Linc-NSC affects cell differentiation, apoptosis and proliferation in mouse neural stem cells and embryonic stem cells in vitro and in vivo.

BACKGROUND: Stem cell therapy is a promising therapeutic strategy. In a previous study, we evaluated tumorigenicity by the stereotactic transplantation of neural stem cells (NSCs) and embryonic stem cells (ESCs) from experimental mice. Twenty-eight days later, there was no evidence of tumor formation or long-term engraftment in the NSCs transplantation group. In contrast, the transplantation of ESCs caused tumor formation; this was due to their high proliferative capacity. Based on transcriptome sequencing, we found that a long intergenic non-coding RNA (named linc-NSC) with unknown structure and function was expressed at 1100-fold higher levels in NSCs than in ESCs. This finding suggested that linc-NSC is negatively correlated with stem cell pluripotency and tumor development, but positively correlated with neurogenesis. In the present study, we investigated the specific role of linc-NSC in NSCs/ESCs in tumor formation and neurogenesis. METHODS: Whole transcriptome profiling by RNA sequencing and bioinformatics was used to predict lncRNAs that are widely associated with enhanced tumorigenicity. The expression of linc-NSC was assessed by quantitative real-time PCR. We also performed a number of in vitro methods, including cell proliferation assays, differentiation assays, immunofluorescence assays, flow cytometry, along with in vivo survival and immunofluorescence assays to investigate the impacts of linc-NSC on tumor formation and neurogenesis in NSCs and ESCs. RESULTS: Following the knockdown of linc-NSC in NSCs, NSCs cultured in vitro and those transplanted into the cortex of mice showed stronger survival ability (P < 0.0001), enhanced proliferation(P < 0.001), and reduced apoptosis (P < 0.05); the opposite results were observed when linc-NSC was overexpressed in ESCs. Furthermore, the overexpression of linc-NSC in ECSs induced enhanced apoptosis (P < 0.001) and differentiation (P < 0.01), inhibited tumorigenesis (P < 0.05) in vivo, and led to a reduction in tumor weight (P < 0.0001). CONCLUSIONS: Our analyses demonstrated that linc-NSC, a promising gene-edited target, may promote the differentiation of mouse NSCs and inhibit tumorigenesis in mouse ESCs. The knockdown of linc-NSC inhibited the apoptosis in NSCs both in vitro and in vivo, and prevented tumor formation, revealing a new dimension into the effect of lncRNA on low survival NSCs and providing a prospective gene manipulation target prior to transplantation. In parallel, the overexpression of linc-NSC induced apoptosis in ESCs both in vitro and in vivo and attenuated the tumorigenicity of ESCs in vivo, but did not completely prevent tumor formation.

Histoplasmosis: An epidemiological and clinical update in China, review and a case report.

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus in the genus Histoplasma. Histoplasmosis is overlooked in China. This study aims to provide an epidemiological and clinical update on histoplasmosis in China by literature review. We reviewed cases of histoplasmosis reported in recent 11 years and described a case of histoplasmosis-triggered hemophagocytic lymphohistiocytosis (HLH) in an immunocompetent patient. A total of 225 cases of histoplasmosis diagnosed in China between 2012 and 2022 were involved in this study, compared with 300 cases reviewed from 1990 to 2011, an increasing number of cases of histoplasmosis have been diagnosed in the last 11 years. The majority of cases of histoplasmosis were autochthonous cases, mainly from provinces Sichuan (56/225, 24.9%), Hunan (50/225, 22.2%), Guangdong (31/225, 13.8%), and Yunnan (24/225, 10.7%). Higher incidence (52.5%, 53/99) of histoplasmosis occurred in immunocompetent patients which is similar to those from the previous 21 years, and the prevalence of the disease did not vary highly over time. Of note, the number of histoplasmosis cases is increasing, and the geographic distribution is shifting southwards over time. Improved awareness is critically important for informing clinical practice in China.

Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification.

Purpose: Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis. Patients and Methods: Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues. Results: Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues. Conclusion: We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis.

Engineering surface framework TiO6 single sites for unprecedented deep oxidative desulfurization.

