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Abstract Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here, it is reported that the development of small molecule degraders of the envelope (E) protein of dengue virus. Two classes of bivalent E‐degraders are developed by linking two previously reported E‐binding small molecules, GNF‐2, and CVM‐2‐12‐2, to a glutarimide‐based recruiter of the CRL4CRBN ligase to effect proteosome‐mediated degradation of the E protein. ZXH‐2‐107 (based on GNF‐2) is an E‐degrader with ABL inhibitory activity while ZXH‐8‐004 (based on CVM‐2‐12‐2) is a selective and potent E‐degrader. These two compounds provide proof of concept that difficult‐to‐drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class of direct‐acting antiviral drugs.

Development of polymer-based flooding technology to improve oil recovery efficiency, water dispersion copolymerization of acrylamide, cationic monomer methacryloxyethyltrimethyl ammonium chloride (METAC), and anionic monomer acrylic acid (AA) were carried out in aqueous ammonium sulfate solution with polyvinyl pyrrolidone (PVP) as the stabilizer. The copolymers were characterized by 1H-NMR, FT-IR, TG, and SEM to confirm that they were prepared successfully and exhibited excellent salt-resistant property. Moreover, the effect of the aqueous solution of ammonium sulfate (AS) concentration, stabilizer concentration, and initiator concentration on the viscosity and size were systematically investigated. To further improve the thermal endurance properties of copolymer, hydrophobic monomers with different alkyl chain lengths were added to the above system. The acrylamide-based quadripolymer possessed prominent thermal and salt endurance properties by utilizing the advantages of zwitterionic structure and hydrophobic monomer. With the temperature rising, the viscosity retention could reach 70.2% in the water and 63.8% in the saline. This work had expected to provide a new strategy to design polymers with excellent salinity tolerance and thermal-resistance performances.

Targeted protein degradation (TPD) is a promising strategy for drug development. In this proof-of-concept study, the authors use telaprevir, which binds hepatitis C virus (HCV) NS3/4A protease, to target the protease for protein degradation, and show inhibition of wildtype as well as drug resistant HCV.

Unregulated Src activity promotes malignant processes in cancer, but no Src-directed targeted therapies are used clinically, possibly because early Src inhibitors produce off-target effects leading to toxicity. Improved selective Src inhibitors may enable Src-directed therapies. Previously, we reported an irreversible Src inhibitor, DGY-06-116, based on the hybridization of dasatinib and a promiscuous covalent kinase probe SM1-71. Here, we report biochemical and biophysical characterization of this compound. An x-ray co-crystal structure of DGY-06-116: Src shows a covalent interaction with the kinase p-loop and occupancy of the back hydrophobic kinase pocket, explaining its high potency, and selectivity. However, a reversible analog also shows similar potency. Kinetic analysis shows a slow inactivation rate compared to other clinically approved covalent kinase inhibitors, consistent with a need for p-loop movement prior to covalent bond formation. Overall, these results suggest that a strong reversible interaction is required to allow sufficient time for the covalent reaction to occur. Further optimization of the covalent linker may improve the kinetics of covalent bond formation.

Acrylamide copolymers are often used as acidizing diverting and thickening agents for their advantageous thickening, flocculation, adhesion and resistance reduction properties. Experimental results indicate that the acid concentration greatly affects the properties of acrylamide polymers, which varies from results reported by other researchers. Considering the theoretical and field application value of the present study, four comparable acrylamide-based polymers were synthesized, and their macro- and micro-changes as well as the related changes in viscosity and molecular weight were studied in high-concentration hydrochloric acid. A proposed mechanism of acrylamide copolymer stability and degradation is provided, and further suggestions are made for the modification of acrylamide copolymers.

Purpose: Once lung cancer is detected due to clinical symptoms or by being visible on chest X-ray, it is usually high stage and non-operable. In order to improve mortality rates in lung cancer, low-dose CT (LDCT) screening of “high risk” individuals is gaining popularity. However, the rate of malignancy in LDCT detected sub-centimetre lung nodules is not clear. We aimed to analyze surgically resected specimens in this patient group to explore cost effectiveness and recommendations for clinical management of these nodules. Material & methods: Our hospital pathology database was searched for sub-centimeter lung nodules detected by LDCT screening which were resected. The patient demographics were collected and the radiologic and pathologic characteristics of those nodules were analyzed. Results: From the records, 44 patients with 46 resected subcentimetre nodules were identified. Patients were selected for surgery based on an irregular shape, growth in size during follow up, family history of lung cancer or personal history of cancer of other sites, previous lung disease, smoking and personal anxiety. Of the 44 patients, 33 were women and the ages ranged from 43 to 76 years (56.75 ± 8.44). All nodules were equal to, or less than 10 mm with a mean diameter of 7.81 ± 1.80 mm (SD). Out of 46 nodules, the pathological diagnoses were: invasive adenocarcinoma (ACa) in 4 (8.7%); adenocarcinoma in situ (AIS) or atypical adenomatous hyperplasia (AAH) in 29 (63%); benign fibrosis/fibrotic scar with inflammation or calcification in 12 (26.1%); an intrapulmonary benign lymph node in 1 (2.2%). Of the ACa, AIS and AAH groups (a total of 31 patients), 77% were women (24 vs. 7). The cancer or pre-cancer nodules (ACa, AIS and AAH) tended to be larger than benign fibrotic scars (P = 0.039). Amongst all characteristics, significant statistical differences were found when the following radiological features were considered: reconstructed nodule shape (P = 0.011), margin (P = 0.003) and ground glass pattern (P = 0.000). The patient’s age, the axial morphology of the lesion, relationship to major vessels or visceral pleura and location within the lung parenchyma were not predictive of the pathologic diagnosis. Only one of the 31 patients with a cancer or pre-cancer nodule was a smoker. Conclusion: ACa, AIS and AAH nodules detected on LDCT included more women (77%) than men in our cohort. Smoking as inclusive criteria for LDCT screening of lung cancer needs to be further evaluated in the Chinese population. The reconstructed nodule shape, density and margin may help radiologists to identify small cancer and pre-cancer nodules from benign conditions. Keywords: LDCT, Lung cancer screen, Lung nodule