The study on the structure of exotic states χc1(3872)\chi_{c 1}(3872) via beauty-hadron decays in pppp collisions at s=8 TeV\sqrt{s}=8\,\mathrm{TeV}

A dynamically constrained phase-space coalescence (DCPC) model was introduced to study the exotic state $\chi_{c 1}(3872)$ yield for three possible structures: tetraquark state, nuclear-like state, and molecular state respectively, where the hadronic final states generated by the parton and hadron cascade model (PACIAE). The $\chi_{c 1}(3872)$/$\psi (2S)$ cross-section ratio from beauty-hadron decays (non-prompt) based on the $\chi_{c 1}(3872)$ or $\psi (2S)\to J/\psi{\pi^+}{\pi^-}$ bound state in the decay chains as a function of charged-particle multiplicity and transverse momentum in $pp$ collisions at $\sqrt{s}=8\,\mathrm{TeV}$ are calculated. A tetraquark state scenario from PACIAE+DCPC model shows better agreement with the LHCb and ATLAS measurements for the non-prompt $\chi_{c 1}(3872)$/$\psi(2S)$ cross-section ratio distributions, indicating that the $\chi_{c 1}(3872)$ is more likely to be a compact tetraquark state

Anthracenedione Derivatives as Anticancer Agents Isolated from Secondary Metabolites of the Mangrove Endophytic Fungi

In this article, we report anticancer activity of 14 anthracenedione derivatives separated from the secondary metabolites of the mangrove endophytic fungi Halorosellinia sp. (No. 1403) and Guignardia sp. (No. 4382). Some of them inhibited potently the growth of KB and KBv200 cells, among which compound 6 displayed strong cytotoxicity with IC50 values of 3.17 and 3.21 μM to KB and KBv200 cells, respectively. Furthermore, we demonstrate that the mechanism involved in the apoptosis induced by compound 6 is probably related to mitochondrial dysfunction. Additionally, the structure-activity relationships of these compounds are discussed

Perforating scleral vessels adjacent to myopic choroidal neovascularization achieved a poor outcome after intravitreal anti-VEGF therapy

BackgroundThis study aimed to summarize the features of perforating scleral vessels (PSVs) in patients with myopic choroidal neovascularization (CNV) (mCNV) using optical coherence tomography angiography (OCTA) and to identify the associations with the response after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.MethodsA consecutive series of naïve patients who had mCNV and received intravitreal anti-VEGF therapy with a follow-up duration of 12 months or more were enrolled. The prevalence, location, and branches of PSVs were analyzed. Projection-resolved OCTA (PR-OCTA) was used to analyze the neovascular signals between CNV and PSVs. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured. The proportion of CMT change relative to baseline was used to assess therapeutic response.ResultsA total of 44 eyes from 42 patients with mCNV were enrolled. PSVs were identified in 41 out of 44 eyes. Branches were identified in the PSVs of 24 eyes (57.14%), and 20 eyes did not have PSV branches (47.62%). In eight eyes (18.18%), PSVs were adjacent to mCNV, and in 36 eyes (81.82%), PSVs were not adjacent to mCNV. After anti-VEGF therapy for mCNV, BCVA increased (F = 6.119, p < 0.001) and CMT decreased (F = 7.664, p < 0.001). In the eyes where PSVs were adjacent to mCNV, BCVA improvements (F = 7.649, p = 0.009) were poor, and changes in CMT were small.ConclusionThe eyes with PSVs adjacent to mCNV showed poor therapeutic responses after intravitreal anti-VEGF therapy

Statistical Research on Marine Natural Products Based on Data Obtained between 1985 and 2008

Since the 1960s, more than 20,000 compounds were discovered from marine organisms. In this paper we performed a quantitative analysis for the novel marine natural products reported between 1985 and 2008. The data was extracted mainly from the reviews of Faulkner and Blunt [1–26]. The organisms producing these marine natural products are divided into three major biological classes: marine microorganisms (including phytoplankton), marine algae and marine invertebrate. The marine natural products are divided into seven classes based on their chemical structure: terpenoids, steroids (including steroidal saponins), alkaloids, ethers (including ketals), phenols (including quinones), strigolactones, and peptides. The distribution and the temporal trend of these classes (biological classes and chemical structure classes) were investigated. We hope this article provides a comprehensive perspective on the research of marine natural products

Identification of Enriched Driver Gene Alterations in Subgroups of Non-Small Cell Lung Cancer Patients Based on Histology and Smoking Status

BACKGROUND: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. METHODS: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. RESULTS: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. CONCLUSION: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies

Ribosomal S6 Kinase 2 (RSK2) Maintains Genomic Stability by Activating the Atm/p53-Dependent DNA Damage Pathway

10.1371/journal.pone.0074334PLoS ONE89-POLN

Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations

<p>Abstract</p> <p>Background</p> <p>Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of <it>ATP7B </it>mutations and to more completely characterize WND in China.</p> <p>Methods</p> <p>The coding and promoter regions of the <it>ATP7B </it>gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old).</p> <p>Results</p> <p>Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065).</p> <p>Conclusions</p> <p>We identified 14 novel mutations and found that the spectrum of mutations of <it>ATP7B </it>in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region