrids (R-loops), which led to DNA damage and p53 activation in both human tumor cells and primary cells. Thus, R-loop–mediated DNA damage and p53 activation offer a mechanistic explanation for apoptosis of cancer cells and senescence of primary cells upon disruption of the dual-function mitotic regulators. This demonstrates the importance of understanding the full range of functions of mitotic regulators to develop antitumor drugs.     

Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.     

Muscle mass,structural and functional investigations of senescence-accelerated mouse P8 (SAMP8)

Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, most of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study.     

Lily Cultivars Have Allelopathic Potential in Controlling Orobanche aegyptiaca Persoon

As a devastating holoparasitic weed, Orobanche aegyptiaca Persoon. (Egyptian broomrape) causes serious damage to agricultural production and threatens economic development, which has raised widespread concern. The present study was conducted to determine whether lilies have the potential to be used as ‘trap crops’ for controlling O. aegyptiaca Persoon. In the experiments, the ability of three popular lily cultivars (Lilium Oriental hybrids ‘Sorbonne’, Lilium LA (Longiflorum hybrids x Asiatic hybrids) hybrids ‘Ceb Dazzle’, and Lilium Longiflorum hybrids (L. formosanum x L. longiflorum) ‘L. formolongo’) to induce O. aegyptiaca Persoon. seed germination was assessed. Parts of the three lily cultivars, including the rhizosphere soil and underground and above-ground organs, all induced “suicidal germination” of parasitic O. aegyptiaca Persoon. seed at four growth stages. Specifically, Sorbonne and Ceb Dazzle behaved with similar allelopathy, and the bulb, scale leaf and aerial stem exhibited stronger allelopathic effects on O. aegyptiaca Pers. germination compared to other organs. Aqueous L. formolongo leaf extracts may contain more stable, effective stimulants given that they induced the highest germination rate at 76.7% even though the extracts were serially diluted. We speculate that these organs may be advantageous in further isolating and purifying economical active substances that can be substitutes for GR24. These results indicate that lilies have the potential to be used as a trap crops or can be processed into green herbicide formulations that can be applied in agriculture production to rapidly deplete the seed bank of O. aegyptiaca Persoon. parasitic weeds in soil.     

Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Importance

Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke.

Objective

To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke.

Data Sources

MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015.

Study Selection

Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected.

Data Extraction and Synthesis

Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes.

Main Outcomes and Measures

The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage.

Results

Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration.

Conclusions and Relevance

This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment.