Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Neonatal brain inflammation enhances methamphetamine-induced reinstated behavioral sensitization in adult rats analyzed with explainable machine learning.

Neonatal brain inflammation produced by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) results in long-lasting brain dopaminergic injury and motor disturbances in adult rats. The goal of the present work is to investigate the effect of neonatal systemic LPS exposure (1 or 2 mg/kg, i.p. injection in postnatal day 5, P5, male rats)-induced dopaminergic injury to examine methamphetamine (METH)-induced behavioral sensitization as an indicator of drug addiction. On P70, subjects underwent a treatment schedule of 5 once daily subcutaneous (s.c.) administrations of METH (0.5 mg/kg) (P70-P74) to induce behavioral sensitization. Ninety-six hours following the 5th treatment of METH (P78), the rats received one dose of 0.5 mg/kg METH (s.c.) to reintroduce behavioral sensitization. Hyperlocomotion is a critical index caused by drug abuse, and METH administration has been shown to produce remarkable locomotor-enhancing effects. Therefore, a random forest model was used as the detector to extract the feature interaction patterns among the collected high-dimensional locomotor data. Our approaches identified neonatal systemic LPS exposure dose and METH-treated dates as features significantly associated with METH-induced behavioral sensitization, reinstated behavioral sensitization, and perinatal inflammation in this experimental model of drug addiction. Overall, the analysis suggests that the implementation of machine learning strategies is sensitive enough to detect interaction patterns in locomotor activity. Neonatal LPS exposure also enhanced METH-induced reduction of dopamine transporter expression and [3H]dopamine uptake, reduced mitochondrial complex I activity, and elevated interleukin-1ß and cyclooxygenase-2 concentrations in the P78 rat striatum. These results indicate that neonatal systemic LPS exposure produces a persistent dopaminergic lesion leading to a long-lasting change in the brain reward system as indicated by the enhanced METH-induced behavioral sensitization and reinstated behavioral sensitization later in life. These findings indicate that early-life brain inflammation may enhance susceptibility to drug addiction development later in life, which provides new insights for developing potential therapeutic treatments for drug addiction.

Extracorporeal membrane oxygenation technology for adults: an evidence mapping based on systematic reviews.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial. METHODS: We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy. RESULTS: A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was "Critically low" to "Moderate". One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics. CONCLUSIONS: There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions.

The Development of the Regenerable Catalytic System in Selective Catalytic Oxidation of Ammonia with High N2 Selectivity.

Supported particulate noble-metal catalysts are widely used in industrial catalytic reactions. However, these metal species, whether in the form of nanoparticles or highly dispersed entities, tend to aggregate during reactions, leading to a reduced activity or selectivity. Addressing the frequent necessity for the replacement of industrial catalysts remains a significant challenge. Herein, we demonstrate the feasibility of the 'regenerable catalytic system' exemplified by selective catalytic oxidation of ammonia (NH3-SCO) employing Ag/Al2O3 catalysts. Results demonstrate that our highly dispersed Ag catalyst (Ag HD) maintains >90% N2 selectivity at 80% NH3 conversion and >80% N2 selectivity at 100% NH3 conversion after enduring 5 cycles of reducible aggregation and oxidative dispersion. Moreover, it consistently upholds over 98% N2 selectivity at 100% NH3 conversion after 10 cycles of Ar treatment. During the aggregation-dispersion process, the Ag HD catalyst intentionally aggregated into Ag nanoparticles (Ag NP) after H2 reduction and exhibited remarkable regenerable capabilities, returning to the Ag HD state after calcination in the air. This structural evolution was characterized through in situ transmission electron microscopy, atomically resolved high-angle annular dark-field scanning transmission electron microscopy, and X-ray absorption spectroscopy, revealing the on-site oxidative dispersion of Ag NP. Additionally, in situ diffuse reflectance infrared Fourier transform spectroscopy provided insights into the exceptional N2 selectivity on Ag HD catalysts, elucidating the critical role of NO+ intermediates. Our findings suggest a sustainable and cost-effective solution for various industry applications.

Demonstration of 651†nm InGaN-based red light-emitting diode with an external quantum efficiency over 6% by InGaN/AlN strain release interlayer.

