Objectives
Simultaneous multi-slice (SMS) imaging with short repetition time (TR) accelerates diffusion tensor imaging (DTI) acquisitions. However, its impact when combined with readout-segmented ...echo planar imaging (RESOLVE) on the cranial nerves given the challenging skull base/posterior fossa terrain is unexplored. We evaluated the reliability of trigeminal nerve DTI metrics using SMS with RESOLVE-DTI.
Methods
Eight healthy controls and six patients with unilateral trigeminal neuralgia (TN) underwent brain MRI scan. Three different RESOLVE-DTI protocols were performed on a 3-T MRI system: non-SMS (TR = 4330 ms), SMS with identical TR (4330 ms), and SMS with short TR (2400 ms). Pontine signal-to-noise ratio (SNR) and DTI metrics of the trigeminal nerve streamlines tracked by two independent raters using deterministic tractography and standardized tracking protocol were obtained. These were statistically analyzed and compared across the three protocols using intra-rater and inter-rater intraclass correlation coefficients (ICCs), one-way analysis of variance (ANOVA), post hoc analysis, and linear regression.
Results
On visual screening, there were no artifacts across the trigeminal nerves. All data also cleared objective image quality assurance analysis. Pontine SNR was similar for the two SMS protocols and higher for the non-SMS RESOLVE-DTI (
F
(2,36)
= 4.40,
p
= 0.02). Intra-rater and inter-rater ICCs were very good (> 0.85). Trigeminal nerve DTI metrics were consistently measured by the three protocols, revealing significant linear relationships between non-SMS- and SMS-derived DTI metrics.
Conclusion
SMS RESOLVE-DTI enables fast and reliable evaluation of microstructural integrity of the trigeminal nerve, with potential application in the clinical management of TN.
Key Points
•
Readout-segmented diffusion-weighted echo planar imaging (RESOLVE-DTI) reduces image distortion artifacts in the posterior fossa but its long acquisition time limits clinical utility
.
•
Simultaneous multi-slice (SMS) imaging combined with RESOLVE-DTI provides reliable trigeminal nerve tractography with potential applications in trigeminal neuralgia
.
•
Two-fold-accelerated RESOLVE-DTI yields comparable trigeminal nerve streamlines and DTI metrics while near-halving acquisition time
.
The lack of reliable near-surface wind data products in lake district regions significantly limits the efficiency of meteorological models, forecasts, services, and wind resource development. This is ...primarily due to a shortage of observation data and related studies, as well as insufficient validation and promotion of existing data products, which further hinders the comprehension and monitoring of local wind fields. In this study, comprehensive verification research was conducted on mainstream wind field products, namely, ERA5-Land (EC), GLDAS (GL), and HRCLDAS (HR) in the Dongting Lake area of China. This was achieved by utilizing a large volume of measured data and a triple collocation analysis (TCA) method. Additionally, an exploration into the optimal wind field data fusion method was undertaken. HR products demonstrate superior performance in capturing wind speed at the
in situ
measured scale, while GL outperforms at the grid scale, and EC products show relatively stable performance with minimal outliers. The long short-term memory (LSTM) neural network model, combined with time-series features, emerges as the most optimal data fusion model. LSTM fusion product is superior to the original product (except for HR products at the
in situ
measured scale), TCA-based weighted fusion products, and multi-layer fully connected neural network (MFCNN) on various parameters. This study quantifies the performance of mainstream wind products in lake areas and provides a benchmark for further application of these products. Furthermore, the successful implementation of an optimal wind data fusion method can provide valuable insights for related research, and the resulting wind fusion products can offer superior basic data support for local terminal applications.
Traditional medicinal herbs are an untapped source of potential pharmaceutical compounds. This study aims to determine whether the proliferation of breast cancer cell lines could be inhibited by ...germacrone, a natural product isolated from
Rhizoma curcuma. Germacrone treatment significantly inhibited cell proliferation, increased lactate dehydrogenase (LDH) release, and induced mitochondrial membrane potential (Δ
Ψm) depolarization in both MCF-7 and MDA-MB-231 cells in a dose-dependent manner. Germacrone induced MDA-MB-231 and MCF-7 cell cycle arrest at the G0/G1 and G2/M phases respectively and induced MDA-MB-231 cell apoptosis. Furthermore, germacrone treatment significantly increased Bok expression and cytochrome
c release from mitochondria without affecting Bcl-2, Bcl-xL, Bax, and Bim protein expressions. In addition, germacrone treatment induced caspase-3, 7, 9, PARP cleavage. We concluded that germacrone inhibited the proliferation of breast cancer cell lines by inducing cell cycle arrest and apoptosis through mitochondria-mediated caspase pathway. These results might provide some molecular basis for the anti-tumor activity of
Rhizoma curcuma.
Double‐cable conjugated polymers with near‐infrared (NIR) electron acceptors are synthesized for use in single‐component organic solar cells (SCOSCs). Through the development of a judicious synthetic ...pathway, the highly sensitive nature of the 2‐(3‐oxo‐2,3‐dihydroinden‐1‐ylidene)malononitrile (IC)‐based electron acceptors in basic and protonic solvents is overcome. In addition, an asymmetric design motif is adopted to optimize the packing of donor and acceptor segments, enhancing charge separation efficiency. As such, the new double‐cable polymers are successfully applied in SCOSCs, providing an efficiency of over 10 % with a broad photo response from 300 to 850 nm and exhibiting excellent thermal/light stability. These results demonstrate the powerful design of NIR‐acceptor‐based double‐cable polymers and will enable SCOSCs to enter a new stage.
