Microstructure and Perfusion Alterations of Globus Pallidus in Neonates with Hyperbilirubinemia.

BACKGROUND: Previous studies have indicated the abnormality of the globus pallidus in neonates with hyperbilirubinemia. OBJECTIVE: This study aims to explore the microstructure and cerebral perfusion of globus pallidus in neonatal hyperbilirubinemia by using Diffusion Tensor Imaging (DTI) and Arterial Spin Labeling (ASL) approaches. METHODS: Thirty-seven neonates were enrolled in this study, which were classified into Bilirubin-Induced Neurologic Dysfunction (BIND) group (hyperbilirubinemia with BIND, n=12), non-BIND group (hyperbilirubinemia without BIND, n=15), and healthy controls (HC) group (n=10). The quantitative values of globus pallidus were calculated from DTI, including the Apparent Diffusion Coefficient (ADC), the Fractional Anisotropy (FA), and Volume Ratio (VR) values. Additionally, the relative Cerebral Blood Flow (rCBF) values were obtained from ASL. RESULTS: It was observed that the mean DTI signal of globus pallidus was significantly different among the three groups (p < 0.05). However, there were no significant differences in the rCBF of globus pallidus among the three groups (p > 0.05). A positive correlation was also observed between the fractional anisotropy (FA) value and serum bilirubin level (r = 0.561, p = 0.002), while the VR value showed a negative correlation with serum bilirubin level (r=-0.484, p=0.011). The area under the curve (AUC) of FA, VR, and FA and VR combined was 0.897, 0.858, and 0.933, respectively. CONCLUSION: The alterations of microstructure in globus pallidus, especially FA and VR value, may be valuable and sensitive at the early stage of hyperbilirubinemia encephalopathy, suggesting that early hyperbilirubinemia may lead to cytotoxic edema and decreased permeability of the cell membrane.

Dual-specificity phosphatase 26 protects against kidney injury caused by ischaemia-reperfusion through restraint of TAK1-JNK/p38-mediated apoptosis and inflammation of renal tubular epithelial cells.

Dual-specificity phosphatase 26 (DUSP26) acts as a pivotal player in the transduction of signalling cascades with its dephosphorylating activity. Currently, DUSP26 attracts extensive attention due to its particular function in several pathological conditions. However, whether DUSP26 plays a role in kidney ischaemia-reperfusion (IR) injury is unknown. Aims of the current work were to explore the relevance of DUSP26 in kidney IR damage. DUSP26 levels were found to be decreased in renal tubular epithelial cells following hypoxia-reoxygenation (HR) and kidney samples subjected to IR treatments. DUSP26-overexpressed renal tubular epithelial cells exhibited protection against HR-caused apoptosis and inflammation, while DUSP26-depleted renal tubular epithelial cells were more sensitive to HR damage. Upregulation of DUSP26 in rat kidneys by infecting adenovirus expressing DUSP26 markedly ameliorated kidney injury caused by IR, while also effectively reducing apoptosis and inflammation. The mechanistic studies showed that the activation of transforming growth factor-ß-activated kinase 1 (TAK1)-JNK/p38 MAPK, contributing to kidney injury under HR or IR conditions, was restrained by increasing DUSP26 expression. Pharmacological restraint of TAK1 markedly diminished DUSP26-depletion-exacebated effects on JNK/p38 activation and HR injury of renal tubular cells. The work reported a renal-protective function of DUSP26, which protects against IR-related kidney damage via the intervention effects on the TAK1-JNK/p38 axis. The findings laid a foundation for understanding the molecular pathogenesis of kidney IR injury and provide a prospective target for treating this condition.

White matter hyperintensity, parent artery steno-occlusion, and neurological deterioration in anterior circulation single subcortical infarction patients.

