Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR-342-5p/CFL1.

BACKGROUND: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. METHODS: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. RESULTS: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. CONCLUSION: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.

Multicenter evaluation of the safety and efficacy of selective internal radiation therapy with yttrium-90 resin microspheres in Taiwan: data from the RESIN registry.

BACKGROUND AND AIM: The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. METHODS: Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). RESULTS: Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n = 8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. CONCLUSIONS: Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.

Reversible Mn2+/Mn4+ double redox in lithium-excess cathode materials.

There is an urgent need for low-cost, resource-friendly, high-energy-density cathode materials for lithium-ion batteries to satisfy the rapidly increasing need for electrical energy storage. To replace the nickel and cobalt, which are limited resources and are associated with safety problems, in current lithium-ion batteries, high-capacity cathodes based on manganese would be particularly desirable owing to the low cost and high abundance of the metal, and the intrinsic stability of the Mn4+ oxidation state. Here we present a strategy of combining high-valent cations and the partial substitution of fluorine for oxygen in a disordered-rocksalt structure to incorporate the reversible Mn2+/Mn4+ double redox couple into lithium-excess cathode materials. The lithium-rich cathodes thus produced have high capacity and energy density. The use of the Mn2+/Mn4+ redox reduces oxygen redox activity, thereby stabilizing the materials, and opens up new opportunities for the design of high-performance manganese-rich cathodes for advanced lithium-ion batteries.

Prediction of surgical outcomes in severe encapsulating peritoneal sclerosis using a computed tomography scoring system.

BACKGROUND/PURPOSE: Encapsulating peritoneal sclerosis (EPS) is a rare and potential lethal complication of peritoneal dialysis characterized by bowel obstruction. Surgical enterolysis is the only curative therapy. Currently, there are no tools for predicting postsurgical prognosis. This study aimed to identify a computed tomography (CT) scoring system that could predict mortality after surgery in patients with severe EPS. METHODS: This retrospective study enrolled patients with severe EPS who underwent surgical enterolysis in a tertiary referral medical center. The association of CT score with surgical outcomes including mortality, blood loss, and bowel perforation was analyzed. RESULTS: Thirty-four patients who underwent 37 procedures were recruited and divided into a survivor and non-survivor group. The survivor group had higher body mass indices (BMIs, 18.1 vs. 16.7 kg/m2, p = 0.035) and lower CT scores (11 vs. 17, p < 0.001) than the non-survivor group. The receiver operating characteristic curve revealed that a CT score of ≥15 could be considered a cutoff point to predict surgical mortality, with an area under the curve of 0.93, sensitivity of 88.9%, and specificity of 82.1%. Compared with the group with CT scores of <15, the group with CT scores of ≥15 had a lower BMI (19.7 vs. 16.2 kg/m2, p = 0.004), higher mortality (4.2% vs. 61.5%, p < 0.001), greater blood loss (50 vs. 400 mL, p = 0.007), and higher incidence of bowel perforation (12.5% vs. 61.5%, p = 0.006). CONCLUSION: The CT scoring system could be useful in predicting surgical risk in patients with severe EPS receiving enterolysis.

Combined model integrating deep learning, radiomics, and clinical data to classify lung nodules at chest CT.

OBJECTIVES: The study aimed to develop a combined model that integrates deep learning (DL), radiomics, and clinical data to classify lung nodules into benign or malignant categories, and to further classify lung nodules into different pathological subtypes and Lung Imaging Reporting and Data System (Lung-RADS) scores. MATERIALS AND METHODS: The proposed model was trained, validated, and tested using three datasets: one public dataset, the Lung Nodule Analysis 2016 (LUNA16) Grand challenge dataset (n = 1004), and two private datasets, the Lung Nodule Received Operation (LNOP) dataset (n = 1027) and the Lung Nodule in Health Examination (LNHE) dataset (n = 1525). The proposed model used a stacked ensemble model by employing a machine learning (ML) approach with an AutoGluon-Tabular classifier. The input variables were modified 3D convolutional neural network (CNN) features, radiomics features, and clinical features. Three classification tasks were performed: Task 1: Classification of lung nodules into benign or malignant in the LUNA16 dataset; Task 2: Classification of lung nodules into different pathological subtypes; and Task 3: Classification of Lung-RADS score. Classification performance was determined based on accuracy, recall, precision, and F1-score. Ten-fold cross-validation was applied to each task. RESULTS: The proposed model achieved high accuracy in classifying lung nodules into benign or malignant categories in LUNA 16 with an accuracy of 92.8%, as well as in classifying lung nodules into different pathological subtypes with an F1-score of 75.5% and Lung-RADS scores with an F1-score of 80.4%. CONCLUSION: Our proposed model provides an accurate classification of lung nodules based on the benign/malignant, different pathological subtypes, and Lung-RADS system.

Hydrogen Storage in Partially Exfoliated Magnesium Diboride Multilayers.

Metal boride nanostructures have shown significant promise for hydrogen storage applications. However, the synthesis of nanoscale metal boride particles is challenging because of their high surface energy, strong inter- and intraplanar bonding, and difficult-to-control surface termination. Here, it is demonstrated that mechanochemical exfoliation of magnesium diboride in zirconia produces 3-4 nm ultrathin MgB2 nanosheets (multilayers) in high yield. High-pressure hydrogenation of these multilayers at 70 MPa and 330 °C followed by dehydrogenation at 390 °C reveals a hydrogen capacity of 5.1 wt%, which is ≈50 times larger than the capacity of bulk MgB2 under the same conditions. This enhancement is attributed to the creation of defective sites by ball-milling and incomplete Mg surface coverage in MgB2 multilayers, which disrupts the stable boron-boron ring structure. The density functional theory calculations indicate that the balance of Mg on the MgB2 nanosheet surface changes as the material hydrogenates, as it is energetically favorable to trade a small number of Mg vacancies in Mg(BH4 )2 for greater Mg coverage on the MgB2 surface. The exfoliation and creation of ultrathin layers is a promising new direction for 2D metal boride/borohydride research with the potential to achieve high-capacity reversible hydrogen storage at more moderate pressures and temperatures.

Microstructural Differences of the Cerebellum-Thalamus-Basal Ganglia-Limbic Cortex in Patients with Somatic Symptom Disorders: a Diffusion Kurtosis Imaging Study.

Somatic symp tom disorders (SSDs) are a group of psychiatric disorders characterized by persistent disproportionate concern and obsessive behaviors regarding physical conditions. Currently, SSDs lack effective treatments and their pathophysiology is unclear. In this paper, we aimed to examine microstructural abnormalities in the brains of patients with SSD using diffusion kurtosis imaging (DKI) and to investigate the correlation between these abnormalities and clinical indicators. Diffusion kurtosis images were acquired from 30 patients with SSD and 30 healthy controls (HCs). Whole-brain maps of multiple diffusion measures, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), mean kurtosis (MK), radial kurtosis (RK), and axial kurtosis (AK), were calculated. To analyze differences between the two groups, nonparametric permutation testing with 10,000 randomized permutations and threshold-free cluster enhancement was used with family-wise error-corrected p values < 0.05 as the threshold for statistical significance. Then, the correlations between significant changes in these diffusion measures and clinical factors were examined. Compared to HCs, patients with SSD had significantly higher FA, MK, and RK and significantly lower MD and RD in the cerebellum, thalamus, basal ganglia, and limbic cortex. The FA in the left caudate and the pontine crossing tract were negatively correlated with disease duration; the MD and the RD in the genu of the corpus callosum were positively correlated with disease duration. Our findings highlight the role of the cerebellum-thalamus-basal ganglia-limbic cortex pathway, especially the cerebellum, in SSDs and enhance our understanding of the pathogenesis of SSDs.

Improving puncture accuracy in percutaneous CT-guided needle insertion with wireless inertial measurement unit: a phantom study.

