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Background Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. Methods We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. Results The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR , with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. Conclusion The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.

Purpose To evaluate the feasibility and effectiveness of intraoperative ultrasonic biomicroscopy (UBM)-guided direct cyclopexy for treating traumatic cyclodialysis clefts. Methods Intraoperative UBM-guided direct cyclopexy was performed on a total of four eyes. Prior to the conjunctival incision, UBM evaluation was facilitated with a self-designed eye cup. Scleral flaps were generated according to their respective locations. Before the scleral flaps and conjunctiva were closed, UBM was used to promptly assess the repositioning status. Results 1.UBM-guided direct cyclopexies were performed on four male patients (mean age: 39.7 years). In all instances, the cyclodialysis cleft resulted from blunt ocular trauma, with an average time interval between injury and surgical treatment of 29.5 days. 2. A simple cyclodialysis cleft was observed in two patients. One patient had retinal detachment and subluxation of the lens, and one presented with a shallow anterior chamber, iridodialysis, cataract, vitreous hemorrhage, papilledema, and hypotony maculopathy. 3. Prior to surgery, the mean IOP in all four patients was 7 mmHg (range: 6–9 mmHg), which increased to an average of 16.5 mmHg on postsurgical day three (range: 11–22 mmHg). 4. UBM examination confirmed successful closure of the cleft in all patients. Conclusion During the procedure, UBM-guided direct cyclopexies can accurately assess cyclodialysis cleft repair without being affected by the optical clarity of the refractive media. Preliminary findings demonstrate the feasibility of this approach.

Here we use a Discriminant Genetic Algorithm Extended （DGAE） model to diagnose and predict seasonal sand and dust storm （SDS） activities occurring in Northeast Asia. The study employed the regular meteorological data, including surface data, upper air data, and NCEP reanalysis data, collected from 1980-2006. The regional, seasonal, and annual differences of 3-D atmospheric circulation structures and SDS activities in the context of spatial and temporal distributions were given. Genetic al- gorithms were introduced with the further extension of promoting SDS seasonal predication from multi-level resolution. Ge- netic probability was used as a substitute for posterior probability of multi-level discriminants, to show the dual characteristics of crossover inheritance and mutation and to build a non-linear adaptability function in line with extended genetic algorithms. This has unveiled the spatial distribution of the maximum adaptability, allowing the forecast field to be defined by the popula- tion with the largest probability, and made discriminant genetic extension possible. In addition, the effort has led to the establishment of a regional model for predicting seasonal SDS activities in East Asia. The model was tested to predict the spring SDS activities occurring in North China from 2007 to 2009. The experimental forecast resulted in highly discriminant intensity ratings and regional distributions of SDS activities, which are a meaningful reference for seasonal SDS predictions in the future.

Alterations in cellular ubiquitin （Ub） homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. Here we report that autophagy receptor p62/sequestosome-1 interacts with E2 Ub conjugating enzymes, UBE2D2 and UBE2D3. Endogenous p62 undergoes E2-dependent ubiquitylation during upregulation of Ub homeostasis, a condition termed as Ub~ stress, that is intrinsic to Ub overexpression, heat shock or prolonged proteasomal inhibition by bortezomib, a chemothera- peutic drug. Ubiquitylation of p62 disrupts dimerization of the UBA domain of p62, liberating its ability to recognize polyubiquitylated cargoes for selective autophagy. We further demonstrate that this mechanism might be critical for autophagy activation upon Ub stress conditions. Delineation of the mechanism and regulatory roles of p62 in sensing Ub stress and controlling selective autophagy could help to understand and modulate cellular responses to a variety of endogenous and environmental challenges, potentially opening a new avenue for the development of therapeutic strategies against autophagy-related maladies.

Chest computed tomography （CT） screening is becoming more popular in China. Therefore, more and more rare diseases and early stages of lung diseases were found. Here, we reported a case who presented as multiple ground glass nodules incidentally found in chest CT scan who had been suspected as synchronous multiple primary lung cancer （SMPLC） and/or metastatic cancer. She was finally diagnosed as tuberous sclerosis complex （TSC）, an autosomal-dominant disorder characterized by the fort-nation of hanaartomatous lesions in the skin, eyes, kidney, and central nervous system. Tuberous sclerosis complex 1 （TSC1） gene mutation （c.1030-1G〉A） was found in her and her family members. This is a very rare report in China.

