Engineering最新文献

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.

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.

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.

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.

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.

The Advanced Geosynchronous Radiation Imager (AGRI) is a mission-critical instrument for the Fengyun series of satellites. AGRI acquires full-disk images every 15 min and views East Asia every 5 min through 14 spectral bands, enabling the detection of highly variable aerosol optical depth (AOD). Quantitative retrieval of AOD has hitherto been challenging, especially over land. In this study, an AOD retrieval algorithm is proposed that combines deep learning and transfer learning. The algorithm uses core concepts from both the Dark Target (DT) and Deep Blue (DB) algorithms to select features for the machine-learning (ML) algorithm, allowing for AOD retrieval at 550 nm over both dark and bright surfaces. The algorithm consists of two steps: ① A baseline deep neural network (DNN) with skip connections is developed using 10 min Advanced Himawari Imager (AHI) AODs as the target variable, and ② sunphotometer AODs from 89 ground-based stations are used to fine-tune the DNN parameters. Out-of-station validation shows that the retrieved AOD attains high accuracy, characterized by a coefficient of determination (R²) of 0.70, a mean bias error (MBE) of 0.03, and a percentage of data within the expected error (EE) of 70.7%. A sensitivity study reveals that the top-of-atmosphere reflectance at 650 and 470 nm, as well as the surface reflectance at 650 nm, are the two largest sources of uncertainty impacting the retrieval. In a case study of monitoring an extreme aerosol event, the AGRI AOD is found to be able to capture the detailed temporal evolution of the event. This work demonstrates the superiority of the transfer-learning technique in satellite AOD retrievals and the applicability of the retrieved AGRI AOD in monitoring extreme pollution events.