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Background: Microtubule polymerization is usually considered as the upstream of apoptotic cell death induced by taxanes, but recently published studies provide more insights into the mechanisms responsible for the antineoplastic effect of taxanes. In this study, we figure out the role of the stress-related PERK/eIF2α axis in tumor cell death upon taxane treatment along with paclitaxel resistance. Methods: Utilizing immunoblot assay, the activation status of PERK-eIF2α signaling was detected in a panel of cancer cell lines after the treatment of taxanes. The causal role of PERK-eIF2α signaling in the cancer cell apoptosis induced by taxanes was examined via pharmacological and genetic inhibitions of PERK. The relationship between microtubule polymerization and PERK-eIF2α activation was explored by immunofluorescent and immunoblotting assays. Eventaually, the combined therapeutic effect of paclitaxel (PTX) and CCT020312, a PERK agonist, was investigated in PTX-resistant breast cancer cells in vitro and in vivo. Results: PERK-eIF2α axis was dramatically activated by taxanes in several cancer cell types. Pharmacological or genetic inhibition of PERK efficiently impaired taxane-induced apoptotic cell death, independent of the cellular microtubule polymerization status. Moreover, PTX was able to activate the PERK/eIF2α axis in a very low concentration without triggering microtubule polymerization. In PTX-resistant breast cancer cells, the PERK/eIF2α axis was attenuated in comparison with the PTX-sensitive counterparts. Reactivation of the PERK/eIF2α axis in the PTX-resistant breast cancer cells with PERK agonist sensitized them to PTX in vitro. Combination treatment of the xenografted PTX-resistant breast tumors with PERK agonist and PTX validated the synergic effect of PTX and PERK activation in vivo. Conclusion: Activation of the PERK/eIF2α axis is a pivotal prerequisite of taxanes to initiate cancer cell apoptosis, which is independent of the well-known microtubule polymerization-dependent manner. Simultaneous activation of PERK-eIF2α signaling would be a promising therapeutic strategy to overcome PTX resistance in breast cancer or other cancers. [ABSTRACT FROM AUTHOR]

Purpose: Coronary artery disease (CAD) patients frequently face readmissions due to suboptimal disease management. Prediction models are pivotal for detecting early unplanned readmissions. This review offers a unified assessment, aiming to lay the groundwork for enhancing prediction models and informing prevention strategies. Methods: A search through five databases (PubMed, Web of Science, EBSCOhost, Embase, China National Knowledge Infrastructure) up to September 2023 identified studies on prediction models for coronary artery disease patient readmissions for this review. Two independent reviewers used the CHARMS checklist for data extraction and the PROBAST tool for bias assessment. Results: From 12,457 records, 15 studies were selected, contributing 30 models targeting various CAD patient groups (AMI, CABG, ACS) from primarily China, the USA, and Canada. Models utilized varied methods such as logistic regression and machine learning, with performance predominantly measured by the c-index. Key predictors included age, gender, and hospital stay duration. Readmission rates in the studies varied from 4.8% to 45.1%. Despite high bias risk across models, several showed notable accuracy and calibration. Conclusion: The study highlights the need for thorough external validation and the use of the PROBAST tool to reduce bias in models predicting readmission for CAD patients. [ABSTRACT FROM AUTHOR]

Ovarian fibrosis is a reproduction obstacle leading to female infertility in vertebrates, but the cause underlying the cellular events is unclear. Here, we found that the small adaptor protein SH3‐domain‐binding glutamate‐rich protein like (Sh3bgrl) plays an important role in female reproduction in zebrafish. Two sh3bgrl mutant alleles that result in sh3bgrl depletion contribute to female spawning inability. Comparative transcriptome analysis revealed that sh3bgrl knockout mechanistically causes the upregulation of genes associated with extracellular matrix (ECM) and fiber generation in the zebrafish ovary. Consequently, extra ECM or fibers accumulate and are deposited in the ovary, resulting in eventual spawning inability. Our findings thus provide insights into understanding the underlying mechanism of infertility by ovarian fibrosis and provide a novel and valuable model to study female reproduction abnormality. [ABSTRACT FROM AUTHOR]