This work reports a high-performance InGaN-based red-emitting LED with a strain-release interlayer (SRI) consisting of an InGaN stress-release layer (SRL) and an AlN dislocation confinement layer (DCL) in unintentionally doped GaN (u-GaN). The SRL introduces a tensile strain which could decrease the in-plane compressive stress of the u-GaN layer, while the DCL could reduce the dislocation density and thus improve the crystal quality of the u-GaN layer. Consequently, a high-efficiency InGaN-based red-emitting LED with a peak wavelength of 651 nm and an external quantum efficiency of 6.04% is realized. In addition, the room-temperature photoluminescence (PL) mapping emission wavelength is uniform across a 4-inch wafer with a standard deviation of 3.3 nm. Therefore, the proposed SRI offers good potential for mass-producing high-performance and long-wavelength InGaN-based red-emitting LEDs.

DPP: deep phase prior for parallel imaging with wave encoding.

OBJECTIVE: In MR parallel imaging with virtual channel-expanded Wave encoding, limitations are imposed on the ability to comprehensively and accurately characterize the background phase. These limitations are primarily attributed to the calibration process relying solely on center low-frequency ACS data for calibration. Approach: To tackle the challenge of accurately estimating the background phase in wave encoding, a novel deep neural network model guided by deep phase priors (DPP) is proposed with integrated virtual conjugate coil (VCC) extension. Concretely, within the proposed framework, the background phase is implicitly characterized by employing a carefully designed decoder convolutional neural network, leveraging the inherent characteristics of phase smoothness and compact support in the transformed domain. Furthermore, the proposed model with wave encoding benefits from additional priors, which incorporate transmission sparsity of the latent image and coil sensitivity smoothness. Main results: Ablation experiments were conducted to ascertain the proposed method's capability to implicitly represent CSM and the background phase. Subsequently, the superiority of the proposed method is demonstrated through confidence comparisons with competing methods, employing 4-fold and 5-fold acceleration experiments. In achieving 4-fold and 5-fold acceleration, the optimal quantitative metrics (PSNR/SSIM/NMSE) are 44.1359 dB/0.9863/0.0008 (4-fold) and 41.2074/0.9846/0.0017 (5-fold), respectively. Furthermore, the generalizability of the proposed method is further validated by conducting acceleration experiments with T1, T2, T2*, and various undersampling patterns. In addition, the DPP delivered much better performance than the conventional methods by exploring accelerated phase-sensitive SWI imaging. In SWI accelerated imaging, it also surpasses the optimal competing method in terms of (PSNR/SSIM/NMSE) with 0.096%/0.009%/0.0017%. Significance: The proposed method enables precise characterization of the background phase in the integrated VCC and wave encoding framework, supported via theoretical analysis and empirical findings. Our code is available at: https://github.com/sober235/DPP.

Establishment of the HPLC fluorescence detection method for plasma trace ivermectin and its pharmacokinetics in Bactrian camel.

BACKGROUND AND OBJECTIVE: Ivermectin (IVM), a widely used veterinary anthelmintic, lacks recommended doses for Bactrian camels. This study aims to establish its pharmacokinetics in Bactrian camels, comparing with other livestock. METHODS: A method for high-performance liquid chromatography fluorescence detection of IVM in plasma was developed. RESULTS: IVM exhibited linear scaling (y = 0.6946x + 0.0088, R2 = 0.9988) within 0.025-5 ng/mL, with a lower limit of quantification of 25.00 pg/mL, high recovery (>70%) and low RSD (<7%). In Bactrian camels, IVM injection showed a low Cmax, extended Tmax and apparent secondary absorption compared to cattle and sheep. CONCLUSIONS: Slow absorption and widespread distribution were observed, with peak concentration and area under the curve correlating positively with the dose. This study provides insights into IVM pharmacokinetics in Bactrian camels, informing dose determination and highlighting potential metabolic differences compared to other livestock.

HP3D-V2V: High-Precision 3D Object Detection Vehicle-to-Vehicle Cooperative Perception Algorithm.

