Abstract Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in ageing-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate ageing remains unclear. Here we report a fat-to-neuron lipid signalling pathway induced by lysosomal metabolism and its longevity-promoting role in Caenorhabditis elegans . We discovered that induced lysosomal lipolysis in peripheral fat storage tissue upregulates the neuropeptide signalling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a specific polyunsaturated fatty acid, dihomo-γ-linolenic acid, and LBP-3 lipid chaperone protein transported from the fat storage tissue to neurons. LBP-3 binds to dihomo-γ-linolenic acid, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signalling hub to coordinate metabolism and ageing, and lysosomal signalling mediated inter-tissue communication in promoting longevity.
We aimed to investigate the value of inflammation-based prognostic scores for predicting early complications after radical surgery for colorectal carcinoma.We retrospectively analyzed data of 154 patients who underwent elective resection of colorectal carcinoma between January 2017 and December 2018 at Beijing Friendship Hospital. Univariate, multivariate, and receiver operating characteristic curve analyses were conducted. As inflammation indices, we evaluated the preoperative modified Glasgow Prognostic Score (GPS), as well as the C-reactive protein/albumin ratio (CAR), postoperative GPS, and C-reactive protein levels on postoperative day 3 (POD3).Within 30 days postoperatively, complications occurred in 80 patients (51.9%). And high levels of preoperative mGPS (P=0.002), preoperative CAR (P=0.019), POD3 CAR (P<0.001) and POD3 poGPS (P<0.001) can significantly affect postoperative complications after surgery for colorectal cancer, with CRP on POD3 (odds ratio, 1.015; 95% confidence interval, 1.006-1.024; P=0.001) as independent risk factors. Among all inflammation-based indicators, POD3 CAR had the highest area under the curve (0.711) and positive predictive value (83.2%). Higher CAR (≥2.6) on POD3 was associated with a higher rate of complications (92.9% vs 36.6%, P<0.001), especially of infectious nature (54.8% vs 16.1%, P<0.001).CAR≥2.6 on POD3 reflects sustained systemic inflammation and represents a useful predictor of complications after surgery for colorectal carcinoma, facilitating early detection, timely intervention, and enhanced recovery.
The etymology of the terms in Hui hui yao fang (Huihui Formularies) is complicated. Their origin might be Arabian, Persian, or Sanskrit, or even the northern dialects of Han language during the Yuan and Ming Dynasties. There are obvious mistakes or indefinite decipherments and interpretations of the terms in Song Xian's Investigated Annotations of Huihui Formularies. There are also missing annotations for those transliterated terms. To tackle such defects, 12 such terms are deciphered and annotated here.《回回药方》残卷名词术语的语源复杂，既有来自阿拉伯语、波斯语、梵语者，也有来自元明之际中国北方汉语方言者。宋岘的《〈回回药方〉考释》一书对《回回药方》的诸多术语进行了释读，然而却有明显误释的，也有释读不确的，还有对非音译术语未释的。对前人未释、误释或释读不确的12个术语予以释读，可以弥补其憾。.
Abstract Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton’s Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs. Importantly, this reversible covalent strategy is generalizable to improve other PROTACs, opening a path to enhance PROTAC efficacy.
Although the advent of chemotherapy has made some progress in the comprehensive treatment of breast cancer, drug resistance of tumor cells remains to be one of the main challenges for the treatment of breast cancers. Several microRNAs have been implicated in the resistant process, but the role of miR-130a in drug resistance in breast cancer remains unclear. The present study aims to investigate the role and mechanisms of miR-130a in drug resistance in breast cancer cells and tissues.miR-130a mimics was used to up-regulate miR-130a expression in Doxorubicin-resistant MCF-7/Adr breast cancer cell line, followed by MTT assay and colony formation to determine cell viability and relative colony number. The relationship between the expression of miR-130a and drug resistance was detected by in situ hybridization in the formalin-fixed paraffin-embedded (FFPE) tissues from 50 breast cancer patients before and after Epirubicin-based neoadjuvant chemotherapy.Up-regulation of miR-130a level in MCF-7/Adr cells decreased the cell viability and colony number, and reversed Doxorubicin resistance of MCF-7/Adr cells. In breast cancer tissue from patients, the miR-130a level was lower before neoadjuvant chemotherapy than that after neoadjuvant chemotherapy (P < 0.05). Moreover, a significant increase in the expression of miR-130a was observed in breast tumor tissues from patients sensitive to neoadjuvant chemotherapy compared to the patients who were resistant to neoadjuvant chemotherapy (P < 0.05).We concluded that miR-130a might weaken drug resistance of human breast cancer cells, and act as an important factor in prediction of therapeutic responses in chemotherapy of breast cancer.
Objective: To construct pcDNAS. 0-ING4 recombinant eukaryotic expression plasmid and explore the effect of ING4 on cell cycle and cell apoptosis of SMMC7721. Methods: Using RT-PCR method, the cDNA encoding the mouse ING4 was isolated and total RNA was extracted from mouse liver tissue. The cDNA fragment was subcloned into the eukaryotic expression vector pcDNA3. 0. Analysis by PCR, restricting enzyme digestion and DNA sequencing were carried out to demonstrate the sequence of the plasmid, then the plasmid was transfected into SMMC7721 cell lines by lipofectamine-mediated transfection. Cell cycle was examined by flow cytometry after transfection with pcDNA3. 0-ING4; apoptosis was deteced by fluorescence microscope with Ho-echst 33258 staining and laser scanning confocal microscope. Results: RT-PCR product was a 750 bp specific fragment. DNA sequencing revealed that ING4 cloning was successful. Flow cytometric analysis displayed an accumulation of cells in the G2 phase of cell cycle after transfection with pcDNA3. 0-ING4. With Hoechst fluorescence staining, we found that the apoptotic rate in SMMC7721 cells transfected with pcDNA3. 0-ING4 (23. 66%) was higher than that in HeLa cells transfected with pcDNA3. 0 (13. 75%, P0. 01). Conclusion: The gene encoding mouse ING4 and pcDNA3. 0-ING4 eukaryotic expression vector are obtained. An accumulation of cells in the G2 phase of cell cycle was achieved after transfection with pcDNA3. 0-ING4, and ING4 can enhance apoptosis of SMMC7721 cells.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