BACKGROUND: The evidence for the association between white matter hyperintensity (WMH) severity and neurological deterioration (ND) in patients with single subcortical infarction (SSI) remains unclear and whether the association between them is modified by anterior circulation parent artery steno-occlusion (PAS) is unknown. Herein, we aimed to prospectively investigate the internal relevance. METHODS: In this prospective study, the severity of WMH and PAS were assessed in 288 consecutive patients with anterior circulation SSI arriving at our hospital, a tertiary teaching hospital affiliated with Fudan University, 24 h after onset from January 2017 to December 2018. The multivariable logistic regression model was used to estimate the association between WMH severity and the risk of ND within 7 days after stroke onset as well as the interactive effect between WMH severity and PAS on ND among patients with SSI. RESULTS: PAS modified the association between WMH severity and ND among patients with SSI (pinteraction = .029). After multivariate adjustment, the odds ratios of moderate-severe WMH associated with ND were 1.61 (95% CI, 0.50-5.19; ptrend = .428) for patients with PAS, and 0.37 (95% CI, 0.14-0.97; ptrend = .043) for those without PAS. Adding WMH severity to conventional risk factors improved risk prediction for ND in patients without PAS (net reclassification improvement: 48.2%, p = .005; integrated discrimination index: 2.5%, p = .004) but not in those with PAS. CONCLUSION: There was a modified effect of PAS on the association between WMH severity and ND within 7 days after stroke onset among patients with anterior circulation SSI, which deserves more research attention. WMH was negatively associated with ND in anterior circulation SSI patients without PAS.

Associations between immune cell phenotypes and lung cancer subtypes: insights from mendelian randomization analysis.

INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.

The value of LCI-based modified Kyoto classification risk scoring system in predicting the risk of early gastric cancer.

OBJECTIVE: To study and compare the value of the Kyoto classification risk scoring system and the modified Kyoto classification risk scoring system based on linked color imaging (LCI) in predicting the risk of early gastric cancer. METHODS: One hundred and fifty patients with pathologically confirmed non-cardia early gastric cancer by endoscopic LCI and 150 non-gastric cancer patients matched for age and gender were included. Basic patient data and whole gastric endoscopic images under LCI were collected, and the images were scored according to the LCI-based Kyoto classification risk scoring system and the LCI-based modified Kyoto classification risk scoring system. RESULTS: Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based modified Kyoto classification risk scoring system had a higher AUC for predicting the risk of early gastric cancer (0.723 vs. 0.784, p = 0.023), with a score of ≥3 being the best cutoff value for predicting the risk of early gastric cancer (sensitivity 61.33%, specificity 86.00%), and scores of 3 to 5 were significantly associated with early gastric carcinogenesis significantly (OR = 9.032, 95% CI: 4.995-16.330, p < 0.001). CONCLUSIONS: Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based Kyoto modified classification risk scoring system has a better value for predicting the risk of early gastric cancer, and the score of 3 to 5 is a high-risk factor for the risk of early gastric cancer development, which is more strongly correlated with the risk of early gastric cancer.

The status of nuclear medicine in China: the first official national survey.

AIM/INTRODUCTION: The National Nuclear Medicine Quality Control Center of China conducted the first official survey to investigate the nationwide situation of nuclear medicine in 2020. The survey aimed to unveil the current nuclear medicine situation and its quality control in China. MATERIALS AND METHODS: The web-based survey was conducted and the data was collected via the National Clinical Improvement System (NCIS) of China from 1st April to 31st May 2021. RESULTS: A total of 808 institutes across 30 provinces responded to the national survey. For human resources, there are 4460 physicians, 3077 technologists, 339 physicists, and 309 radiochemists. There are 887 single-photon imaging instruments, including 823 SPECT or SPECT/CT, and 365 PET instruments including 314 PET/CT. Six hundred twenty-four institutes perform SPECT examinations and 319 institutes perform PET examinations. 60% of SPECT scans are bone scintigraphy. A total of 97% of PET scans use an [18F]F-FDG tracer. Furthermore, 587 institutes provide radionuclide therapy services but only 280 institutes have admission rooms. The top three radionuclide therapies are [131I] therapy of hyperthyroidism with 546 institutes, [89Sr] therapy of bone metastasis with 400 institutes, and [131I] therapy of differentiated thyroid cancer with 286 institutes. Finally, for the frequency of equipment quality control per year, there are about 67 times self-test within the department for SPECT instruments and 111 times for PET instruments on average in each province. There are about three failures of SPECT and five failures of PET on average per year in each province. There are 408 institutes (of 624 SPECT institutes) performing quality control of SPECT radiopharmaceuticals, 216 (of 319) for PET radiopharmaceuticals, and 373 (of 587) for radionuclide therapy. CONCLUSION: These results of the first official survey towards current status of nuclear medicine in China are the foundation for the establishment of the quality control management system.

A Quantum Spatial Graph Convolutional Neural Network Model on Quantum Circuits.

