Progression from cardiomyopathy to heart failure with reduced ejection fraction: A CORIN deficient course.

Cardiomyopathies, encompassing hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), constitute a diverse spectrum of heart muscle diseases that often culminating in heart failure (HF). The inherent molecular heterogeneity of these conditions has implications for prognosis and therapeutic strategies. Publicly available microarray and RNA sequencing (RNA-seq) data sets of HCM (n = 106 from GSE36961) and DCM (n = 18 from GSE135055 and 166 from GSE141910) patients were employed for our analysis. The Non-negative Matrix Factorization (NMF) algorithm was applied to explore the molecular stratification within HCM and DCM, and enrichment analysis was performed to delineate their biological characteristics. By integrating bulk and single-nucleus RNA-seq (snRNA-seq) data, we identified a potential biomarker for HCM progression and cardiac fibrosis, which was subsequently validated using mendelian randomization and in vitro. Our application of NMF identified two distinct molecular clusters. Particularly, a profibrotic, heart failure with reduced ejection fraction (HFrEF)-resembling Cluster 1 emerged, characterized by diminished expression of CORIN and a high degree of fibroblast activation. This cluster also exhibited lower left ventricular ejection fraction (LVEF) and worse prognostic outcomes, establishing the significance of this molecular subclassification. We further found that overexpression of CORIN could mitigate TGFß1-induced expression of col1a1 and α-SMA in neonatal rat cardiac fibroblasts. Our results indicated the heterogeneity of HCM population, and further evidenced the participation of corin in the progression of HCM, DCM and HFrEF. Nevertheless, our study is constrained by the lack of corresponding clinical data and experimental validation of the identified subtypes. Therefore, further studies are warranted to elucidate the downstream pathways of corin and to validate these findings in independent patient cohorts.

Piezo1 regulates TGF-ß1 induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is involved in local tissue remodeling in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the function of Piezo1 in EMT process remains unclear. This study aimed to characterize potential roles of Piezo1 in EMT process in CRSwNP. METHODS: Overall, 22 nasal polyp (NP) tissues from patients with CRSwNP and 20 middle turbinate from healthy individuals were obtained during surgery. The expression of Piezo1, E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) was measured by using western blot (Wb) in NP tissues and primary human nasal epithelial cells (pHNECs) and the location and level were assessed by immunofluorescence staining. BEAS-2B cells were stimulated with transforming growth factor (TGF)-ß1 to induce EMT in vitro model and examined using qRT-PCR. BEAS-2B cells were treated with Yoda1 and RuR to calculate protein level by Wb analysis. Yoda1 and RuR treated NP murine model was evaluated by H&E (hematoxylin-eosin) staining and immunohistochemistry. RESULTS: Compared with the control group, E-cadherin was decreased while the level of Piezo1, vimentin, and α-SMA was increased in NP group. Piezo1, vimentin, and α-SMA were upregulated in TGF-ß1-induced BEAS-2B cells. Yoda1 inhibited E-cadherin expression and promoted Piezo1 and the aforementioned mesenchymal markers, whereas RuR showed contrary results. The results from the murine model treated with Yoda1 and RuR were consistent with those results in the EMT model in vitro. CONCLUSION: Piezo1 is linked with EMT process in CRSwNP and the activation of Piezo1 exacerbates EMT process of nasal polyps.

Corynoline alleviates hepatic ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation through enhancing Nrf2/HO-1 signaling.

