A recombinant fungal photolyase autonomously enters human cell nuclei to fix UV-induced DNA lesions.

Solar ultraviolet radiations induced DNA damages in human skin cells with cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts (6-4PPs) as the most frequent lesions. CPDs are repaired much slower than 6-4PPs by the nucleotide excision repair pathway, which are thus the major lesions that interfere with key cellular processes and give rise to gene mutations, possibly resulting in skin cancer. In prokaryotes and multicellular eukaryotes other than placental mammals, CPDs can be rapidly repaired by CPD photolyases in one simple enzymatic reaction using the energy of blue light. In this study, we aim to construct recombinant CPD photolyases that can autonomously enter human cell nuclei to fix UV-induced CPDs. A fly cell penetration peptide and a viral nucleus localization signal peptide were recombined with a fungal CPD photolyase to construct a recombinant protein. This engineered CPD photolyase autonomously crosses cytoplasm and nuclear membrane of human cell nuclei, which then efficiently photo-repairs UV-induced CPD lesions in the genomic DNA. This further protects the cells by increasing SOD activity, and decreasing cellular ROSs, malondialdehyde and apoptosis.

Preoperative assessment of meningioma consistency using a combination of magnetic resonance elastography and diffusion tensor imaging.

BACKGROUND AND PURPOSE: Preoperative assessment of meningioma consistency is beneficial for optimizing surgical strategy and prognosis of patients. We aim to develop a non-invasive prediction model for meningioma consistency utilizing magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI). MATERIALS AND METHODS: Ninety-four patients (52yr ± 22, 69 females, 25 males) diagnosed with meningioma were recruited in the study. Each patient underwent preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), DTI, and MRE. Combined MRE-DTI model was developed based on multiple logistic regression. Intraoperative tumor descriptions served as clinical criteria for evaluating meningioma consistency. The diagnostic efficacy in determining meningioma consistency was evaluated using receiver operating characteristic (ROC) curve. Further validation was conducted in twenty-seven stereotactic biopsies using indentation tests and underlying mechanism was investigated by histologic analysis. RESULTS: Among all the imaging modalities, MRE demonstrated the highest efficacy with the shear modulus magnitude (|G*|) achieving an area under the curve (AUC) of 0.81 (95% CI: 0.70-0.93). When combined with DTI, the diagnostic accuracy further increased (AUC: 0.88, 95% CI: 0.78-0.97), surpassing any modality alone. Indentation measurement based on stereotactic biopsies further demonstrated that the MRE-DTI model was suitable for predicting intra-tumor consistency. Histological analysis suggested that meningioma consistency may be correlated with tumor cell density and fibrous content. CONCLUSIONS: The MRE-DTI combined model is effective in noninvasive prediction of meningioma consistency. ABBREVIATIONS: MRE = magnetic resonance elastography; FA = fractional anisotropy; ROC = receiver operating characteristic; AUC = area under curve.

Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development. METHODS: Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs. RESULTS: Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis. CONCLUSION: This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes-PFDN4, CEMIP, and BTBD10-may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.

Study on the thawing characteristics of beef in ultrasound combined with plasma-activated water.

The effects of deionized water thawing (DT), plasma-activated water thawing (PT), ultrasound (150 W, 40 kHz) combined with deionized water thawing (UDT), and ultrasound combined with plasma-activated water thawing (UPT) on the thawing characteristics and the physicochemical properties of the beef were investigated. The results showed that the UPT group had a faster thawing rate (38 % higher compared to the PT group) and good bactericidal ability (75 % higher compared to the UDT group), and had no adverse effect on the color and pH value of the beef. Plasma-activated water (PAW) can maintain the stability of the beef fiber, improve the water holding capacity (WHC), inhibit lipid oxidation, and reduce the loss of soluble substances such as protein. Therefore, UPT thawing is a promising meat thawing technology, which provides practical guidance and methods for the wide application of UPT in the field of meat thawing.

Cell dehydration enables massive production of engineered membrane vesicles with therapeutic functions.

Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.

Influence of electrohydrodynamics on the drying characteristics and volatile components of iron stick yam.