This article proposes a quantum spatial graph convolutional neural network (QSGCN) model that is implementable on quantum circuits, providing a novel avenue to processing non-Euclidean type data based on the state-of-the-art parameterized quantum circuit (PQC) computing platforms. Four basic blocks are constructed to formulate the whole QSGCN model, including the quantum encoding, the quantum graph convolutional layer, the quantum graph pooling layer, and the network optimization. In particular, the trainability of the QSGCN model is analyzed through discussions on the barren plateau phenomenon. Simulation results from various types of graph data are presented to demonstrate the learning, generalization, and robustness capabilities of the proposed quantum neural network (QNN) model.

The novel HLA-DPB1*1500:01N allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*1500:01N differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.

Exploring the optimal indicator of short-term peridiagnosis weight dynamics to predict cancer survival: A multicentre cohort study.

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.

Development and validation of a novel nomogram model for predicting delayed graft function in deceased donor kidney transplantation based on pre-transplant biopsies.

BACKGROUND: Delayed graft function (DGF) is an important complication after kidney transplantation surgery. The present study aimed to develop and validate a nomogram for preoperative prediction of DGF on the basis of clinical and histological risk factors. METHODS: The prediction model was constructed in a development cohort comprising 492 kidney transplant recipients from May 2018 to December 2019. Data regarding donor and recipient characteristics, pre-transplantation biopsy results, and machine perfusion parameters were collected, and univariate analysis was performed. The least absolute shrinkage and selection operator regression model was used for variable selection. The prediction model was developed by multivariate logistic regression analysis and presented as a nomogram. An external validation cohort comprising 105 transplantation cases from January 2020 to April 2020 was included in the analysis. RESULTS: 266 donors were included in the development cohort, 458 kidneys (93.1%) were preserved by hypothermic machine perfusion (HMP), 96 (19.51%) of 492 recipients developed DGF. Twenty-eight variables measured before transplantation surgery were included in the LASSO regression model. The nomogram consisted of 12 variables from donor characteristics, pre-transplantation biopsy results and machine perfusion parameters. Internal and external validation showed good discrimination and calibration of the nomogram, with Area Under Curve (AUC) 0.83 (95%CI, 0.78-0.88) and 0.87 (95%CI, 0.80-0.94). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: A DGF predicting nomogram was developed that incorporated donor characteristics, pre-transplantation biopsy results, and machine perfusion parameters. This nomogram can be conveniently used for preoperative individualized prediction of DGF in kidney transplant recipients.

Effects of warming on soil organic carbon pools mediated by mycorrhizae and hyphae on the Eastern Tibetan Plateau, China.

Mycorrhizae and their hyphae play critical roles in soil organic carbon (SOC) accumulation. However, their individual contributions to SOC components and stability under climate warming conditions remain unclear. This study investigated the effects of warming on the SOC pools of Picea asperata (an ectomycorrhizal plant) and Fargesia nitida (an arbuscular mycorrhizal plant) mycorrhizae/hyphae on the eastern Tibetan Plateau. The results indicated that mycorrhizae made greater contributions to SOC accumulation than hyphae did by increasing labile organic carbon (LOC) components, such as particle organic carbon (POC), easily oxidizable organic carbon, and microbial biomass carbon, especially under warming conditions. Plant species also had different effects on SOC composition, resulting in higher mineral-associated organic carbon (MAOC) contents in F. nitida plots than in P. asperata plots; consequently, the former favored SOC stability more than the latter, with a lower POC/MAOC. Partial least-squares path modelling further indicated that mycorrhizae/hyphae indirectly affected LOC pools, mainly by changing soil pH and enzyme activities. Warming had no significant effect on SOC content but did change SOC composition by reducing LOC through affecting soil pH and iron oxides and ultimately increasing SOC stability in the presence of mycorrhizae for both plants. Therefore, the mycorrhizae of both plants are major contributors to the variation of SOC components and stability under warming conditions.

Local symmetry-driven interfacial magnetization and electronic states in (ZnO)n/(w-FeO)n superlattices.

Superlattices constructed with the wide-band-gap semiconductor ZnO and magnetic oxide FeO, both in the wurtzite structure, have been investigated using spin-polarized first-principles calculations. The structural, electronic and magnetic properties of the (ZnO)n/(w-FeO)n superlattices were studied in great detail. Two different interfaces in the (ZnO)n/(w-FeO)n superlattices were identified and they showed very different magnetic and electronic properties. Local symmetry-driven interfacial magnetization and electronic states can arise from different Fe/Zn distributions at different interfaces or spin ordering of Fe in the superlattice. The local symmetry-driven interfacial magnetization and electronic states, originating either from different Fe/Zn distribution across interfaces I and II, or by spin ordering of Fe in the superlattice, can be identified. It was also found that, in the case of the ferromagnetic phase, the electrons are more delocalized for the majority spin but strongly localized for the minority spin, which resulted in interesting spin-dependent transport properties. Our results will pave the way for designing novel spin-dependent electronic devices through the construction of superlattices from semiconductors and multiferroics.

