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Anti-CRISPR (Acr) proteins are natural inhibitors of CRISPR-Cas systems, found in bacteriophages and other genetic elements. AcrIE3, identified in a Pseudomonas phage, inactivates the type I-E CRISPR-Cas system in Pseudomonas aeruginosa by engaging with the Cascade complex. However, its precise inhibition mechanism has remained elusive. In this study, we present a comprehensive structural and biochemical analysis of AcrIE3, providing mechanistic insight into its anti-CRISPR function. Our results reveal that AcrIE3 selectively binds to the Cas8e subunit of the Cascade complex. The crystal structure of AcrIE3 exhibits an all-helical fold with a negatively charged surface. Through extensive mutational analyses, we show that AcrIE3 interacts with the protospacer adjacent motif (PAM) recognition site in Cas8e through its negatively charged surface residues. These findings enhance our understanding of the structure and function of type I-E Acr proteins, suggesting PAM interaction sites as primary targets for divergent Acr inhibitors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Unilateral hemispheric stroke can impair the ipsilesional motor performance, which is crucial for attaining optimal functional outcomes poststroke. However, the specific brain structures contributing to ipsilesional motor performance impairment remain unclear., Objective: To explore the link between ipsilesional motor performance and the microstructural integrity of relevant neural pathways., Methods: This study enrolled 60 consecutive patients in the early subacute phase of stroke recovery. Ipsilesional motor performance was assessed using the Box and Block Test. Multiple linear regression was used to evaluate the associations between ipsilesional motor performance and the microstructural integrity of relevant white matter tracts (Biomarker models) and cognitive function test scores (Cognition models)., Results: Biomarker models, including the genu of the corpus callosum, ipsilesional cingulum, fornix, uncinate fasciculus, superior longitudinal fasciculus, and contralesional inferior longitudinal fasciculus, showed a significant association with ipsilesional motor performance. Cognition models, including Mini-Mental State Examination and Trail Making Test-B, were significantly associated with ipsilesional motor performance. Final regression models (combined Cognition and Biomarker models) revealed that the performance time of Trail Making Test-B, in combination with biomarkers, including the genu of the corpus callosum, ipsilesional superior longitudinal fasciculus, and ipsilesional cingulum, predicted ipsilesional motor performance with high explanatory power ( adjusted R 2  = .721, .709, and .696, respectively)., Conclusions: This study demonstrated that executive function is associated with poststroke ipsilesional motor performance, as evidenced by the microstructural biomarkers involved in executive function. Our findings highlight that the comprehensive role of cognitive functioning rather than the motor system is closely linked to poststroke ipsilesional motor performance., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Glioblastoma multiforme (GBM) is a devastating primary tumor of the central nervous system with a significantly poor prognosis. The primary challenge in treating GBM lies in the restrictive nature of the blood-brain barrier (BBB), impeding effective drug delivery to the brain. In this study, intranasal polymeric micelles encapsulating a quercetin-etoposide combination were developed to induce synergistic apoptotic effects and enhance direct drug delivery to the brain. However, the in vivo anticancer efficacy of the unmodified micelle formulation via intranasal administration remains limited. Therefore, this aims to investigate the enhancement of the formulation by conjugating the micelles with a novel and highly potent cell-penetrating peptide (CPP), RMMR1, identified using the intra-dermal delivery technology platform developed by REMEDI Co., Ltd. This modification seeks to enhance the brain-targeting capability of the micelles. The CPP-modified micelles encapsulating the quercetin-etoposide combination (CM(QE)) demonstrated superior in vivo brain-delivery efficiency and enhanced cellular uptake after intranasal administration. Furthermore, animal studies showed significant tumor reduction and increased survival rates, with no significant changes in body weight observed. These findings suggest that intranasal administration of CM(QE) holds promise as a significant advancement in chemotherapy for GBM., Competing Interests: Declaration of competing interest S. Cho and C. Park are listed on the patent entitled “Cargo molecule transport domain RMMR1, variant thereof, recombinant cargo molecule containing thereof and cargo molecule transport method using the same” (Application number: PCT/KR2022/007344). The remaining authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biomass-based functional polymers have received significant attention across various fields, in view of eco-friendly human society and sustainable growth. In this context, there are efforts to functionalize the biomass polymers for next-generation polymer materials. Here, stretchable heat transfer materials are focused on which are essential for stretchable electronics and future robotics. To achieve this goal, natural rubber (NR) is chemically modified with a thiol-terminated phenylnaphthalene (TTP), and then utilized as a thermally conductive NR (TCNR) matrix. Hexagonal boron nitride (h-BN), renowned for its high thermal conductivity and low electrical conductivity, is incorporated as a filler to develop stretchable heat transfer eco-materials. The optimized TCNR/h-BN composite elongates to 140% due to great elasticity of NR, and exhibits excellent dielectric properties (a low dielectric constant of 2.26 and a low dielectric loss of 0.006). Furthermore, synergetic phonon transfer of phenylnaphthalene crystallites and h-BN particles in the composite results in a high thermal conductivity of 0.87 W m -1  K -1 . The outstanding thermal, mechanical, and dielectric properties of the newly developed TCNR/h-BN composite enable the successful demonstration as stretchable and shape-adaptable thermal management materials., (© 2024 Wiley‐VCH GmbH.)

Soft tissue sarcomas (STSs) constitute a heterogeneous group of tumors that originate from mesenchymal cells. Imaging plays an important role in the assessment of the oncological stage of STSs. Computed tomography findings facilitate the identification of the tumor location and margins in relation to the surrounding anatomic boundaries and thereby enable preoperative planning of tumor management. The histological grade is among the most important parameters that affect tumor recurrence and metastasis rates. However, the prediction of STS histological grades using CT characteristics has not yet been elucidated. This study retrospectively investigated CT findings of patients with different STS grades for differentiation. Thirty dogs with STSs (12 Grade 1, 10 Grade 2, and 8 Grade 3) were included from three animal hospitals. The investigated CT features included tumor delineation, dysmorphic intratumoral or peritumoral vessels, contrast enhancement patterns, peripheral rim enhancement, intratumoral calcification, degree of intratumoral cystic lesions, peritumoral fat stranding, metastatic regional lymphadenopathy, and lung metastasis. Quantitative findings included tumor size and pre- and postcontrast attenuation. Tumor size, dysmorphic intratumoral or peritumoral vessels, peritumoral fat stranding, and metastatic regional lymphadenopathy significantly differed among tumor grades. On post hoc analysis, Grade 3 tumors were significantly larger, had a higher prevalence of dysmorphic vessels than Grade 1 tumors, and had a significantly higher rate of adjacent metastatic lymphadenopathy than Grade 2 tumors. Predicting STS grades before the histopathological examination could potentially aid in the planning of the STS resection margins., (© 2024 American College of Veterinary Radiology.)