Cooperative perception in the field of connected autonomous vehicles (CAVs) aims to overcome the inherent limitations of single-vehicle perception systems, including long-range occlusion, low resolution, and susceptibility to weather interference. In this regard, we propose a high-precision 3D object detection V2V cooperative perception algorithm. The algorithm utilizes a voxel grid-based statistical filter to effectively denoise point cloud data to obtain clean and reliable data. In addition, we design a feature extraction network based on the fusion of voxels and PointPillars and encode it to generate BEV features, which solves the spatial feature interaction problem lacking in the PointPillars approach and enhances the semantic information of the extracted features. A maximum pooling technique is used to reduce the dimensionality and generate pseudoimages, thereby skipping complex 3D convolutional computation. To facilitate effective feature fusion, we design a feature level-based crossvehicle feature fusion module. Experimental validation is conducted using the OPV2V dataset to assess vehicle coperception performance and compare it with existing mainstream coperception algorithms. Ablation experiments are also carried out to confirm the contributions of this approach. Experimental results show that our architecture achieves lightweighting with a higher average precision (AP) than other existing models.

A chromosomal-scale genome assembly of modern cultivated hybrid sugarcane provides insights into origination and evolution.

Sugarcane is a vital crop with significant economic and industrial value. However, the cultivated sugarcane's ultra-complex genome still needs to be resolved due to its high ploidy and extensive recombination between the two subgenomes. Here, we generate a chromosomal-scale, haplotype-resolved genome assembly for a hybrid sugarcane cultivar ZZ1. This assembly contains 10.4 Gb genomic sequences and 68,509 annotated genes with defined alleles in two sub-genomes distributed in 99 original and 15 recombined chromosomes. RNA-seq data analysis shows that sugar accumulation-associated gene families have been primarily expanded from the ZZSO subgenome. However, genes responding to pokkah boeng disease susceptibility have been derived dominantly from the ZZSS subgenome. The region harboring the possible smut resistance genes has expanded significantly. Among them, the expansion of WAK and FLS2 families is proposed to have occurred during the breeding of ZZ1. Our findings provide insights into the complex genome of hybrid sugarcane cultivars and pave the way for future genomics and molecular breeding studies in sugarcane.

The lemon genome and DNA methylome unveil epigenetic regulation of citric acid biosynthesis during fruit development.

Citric acid gives lemons their unique flavor, which impacts their sensory traits and market value. However, the intricate process of citric acid accumulation during lemon fruit growth remains incompletely understood. Here, we achieved a chromosomal-level genome assembly for the 'Xiangshui' lemon variety, spanning 364.85 Mb across nine chromosomes. This assembly revealed 27 945 genes and 51.37% repetitive sequences, tracing the divergence from citron 2.85 million years ago. DNA methylome analysis of lemon fruits across different developmental stages revealed significant variations in DNA methylation. We observed decreased CG and CHG methylation but increased CHH methylation. Notably, the expression of RdDM pathway-related genes increased with fruit development, suggesting a connection with elevated CHH methylation, which is potentially influenced by the canonical RdDM pathway. Furthermore, we observed that elevated CHH DNA methylation within promoters significantly influenced the expression of key genes, critically contributing to vital biological processes, such as citric acid accumulation. In particular, the pivotal gene phosphoenolpyruvate carboxykinase (ClPEPCK), which regulates the tricarboxylic acid cycle, was strikingly upregulated during fruit development, concomitant with increased CHH methylation in its promoter region. Other essential genes associated with citric acid accumulation, such as the MYB transcription factor (ClPH1/4/5) and ANTHOCYANIN 1 (ClAN1), were strongly correlated with DNA methylation levels. These results strongly indicate that DNA methylation crucially orchestrates the metabolic synthesis of citric acid. In conclusion, our study revealed dynamic changes in DNA methylation during lemon fruit development, underscoring the significant role of DNA methylation in controlling the citric acid metabolic pathway.

A Two-Stage Generative Model with CycleGAN and Joint Diffusion for MRI-based Brain Tumor Detection.

