Gasdermin D-mediated metabolic crosstalk promotes tissue repair.

The establishment of an early pro-regenerative niche is crucial for tissue regeneration1,2. Gasdermin D (GSDMD)-dependent pyroptosis accounts for the release of inflammatory cytokines upon various insults3-5. However, little is known about its role in tissue regeneration followed by homeostatic maintenance. Here we show that macrophage GSDMD deficiency delays tissue recovery but has little effect on the local inflammatory milieu or the lytic pyroptosis process. Profiling of the metabolite secretome of hyperactivated macrophages revealed a non-canonical metabolite-secreting function of GSDMD. We further identified 11,12-epoxyeicosatrienoic acid (11,12-EET) as a bioactive, pro-healing oxylipin that is secreted from hyperactive macrophages in a GSDMD-dependent manner. Accumulation of 11,12-EET by direct supplementation or deletion of Ephx2, which encodes a 11,12-EET-hydrolytic enzyme, accelerated muscle regeneration. We further demonstrated that EPHX2 accumulated within aged muscle, and that consecutive 11,12-EET treatment rejuvenated aged muscle. Mechanistically, 11,12-EET amplifies fibroblast growth factor signalling by modulating liquid-liquid phase separation of fibroblast growth factors, thereby boosting the activation and proliferation of muscle stem cells. These data depict a GSDMD-guided metabolite crosstalk between macrophages and muscle stem cells that governs the repair process, which offers insights with therapeutic implications for the regeneration of injured or aged tissues.

Development of a proton CT imaging system using scintillator-based range detection.

BACKGROUND: The accuracy of proton therapy and preclinical proton irradiation experiments is susceptible to proton range uncertainties, which partly stem from the inaccurate conversion between CT numbers and relative stopping power (RSP). Proton computed tomography (PCT) can reduce these uncertainties by directly acquiring RSP maps. PURPOSE: This study aims to develop a novel PCT imaging system based on scintillator-based proton range detection for accurate RSP reconstruction. METHODS: The proposed PCT system consists of a pencil-beam brass collimator with a 1 mm aperture, an object stage capable of translation and 360° rotation, a plastic scintillator for dose-to-light conversion, and a complementary metal oxide semiconductor (CMOS) camera for light distribution acquisition. A calibration procedure based on Monte Carlo (MC) simulation was implemented to convert the obtained light ranges into water equivalent ranges. The water equivalent path lengths (WEPLs) of the imaged object were determined by calculating the differences in proton ranges obtained with and without the object in the beam path. To validate the WEPL calculation, measurements of WEPLs for eight tissue-equivalent inserts were conducted. PCT imaging was performed on a custom-designed phantom and a mouse, utilizing both 60 and 360 projections. The filtered back projection (FBP) algorithm was employed to reconstruct the RSP from WEPLs. Image quality was assessed based on the reconstructed RSP maps and compared to reference and simulation-based reconstructions. RESULTS: The differences between the calibrated and reference ranges of 110-150 MeV proton beams were within 0.18 mm. The WEPLs of eight tissue-equivalent inserts were measured with accuracies better than 1%. Phantom experiments exhibited good agreement with reference and simulation-based reconstructions, demonstrating average RSP errors of 1.26%, 1.38%, and 0.38% for images reconstructed with 60 projections, 60 projections after penalized weighted least-squares algorithm denoising, and 360 projections, respectively. Mouse experiments provided clear observations of mouse contours and major tissue types. MC simulation estimated an imaging dose of 3.44 cGy for decent RSP reconstruction. CONCLUSIONS: The proposed PCT imaging system enables RSP map acquisition with high accuracy and has the potential to improve dose calculation accuracy in proton therapy and preclinical proton irradiation experiments.

Stabilization of Cuδ+ Sites Within MnO2 for Superior Urea Electro-Synthesis.

Electrocatalytic C-N coupling between NO3 - and CO2 has emerged as a sustainable route for urea production. However, identifying catalytic active sites and designing efficient electrocatalysts remain significant challenges. Herein, the synthesis of Cu-doped MnO2 nanotube (denoted as Cu-MnO2) with stable Cuδ+-oxygen vacancies (Ovs)-Mn3+ dual sites is reported. Compared with pure MnO2, Cuδ+ doping can effectively enhance urea production performance in the co-reduction of CO2 and NO3 -. Thus, Cu-MnO2 catalyst exhibits a maximum Faradaic efficiency (FE) of 54.7% and the highest yield rate of 116.7 mmol h-1 gcat. -1 in a flow cell. Remarkably, the urea yield rate remains over 78 mmol h-1 gcat. -1 across a wide potential range. Further experimental and theoretical results elucidate the unique role of Cu-MnO2 solid-solution for stabilizing Cuδ+ sites in Cuδ+-Ovs-Mn3+, endowing the catalyst with superior structural and electrochemical stabilities. This thermodynamically promotes urea formation and kinetically lowers the energy barrier of C-N coupling.

