Engineering最新文献

The anticancer potential of quassinoids has attracted a great deal of attention for decades, and scientific data revealing their possible applications in cancer management are continuously increasing in the literature. Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes, several quassinoids have exhibited synergistic effects with anticancer drugs. This article provides an overview of the potential anticancer properties of quassinoids, including their cytotoxic and antitumor activities, mechanisms of action, safety evaluation, and potential benefits in combination with anticancer drugs.

Efficient metal recovery from industrial wastewater facilitates addressing of the environmental hazards and resource requirements of heavy metals. The conventional electrodeposition recovery method is hampered by the limitations of interfacial ion transport in charge-transfer reactions, creating challenges for simultaneous rapid and high-quality metal recovery. Therefore, we proposed integrating a transient electric field (TE) and swirling flow (SF) to synchronously enhance bulk mass transfer and promote interfacial ion transport. We investigated the effects of the operation mode, transient frequency, and flow rate on metal recovery, enabling determination of the optimal operating conditions for rapid and efficient sequential recovery of Cu in TE&SF mode. These conditions included low and high electric levels of 0 and 4 V, a 50% duty cycle, 1 kHz frequency, and 400 L·h⁻¹ flow rate. The kinetic coefficients of TE&SF electrodeposition were 3.5–4.3 and 1.37–1.97 times that of single TE and SF electrodeposition, respectively. Simulating the deposition process under TE and SF conditions confirmed the efficient concurrence of interfacial ion transport and charge transfer under TE and SF synergy, which achieved rapid and high-quality metal recovery. Therefore, the combined deposition strategy is considered an effective technique for reducing metal pollution and promoting resource recycling.

Infectious diseases are a global public health problem, with emerging and re-emerging infectious diseases on the rise worldwide. Therefore, their prevention and treatment are still major challenges. Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids, glucose, and energy. Bile acids have historically been utilized as first-line, valuable therapeutic agents for related metabolic and hepatobiliary diseases. Notably, bile acids are the major active ingredients of cow bezoar and bear bile, which are commonly used traditional Chinese medicines (TCMs) with the therapeutic effects of clearing heat, detoxification, and relieving wind and spasm. In recent years, the promising performance of bile acids against infectious diseases has attracted attention from the scientific community. This paper reviews for the first time the biological activities, possible mechanisms, production routes, and potential applications of bile acids in the treatment and prevention of infectious diseases. Compared with previous reviews, we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality. In addition, to ensure a stable supply of bile acids at affordable prices, it is necessary to clarify the biosynthesis of bile acids in vivo, which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis, biosynthesis, and chemoenzymatic synthesis. Finally, we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids. The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 centuries. However, the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare. Here, we present a new approach for creating artificial bear bile (ABB) as a high-quality and sustainable alternative to natural bear bile. This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields, including resources, chemistry, biology, medicine, pharmacology, and TCM. A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established, allowing for the systematic screening of therapeutic constituents. Through the utilization of chemical synthesis and enzyme engineering technologies, our research has achieved the environmentally friendly, large-scale production of bear bile therapeutic compounds, as well as the optimization and recomposition of ABB formulations. The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality, availability of raw materials, and independence from threatened or wild resources. Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB). Furthermore, preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB. This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs, thereby strengthening the integrity and sustainability of TCM.

The β-1–6-linked poly-N-acetylglucosamine (PNAG) polymer is a conserved surface polysaccharide produced by many bacteria, fungi, and protozoan (and even filarial) parasites. This wide-ranging expression makes PNAG an attractive target for vaccine development, as it potentially encompasses a broad range of microorganisms. Significant progress has been made in discovering important properties of the biology of PNAG expression in recent years. The molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many bacteria. In addition, the physiological function of PNAG has been further elucidated. PNAG-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical research. Furthermore, clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals, and the results are promising. Although it is not destined to be a smooth road, we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