Accurate detection and segmentation of brain tumors is critical for medical diagnosis. However, current supervised learning methods require extensively annotated images and the state-of-the-art generative models used in unsupervised methods often have limitations in covering the whole data distribution. In this paper, we propose a novel framework Two-Stage Generative Model (TSGM) that combines Cycle Generative Adversarial Network (CycleGAN) and Variance Exploding stochastic differential equation using joint probability (VE-JP) to improve brain tumor detection and segmentation. The CycleGAN is trained on unpaired data to generate abnormal images from healthy images as data prior. Then VE-JP is implemented to reconstruct healthy images using synthetic paired abnormal images as a guide, which alters only pathological regions but not regions of healthy. Notably, our method directly learned the joint probability distribution for conditional generation. The residual between input and reconstructed images suggests the abnormalities and a thresholding method is subsequently applied to obtain segmentation results. Furthermore, the multimodal results are weighted with different weights to improve the segmentation accuracy further. We validated our method on three datasets, and compared with other unsupervised methods for anomaly detection and segmentation. The DSC score of 0.8590 in BraTs2020 dataset, 0.6226 in ITCS dataset and 0.7403 in In-house dataset show that our method achieves better segmentation performance and has better generalization.

Multi-omics landscape analysis reveals the pan-cancer association of arginine biosynthesis genes with tumor immune evasion and therapy resistance.

Background: The metabolism of arginine, a conditionally essential amino acid, plays a crucial role in cancer progression and prognosis. However, a more detailed understanding of the influence of arginine biosynthesis genes in cancer is currently unavailable. Methods: We performed an integrative multi-omics analysis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to determine the characteristics of these genes across multiple cancer types. To measure the overall activity of arginine biosynthesis genes in cancer, we calculated arginine biosynthesis scores based on gene expression. Results: Our results indicated that the arginine biosynthesis score was negatively correlated with immune-related pathways, immune infiltration, immune checkpoint expression, and patient prognosis, and single-cell data further clarified that patients with high arginine biosynthesis scores showed a reduced proportion of T and B cells in an immune desert tumor microenvironment and were insensitive to immunotherapy. We also identified several potential drugs through the Cancer Therapeutic Response Portal (CTRP) and Genomics of Drug Sensitivity in Cancer (GDSC) databases that could target arginine biosynthesis genes and potentially improve the response rate to immunotherapy in patients with a high arginine biosynthesis fraction. Conclusion: Overall, our analyses emphasize that arginine biosynthesis genes are associated with immune evasion in several cancers. Targeting these genes may facilitate more effective immunotherapy.

IgA-mediated control of host-microbial interaction during weaning reaction influences gut inflammation.

The mechanisms of how host-microbe mutualistic relationships are established at weaning contingently upon B-cell surveillance remain inadequately elucidated. We found that CD138+ plasmacyte (PC)-mediated promotion of IgA response regulates the symbiosis between Bacteroides uniformis (B. uniformis) and the host during the weaning period. The IgA-skewed response of CD138+ PCs is essential for B. uniformis to occupy a defined gut luminal niche, thereby fostering stable colonization. Furthermore, B. uniformis within the natural gut niche was perturbed in the absence of IgA, resulting in exacerbated gut inflammation in IgA-deficient mice and weaned piglets. Thus, we propose that the priming and maintenance of intestinal IgA response from CD138+ PCs are required for host-microbial symbiosis, whereas the perturbation of which would enhance inflammation in weaning process.

Influence of a Mixture of Protein Hydrolysate from Black Soldier Fly Larvae and Schizochytrium on Palatability, Plasma Biochemistry, and Antioxidative and Anti-Inflammatory Capacity in Cat Diets.

