The value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure

OBJECTIVE: To investigate the value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure. METHODS: A single-center, prospective, randomized, controlled pilot trial was conducted between January 2013 and December 2014. Sixty enrolled patients were randomized immediately after extubation into either a high-flow nasal cannula group (n=30) or an air entrainment mask group (n=30) at a fixed inspired oxygen fraction (40%). The success rate of oxygen therapy, respiratory and hemodynamic parameters and subjective discomfort (using a visual analogue scale) were assessed at 24h after extubation. RESULTS: The two groups were comparable at extubation. A total of 46 patients were successfully treated including 27 patients in the high-flow nasal cannula group and 19 patients in the air entrainment mask group. Compared to the air entrainment mask group, the success rate of oxygen therapy and the partial pressure of arterial oxygen were significantly higher and the respiratory rate was lower in the high-flow nasal cannula group. In addition, less discomfort related to interface displacement and airway dryness was observed in the high-flow nasal cannula group than in the air entrainment mask group. CONCLUSIONS: At a fixed inspired oxygen fraction, the application of a high-flow nasal cannula after extubation achieves a higher success rate of oxygen therapy and less discomfort at 24h than an air entrainment mask in patients with acute respiratory failure

ISP1-anchored Polarization of GCβ/CDC50A Complex Initiates Malaria Ookinete Gliding Motility

该工作历时四年，由博士毕业生高涵（第一作者）、博士生杨振科和王旭（共同第一作者）、硕士生钱鹏戈和洪仁杰完成；袁晶教授为通讯作者；厦门大学为第一完成单位。 该工作揭示了疟疾病原疟原虫通过媒介按蚊传播过程中的关键步骤---控制动合子运动的环磷酸鸟苷cGMP信号的激活机制。 疟原虫属于顶复体亚门原生动物，每年导致数亿人口感染疟疾和超过40万病人死亡。疟原虫通过雌性按蚊在哺乳动物宿主间传播。疟疾病人被按蚊叮咬吸血，疟原虫雌雄配子在按蚊消化道中受精形成合子，进一步变形发育为具有运动能力的新月形动合子。只有获得运动能力的动合子，才能穿越按蚊消化道单层上皮细胞，成功感染按蚊媒介。在本研究中，通过大量基因修饰模型，发现GCβ缺失导致动合子运动完全丢失，进而失去按蚊感染和传播能力。研究还发现，GCβ由细胞质均匀分布改变为在动合子顶体突出一侧聚集，并且GCβ聚集和动合子成熟完全同步，显示GCβ聚集可能直接激活cGMP信号。 本工作还发现GCβ结合蛋白CDC50A，后者承担分子伴侣功能，在动合子转化和成熟动合子中，稳定GCβ。此外，进一步筛选发现动合子内膜复合物蛋白ISP1，能够结合和锚定GCβ/CDC50A复合物，在成熟动合子中维持复合物的聚集。本研究为深入开展寄生性原生动物的发育转化和信号调控提供了线索和借鉴。【Abstract】Ookinete gliding motility is essential for penetration of the mosquito midgut wall and transmission of malaria parasites. Cyclic guanosine monophosphate (cGMP) signaling has been implicated in ookinete gliding. However, the upstream mechanism of how the parasites activate cGMP signaling and thus initiate ookinete gliding remains unknown. Using real-time imaging to visualize Plasmodium yoelii guanylate cyclase β (GCβ), we show that cytoplasmic GCβ translocates and polarizes to the parasite plasma membrane at “ookinete extrados site” (OES) during zygote to ookinete differentiation. The polarization of enzymatic active GCβ at OES initiates gliding of matured ookinete. Both the P4-ATPase-like domain and guanylate cyclase domain are required for GCβ polarization and ookinete gliding. CDC50A, a co-factor of P4-ATPase, binds to and stabilizes GCβ during ookinete development. Screening of inner membrane complex proteins identifies ISP1 as a key molecule that anchors GCβ/CDC50A complex at the OES of mature ookinetes. This study defines a spatial-temporal mechanism for the initiation of ookinete gliding, where GCβ polarization likely elevates local cGMP levels and activates cGMP-dependent protein kinase signaling.We thank Dr. David Baker (London School of Hygiene and Tropical Medicine) for his comments on this manuscript. This work was supported by the National Natural Science Foundation of China (81522027, 31772443, and 31501912), the Fundamental Research Funds for the Central Universities (20720160069, 20720150165, and 2013121033), the China's 1000 Young Talents Program, the “111” Project of the Ministration of Education of China (B06016), and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH (X.S.). The authors thank Cindy Clark, NIH Library Writing Center, for manuscript editing assistance. 该研究得到国家自然科学基金委、中组部“青年千人计划”和厦门大学校长基金的资助

Genetic basis of the early heading of high-latitude weedy rice

Japonica rice (Oryza sativa L.) is an important staple food in high-latitude regions and is widely distributed in northern China, Japan, Korea, and Europe. However, the genetic diversity of japonica rice is relatively narrow and poorly adapted. Weedy rice (Oryza sativa f. spontanea) is a semi-domesticated rice. Its headings are earlier than the accompanied japonica rice, making it a potential new genetic resource, which can make up for the defects of wild rice that are difficult to be directly applied to japonica rice improvement caused by reproductive isolation. In this study, we applied a natural population consisting of weedy rice, japonica landrace, and japonica cultivar to conduct a genome-wide association study (GWAS) of the heading date and found four loci that could explain the natural variation of the heading date in this population. At the same time, we developed recombinant inbred lines (RILs) crossed by the early-heading weedy rice WR04-6 and its accompanied japonica cultivar ShenNong 265 (SN265) to carry out a QTL mapping analysis of the heading date and mapped four quantitative trait locus (QTLs) and three epistatic effect gene pairs. The major locus on chromosome 6 overlapped with the GWAS result. Further analysis found that two genes, Hd1 and OsCCT22, on chromosome 6 (Locus 2 and Locus 3) may be the key points of the early-heading character of weedy rice. As minor effect genes, Dth7 and Hd16 also have genetic contributions to the early heading of weedy rice. In the process of developing the RIL population, we introduced fragments of Locus 2 and Locus 3 from the weedy rice into super-high-yielding japonica rice, which successfully promoted its heading date by at least 10 days and expanded the rice suitable cultivation area northward by about 400 km. This study successfully revealed the genetic basis of the early heading of weedy rice and provided a new idea for the genetic improvement of cultivated rice by weedy rice

