Recent Advances in Peptide Linkers of Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) represent a promising class of cancer therapeutics. This innovative molecular design perfectly integrates the targeting and extended half-life of antibodies with the cytotoxicity of small molecules, enabling the selective delivery of payloads to cancer cells. The linker molecule is crucial to the efficacy of an ADC.

Engineering HS-Activatable Aptameric Binders for Tailored Cell Manipulation.

Cell surface receptors play a crucial role in mediating cellular communication and precisely regulating cellular functions. Dysregulation of these receptors is closely associated with various diseases. To enable precise and dynamic receptor control, we developed a gas-responsive aptameric binder based on a chemically masked configuration, enabling stimulus-triggered reactivation.

A study on the status of myopia and pre-myopia among primary school students in different regions of Shaanxi Province, China.

Objective: This cross-sectional study aimed to investigate the geographic disparities in myopia and pre-myopia prevalence among elementary school students across three distinct regions of Shaanxi Province (southern Hanzhong, Guanzhong, and northern Yulin) to inform region-specific myopia control strategies.

Methods: From March to May 2024, we employed multistage cluster sampling to recruit 8,207 eligible students (2,724 southern Shaanxi, 2,761 Guanzhong, 2,722 northern Shaanxi) from 12 randomly selected primary schools. Comprehensive ophthalmic examinations including uncorrected visual acuity and non-cycloplegic autorefraction were conducted.

Effect of PWHT process on carbide precipitation behavior and impact toughness of pressure vessel steel.

The effects of the post-weld treatment on the impact performance, microstructure, and carbide precipitation behavior of pressure vessel steel were evaluated under simulated post-weld conditions. The continuous cooling transformation and isothermal transformation curves of undercooled austenite for the steel were constructed based on the expansion curve, serving as a guide for the potential heat treatment of the steel plates. A more detailed study was conducted on the simulated post-weld process with an insulation temperature of 690 ℃ and an insulation time of 24 h, based on the delivery status of the steel plate.

Fingerprint Recognition Matrix Based on Photomultiplication-Type Organic Photodetectors with a Signal-to-Noise Ratio of 51,400.

Large-area and highly sensitive image sensors are vital for undercell fingerprint recognition technology. The photomultiplication-type organic photodetector (PM-OPD) is one of the alternative choices due to its special active layers with the ratio of donor to acceptor by weight of about 100:3 for achieving single charge carrier transport channels, resulting in relatively low dark current density and high external quantum efficiency under low bias. The optimal PM-OPDs exhibit a maximal 2.

Discovery of MD-265: A Potent MDM2 Degrader That Achieves Complete Tumor Regression and Improves Long-Term Survival of Mice with Leukemia.

MDM2 has been pursued as an attractive therapeutic target for human cancers. Herein, we describe our discovery of MD-265 as a promising PROTAC MDM2 degrader and extensive and evaluations of its therapeutic potential and mechanism of action. MD-265 effectively depleted MDM2 protein in cancer cells at concentrations as low as 1 nM, leading to strong activation of p53 in cancer cells carrying wild-type p53.

Performance Investigation of Asphaltene Adsorption at a Carbonate Rock Surface: Spectroscopy Experiment and Molecular Simulation.

Investigation of asphaltene adsorption at rock surfaces plays an important role in enhanced oil recovery (EOR) for the petroleum industry. In this work, the interaction performances of asphaltene adsorption at carbonate dolomite and calcite surfaces are investigated based on experimental and simulation insights. On the one hand, macroscopic interaction performances were investigated by spectroscopy experiments to obtain the Langmuir thermodynamic model and pseudo-second-order (PSO) kinetic model.

Driving model of land use change on the evolution of carbon stock: a case study of Chongqing, China.

Terrestrialecosystems are significant carbon sinks and are crucial for understanding the regional and global carbon cycles, energy flow, and climate change. As land use change is a significant process affecting ecosystem carbon stocks and striving for land degradation neutrality (LDN), studying it is essential for comprehending the evolution of regional carbon sink functions and achieving sustainable development goals. The drastically diverse land use patterns in each of the study area's regions resulted in significant differences in carbon stock.

FDA Approval Summary: Dabrafenib in Combination with Trametinib for BRAFV600E Mutation-Positive Low-Grade Glioma.