The Critical Trigger for Cognitive Penetration: Cognitive Processing Priority over Perceptual Processing.

The visual perception system of humans is susceptible to cognitive influence, which implies the existence of cognitive perception. However, the specifical trigger for cognitive penetration is still a matter of controversy. The current study proposed that the cognitive processing priority over perceptual processing might be critical for inducing cognitive penetration. We tested this hypothesis by manipulating the processing priority between cognition and perception across three experiments where participants were asked to complete a size-judging task under different competing conditions between cognition and perception. To sum up, we proved that the cognitive processing priority over perceptual processing is critical for cognitive penetration. This study provided empirical evidence for the critical trigger for cognitive penetration.

p-d Orbital Hybridization in Ag-based Electrocatalysts for Enhanced Nitrate-to-Ammonia Conversion.

Considering the substantial role of ammonia, developing highly efficient electrocatalysts for nitrate-to-ammonia conversion has attracted increasing interest. Herein, we proposed a feasible strategy of p-d orbital hybridization via doping p-block metals in an Ag host, which drastically promotes the performance of nitrate adsorption and disassociation. Typically, a Sn-doped Ag catalyst (SnAg) delivers a maximum Faradaic efficiency (FE) of 95.5±1.85 % for NH3 at -0.4 V vs. RHE and reaches the highest NH3 yield rate to 482.3±14.1 mg h-1 mgcat. -1. In a flow cell, the SnAg catalyst achieves a FE of 90.2 % at an ampere-level current density of 1.1 A cm-2 with an NH3 yield of 78.6 mg h-1 cm-2, during which NH3 can be further extracted to prepare struvite as high-quality fertilizer. A mechanistic study reveals that a strong p-d orbital hybridization effect in SnAg is beneficial for nitrite deoxygenation, a rate-determining step for NH3 synthesis, which as a general principle, can be further extended to Bi- and In-doped Ag catalysts. Moreover, when integrated into a Zn-nitrate battery, such a SnAg cathode contributes to a superior energy density of 639 Wh L-1, high power density of 18.1 mW cm-2, and continuous NH3 production.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

A novel relative-equilibrium graphical plot for rapid reversible tracer studies in dynamic PET imaging.

Objective.This study aims to address the issue of long scan durations required by traditional graphical analysis methods, such as the Logan plot and its variant, the reversible equilibrium (RE) Logan plot, for dynamic PET imaging of tracer kinetics.Approach.We propose a relative RE Logan model that builds on the principles of the Logan plot and its variant to significantly reduce scan time without compromising the accuracy of tracer kinetics analysis. The model is supported by theoretical evidence and experimental validations, including two computer simulations and one clinical data analysis.Main results.The proposed model demonstrates a significant linear relationship between the variablexand the slopeDVTof the RE Logan plot, and the variablex' and the slopeDVT'of the relative RE Logan plot. The Pearson correlation coefficients (r) of the linear fitting of thex' to thexequal 0.9849 in the simulated data and 0.9912 in the clinical data. Similarly, thervalues for the linear fitting ofDVT'toDVTequal 0.9989 and 0.9988 in the simulated data, and 0.9954 in the clinical data.Significance.These results demonstrate the model's capability to maintain strong linear relationships and produce parametric images comparable to the traditional RE Logan plot, but with the considerable advantage of shorter scan durations. This innovation holds significant potential for enhancing the efficiency and feasibility of PET imaging in clinical settings.

A rotating beam-blocker method for cone beam CT scatter correction.

