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A novel and concise synthetic method for arenastatin A, a cytotoxic cyclic depsipeptide of marine origin, was developed in this study. The convergent assembly of the four segments, including the cross-metathesis reaction, gave a cyclization precursor, and Fmoc deprotection caused simultaneous macrocyclization. The Corey–Chaykovsky reaction using a chiral sulfur ylide afforded arenastatin A with complete stereoselectivity in the longest linear sequence of seven reaction steps from the known compound. Using this synthetic method, some analogs of segment B were prepared through a late-stage diversification strategy. The simple SN2 reaction of the thiolate toward the tosylate precursor, prepared using almost the same synthetic method as described above, provided the desired sulfide analogs. [ABSTRACT FROM AUTHOR]

An application of CO2/HCO3−-free solution (Zero-CO2) did not increase intracellular pH (pHi) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in frequency (CBF) or amplitude (CBA) of the ciliary beating. This study demonstrated that the pHi of c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while the pHi of ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). An extremely high pHi of c-hNECs caused pHi, CBF and CBA to decrease upon Zero-CO2 application, while a low pHi of c-hBECs caused them to increase. An extremely high pHi was generated by a high rate of HCO3− influx via interactions between CAIV and Na+/HCO3− cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased pHi, CBF and CBA and increased CBF and CBA in c-hNECs upon Zero-CO2 application. In conclusion, the interactions of CAIV and NBC maximize HCO3− influx to increase pHi in c-hNECs. This novel mechanism causes pHi to decrease, leading to no increase in CBF and CBA in c-hNECs upon Zero-CO2 application, and appears to play a crucial role in maintaining pHi, CBF and CBA in c-hNECs periodically exposed to air (0.04% CO2) with respiration. [ABSTRACT FROM AUTHOR]

Single cilia, 100 nm in diameter and 10 µm in length, were isolated from mouse tracheae with Triton X-100 (0.02%) treatment, and the effects of pH on ciliary beating were examined by measuring the ciliary beat frequency (CBF) and the ciliary bend distance (CBD—an index of amplitude) using a high-speed video microscope (250 fps). ATP (2.5 mM) plus 8Br-cAMP (10 µM) reactivated the CBF and CBD in the isolated cilia, similar to the cilia of in vivo tracheae. In the reactivated isolated cilia, an elevation in pH from 7.0 to 8.0 increased the CBF from 3 to 15 Hz and the CBD from 0.6 to 1.5 µm. The pH elevation also increased the velocity of the effective stroke; however, it did not increase the recovery stroke, and, moreover, it decreased the intervals between beats. This indicates that H+ (pHi) directly acts on the axonemal machinery to regulate CBF and CBD. In isolated cilia priorly treated with 1 µM PKI-amide (a PKA inhibitor), 8Br-cAMP did not increase the CBF or CBD in the ATP-stimulated isolated cilia. pH modulates the PKA signal, which enhances the axonemal beating generated by the ATP-activated inner and outer dyneins. [ABSTRACT FROM AUTHOR]

Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoquinone core structure, was synthesized through Bartoli indole synthesis and IBX-mediated oxidation. Late-stage diversification at N-5 and N-9 yielded makaluvamine J and several analogs. A structure–activity relationship (SAR) analysis highlighted the significance of the lipophilic side chain at N-9 for the growth inhibitory activity of PANC-1 cells. The modest alkyl group at N-5 was found to improve selectivity against other cancer cells. Among the prepared analogs, the tryptamine analog 24 showed potent and selective cytotoxicity (IC50 = 0.029 µM, selective index = 13.1), exceeding those of natural products. [ABSTRACT FROM AUTHOR]

Ambroxol (ABX), a frequently prescribed secretolytic agent which enhances the ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of amplitude) by 30%, activates a voltage-dependent Ca2+ channel (CaV1.2) and a small transient Ca2+ release in the ciliated lung airway epithelial cells (c-LAECs) of mice. The activation of CaV1.2 alone enhanced the CBF and CBA by 20%, mediated by a pHi increasei and a [Cl−]i decrease in the c-LAECs. The increase in pHi, which was induced by the activation of the Na+-HCO3− cotransporter (NBC), enhanced the CBF (by 30%) and CBA (by 15–20%), and a decrease in [Cl−]i, which was induced by the Cl− release via anoctamine 1 (ANO1), enhanced the CBA (by 10–15%). While a Ca2+-free solution or nifedipine (an inhibitor of CaV1.2) inhibited 70% of the CBF and CBA enhancement using ABX, CaV1.2 enhanced most of the CBF and CBA increases using ABX. The activation of the CaV1.2 existing in the cilia stimulates the NBC to increase pHi and ANO1 to decrease the [Cl−]i in the c-LAECs. In conclusion, the pHi increase and the [Cl−]i decrease enhanced the CBF and CBA in the ABX-stimulated c-LAECs. [ABSTRACT FROM AUTHOR]

A shorter synthesis of the demethyl(oxy)aaptamine skeleton was developed via oxidative intramolecular cyclization of 1-(2-azidoethyl)-6-methoxyisoquinolin-7-ol followed by dehydrogenation with a hypervalent iodine reagent. This is the first example of oxidative cyclization at the ortho-position of phenol that does not involve spiro-cyclization, resulting in the improved total synthesis of 3-(phenethylamino)demethyl(oxy)aaptamine, a potent anti-dormant mycobacterial agent. [ABSTRACT FROM AUTHOR]

The synthesis and evaluation of simplified analogs of marine sponge-derived alkaloid 3-(phenethylamino)demethyl(oxy)aaptamine were performed to develop novel anti-mycobacterial substances. Ring truncation of the tricyclic benzo[de][1,6]-naphthyridine skeleton effectively weakened the cytotoxicity of the natural product, and the resulting AC-ring analog exhibited good anti-mycobacterial activity. A structure–activity relationship (SAR) study, synthesizing and evaluating some analogs, demonstrated the specificity and importance of the N-(2-arylethyl)quinolin-3-amine skeleton as a promising scaffold for anti-mycobacterial lead compounds. [ABSTRACT FROM AUTHOR]

Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure about forty years ago. Since then, it has been revealed as a key protein with functions in a variety of fields including cell migration, survival, and signal transduction, as well as functioning as a structural component. Ezrin acts as a cross-linker of membrane proteins or phospholipids in the plasma membrane and the actin cytoskeleton. It also functions as a platform for signaling molecules at the cell surface. Moreover, ezrin is regarded as an important target protein in cancer diagnosis and therapy because it is a key protein involved in cancer progression and metastasis, and its high expression is linked to poor survival in many cancers. Small molecule inhibitors of ezrin have been developed and investigated as candidate molecules that suppress cancer metastasis. Here, we wish to comprehensively review the roles of ezrin from the pathophysiological points of view. [ABSTRACT FROM AUTHOR]