Catalytic oxidative desulfurization (ODS) using titanium silicate catalysts has emerged as an efficient technique for the complete removal of organosulfur compounds from automotive fuels. However, the precise control of highly accessible and stable-framework Ti active sites remains highly challenging. Here we reveal for the first time by using density functional theory calculations that framework hexa-coordinated Ti (TiO6) species of mesoporous titanium silicates are the most active sites for ODS and lead to a lower-energy pathway of ODS. A novel method to achieve highly accessible and homogeneously distributed framework TiO6 active single sites at the mesoporous surface has been developed. Such surface framework TiO6 species exhibit an exceptional ODS performance. A removal of 920 ppm of benzothiophene is achieved at 60°C in 60 min, which is 1.67 times that of the best catalyst reported so far. For bulky molecules such as 4,6-dimethyldibenzothiophene (DMDBT), it takes only 3 min to remove 500 ppm of DMDBT at 60°C with our catalyst, which is five times faster than that with the current best catalyst. Such a catalyst can be easily upscaled and could be used for concrete industrial application in the ODS of bulky organosulfur compounds with minimized energy consumption and high reaction efficiency.

Hierarchical Hollow TiO2@Bi2WO6 with Light-Driven Excited Bi(3-x)+ Sites for Efficient Photothermal Catalytic CO2 Reduction.

Converting CO2 into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO2 reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO2@Bi2WO6 heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO2@Bi2WO6 photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi(3-x)+ sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 µmol h-1 g-1, which is 15 and 4.7 times higher than that of pure Bi2WO6 and that of physically mixed TiO2/Bi2WO6, respectively. An in situ study shows that the pathway for the transformation of CO2 into CO over our TiO2@Bi2WO6 proceeds via two important intermediates, including COO- and COOH-. Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO2 conversion.

TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model.

Intrauterine adhesion (IUA) is characterized by the formation of fibrous scar tissue within the uterine cavity, which significantly impacts female reproductive health and even leads to infertility. Unfortunately, severe cases of IUA currently lack effective treatments. This study presents a novel approach that utilizes tumor necrosis factor-(TNF) stimulated gene 6 (TSG6)-modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. This study demonstrate that TSG6-modified Exos effectively inhibits the activation of inflammatory M1-like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, this research indicates that CS/GP facilitates the sustained release of TSG6-modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6-modified Exos, a reduction in the occurrence and progression of IUA is achieved by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.

Polyphosphazene-Based Anion-Anchored Polymer Electrolytes For All-Solid-State Lithium Metal Batteries.

Safety concerns of traditional liquid electrolytes, especially when paired with lithium (Li) metal anodes, have stimulated research of solid polymer electrolytes (SPEs) to exploit the superior thermal and mechanical properties of polymers. Polyphosphazenes are primarily known for their use as flame retardant materials and have demonstrated high Li-ion conductivity owing to their highly flexible P = N backbone which promotes Li-ion conduction via inter- and intrachain hopping along the polymer backbone. While polyphosphazenes are largely unexplored as SPEs in the literature, a few existing examples showed promising ionic conductivity. By anchoring the anion to the polymer backbone, one may primarily allow the movement of Li ions, alleviating the detrimental effects of polarization that are common in conventional dual-ion conducting SPEs. Anion-anchored SPEs, known as single Li-ion conducting solid polymer electrolytes (SLiC-SPEs), exhibit high Li-ion transference numbers (tLi+), which limits Li dendrite growth, thus further increasing the safety of SPEs. However, previously reported SLiC-SPEs suffer from inadequate ionic conductivity, small electrochemical stability windows (ESWs), and limited cycling stability. Herein, we report three polyphosphazene-based SLiC-SPEs comprising lithiated polyphosphazenes. The SLiC polyphosphazenes were prepared through a facile synthesis route, opening the door for enhanced tunability of polymer properties via facile macromolecular nucleophilic substitution and subsequent lithiation. State-of-the-art characterization techniques, such as differential scanning calorimetry (DSC), electrochemical impedance spectroscopy (EIS), and solid-state nuclear magnetic resonance spectroscopy (ssNMR) were employed to probe the effect of the polymer structure on Li-ion dynamics and other electrochemical properties. Produced SPEs showed thermal stability up to ∼208 °C with ionic conductivities comparable to that of the best-reported SLiC-SPEs that definitively comprise no solvents or plasticizers. Among the three lithiated polyphosphazenes, the SPE containing dilithium poly[bis(trifluoroethylamino)phosphazene] (pTFAP2Li) exhibited the most promising electrochemical characteristics with tLi+ of 0.76 and compatibility with both Li metal anodes and LiFePO4 (LFP) cathodes; through 40 cycles at 100 °C, the PEO-pTFAP2Li blend showed 81.2% capacity utilization and 86.8% capacity retention. This work constitutes one of the first successful demonstrations of the cycling performance of a true all-solid-state Li-metal battery using SLiC polyphosphazene SPEs.

Recent advances and progress on the design, fabrication and biomedical applications of Gallium liquid metals-based functional materials.

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

Interplay of Adolescents' and Parents' Mindsets of Socioeconomic Status on Adolescents' Stress-Related Outcomes.