OBJECTIVES: A novel method applying inertial measurement units (IMUs) was developed to assist CT-guided puncture, which enables real-time displays of planned and actual needle trajectories. The method was compared with freehand and laser protractor-assisted methods. METHODS: The phantom study was performed by three operators with 8, 2, and 0 years of experience in CT-guided procedure conducted five consecutive needle placements for three target groups using three methods (freehand, laser protractor-assisted, or IMU-assisted method). The endpoints included mediolateral angle error and caudocranial angle error of the first pass, the procedure time, the total number of needle passes, and the radiation dose. RESULTS: There was a significant difference in the number of needle passes (IMU 1.2 ± 0.42, laser protractor 2.9 ± 1.6, freehand 3.6 ± 2.0 time, p < 0.001), the procedure time (IMU 3.0 ± 1.2, laser protractor 6.4 ± 2.9, freehand 6.2 ± 3.1 min, p < 0.001), the mediolateral angle error of the first pass (IMU 1.4 ± 1.2, laser protractor 1.6 ± 1.3, freehand 3.7 ± 2.5 degree, p < 0.001), the caudocranial angle error of the first pass (IMU 1.2 ± 1.2, laser protractor 5.3 ± 4.7, freehand 3.9 ± 3.1 degree, p < 0.001), and the radiation dose (IMU 250.5 ± 74.1, laser protractor 484.6 ± 260.2, freehand 561.4 ± 339.8 mGy-cm, p < 0.001) among three CT-guided needle insertion methods. CONCLUSION: The wireless IMU improves the angle accuracy and speed of CT-guided needle punctures as compared with laser protractor guidance and freehand techniques. KEY POINTS: • The IMU-assisted method showed a significant decrease in the number of needle passes (IMU 1.2 ± 0.42, laser protractor 2.9 ± 1.6, freehand 3.6 ± 2.0 time, p < 0.001). • The IMU-assisted method showed a significant decrease in the procedure time (IMU 3.0 ± 1.2, laser protractor 6.4 ± 2.9, freehand 6.2 ± 3.1 min, p < 0.001). • The IMU-assisted method showed a significant decrease in the mediolateral angle error of the first pass and the caudocranial angle error of the first pass.

Short-Term Effects of Genicular Artery Embolization on Symptoms and Bone Marrow Abnormalities in Patients with Refractory Knee Osteoarthritis.

PURPOSE: To evaluate the short-term outcomes of genicular artery embolization (GAE) for knee osteoarthritis (OA) with and without bone marrow lesion (BML) and/or subchondral insufficiency fracture of the knee (SIFK). MATERIALS AND METHODS: This single-institution prospective observational pilot study analyzed 24 knees in 22 patients with mild to moderate knee OA, including 8 knees without BML, 13 knees with BML, and 3 knees with both BML and SIFK. The area and volume of BMLs on magnetic resonance images were measured before and after GAE. Baseline and postoperative pain and physical function were assessed using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: GAE significantly reduced the BML area and volume 3 months after embolization in the knees with BML (both P < .0005). GAE significantly decreased the VAS scores at 3 and 6 months after embolization in patients without BML (both P = .04) and those with BML (both P = .01). GAE also lowered the WOMAC scores 3 months after embolization in patients without and with BML (P = .02 and P = .0002, respectively). However, GAE did not significantly alter the BML area and volume (both P = .25), VAS scores (P = 1.00), and WOMAC scores (P = .08) in patients with BML and SIFK at 3 months after GAE. CONCLUSIONS: This observational pilot study suggested that GAE effectively reduces the BML area and volume and improves pain and physical function in patients with knee OA accompanied by BML but is inefficacious in those with both BML and SIFK.

Enhanced and stabilized hydrogen production from methanol by ultrasmall Ni nanoclusters immobilized on defect-rich h-BN nanosheets.