Oral dictyoceratin-C (1) and A (2), hypoxia-selective growth inhibitors, showed potent in vivo antitumor effects in mice subcutaneously inoculated with sarcoma S180 cells. Structurally modified analogs were synthesized to assess the structure-activity relationship of the natural compounds 1 and 2 isolated from a marine sponge. Biological evaluation of these analogs showed that the exo-olefin and hydroxyl and methyl ester moieties were important for the hypoxia-selective growth inhibitory activities of 1 and 2. Thus far, only substitution of the methyl ester with propargyl amide in 1 was found to be effective for the synthesis of probe molecules for target identification. [ABSTRACT FROM AUTHOR]

The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential. The compound 3-(phenethylamino)demethyl(oxy)aaptamine (PDOA, 1), isolated from marine sponge of Aaptos sp., is known as an anti-dormant mycobacterial substance, and has been reported to be effective against the drug resistant strains of M. tuberculosis. However, its target protein still remains unclear. This study aims to clarify the structure–activity relationship of 1 using 15 synthetic analogues, in order to prepare a probe molecule for detecting the target protein of 1. We succeeded in creating the compound 15 with a photoaffinity group that retained antimicrobial activity, which proved to be a suitable probe molecule for identifying the target protein of 1. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the rumen fermentation characteristics, bacterial diversity, community composition, and metabolite profiles of rice straw from three distinct varieties. Straws from two hybrid rice varieties, Lingliangyou 268 (L268) and Yueyou 9113 (Y9113), and one inbred rice variety, Zhongzao 39 (Z39), were selected for a 72 h in vitro rumen fermentation test. The fermentation products were analyzed for rumen fermentation characteristics, bacterial community, and rumen metabolomics. The results showed that Y9113 had higher total gas and methane production, greater dry matter digestibility, and higher concentrations of ammonium nitrogen and volatile fatty acids compared to Z39 (p < 0.05). The variety of rice straw did not affect the richness or diversity of the rumen bacterial community (p > 0.05). However, the relative abundances of Verrucomicrobiota, Euryarchaeota, Elusimicrobiota, Probable genus 10, Lachnospiraceae AC2044 group, WCHB1-41, and VadinBE97 were higher in Z39 than in Y9113, while the opposite was observed for Saccharofermentans, UCG-010, and NK4A214 group (p < 0.05). Both principal coordinates analysis (PCoA) and partial least squares discrimination analysis (PLS-DA) revealed clear distinctions in the rumen bacterial communities between Y9113 and Z39. Metabolomic analysis identified eighteen differential metabolites among L268, Z39, and Y9113, with six showing strong correlations with the rumen microbiota. These findings suggest that the feed value of rice straw is influenced by the variety under the same cultivation conditions, due to nutritional disparities that subsequently affect the rumen microbial community and metabolite profiles. This study offers valuable data and insights for the strategic resource utilization of rice straw from different varieties in the livestock industry. [ABSTRACT FROM AUTHOR]

Background: as transcatheter technologies have advanced, the patient population that is referred to open heart surgeries has shifted. This study's objective was to evaluate recent trends in the characteristics of patients undergo surgical valvular interventions and coronary revascularizations (CABG) in our center over a period of 14 years. Methods: this is a retrospective analysis of ecological trends in the age, sex, and risk profile (Charlson comorbidity index—CCI) of patients who, from January 2010 to December 2023, underwent CABG, aortic valve replacement (AVR), or mitral valve repair or replacement (with or without tricuspid valve intervention). The data were extracted from electronic clinical files using MD-Clone software. Results: for the CABG procedures, the respective data for 2010 and 2023 were: mean ages 68.0 and 64.6 years; 79.7% and 83.1% males; and mean CCI scores 3.16 and 2.51. The p-values for the cumulative differences over the study period were 0.001, 0.005, and 0.013, respectively. The respective data for isolated AVR were mean ages of 69.2 and 62.9 years; 64.1% and 59.1% males; mean CCI 3.64 and 2.32; p-values: <0.001, 0.229, and 0.019. The respective data for mitral valve procedures were mean ages of 63.6 and 59.8 years, 71.4% and 65.5% males; mean CCI 2.90 and 1.79; p-values: 0.84, 0.422, and 0.318. Conclusions: over a 14-year period, changes were evident in the age, sex distribution, and CCI for operations performed in our center. These changes most likely resulted from accumulated data regarding the advantages and detriments of treatment strategies, mostly of CABG vs. percutaneous coronary intervention; major advancements in transcatheter technologies, mostly in transcatheter AVR; and clinical guidelines facilitating a more collaborative decision-making, open-minded, and personalized approach. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we compared two artificial intelligence (AI) tools, OncoStudio and Protégé AI, for their ability to automatically segment organs in Korean cancer patients undergoing radiation therapy. Manual contouring of organs is time-consuming and can vary among clinicians, potentially impacting treatment accuracy. We aimed to evaluate how well the aforementioned AI tools can assist clinicians by speeding up this process and ensuring precision. Our findings showed that OncoStudio, which was specifically developed for Korean patients, performed better in most cases than Protégé AI, a globally developed tool. These results suggest that population-specific AI tools can improve radiation therapy planning, ultimately enhancing patient outcomes and reducing clinician workload. Background: Accurate delineation of tumors and organs at risk (OARs) is crucial for intensity-modulated radiation therapy. This study aimed to evaluate the performance of OncoStudio, an AI-based auto-segmentation tool developed for Korean patients, compared with Protégé AI, a globally developed tool that uses data from Korean cancer patients. Methods: A retrospective analysis of 1200 Korean cancer patients treated with radiotherapy was conducted. Auto-contours generated via OncoStudio and Protégé AI were compared with manual contours across the head and neck and thoracic, abdominal, and pelvic organs. Accuracy was assessed using the Dice similarity coefficient (DSC), mean surface distance (MSD), and 95% Hausdorff distance (HD). Feedback was obtained from 10 participants, including radiation oncologists, residents, and radiation therapists, via an online survey with a Turing test component. Results: OncoStudio outperformed Protégé AI in 85% of the evaluated OARs (p < 0.001). For head and neck organs, OncoStudio achieved a similar DSC (0.70 vs. 0.70, p = 0.637) but significantly lower MSD and 95% HD values (p < 0.001). In thoracic organs, OncoStudio performed excellently in 90% of cases, with a significantly greater DSC (male: 0.87 vs. 0.82, p < 0.001; female: 0.95 vs. 0.87, p < 0.001). OncoStudio also demonstrated superior accuracy in abdominal (DSC 0.88 vs. 0.81, p < 0.001) and pelvic organs (male: DSC 0.95 vs. 0.85, p < 0.001; female: DSC 0.82 vs. 0.73, p < 0.001). Clinicians favored OncoStudio in 70% of cases, with 90% endorsing its clinical suitability for Korean patients. Conclusions: OncoStudio, which is tailored for Korean patients, demonstrated superior segmentation accuracy across multiple anatomical regions, suggesting its suitability for radiotherapy planning in this population. [ABSTRACT FROM AUTHOR]