The reciprocity and variation of values and beliefs are dynamic features of the parent-child relationship. Parents and adolescents may hold congruent or incongruent views regarding the malleability of socioeconomic status (mindset of SES), potentially influencing adolescents' psychological and physiological stress outcomes, as reflected in stress perceptions and the hypothalamic-pituitary-adrenal (HPA) axis functioning. The current study investigated how patterns of parent-adolescent congruence and incongruence in mindset of SES were associated with adolescents' perceived stress and diurnal cortisol patterns four months later. A total of 253 adolescents (Mage = 12.60, 46.2% girls) and their parents (Mage = 40.09 years, 59.5% mothers) participated in this study. Polynomial regression analyses and response surface analyses showed that adolescents perceived lower levels of stress when they themselves or their parents reported a stronger growth mindset of SES. Additionally, adolescents with a stronger growth mindset of SES also exhibited a steeper diurnal cortisol slope. Moreover, parents' mindset significantly interacted with adolescents' mindset to influence adolescents' diurnal cortisol patterns such that when adolescents hold weaker growth mindset of SES, those with higher parental growth mindsets had significantly higher cortisol awakening response and steeper diurnal cortisol slope. Furthermore, adolescents who showed incongruence with their parents but had averagely stronger growth mindsets of SES reported a significantly steeper diurnal cortisol slope than those who had averagely weaker growth mindsets with their parents. The findings point to the beneficial impacts of the growth mindset of SES on stress-related outcomes among adolescents, as well as the significance of considering both parents' and adolescents' mindsets when exploring these associations.

SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study employed APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of SIRT4. Subsequently, the binding of transcription factors to SIRT4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells in comparison to their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.

Generation of SST-P2A-mCherry reporter human embryonic stem cell line using the CRISPR/Cas9 system (WAe001-A-2C).

Somatostatin (SST)-producing pancreatic delta-cells play an important role in maintaining the balance of insulin and glucagon secretion within the islets. This study aimed to generate a human embryonic stem cell (hESC) line with a SST-P2A-mCherry reporter using CRISPR/Cas9 system. The SST-P2A-mCherry reporter cell line was shown to maintain typical pluripotent characteristics and able to be induced into SST-producing pancreatic delta-cells. The generation of the cell line would provide useful platform for the characterization of stem cell-derived delta-cells, discovery of delta-cell surface markers and investigation of paracrine mechanisms, which will ultimately promote the drug discovery and cell therapy of diabetes mellitus.

Sacrificial template synthesis of hollow sulfonate group functionalized microporous organic network for efficient solid phase extraction of sulfonamide antibiotics from milk and honey samples.

The highly conjugated and hydrophobic characteristics of microporous organic networks (MONs) have largely impeded their broad applications in sample pretreatment especially for the polar or ionic analytes. In this work, a novel uniform hollow shaped sulfonate group functionalized MON (H-MON-SO3H-2) was synthesized via the sacrificial template method for the efficient solid phase extraction (SPE) of sulfonamides (SAs) from environmental water, milk, and honey samples prior to HPLC analysis. H-MON-SO3H-2 exhibited large specific surface area, penetrable space, good stability, and numerous hydrogen bonding, electrostatic, hydrophobic and π-π interaction sites, allowing sensitive SPE of SAs with wide linear range (0.150-1000 µg L-1), low limit of detection (0.045-0.188 µg L-1), good precisions (intra-day and inter-day RSD < 7.3%, n = 5), large enrichment factors (95.7-98.5), high adsorption capacities (250.4-545.0 mg g-1), and satisfactory reusability (more than 80 times). Moreover, the established method was successfully applied to extract SAs from spiked samples with the recoveries of 86.1-104.3%. This work demonstrated the great potential of H-MON-SO3H-2 in the efficient SPE of trace SAs in complex environmental water and food samples and revealed the prospect of hollow MONs in sample pretreatment.

The Utilization of Metal-Organic Frameworks and Their Derivatives Composite in Supercapacitor Electrodes.

Up to now, the mainstream adoption of renewable energy has brought about substantial transformations in the electricity and energy sector. This shift has garnered considerable attention within the scientific community. Supercapacitors, known for their exceptional performance metrics like good charge/discharge capability, strong power density, as well as extended cycle longevity, have gained widespread traction across various sectors, including transportation and aviation. Metal-organic frameworks (MOFs) with unique traits including adaptable structure, highly customizable synthetic methods, and high specific surface area, have emerged as strong candidates for electrode materials. For enhancing the performance, MOFs are commonly compounded with other conducting materials to increase capacitance. This paper provides a detailed analysis of various common preparation strategies and characteristics of MOFs. It summarizes the recent application of MOFs and their derivatives as supercapacitor electrodes alongside other carbon materials, metal compounds, and conductive polymers. Additionally, the challenges encountered by MOFs in the realm of supercapacitor applications are thoroughly discussed. Compared to previous reviews, the content of this paper is more comprehensive, offering readers a deeper understanding of the diverse applications of MOFs. Furthermore, it provides valuable suggestions and guidance for future progress and development in the field of MOFs.

