Design, Synthesis, and Antitumor Activity Evaluation of Proteolysis-Targeting Chimeras as Degraders of Extracellular Signal-Regulated Kinases 1/2.

Inhibition of the extracellular signal-regulated kinases 1/2 (ERK1/2) alone or in combination with other targets has emerged as a promising treatment strategy for a variety of human tumors. In addition to the development of inhibitors, the development of ERK1/2 degraders is an alternative approach to decrease its activity. We synthesized proteolysis-targeting chimeras (PROTACs) as effective ERK1/2 degraders, among which showed high degradative activity, with DC of 102 nM and cytotoxic IC of 2.

Discovery of novel benzimidazole derivatives as potent potassium-competitive acid blockers for the treatment of acid-related diseases.

H, K-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC = 9.

Negotiating Complexity: Challenges to Implementing Community-Led Nature-Based Solutions in England Pre- and Post-COVID-19.

Nature-based solutions (NbS), including green social prescribing (GSP), are sustainable ways to address health and wellbeing, especially since the COVID-19 pandemic exacerbated the strain on healthcare. NbS require national and local cross-sector coordination across complex, interrelated systems, but little is known about the specific challenges this poses for community-led NbS. We carried out a traditional literature review to establish the context and knowledge base for this study and interviewed 26 stakeholders.

Group Testing with Multiple Inhibitor Sets and Error-Tolerant and Its Decoding Algorithms.

In this article, we advance a new group testing model [Formula: see text] with multiple inhibitor sets and error-tolerant and propose decoding algorithms for it to identify all its positives by using [Formula: see text]-disjunct matrix. The decoding complexity for it is [Formula: see text], where [Formula: see text]. Moreover, we extend this new group testing to threshold group testing and give the threshold group testing model [Formula: see text] with multiple inhibitor sets and error-tolerant.

Expression and purification of bioactive, low-endotoxin recombinant human vitronectin.

The secreted adhesive glycoprotein vitronectin (VTN) is a multifunctional component of plasma and the extracellular matrix. A high-yielding, inexpensive, low endotoxin source of bioactive recombinant human vitronectin (rhVTN) is highly desirable for in vitro use in diverse cell culture systems ranging from basic research settings to clinical-grade production of human cells. We describe modifications to a previously reported heparin-based affinity chromatography procedure that improve yield and achieve efficient removal of endotoxin from washed and urea-solubilized human VTN inclusion bodies following standard autoinduction of expression in Escherichia coli.

An improved hybrid encoding cuckoo search algorithm for 0-1 knapsack problems.

Cuckoo search (CS) is a new robust swarm intelligence method that is based on the brood parasitism of some cuckoo species. In this paper, an improved hybrid encoding cuckoo search algorithm (ICS) with greedy strategy is put forward for solving 0-1 knapsack problems. First of all, for solving binary optimization problem with ICS, based on the idea of individual hybrid encoding, the cuckoo search over a continuous space is transformed into the synchronous evolution search over discrete space.

Nonadaptive algorithms for threshold group testing with inhibitors and error-tolerance.

A group test gives a positive (negative) outcome if it contains at least u (at most l) positive items, and an arbitrary outcome if the number of positive items is between thresholds l and u. This problem introduced by Damaschke is called threshold group testing. It is a generalization of classical group testing.