Molecular monitoring of Dinophysis species assemblage in mussel farms in the Northwestern Adriatic Sea.

Several Dinophysis species can produce potent lipophilic toxins that pose a risk to human health when contaminated seafood is consumed, especially filter-feeding bivalve mussels. In the mussel farms of the Northwestern Adriatic Sea, seawater and seafood are regularly monitored for the presence of Dinophysis species and their associated toxins, but the current methodological approaches, such as light microscopy determinations, require a long time to make results available to local authorities. A molecular qPCR-based assay can be used to quantify various toxic Dinophysis species in a shorter timeframe. However, this approach is not currently employed in official testing activities. In this study, field samples were collected monthly or bi-weekly over one year from various mussel farms along the Northwestern Adriatic coast. The abundance of Dinophysis species in the seawater was determined using both traditional microscopy and qPCR assays. In addition, the concentration of lipophilic toxins for DSP in mussel flesh was quantified using LC-MS/MS focusing on the okadaic acid group. Dinophysis spp. site-specific single cells were isolated and analysed by qPCR yielding a mean rDNA copy number per cell of 1.21 × 104 ± 1.81 × 103. The qPCR assay gave an efficiency of 98 % and detected up to 10 copies of the rDNA target gene. The qPCR and light microscopy determinations in environmental samples showed a significant positive correlation (Spearman rs = 0.57, p-value < 0.001) with a ratio of 2.24 between the two quantification methods, indicating that light microscopy estimates were generally 44.6 % lower than those obtained by the qPCR assay. The qPCR approach showed several advantages such as rapidity, sensitivity and efficiency over conventional microscopy analysis, showing its potential future role in phytoplankton monitoring under the Official Controls Regulations for shellfish.

A veracity dissemination consistency-based few-shot fake news detection framework by synergizing adversarial and contrastive self-supervised learning.

With the rapid growth of social media, fake news (rumors) are rampant online, seriously endangering the health of mainstream social consciousness. Fake news detection (FEND), as a machine learning solution for automatically identifying fake news on Internet, is increasingly gaining the attentions of academic community and researchers. Recently, the mainstream FEND approaches relying on deep learning primarily involves fully supervised fine-tuning paradigms based on pre-trained language models (PLMs), relying on large annotated datasets. In many real scenarios, obtaining high-quality annotated corpora are time-consuming, expertise-required, labor-intensive, and expensive, which presents challenges in obtaining a competitive automatic rumor detection system. Therefore, developing and enhancing FEND towards data-scarce scenarios is becoming increasingly essential. In this work, inspired by the superiority of semi-/self- supervised learning, we propose a novel few-shot rumor detection framework based on semi-supervised adversarial learning and self-supervised contrastive learning, named Detection Yet See Few (DetectYSF). DetectYSF synergizes contrastive self-supervised learning and adversarial semi-supervised learning to achieve accurate and efficient FEND capabilities with limited supervised data. DetectYSF uses Transformer-based PLMs (e.g., BERT, RoBERTa) as its backbone and employs a Masked LM-based pseudo prompt learning paradigm for model tuning (prompt-tuning). Specifically, during DetectYSF training, the enhancement measures for DetectYSF are as follows: (1) We design a simple but efficient self-supervised contrastive learning strategy to optimize sentence-level semantic embedding representations obtained from PLMs; (2) We construct a Generation Adversarial Network (GAN), utilizing random noises and negative fake news samples as inputs, and employing Multi-Layer Perceptrons (MLPs) and an extra independent PLM encoder to generate abundant adversarial embeddings. Then, incorporated with the adversarial embeddings, we utilize semi-supervised adversarial learning to further optimize the output embeddings of DetectYSF during its prompt-tuning procedure. From the news veracity dissemination perspective, we found that the authenticity of the news shared by these collectives tends to remain consistent, either mostly genuine or predominantly fake, a theory we refer to as "news veracity dissemination consistency". By employing an adjacent sub-graph feature aggregation algorithm, we infuse the authenticity characteristics from neighboring news nodes of the constructed veracity dissemination network during DetectYSF inference. It integrates the external supervisory signals from "news veracity dissemination consistency" to further refine the news authenticity detection results of PLM prompt-tuning, thereby enhancing the accuracy of fake news detection. Furthermore, extensive baseline comparisons and ablated experiments on three widely-used benchmarks demonstrate the effectiveness and superiority of DetectYSF for few-shot fake new detection under low-resource scenarios.