The objective of this research was to evaluate palatability, plasma biochemistry, antioxidative and anti-inflammatory capacity, and immune levels in cats by feeding supplementing inclusion of different levels of a mixture of protein hydrolysate from black soldier fly larvae and schizochytrium (BSFPs) in diets. In the feed experiment, a total of 24 adult cats (12 females and 12 males; BW: 3.02 ± 0.06 kg) were randomly divided into four groups: (1) diet with chicken and fish meal as primary protein resource (CON); (2) diet with 5% BSFPs replacing chicken meal, fish meal, chicken oil, and fish oil (5% BSFPs); (3) 10% BSFPs; and (4) 15% BSFPs. The body weight and feed intake were recorded, and a blood sample was collected for analysis. In the palatability experiment, three diets containing 5%, 10%, and 15% BSFPs were evaluated by comparing with CON. These results suggested that different levels of BSFPs could improve palatability in cat diets by enhancing the first sniff, the first bite, and feed intake (p < 0.05). However, no significant influence existed in body weight and average daily feed intake (p > 0.05). In comparison to the CON group, 5% and 15% BSFPs significantly increased the total protein content, and all treatment groups decreased the triglyceride content and enhanced the calcium concentration in plasma; in addition, the activity of aspartate aminotransferase and alanine aminotransferase and the content of creatinine and urea nitrogen were significantly reduced by the supplementation inclusion of BSFPs in the diets (p < 0.05). The enzyme activity of glutathione peroxidase was dramatically enhanced by the supplementation of 10% and 15% BSFPs in diets compared with the CON diet, and the activity of superoxide dismutase was increased and the malondialdehyde concentration was remarkably reduced in all three treatments (p < 0.05). Compared with the CON group, different levels of BSFPs in the diets significantly increased the immunoglobulin A content in plasma; similarly, the immunoglobulin G concentration was significantly enhanced by the supplementation of 10% and 15% BSFPs in the diets (p < 0.05). Furthermore, the interleukin-1ß content was significantly reduced in the inclusion of 10% and 15% BSFPs in the diets, and 15% BSFPs remarkably decreased the content of interleukin-8 in plasma compared with the CON diet (p < 0.05). To sum up, the supplementation of different levels of BSFPs exhibited a positive effect on palatability and enhanced the antioxidant, anti-inflammatory, and immune capacity. Particularly, the addition levels of 10% and 15% BSFPs were more effective in antioxidation, anti-inflammation, and immunity.

Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.

Association between the American Heart Association's new "Life's Essential 8" metrics and kidney stone.

PURPOSE: The incidence of kidney stone disease has increased worldwide, resulting in high medical costs and social burden. Kidney stone disease shares some common features with the risk factors of cardiovascular diseases (CVDs). We investigated the association between cardiovascular health (CVH) based on the Life's Essential 8 (LE8) score developed by the American Heart Association and the incidence of kidney stone disease. METHODS: We analyzed the data of 29,469 US adults aged 20 years or above from the National Health and Nutrition Examination Survey, 2007-2018. According to the LE8 score, CVH was divided into three categories: poor, intermediate, and ideal. Logistic regression was used to determine the association between CVH and the incidence of kidney stone disease by estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The average age of the participants was 48.6 years, and 50% of the participants were women. The numbers of participants with poor, intermediate, and ideal CVH were 4149, 19,782, and 5538, respectively. After adjusting for related confounding factors, ideal CVH was associated with a reduction in the odds of kidney stone occurrence as compared to poor CVH (adjusted OR [aOR]: 0.45, 95% CI: 0.35-0.57, p < 0.001). Moreover, if the ideal CVH metrics was ≥ 6, the odds of kidney stone occurrence decreased by up to 61% (aOR: 0.39, 95% CI: 0.30-0.51). CONCLUSIONS: In the present study, ideal CVH, a factor indicative of a healthy lifestyle, was associated with lower odds of kidney stone occurrence.

Medicarpin suppresses lung cancer cell growth in vitro and in vivo by inducing cell apoptosis.

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

Mechanisms of Coronary Sinus Reducer for Treatment of Myocardial Ischemia: In Silico Study.

The coronary sinus reducer (CSR) is an emerging medical device for treating patients with refractory angina, often associated with myocardial ischemia. Patients implanted with CSR have shown positive outcomes, but the underlying mechanisms are unclear. This study sought to understand the mechanisms of CSR by investigating its effects on coronary microcirculation hemodynamics that may help explain the therapy's efficacy. We applied a validated computer model of the coronary microcirculation to investigate how CSR affects hemodynamics under different degrees of coronary artery stenosis. With moderate coronary stenosis, an increase in capillary transit time (CTT) (up to 69% with near-complete coronary sinus (CS) occlusion) is the key change associated with CSR. Because capillaries in the microcirculation can still receive oxygenated blood from the upstream artery with moderate stenosis, the increase in CTT allows more time for the exchange of gases and nutrients, aiding tissue oxygenation. With severe coronary stenosis, however, the redistribution of blood draining from the non-ischemic region to the ischemic region (up to 96% with near-complete CS occlusion) and the reduction in capillary flow heterogeneity are the key changes associated with CSR. Because blood draining from the non-ischemic region is not completely devoid of O2, the redistribution of blood to the capillaries in the ischemic region by CSR is beneficial especially when little or no oxygenated blood reaches these capillaries. This simulation study provides insights into the mechanisms of CSR in improving clinical symptoms. The mechanisms differ with the severity of the upstream stenosis.