OBJECTIVE: Corynoline has displayed pharmacological effects in reducing oxidative stress and inflammatory responses in many disorders. However, its effects on hepatic ischemia-reperfusion (I/R) injury remain unclear. This study aimed to investigate the protective effects of corynoline against hepatic I/R injury and the underlying mechanisms. METHODS: Rat models with hepatic I/R injury and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult were constructed. Models were pretreated with corynoline and/or other inhibitors for functional and mechanistic examination. RESULTS: Corynoline pretreatment effectively mitigated hepatic I/R injury verified by reduced serum transaminase levels, improved histological damage scores, and decreased apoptosis rates. Additionally, corynoline pretreatment significantly inhibited I/R-triggered oxidative stress and inflammatory responses, as indicated by enhanced mitochondrial function, reduced levels of ROS and MDA, reduced neutrophil infiltration and suppressed proinflammatory cytokine release. In vitro experiments further showed that corynoline pretreatment increased cellular viability, decreased LDH activity, reduced cellular apoptosis, and inhibited oxidative stress and inflammatory injury in H/R-induced BRL-3A cells. Mechanistically, corynoline significantly increased Nrf2 nuclear translocation and expression levels of its target gene, HO-1. It also blocked NLRP3 inflammasome activation both in vivo and in vitro. Furthermore, pretreatment with Nrf2 inhibitor ML-385 counteracted the protective effect of corynoline on hepatic I/R injury. Ultimately, in vitro studies revealed that the NLRP3 activator nigericin could also nullified the protective effects of corynoline in BRL-3A cells, but had minimal impact on Nrf2 nuclear translocation. CONCLUSIONS: Corynoline can exert protective effects against hepatic I/R injury by inhibiting oxidative stress, inflammatory responses, and apoptosis. These effects may be associated with inhibiting ROS-induced NLRP3 inflammasome activation by enhancing Nrf2/HO-1 signaling. These data provide new understanding about the mechanism of corynoline action, suggesting it is a potential drug applied for the treatment and prevention of hepatic I/R injury.

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.

Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease.

OBJECTIVE: Mitochondrial DNA (mtDNA) depletion/deletions syndrome (MDDS) comprises a group of diseases caused by primary autosomal defects of mtDNA maintenance. Our objective was to study the etiology of MDDS in 4 patients who lack pathogenic variants in known genetic causes. METHODS: Whole exome sequencing of the probands was performed to identify pathogenic variants. We validated the mitochondrial defect by analyzing mtDNA, mitochondrial dNTP pools, respiratory chain activities, and GUK1 activity. To confirm pathogenicity of GUK1 deficiency, we expressed 2 GUK1 isoforms in patient cells. RESULTS: We identified biallelic GUK1 pathogenic variants in all 4 probands who presented with ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy and altered T-lymphocyte profiles. Muscle biopsies from all probands showed mtDNA depletion, deletions, or both, as well as reduced activities of mitochondrial respiratory chain enzymes. GUK1 encodes guanylate kinase, originally identified as a cytosolic enzyme. Long and short isoforms of GUK1 exist. We observed that the long isoform is intramitochondrial and the short is cytosolic. In probands' fibroblasts, we noted decreased GUK1 activity causing unbalanced mitochondrial dNTP pools and mtDNA depletion in both replicating and quiescent fibroblasts indicating that GUK1 deficiency impairs de novo and salvage nucleotide pathways. Proband fibroblasts treated with deoxyguanosine and/or forodesine, a purine phosphatase inhibitor, ameliorated mtDNA depletion, indicating potential pharmacological therapies. INTERPRETATION: Primary GUK1 deficiency is a new and potentially treatable cause of MDDS. The cytosolic isoform of GUK1 may contribute to the T-lymphocyte abnormality, which has not been observed in other MDDS disorders. ANN NEUROL 2024.

Air-ventilated normothermic mechanical perfusion improves susceptibility to donation after circulatory death and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis.

End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model. Here, metabolomics analysis revealed that air-ventilated NMP alleviated DCD- and cold preservation-induced cholestatic liver injury, as shown by the elevated release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and γ-glutamyl transferase (GGT) in the perfusate (p < .05) and the reduction in the levels of bile acid metabolites, including ω-muricholic acid, glycohyodeoxycholic acid, glycocholic acid, and glycochenodeoxycholate (GCDC) in the perfused livers (p < .05). In addition, the expression of the key bile acid metabolism enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is predominantly expressed in hepatocytes, was substantially elevated in the DCD rat liver, followed by air-ventilated NMP (p < .05), and in vitro, this increase was induced by decreased GCDC and hypoxia-reoxygenation in the hepatic cells HepG2 and L02 (p < .05). Knockdown of UGT1A1 in hepatic cells by siRNA aggravated hepatic injury caused by GCDC and hypoxia-reoxygenation, as indicated by the ALT and AST levels in the supernatant. Mechanistically, UGT1A1 is transcriptionally regulated by peroxisome proliferator-activator receptor-γ (PPAR-γ) under hypoxia-physoxia. Taken together, our data revealed that air-ventilated NMP could alleviate DCD- and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis. Based on the results from this study, air-ventilated NMP confers a promising approach for predicting and alleviating cholestatic liver injury through PPAR-γ/UGT1A1 axis.