12,13-diHOME attenuates high glucose-induced calcification of vascular smooth muscle cells through repressing CPT1A-mediated HMGB1 succinylation.

Diabetes is closely associated with vascular calcification (VC). Exorbitant glucose concentration activates pro-calcific effects in vascular smooth muscle cells (VSMCs). This study enrolled 159 elderly patients with type 2 diabetes and divided them into three groups, T1, T2 and T3, according to brachial-ankle pulse wave velocity(BaPWV). There were statistically significant differences in the waist circumference, waist hip ratio, systolic blood pressure, 12,13-diHOME (a lipokin) concentration among T1, T2 and T3. 12,13-diHOME levels were positively correlated to high density lipoprotein cholesterol and total cholesterol, but negatively correlated to with waist circumference, waist hip ratio, systolic blood pressure and baPWV. Studies in vitro showed that 12,13-diHOME effectively inhibits calcification in VSMCs under high glucose conditions. Notably, 12,13-diHOME suppressed the up-regulation of carnitine O-palmitoyltransferase 1 (CPT1A) and CPT1A-induced succinylation of HMGB1. The succinylation of HMGB1 at the K90 promoted the protein stability and induced the enrichment of HMGB1 in cytoplasm, which induced the calcification in VSMCs. Together, 12,13-diHOME attenuates high glucose-induced calcification in VSMCs through repressing CPT1A-mediated HMGB1 succinylation.

Precision Prediction for Dengue Fever in Singapore: A Machine Learning Approach Incorporating Meteorological Data.

OBJECTIVE: This study aimed to improve dengue fever predictions in Singapore using a machine learning model that incorporates meteorological data, addressing the current methodological limitations by examining the intricate relationships between weather changes and dengue transmission. METHOD: Using weekly dengue case and meteorological data from 2012 to 2022, the data was preprocessed and analyzed using various machine learning algorithms, including General Linear Model (GLM), Support Vector Machine (SVM), Gradient Boosting Machine (GBM), Decision Tree (DT), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) algorithms. Performance metrics such as Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and R-squared (R2) were employed. RESULTS: From 2012 to 2022, there was a total of 164,333 cases of dengue fever. Singapore witnessed a fluctuating number of dengue cases, peaking notably in 2020 and revealing a strong seasonality between March and July. An analysis of meteorological data points highlighted connections between certain climate variables and dengue fever outbreaks. The correlation analyses suggested significant associations between dengue cases and specific weather factors such as solar radiation, solar energy, and UV index. For disease predictions, the XGBoost model showed the best performance with an MAE = 89.12, RMSE = 156.07, and R2 = 0.83, identifying time as the primary factor, while 19 key predictors showed non-linear associations with dengue transmission. This underscores the significant role of environmental conditions, including cloud cover and rainfall, in dengue propagation. CONCLUSION: In the last decade, meteorological factors have significantly influenced dengue transmission in Singapore. This research, using the XGBoost model, highlights the key predictors like time and cloud cover in understanding dengue's complex dynamics. By employing advanced algorithms, our study offers insights into dengue predictive models and the importance of careful model selection. These results can inform public health strategies, aiming to improve dengue control in Singapore and comparable regions.

Fluorocarbon Nanodroplets: Their Formation and Stability in Complex Solution Systems.

Perfluorocarbon (PFC) nanodroplets (NDs) are expanding in a wide range of applications in biotechnology and nanotechnology. Their efficacy in biological systems is significantly influenced by their size uniformity and stability within bioelectrolyte contexts. Presently, methods for creating monodisperse, highly concentrated, and well-stabilized PFC NDs under harsh conditions using low energy consumption methods have not been thoroughly developed, and their stability has not been sufficiently explored. This gap restricts their applicability for advanced medical interventions in tissues with high pH levels and various electrolytic conditions. To tackle these challenges and to circumvent potential toxicity from surface stabilizers, we have conducted an in-depth investigation into the formation and stability of uncoated perfluorohexane (PFH) NDs, which were synthesized by using a low-energy consumption solvent exchange technique, across complex electrolyte compositions or a broad spectrum of pH levels. The results indicated that low concentrations of low-valent electrolyte ions facilitate the nucleation of NDs and consistently accelerate Ostwald ripening over an extended period. Conversely, high concentrations of highly valent electrolyte ions inhibit nucleation and decelerate the ripening process over time. Given the similarities between the properties of NDs and nanobubbles, we propose a potential stabilization mechanism. Electrolytes influence the Ostwald ripening of NDs by adjusting the adsorption and distribution of ions on the NDs' surface, modifying the thickness of the electric double layer, and fine-tuning the energy barrier between droplets. These insights enable precise control over the stability of PFC NDs through the meticulous adjustment of the surrounding electrolyte composition. This offers an effective preparation method and a theoretical foundation for employing bare PFC NDs in physiological settings.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Clonal hematopoiesis-derived therapy-related myeloid neoplasms after autologous hematopoietic stem cell transplant for lymphoid and non-lymphoid disorders.

Therapy-related myeloid neoplasms (tMN) are complications of cytotoxic therapies. Risk of tMN is high in recipients of autologous hematopoietic stem cell transplantation (aHSCT). Acquisition of genomic mutations represents a key pathogenic driver but the origins, timing and dynamics, particularly in the context of preexisting or emergent clonal hematopoiesis (CH), have not been sufficiently clarified. We studied a cohort of 1507 patients undergoing aHSCT and a cohort of 263 patients who developed tMN without aHSCT to determine clinico-molecular features unique to post-aHSCT tMN. We show that tMN occurs in up to 2.3% of patients at median of 2.6 years post-AHSCT. Age ≥ 60 years, male sex, radiotherapy, high treatment burden ( ≥ 3 lines of chemotherapy), and graft cellularity increased the risk of tMN. Time to evolution and overall survival were shorter in post-aHSCT tMN vs. other tMN, and the earlier group's mutational pattern was enriched in PPM1D and TP53 lesions. Preexisting CH increased the risk of adverse outcomes including post-aHSCT tMN. Particularly, antecedent lesions affecting PPM1D and TP53 predicted tMN evolution post-transplant. Notably, CH-derived tMN had worse outcomes than non CH-derived tMN. As such, screening for CH before aHSCT may inform individual patients' prognostic outcomes and influence their prospective treatment plans. Presented in part as an oral abstract at the 2022 American Society of Hematology Annual Meeting, New Orleans, LA, 2022.

Effect of an Airbag-selective Portal Vein Blood Arrester on the Liver after Hepatectomy: A New Technique for Selective Clamping of the Portal Vein.

OBJECTIVE: A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions. METHODS: Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels. RESULTS: Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group. CONCLUSION: Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy.

TGF-ß1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.

Effects of Nanobubbles on Photochemical Processes of Levofloxacin Photosensitizer.

Photodynamic therapy (PDT) stands as an efficacious modality for the treatment of cancer and various diseases, in which optimization of the electron transfer and augmentation of the production of lethal reactive oxygen species (ROS) represent pivotal challenges to enhance its therapeutic efficacy. Empirical investigations have established that the spontaneous initiation of redox reactions associated with electron transfer is feasible and is located in the gas-liquid interfaces. Meanwhile, nanobubbles (NBs) are emerging as entities capable of furnishing a plethora of such interfaces, attributed to their stability and large surface/volume ratio in bulk water. Thus, NBs provide a chance to expedite the electron-transfer kinetics within the context of PDT in an ambient environment. In this paper, we present a pioneering exploration into the impact of nitrogen nanobubbles (N2-NBs) on the electron transfer of the photosensitizer levofloxacin (LEV). Transient absorption spectra and time-resolved decay spectra, as determined through laser flash photolysis, unequivocally reveal that N2-NBs exhibit a mitigating effect on the decay of the LEV excitation triplet state, thereby facilitating subsequent processes. Of paramount significance is the observation that the presence of N2-NBs markedly accelerates the electron transfer of LEV, albeit with a marginal inhibitory influence on its energy-transfer reaction. This observation is corroborated through absorbance measurements and offers compelling evidence substantiating the role of NBs in expediting electron transfer within the ambit of PDT. The mechanism elucidated herein sheds light on how N2-NBs intricately influence both electron-transfer and energy-transfer reactions in the photosensitizer LEV. These findings not only contribute to a nuanced understanding of the underlying processes but also furnish novel insights that may inform the application of NBs in the realm of photodynamic therapy.