Synergistic Protecting-Etching Synthesis of Carbon Nanoboxes@Silicon for High-Capacity Lithium-Ion Battery.

Silicon (Si) is considered as the most likely choice for the high-capacity lithium-ion batteries owing to its ultrahigh theoretical capacity (4200 mA h g-1) being over 10 times than that of traditional graphite anode materials (372 mA h g-1). However, its widespread application is limited by problems such as a large volume expansion and low electrical conductivity. Herein, we design a hollow nitrogen-doped carbon-coated silicon (Si@Co-HNC) composite in a water-based system via a synergistic protecting-etching strategy of tannic acid. The prepared Si@Co-HNC composite can effectively mitigate the volume change of silicon and improve the electrical conductivity. Moreover, the abundant voids inside the carbon layer and the porous carbon layer accelerate the transport of electrons and lithium ions, resulting in excellent electrochemical performance. The reversible discharge capacity of 1205 mA h g-1 can be retained after 120 cycles at a current density of 0.5 A g-1. In particular, the discharge capacity can be maintained at 1066 mA h g-1 after 300 cycles at a high current density of 1 A g-1. This study provides a new strategy for the design of Si-based anode materials with excellent electrical conductivity and structural stability.

Simulated microgravity increases CD226+ Lin- CD117- Sca1+ mesenchymal stem cells in mice.

Microgravity is one of the most common causes counting for the bone loss. Mesenchymal stem cells (MSCs) contribute greatly to the differentiation and function of bone related cells. The development of novel MSCs biomarkers is critical for implementing effective therapies for microgravity induced bone loss. We aimed to find the new molecules involved in the differentiation and function of MSCs in mouse simulated microgravity model. We found CD226 was preferentially expressed on a subset of MSCs. Simulation of microgravity treatment significantly increased the proportion of CD226+ Lin- CD117- Sca1+ MSCs. The CD226+ MSCs produced higher IL-6, M-CSF, RANKL and lower CD200 expression, and promoted osteoclast differentiation. This study provides pivotal information to understand the role of CD226 in MSCs, and inspires new ideas for prevention of bone loss related diseases.

Associations between neutrophil-to-lymphocyte/platelet-to-lymphocyte and recovery in sudden sensorineural hearing loss.

Aims: This study investigated the nonlinear associations between neutrophil-to-lymphocyte (NLR)/platelet-to-lymphocyte (PLR) and recovery rates in sudden sensorineural hearing loss (SSNHL). Methods: Total of 244 SSNHL patients were included. The primary outcome was recovery rate. Results: A nonlinear association was detected between NLR and recovery rate using the LOWESS method, with a knot of 3. Patients with NLR ≥3 had a higher recovery rate than NLR <3. Using the linear-spline function, NLR was significantly associated with high recovery rate when NLR was <3. However, when NLR was ≥3, this association became nonsignificant. The trend test showed a similar result. PLR was not associated with recovery rate. Conclusion: The association between NLR and recovery rate is nonlinear, with a knot of around three. PLR is not associated with recovery rate.

The Evaluation of Clinical and Intravoxel Incoherent Motion Parameters of Primary Lesion in Oligometastatic Prostate Cancer.

