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"Degradation technology"
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Protein degradation technology: a strategic paradigm shift in drug discovery
Targeting pathogenic proteins with small-molecule inhibitors (SMIs) has become a widely used strategy for treating malignant tumors. However, most intracellular proteins have been proven to be undruggable due to a lack of active sites, leading to a significant challenge in the design and development of SMIs. In recent years, the proteolysis-targeting chimeric technology and related emerging degradation technologies have provided additional approaches for targeting these undruggable proteins. These degradation technologies show a tendency of superiority over SMIs, including the rapid and continuous target consumption as well as the stronger pharmacological effects, being a hot topic in current research. This review mainly focuses on summarizing the development of protein degradation technologies in recent years. Their advantages, potential applications, and limitations are also discussed. We hope this review would shed light on the design, discovery, and clinical application of drugs associated with these degradation technologies.
Journal Article
The last drop : solving the world's water crisis
\"Water scarcity is the next big climate crisis. Water stress - not just scarcity, but also water-quality issues caused by pollution - is already driving the first waves of climate refugees. Rivers are drying out before they meet the oceans, and ancient lakes are disappearing. Fourteen of the world's twenty megacities are now experiencing water scarcity or drought conditions. It's increasingly clear that human mismanagement of water is dangerously unsustainable, for both ecological and human survival. And yet in recent years some key countries have been quietly and very successfully addressing water stress. How are Singapore and Israel, for example - both severely water-stressed countries - not in the same predicament as Chennai or California, but now boast surplus water? What can we learn from them and how can we use this knowledge to turn things around for the wider global community? Do we have to stop eating almonds and asparagus grown in the deserts of California and Peru? Could desalination of seawater be the answer? Or rainwater capture? Are some of the wilder 'solutions' - such as the plan to tow icebergs to Cape Town - pure madness, or necessary innovation? Award-winning environmental journalist Tim Smedley will travel the world to meet the experts, the victims, the activists and pioneers, to find out how we can mend the water table that our survival depends upon. His book will take an unblinking look at the current situation and how we got there. And then look to the solutions. The Last Drop promises to offer a fascinating, universally relevant account of the environmental and human factors that have led us to this point, and suggests practical ways in which we might address the crisis, before it's too late\"--Publisher's description.
Book
Recent Advances of Degradation Technologies Based on PROTAC Mechanism
PROTAC (proteolysis-targeting chimeras), which selectively degrades target proteins, has become the most popular technology for drug development in recent years. Here, we introduce the history of PROTAC, and summarize the recent advances in novel types of degradation technologies based on the PROTAC mechanism, including TF-PROTAC, Light-controllable PROTAC, PhosphoTAC, LYTAC, AUTAC, ATTEC, CMA, RNA-PROTAC and RIBOTACs. In addition, the clinical progress, current challenges and future prospects of degradation technologies based on PROTAC mechanism are discussed.
Journal Article
Degradation of PCDD/Fs from incineration of waste at low temperatures for resource utilization of fly ash
Municipal solid waste incineration fly ash (MSWIFA) is of great value in resource utilization. Harmless pretreatment is a crucial prerequisite for the resource utilization of MSWIFA. The detoxification process is a crucial step in the harmless pretreatment of MSWIFA. This includes polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), which are among the most toxic substances to humans and other living organisms. Low-temperature degradation technology has broad prospects in engineering applications due to the advantages of low technical difficulty and operating costs. This work conducts a pilot test on the degradation of 17 toxic PCDD/Fs in MSWIFA at low temperatures. The pilot test investigates the effects of reaction temperature and oxygen content on the degradation of PCDD/Fs in MSWIFA. Furthermore, based on the perspective of MSWIFA resource utilization, an analysis and a proposal are made to judge the degradation effect of low-temperature thermal treatment technology on PCDD/Fs in MSWIFA. Further, taking the soil sludge field as the application scenario, the application feasibility of MSWIFA after detoxification is analyzed. The flotation process markedly reduces both the carbon content and the levels of PCDD/Fs in MSWIFA. The hydrothermal method facilitates the degradation of dioxins in fly ash while introducing oxygen significantly lowers the reaction temperature required for fly ash treatment. This can enhance the degradation rate and reduce the demands on reaction equipment. The results indicate that the low-temperature thermal treatment technology can effectively degrade PCDD/Fs in MSWIFA, satisfying the requirements of some application scenarios. Notably, evaluating the effect of low-temperature thermal treatment technology on the degradation and detoxification of PCDD/Fs in MSWIFA should satisfy the residue requirements of different industries and achieve a certain detoxication efficiency.
Journal Article
Insight into the environmental fate, hazard, detection, and sustainable degradation technologies of chlorpyrifos—an organophosphorus pesticide
Pesticides play a critical role in terms of agricultural output nowadays. On top of that, pesticides provide economic support to our farmers. However, the usage of pesticides has created a public health issue and environmental hazard. Chlorpyrifos (CPY), an organophosphate pesticide, is extensively applied as an insecticide, acaricide, and termiticide against pests in various applications. Environmental pollution has occurred because of the widespread usage of CPY, harming several ecosystems, including soil, sediment, water, air, and biogeochemical cycles. While residual levels in soil, water, vegetables, foodstuffs, and human fluids have been discovered, CPY has also been found in the sediment, soil, and water. The irrefutable pieces of evidence indicate that CPY exposure inhibits the choline esterase enzyme, which impairs the ability of the body to use choline. As a result, neurological, immunological, and psychological consequences are seen in people and the natural environment. Several research studies have been conducted worldwide to identify and develop CPY remediation approaches and its derivatives from the environment. Currently, many detoxification methods are available for pesticides, such as CPY. However, recent research has shown that the breakdown of CPY using bacteria is the most proficient, cost-effective, and sustainable. This current article aims to outline relevant research events, summarize the possible breakdown of CPY into various compounds, and discuss analytical summaries of current research findings on bacterial degradation of CPY and the potential degradation mechanism.