LM11A-31, a modulator of p75 neurotrophin receptor, suppresses HIV-1 replication and inflammatory response in macrophages.

Antiretroviral drugs have made significant progress in treating HIV-1 and improving the quality of HIV-1-infected individuals. However, due to their limited permeability into the brain HIV-1 replication persists in brain reservoirs such as perivascular macrophages and microglia, which cause HIV-1-associated neurocognitive disorders. Therefore, it is highly desirable to find a novel therapy that can cross the blood-brain barrier (BBB) and target HIV-1 pathogenesis in brain reservoirs. A recently developed 2-amino-3-methylpentanoic acid [2-morpholin-4-yl-ethyl]-amide (LM11A-31), which is a p75 neutrotrophin receptor (p75NTR) modulator, can cross the BBB. In this study, we examined whether LM11A-31 treatment can suppress HIV-1 replication, oxidative stress, cytotoxicity, and inflammatory response in macrophages. Our results showed that LM11A-31 (100 nM) alone and/or in combination with positive control darunavir (5.5 µM) significantly suppresses viral replication and reduces cytotoxicity. Moreover, the HIV-1 suppression by LM11A-31 was comparable to the HIV-1 suppression by darunavir. Although p75NTR was upregulated in HIV-1-infected macrophages compared to uninfected macrophages, LM11A-31 did not significantly reduce the p75NTR expression in macrophages. Furthermore, our study illustrated that LM11A-31 alone and/or in combination with darunavir significantly suppress pro-inflammatory cytokines including IL-1ß, IL-8, IL-18, and TNF-α and chemokines MCP-1 in HIV-induced macrophages. The suppression of these cytokines and chemokines by LM11A-31 was comparable to darunavir. In contrast, LM11A-31 did not significantly alter oxidative stress, expression of antioxidant enzymes, or autophagy marker proteins in U1 macrophages. The results suggest that LM11A-31, which can cross the BBB, has therapeutic potential in suppressing HIV-1 and inflammatory response in brain reservoirs, especially in macrophages.

Limonin (LM) and its derivatives: Unveiling the neuroprotective and anti-inflammatory potential of LM and V-A-4 in the management of Alzheimer's disease and Parkinson's disease.

Neuroinflammation and neuronal apoptosis are central pathogenic consequences associated with Alzheimer's Disease (AD) and Parkinson's Disease (PD). Limonin (LM), a tetracyclic triterpenoid available in citrus fruits, has anti-tumor, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective actions. LM derivative, V-A-4 emerged as a potential neuroprotective drug due to their ability to target multiple molecular pathways intertwined with neuroinflammation and neuronal apoptosis. To date, the treatment of AD and PD is not successful even though the understanding of the mechanism of neuroinflammation and neuronal apoptosis is vast in the literature. Thus, there is an urgent need to identify novel neuroprotective drugs that could target the multiple molecular pathways associated with neuroinflammation and neuronal apoptosis. The various online databases (Google scholar, Pubmed, Scopus) were searched via keywords: limonin, limonin derivatives and neuroprotection. This review highlights the multifunctional nature of LM and derivatives in combating neuroinflammation and neuronal apoptosis by stimulating PI3K/AKT and downregulating TLR4/NF-κB critical pathways. By intervening in the secretion of NO and TNF-α from glial cells, V-A-4 attenuates the damaging cascade of neuroinflammation by suppressing IKK-α and IKK-ß. Furthermore, V-A-4 demonstrates its versatility by suppressing the manifestation of miR-146a and miR-155, both intimately linked to neuroinflammation, this review summarized the activities of LM and its derivatives against AD and PD, with a special focus on V-A-4 as an effective neuroprotective drug. V-A-4's ability to stimulate PI3K/AKT signaling further underscores its neuroprotective effect in combating AD and PD. More in-vitro cell line studies are needed to develop V-A-4 as an upcoming neuroprotective compound.

Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with leptomeningeal metastases harboring targetable mutations.