Background: diatoms are unicellular algae that have been used for more than a century for forensic purposes to diagnose drowning, with more or less success depending on the historical era. Although many years have passed, scientific research on diatoms has never ceased, which testifies to their enduring allure in forensics. Of course, diatom research has evolved and expanded over time, changing with the availability of new techniques and technologies. The volume of articles and their production over a period of many years has resulted in old, current, and new knowledge on diatoms being scattered over a large number of books and articles. Objectives: the purpose of this narrative literature review is, therefore, to summarize all this information and bring it together in a single work that can be useful for those who are studying diatoms and their usefulness for forensics for the first time, for those who are looking for proven methods of analysis, and finally for those who are interested in exploring new frontiers of research. Methods: a comprehensive literature search that included all studies dealing with the applications of diatoms in forensic science was performed in the most popular electronic databases. Results: traditional methods have been complemented by molecular and imaging methods and, more recently, by artificial intelligence. In addition, new biological substrates have been found for the analysis of diatoms. Conclusions: all this has led, on the one hand, to the consolidation of a whole body of knowledge on diatoms, on which this forensic analysis is still based, and, on the other hand, has opened up numerous new research directions. [ABSTRACT FROM AUTHOR]

The delivery of nutrients to the brain is provided by a 600 km network of capillaries and microvessels. Indeed, the brain is highly energy demanding and, among a total amount of 100 billion neurons, each neuron is located just 10–20 μm from a capillary. This vascular network also forms part of the blood–brain barrier (BBB), which maintains the brain's stable environment by regulating chemical balance, immune cell transport, and blocking toxins. Typically, brain microvascular endothelial cells (BMECs) have low turnover, indicating a stable cerebrovascular structure. However, this structure can adapt significantly due to development, aging, injury, or disease. Temporary neural activity changes are managed by the expansion or contraction of arterioles and capillaries. Hypoxia leads to significant remodeling of the cerebrovascular architecture and pathological changes have been documented in aging and in vascular and neurodegenerative conditions. These changes often involve BMEC proliferation and the remodeling of capillary segments, often linked with local neuronal changes and cognitive function. Cerebrovascular plasticity, especially in arterioles, capillaries, and venules, varies over different time scales in development, health, aging, and diseases. Rapid changes in cerebral blood flow (CBF) occur within seconds due to increased neural activity. Prolonged changes in vascular structure, influenced by consistent environmental factors, take weeks. Development and aging bring changes over months to years, with aging-associated plasticity often improved by exercise. Injuries cause rapid damage but can be repaired over weeks to months, while neurodegenerative diseases cause slow, varied changes over months to years. In addition, if animal models may provide useful and dynamic in vivo information about vascular plasticity, humans are more complex to investigate and the hypothesis of glymphatic system together with Magnetic Resonance Imaging (MRI) techniques could provide useful clues in the future. [ABSTRACT FROM AUTHOR]

The field cricket, Gryllus madagascarensis, is a sustainable and nutritious food resource that has the potential to mitigate global malnutrition. Feeds provided to this cricket can influence its growth parameters, nutritional content, and the cost of raising it for food. The current study aimed to evaluate the effects of feeds formulated from weeds, agro-byproducts, and chicken feed (control) on the growth parameters and nutritional content of G. madagascarensis. The formulated feeds included CFB (25.0% protein), CFC (24.5% protein), CFD (24.0% protein), CFE (23.5% protein), CFF (22.5% protein), CFG (21.5% protein), CFH (20.0% protein), CFI (14.5% protein), and CFJ (13.5% protein), and chicken feed (CFA) (28% protein) was used as the control. The formulation of the feeds was based on the acceptability and protein content of the 12 selected weeds and agro-byproducts. Proximate, mineral, and fatty acid analyses were conducted to determine the nutrient content of each feed, as well as the crickets raised on these feeds. The fastest development time was recorded with CFE and CFC. The highest survivorship (98%) was observed in CFG, CFE, and CFC. The highest body mass (1.15 g) and body length (26.80 mm) were observed in crickets fed CFG. By comparison, crickets fed control feed averaged a body mass of 0.81 g and a body length of 23.55 mm. The feed conversion ratio for G. madagascarensis fed CFG, CFE, and CFC was 1.71. Crickets raised on CFH and CFG had the lowest cost of feeding per kg live mass gain. Crickets fed on CFF had the highest quantity of protein (67%), followed by those fed CFG (65% protein); crickets with the lowest protein content (50%) were fed CFJ. Crickets fed on CFG had the highest mineral content. Linoleic acid, oleic acid, and palmitic acid were the major fatty acids. The findings indicate that formulated feeds from weeds and agro-byproducts have great potential to be used as an alternative feed source for crickets for two reasons: their capacity to positively influence the biology and nutrition of the cricket, and they can serve as an inexpensive replacement for chicken feed. [ABSTRACT FROM AUTHOR]

Hypoxia-adapted cancer cells in tumors contribute to the pathological progression of cancer. The marine spongean sesquiterpene phenols dictyoceratin-A (1) and -C (2) have been shown to induce hypoxia-selective growth inhibition in cultured cancer cells and exhibit in vivo antitumor effects. These compounds inhibit the accumulation of hypoxia-inducible factor-1α (HIF-1α), which is a drug target in hypoxia-adapted cancer cells, under hypoxic conditions. However, the target molecules of compounds 1 and 2, which are responsible for decreasing HIF-1α expression under hypoxic conditions, remain unclear. In this study, we synthesized probe molecules for compounds 1 and 2 to identify their target molecules and found that both compounds bind to RNA polymerase II-associated protein 3 (RPAP3), which is a component of the R2TP/Prefoldin-like (PEDL) complex. In addition, RPAP3-knockdown cells showed a phenotype similar to that of compound-treated cells. [ABSTRACT FROM AUTHOR]

Osteoarthritis of the knee (OAK), a progressive degenerative disease affecting quality of life, is characterized by cartilage degeneration, synovial inflammation, and osteophyte formation causing pain and disability. Platelet-rich plasma (PRP) is an autologous blood product effective in reducing OAK-associated pain. PRP compositions depend on their purification. In clinical practice, PRP is typically administered immediately after purification, while cryopreserved PRP is used in research. Platelets are activated by freezing followed by release of their humoral factors. Therefore, PRP without any manipulation after purification (utPRP) and freeze–thawed PRP (fPRP) may differ in their properties. We purified leukocyte-poor PRP (LPPRP) and autologous protein solution (APS) to compare the properties of utPRPs and fPRPs and their effects on OAK target cells. We found significant differences in platelet activation and humoral factor content between utPRPs and fPRPs in both LPPRP and APS. Freeze–thawing affected the anti-inflammatory properties of LPPRP and APS in chondrocytes and synovial cells differed. Both utPRPs and fPRPs inhibited polarization toward M1 macrophages while promoting polarization toward M2 macrophages. Freeze–thawing specifically affected humoral factor production in macrophages, suggesting that evaluating the efficacy of PRPs requires considering PRP purification methods, properties, and conditions. Understanding these variations may enhance therapeutic application of PRPs in OAK. [ABSTRACT FROM AUTHOR]