In three-dimensional (3D) stacking, the thermal stress of through-silicon via (TSV) has a significant influence on chip performance and reliability, and this problem is exacerbated in high-density TSV arrays. In this study, a novel hollow tungsten TSV (W–TSV) is presented and developed. The hollow structure provides space for the release of thermal stress. Simulation results showed that the hollow W–TSV structure can release 60.3% of thermal stress within the top 2 μm from the surface, and thermal stress can be decreased to less than 20 MPa in the radial area of 3 μm. The ultra-high-density (1600 TSV∙mm⁻²) TSV array with a size of 640 × 512, a pitch of 25 μm, and an aspect ratio of 20.3 was fabricated, and the test results demonstrated that the proposed TSV has excellent electrical and reliability performances. The average resistance of the TSV was 1.21 Ω. The leakage current was 643 pA and the breakdown voltage was greater than 100 V. The resistance change is less than 2% after 100 temperature cycles from −40 to 125 °C. Raman spectroscopy showed that the maximum stress on the wafer surface caused by the hollow W–TSV was 31.02 MPa, which means that there was no keep-out zone (KOZ) caused by the TSV array. These results indicate that this structure has great potential for applications in large-array photodetectors and 3D integrated circuits.

DNA guanine (G)-quadruplexes (G4s) are unique secondary structures formed by two or more stacked G-tetrads in G-rich DNA sequences. These structures have been found to play a crucial role in highly transcribed genes, especially in cancer-related oncogenes, making them attractive targets for cancer therapeutics. Significantly, targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins, such as MYC, BCL2, KRAS, and EGFR. Natural products have long been an important source of drug discovery, particularly in the fields of cancer and infectious diseases. Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs. Numerous DNA G4s, such as MYC-G4, BCL2-G4, KRAS-G4, PDGFR-β-G4, VEGF-G4, and telomeric-G4, have been identified as potential targets of natural products, including berberine, telomestatin, quindoline, sanguinarine, isaindigotone, and many others. Herein, we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders, focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature. We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

A substantial reduction in groundwater level, exacerbated by coal mining activities, is intensifying water scarcity in western China’s ecologically fragile coal mining areas. China’s national strategic goal of achieving a carbon peak and carbon neutrality has made eco-friendly mining that prioritizes the protection and efficient use of water resources essential. Based on the resource characteristics of mine water and heat hazards, an intensive coal–water–thermal collaborative co-mining paradigm for the duration of the mining process is proposed. An integrated system for the production, supply, and storage of mining companion resources is achieved through technologies such as roof water inrush prevention and control, hydrothermal quality improvement, and deep-injection geological storage. An active preventive and control system achieved by adjusting the mining technology and a passive system centered on multi-objective drainage and grouting treatment are suggested, in accordance with the original geological characteristics and dynamic process of water inrush. By implementing advanced multi-objective drainage, specifically designed to address the “skylight-type” water inrush mode in the Yulin mining area of Shaanxi Province, a substantial reduction of 50% in water drillings and inflow was achieved, leading to stabilized water conditions that effectively ensure subsequent safe coal mining. An integrated-energy complementary model that incorporates the clean production concept of heat utilization is also proposed. The findings indicate a potential saving of 8419 t of standard coal by using water and air heat as an alternative heating source for the Xiaojihan coalmine, resulting in an impressive energy conservation of 50.2% and a notable 24.2% reduction in carbon emissions. The ultra-deep sustained water injection of 100 m³·h⁻¹ in a single well would not rupture the formation or cause water leakage, and 7.87 × 10⁵ t of mine water could be effectively stored in the Liujiagou Formation, presenting a viable method for mine–water management in the Ordos Basin and providing insights for green and low-carbon mining.

Myocardial ischemia is a serious threat to human health, and vascular dysfunction is its main cause. Buxu Tongyu (BXTY) Granule is an effective traditional Chinese medicine (TCM) for treating myocardial ischemia. However, the underlying mechanism of BXTY is still unclear. In this study, we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase (sGC)–3′,5′-cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin. The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice, including electrocardiogram abnormalities and changes in plasma enzymes. In addition, BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner. These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ, or with the PKG inhibitor KT 5823. Moreover, BXTY increased the protein expression of sGC-β₁ and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells (MOVAs). NS 2028 or ODQ reversed these effects of BXTY. The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY. NS 2028, ODQ, or KT 5823 also reversed this effect of BXTY. In conclusion, BXTY can improve the symptoms of acute myocardial ischemia in mice, and activating the sGC–cGMP–PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.