Background: Driver gene-positive non-small cell lung cancer (NSCLC) patients are prone to develop leptomeningeal metastasis (LM), leading to an extremely high mortality. The objective of this study was to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) treatments for patients with NSCLC and LM harboring targetable mutations. Methods: We retrospectively collected records of patients with NSCLC harboring targetable mutations and prescribed ICIs following the diagnosis of LM at Huashan Hospital, Fudan University. In addition, we reviewed relevant literature and enrolled patients who met the inclusion criteria. Clinical characteristics were statistically analyzed, and the Kaplan-Meier method and log-rank test were employed to assess the median progression-free survival (mPFS) and median overall survival (mOS). Results: A total of 37 patients with NSCLC harboring targetable mutations who received ICIs after LM diagnosis were included. The median age of the enrolled patients was 54 years (range, 33-70 years), and 62.2% were female. Following ICI administration, the intracranial objective response rate (iORR) and intracranial disease control rate (iDCR) for all enrolled patients were 18.9% and 62.2%, respectively. The mPFS of all patients was 2.5 months [95% confidence interval (CI): 2.166-2.834 months] and the mOS was 5.8 months (95% CI: 5.087-6.513 months). Both univariate and multivariate analyses revealed a significant increase in mOS or individuals who had previously undergone cranial radiation therapy compared to those who had not. Furthermore, different histology molecular types were found to be potentially associated with survival time. Conclusions: Some patients with NSCLC harboring targetable gene mutations following LM diagnosis may benefit from ICI treatment with relatively good tolerance. However, further screening of the most suitable patient populations for ICIs is required.

Lung Cancer Screening-Trends and Current Studies.

Lung cancer is the leading cause of death among all the oncological diseases worldwide. This applies to both women and men; however, the incidence and mortality among women is on the rise. In 2020, lung cancer was responsible for 1.8 million deaths (18%). More than 90% of lung cancer cases and 77.1% of lung cancer deaths occur in countries with high and very high HDI (human development index) values. The aim of our study is to the present trends and most recent studies aimed at lung cancer screening. In the face of the persistently high mortality rate, conducting research aimed at extending already-implemented diagnostic algorithms and behavioural interventions focused on smoking cessation is recommended.

Neoadjuvant Statistical Algorithm to Predict Individual Risk of Relapse in Patients with Resected Liver Metastases from Colorectal Cancer.

(1) Background: Liver metastases (LM) are the leading cause of death in colorectal cancer (CRC) patients. Despite advancements, relapse rates remain high and current prognostic nomograms lack accuracy. Our objective is to develop an interpretable neoadjuvant algorithm based on mathematical models to accurately predict individual risk, ensuring mathematical transparency and auditability. (2) Methods: We retrospectively evaluated 86 CRC patients with LM treated with neoadjuvant systemic therapy followed by complete surgical resection. A comprehensive analysis of 155 individual patient variables was performed. Logistic regression (LR) was utilized to develop the predictive model for relapse risk through significance testing and ANOVA analysis. Due to data limitations, gradient boosting machine (GBM) and synthetic data were also used. (3) Results: The model was based on data from 74 patients (12 were excluded). After a median follow-up of 58 months, 5-year relapse-free survival (RFS) rate was 33% and 5-year overall survival (OS) rate was 60.7%. Fifteen key variables were used to train the GBM model, which showed promising accuracy (0.82), sensitivity (0.59), and specificity (0.96) in predicting relapse. Similar results were obtained when external validation was performed as well. (4) Conclusions: This model offers an alternative for predicting individual relapse risk, aiding in personalized adjuvant therapy and follow-up strategies.

Hepatocyte transformation is induced by laminin γ2 monomer.