On March 16, 2023, the FDA approved dabrafenib in combination with trametinib (Tafinlar, Mekinist; Novartis Pharmaceuticals Corporation) for the treatment of pediatric patients with low-grade glioma (LGG) with a BRAFV600E mutation who require systemic therapy. FDA also approved oral formulations of both drugs suitable for patients who cannot swallow pills. This approval was based on the LGG cohort from study CDRB436G2201 (NCT02684058), a multicenter, open-label trial in which pediatric patients with LGG with a BRAFV600E mutation were randomly assigned 2:1 to dabrafenib plus trametinib (D+T) or carboplatin plus vincristine (C+V).

FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer.

On January 19, 2023, the FDA granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of patients with unresectable or metastatic RAS wild-type, HER2-positive colorectal cancer who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Approval was based on the pooled analysis of patients receiving tucatinib in combination with trastuzumab in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. The primary endpoint was overall response rate (ORR) by RECIST 1.

FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors.

On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. The approval was based on data from Study LOXO-RET-17001 (LIBRETTO-001; NCT03157128), an international, non-randomized, multi-cohort clinical trial that included patients with advanced solid tumors harboring RET alterations. The overall response rate in 41 patients with locally advanced or metastatic RET fusion-positive solid tumors other than non-small cell lung cancer (NSCLC) or thyroid cancer was 44% [95% confidence interval (CI), 28%-60%], with median duration of response 24.

FDA Approval Summary: Amivantamab for the Treatment of Patients with Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.

The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS, NCT02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% [95% confidence interval (CI): 29-51] and a median response duration of 11.1 months (95% CI: 6.

Understanding the Relationships between Landscape Eco-Security and Multifunctionality in Cropland: Implications for Supporting Cropland Management Decisions.

Cropland is an essential strategic resource, for which landscape ecological security and multifunctionality evolution are related to regional stability and sustainable social development. However, few studies have explored the spatial heterogeneity of the coupling between the two from a multiregional and systematic perspective, and the interaction mechanisms have still not been thoroughly analyzed. In this study, a typical karst trough and valley area in the mountainous regions of southwest China was selected as the research object, and by establishing a multi-indicator evaluation system using a landscape pattern index, a multifunctional identification model, a coupled coordination model, and a geodetector model, the spatial variability in the evolutionary characteristics and the coupling and coordination of cropland landscape ecological security (CLES) and cropland multifunctionality (CM) in the mountainous regions of the southwest and their driving mechanisms were explored.

The coupling effect of socio-economic and eco-environment and land use transformation in mountainous areas-a case of the Fengjie County in the Three Gorges Reservoir Area, China.

Revealing the general laws of land use transformation (LUT) under the coupling evolution of different socio-economic and eco-environment (SE-EE) in mountainous areas is of great significance for rational use of land resources, regional socio-economic development, and eco-environment protection. This paper constructs a research framework of LUT under the coupling evolution of SE-EE and takes Fengjie County as an example to conduct a case study. The results show (1) the socio-economic development level and eco-environment quality showed an overall growth trend from 2000 to 2020, showed the distribution pattern of high in the Yangtze River valley and low in the mountainous areas, and low in the Yangtze River valley and high in the mountainous areas respectively.

Model-Informed Approach Supporting Drug Development and Regulatory Evaluation for Rare Diseases.

A rare disease is defined as a condition affecting fewer than 200 000 people in the United States by the Orphan Drug Act. For rare diseases, it is challenging to enroll a large number of patients and obtain all critical information to support drug approval through traditional clinical trial approaches. In addition, over half of the population affected by rare diseases are children, which presents additional drug development challenges.

FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement.

On April 17, 2020, the FDA granted accelerated approval to pemigatinib (PEMAZYRE, Incyte Corporation) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. Approval was based on FIGHT-202 (NCT02924376), a multicenter open-label single-arm trial. Efficacy was based on 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma whose disease had progressed on or after at least one prior therapy and had an FGFR2 gene fusion or rearrangement.

In Vitro Predictive Dissolution Test Should Be Developed and Recommended as a Bioequivalence Standard for the Immediate-Release Solid Oral Dosage Forms of the Highly Variable Mycophenolate Mofetil.

The prodrug mycophenolate mofetil (MMF), which is presystemically hydrolyzed into the pharmacologically active compound mycophenolic acid (MPA), has been widely used for the prophylaxis of acute allograft rejection in solid organ transplantation. However, the huge variability in the plasma concentration level makes the development of MMF drug products difficult due to the great challenge of meeting the traditional bioequivalence (BE) limits. Numerous models have been developed in the past decade to explain the variability, with the emphasis on characterizing the enterohepatic circulation.

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy.

In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance.

FDA Approval Summary: Capmatinib and Tepotinib for the Treatment of Metastatic NSCLC Harboring MET Exon 14 Skipping Mutations or Alterations.

The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations.