Gapless biosynthetic pathway enables sustainable paclitaxel production.

A recent leading-edge study by Jiang et al. identified two enzymes that are responsible for key reactions in the biosynthesis of baccatin III. The authors successfully reconstructed the baccatin III synthesis pathway with a minimal number of synthetic enzymes in tobacco leaves, laying the foundation for industrial-scale sustainable production of the anticancer drug paclitaxel.

Shear Mechanism of a Novel SFCBs-Reinforced Composite Shear Connector: Experimental, Theoretical Investigations and Numerical Model.

Traditional stud and perfobond leiste (PBL) shear connectors are commonly used as load-transferring components in steel-concrete composite structures. Composite shear connectors fully utilize the advantages of traditional stud and PBL shear connectors. In order to maximize the advantages of composite shear connectors, a novel shear connector for complex environments was proposed. The steel-FRP composite bars (SFCBs) with excellent fatigue resistance and corrosion resistance were introduced to replace the steel bars. This study discussed the failure modes, load-slip curves, and load-strain curves of the composite shear connector. In addition, a finite element analysis (FEA) model was developed to analyze the influence of various factors on its shear behavior. Results showed that compared with traditional composite shear connectors, the introduction of SFCB resulted in a promotion of 7.85% in shear stiffness, and it also led to a significant increase of 63.61% in ductility, further enhancing the mechanical performance. Meanwhile, FEA models were well fitted to the test results, and parametric analysis showed variate effects on shear bearing capacity. In the end, an equation was established to calculate the shear capacity of composite shear connectors, which could provide a reference for further research and engineering applications.

Nano-flow cytometry unveils mitochondrial permeability transition process and multi-pathway cell death induction for cancer therapy.

Mitochondrial permeability transition (mPT)-mediated mitochondrial dysfunction plays a pivotal role in various human diseases. However, the intricate details of its mechanisms and the sequence of events remain elusive, primarily due to the interference caused by Bax/Bak-induced mitochondrial outer membrane permeabilization (MOMP). To address these, we have developed a methodology that utilizes nano-flow cytometry (nFCM) to quantitatively analyze the opening of mitochondrial permeability transition pore (mPTP), dissipation of mitochondrial membrane potential ( Δ Ψm), release of cytochrome c (Cyt c), and other molecular alternations of isolated mitochondria in response to mPT induction at the single-mitochondrion level. It was identified that betulinic acid (BetA) and antimycin A can directly induce mitochondrial dysfunction through mPT-mediated mechanisms, while cisplatin and staurosporine cannot. In addition, the nFCM analysis also revealed that BetA primarily induces mPTP opening through a reduction in Bcl-2 and Bcl-xL protein levels, along with an elevation in ROS content. Employing dose and time-dependent strategies of BetA, for the first time, we experimentally verified the sequential occurrence of mPTP opening and Δ Ψm depolarization prior to the release of Cyt c during mPT-mediated mitochondrial dysfunction. Notably, our study uncovers a simultaneous release of cell-death-associated factors, including Cyt c, AIF, PNPT1, and mtDNA during mPT, implying the initiation of multiple cell death pathways. Intriguingly, BetA induces caspase-independent cell death, even in the absence of Bax/Bak, thereby overcoming drug resistance. The presented findings offer new insights into mPT-mediated mitochondrial dysfunction using nFCM, emphasizing the potential for targeting such dysfunction in innovative cancer therapies and interventions.