Serum laminin-γ2 monomer (Lm-γ2m) is a potent predictive biomarker for hepatocellular carcinoma (HCC) onset in patients with hepatitis C infection who achieve a sustained virologic response with liver cirrhosis (LC) and for the onset of extrahepatic metastases in early-stage HCC. Although Lm-γ2m involvement in late-stage cancer progression has been well investigated, its precise roles in HCC onset remain to be systematically investigated. Therefore, we analyzed an HCC model, human hepatocytes and cholangiocytes, and surgically resected liver tissues from patients with HCC to understand the roles of Lm-γ2m in HCC onset. Ck-19- and EpCAM-positive hepatic progenitor cells (HPCs) in the liver of pdgf-c transgenic HCC mouse model with ductular reaction showed ectopic expression of Lm-γ2m. Forced expression of Lm-γ2m in hepatocytes adjacent to HPCs resulted in enhanced tumorigenicity, cell proliferation, and migration in immortalized hepatocytes, but not in cholangiocytes in vitro. Further, pharmacological inhibition of epidermal growth factor receptor (EGFR) and c-Jun activator JNK suppressed Lm-γ2m-induced hepatocyte transformation, suggesting the involvement of EGFR/c-Jun signaling in the transformation, leading to HCC development. Finally, immunohistochemical staining of HCC tissues revealed a high level of Lm-γ2 expression in the HPCs of the liver with ductular reaction in normal liver adjacent to HCC tissues. Overall, HPC-derived Lm-γ2m in normal liver with ductular reaction acts as a paracrine growth factor on surrounding hepatocytes and promotes their cellular transformation through the EGFR/c-Jun signaling pathway. Furthermore, this is the first report on Lm-γ2m expression detected in the normal liver with ductular reaction, a human precancerous lesion of HCC.

Intrathecal topotecan with systemic checkpoint inhibitor therapy for gastroesophageal cancer with leptomeningeal involvement: two case reports and review of the literature.

Background: Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments. Case Description: Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed. Conclusions: We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios.

Lactiplantibacillus plantarum LM1001 Improves Digestibility of Branched-Chain Amino Acids in Whey Proteins and Promotes Myogenesis in C2C12 Myotubes.

Lactiplantibacillus plantarum is a valuable potential probiotic species with various proven health-beneficial effects. L. plantarum LM1001 strain was selected among ten strains of L. plantarum based on proteolytic activity on whey proteins. L. plantarum LM1001 produced higher concentrations of total free amino acids and branched-chain amino acids (Ile, Leu, and Val) than other L. plantarum strains. Treatment of C2C12 myotubes with whey protein culture supernatant (1%, 2% and 3%, v/v) using L. plantarum LM1001 significantly increased the expression of myogenic regulatory factors, such as Myf-5, MyoD, and myogenin, reflecting the promotion of myotubes formation (p<0.05). L. plantarum LM1001 displayed ß-galactosidase activity but did not produce harmful ß-glucuronidase. Thus, the intake of whey protein together with L. plantarum LM1001 has the potential to aid protein digestion and utilization.

Cardiac arrhythmia detection using artificial neural network.

This paper outlines the development of the 'Cardiac Abnormality Monitoring' wearable medical device, aimed at creating a compact safety monitor integrating advanced Artificial Neural Network (ANN) algorithms. Given power consumption constraints and cost-effectiveness, a strategy combining sophisticated instruments with neural network algorithms is proposed to enhance performance. This approach aims to compete with high-end wearable devices, utilizing innovative manufacturing techniques. The paper evaluates the feasibility of employing the Levenberg-Marquardt (LM) ANN algorithm in power-conscious wearable devices, considering its potential for offline embedded systems or IoT gadgets capable of cloud-based data uploading. The Levenberg-Marquardt ANN is chosen primarily for its practicality in prototype development, with other neural network algorithms also explored to identify potential alternatives. We have compared the six neural network models and determined the model that has the potential to replace the primary neural network model. We found that the 'Kernelized SVC with PCA' can test accuracy. To be specific, in this paper, we will evaluate the performance of the ANN model and also check its feasibility and practicality by integrating it with a constructed prototypical working model.

Effect of Continuous Casting and Heat Treatment Parameters on the Microstructure and Mechanical Properties of Recycled EN AW-2007 Alloy.