Non-contrast magnetic resonance angiography (NC-MRA), including fresh blood imaging (FBI), is a suitable choice for evaluating patients with peripheral artery disease (PAD). We evaluated standard FBI (sFBI) and centric ky-kz FBI (cFBI) acquisitions, using 1D and 2D parallel imaging factors (PIFs) to assess the trade-off between scan time and image quality due to blurring. The bilateral legs of four volunteers (mean age 33 years, two females) were imaged in the coronal plane using a body array coil with a posterior spine coil. Two types of sFBI and cFBI sequences with 1D PIF factor 5 in the phase encode (PE) direction (in-plane) and 2D PIF 3 (PE) × 2 (slice encode (SE)) (in-plane, through-slice) were studied. Image quality was evaluated by a radiologist, the vessel's signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured, and major vessel width was measured on the coronal maximum intensity projection (MIP) and 80-degree MIP. Results showed significant time reductions from 184 to 206 s on average when using sFBI down to 98 to 162 s when using cFBI (p = 0.003). Similar SNRs (averaging 200 to 370 across all sequences and PIF) and CNRs (averaging 190 to 360) for all techniques (p > 0.08) were found. There was no significant difference in the image quality (averaging 4.0 to 4.5; p > 0.2) or vessel width (averaging 4.1 to 4.9 mm; p > 0.1) on coronal MIP due to sequence or PIF. However, vessel width measured using 80-degree MIP demonstrated a significantly wider vessel in cFBI (5.6 to 6.8 mm) compared to sFBI (4.5 to 4.7 mm) (p = 0.022), and in 1D (4.7 to 6.8 mm) compared to 2D (4.5 to 5.6 mm) (p < 0.05) PIF. This demonstrated a trade-off in T2 blurring between 1D and 2D PIF: 1D using a PIF of 5 shortened the acquisition window, resulting in sharper arterial blood vessels in coronal images but significant blur in the 80-degree MIP. Two-dimensional PIF for cFBI provided a good balance between shorter scan time (relative to sFBI) and good sharpness in both in- and through-plane, while no benefit of 2D PIF was seen for sFBI. In conclusion, this study demonstrated the usefulness of FBI-based techniques for peripheral artery imaging and underscored the need to strike a balance between scan time and image quality in different planes through the use of 2D parallel imaging. [ABSTRACT FROM AUTHOR]

In medical imaging, noise can significantly obscure critical details, complicating diagnosis and treatment. Traditional denoising techniques often struggle to maintain a balance between noise reduction and detail preservation. To address this challenge, we propose an "Efficient Transfer-Learning-Based Fractional Order Image Denoising Approach in Medical Image Analysis (ETLFOD)" method. Our approach uniquely integrates transfer learning with fractional order techniques, leveraging pre-trained models such as DenseNet121 to adapt to the specific needs of medical image denoising. This method enhances denoising performance while preserving essential image details. The ETLFOD model has demonstrated superior performance compared to state-of-the-art (SOTA) techniques. For instance, our DenseNet121 model achieved an accuracy of 98.01%, precision of 98%, and recall of 98%, significantly outperforming traditional denoising methods. Specific results include a 95% accuracy, 98% precision, 99% recall, and 96% F1-score for MRI brain datasets, and an 88% accuracy, 91% precision, 95% recall, and 88% F1-score for COVID-19 lung data. X-ray pneumonia results in the lung CT dataset showed a 92% accuracy, 97% precision, 98% recall, and 93% F1-score. It is important to note that while we report performance metrics in this paper, the primary evaluation of our approach is based on the comparison of original noisy images with the denoised outputs, ensuring a focus on image quality enhancement rather than classification performance. [ABSTRACT FROM AUTHOR]

This article presents a comprehensive overview of recent discoveries and advancements in the field of steroid chemistry, highlighting the isolation and characterization of various steroidal compounds from natural sources. This paper discusses a wide range of steroids, including pregnane steroids, steroidal alkaloids, ketosteroids, and novel triterpenoids, derived from marine organisms, fungi, and plants. Significant findings include the isolation of bioactive compounds such as the cytotoxic erectsterates from microorganisms, soft corals, the unusual tetracyclic steroid penicillitone from a fungal culture, and innovative steroidal derivatives with potential anti-inflammatory and anticancer activities. The synthesis of steroids from microorganisms as a tool for pharmaceutical development is also explored, showcasing the role of microbial biotransformation in generating steroidal drugs. Additionally, this paper emphasizes the ecological and medicinal relevance of these compounds, which are often used in traditional medicine and have potential therapeutic applications in treating diseases like cancer and microbial infections. This article serves as a vital resource for researchers interested in the chemical diversity of steroids and their applications in drug discovery and development. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomographic angiography (CCTA) is a non-invasive imaging technique that possesses the ability to provide detailed anatomical information about coronary arteries, avoiding unnecessary invasive procedures. Our aim was to assess the ability of CCTA to identify coronary artery disease compared to invasive coronary angiography (ICA) in a real-life setting. Methods: We examined 137 consecutive patients who underwent ICA after CCTA. The latter was conducted in various non-selected centers, and data regarding stenosis were taken from individual reports without further analysis. Results: A total of 60.5% of patients who underwent CCTA were found to have at least one critical stenosis, while the remaining 39.5% underwent ICA due to concurrent clinical or instrumental indications. Among these, 29.5% had angiographically critical pathology, 20.3% underwent a percutaneous coronary intervention (PCI), and 1.8% had coronary artery bypass grafting. Among the 83 patients with positive CCTA results, 34.9% had negative ICA findings. CCTA demonstrated low sensitivity (57.8%) and a positive predictive value of 42.6%. However, it retained high specificity (83.6%) and a negative predictive value of 90.4% for identifying critical stenosis. Among the 18.2% of patients who underwent CCTA without a specific indication, 60% had critical coronary lesions on their ICA and 86.6% of these subsequently underwent a PCI. Conclusions: CCTA performed in non-selective centers has a low concordance with ICA. [ABSTRACT FROM AUTHOR]

We present robust pixel design methodologies for a vertical avalanche photodiode-based CMOS image sensor, taking account of three critical practical factors: (i) "guard-ring-free" pixel isolation layout, (ii) device characteristics "insensitive" to applied voltage and temperature, and (iii) stable operation subject to intense light exposure. The "guard-ring-free" pixel design is established by resolving the tradeoff relationship between electric field concentration and pixel isolation. The effectiveness of the optimization strategy is validated both by simulation and experiment. To realize insensitivity to voltage and temperature variations, a global feedback resistor is shown to effectively suppress variations in device characteristics such as photon detection efficiency and dark count rate. An in-pixel overflow transistor is also introduced to enhance the resistance to strong illumination. The robustness of the fabricated VAPD-CIS is verified by characterization of 122 different chips and through a high-temperature and intense-light-illumination operation test with 5 chips, conducted at 125 °C for 1000 h subject to 940 nm light exposure equivalent to 10 kLux. [ABSTRACT FROM AUTHOR]