The drying characteristics, rehydration capacity, color, infrared spectra and volatile components of iron stick yam slices were investigated under different alternating current (AC) voltages (13, 17, 21 kV), hot air drying (HAD) (60 °C) and natural drying (AD) by electrohydrodynamic (EHD) drying and HAD experimental devices. The results showed that slices of iron stick yam dried the quickest with HAD, which also had the fastest drying rate; while drying the slices of iron stick yam with EHD led to a better rehydration capacity, higher brightness L* and whiteness, a more stable protein secondary structure, and a greater variety and content of volatile components compared with AD and HAD. These finding indicated that EHD is a more promising method for drying iron stick yam.

Advancing understanding of Ficus carica: a comprehensive genomic analysis reveals evolutionary patterns and metabolic pathway insights.

Ficus carica L. (dioecious), the most significant commercial species in the genus Ficus, which has been cultivated for more than 11,000 years and was one of the first species to be domesticated. Herein, we reported the most comprehensive F. carica genome currently. The contig N50 of the Orphan fig was 9.78 Mb, and genome size was 366.34 Mb with 13 chromosomes. Based on the high-quality genome, we discovered that F. carica diverged from Ficus microcarpa ~34 MYA, and a WGD event took place about 2─3 MYA. Throughout the evolutionary history of F. carica, chromosomes 2, 8, and 10 had experienced chromosome recombination, while chromosome 3 saw a fusion and fission. It is worth proposing that the chromosome 9 experienced both inversion and translocation, which facilitated the emergence of the F. carica as a new species. And the selections of F. carica for the genes of recombination chromosomal fragment are compatible with their goal of domestication. In addition, we found that the F. carica has the FhAG2 gene, but there are structural deletions and positional jumps. This gene is thought to replace the one needed for female common type F. carica to be pollinated. Subsequently, we conducted genomic, transcriptomic, and metabolomic analysis to demonstrate significant differences in the expression of CHS among different varieties of F. carica. The CHS playing an important role in the anthocyanin metabolism pathway of F. carica. Moreover, the CHS gene of F. carica has a different evolutionary trend compared to other Ficus species. These high-quality genome assembly, transcriptomic, and metabolomic resources further enrich F. carica genomics and provide insights for studying the chromosomes evolution, sexual system, and color characteristics of Ficus.

Quantitative Analysis of Myocaridal Perfusion in Rabbits by Tansthoracic Real-time Myocardial Contrast Echocardiography / 华中科技大学学报（医学）（英德文版）

To evaluate the feasibility of real-time myocardial contrast echocardiography (RTMCE) by quantitative analysis of myocardial perfusion in rabbits,transthoracic RTMCE was performed in 10 healthy rabbits by using continuous infusion of Sono Vue into the auricular vein. The short axis view at the papillary muscle level was obtained. The duration of the time that the contrast took to appear in right heart,left heart and myocardium was recorded. The regional myocardial signal intensity (SI) versus refilling time plots were fitted to an exponential function:y(t) =A(1-e-β(t-t0)) + C,where y is SI at any given time,A is the SI plateau that reflects myocardial blood volume,and β is the slope of the refilling curve that reflects myocardial microbubble velocity. The A,β and A×β values at different infusion rate of SonoVue were analyzed and the A,β and A×β values in each segment in the short axis view at the papillary muscle level were compared. All the animal experiments were successful and high-quality images were obtained. The best intravenous infusion rate for Sono Vue was 30 mL/h. The contrast appeared in fight heart,left heart and myocardium at 7.5±2.2 s,9.1±2.4 s and 12.2±1.6 s respectively. After 16.6±2.3s,myocardial opacification reached a steady state. The mean A,β and A×β value in the short axis view at the papillary muscle level were 9.8±3.0 dB,1.4±0.5 s 1 and 13.5±3.6 dB×s-1 respectively.A,β and A×β values showed no significant differences among 6 segments. It was suggested that RTMCE was feasible for quantitative analysis of myocardial perfusion in rabbits. It provides a non-invasive method to evaluate the myocardial perfusion in rabbit disease models.