Novel antibody-drug conjugates based on DXd-ADC technology.

In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents.

[Effects of Land Use Structure and Spatial Pattern at Different Temporal and Spatial Scales on Water Quality in Suzhou Creek].

Relationships between land use and water quality of rivers and lakes vary spatially and temporally. These variations were analyzed using spatial analysis and mathematical statistical methods for the Suzhou Creek in Shanghai. Based on the data of water quality and land use in 2001， 2005， 2010， 2015， and 2020， five spatial scales （200， 500， 1 000， 2 000， and 5 000 m reach buffer） of the landscape pattern were extracted using correlation and redundancy analysis to explore the impact of land use composition and spatial pattern on water quality at different spatial and temporal scales. The results showed that： ① the water quality of Suzhou Creek has gradually improved in the past 20 years； other indicators were between Class II to Class IV in 2020 except TN， and TN was the main pollutant. ② The main land use type of the buffer zone was construction land， and the proportion of greenland and woodland showed a small growth trend. ③ The water quality was closely related to landscape pattern， showing temporal and spatial scale effects. On the time scale， indicators such as construction land， agricultural land， landscape dominance， aggregation， and diversity had significant correlations with various water quality parameters， and there was an inverse correlation in 2010 compared with that in other years for NH4+-N， TP， and TN. The landscape pattern in 2001 had the greatest explanation for water quality， with an explanation rate of 93.65%. The impact of greenland and woodland on water quality has begun to emerge in the past 10 years. ④ On the spatial scale， there were significant correlations between greenland and woodland， patch number， landscape shape index， diversity index， and water quality. There was a strong positive regulatory effect of greenland and woodland on NH4+-N， TP， and TN at the scale of 2 000 m. The patch number and landscape shape index had relatively strong regulatory effects on water quality on a larger spatial scale， whereas the Shannon diversity index had a better positive regulatory effect on water quality on a small scale. The landscape pattern within a buffer of 2 000 m had the highest interpretation degree for all factors， with an explanation rate of 68.47%. The study showed that rationally planning the proportion of greenland and woodland within the 2 000 m buffer zone and optimizing its landscape configuration is an important measure to purify the surface water quality of Suzhou Creek.

Efficient Fractionation and Catalytic Valorization of Raw Biomass in ϵ-Caprolactone and Water.

Efficient fractionation and utilization of the whole biomass is particularly attractive but remains a great challenge, owing to the recalcitrance of biomass. In this study, a simple and efficient approach is developed to obtain high-purity cellulose with a delignification degree of 97.5 % in ϵ-caprolactone and water. FTIR spectroscopy reveals that ϵ-caprolactone and water act in synergy to remove lignin from raw biomass and afford cellulose with clear macrofibrils. A linear positive correlation between the contents of hemicellulose and lignin is observed for the separated cellulose pulp. This mixed solvent exhibits good performance for the removal of lignin from various agricultural and forestry wastes. Moreover, nearly complete transformation of the whole biomass constituents is achieved with Ni-Al catalyst.

Preparation and Evaluation of Recombinant Human Erythropoietin Loaded Tween 80-Albumin Nanoparticle for Traumatic Brain Injury Treatment.

OBJECTIVE: Traumatic brain injury (TBI) is a serious health problem with few available treatment options. Rh-erythropoietin (rh-EPO) is a potential therapeutic drug for TBI, but it cannot cross the blood-brain barrier (BBB) directly. In this regard, a novel strategy to deliver rh-EPO for enhanced TBI treatment is via the development of Tween 80 modified albumin nanoparticles using electrostatic spray technology. METHODS: The rh-EPO loaded Tween 80 modified albumin nanoparticles (rh-EPO-Tw-ABNPs) were prepared by electrostatic spray technology, while the process parameters were optimized via a single factor design. Investigation of physicochemical properties, bioactivity and stability of rh-EPO-Tw-ABNPs was carried out. The in vitro release and biocompatibility with nerve cells were also analyzed. The in vivo brain targeting efficiency, brain edema relieving effect and the expression of aquaporin 4 (AQP4) and glial fibrillary acidic protein (GFAP) in the brain were evaluated in TBI model rats. RESULTS: The particle size of optimal rh-EPO-Tw-ABNPs was about 438 ± 45 nm, with a zeta potential of -25.42 ± 0.8 mv. The average drug loading ratio of rh-EPO-Tw-ABNPs was 21.3± 3.7 IU/mg with a relative bioactivity of 91.6 ± 4.1%. The in vitro release of rh-EPO from the nanoparticles was rather slow, while neither the blank Tw-ABNPs nor rh-EPO-Tw-ABNPs exhibited toxicity on the microglia cells. Furthermore, in vivo experiments indicated that the rh-EPO-Tw-ABNPs could enhance the distribution of EPO in the brain and relieve brain edema more effectively. Moreover, compared with an rh-EPO injection, the rh-EPO-Tw-ABNPs could increase the AQP4 level but reduced GFAP expression in the brain with more efficiency. CONCLUSION: The rh-EPO-Tw-ABNPs could enhance the transport of rh-EPO into the brain with superior therapeutic effect for TBI.

Significance of ICP-related parameters for the treatment and outcome of severe traumatic brain injury.

OBJECTIVE: To analyze the significance of intracranial pressure (ICP)-related parameters on outcome in patients with severe traumatic brain injury. The ICP-related parameters included ICP, ICP dose (DICP), regression of the correlation coefficient between amplitude and pressure (RAP), pressure reactivity index (PRx), and cerebral perfusion pressure (CPP). METHODS: A retrospective analysis was performed using clinical information from 29 patients with severe traumatic brain injury who were admitted to the Department of Neurosurgery from January 2018 to January 2019. All patients underwent ICP probe implantation after admission. Patients were followed up for 6 months after discharge, and were categorized into either the favorable or unfavorable outcome group based on their Glasgow Outcome Scale score. The differences in ICP, DICP, RAP, PRx, and CPP between the two groups were analyzed for their effects on outcome. RESULTS: The average ICP, DICP, PRx, and RAP values in patients with favorable outcomes were significantly lower than in patients with unfavorable outcomes, while CPP values were significantly higher in the favorable outcome group. CONCLUSION: Average ICP, DICP, PRx, RAP, and CPP values may indicate disease status and relate to patient outcomes. It is important to use multiple parameters to predict patients' disease severity and prognosis.

Reflection phase dispersion editing generates wideband invisible acoustic Huygens's metasurface.

Acoustic metasurfaces show non-traditional abilities in wave manipulation and provide alternate mechanisms for information communication and invisibility technology. However, most of the mechanisms remain narrow band (relative bandwidth ∼5%), and a wideband trait is essential for engineering applications. For example, controllable effective material properties-reflection or transmission phase-has barely been realized in wideband because the intrinsic dispersion relation is not always editable. In this paper, wideband reflection phase editing is realized, and wideband invisibility of a phase preserved Huygens's metasurface on a flat background is achieved with anomalous reflection. This metasurface is built with proposed unsymmetrical twin Helmholtz resonators which reach a predefined dispersion relation target value. The total instantaneous acoustic fields show nearly identical carpeting effects in a consecutive band with relative bandwidth 52.1% (from 5400 to 9200 Hz) in simulation and experiment.