Aaptamine (8,9-dimethoxy-1H-benzo[de][1,6]naphthyridine), an alkaloid obtained from marine sponges of the genus Aaptos (Demospongiae, Suberitida, Suberitidae), has attracted significant attention as a promising scaffold for the development of antioxidant, antibacterial, and anticancer agents. This review offers an extensive overview of updated research on aaptamine, focusing on its multifaceted pharmacological properties. The antioxidant potential of aaptamine reflects its potential ability for use in the DPPH free radical scavenging assay, for suppressing ROS, and subsequently deactivating the MAPK and AP-1 signaling pathway. Moreover, it demonstrates notable antibacterial activity against pathogenic bacteria, including mycobacterial active and dormant states, making it a potential candidate for combating bacterial infections. Additionally, aaptamine shows promising anticancer activity by inhibiting cancer cell proliferation, apoptosis induction, and suppressing tumor growth through various signaling pathways, including the regulation of PTEN/PI3K/Akt and CDK2/4, and the regulation of cyclin D1/E in cell cycle arrest. The unique chemical structure of aaptamine offers opportunities for structural modifications aimed at enhancing its antioxidant, antibacterial, and anticancer activities. The exploration of aaptamine as a scaffold in the development of novel therapeutic agents offers great promise for addressing various challenges associated with oxidative stress, bacterial infections, and cancer. This article underscores the potential of aaptamine as a valuable marine-derived scaffold in the fields of antioxidant, antibacterial, and anticancer therapy. [ABSTRACT FROM AUTHOR]

The opportunistic use of radiological examinations for disease detection can potentially enable timely management. We assessed if an index created by an AI software to quantify chest radiography (CXR) findings associated with heart failure (HF) could distinguish between patients who would develop HF or not within a year of the examination. Our multicenter retrospective study included patients who underwent CXR without an HF diagnosis. We included 1117 patients (age 67.6 ± 13 years; m:f 487:630) that underwent CXR. A total of 413 patients had the CXR image taken within one year of their HF diagnosis. The rest (n = 704) were patients without an HF diagnosis after the examination date. All CXR images were processed with the model (qXR-HF, Qure.AI) to obtain information on cardiac silhouette, pleural effusion, and the index. We calculated the accuracy, sensitivity, specificity, and area under the curve (AUC) of the index to distinguish patients who developed HF within a year of the CXR and those who did not. We report an AUC of 0.798 (95%CI 0.77–0.82), accuracy of 0.73, sensitivity of 0.81, and specificity of 0.68 for the overall AI performance. AI AUCs by lead time to diagnosis (<3 months: 0.85; 4–6 months: 0.82; 7–9 months: 0.75; 10–12 months: 0.71), accuracy (0.68–0.72), and specificity (0.68) remained stable. Our results support the ongoing investigation efforts for opportunistic screening in radiology. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is rapidly advancing, aiming to mimic human cognitive abilities, and is addressing complex medical challenges in the field of biological science. Over the past decade, AI has experienced exponential growth and proven its effectiveness in processing massive datasets and optimizing decision-making. The main content of this review paper emphasizes the active utilization of AI in the field of stem cells. Stem cell therapies use diverse stem cells for drug development, disease modeling, and medical treatment research. However, cultivating and differentiating stem cells, along with demonstrating cell efficacy, require significant time and labor. In this review paper, convolutional neural networks (CNNs) are widely used to overcome these limitations by analyzing stem cell images, predicting cell types and differentiation efficiency, and enhancing therapeutic outcomes. In the biomedical sciences field, AI algorithms are used to automatically screen large compound databases, identify potential molecular structures and characteristics, and evaluate the efficacy and safety of candidate drugs for specific diseases. Also, AI aids in predicting disease occurrence by analyzing patients' genetic data, medical images, and physiological signals, facilitating early diagnosis. The stem cell field also actively utilizes AI. Artificial intelligence has the potential to make significant advances in disease risk prediction, diagnosis, prognosis, and treatment and to reshape the future of healthcare. This review summarizes the applications and advancements of AI technology in fields such as drug development, regenerative medicine, and stem cell research. [ABSTRACT FROM AUTHOR]

Intangible cultural heritage is a people-centered living cultural heritage. Preservation, promotion, and talent cultivation are important aspects of intangible cultural heritage protection and also crucial guarantees for sustainable development. However, traditional video recordings lack three-dimensional spatial information, and the high cost of digital scanning and reconstruction still leaves no convenient, efficient, accurate, realistic, and low-cost solution for the preservation and dissemination of intangible cultural heritage projects. Here we introduce the binocular 180-degree panoramic display method, through which a platform for recording, showcasing, disseminating, and teaching intangible cultural heritage projects in the Sanlin Old Street of Shanghai was implemented. The platform requires only VR filming without the need for 3D modeling technology. The participants can freely select intangible cultural heritage projects on the map and immerse themselves in watching the Sanlin "Three Excellence" porcelain carving, local cuisine, and embroidery. They can also enjoy the dragon dance, experience the textile craftsmanship of Sanlin's "Three Specialties", and even observe the production process and details of the works from the perspective of the inheritor in the first person. The results show that compared to traditional video recordings and digital scanning reconstruction, the binocular 180-degree panoramic display provides a one-to-one, face-to-face, and low-cost solution for the preservation and dissemination of projects. It allows students to increase their knowledge of intangible cultural heritage and enhance their interest in inheritance. [ABSTRACT FROM AUTHOR]

