The mediating effect of body mass index on the relationship between cigarette smoking and atopic sensitization in Chinese adults

Background: It is unclear whether the relationship between cigarette smoking and atopy is mediated by body fat mass, such as the Body Mass Index (BMI). We assessed the mediating role of BMI on the relationship between smoking and atopy in Chinese adults. Methods: A hospital-based case-control study of 786 atopic cases and 2771 controls was conducted in adults aged 18 years or older from March 2010 to September 2014 in Harbin, China. Mediation models were used to estimate the indirect effects of smoking on atopic sensitization through BMI. Results: Compared to non-smokers, light smokers and moderate smokers had a lower risk of inhalant allergen sensitization. The indirect effect of smoking and sensitization to aeroallergens were only observed in light smokers (point estimate, -0.026; 95% CI, -0.062 to -0.004). The mediating roles of BMI on the relationships between smoking and other types of allergic sensitization were not statistically significant. Conclusion: BMI appeared to partially mediate the effect of light smoking on sensitization to aeroallergens. However, considering the other harmful health effects of cigarette smoking, the effective method to lower the incidence of atopy would be to decrease body fat mass by physical exercise and employing other more healthy ways of living rather than smoking

In-Context Sharpness as Alerts: An Inner Representation Perspective for Hallucination Mitigation

Large language models (LLMs) frequently hallucinate and produce factual errors, yet our understanding of why they make these errors remains limited. In this study, we delve into the underlying mechanisms of LLM hallucinations from the perspective of inner representations, and discover a salient pattern associated with hallucinations: correct generations tend to have sharper context activations in the hidden states of the in-context tokens, compared to the incorrect ones. Leveraging this insight, we propose an entropy-based metric to quantify the ``sharpness'' among the in-context hidden states and incorporate it into the decoding process to formulate a constrained decoding approach. Experiments on various knowledge-seeking and hallucination benchmarks demonstrate our approach's consistent effectiveness, for example, achieving up to an 8.6 point improvement on TruthfulQA. We believe this study can improve our understanding of hallucinations and serve as a practical solution for hallucination mitigation.Comment: code repo is available at: https://github.com/hkust-nlp/Activation_decoding.gi

Current monitoring in nanochannels

CBET-1653767 - National Science FoundationAccepted manuscrip

Boosting Few-Shot Text Classification via Distribution Estimation

Distribution estimation has been demonstrated as one of the most effective approaches in dealing with few-shot image classification, as the low-level patterns and underlying representations can be easily transferred across different tasks in computer vision domain. However, directly applying this approach to few-shot text classification is challenging, since leveraging the statistics of known classes with sufficient samples to calibrate the distributions of novel classes may cause negative effects due to serious category difference in text domain. To alleviate this issue, we propose two simple yet effective strategies to estimate the distributions of the novel classes by utilizing unlabeled query samples, thus avoiding the potential negative transfer issue. Specifically, we first assume a class or sample follows the Gaussian distribution, and use the original support set and the nearest few query samples to estimate the corresponding mean and covariance. Then, we augment the labeled samples by sampling from the estimated distribution, which can provide sufficient supervision for training the classification model. Extensive experiments on eight few-shot text classification datasets show that the proposed method outperforms state-of-the-art baselines significantly.Comment: Accepted to AAAI 202

A Novel Splicing Mutation Alters DSPP Transcription and Leads to Dentinogenesis Imperfecta Type II

Dentinogenesis imperfecta (DGI) type II is an autosomal dominant disease characterized by a serious disorders in teeth. Mutations of dentin sialophosphoprotein (DSPP) gene were revealed to be the causation of DGI type II (DGI-II). In this study, we identified a novel mutation (NG_011595.1:g.8662T>C, c.135+2T>C) lying in the splice donor site of intron 3 of DSPP gene in a Chinese Han DGI-II pedigree. It was found in all affected subjects but not in unaffected ones or other unrelated healthy controls. The function of the mutant DSPP gene, which was predicted online and subsequently confirmed by in vitro splicing analysis, was the loss of splicing of intron 3, leading to the extended length of DSPP mRNA. For the first time, the functional non-splicing of intron was revealed in a novel DSPP mutation and was considered as the causation of DGI-II. It was also indicated that splicing was of key importance to the function of DSPP and this splice donor site might be a sensitive mutation hot spot. Our findings combined with other reports would facilitate the genetic diagnosis of DGI-II, shed light on its gene therapy and help to finally conquer human diseases

Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a star medication used to treat non-small-cell lung carcinomas (NSCLCs). It has caused broad public concern that osimertinib has relatively low stability in plasma. We explored why osimertinib and its primary metabolites AZ-5104 and AZ-7550 are unstable in rat plasma. Our results suggested that it is the main reason inducing their unstable phenomenon that the Michael addition reaction was putatively produced between the Michael acceptor of osimertinib and the cysteine in the plasma matrix. Consequently, we identified a method to stabilize osimertinib and its metabolite contents in plasma. The assay was observed to enhance the stability of osimertinib, AZ-5104, and AZ-7550 significantly. The validated method was subsequently applied to perform the pharmacokinetic study for osimertinib in rats with the newly established, elegant, and optimized ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS) strategy. The assay was assessed for accuracy, precision, matrix effects, recovery, and stability. This study can help understand the pharmacological effects of osimertinib and promote a solution for the similar problem of other Michael acceptor-contained third-generation EGFR-TKI

The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense

这是周大旺教授继2009年首次发现了Hippo信号通路在哺乳动物中控制器官大小及肿瘤发生具有重要作用后的又一重大研究成果，该研究系统阐述了 YAP基因在转录调控水平上的的调控机理，进一步完善了人们对Hippo信号通路的认识，也为由YAP调控异常所引发的癌症提供了一个潜在的治疗靶点。 该论文的第一作者为博士生吴黉坦和硕士生肖玉波和张世浩, 通讯作者是周大旺教授和陈兰芬副教授，该工作是与厦门市中医院、中山医院和医学高等专科学校等单位合作完成的。周大旺教授是中央首批“青年千人计划”入选者并获得国家首批“优秀青年科学基金”资助。The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP

The complete reference genome for grapevine (Vitis vinifera L.) genetics and breeding

Grapevine is one of the most economically important crops worldwide. However, the previous versions of the grapevine reference genome consisted of thousands of fragments with missing centromeres and telomeres, which limited the accessibility of the repetitive sequences, the centromeric and telomeric regions, and the inheritance of important agronomic traits in these regions. Here, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the pinot noir cultivar (PN40024) using the PacBio HiFi long reads. The T2T reference genome (PN_T2T) was 69 Mb longer with 9026 more genes identified than the 12X.v2 version (Canaguier et al., 2017). We annotated 67% repetitive sequences, 19 centromeres and 36 telomeres, and incorporated gene annotations of previous versions into the PN_T2T. We detected a total of 377 gene clusters, which showed associations with complex traits, such as aroma and disease resistance. Even though the PN40024 sample had been selfed for nine generations, we still found nine genomic hotspots of heterozygous sites associated with biological processes, such as the oxidation-reduction process and protein phosphorylation. The fully annotated complete reference genome, therefore, provides important resources for grapevine genetics and breeding.This work was supported by the National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas) to Yongfeng Zhou, the National Key Research and Development Program of China(grant2019YFA0906200), the Agricultural Science and Technology Innovation Program (CAAS-ZDRW202101), the Shenzhen Science and Technology Program (grant KQTD2016113010482651), the BMBF funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI). We thank Bianca Frommer, Marie Lahaye, David Navarro-Payá, Marcela K. Tello-Ruiz and Kapeel Chougule for their help in analyzing the RNA-Seq data and in running the gene annotation pipeline. This study is also based upon work from COST Action CA17111 INTEGRAPE and form COST Innovators Grant IG17111 GRAPEDIA, supported by COST (European Cooperation in Science and Technology).ViticultureT2Tgap-fregene clustercentromeretelomerePublishe