Abstract: Background: BCL-2 inhibition with venetoclax has proved to be highly effective treatment for patients with CLL. However, when administered to patients with CLL who have a high tumor burden, venetoclax is associated with an elevated risk of tumor lysis syndrome (TLS). Because of this risk, venetoclax is initiated with a gradual, 5-week dose ramp-up, requiring close laboratory monitoring over an extended period. Lisaftoclax (APG-2575) is a novel, potent, selective BCL-2 inhibitor under clinical development for hematologic malignancies (HMs). Preliminary data in 18 patients with CLL treated in a first-in-human study suggested the feasibility of an abbreviated ramp-up of lisaftoclax that might also result in a lower incidence of neutropenia (Ailawadhi et al, J Clin Oncol 39, 2021; abstr 7502). Methods: This new study is a global, open-label, multicenter, two-part phase 1b dose escalation and dose expansion study to assess the safety and tolerability of lisaftoclax (Part 1) and lisaftoclax combined with rituximab or acalabrutinib (Part 2), including dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). The trial is enrolling adults with (1) histologically confirmed CLL/SLL (by 2018 iwCLL criteria) that is relapsed or refractory to ≥ 1 prior therapy and requires treatment (also by 2018 iwCLL criteria); (2) adequate bone marrow function (in the absence of growth factors), including absolute neutrophils ≥ 1.0 × 10 9/L in patients without bone marrow involvement (not required in CLL/SLL patients with bone marrow involvement); and (3) adequate renal and hepatic function. Exclusion criteria: (1) recent history of allogeneic stem cell transplantation or CAR T-cell therapy ( & lt; 90 days); (2) prior treatment with a BCL-2 inhibitor (unless patient discontinued such therapy without disease progression); (3) treatment with vitamin K anticoagulants or previous discontinuation of treatment due to acalabrutinib toxicity (in acalabrutinib plus lisaftoclax cohort); (4) active Richter's syndrome; (5) infection (e.g. HIV, hepatitis); (6) CNS involvement; (7) prior cancer that has recurred within 2 years of screening and requires treatment (apart from adequately treated cervical or breast carcinoma in situ); (8) uncontrolled and other serious concomitant illnesses, including cardiovascular disease and diabetes; (9) failure to recover adequately after surgical procedures; and (10) active graft-vs-host disease or a requirement for immunosuppressive treatment. In a standard "3+3" dose escalation design (Part 1), lisaftoclax is being administered orally once daily in a 28-day cycle, with full doses of 200 to 1,200 mg (by 200-mg increments at 4 dose levels (400, 600, 800, and 1,000 mg) in parallel. The ramp-up is performed in the hospital with close monitoring for TLS and consists of the following doses and days of lisaftoclax treatment: 20 mg on Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, 400 mg on Day 5, 600 mg on Day 6, 800 mg on Day 7, and 1,000 mg on Day 8. Patients who experience TLS on any of these days have their dose held until resolution of TLS before proceeding to the next dose. Part 2 includes a further standard 3+3 dose escalation of lisaftoclax combined with rituximab or acalabrutinib (in separate cohorts), with a further planned dose expansion at recommended phase 2 doses of these combination regimens. Primary outcome measures are (1) DLTs observed during cycle 1; and (2) MTD (measured over the same interval). DLT criteria are defined as grade 4 thrombocytopenia or neutropenia lasting & gt; 7 days, grade 3 ≥ thrombocytopenia with bleeding, grade 4 febrile neutropenia, or grade 3 ≥ non-hematologic toxicities. As of July 19, 2021, 71 patients have been enrolled (of 144 planned). Clinicaltrial.gov identifier: NCT04215809. Disclosures Davids: Ascentage Pharma: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Surface Oncology: Research Funding; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; BeiGene: Consultancy; Celgene: Consultancy; Eli Lilly and Company: Consultancy; Janssen: Consultancy; MEI Pharma: Consultancy; Merck: Consultancy; Research to Practice: Consultancy; Takeda: Consultancy. Siddiqi: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Juno therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Other: DSM Member, Speakers Bureau; PCYC: Speakers Bureau; Jannsen: Speakers Bureau; Dava Oncology: Honoraria; ResearchToPractice: Honoraria. Pagel: Gilead: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Incyte/MorphoSys: Consultancy; Epizyme: Consultancy; Kite, a Gilead Company: Consultancy; Actinium Pharmaceuticals: Consultancy; MEI Pharma: Consultancy; Pharmacyclics/AbbVie: Consultancy. Pylypenko: Communal nonprofit enterprise "Cherkasy regional oncology dispensary of Cherkasy oblast council: Current Employment. Kriachok: Takeda, Roche, Abbivie, Janssen, MSD: Consultancy; Takeda, Roche, Abbvie, Janssen, MSD, Pfizer: Honoraria, Speakers Bureau. Usenko: Abbvie: Honoraria; Acerta: Honoraria; Ascentage: Honoraria; AstraZeneca: Honoraria; Celgene: Honoraria; Il Yang: Honoraria; Janssen: Honoraria; Karyopharm: Honoraria; Oncopeptides: Honoraria; Rigel: Honoraria; Takeda: Honoraria; UCB: Honoraria. Chen: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company. Huang: Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company. Li: Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company. Ahmad: Ascentage Pharma Group Inc.: Current Employment, Current equity holder in publicly-traded company. Mudenda: Ascentage Pharma Group Inc.: Current Employment, Current equity holder in publicly-traded company. Yang: Ascentage Pharma (Suzhou) Co., Ltd: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding. Zhai: Ascentage Pharma (Suzhou) Co., Ltd.: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding; Ascentage Pharma Group Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Leadership and other ownership interests, Patents & Royalties, Research Funding.

