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This study developed and validated a five-dimension scale of tourist rural destination restorative capacity. Following the scale development procedure recommended by Churchill, the present study validated that such capacity comprises the dimensions of fascination, compatibility, extent, being away, and life atmosphere. The results showed that restorative capacity directly affects restorative outcomes for tourists. This study contributes to the scarce literature on the issue of interest and provides an important index that destination managers can use to improve the restorative capacity of their vacation sites and promote the image of these attractions among travelers. [ABSTRACT FROM AUTHOR]

Background: Muscle-invasive bladder cancer (MIBC) is a prevalent cancer characterized by molecular and clinical heterogeneity. Assessing the spatial heterogeneity of the MIBC microenvironment is crucial to understand its clinical significance. Methods: In this study, we used imaging mass cytometry (IMC) to assess the spatial heterogeneity of MIBC microenvironment across 185 regions of interest in 40 tissue samples. We focused on three primary parameters: tumor (T), leading-edge (L), and nontumor (N). Cell gating was performed using the Cytobank platform. We calculated the Euclidean distances between cells to determine cellular interactions and performed single-cell RNA sequencing (scRNA-seq) to explore the molecular characteristics and mechanisms underlying specific fibroblast (FB) clusters. scRNA-seq combined with spatial transcriptomics (ST) facilitated the identification of ligand–receptor (L–R) pairs that mediate interactions between specific FB clusters and endothelial cells. Machine learning algorithms were used to construct a prognostic gene signature. Results: The microenvironments in the N, L, and T regions of MIBC exhibited spatial heterogeneity and regional diversity in their components. A distinct FB cluster located in the L region—identified as S3—is strongly associated with poor prognosis. IMC analyses demonstrated a close spatial association between S3 and endothelial cells, with S3-positive tumors exhibiting increased blood vessel density and altered vascular morphology. The expression of vascular endothelial growth factor receptor and active vascular sprouting were significant in S3-positive tumors. scRNA-seq and ST analyses indicated that the genes upregulated in S3 were associated with angiogenesis. NOTCH1–JAG2 signaling pathway was identified as a significant L–R pair specific to S3 and endothelial cell interactions. Further analysis indicated that YAP1 was a potential regulator of S3. Machine learning algorithms and Gene Set Variation Analysis were used to establish an S3-related gene signature that was associated with the poor prognosis of tumors including MIBC, mesothelioma, glioblastoma multiforme, lower-grade glioma, stomach adenocarcinoma, uveal melanoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, and lung squamous cell carcinoma. Conclusions: We assessed the spatial landscape of the MIBC microenvironment and revealed a specific FB cluster with prognostic potential. These findings offer novel insights into the spatial heterogeneity of the MIBC microenvironment and highlight its clinical significance. [ABSTRACT FROM AUTHOR]

The cocrystallization of 1,3,5,7-tetranitro-1,3,5,7-tetrazolidine (HMX) with cyclopentanone was achieved via a controlled cooling method, followed by comprehensive characterization that confirmed the α-configuration of HMX within the cocrystal. The enthalpy of dissolution of HMX in cyclopentanone was assessed across a range of temperatures using a C-80 Calvert microcalorimeter, revealing an endothermic dissolution process. Subsequently, the molar enthalpy of dissolution was determined, and kinetic equations describing the dissolution rate were derived for temperatures of 303.15, 308.15, 313.15, 318.15, and 323.15 K as follows: dα⁄dt = 10−2.46(1 − α)0.35, dα⁄dt = 10−2.19(1 − α)0.79, dα⁄dt = 10−1.76(1 − α)1.32, dα⁄dt = 10−1.86(1 − α)0.46, and dα⁄dt = 10−2.02(1 − α)0.70, respectively. Additionally, molecular dynamics (MD) simulations investigated the intermolecular interactions of the HMX/cyclopentanone cocrystallization process, demonstrating a transformation of HMX from β- to α-conformation within the cyclopentanone environment. Theoretical calculations performed at the ωB97XD/6-311G(d,p) level affirmed that α-HMX exhibited stronger binding affinity toward cyclopentanone compared to β-HMX, corroborating experimental findings. A comprehensive understanding of the dissolution behavior of HMX in cyclopentanone holds significant implications for crystal growth methodologies and cocrystallization processes. Such insights are pivotal for optimizing HMX dissolution processes and offer valuable perspectives for developing and designing advanced energetic materials. [ABSTRACT FROM AUTHOR]

Lymphocyte activation gene-3 (LAG3) positive B cells have been identified as a novel regulatory B cell subset, while the role of LAG3+ B cells in the pathogenesis of rheumatoid arthritis (RA) remains elusive. Peripheral blood mononuclear cells (PBMCs) from RA, osteoarthritis (OA) patients and healthy volunteers were collected for flow cytometry staining of LAG3+ B cells. Their correlation with RA patient clinical and immunological features were analyzed. Moreover, the frequencies of LAG3+ B cells in collagen-induced arthritis (CIA) mice and naive mice were also detected. A significant decrease of LAG3+ B cells was observed in RA patients as compared with healthy individuals and OA patients. Notably, the frequencies of LAG3+ B cells were negatively correlated with tender joint count (r = −0.4301, p =.0157) and DAS28-ESR (r = −0.4018, p =.025) in RA patients. In CIA mice, LAG3+ B cell frequencies were also decreased and negatively correlated with the CIA arthritis score. Impairment of LAG3+ B cells potentially contributes to RA development. Reconstituting LAG3+ B cells might provide novel therapeutic strategies for the persistent disease. LAG3+ B cells have been identified as a novel regulatory B cell subset. However, its role in the pathogenesis of RA remains unknown. This study revealed the decreased frequency of LAG3+ B cells in RA patients. Notably, LAG3+ B cells were negatively correlated with RA disease activity including the tender joint count and DAS28-ESR. In CIA mice, LAG3+ B cell frequencies were also decreased and negatively correlated with the CIA arthritis score. Reconstitution of LAG3+ B cells might provide novel therapeutic strategies for disease perpetuation. [ABSTRACT FROM AUTHOR]