Winter wheat is an important grain that plays a crucial role in agricultural production and ensuring food security. Its yield directly impacts the stability and security of the global food supply. The accurate monitoring of grain yield is imperative for precise agricultural management. This study aimed to enhance winter wheat yield predictions with UAV remote sensing and investigate its predictive capability across diverse environments. In this study, RGB and multispectral (MS) data were collected on 6 May 2020 and 10 May 2022 during the grain filling stage of winter wheat. Using the Pearson correlation coefficient method, we identified 34 MS features strongly correlated with yield. Additionally, we identified 24 texture features constructed from three bands of RGB images and a plant height feature, making a total of 59 features. We used seven machine learning algorithms (Cubist, Gaussian process (GP), Gradient Boosting Machine (GBM), Generalized Linear Model (GLM), K-Nearest Neighbors algorithm (KNN), Support Vector Machine (SVM), Random Forest (RF)) and applied recursive feature elimination (RFE) to nine feature types. These included single-sensor features, fused sensor features, single-year data, and fused year data. This process yielded diverse feature combinations, leading to the creation of seven distinct yield prediction models. These individual machine learning models were then amalgamated to formulate a Bayesian Model Averaging (BMA) model. The findings revealed that the Cubist model, based on the 2020 and 2022 dataset, achieved the highest R2 at 0.715. Notably, models incorporating both RGB and MS features outperformed those relying solely on either RGB or MS features. The BMA model surpassed individual machine learning models, exhibiting the highest accuracy (R2 = 0.725, RMSE = 0.814 t·ha−1, MSE = 0.663 t·ha−1). Additionally, models were developed using one year's data for training and another year's data for validation. Cubist and GLM stood out among the seven individual models, delivering strong predictive performance. The BMA model, combining these models, achieved the highest R2 of 0.673. This highlights the BMA model's ability to generalize for multi-year data prediction. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the amide proton transfer (APT), tumor blood flow (TBF), and apparent diffusion coefficient (ADC) combined diagnostic value for differentiating intracranial malignant tumors (MTs) from benign tumors (BTs) in young patients, as defined by the 2021 World Health Organization classification of central nervous system tumors. Methods: Fifteen patients with intracranial MTs and 10 patients with BTs aged 0–30 years underwent MRI with APT, pseudocontinuous arterial spin labeling (pCASL), and diffusion-weighted imaging. All tumors were evaluated through the use of histogram analysis and the Mann–Whitney U test to compare 10 parameters for each sequence between the groups. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The APT maximum, mean, 10th, 25th, 50th, 75th, and 90th percentiles were significantly higher in MTs than in BTs; the TBF minimum (min) was significantly lower in MTs than in BTs; TBF kurtosis was significantly higher in MTs than in BTs; the ADC min, 10th, and 25th percentiles were significantly lower in MTs than in BTs (all p < 0.05). The APT 50th percentile (0.900), TBF min (0.813), and ADC min (0.900) had the highest area under the curve (AUC) values of the parameters in each sequence. The AUC for the combination of these three parameters was 0.933. Conclusions: The combination of APT, TBF, and ADC evaluated through histogram analysis may be useful for differentiating intracranial MTs from BTs in young patients. [ABSTRACT FROM AUTHOR]

This study assessed AI-processed low-dose cone-beam computed tomography (CBCT) images for single-tooth diagnosis. Human-equivalent phantoms were used to evaluate CBCT image quality with a focus on the right mandibular first molar. Two CBCT machines were used for evaluation. The first CBCT machine was used for the experimental group, in which images were acquired using four protocols and enhanced with AI processing to improve quality. The other machine was used for the control group, where images were taken in one protocol without AI processing. The dose-area product (DAP) was measured for each protocol. Subjective clinical image quality was assessed twice by five dentists, with a 2-month interval in between, using 11 parameters and a six-point rating scale. Agreement and statistical significance were assessed with Fleiss' kappa coefficient and intra-class correlation coefficient. The AI-processed protocols exhibited lower DAP/field of view values than non-processed protocols, while demonstrating subjective clinical evaluation results comparable to those of non-processed protocols. The Fleiss' kappa coefficient value revealed statistical significance and substantial agreement. The intra-class correlation coefficient showed statistical significance and almost perfect agreement. These findings highlight the importance of minimizing radiation exposure while maintaining diagnostic quality as the usage of CBCT increases in single-tooth diagnosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Carbon monoxide (CO) intoxication is one of the most common causes of poisoning-related deaths and complications. Myocardial injury is an important complication of CO poisoning. In our study, we aimed to evaluate the relationship between the presence and prevalence of fragmented QRS (fQRS) and myocardial injury in patients with CO intoxication. Materials and Methods: We retrospectively evaluated patients who presented to the emergency department of our tertiary care center with CO intoxication between January 2020 and December 2023. In our study, we performed subgroup analyses according to the presence of myocardial injury and fQRS. We evaluated the parameters and risk factors associated with myocardial injury. Results: Myocardial injury was detected in 44 patients, and fQRS was detected in 38 patients. In the myocardial injury (+) group, the fQRS rate was 38.6%, and the median number of leads with fQRS was 3 (2–6) and was significantly higher than in the myocardial injury (−) group (p < 0.001). We found that carboxyhemoglobin had a significant positive correlation with troponin (p = 0.001) and pro-B-type natriuretic peptide (proBNP) (p = 0.009). As a result of multivariate analysis, we determined that age, creatinine, proBNP, fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury. Conclusions: Myocardial injury in CO intoxication patients is associated with proBNP, the presence of fQRS, and the number of leads with fQRS. Age, creatinine level, proBNP, the presence of fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury in patients with CO intoxication. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) can radically change almost every aspect of the human experience. In the medical field, there are numerous applications of AI and subsequently, in a relatively short time, significant progress has been made. Cardiology is not immune to this trend, this fact being supported by the exponential increase in the number of publications in which the algorithms play an important role in data analysis, pattern discovery, identification of anomalies, and therapeutic decision making. Furthermore, with technological development, there have appeared new models of machine learning (ML) and deep learning (DP) that are capable of exploring various applications of AI in cardiology, including areas such as prevention, cardiovascular imaging, electrophysiology, interventional cardiology, and many others. In this sense, the present article aims to provide a general vision of the current state of AI use in cardiology. Results: We identified and included a subset of 200 papers directly relevant to the current research covering a wide range of applications. Thus, this paper presents AI applications in cardiovascular imaging, arithmology, clinical or emergency cardiology, cardiovascular prevention, and interventional procedures in a summarized manner. Recent studies from the highly scientific literature demonstrate the feasibility and advantages of using AI in different branches of cardiology. Conclusions: The integration of AI in cardiology offers promising perspectives for increasing accuracy by decreasing the error rate and increasing efficiency in cardiovascular practice. From predicting the risk of sudden death or the ability to respond to cardiac resynchronization therapy to the diagnosis of pulmonary embolism or the early detection of valvular diseases, AI algorithms have shown their potential to mitigate human error and provide feasible solutions. At the same time, limits imposed by the small samples studied are highlighted alongside the challenges presented by ethical implementation; these relate to legal implications regarding responsibility and decision making processes, ensuring patient confidentiality and data security. All these constitute future research directions that will allow the integration of AI in the progress of cardiology. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to investigate the influence of the root canal morphology and various treatment variables on the outcomes of root canal treatments (RCTs) in mandibular second molars, assessed through cone-beam computed tomography (CBCT) imaging. Methods: A total of 150 CBCT images were examined, comprising 100 cases of persistent endodontic infections and 50 of previously treated root canals with normal apices in the mandibular second molars. CBCT was utilized to evaluate the root canal configuration, the radiographic quality of coronal restorations and treated canal systems, and the presence of periapical lesions. Statistical analyses were performed to explore the correlations between these factors. Results: The presence of a C-shaped root canal configuration did not demonstrate a significant correlation with periapical lesions (p = 0.05). Factors influencing endodontic treatment outcomes included missing canals (p = 0.018), underfilling or overfilling (p = 0.045), and inadequate coronal restoration (p = 0.006). Missing a canal was identified as the variable most significantly associated with periapical lesions (OR = 3.103). Inhomogeneous root canal obturation was more commonly observed in C-shaped root canals (p < 0.001). Conclusions: Regardless of the root canal morphology of mandibular second molars, successful RCT depends on thorough disinfection to eliminate any untreated canals, precise three-dimensional filling of the canals at the correct working length, and a securely sealed coronal restoration to prevent leakage. [ABSTRACT FROM AUTHOR]