BACKGROUND: Cone beam CT (CBCT) is widely utilized in clinics. However, the scatter artifact degrades the CBCT image quality, hampering the expansion of CBCT applications. Recently, beam-blocker methods have been used for CBCT scatter correction and proved their high cost-effectiveness. PURPOSE: A rotating beam-blocker (RBB) method for CBCT scatter correction was proposed to complete scatter correction and image reconstruction within a single scan in both full- and half-fan scan scenarios. METHODS: The RBB consisted of two open regions and two blocked regions, and was designed as a centrosymmetric structure. The open and blocked projections could be alternatively obtained within one single rotation. The open projections were corrected with the scatter signal calculated from the blocked projections, and then used to reconstruct the 3D image via the Feldkamp-Davis-Kress algorithm. The performance of the RBB method was evaluated on head and pelvis phantoms in scenarios with and without a bowtie filter. The images obtained from nine repeated scans in each scenario were used to calculate the evaluation metrics including the CT number error, spatial nonuniformity (SNU) and contrast-to-noise ratio (CNR). RESULTS: For the head phantom, the CT number error was decreased to <5 after scatter correction from >200 HU before correction when scanned without a bowtie filter, and to <4 from >160 HU when scanned with a full bowtie filter. For the pelvis phantom, the CT number error was reduced to <12 after scatter correction from >250 HU before correction when scanned without a bowtie filter, and to <10 from >190 HU when scanned with a half bowtie filter. After scatter correction, the uniformity and contrast were both improved, resulting in an SNU of >79% decrease and CNR of >2 times increase, respectively. CONCLUSIONS: High-quality CBCT images could be obtained in a single scan after using the proposed RBB method for scatter correction, enabling more accurate image guidance for surgery and radiation therapy applications. With almost no time delay between the successive open and blocked projections, the RBB method could eliminate the motion-induced anatomical mismatches between the corresponding open and blocked projections and could find particular usefulness in thoracic and abdominal imaging.

A deep learning-based method for the detection and segmentation of breast masses in ultrasound images.

Objective.Automated detection and segmentation of breast masses in ultrasound images are critical for breast cancer diagnosis, but remain challenging due to limited image quality and complex breast tissues. This study aims to develop a deep learning-based method that enables accurate breast mass detection and segmentation in ultrasound images.Approach.A novel convolutional neural network-based framework that combines the You Only Look Once (YOLO) v5 network and the Global-Local (GOLO) strategy was developed. First, YOLOv5 was applied to locate the mass regions of interest (ROIs). Second, a Global Local-Connected Multi-Scale Selection (GOLO-CMSS) network was developed to segment the masses. The GOLO-CMSS operated on both the entire images globally and mass ROIs locally, and then integrated the two branches for a final segmentation output. Particularly, in global branch, CMSS applied Multi-Scale Selection (MSS) modules to automatically adjust the receptive fields, and Multi-Input (MLI) modules to enable fusion of shallow and deep features at different resolutions. The USTC dataset containing 28 477 breast ultrasound images was collected for training and test. The proposed method was also tested on three public datasets, UDIAT, BUSI and TUH. The segmentation performance of GOLO-CMSS was compared with other networks and three experienced radiologists.Main results.YOLOv5 outperformed other detection models with average precisions of 99.41%, 95.15%, 93.69% and 96.42% on the USTC, UDIAT, BUSI and TUH datasets, respectively. The proposed GOLO-CMSS showed superior segmentation performance over other state-of-the-art networks, with Dice similarity coefficients (DSCs) of 93.19%, 88.56%, 87.58% and 90.37% on the USTC, UDIAT, BUSI and TUH datasets, respectively. The mean DSC between GOLO-CMSS and each radiologist was significantly better than that between radiologists (p< 0.001).Significance.Our proposed method can accurately detect and segment breast masses with a decent performance comparable to radiologists, highlighting its great potential for clinical implementation in breast ultrasound examination.

Proton pump inhibitor use is associated with increased liver steatosis.

Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the association between PPI therapy and the incidence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. The present study included 7,395 individuals aged ≥20 years who underwent hepatic vibration-controlled transient elastography (VCTE) examination. The data were obtained from the January 2017 to March 2020 pre-pandemic National Health and Nutrition Examination Survey. Among the 7,395 adults who were included (mean age, 50.59 years; 3,656 male), 9.8% were prescribed PPIs. Following multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.02-1.53]. Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (P=0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as a controlled attenuation parameter ≥285 dB/m (OR, 1.19; CI, 1.01-1.40), non-alcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16-1.93) and metabolic dysfunction-associated steatotic liver disease (OR, 1.26; 95% CI, 1.05-1.52), consistently demonstrated an association between PPI prescription and hepatic steatosis. The administration of PPI therapy was linked with hepatic steatosis in US adults, although no significant association was observed with liver stiffness, as determined by VCTE.

Development of an algorithm for proton dose calculation in magnetic fields.