Symmetric and asymmetric near‐infrared double‐cable conjugated polymers based on a non‐fused‐ring thieno3,4‐cpyrrole‐4,6‐dione (TPD) core with 2‐(3‐oxo‐2,3‐dihydroinden‐1‐ylidene)malononitrile (IC) side units were successfully synthesized for application in single‐component organic solar cells (SCOSCs). The asymmetric polymer exhibited improved hole mobility, leading to SCOSCs with high quantum efficiencies over 0.80 and power conversion efficiencies over 10 %.
Esophageal squamous-cell carcinoma (ESCC) is commonly treated with radiotherapy; however, radioresistance hinders its clinical effectiveness, and the underlying mechanism remains elusive. Here, we ...develop patient-derived xenografts (PDXs) from 19 patients with ESCC to investigate the mechanisms driving radioresistance. Using RNA sequencing, cytokine arrays, and single-cell RNA sequencing, we reveal an enrichment of cancer-associated fibroblast (CAF)-derived collagen type 1 (Col1) and tumor-cell-derived CXCL1 in non-responsive PDXs. Col1 not only promotes radioresistance by augmenting DNA repair capacity but also induces CXCL1 secretion in tumor cells. Additionally, CXCL1 further activates CAFs via the CXCR2-STAT3 pathway, establishing a positive feedback loop. Directly interfering with tumor-cell-derived CXCL1 or inhibiting the CXCL1-CXCR2 pathway effectively restores the radiosensitivity of radioresistant xenografts in vivo. Collectively, our study provides a comprehensive understanding of the molecular mechanisms underlying radioresistance and identifies potential targets to improve the efficacy of radiotherapy for ESCC.
Display omitted
•Estimation of responsiveness to radiotherapy using ESCC PDX models•CXCL1-mediated collagen deposition confers radioresistance•CAF-derived collagen promotes the secretion of CXCL1 from tumor cells•Targeting collagen synthesis or CXCL1/CXCR2 pathway restores radiosensitivity
Yang et al. investigate the mechanisms of radioresistance using well-established ESCC PDX models. They identify a positive feedback loop between tumor-cell-derived CXCL1 and CAF-derived collagen that ultimately leads to radioresistance, providing a potential target to predict and overcome radioresistance.
Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic ...disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.
A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was ...evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.
A novel quinic acid derivative, 5-O-trans-o-coumaroylquinic acid methyl ester (1), together with three known ones, chlorogenic acid methyl ester (2), macranthoin F (3) and macranthoin G (4), were ...isolated from the aerial parts of the invasive plant Ageratina adenophora (Spreng.). The structure of new compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 2-4 were isolated from plant A. adenophora for the first time. All the compounds showed in vitro antibacterial activity toward five assayed bacterial strains, especially 3 and 4, which showed in vitro antibacterial activity against Salmonella enterica with MIC values of 7.4 and 14.7 μM, respectively. Compound 1 was further found to display in vitro anti-fungal activity against spore germination of Magnaporthe grisea with an IC₅₀ value 542.3 µM. These four compounds were also tested for their antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical.
We performed a screen for genes whose expression correlates with invasiveness of esophageal squamous cell carcinoma (ESCC) cells. We studied the effects of overexpression and knockdown of these genes ...in cell lines and expression levels in patient samples.
We selected genes for analysis from 11 loci associated with risk of ESCC. We analyzed the effects of knocking down expression of 47 of these genes using RNA interference on-chip analysis in ESCC cells and HeLa cells. Cells with gene overexpression and knockdown were analyzed in migration and invasion assays or injected into nude mice and metastasis of xenograft tumors was quantified. We collected ESCC and non-tumor esophageal tissues from 94 individuals who underwent surgery in China from 2010 and 2014; clinical information was collected and survival time was measured from the date of diagnosis to the date of last follow-up or death. Levels of messenger RNAs (mRNAs) were quantified by RNA sequencing, and levels of proteins were determined from immunoblot analyses. Patient survival was compared with mRNA levels using Kaplan-Meier methods and hazard ratios were calculated by Cox models.
We identified 8 genes whose disruption increased migration and 10 genes whose disruption reduced migration. Knockdown of BRCA1-associated protein gene (BRAP) significantly reduced migration of KYSE30, KYSE150, and HeLa cells. In patient tumors, 90% of ESCCs examined had higher levels of BRAP protein than paired non-tumor tissues, and 63.8% had gains in BRAP DNA copy number. Levels of BRAP mRNA in ESCC tissues correlated with patient survival time, and high expression increased risk of death 2.4-fold compared with low expression. ESCCs that had metastasized to lymph node had significantly higher levels of BRAP mRNA than tumors without metastases. Knockdown of BRAP in ESCC and HeLa cell lines significantly reduced migration and invasiveness; these cell lines formed less metastases in mice than control cells. Nuclear translocation of the nuclear factor−κB (NF-κB) P65 subunit and phosphorylation of inhibitor of NF-κB kinase subunit β (IKBKB or IKKβ) increased in cells that overexpressed BRAP and decreased in cells with BRAP knockdown. In immunoprecipitation assays, BRAP interacted directly with IKKβ. Expression of matrix metalloproteinase 9 and vascular epithelial growth factor C, which are regulated by NF-κB, was significantly reduced in cells with knockdown of BRAP and significantly increased in cells that overexpressed BRAP.
Expression of BRAP is increased in ESCC samples compared with non-tumor esophageal tissues; increased expression correlates with reduced patient survival time and promotes metastasis of xenograft tumors in mice. BRAP overexpression leads to increased activity of NF-κB and expression of matrix metalloproteinase 9 and vascular epithelial growth factor C.
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