Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution.

We designed an epi-illumination SPIM system that uses a single objective and has a sample interface identical to that of an inverted fluorescence microscope with no additional reflection elements. It achieves subcellular resolution and single-molecule sensitivity, and is compatible with common biological sample holders, including multi-well plates. We demonstrated multicolor fast volumetric imaging, single-molecule localization microscopy, parallel imaging of 16 cell lines and parallel recording of cellular responses to perturbations

Deep Variational Free Energy Approach to Dense Hydrogen

We developed a deep generative model-based variational free energy approach to the equations of state of dense hydrogen. We employ a normalizing flow network to model the proton Boltzmann distribution and a fermionic neural network to model the electron wave function at given proton positions. By jointly optimizing the two neural networks we reached a comparable variational free energy to the previous coupled electron-ion Monte Carlo calculation. The predicted equation of state of dense hydrogen under planetary conditions is denser than the findings of ab initio molecular dynamics calculation and empirical chemical model. Moreover, direct access to the entropy and free energy of dense hydrogen opens new opportunities in planetary modeling and high-pressure physics research.Comment: 7+5 pages, 3+4 figures, code: https://github.com/fermiflow/hydroge

Neural Simile Recognition with Cyclic Multitask Learning and Local Attention

Simile recognition is to detect simile sentences and to extract simile components, i.e., tenors and vehicles. It involves two subtasks: {\it simile sentence classification} and {\it simile component extraction}. Recent work has shown that standard multitask learning is effective for Chinese simile recognition, but it is still uncertain whether the mutual effects between the subtasks have been well captured by simple parameter sharing. We propose a novel cyclic multitask learning framework for neural simile recognition, which stacks the subtasks and makes them into a loop by connecting the last to the first. It iteratively performs each subtask, taking the outputs of the previous subtask as additional inputs to the current one, so that the interdependence between the subtasks can be better explored. Extensive experiments show that our framework significantly outperforms the current state-of-the-art model and our carefully designed baselines, and the gains are still remarkable using BERT.Comment: AAAI 202

Analysis of tumor-related features of non-small cell lung cancer based on TCR repertoire workflow

Objective·To explore the immune-related characteristics of non-small cell lung cancer (NSCLC), discover potential tumor markers in V-J genes, and lay the foundation for establishing a TCR-antigen recognition prediction model.Methods·A total of 704 NSCLC samples were collected to establish a comprehensive T-cell receptor (TCR) repertoire analysis workflow. The upstream analysis included steps such as raw data processing, quality control, filtering, TCR sequence identification, and extraction. The downstream analysis included repertoire clone distribution, clone typing, V-J gene sharing, CDR3 distribution characteristics, and clone tracking. The sample clone distribution was analyzed by using indices such as Shannon-Weiner index and Chao1 index. Clone typing was performed based on the number of clone amplifications to explore differences among different types. The degree of V-J gene segment sharing was analyzed, and the sharing of low-frequency clone types was determined through clone amplification weight analysis of V-J genes by using two samples of papillary thyroid carcinoma. Finally, analysis of the distribution characteristics of V genes and high-frequency clone type CDR3, and clone tracking analysis were conducted to monitor changes in tumor immune clone frequencies before and after analysis, aiming to identify potential tumor markers.Results·① Significant differences were observed in clone distribution and clone typing among different NSCLC tissues, as well as among different ages and genders. ② Specific highly-shared V-J genes were identified in the analysis of V-J gene sharing, and non-normal distribution of high-clone V genes and amino acid high-frequency clone types were found in the CDR3 distribution analysis. ③ In the analysis of high-frequency clone type clone tracking, highly expressed or newly expressed high-frequency clone types were observed in NSCLC, suggesting that these clone types could serve as potential tumor-associated antigens or bind with CDR3 reference sequences of new antigens. ④ It was found that the expression frequency of TRBJ2-5 gene, originally low-expressed, significantly increased, indicating its potential role as a key low-frequency gene in tumor immune response.Conclusion·The TRAV21 and TRBV6.5 genes show high clone amplification in NSCLC and could serve as potential tumor biomarkers

A pathway for mitotic chromosome formation

Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central spiral staircase condensin scaffold. The size of helical turns progressively increases to ~12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding

Towards Reaction Control: cis-Diastereoselective Reductive Dehydroxylation of 5-Alkyl-4-Benzyloxy-5-Hydroxy-2-Pyrrolidinones

通讯作者地址: Huang, PQA chemo-, regio-, and stereoselectively controlled reaction is highly desirable, yet challenging in organic synthesis. Diversely substituted cis and trans isomers of 2-alkyl-3-pyrrolidinols, 5-alkyl-4-hydroxy-2-pyrrolidinones, beta-hydroxy-gamma-amino acids, and their higher homologues are key structural units found in numerous drugs, drug candidates, and bioactive natural products. Previously, we established a flexible approach to trans-5-alkyl-4-benzyloxy-2-pyrrolidinones 14 and trans-6-alkyl-5-benzyloxy-2-piperidinones 15. Herein, we report a direct, flexible, moisture insensitive, and highly diastereoselective approach to the corresponding cis diastereomers 16. This stereocontrolled method is based on the MsOH-mediated (Ms=methane sulfonyl) reductive dehydroxylation of hemiaminal 12 with NaBH(OAc)(3). cis-5-Alkyl-4-benzyloxy-2-pyrrolidinones 16 are useful building blocks for the syntheses of natural products such as (+)-preussin (4) and streptopyrrolidine (5) as well as (3S,4S)-gamma-alkyl-beta-hydroxy-gamma-amino acids (6).National Basic Research Program (973 Program) of China 2010CB833200 NSF of China 20832005 21072160 Natural Science Foundation of Fujian Province 2011J0105

Efficacy and safety of Danggui Niantong Decoction in patients with gout: a systematic review and meta-analysis

Background: This study aims to evaluate the efficacy and safety of Danggui Niantong Decoction (DGNT) systematically on gout treating.Methods: This study was registered in PROSPERO, and the registration number was CRD42021271607. By the end of December, 2022, literature research was conducted among eight electronic databases. Main results of this study were blood uric acid (BUA) and Creactive protein (CRP). Secondary outcomes were erythrocyte sedimentation rate (ESR), serum creatinine (Scr), urinary protein quantified at 24 h (Upro), and interleukin-8 (IL-8). Study screening, data collection, as well as quality assessment were performed by two reviewers independently, and analysis was completed using Stata (SE15.0) and Review Manager (5.4).Results: A total number of 13 studies were included in our meta-analysis (n = 1,094 participants). Results showed DGNT combined with conventional western medicine (CWM) was more effective than WM alone in BUA (weighted mean differences (WMD) = −3.49, 95% confidence interval (CI) [−50.36, −32.59], p = 0.000), CRP (WMD = −41.48, 95% CI [−4.32, −2.66], p = 0.017), ESR (WMD = −6.23, 95% CI [−9.28, −3.17], p = 0.019), Scr (WMD = −18.64, 95% CI [−23.09, −14.19], p = 0.001), Upro (WMD = −0.72, 95% CI [−0.91, −0.53], p = 0.000), and IL-8 (WMD = −4.77, 95% CI [−11.48, 1.94], p = 0.000). None of the adverse effects noted were severe, and no life-threatening event was reported.Conclusion: This study shows that DGNT combined with CWM seems to have an effective clinical therapeutic potential. In addition, it also provides a scientific basis for better clinical application of DGNT in the future.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271607; Identifier: PROSPERO, CRD42021271607