目的：通过pEnho基因的克隆,分析p Enho基因在仔猪相关组织的分布情况,增加仔猪糖脂代谢方面相关的知识,为通过调控adropin来促进仔猪的健康和生长提供理论基础。创新点：首次克隆了猪Enho基因,命名为p Enho,其基因序列提交至美国国立生物技术信息中心（NCBI）（No.GQ414763）。方法：通过实时荧光定量逆转录聚合酶链式反应（real-time RT-PCR）方法获得猪Enho基因序列,并应用BLAST、Clustal W、PHYLIP、TMHMM、Helixturnhelix等生物信息学软件对其基因序列进行分析;通过荧光定量PCR方法检测了不同日龄（出生后1、7、14和21天）猪Enho基因的组织分布（肝脏、肌肉、空肠前端、空肠后端和回肠）。结论：克隆得到p Enho基因序列;发现随着仔猪日龄的增加,其表达量有下降;在组织分布上,产后7天内p Enho在肠道（特别是回肠）的表达量较高,在第14天和第21天,各被检组织的表达量无显著差异。

ObjectiveCelastrus orbiculatus Thunb. has been used for thousands of years in China as a remedy against cancer and inflammatory diseases. This study aims to investigate whether C. orbiculatus extract (COE) could inhibit angiogenesis, which is the pivotal step in tumor growth, invasiveness, and metastasis.MethodsIn this study, the extract from the stem of C. orbiculatus was used. Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations (10, 20, 40, 80, and 160 μg/mL). The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively; the active fractions were further tested on C57BL/6 mice and human umbilical vein endothelial cells (HUVEC) for any antiangiogenic effects.ResultsCOE significantly inhibited proliferation and induced apoptosis in Hepa1-6 cells and inhibited VEGF expression at both mRNA and protein levels. Furthermore, this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner. In vivo, COE significantly reduced the volume and weight of solid tumors with low adverse effects and decreased tumor angiogenesis.ConclusionsIn summary, COE could be used to treat hepatic carcinoma. The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein.

The Sanchahe River in southwest China is a tributary of the Wujiang River and experiences high erosion rates. Geochemical analysis was conducted on Sanchahe River basin samples collected in the wet and dry seasons of 2014 in order to better understand local chemical weathering processes, anthropogenic influences, and associated CO2 consumption. The samples＇ total dissolved solid concentrations were found to be significantly higher than that of the global river average. Ca^2＋was the dominant cation in the samples and accounted for 64 % and73 % of the total cations in the dry and wet seasons,respectively. HCO3^-and SO4^2-were the dominant anions,accounting for 92 % of the total anions. Stoichiometry analyses of the river waters suggested that the water chemistry is controlled by carbonate dissolution by both carbonic and sulfuric acid. The chemical weathering rates of carbonate and silicate evaporites in the Sanchahe River basin were estimated to be approximately 109.2 and 11.0 t/（km^2a）, respectively, much higher than both the global mean values and the Wujiang River, a typical karstic river.The CO2 consumption by carbonate and silicate weathering are estimated to be 597.4×10^3 and 325.5×10^3mol/（km^2a）, which are much higher than corresponding values in the Wujiang River, indicating a high erosion rate in the Sanchahe River basin.

The aim of this study was to develop and validate an oligonucleotide suspension array for rapid identification of 15 bacterial species responsible for bacteremia, particularly prevalent in Chinese hospitals. The multiplexed array, based on the QIAGEN LiquiChip Workstation, included 15 oligonucleotide probes which were covalently bound to different bead sets. PCR amplicons of a variable region of the bacterial 23S rRNA genes were hybridized to the bead-bound probes. Thirty-eight strains belonging to 15 species were correctly identified on the basis of their corresponding species-specific hybridization profiles. The results show that the suspension array, in a single assay, can differentiate isolates over a wide range of strains and species, and suggest the potential utility of suspension array system to clinical laboratory diagnosis.

Plants transport fixed carbon predominantly as sucrose, which is produced in mesophyll cells and imported into phloem cells for translocation throughout the plant. It is not known how sucrose migrates from sites of synthesis in the mesophyll to the phloem, or which cells mediate efflux into the apoplasm as a prerequisite for phloem loading by the SUT sucrose-H⁺ (proton) cotransporters. Using optical sucrose sensors, we identified a subfamily of SWEET sucrose efflux transporters. AtSWEET11 and 12 localize to the plasma membrane of the phloem. Mutant plants carrying insertions in AtSWEET11 and 12 are defective in phloem loading, thus revealing a two-step mechanism of SWEET-mediated export from parenchyma cells feeding H⁺-coupled import into the sieve element-companion cell complex. We discuss how restriction of intercellular transport to the interface of adjacent phloem cells may be an effective mechanism to limit the availability of photosynthetic carbon in the leaf apoplasm in order to prevent pathogen infections.