Research note: A method for recognizing and evaluating typical behaviors of laying hens in a thermal environment.

Automatically identifying abnormal behaviors of caged laying hens in a thermal environment improves manual management efficiency. It also provides reference indicators for breeding heat-tolerant hens. In this study, we propose a deep learning-based method for automatic recognition and evaluation of typical heat stress behaviors in hens. We developed a lightweight object detection algorithm, YOLO-HGP, based on the YOLOv8n as the baseline model. YOLO-HGP achieves Precision (P), Recall (R), and mean average precision (mAP) of 95.952%, 94.127%, and 97.667%, respectively, effectively detecting typical heat stress behaviors in hens. Compared to the original YOLO v8n, YOLO-HGP improves R, and mAP by 6.257%, and 1.963%, respectively. The FLOPs (floating point operations) and parameter count of YOLO-HGP are 4.3G and 1.729M, reducing by 47.56% and 42.58% compared to the original model. Additionally, we introduce the "ORC-ratio" (The ratio of the combined frequency of open-beak breathing and retching behaviors to the frequency of closed-beak behaviors.) as an evaluation indicator for the frequency of typical heat stress behaviors in hens and combine it with the Hybrid-SORT multiobject tracking algorithm to achieve tracking detection of individual hens. The study demonstrates that the proposed model effectively identifies and quantitatively evaluates typical behaviors of hens in a thermal environment, providing an effective approach for the automated recognition of heat stress behaviors in hens.

New perspectives in prognostication of hepatocellular carcinoma: The role and clinical implications of transient receptor potential family genes.

The study titled "Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients" is a significant contribution to hepatocellular carcinoma (HCC) research, highlighting the role of transient receptor potential (TRP) family genes in the disease's progression and prognosis. Utilizing data from The Cancer Genome Atlas database, it establishes a new risk assessment model, emphasizing the interaction of TRP genes with tumor proliferation pathways, key metabolic reactions like retinol metabolism, and the tumor immune microenvironment. Notably, the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes, suggesting its potential as a prognostic biomarker and a target for personalized therapy, particularly in strategies combining immunotherapy and anti-TRP agents.

The determination of 11 sulfonamide antibiotics in water and foods by developing a N-rich magnetic covalent organic framework combined with ultra-high performance liquid chromatography-tandem mass spectrometry.

The concentration of antibiotic residues in water and animal-derived foods is low and the matrix is complex, and effective extraction of antibiotic residues in them is a key factor for accurate quantification. It is important to establish a rapid and effective method for the analytical determination of antibiotics in water and foods. In this study, a type of novel magnetic COF (Fe3O4@SiO2@PDE-TAPB-COF) was synthesized and characterized. Moreover, Fe3O4@SiO2@PDE-TAPB-COF combined with ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the 11 sulfonamide antibiotics (SAs) in water and food. The parameters including pH, adsorption amount, adsorption time, type of elution solvent and elution time were optimized. Under the optimal conditions, the standard curves of 11 SAs showed good linearity (R 2 > 0.999) in their respective concentration ranges and had lower detection and quantification limits. The spiked recoveries of the developed MSPE-UPLC-MS/MS method for the 11 SAs in water and foods were 74.3-107.2% and 75.1-102.5%, respectively. And the relative standard deviations (RSDs) were less than 9.56% (n = 7). The results indicated that the method can be used for the determination of SAs in foods and water with low detection limits and high sensitivity.

Pediatric-Type Follicular Lymphoma of the Conjunctiva in Two Adolescents.

The authors present two cases of conjunctival pediatric-type follicular lymphoma. A 14-year-old Black boy and 14-year-old Black girl were each referred for evaluation of a painless salmon-colored conjunctival lesion. Both patients underwent excisional biopsy. Histopathology demonstrated follicles with germinal centers composed of atypical B-cells with high Ki67 proliferation index, positive staining for CD20, CD10, and BCL6, and negative for BCL2. This series contributes two cases to the limited literature and presents the first case reported in a female. [J Pediatr Ophthalmol Strabismus. 2024;61(4):e33-e38.].