BACKGROUND: The advantages of proton therapy can be further enhanced with online magnetic resonance imaging (MRI) guidance. One of the challenges in the realization of MRI-guided proton therapy (MRPT) is accurately calculating the radiation dose in the presence of magnetic fields. PURPOSE: This study aims to develop an efficient and accurate proton dose calculation algorithm adapted to the presence of magnetic fields. METHODS: An analytical-numerical radiation dose calculation algorithm, Proton and Ion Dose Engine (PRIDE), was developed. The algorithm combines the pencil beam algorithm (PBA) with a novel iterative voxel-based ray-tracing algorithm. The new ray-tracing method uses fewer assumptions and ensures broader applicability for proton beam trajectory prediction in magnetic fields, and has been compared to Wolf's method and Schellhammer's method. The accuracy of PRIDE algorithm was validated on three phantoms and two practical plans (one single-field water plan and one prostate tumor plan) in different magnetic field strengths up to 3.0 T. The validation was performed by comparing the results against the Monte Carlo (MC) simulations, using the global gamma index criteria of 2%/2 mm and 3%/3 mm with a 10% threshold. RESULTS: PRIDE showed good agreement with MC in homogeneous and slab heterogeneous phantom, achieving gamma passing rates (%GPs) above 99% for 2%/2 mm criteria when magnetic field strength is not greater than 1.5 T. Although the agreement decreased for scenarios involving high proton energy (240 MeV) and strong magnetic field (3.0 T), the 2%/2 mm %GPs still remained above 98%. In lateral heterogeneous phantom, the accuracy of PRIDE decreased due to the PBA's limitation. For the two practical plans in different magnetic fields, %GPs exceeded 98% and 99% for 2%/2 mm and 3%/3 mm criteria, respectively. CONCLUSIONS: PRIDE can perform efficient and accurate proton dose calculation in magnetic fields up to 3.0 T, and is expected to work as a useful tool for proton dose calculation in MRPT.

The steatosis-associated fibrosis estimator (SAFE) outperformed the FIB-4 score in screening the population for liver disease.

INTRODUCTION AND OBJECTIVES: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. PATIENTS AND METHODS: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017-2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999-2016) to assess the correlation with mortality. RESULTS: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. CONCLUSIONS: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

Corrigendum: Targeting JUN, CEBPB and HDAC3: a novel strategy to overcome drug resistance in hypoxic glioblastoma.

[This corrects the article DOI: 10.3389/fonc.2019.00033.].

Cu-Mo Dual Sites in Cu-Doped MoSe2 for Enhanced Electrosynthesis of Urea.

The quest for sustainable urea production has directed attention toward electrocatalytic methods that bypass the energy-intensive traditional Haber-Bosch process. This study introduces an approach to urea synthesis through the coreduction of CO2 and NO3- using copper-doped molybdenum diselenide (Cu-MoSe2) with Cu-Mo dual sites as electrocatalysts. The electrocatalytic activity of the Cu-MoSe2 electrode is characterized by a urea yield rate of 1235 µg h-1 mgcat.-1 at -0.7 V versus the reversible hydrogen electrode and a maximum Faradaic efficiency of 23.43% at -0.6 V versus RHE. Besides, a continuous urea production with an enhanced average yield rate of 9145 µg h-1 mgcat.-1 can be achieved in a flow cell. These figures represent a substantial advancement over that of the baseline MoSe2 electrode. Density functional theory (DFT) calculations elucidate that Cu doping accelerates *NO2 deoxygenation and significantly decreases the energy barriers for C-N bond formation. Consequently, Cu-MoSe2 demonstrates a more favorable pathway for urea production, enhancing both the efficiency and feasibility of the process. This study offers valuable insights into electrode design and understanding of the facilitated electrochemical pathways.

Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 25:174-185, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Hypoxia-Induced Myocardial Hypertrophy Companies with Apoptosis Enhancement and p38-MAPK Pathway Activation.

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 25:186-196, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

Evaluation of the effectiveness of surgical resection and ablation for the treatment of early-stage hepatocellular carcinoma: A retrospective cohort study.