Journal Article
\Forever chemicals\: a sticky environmental problem
● \"Forever chemicals\" are being redefined in terms of environmental lifespans. ● Novel degradation technologies offer promising PFAS remediation solutions. ● Global Collaboration in responding to the PFAS crisis is emphasized.
The discovery and widespread use of per- and poly-fluoroalkyl substances (PFAS) have exemplified the beneficial role of chemistry in modern life, yet they have also underscored significant environmental and health concerns. Termed \"forever chemicals\" due to their remarkable persistence, PFAS present formidable challenges in terms of contamination and toxicity. Efforts to address these challenges have led to the development of innovative degradation technologies, such as hydrothermal alkali treatment (HALT), low-temperature mineralization, and mechanochemical degradation, offering promising solutions to PFAS remediation. However, these advancements must be accompanied by robust investment in research, collaboration among stakeholders, and global responsibility to ensure effective management of PFAS contamination and mitigate its adverse impacts on ecosystems and human health.
Journal Article
Unveiling p65 as the target of diphyllin in ameliorating metabolic dysfunction-associated steatotic liver disease via targeted protein degradation technology
Metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by hepatic steatosis, inflammation and fibrosis, is becoming a global epidemic. However, the currently available effective clinical strategies remain limited.
We conducted the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) induced MASH mouse model to explore the effects of diphyllin on MASLD mice. We employ the targeted protein degradation technology applied for the discovery of compound/protein-protein interaction to identify p65 as a potential target protein.
We determine that diphyllin, a natural arylnaphthalene lignan lactone, is effective on MASLD, evidenced by the inhibition of hepatic lipid accumulation through promoting fatty acid oxidation in vivo and in vitro. To uncover the underlying mechanisms, we design and synthesis diphyllin-based protac and identify p65 as a potential target protein. Under p65 deficiency, the effects of diphyllin on lipid metabolism are blocked in vitro. As p65 as an antagonist of NRF2, diphyllin interacts with p65, leading to the induction of the NRF2 transcriptional activity and the enhancement of antioxidant capacity. When NFR2 is inhibited, the lowering effects of diphyllin on lipid is abolished.
Our study presents diphyllin as a potential lead compound for MASLD therapy but also offers a novel approach for elucidating the mechanisms of action of natural products.
Journal Article
Enhancing the Nutritional Value and Antioxidant Activity of Auricularia polytricha Through Efficient Utilization of Agricultural Waste
Auricularia polytricha , a nutritious edible wood‐rotting mushroom, faces cultivation challenges due to the limited availability of wood chips. It is urgent to find suitable flat substitutes to replace the current material. This study explores the use of 12 types of agricultural waste as alternative growth substrates, analyzing their effects on the physiological and biochemical characteristics of both mycelia and fruiting bodies. The agricultural waste that demonstrated greater suitability for the growth of A. polytricha was then selected as a substrate to evaluate its effect on the nutritional composition and antioxidant capacity of the fruiting bodies. The research findings have highlighted the potential for cotton straw, coix seed straw, and wheat straw to serve as the most efficient substrates in the cultivation of A. polytricha . The utilization of agricultural waste as a growth medium has been found to markedly enhance the activity of enzymes such as laccase, cellulase, and polyphenol oxidase within the mycelia, resulting in a significant reduction of the cultivation cycle by 16 days. These substrates also improved the nutritional composition of fruiting bodies, increasing crude fat, crude protein, total sugars, and mineral contents of iron (Fe) and zinc (Zn) in the fruiting bodies, with increases of 1.6‐fold, 2.6‐fold, 2.2‐fold, fourfold, and sevenfold, respectively. Additionally, the in vitro antioxidant activity of A. polytricha was assessed, revealing an enhancement in the DPPH free radical scavenging ability by up to 36.06%. This study highlights the utilization of agricultural waste to enhance the nutrient profile of A . polytricha , providing innovative approaches for optimizing its production. Additionally, it offers significant insights into advancing technologies related to “transforming wood‐rotting mushrooms into agents for straw degradation.”
Journal Article
How does information technology-based service degradation influence consumers’ use of services? An information technology-based service degradation decision theory
Information technology is crucial for modern services. Service delivery may include a complex mix of information technology and telecommunication providers, global networks and customers’ information technology devices. This research focuses on service failures that are caused by information technology problems, which we conceptualize as information technology-based service degradation (ITSD). When information technology-based service degradation occurs in a modern service, the information technology problem may originate from the service provider, another partner or any information technology equipment involved. But the customer may not be able to pinpoint the source of the problem immediately. We argue that existing research can only partially explain customers’ behavior following information technology-based service degradation; current research cannot account for the way in which information technology characteristics in information technology-based service degradation influence customers’ decisions to continue using or rejecting the service. To fulfill this gap, we interviewed information technology-based services’ customers. Our interviews suggest that the reasons affecting customers’ behavior may change and have differing importance during the information technology-based service degradation experience. We theorized the information technology-based service degradation experience into five stages: blaming, bypassing, tolerating, abandoning and overcoming. The first two stages contain stage-specific factors influencing the progression of service usage, and the final three stages contain stage-specific factors that matter in the decision to use or quit the service. As a new contribution, we propose a stage theory for explaining customers’ behavior following information technology-based service degradation. Our results outline new research directions in information technology-based service degradation, including further testing and refinement of our proposed theory in the case of different services. For service providers, our findings provide new information for improving service recovery strategies to keep customers engaged.
Journal Article