Spectral computed tomography (CT)-reconstructed images often exhibit severe noise and artifacts, which compromise the practical application of spectral CT imaging technology. Methods that use tensor dictionary learning (TDL) have shown superior performance, but it is difficult to obtain a high-quality pre-trained global tensor dictionary in practice. In order to resolve this problem, this paper develops an algorithm called tensor decomposition with total generalized variation (TGV) for sparse-view spectral CT reconstruction. In the process of constructing tensor volumes, the proposed algorithm utilizes the non-local similarity feature of images to construct fourth-order tensor volumes and uses Canonical Polyadic (CP) tensor decomposition instead of pre-trained tensor dictionaries to further explore the inter-channel correlation of images. Simultaneously, introducing the TGV regularization term to characterize spatial sparsity features, the use of higher-order derivatives can better adapt to different image structures and noise levels. The proposed objective minimization model has been addressed using the split-Bregman algorithm. To assess the performance of the proposed algorithm, several numerical simulations and actual preclinical mice are studied. The final results demonstrate that the proposed algorithm has an enormous improvement in the quality of spectral CT images when compared to several existing competing algorithms. [ABSTRACT FROM AUTHOR]

The integration of Virtual Reality with radiology is the focus of this study. A narrative review has been proposed to delve into emerging themes within the integration of Virtual Reality in radiology by scrutinizing reviews gathered from PubMed and Scopus. The proposed approach was based on a standard narrative checklist and a qualification process. The selection process identified 20 review studies. Integration of Virtual Reality (VR) in radiology offers potential transformative opportunities also integrated with other emerging technologies. In medical education, VR and AR, using 3D images from radiology, can enhance learning, emphasizing the need for standardized integration. In radiology, VR combined with Artificial Intelligence (AI) and Augmented Reality (AR) shows promising prospectives to give a complimentary contribution to diagnosis, treatment planning, and education. Challenges in clinical integration and User Interface design must be addressed. Innovations in medical education, like 3D modeling and AI, has the potential to enable personalized learning, but face standardization challenges. While robotics play a minor role, advancements and potential perspectives are observed in neurosurgery and endovascular systems. Ongoing research and standardization efforts are crucial for maximizing the potential of these integrative technologies in healthcare. In conclusion, the synthesis of these findings underscores the opportunities for advancements in digital radiology and healthcare through the integration of VR. However, challenges exist, and continuous research, coupled with technological refinements, is imperative to unlock the full potential of these integrative approaches in the dynamic and evolving field of medical imaging. [ABSTRACT FROM AUTHOR]

The inadequate vascularization seen in fast-growing solid tumors gives rise to hypoxic areas, fostering specific changes in gene expression that bolster tumor cell survival and metastasis, ultimately leading to unfavorable clinical prognoses across different cancer types. Hypoxia-inducible factors (HIF-1 and HIF-2) emerge as druggable pivotal players orchestrating tumor metastasis and angiogenesis, thus positioning them as prime targets for cancer treatment. A range of HIF inhibitors, notably natural compounds originating from marine organisms, exhibit encouraging anticancer properties, underscoring their significance as promising therapeutic options. Bioprospection of the marine environment is now a well-settled approach to the discovery and development of anticancer agents that might have their medicinal chemistry developed into clinical candidates. However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy. [ABSTRACT FROM AUTHOR]

Public–private partnership (PPP) is a prominent tool for sustainable infrastructure development. However, the positive contributions of PPPs toward the attainment of sustainable, climate resilience and zero-carbon infrastructure projects are hampered by poor financial risk management. This problem is more prevalent in developing countries like Ghana where private investment inflow has plummeted due to the COVID-19 recession and poor project performance. Thus, this study aims to assess the key financial risk management strategies in ensuring sustainable PPP infrastructure projects in Ghana. The study utilised primary data from PPP practitioners in Ghana solicited through survey questionnaires. Factor analysis, mean scores and fuzzy synthetic analysis are the data analysis techniques for this study. The results revealed that sustainable and green funding models, effective cost-reduction initiatives, a competent team with committed leadership and emerging technologies and regulations constitute the key strategies for managing the financial risks of sustainable PPP infrastructure projects. Although future studies must expand the scope of data gathering, the findings of the study enrich the theoretical understanding of financial risks in sustainable investments in PPP infrastructures. Relevant remedies that will aid the development of practical financial risk management guidelines are also provided in this study for PPP practitioners. [ABSTRACT FROM AUTHOR]

The development of sustainable alternatives to chemical and mechanical biofilm removal for submerged technical devices used in freshwater and marine environments represents a major technical challenge. In this context, the antibiotic impact of blue light with its low absorption underwater provides a potentially useful alternative. However, former technical limitations led to hours of treatment. Here, we applied high-power blue laser irradiation (1500 W) with a wavelength of 448 nm to demonstrate its strong antibiotic and algicidal effect on different bacteria and algae in seconds. High-power blue light treatment (139 W/cm2) for only 8.9 s led to the efficient deactivation of all tested organisms. Analyses of the underlying biological mechanisms revealed the absorption of the blue light by endogenous chromophores (flavins, tetrapyrroles) with the generation of reactive oxygen species (ROS). In agreement, Escherichia coli transcriptome analyses demonstrated a stress response at the level of DNA damage repair, respiration, and protein biosynthesis. Spectroscopic measurements of the irradiated algae indicated the irreversible damage of chlorophyll by photooxidation with the formation of singlet oxygen. In conclusion, high-power blue laser radiation provides a strong sustainable tool for the removal of biofouling in a very short time for applications in aquatic systems. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper presents a novel approach to produce virtual contrast enhanced (VCE) images for nasopharyngeal cancer (NPC) without the use of contrast agents, which carry certain risks. This model uses pixelwise gradient term to capture the shape and a GAN terms to capture the texture of the real contrast enhanced T1C images With similar accuracy to existing models, our method shows an advantage in reproducing texture closer to the realistic contrast-enhanced images. This results are tested by various measures, including mean absolute error (MAE), mean square error (MSE) and structural similarity index (SSIM) for similarity accuracy; total mean square variation per mean intensity (TMSVPMI), the total absolute vari-ation per mean intensity (TAVPMI), Tenengrad function per mean intensity (TFPMI) and variance function per mean intensity (VFPMI) Various variations of the model, including fine-tuning of the hyperparameters, normalization methods on the images and using single modality, have also been investigated to test the optimal performance. Background: The development of advanced computational models for medical imaging is crucial for improving diagnostic accuracy in healthcare. This paper introduces a novel approach for virtual contrast enhancement (VCE) in magnetic resonance imaging (MRI), particularly focusing on nasopharyngeal cancer (NPC). Methods: The proposed model, Pixelwise Gradient Model with GAN for Virtual Contrast Enhancement (PGMGVCE), makes use of pixelwise gradient methods with Generative Adversarial Networks (GANs) to enhance T1-weighted (T1-w) and T2-weighted (T2-w) MRI images. This approach combines the benefits of both modalities to simulate the effects of gadolinium-based contrast agents, thereby reducing associated risks. Various modifications of PGMGVCE, including changing hyperparameters, using normalization methods (z-score, Sigmoid and Tanh) and training the model with T1-w or T2-w images only, were tested to optimize the model's performance. Results: PGMGVCE demonstrated a similar accuracy to the existing model in terms of mean absolute error (MAE) (8.56 ± 0.45 for Li's model; 8.72 ± 0.48 for PGMGVCE), mean square error (MSE) (12.43 ± 0.67 for Li's model; 12.81 ± 0.73 for PGMGVCE) and structural similarity index (SSIM) (0.71 ± 0.08 for Li's model; 0.73 ± 0.12 for PGMGVCE). However, it showed improvements in texture representation, as indicated by total mean square variation per mean intensity (TMSVPMI) (0.124 ± 0.022 for ground truth; 0.079 ± 0.024 for Li's model; 0.120 ± 0.027 for PGMGVCE), total absolute variation per mean intensity (TAVPMI) (0.159 ± 0.031 for ground truth; 0.100 ± 0.032 for Li's model; 0.153 ± 0.029 for PGMGVCE), Tenengrad function per mean intensity (TFPMI) (1.222 ± 0.241 for ground truth; 0.981 ± 0.213 for Li's model; 1.194 ± 0.223 for PGMGVCE) and variance function per mean intensity (VFPMI) (0.0811 ± 0.005 for ground truth; 0.0667   ± 0.006 for Li's model; 0.0761   ± 0.006 for PGMGVCE). Conclusions: PGMGVCE presents an innovative and safe approach to VCE in MRI, demonstrating the power of deep learning in enhancing medical imaging. This model paves the way for more accurate and risk-free diagnostic tools in medical imaging. [ABSTRACT FROM AUTHOR]