Integrated multi-omics investigation revealed the importance of phenylpropanoid metabolism in the defense response of Lilium regale Wilson to fusarium wilt.

Lilies (genus Lilium) play a significant role in the global cut-flower industry, but they are highly susceptible to fusarium wilt caused by Fusarium oxysporum. However, Lilium regale, a wild lily species, exhibits remarkable resistance to F. oxysporum. To investigate the quantitative resistance of L. regale to fusarium wilt, a comprehensive multi-omics analysis was conducted. Upon inoculation with F. oxysporum, L. regale roots showed a significant accumulation of phenylpropane metabolites, including lignin precursors, flavonoids, and hydroxycinnamic acids. These findings were consistent with the upregulated expression of phenylpropanoid biosynthesis-related genes encoding various enzymes, as revealed by transcriptomics and proteomics analyses. Furthermore, metabolomics and proteomics data demonstrated differential activation of monoterpenoid and isoquinoline alkaloid biosynthesis. Colorimetry and high-performance liquid chromatography analyses revealed significantly higher levels of total flavonoids, lignin, ferulic acid, phlorizin, and quercetin contents in L. regale scales compared with susceptible lily 'Siberia' scales during F. oxysporum infection. These phenylpropanes exhibited inhibitory effects on F. oxysporum growth and suppressed the expression of pathogenicity-related genes. Transcriptional regulatory network analysis suggested that ethylene-responsive transcription factors (ERFs) may positively regulate phenylpropanoid biosynthesis. Therefore, LrERF4 was cloned and transiently overexpressed in the fusarium wilt-susceptible Oriental hybrid lily 'Siberia'. The overexpression of LrERF4 resulted in increased levels of total flavonoids, lignin, ferulic acid, phlorizin, and quercetin, while the silencing of LrERF4 in L. regale through RNAi had the opposite effect. In conclusion, phenylpropanoid metabolism plays a crucial role in the defense response of L. regale against fusarium wilt, with LrERF4 acting as a positive regulator of phenylpropane biosynthesis.

Short-term inhalation of xenon during anesthesia for prevention of postoperative delirium in elderly patients undergoing laparoscopic radical colectomy: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. METHODS/DESIGN: This is a prospective, randomized, controlled trial and 132 patients aged 65-80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. DISCUSSION: Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn .

Physicochemical characteristics of tea seed starches from twenty-five cultivars.

The physicochemical features of starches separated from tea seeds of 25 cultivars were analyzed. The distinct characteristic of tea seed starches was that they had high apparent amylose content (AAC, 28.94-39.91 %) and resistant starch contents (4.64-8.24 %), suggesting that tea starch can be used for production of low glycemic index food. One cultivar (T12) had smallest breakdown (74.2 RVU) and highest gel hardness, indicating it performed stably during shear thinning, resulting in a firm texture. Another cultivar (T25) had a peak viscosity of 417.6 RVU, a large breakdown and small setback, suggesting a low tendency for retrogradation. There was a range of 61.6 °C to 77.5 °C for the peak gelatinization temperature and 0.163 to 0.390 for the flow behavior index values. These parameters could serve for selecting suitable starches with minor differences in physicochemical properties for food use. Correlation analysis indicated that AAC is a key factor determining starch retrogradation properties. The broad genetic diversity in the tea seed starch physicochemical features provided potentially versatile applications in the food industry. The results gained from the present study contribute to a better understanding of tea seed starch quality, and encourage its application in many value-added food products.

BCL7A inhibits the progression and drug-resistance in acute myeloid leukemia.