Employing liquid organic hydrogen carriers (LOHCs) to transport hydrogen to where it can be utilized relies on methods of efficient chemical dehydrogenation to access this fuel. Therefore, developing effective strategies to optimize the catalytic performance of cheap transition metal-based catalysts in terms of activity and stability for dehydrogenation of LOHCs is a critical challenge. Here, we report the design and synthesis of ultrasmall nickel nanoclusters (∼1.5 nm) deposited on defect-rich boron nitride (BN) nanosheet (Ni/BN) catalysts with higher methanol dehydrogenation activity and selectivity, and greater stability than that of some other transition-metal based catalysts. The interface of the two-dimensional (2D) BN with the metal nanoparticles plays a strong role both in guiding the nucleation and growth of the catalytically active ultrasmall Ni nanoclusters, and further in stabilizing these nanoscale Ni catalysts against poisoning by interactions with the BN substrate. We provide detailed spectroscopy characterizations and density functional theory (DFT) calculations to reveal the origin of the high productivity, high selectivity, and high durability exhibited with the Ni/BN nanocatalyst and elucidate its correlation with nanocluster size and support-nanocluster interactions. This study provides insight into the role that the support material can have both regarding the size control of nanoclusters through immobilization during the nanocluster formation and also during the active catalytic process; this twofold set of insights is significant in advancing the understanding the bottom-up design of high-performance, durable catalytic systems for various catalysis needs.

Kinetic Control via Binding Sites within the Confined Space of Metal Metalloporphyrin-Frameworks for Enhanced Shape-Selectivity Catalysis.

One striking feature of enzyme is its controllable ability to trap substrates via synergistic or cooperative binding in the enzymatic pocket, which renders the shape-selectivity of product by the confined spatial environment. The success of shape-selective catalysis relies on the ability of enzyme to tune the thermodynamics and kinetics for chemical reactions. In emulation of enzyme's ability, we showcase herein a targeting strategy with the substrate being anchored on the internal pore wall of metal-organic frameworks (MOFs), taking full advantage of the sterically kinetic control to achieve shape-selectivity for the reactions. For this purpose, a series of binding site-accessible metal metalloporphyrin-frameworks (MMPFs) have been investigated to shed light on the nature of enzyme-mimic catalysis. They exhibit a different density of binding sites that are well arranged into the nanospace with corresponding distances of opposite binding sites. Such a structural specificity results in a facile switch in selectivity from an exclusive formation of the thermodynamically stable product to the kinetic product. Thus, the proposed targeting strategy, based on the combination of porous materials and binding events, paves a new way to develop highly efficient heterogeneous catalysts for shifting selectivity.

Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke When Multiple Passes Are Required and Associated Risk Factors.

INTRODUCTION: This study aimed to evaluate the outcomes of mechanical thrombectomy for acute ischemic stroke when multiple passes are required and to identify the associated risk factors. METHODS: Consecutive patients with acute ischemic stroke treated with mechanical thrombectomy at the Neurology Department of Ninth People's Hospital and the Neurosurgery Department of Xinhua Hospital of Shanghai Jiao Tong University School of Medicine from 2013 to 2018 were included. Patients were divided into 2 groups: those who received ≤2 passes and those who received >2 passes. Outcomes of the 2 groups were compared. Multivariate linear regression was used to determine factors associated with the need for >2 passes. All patient data were reviewed retrospectively. RESULTS: A total of 122 patients were included, of whom 83 patients required ≤2 passes and 39 patients required >2 passes. After adjusting for sex, atrial fibrillation history, smoking history, and involvement of middle cerebral artery and internal cerebral artery, the National Institutes of Health Stroke Scale (NIHSS) score was associated with a 1.08-times greater risk of >2 passes (95% confidence interval [CI]: 1.01-1.17), and internal carotid artery with a 5.13-times greater risk of >2 passes (95% CI: 1.02-25.69). Having more than 2 passes was associated with significantly higher 7-day (25.6% vs. 6%), 90-day mortality rates (34.2% vs. 16%) and a significantly lower recanalization rate (66.7% vs. 89.2%). CONCLUSION: Needing more than 2 passes during mechanical thrombectomy is associated with poorer outcomes. Higher preprocedural NIHSS scores and internal carotid artery thrombi are associated with more than 2 passes.