Abstract: Technology plays a crucial role in modern teaching, providing both, educators and students fundamental theoretical insights as well as supporting the interpretation of experimental data. In the long term it gives students a clear stake in their learning processes. Advancing in education furthermore largely depends on providing valuable experiences and tools throughout digital and computer literacy. Here and after, the computer’s benefit makes no exception in the chemistry as a science. The major part of computer revolutionizing in the chemistry laboratory is with the use of images, diagrams, molecular models, graphs and specialized chemistry programs. In the sense of this, the teacher provides more interactive classes and numerous dynamic teaching methods along with advanced technology. All things considered, the aim of this article is to implement interactive teaching methods of chemistry subjects using chemistry computer graphics. A group of students (n = 30) at the age of 18–20 were testing using methods such as brainstorming, demonstration, working in pairs, and writing laboratory notebooks. The results showed that demonstration is the most acceptable interactive method (95%). This article is expected to be of high value to teachers and researchers of chemistry, implementing interactive methods, and operating computer graphics

Abstract: The major bioactive component of black pepper ( Piper nigrum ) is piperine which has demonstrated beneficial therapeutic properties. The purpose of this research was to investigate the effects of different irradiation doses on the content of piperine in black pepper. Samples were irradiated with 60 Co γ-rays (at absorbed doses of 0.5, 1, 3, 5, 7, 10, and 12 kGy). Thin-layer chromatography (TLC) and UV–Vis spectrophotometry methods were used for measuring the piperine content in the samples. TLC was performed using three mobile phases (1. toluene:ethyl acetate, 7:3 v/v; 2. acetone: n -hexane, 6:4 v/v; 3. toluene:methanol, 8.5:1.5 v/v) and the retention factor ( R f ) value for piperine was equal to 0.66, 0.94, and 0.67, respectively. The content of piperine in γ-irradiated samples of black pepper was found to be between 0.04 and 1.05% w/w from the spectrophotometry analyses. Irradiation slightly decreased the piperine content of black pepper. It was found that piperine crude yield from black pepper was from 1.10 (the unirradiated sample) to 1.69, 1.07, 0.60, 0.90, 0.30, 1.20, 0.80% for irradiated samples, respectively. Microbiological analyses were performed with standard plate count method, which resulted in a decreasing number of the total cell count of microbial cells with increasing the radiation dose. Treatment with irradiation reduced the population of bacteria by 4 logs.

Abstract: Caffeine is naturally present in tea and coffee giving the pleasant and stimulant effect. Several different types of teas, black, green, and white teas bought in market were analysis for caffeine content. The boiled sample tea was filtered through filter paper. Lead(II) acetate was used to separate tannins from caffeine followed by filtration through filter paper with a black ribbon. The liquid-liquid extraction was carried out using dichloromethane (3×5 mL) and sodium sulfate as a drying agent. The TLC method was performed on Merck precoated silica gel plates 5×10 cm (60F254, 200 μm) using either methanol or dichloromethane as solvents and the mobile phases were glacial acetic acid and ethyl acetate (95:5, v/v), while the second one was consisted of ethyl acetate and ethanol (80:20, v/v), respectfully. The Rf values were 0.36 and 0.86 for the first and the second mobile phase, respectively, in comparison to the standard caffeine. The values for pH of boiled sample teas were in the range from 4.85 to 5.80. The most abundant tea sample for caffeine was determined in green tea bought in the grocery store for health nutrition (2.04 %). The yield for tea samples from green market, white tea and two tea black samples were 0.06, 0.71, 0.07, and 0.05%, respectively. The developed TLC method can be used for determination of caffeine content in tea samples.