AIMS: This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on cancer progression and drug resistance. METHODS: BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with promoter hypermethylation. Interaction with PTBP1 and effects of differential expression of BCL7A were examined in vitro and in vivo. The impacts on cell proliferation, cycle progression, apoptosis, and differentiation were studied. Additionally, the regulatory roles of BCL7A on interferon regulatory factor 7 (IRF7) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were assessed. RESULTS: BCL7A was downregulated in AML due to promoter hypermethylation and negatively regulated by PTBP1. Upregulation of BCL7A impeded AML cell growth, induced apoptosis, promoted cell differentiation, and decreased cell infiltration into lymph nodes, enhancing survival in mouse models. Overexpression of BCL7A upregulated IRF7 and downregulated HMGCS1, linking to reduced AML cell malignancy and decreased resistance to cytarabine. CONCLUSIONS: BCL7A acts as a tumor suppressor in AML, inhibiting malignant progression and enhancing drug sensitivity through the IRF7/HMGCS1 pathway. These findings suggest potential therapeutic targets for improving AML treatment outcomes.

Preparation of magnetic cationic Schiff base polymeric material for highly selective enrichment of avermectins from surface water and milk samples.

Herein, a magnetic cationic Schiff base polymeric material (Fe3O4@SiO2-Schiff-TAPB-DA) was fabricated simply and rapidly, which was explored as a magnetic adsorbent for magnetic solid-phase extraction (MSPE) for enriching seven avermectins insecticides in surface water and milk matrices combined with ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS). Under the optimized pretreatment and instrumental parameters, the analytes showed good linearity in the range of 0.5-200.0 ng·mL-1 with a correlation coefficient (R2) greater than 0.9990 and high precision. The limits of detection for the analytes were 0.004-0.047 µg·L-1 for surface water sample and 0.008-0.250 µg·kg-1 for milk samples. Satisfactory recoveries of spiked target compounds were in the range of 82.25- 100.87 % for surface water sample and 72.73- 119.62 % for milk samples. The results indicated powerfully Fe3O4@SiO2-Schiff-TAPB-DA was of significant potential as an MSPE adsorbent for the detection of avermectin insecticides in surface water and milk, which provides a quick and efficient idea for enriching avermectins insecticides in complicated matrices.

Delivery of exogenous miR-19b by Wharton's Jelly Mesenchymal Stem Cells attenuates transplanted kidney ischemia/reperfusion injury by regulating cellular metabolism.

Renal ischemia-reperfusion injury (IRI) frequently occurs following kidney transplantation, and exosomes derived from umbilical cord mesenchymal stem cells (WJ-MSC-Exos) have shown promise in treating IRI in transplanted kidneys. Our study delved into the potential mechanism of WJ-MSC-Exos in ameliorating IRI in transplanted kidneys, revealing that miR-19b is abundantly present in WJ-MSC-Exos. Both in vivo and in vitro experiments demonstrated that the absence of miR-19b abolished the protective effects of WJ-MSC-Exos against renal IRI. Mechanistically, miR-19b suppressed glycogen synthase kinase-3ß (GSK3ß) expression, thereby stabilizing PDXK protein through direct binding. Treatment with WJ-MSC-Exos led to reduced PDXK levels and enhanced pyridoxine accumulation, ultimately mitigating IRI in transplanted kidneys and I/R-induced HK2 cell apoptosis. These findings elucidate the underlying mechanism of WJ-MSC-Exos in alleviating IRI in transplanted kidneys, unveiling novel therapeutic targets for post-kidney transplantation IRI and providing a solid theoretical foundation for the clinical application of WJ-MSC-Exos in IRI treatment post-transplantation.

Serum high-density lipoprotein cholesterol levels predict early recurrence and prognosis of intrahepatic cholangiocarcinoma after surgical resection.