Additive Destabilization of Porous Magnesium Borohydride Framework with Core-Shell Structure.

Design of interfaces with thermodynamic and kinetic specificity is of great importance for hydrogen storage from both an applied and fundamental perspective. Here, in order to destabilize the metal hydride and protect the dehydrogenated products from oxidizing, a unique core-shell structure of porous Mg(BH4 )2 -based framework with a thin layer (no more than 5 nm) of MgCl2 additives on the surface, has been proposed and synthesized via a wet-chemical method. The local structure and electronic state of the present complex system are systematically investigated to understand the correlation between the distribution of additives and dehydrogenation property of Mg(BH4 )2 . A significant improvement is achieved for hydrogen desorption with chlorides: initial hydrogen release from MgCl2 decorated γ-phase Mg(BH4 )2 particles commences at 100 °C and reaches a maximum of 9.4 wt% at 385 °C. Besides the decreased decomposition temperature, an activation barrier of about 76.4 kJ mol-1 lower than that of Mg(BH4 )2 without MgCl2 is obtained. Moreover, MgCl2 decoration can also prevent the whole decomposed system (both Mg- and B- elements) from oxidizing, which is a necessary condition to reversibility.

Disparate Exciton-Phonon Couplings for Zone-Center and Boundary Phonons in Solid-State Graphite.

The exciton-phonon coupling in highly oriented pyrolytic graphite is studied using resonant inelastic x-ray scattering (RIXS) spectroscopy. With ∼70 meV energy resolution, multiple low energy excitations associated with coupling to phonons can be clearly resolved in the RIXS spectra. Using resonance dependence and the closed form for RIXS cross section without considering the intermediate state mixing of phonon modes, the dimensionless coupling constant g is determined to be 5 and 0.35, corresponding to the coupling strength of 0.42 eV+/-20 meV and 0.20 eV+/-20 meV, for zone center and boundary phonons, respectively. The reduced g value for the zone-boundary phonon may be related to its double resonance nature.

Evaluation of toxoplasmosis in pregnant women using dot-immunogold-silver staining with recombinant Toxoplasma gondii peroxiredoxin protein.

BACKGROUND: Toxoplasma gondii infection endangers human health and affects animal husbandry. Serological detection is the main method used for epidemiological investigations and diagnosis of toxoplasmosis. The key to effective diagnosis of toxoplasmosis is the use of a standardized antigen and a specific and sensitive detection method. Peroxiredoxin is an antigenic protein and vaccine candidate antigen of T. gondii that has not yet been exploited for diagnostic application. METHODS: In this study, recombinant T. gondii peroxiredoxin protein (rTgPrx) was prepared and used in dot-immunogold-silver staining (Dot-IGSS) to detect IgG antibodies in serum from mice and pregnant women. The rTgPrx-Dot-IGSS method was established and optimized using mouse serum. Furthermore, serum samples from pregnant women were analyzed by rTgPrx-Dot-IGSS. RESULTS: Forty serum samples from mice infected with T. gondii and twenty negative serum samples were analyzed. The sensitivity and specificity of rTgPrx-Dot-IGSS were 97.5 and 100%, respectively, equivalent to those of a commercial ELISA kit for anti-Toxoplasma IgG antibody. Furthermore, 540 serum samples from pregnant women were screened with a commercial ELISA kit. Eighty-three positive and 60 negative serum samples were analyzed by rTgPrx-Dot-IGSS. The positive rate was 95.18%, comparable to that obtained with the commercial ELISA kit. CONCLUSIONS: The Dot-IGSS method with rTgPrx as an antigen might be useful for diagnosing T. gondii infection in individuals.

Disrupted functional connectivity between sub-regions in the sensorimotor areas and cortex in migraine without aura.

BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. RESULTS: We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. CONCLUSION: In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.

