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991.
Recent developments of single cell RNA-sequencing technologies lead to the exponential growth of single cell sequencing datasets across different conditions. Combining these datasets helps to better understand cellular identity and function. However, it is challenging to integrate different datasets from different laboratories or technologies due to batch effect, which are interspersed with biological variances. To overcome this problem, we have proposed Single Cell Integration by Disentangled Representation Learning (SCIDRL), a domain adaption-based method, to learn low-dimensional representations invariant to batch effect. This method can efficiently remove batch effect while retaining cell type purity. We applied it to thirteen diverse simulated and real datasets. Benchmark results show that SCIDRL outperforms other methods in most cases and exhibits excellent performances in two common situations: (i) effective integration of batch-shared rare cell types and preservation of batch-specific rare cell types; (ii) reliable integration of datasets with different cell compositions. This demonstrates SCIDRL will offer a valuable tool for researchers to decode the enigma of cell heterogeneity. 相似文献
992.
Lingyue Zhao Qian Yang Yiqun Tang Qidong You Xiaoke Guo 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):462
Kv1.5 potassium channel, encoded by KCNA5, is a promising target for the treatment of atrial fibrillation, one of the common arrhythmia. A new series of arylmethylpiperidines derivatives based on DDO-02001 were synthesised and evaluated for their ability to inhibit Kv1.5 channel. Among them, compound DDO-02005 showed good inhibitory activity (IC50 = 0.72 μM), preferable anti-arrhythmic effects and favoured safety. These results indicate that DDO-02005 can be a promising Kv1.5 inhibitor for further studies.Key Words: Kv1.5 inhibitors, atrial fibrillation, anti-arrhythmia 相似文献
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994.
Xiaohu Li Xin Zhang Inam
Ullah Khan Nina
N. Guo Bing Wang Yifeng Guo Bufan Xiao Yueshan Zhang Yimin Chu Junsong Chen Fang Guo 《Bioscience reports》2022,42(2)
Background: Breast cancer is the main lethal disease among females. The combination of lobaplatin and microwave hyperthermia plays a crucial role in several kinds of cancer in the clinic, but its possible mechanism in breast cancer has remained indistinct.Methods: Mouse models were used to detect breast cancer progression. Cell growth was explored with MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphonyl)-2H-tetrazolium) and colony formation assays. Cell migration and invasion were investigated with a transwell assay. Cell apoptosis was probed with flow cytometry. The expression of apoptosis-associated proteins was examined with Western blots.Result: Combination treatment decreased breast cancer cell viability, colony formation, cell invasion and metastasis. In addition, the treatment-induced breast cancer cell apoptosis and autophagy, activated the c-Jun N-terminal kinase (JNK) signaling pathway, suppressed the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, and down-regulated IAP and Bcl-2 family protein expression.Conclusion: These results indicate that lobaplatin is an effective breast cancer anti-tumor agent. Microwave hyperthermia was a useful adjunctive treatment. Combination treatment was more efficient than any single therapy. The possible mechanism for this effect was mainly associated with activation of the JNK signaling pathway, inactivation of the AKT/mTOR signaling pathway and down-regulation of the Bcl-2 and IAP families. 相似文献
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996.
Yi-Chin Candace Tsai Lynette Liew Zhijun Guo Di Liu Oliver Mueller-Cajar 《The Journal of biological chemistry》2022,298(1)
The CO2-fixing enzyme rubisco is responsible for almost all carbon fixation. This process frequently requires rubisco activase (Rca) machinery, which couples ATP hydrolysis to the removal of inhibitory sugar phosphates, including the rubisco substrate ribulose 1,5-bisphosphate (RuBP). Rubisco is sometimes compartmentalized in carboxysomes, bacterial microcompartments that enable a carbon dioxide concentrating mechanism (CCM). Characterized carboxysomal rubiscos, however, are not prone to inhibition, and often no activase machinery is associated with these enzymes. Here, we characterize two carboxysomal rubiscos of the form IAC clade that are associated with CbbQO-type Rcas. These enzymes release RuBP at a much lower rate than the canonical carboxysomal rubisco from Synechococcus PCC6301. We found that CbbQO-type Rcas encoded in carboxysome gene clusters can remove RuBP and the tight-binding transition state analog carboxy-arabinitol 1,5-bisphosphate from cognate rubiscos. The Acidithiobacillus ferrooxidans genome encodes two form IA rubiscos associated with two sets of cbbQ and cbbO genes. We show that the two CbbQO activase systems display specificity for the rubisco enzyme encoded in the same gene cluster, and this property can be switched by substituting the C-terminal three residues of the large subunit. Our findings indicate that the kinetic and inhibitory properties of proteobacterial form IA rubiscos are diverse and predict that Rcas may be necessary for some α-carboxysomal CCMs. These findings will have implications for efforts aiming to introduce biophysical CCMs into plants and other hosts for improvement of carbon fixation of crops. 相似文献
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