Carbocisteine Improves Histone Deacetylase 2 Deacetylation Activity via Regulating Sumoylation of Histone Deacetylase 2 in Human Tracheobronchial Epithelial Cells

Histone deacetylase (HDAC) 2 plays a vital role in modifying histones to mediate inflammatory responses, while HDAC2 itself is commonly regulated by post-translational modifications. Small ubiquitin-related modifier (SUMO), as an important PTM factor, is involved in the regulation of multiple protein functions. Our previous studies have shown that carbocisteine (S-CMC) reversed cigarette smoke extract (CSE)-induced down-regulation of HDAC2 expression/activity in a thiol/GSH-dependent manner and enhanced sensitivity of steroid therapy. However, the mechanism by which S-CMC regulates HDAC2 is worth further exploring. Our study aimed to investigate the relationships between HDAC2 sumoylation and its deacetylase activity under oxidative stress and the molecular mechanism of S-CMC to regulate HDAC2 activity that mediates inflammatory responses in human bronchial epithelial cells. We found that modification of HDAC2 by SUMO1 and SUMO2/3 occurred in 16HBE cells under physiological conditions, and CSE induced SUMO1 modification of HDAC2 in a dose and time-dependent manner. K462 and K51 of HDAC2 were the two major modification sites of SUMO1, and the K51 site mediated deacetylation activity and function of HDAC2 on histone H4 that regulates IL-8 secretion. S-CMC inhibited CSE-induced SUMO1 modification of HDAC2 in the presence of thiol/GSH, increased HDAC activity, and decreased IL-8 expression. Our study may provide novel mechanistic explanation of S-CMC to ameliorate steroid sensitivity treatment in chronic obstructive pulmonary disease

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte

Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD(+) levels in aged muscles, rejuvenating the animals' running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose

Genetic Diversity and Lack of Artemisinin Selection Signature on the Plasmodium falciparum ATP6 in the Greater Mekong Subregion

The recent detection of clinical Artemisinin (ART) resistance manifested as delayed parasite clearance in the Cambodia-Thailand border area raises a serious concern. The mechanism of ART resistance is not clear; but the P. falciparum sarco/endoplasmic reticulum Ca2+-ATPase (PfSERCA or PfATP6) has been speculated to be the target of ARTs and thus a potential marker for ART resistance. Here we amplified and sequenced pfatp6 gene (~3.6 Kb) in 213 samples collected after 2005 from the Greater Mekong Subregion, where ART drugs have been used extensively in the past. A total of 24 single nucleotide polymorphisms (SNPs), including 8 newly found in this study and 13 nonsynonymous, were identified. However, these mutations were either uncommon or also present in other geographical regions with limited ART use. None of the mutations were suggestive of directional selection by ARTs. We further analyzed pfatp6 from a worldwide collection of 862 P. falciparum isolates in 19 populations from Asia, Africa, South America and Oceania, which include samples from regions prior to and after deployments ART drugs. A total of 71 SNPs were identified, resulting in 106 nucleotide haplotypes. Similarly, many of the mutations were continent-specific and present at frequencies below 5%. The most predominant and perhaps the ancestral haplotype occurred in 441 samples and was present in 16 populations from Asia, Africa, and Oceania. The 3D7 haplotype found in 54 samples was the second most common haplotype and present in nine populations from all four continents. Assessment of the selection strength on pfatp6 in the 19 parasite populations found that pfatp6 in most of these populations was under purifying selection with an average dN/dS ratio of 0.333. Molecular evolution analyses did not detect significant departures from neutrality in pfatp6 for most populations, challenging the suitability of this gene as a marker for monitoring ART resistance

Compound-based Chinese medicine formula: From discovery to compatibility mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese medicine formula (CMF) has a long history of clinical use in the treatment of various diseases under the guidance of traditional Chinese medicine (TCM) theory. The application of CMF can be divided into three levels, crude extracts, homologous compounds mixture, and specific compounds. However, the modern scientific connotation of the CMF theory has not been clarified. AIM OF THE REVIEW: To critically evaluate the research strategy for the investigation of compound-based CMF (CCMF). MATERIALS AND METHODS: The related information was collected from the scientific databases, including CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Web of Science, and Wiley Online. RESULTS: The research design including discovery, screening, optimization, pharmacodynamics models, and target research techniques including the targets for compatibility compounds were evaluated. Essentially it has been evaluated that the in vitro multicellular three-dimensional culture or organoid model has been proposed for the optimization model for compatibility research of CCMF. Based on these, the traditional compatibility theory of CMF, such as Monarch-Minister-Assistant-Guide (Jun-Chen-Zuo-Shi in Chinese), can probably be elucidated by the CCMF research. CONCLUSIONS: CCMF has the clear advantage of providing the exact composition and controllable quality of modern medicines, in addition to having the characteristics of multi-ingredients and multi-targets synergistic effects of TCM. However, CCMF is still associated with challenges which need to be addressed for its future use