BACKGROUND: In the realm of cancer studies,the differences among the biological behavior of oligometastatic prostate cancer (OPCa), localized prostate cancer (LPCa), and widely prostate cancer (WPCa) are still unclear. OBJECTIVES: The purpose of our study was to assess the clinical and intravoxel incoherent motion (IVIM) parameters of tumor burden in OPCa. In addition, the correlation between clinical and IVIM parameters and the prostate-specific antigen nadir (PSAN) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) in OPCa was explored. It was found that the IVIM parameters could effectively differentiate LPCa and WPCa, as well as LPCa and OPC. Moreover, Gleason score (GS) was positively correlated with PSAN, while prostate volume was positively correlated with TTN. METHODS: About 54 patients were included in this retrospective study (mean age=74±7.4 years). ADC, D, D*, and f were acquired according to the biexponential Diffusion Weighted Imaging (DWI) model. The Kruskal-Wallis test was used to test the differences in clinical and IVIM parameters among the three groups. The Receiver Operating Characteristic (ROC) curve was used to evaluate the discrimination abilities. The Area Under the Curve (AUC) was compared using the DeLong test. Furthermore, Spearman correlation analysis was performed to assess the correlation between clinical and IVIM parameters of PSAN and TTN during initial ADT with OPCa. RESULTS: There were significant differences among the three groups observed for age, PSA, GS, ADC, D and D* values (P<0.05). Multi-parameter pairwise comparison results showed that significant differences between LPCa and WPCa were observed for the age, PSA, GS, ADC, D and D* values (P<0.05). However, D* was different between the LPCa and OPCa groups (P=0.032). GS showed a significant positive correlation with PSAN (Rho=0.594, P=0.042), and prostate volume showed a significant positive correlation with TTN (Rho=0.777, P=0.003). CONCLUSIONS: The IVIM parameters can effectively differentiate LPCa and WPCa, as well as LPCa and OPCa. Moreover, there was a certain trend in their distribution, which could reflect the tumor burden of PCa.

High-resolution free-breathing hepatobiliary phase MRI of the liver using XD-GRASP.

PURPOSE: To evaluate the performance of high-resolution free-breathing (FB) hepatobiliary phase imaging of the liver using the eXtra-Dimension Golden-angle RAdial Sparse Parallel (XD-GRASP) MRI technique. METHODS: Fifty-eight clinical patients (41 males, mean age = 52.9 ± 12.9) with liver lesions who underwent dynamic contrast-enhanced MRI with a liver-specific contrast agent were prospectively recruited for this study. Both breath-hold volumetric interpolated examination (BH-VIBE) imaging and FB imaging were performed during the hepatobiliary phase. FB images were acquired using a stack-of-stars golden-angle radial sequence and were reconstructed using the XD-GRASP method. Two experienced radiologists blinded to acquisition schemes independently scored the overall image quality, liver edge sharpness, hepatic vessel clarity, conspicuity of lesion, and overall artifact level of each image. The non-parametric paired two-tailed Wilcoxon signed-rank test was used for statistical analysis. RESULTS: Compared to BH-VIBE images, XD-GRASP images received significantly higher scores (P < 0.05) for the liver edge sharpness (4.83 ± 0.45 vs 4.29 ± 0.46), the hepatic vessel clarity (4.64 ± 0.67 vs 4.15 ± 0.56) and the conspicuity of lesion (4.75 ± 0.53 vs 4.31 ± 0.50). There were no significant differences (P > 0.05) between BH-VIBE and XD-GRASP images for the overall image quality (4.61 ± 0.50 vs 4.74 ± 0.47) and the overall artifact level (4.13 ± 0.44 vs 4.05 ± 0.61). CONCLUSION: Compared to conventional BH-VIBE MRI, FB radial acquisition combined with XD-GRASP reconstruction facilitates higher spatial resolution imaging of the liver during the hepatobiliary phase. This enhancement can significantly improve the visualization and evaluation of the liver.

Platinum (IV) drugs with cannabidiol inducing mitochondrial dysfunction and synergistically enhancing anti-tumor effects.

Chemotherapy resistance is an insurmountable problem in clinical anticancer therapy. Although Oxaliplatin is an effective chemotherapeutic agent for the treatment of colorectal cancer (CRC), it still suffers from serious toxicities as well as drug resistance. In this work, three Oxaliplatin tetravalent platinum prodrugs(O1-O3) and three novel mixed ammine/amine analogs(C1-C3) were constructed, introducing cannabidiol with anti-tumor activity in their axial position. All Pt(IV) prodrugs exhibited potent antitumor effects in a variety of tumor cell lines, especially in HCT-116 cells, where complex O3 showed strong inhibitory effects with the half maximal inhibitory concentrations (IC50) value of 6.02 ± 0.69 µM and about 2.6 times higher than that of Oxaliplatin. Further studies revealed that complex O3 decreased cellular mitochondrial membrane potential in a concentration-dependent manner and enhanced reactive oxygen species (ROS) accumulation by decreasing the expression of catalase, superoxide dismutase 2 (SOD2) and superoxide dismutase 3 (SOD3). Complex O3 induces mitochondrial dysfunction and upregulates the pro-apoptotic protein Noxa, ultimately leading to severe DNA damage. The upregulation of Phosphorylated histone protein H2AX (γ-H2AX) expression is clear evidence. In addition, O3 inhibits the expression of RAD51 protein and prevents DNA damage repair, thus overcoming drug resistance. This strategy of combining bioactive molecules cannabidiol with platinum drugs to improve therapeutic efficacy and overcome drug resistance has been proven to be very effective and deserves further investigation.