The electroplating, electrolysis, and pickling industrial processes would generate numerous gas pollutes, acid mist, which could not be essentially diminished due to its synthesis mechanism and cause gaseous environmental pollution, equipment corrosion, and endanger workers' health. In this study, a facile, practical, and energy-saving acid mist suppression system was constructed by introducing a stacking microsphere matrix as a floating porous phase on the acid solution and not causing secondary pollution. The mechanism of this green acid mist suppression strategy mainly focused on size-selective blocking of acid mist droplets by dense stacking microsphere layer and dissipation of floating kinetic energy of bubbles in the acid mist. The factors relating to the matrix's microstructure, the particle size of microspheres, the combination of the complex particles with a wide range of particle sizes, and the thickness of the matrix on the acid mist suppression were explored. It found that the matrix constituted of a medium-sized polymer sphere (1.075 ± 0.175 mm) presents a better appearance in the acid mist suppression. When the thickness of this matrix reached 15 mm, its acid mist efficiency also came up to 100%, totally blocking the acid mist. Meanwhile, complex particles with different particle sizes and PMMA porous blocks are beneficial for suppressing acid mist. Herein, this research opened up a green and effective strategy for regulating this hazardous gas pollute, acid mist. [ABSTRACT FROM AUTHOR]

Acquired chemotherapy resistance is one of the main culprits in the relapse of breast cancer. But the underlying mechanism of chemotherapy resistance remains elusive. Here, we demonstrate that a small adaptor protein, SH3BGRL, is not only elevated in the majority of breast cancer patients but also has relevance with the relapse and poor prognosis of breast cancer patients. Functionally, SH3BGRL upregulation enhances the chemoresistance of breast cancer cells to the first-line doxorubicin treatment through macroautophagic/autophagic protection. Mechanistically, SH3BGRL can unexpectedly bind to ribosomal subunits to enhance PIK3C3 translation efficiency and sustain ATG12 stability. Therefore, inhibition of autophagy or silence of PIK3C3 or ATG12 can effectively block the driving effect of SH3BGRL on doxorubicin resistance of breast cancer cells in vitro and in vivo. We also validate that SH3BGRL expression is positively correlated with that of PIK3C3 or ATG12, as well as the constitutive occurrence of autophagy in clinical breast cancer tissues. Taken together, our data reveal that SH3BGRL upregulation would be a key driver to the acquired chemotherapy resistance through autophagy enhancement in breast cancer while targeting SH3BGRL could be a potential therapeutic strategy against breast cancer. Abbreviations: ABCs: ATP-binding cassette transporters; Act D: actinomycin D; ACTB/β-actin: actin beta; ATG: autophagy-related; Baf A1: bafilomycin A1; CASP3: caspase 3; CHX: cycloheximide; CQ: chloroquine; Dox: doxorubicin; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GEO: gene expression omnibus; GFP: green fluorescent protein; G6PD: glucose-6-phosphate dehydrogenase; GSEA: gene set enrichment analysis; IHC: immunochemistry; KEGG: Kyoto Encyclopedia of Genes and Genomes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; 3-MA: 3-methyladenine; mRNA: messenger RNA; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; SH3BGRL: SH3 domain binding glutamate-rich protein-like; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1 [ABSTRACT FROM AUTHOR]

Background: The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase-like 1 (METTL1)-regulated m 7 G tRNA modification in bladder cancer (BC) remain obscure., Results: In this research, we show that METTL1 was highly expressed in BC, and its level was correlated with poor patient prognosis. Silencing METTL1 suppresses the proliferation, migration and invasion of BC cells in vitro and in vivo. Multi-omics analysis reveals that METTL1-mediated m 7 G tRNA modification altered expression of certain target genes, including EGFR/EFEMP1. Mechanistically, METTL1 regulates the translation of EGFR/EFEMP1 via modifying certain tRNAs. Furthermore, forced expression of EGFR/EFEMP1 partially rescues the effect of METTL1 deletion on BC cells., Conclusions: Our findings demonstrate the oncogenic role of METTL1 and the pathological significance of the METTL1-m 7 G-EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)