The growing use of aluminum and its compounds has increased the volume of aluminum waste. To mitigate environmental impacts and cut down on manufacturing expenses, extensive investigations have recently been undertaken to recycle aluminum compounds. This paper outlines the outcomes of a study on fabricating standard EN AW-2007 alloy using industrial and secondary scrap through continuous casting. The resultant recycled bars were analyzed for their chemical makeup and examined for microstructural features in both the cast and T4 states, undergoing mechanical property evaluations. The study identified several phases in the cast form through LM, SEM + EDS, and XRD techniques: Al7Cu2Fe, θ-Al2Cu, ß-Mg2Si, Q-Al4Cu2Mg8Si7, and α-Al15(FeMn)3 (SiCu)2, along with Pb particles. Most primary intermetallic precipitates such as θ-Al2Cu, ß-Mg2Si, and Q-Al4Cu2Mg8Si7 dissolved into the α-Al solid solution during the solution heat treatment. In the subsequent natural aging process, the θ-Al2Cu phase predominantly emerged as a finely dispersed hardening phase. The peak hardness achieved in the EN AW-2007 alloy was 124.8 HB, following a solution heat treatment at 500 °C and aging at 25 °C for 80 h. The static tensile test assessed the mechanical and ductility properties of the EN AW-2007 alloy in both the cast and T4 heat-treated states. Superior strength parameters were achieved after solution heat treatment at 500 °C for 6 h, followed by water quenching and natural aging at 25 °C/9 h, with a tensile strength of 435.0 MPa, a yield strength of 240.5 MPa, and an appreciable elongation of 18.1% at break. The findings demonstrate the feasibility of producing defect-free EN AW-2007 alloy ingots with excellent mechanical properties from recycled scrap using the continuous casting technique.

High-Resolution Characterization of DNA/Protein Complexes in Living Bacteria.

The occurrence of DNA looping is ubiquitous. This process plays a well-documented role in the regulation of prokaryotic gene expression, such as in regulation of the Escherichia coli lactose (lac) operon. Here we present two complementary methods for high-resolution in vivo detection of DNA/protein binding within the bacterial nucleoid by using either chromatin immunoprecipitation combined with phage λ exonuclease digestion (ChIP-exo) or chromatin endogenous cleavage (ChEC), coupled with ligation-mediated polymerase chain reaction (LM-PCR) and Southern blot analysis. As an example, we apply these in vivo protein-mapping methods to E. coli to show direct binding of architectural proteins in the Lac repressor-mediated DNA repression loop.

Bacillus amyloliquefaciens LM-1 Affects Multiple Cell Biological Processes in Magnaporthe oryzae to Suppress Rice Blast.

Magnaporthe oryzae, one of the most destructive rice pathogens, causes significant losses during the rice harvest every year. Bacillus amyloliquefaciens has been explored in many crops as a potential biocontrol agent. However, the mechanisms of B. amyloliquefaciens controled rice blast are not fully understood. Here, a biocontrol strain LM-1, isolated from a contaminated medium, was identified as B. amyloliquefaciens using morphological observation, physiological and biochemical tests, and 16S rDNA sequencing. LM-1 inhibited the growth and pathogenicity of M. oryzae and Bipolaris oryzae (Breda de Haan) Shoem. The mycelia of M. oryzae co-cultured with LM-1 were enlarged and broken by fluorescence microscopy using calcofluor white. LM-1 inhibited the mycelia of M. oryzae from producing conidia. Genes itu, srf, and fenB were detected in LM-1. Furthermore, the supernatant of LM-1 interfered with the appressorium formation of M. oryzae, blocked conidial cell death, and reduced autophagy degradation but did not affect the normal germination of rice seeds and seeding growth. Additionally, we observed hypersensitivity reactions, reactive oxygen species, and iron accumulation reduction in rice cells inoculated with supernatant. Our study reveals that LM-1 has a control effect on rice blast and affects cell wall integrity, sporulation, appressorium formation, cell death, and autophagy.

Anatomy and micromorphology of Tilia species from Turkey and its taxonomic implication.

The genus Tilia L. belongs to Malvaceae and it is represented by four species in Turkey. These are T. cordata, T. platyphyllos, T. rubra subsp. caucasica, and T. tomentosa. Tilia species have medicinal importance, especially to treat colds, flu, and coughs, and are also used as sedatives. Inflorescence with bract is recorded in the pharmacopeia as used parts. This study aimed to investigate the differences in leaf and bract characteristics in distinguishing Tilia species. Leaves and bracts were examined anatomically and micromorphologically under light and scanning electron microscopes (LM and SEM). There is no comparative anatomical and micromorphological study of Tilia species from Turkey. Microscopic examination allows for the observation of stomata types, trichomes, and other anatomical structures. These features can vary among species and can aid in differentiation. Features of bract that is medicinally used part were evaluated to find efficient diagnostic characters. The leaves also possess distinct characteristics, and leaf morphology is already used in the identification key in Flora. The emphasis is on identifying the species of medically used drugs. A diagnostic key was created using LM and SEM based on bract features to differentiate taxa for the first time. RESEARCH HIGHLIGHTS: Leaf and bract anatomy of Tilia taxa was studied via LM and SEM. The raw plant material is inflorescence with bract so identification by bract is important for species adulteration. An diagnostic key based on bract features was created for the first time.

Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

PURPOSE: 18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. METHODS: Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. RESULTS: [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. CONCLUSION: [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.

Enhanced Detection of Early Pulmonary Fibrosis Disease Using 68Ga-FAPI-LM3 PET.

Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3 alongside the heterobivalent probe 68Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.

A Numerical simulation method for analyzing 1H spin diffusion NMR for Multicomponent and multiphase polymer systems.

A numerical simulation method, namely, SDNMR-WEBFIT, is reported for simulating proton spin diffusion NMR based on the Levenberg-Marquardt algorithm and a pseudo-2D diffusion model. This method is used for the precise quantification of dynamics heterogeneity of the interphase within multiphase polymer systems. The numerical simulation method provides measurements of spin-lattice relaxation time (T1), proton density (ρH), lamellar thickness (d), and spin diffusion coefficient (D) for each component. The pseudo-2D diffusion model is employed to simulate the proton spin diffusion build-up/decay curves, simultaneously calculating the lateral fraction of island-like structures (x-ratio). Such approach was successfully applied to various polymer systems, such as semi-crystalline polymer (Poly(ε-caprolactone), PCL), block copolymers (Styrene-butadiene-styrene triblock copolymer, SBS), and plasticized semi-polymers (Polvinyl alcohol, PVA).

Robust PWM control scheme for switched-capacitor MLI with leakage current suppression in grid-connected renewable energy application.

Typically, parasitic capacitances exist between the ground and the solar panel terminals in grid-connected PV systems. These parasitic capacitances provide a path for a leakage current, which leads to significant safety concerns, observable and seriously hazardous harmonic orders aligned with the injected grid current, and significant safety difficulties. In this research, a robust PWM controlling method that used competently in reducing the level of the leakage current and improving the power quality of a switched-capacitor Multilevel Inverter. This technique creates developed reference signals from the main signal to generate the switching scheme for the converter circuit. Additionally, the suggested control strategy only works with a small number of carrier signals, resulting in a quick system response and a simpler controller algorithm. Likewise, this controlling approach offers a stable way to maintain a constant output voltage in the suggested converter by adjusting the switching capacitors' voltages, which is not possible with traditional control techniques. MATLAB/Simulink is used to simulate the outcomes for both the suggested control approach and the traditional Phase Disposition (PD) PWM control method whereas the leakage current component reduces to 25 % compared to the captured component with the PDPWM. The simulation and the practical results based on the dSPACE-1103 hardware are quite similar.

Advances in physical vapor deposited silicon/carbon based anode materials for Li-ion batteries.

This paper explores the latest developments in physical vapor deposition (PVD) techniques for fabricating silicon-carbon (Si/C) based thin films as anodes of Lithium-Ion batteries (LiBs). Properties of Si/C based materials, such as high thermal stability, electrical conductivity and mechanical strength, have addressed the critical challenges associated with the use silicon as anode material for LiBs, including as volume expansion during lithiation, structural stability and electrode degradation. The review article aims to provide recent advances in the use of Si/C-based thin film materials deposited via PVD processes as anodes for LiBs. PVD deposition processes provide numerous benefits including the precise control over the structure, thickness, morphology, as well as the design of deposited thin-film materials, and this article provides an in-depth analysis on the design and synthesis of Si/C thin films, as well as its electrochemical performance and stability when used as anode for LiBs. The primary aim of this paper is to underscore the advantages provided by PVD processes in overcoming challenges associated with using pure silicon as anode material for LiBs, or in improving the electrochemical performance of Si/C-based anode materials through the design of several Si/C films, covering both multilayer and nanocomposite Si/C film configurations outlined in sections 2 and 3, respectively. Insights into the mechanisms governing lithium-ion insertion/extraction processes within the Si/C matrix are provided, offering an understanding of the material's behavior during battery cycling.