BACKGROUND: The optimal treatment strategy for early-stage hepatocellular carcinoma (HCC) remains controversial, specifically in regard to surgical resection (SR) and ablation. The aim of this study was to investigate the impact of SR and ablation on recurrence and prognosis in early-stage HCC patients, to optimize treatment strategies and improve long-term survival. METHODS: A retrospective analysis was conducted on 801 patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC and treated with SR or ablation between January 2015 and December 2019. The effectiveness and complications of both treatments were analyzed, and patients were followed up to measure recurrence and survival. Propensity score matching (PSM) was employed to increase comparability between the two groups. The Kaplan-Meier method was used to analyze recurrence and survival, and a Cox risk proportional hazard model was used to identify risk factors that affect recurrence and surviva. RESULTS: Before PSM, the overall survival (OS) rates were similar in both groups, with recurrence-free survival (RFS) rates better in the SR group than in the ablation group. After PSM, there was no significant difference in OS between the two groups. However, the RFS rates were significantly better in the SR group than in the ablation group. The ablation group exhibited superior outcomes compared to the SR group, with shorter treatment times, reduced bleeding, shorter hospital stays, and lower hospital costs. Concerning the location of the HCC within the liver, comparable efficacy was observed between SR and ablation for disease located in the noncentral region or left lobe. However, for HCCs located in the central region or right lobe of the liver, SR was more effective than ablation. CONCLUSIONS: This study revealed no significant difference in OS between SR and ablation for early-stage HCC, with SR providing better RFS and ablation demonstrating better safety profiles and lower hospital costs. These findings offer valuable insights for clinicians in determining optimal treatment strategies for early-stage HCC patients, particularly in terms of balancing efficacy, safety, and cost considerations.

Improvement of 2D cine image quality using 3D priors and cycle generative adversarial network for low field MRI-guided radiation therapy.

BACKGROUND: Cine magnetic resonance (MR) images have been used for real-time MR guided radiation therapy (MRgRT). However, the onboard MR systems with low-field strength face the problem of limited image quality. PURPOSE: To improve the quality of cine MR images in MRgRT using prior image information provided by the patient planning and positioning MR images. METHODS: This study employed MR images from 18 pancreatic cancer patients who received MR-guided stereotactic body radiation therapy. Planning 3D MR images were acquired during the patient simulation, and positioning 3D MR images and 2D sagittal cine MR images were acquired before and during the beam delivery, respectively. A deep learning-based framework consisting of two cycle generative adversarial networks (CycleGAN), Denoising CycleGAN and Enhancement CycleGAN, was developed to establish the mapping between the 3D and 2D MR images. The Denoising CycleGAN was trained to first denoise the cine images using the time domain cine image series, and the Enhancement CycleGAN was trained to enhance the spatial resolution and contrast by taking advantage of the prior image information from the planning and positioning images. The denoising performance was assessed by signal-to-noise ratio (SNR), structural similarity index measure, peak SNR, blind/reference-less image spatial quality evaluator (BRISQUE), natural image quality evaluator, and perception-based image quality evaluator scores. The quality enhancement performance was assessed by the BRISQUE and physician visual scores. In addition, the target contouring was evaluated on the original and processed images. RESULTS: Significant differences were found for all evaluation metrics after Denoising CycleGAN processing. The BRISQUE and visual scores were also significantly improved after sequential Denoising and Enhancement CycleGAN processing. In target contouring evaluation, Dice similarity coefficient, centroid distance, Hausdorff distance, and average surface distance values were significantly improved on the enhanced images. The whole processing time was within 20 ms for a typical input image size of 512 × 512. CONCLUSION: Taking advantage of the prior high-quality positioning and planning MR images, the deep learning-based framework enhanced the cine MR image quality significantly, leading to improved accuracy in automatic target contouring. With the merits of both high computational efficiency and considerable image quality enhancement, the proposed method may hold important clinical implication for real-time MRgRT.

Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients.

BACKGROUND: The clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear. AIM: To explore the impact of varying the threshold of alanine aminotransferase (ALT) levels in identifying significant liver injury among GZ patients. METHODS: This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2). RESULTS: The results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136). CONCLUSION: These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

Emerging Electrocatalysts in Urea Production.

Urea synthesis from abundant CO2 and N-feedstocks via renewable electricity has attracted increasing interests, offering a promising alternative to the industrial-applied Haber-Meiser process. However, the studies toward electrochemical urea production remain scarce and appeal for more research. Herein, in this perspective, an up-to-date overview on the urea electrosynthesis is highlighted and summarized. Firstly, the reaction pathways of urea formation through various feedstocks are comprehensively discussed. Then, we focus on the strategies of materials design to improve C-N coupling efficiency by identifying the descriptor and understanding the reaction mechanism. Finally, the current challenges and disadvantages in this field are reviewed and some future development directions of electrocatalytic urea synthesis are also prospected. This Minireview aims to promote future investigations of the electrochemical urea synthesis.