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We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal-dominant genetic disorder, and mutations in the forkhead box L2 (FOXL2) gene are one of the major genetic causes. As this study shows, there are many patients with BPES who do not have FOXL2 mutations, as the screening results in all family members were negative. Using whole-exome sequence analysis, we discovered another possible mutational cause of BPES in integrin subunit beta 5 (ITGB5). The ITGB5 mutation (c.608T>C, p.Ile203Thr) appears in the base sequence of all BPES+ patients in this family, and it appears to be a three-generation-inherited mutation. It can cause changes in base sequence and protein function, and there may be cosegregation of disease phenotypes. ITGB5 is located on the long arm of chromosome three (3q21.2) and is close to the known pathogenic gene FOXL2 (3q23). This study is the first to report ITGB5 mutations in BPES, and we speculate that it may be directly involved in the pathogenesis of BPES or indirectly through the regulation of FOXL2.

Objectives: To compare the clinical efficacy and safety of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones. Methods: We enrolled 135 patients underwent reusable flexible ureteroscopy (FURS) and 78 patients underwent single-use digital FURS. Demographic, clinical variables, anatomical parameters of the lower calyx and perioperative indicators were compared in the two groups. Results: Thirty-six patients in the infundibuloureter angle (IPA) < 45° subgroup had a mini-percutaneous nephrolithotomy (mini-PCNL), including 25 patients in the reusable FURS group and 11 patients in the single-use FURS group. The demographic and clinical variables in the two FURS groups were comparable. There was no statistical difference in the success rate of stone searching (P > 0.05). In terms of the success rate of lithotripsy, there was also no statistical difference in the IPA ≥ 45° subgroup (P > 0.05), whereas single-use FURS was superior in the IPA < 45° subgroup (χ2 = 6.513, P = 0.011). The length of the working fiber in the reusable FURS and single-use FURS groups was 3.20 ± 0.68 mm and 1.75 ± 0.47 mm, respectively (t = 18.297, P < 0.05). The use of a stone basket in the reusable FURS (31/135, 23.0%) was significantly higher than that in the single-use FURS (8/78, 10.3%) (χ2 = 5.336, P = 0.021). Compared with the reusable FURS group, the single-use FURS group had shorter operation times (P < 0.05) and higher stone-free rate (SFR) (χ2 = 4.230, P = 0.040). There was no statistical difference in the intraoperative transfer of mini-PCNL and postoperative complications between the two groups (P > 0.05). Conclusions: Single-use and reusable FURS are alternative methods for removal of lower pole stones (i.e., 2 cm or less). Single-use FURS has a high success rate of lithotripsy, shorter operation time, and high stone-free rate. [ABSTRACT FROM AUTHOR]

This article explores a new method for synthesizing carbamoyl azides, which are important for creating amines. The authors propose using NHP esters and TMSN3 to form C-N bonds through a nucleophilic substitution process. They optimized the reaction conditions and demonstrated the method's effectiveness with various NHP esters. Control experiments were conducted to understand the mechanism, which involves the coordination of NHP esters with ferric acetate, nucleophilic attack, and Curtius rearrangement. This method offers a convenient and efficient approach for synthesizing carbamoyl azides. The authors of the article are Xiaobin Yuan, Yanjie Qu, Yajun Li, and Hongli Bao. [Extracted from the article]

This article explores a new method for synthesizing carbamoyl azides, which are important for creating amines. The authors propose using NHP esters and TMSN3 to form C-N bonds through a nucleophilic substitution process. They optimized the reaction conditions and demonstrated the method's effectiveness with various NHP esters. Control experiments were conducted to understand the mechanism, which involves the coordination of NHP esters with ferric acetate, nucleophilic attack, and Curtius rearrangement. This method offers a convenient and efficient approach for synthesizing carbamoyl azides. The authors of the article are Xiaobin Yuan, Yanjie Qu, Yajun Li, and Hongli Bao. [Extracted from the article]

Remote sensing image classification (RSIC) is designed to assign specific semantic labels to aerial images, which is significant and fundamental in many applications. In recent years, substantial work has been conducted on RSIC with the help of deep learning models. Even though these models have greatly enhanced the performance of RSIC, the issues of diversity in the same class and similarity between different classes in remote sensing images remain huge challenges for RSIC. To solve these problems, a duplex-hierarchy representation learning (DHRL) method is proposed. The proposed DHRL method aims to explore duplex-hierarchy spaces, including a common space and a label space, to learn discriminative representations for RSIC. The proposed DHRL method consists of three main steps: First, paired images are fed to a pretrained ResNet network for extracting the corresponding features. Second, the extracted features are further explored and mapped into a common space for reducing the intra-class scatter and enlarging the inter-class separation. Third, the obtained representations are used to predict the categories of the input images, and the discrimination loss in the label space is minimized to further promote the learning of discriminative representations. Meanwhile, a confusion score is computed and added to the classification loss for guiding the discriminative representation learning via backpropagation. The comprehensive experimental results show that the proposed method is superior to the existing state-of-the-art methods on two challenging remote sensing image scene datasets, demonstrating that the proposed method is significantly effective. [ABSTRACT FROM AUTHOR]

The hydroisomerization unit of SINOPEC Tahe Petrochemical Co., Ltd. is an important unit for the production of gasoline blending components. The unit adopts Penex-DIH hydroisomerization technology of UOP company, ad uses light naphtha from pre hydrogenation unit of 0.6 MM TPY continuous reforming unit as feedstock to mainly produce blending components of high octane number gasoline. I-82 catalyst had been in operation for 80 months by March 2021, 26 months beyond is design life (54 months). The catalyst has been running normally so far, and the quality indexes of each product are good. Based on the actual operation of the unit, the long-term operation of I-82 catalyst is discussed to provide reference for subsequent operation. [ABSTRACT FROM AUTHOR]

Aim: To report the efficacy and safety of ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, in treating patients with ALK-positive advanced lung squamous cell carcinoma (LUSC) or lung adenosquamous carcinoma (LASC) in China., Methods: This retrospective study analyzed data for 36 advanced-stage patients with ALK-positive LUSC (cohort A) and 13 patients with ALK-positive LASC (cohort B) between December 16, 2020 and December 16, 2021. All patients received once-daily ensartinib 225 mg. Outcome analysis included the demographic characteristics, tumor response, progression-free survival (PFS), and treatment-related adverse events (TRAE)., Results: Among the 49 patients, the majority were under 65 years old (73.5%), non-smokers (85.7%), had an Eastern Cooperative Oncology Group Performance Status of 0-1 (77.6%), and were at stage IV (71.4%). All patients were included in the efficacy and safety analysis. Seven PFS events were reported in cohort A while no patients experienced PFS events in cohort B. The median PFS was not estimable for both cohorts. In cohort A, the objective response rate (ORR) was 63.9%, and the disease control rate (DCR) was 83.3%. In the cohort B, the ORR was 76.9% and the DCR was 100.0%. Rash was the only TRAE reported in the cohort A (8.3%) and cohort B (23.1%). No patients had grade 3 or higher TRAE., Conclusion: Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK-positive advanced LUSC or LASC in the real-world. However, confirmatory studies are still needed in larger sample sizes., (© 2024 John Wiley & Sons Australia, Ltd.)

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2- a ]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2- a ]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)