Introduction: Dysregulation in lipid metabolism contributes to the occurrence and development of various cancers. The connection between changes in lipid metabolism and the development of intrahepatic cholangiocarcinoma remains uncertain. Our objective was to investigate the significance of blood lipid levels in patients with intrahepatic cholangiocarcinoma who have undergone surgery. Methods: Ninety-seven ICC patients who underwent surgery were retrospectively enrolled. After 92.2 months of follow-up, the Kaplan-Meier analysis and Cox proportional hazard model were used to calculate overall survival and recurrence-free survival. Results: The median age of this cohort was 56 years, and 79 (81.4 %) of them were male. Eighty-eight (90.7 %) patients presented with tumor recurrence and 73 (75.3 %) died. In multivariate analyses, high-density lipoprotein cholesterol level (<0.91 vs. ≥ 0.91 mmol/L, hazard ratio [HR] = 2.55; 95 % CI: 1.38-4.71), lymph node metastasis (Yes vs. No, HR = 2.58; 95 % CI: 1.28-5.19), etiology factor (chronic HBV infection vs. others, HR = 0.5; 95 % CI: 0.28-0.88) and multiple tumor lesions (Yes vs. No, HR = 1.85; 95 % CI: 1.01-3.39) were independent predictors of overall survival. However, only high-density lipoprotein cholesterol level (HR = 1.86; 95 % CI: 1.19-2.92) emerged as the independent factor for recurrence-free survival. High-density lipoprotein cholesterol level (HR = 2.07; 95 % CI: 1.26-3.41), etiology factor (HR = 0.49; 95 % CI: 0.29-0.84), and multiple tumor lesions (HR = 2.00; 95 % CI: 1.14-3.51) were independent predictors of early recurrence. For patients who did not experience the spread of cancer to the lymph nodes, there was a significant correlation between the level of high-density lipoprotein cholesterol and their overall survival, recurrence-free survival, and early recurrence. For patients with low pre-operation high-density lipoprotein cholesterol levels, high post-operation high-density lipoprotein cholesterol levels were associated with better prognosis. Conclusions: Low serum high-density lipoprotein cholesterol level might serve as a sign of poor clinical outcomes (overall survival and recurrence-free survival) and early recurrence among intrahepatic cholangiocarcinoma patients. Strengthening the monitoring and intervention of intrahepatic cholangiocarcinoma patients with poor prognosis might be critical for improving the prognosis.

A ratiometric fluorescent probe with a large Stokes shift for rapid and sensitive detection of Hg2+ in environmental water samples and its applications in living cells and zebrafish.

Detection of highly toxic mercury ions (Hg2+) in actual environmental and biological samples is of significant importance for protecting environment and human health. In this paper, a new ratiometric fluorescent probe BTIA was designed and synthesized from 3-pinone based on Internal Charge Transfer (ICT) mechanism. BTIA could selectively recognize Hg2+ over other competitive analytes with short reaction time (5 s), distinct ratiometric response, strong anti-interference ability, large Stokes shift (200 nm), and low detection limit (2.36 × 10-7 M). Furthermore, BTIA was applicable for detecting Hg2+ in actual water samples and it also performed an excellent imaging capability in living RAW264.7 cells, zebrafish and onion tissue.

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.

Assessment of PD-L1 Expression in Non-Small Cell Lung Cancers Using [68Ga]Ga-DOTA-WL12 PET/CT.

Assessing programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC), particularly in metastatic cases, remains challenging. In this study, surface plasmon resonance (SPR) analysis and [68Ga]Ga-DOTA-WL12 micro-PET/CT imaging are performed. [68Ga]Ga-DOTA-WL12 PET/CT and [18F]FDG PET/CT are performed on a cohort of 20 patients with NSCLC. Semi-quantitative assessments include SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and target-to-background ratio (TBR). DOTA-WL12 exhibits robust PD-L1 binding with a KD value of 0.2 nM. Subsequent human studies reveal significant correlations between PD-L1 expression and the [68Ga]Ga-DOTA-WL12 SUVmax in primary and metastatic lesions, surpassing the [18F]FDG results (r = 0.8889, p <0.0001 vs r = 0.0469, p = 0.8127). Notably, [68Ga]Ga-DOTA-WL12 imaging discerned SUVmax and TBR differences between PD-L1 TPS ≤1% and PD-L1 TPS > 1% groups (p all <0.001). In an NSCLC patient with brain metastases, [68Ga]Ga-DOTA-WL12 shows a SUVmean of 0.04 in the brain background, with TBR values of 17 and 23, underscoring its potential for detecting brain metastases. The study provides initial evidence for the clinical utility of [68Ga]Ga-DOTA-WL12 PET/CT for lesion detection, immunotherapy selection, and therapeutic efficacy evaluation in PD-L1-expressing NSCLC, demonstrating its potential as a valuable tool in NSCLC research and management.