Dual-Site Cascade Oxygen Reduction Mechanism on SnO x/Pt-Cu-Ni for Promoting Reaction Kinetics.

Designing highly active oxygen reduction reaction (ORR) catalysts is crucial to boost the fuel cell economy. Previous research has mainly focused on Pt-based alloy catalysts in which surface Pt is the solely active site and the activity improvement was challenged by the discovered scaling relationship. Herein we report a new concept of utilizing dual active sites for the ORR and demonstrate its effectiveness by synthesizing a SnO x/Pt-Cu-Ni heterojunctioned catalyst. A maximum of 40% enhancement in the apparent specific activity, which corresponds to 10-fold enhancement on interface sites, is measured compared with pure Pt-Cu-Ni. Detailed investigations suggest an altered dual-site cascade mechanism wherein the first two steps occur on SnO x sites and the remaining steps occur on adjacent Pt sites, allowing a significant decrease in the energy barrier. This study with the suggested dual-site cascade mechanism shows the potential to overcome the ORR energy barrier bottleneck to develop highly active catalysts.

Efficient Hydrogen Production from Methanol Using a Single-Site Pt1/CeO2 Catalyst.

Hydrogen is regarded as an attractive alternative energy carrier due to its high gravimetric energy density and only water production upon combustion. However, due to its low volumetric energy density, there are still some challenges in practical hydrogen storage and transportation. In the past decade, using chemical bonds of liquid organic molecules as hydrogen carriers to generate hydrogen in situ provided a feasible method to potentially solve this problem. Research efforts on liquid organic hydrogen carriers (LOHCs) seek practical carrier systems and advanced catalytic materials that have the potential to reduce costs, increase reaction rate, and provide a more efficient catalytic hydrogen generation/storage process. In this work, we used methanol as a hydrogen carrier to release hydrogen in situ with the single-site Pt1/CeO2 catalyst. Moreover, in this reaction, compared with traditional nanoparticle catalysts, the single site catalyst displays excellent hydrogen generation efficiency, 40 times higher than 2.5 nm Pt/CeO2 sample, and 800 times higher compared to 7.0 nm Pt/CeO2 sample. This in-depth study highlights the benefits of single-site catalysts and paves the way for further rational design of highly efficient catalysts for sustainable energy storage applications.

Radiotherapy for inferior vena cava tumor thrombus in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) involvement is a rare disease with poor prognosis. This study aimed to evaluate the outcome of HCC patients receiving radiotherapy (RT) to IVC tumor thrombus. METHODS: A total of 42 consecutive HCC patients treated with RT to IVC tumor thrombus between September 2007 and October 2018 were enrolled. Overall survival (OS), the response of IVC thrombus, prognostic factors and failure pattern were assessed. RESULTS: The median follow-up time was 4.4 months. The median RT equivalent dose in 2-Gy fractions was 48.75 Gy (range, 3.25-67.10). The objective response rate of IVC thrombus was 47.6% (95% confidence interval [CI], 33.3-64.3%). The OS rate at 1 year was 30.0%, with a median OS of 6.6 months (95% CI, 3.7-9.5) from the start of RT. On multivariate analysis, Child-Pugh class, lymph node metastasis, lung metastasis and objective response of IVC thrombus were independent predictors for OS. Lung was the most common site of first progression in 14 (33.3%) patients. For 32 patients without lung metastasis before RT, use of systemic treatment concurrent with and/or after RT was associated with a significantly longer lung metastasis-free survival (5.9 vs. 1.5 months, p = 0.0033). CONCLUSIONS: RT is effective for IVC tumor thrombus of HCC with acceptable adverse effects. RT might be a treatment option incorporated into combination therapy for HCC involving IVC.

Cathepsin K Knockout Exacerbates Haemorrhagic Transformation Induced by Recombinant Tissue Plasminogen Activator After Focal Cerebral Ischaemia in Mice.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk-/- mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood-brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk-/- than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk-/- than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood-brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.