Ginseng Radix et Rhizoma Rubra (Panax ginseng C.A. Mey, Hongshen, in Chinese) and Ophiopogonis Radix (Ophiopogon japonicus (L.f) Ker-Gawl., Maidong, in Chinese) are traditional Chinese herbal pairs, which were clinically employed to enhance the immune system of cancer patients. This study employed the pharmacokinetic and pharmacodynamic (PK–PD) spectrum-effect association model to investigate the antitumor active substances of P. ginseng and O. japonicus (PG–OJ). The metabolic processes of 20 major bioactive components were analyzed using Ultra-Performance Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (UPLC–MS/MS) in the lung tissue of tumor-bearing mice treated with PG–OJ. The ELISA method was employed to detect the levels of TGF-β1, TNF-α, and IFN-γ in the lung tissue of mice at various time points, and to analyze their changes after drug administration. The results showed that all components presented a multiple peaks absorption pattern within 0.083 to 24 h post-drug administration. The tumor inhibition rate of tumor and repair rate of IFN-γ, TNF-α, and TGF-β1 all increased, indicating a positive therapeutic effect of PG–OJ on A549 tumor-bearing mice. Finally, a PK–PD model based on the GBDT algorithm was developed for the first time to speculate that Methylophiopogonanone A, Methylophiopogonanone B, Ginsenoside Rb1, and Notoginsenoside R1 are the main active components in PG–OJ for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Mitochondria are double-membrane organelles within eukaryotic cells that act as cellular power houses owing to their ability to efficiently generate the ATP required to sustain normal cell function. Also, they represent a "hub" for the regulation of a plethora of processes, including cellular homeostasis, metabolism, the defense against oxidative stress, and cell death. Mitochondrial dysfunctions are associated with a wide range of human diseases with complex pathologies, including metabolic diseases, neurodegenerative disorders, and cancer. Therefore, regulating dysfunctional mitochondria represents a pivotal therapeutic opportunity in biomedicine. Marine ecosystems are biologically very diversified and harbor a broad range of organisms, providing both novel bioactive substances and molecules with meaningful biomedical and pharmacological applications. Recently, many mitochondria-targeting marine-derived molecules have been described to regulate mitochondrial biology, thus exerting therapeutic effects by inhibiting mitochondrial abnormalities, both in vitro and in vivo, through different mechanisms of action. Here, we review different strategies that are derived from marine organisms which modulate specific mitochondrial processes or mitochondrial molecular pathways and ultimately aim to find key molecules to treat a wide range of human diseases characterized by impaired mitochondrial function. [ABSTRACT FROM AUTHOR]

Simple Summary: The environmental issue posed by the distribution of plastic is largely due to their fragmentation into micro- and nanoplastics (MNPs), which are spread across aquatic, atmospheric, and terrestrial ecosystems. The discovery that these particles can easily accumulate in aquatic organisms and edible plants has rapidly drawn global attention to their potential impact on human health. Therefore, based on the One Health approach, this paper will first provide an overview of soil contamination as well as human exposure routes and toxicity pathways of MNPs. It then describes the significant role of livestock animals as a critical link between soil and human exposure, focusing on the lack of the available literature and on the role of livestock animals as reservoirs and carriers of MNP contamination along the food chain. The lack of a standardized method to detect, quantify, and characterize plastic particles in different matrices prevents the determination of their realistic load. For this reason, the development of a database where researchers can document data, both on MNP characteristics and assessment procedures, is also suggested with the perspective of training, in the future, artificial intelligence (AI) tools capable of predicting the most abundant/dangerous polymer(s) and help in guiding decisions to reduce risks to global health. Plastic pollution is a global diffuse threat, especially considering its fragmentation into microplastics (MPs) and nanoplastics (NPs). Since the contamination of the aquatic environment is already well studied, most studies have now focused on the soil. Moreover, the number of studies on the exposure routes and toxic effects of MNPs in humans is continuously increasing. Although MNPs can cause inflammation, cytotoxicity, genotoxicity and immune toxicity in livestock animals, which can accumulate ingested/inhaled plastic particles and transfer them to humans through the food chain, research on this topic is still lacking. In considering farm animals as the missing link between soil/plant contamination and human health effects, this paper aims to describe their importance as carriers and vectors of MNP contamination. As research on this topic is in its early stages, there is no standard method to quantify the amount and the characteristics of MNPs in different matrices. Therefore, the creation of a common database where researchers can report data on MNP characteristics and quantification methods could be helpful for both method standardization and the future training of an AI tool for predicting the most abundant/dangerous polymer(s), thus supporting policy decisions to reduce plastic pollution and perfectly fitting with One Health principles. [ABSTRACT FROM AUTHOR]

The lanthanide metal gadolinium has been used in the healthcare industry as a paramagnetic contrast agent for years. Gadolinium deposition in brain tissue and kidneys has been reported following gadolinium-based contrast agent administration to patients undergoing MRI. This study demonstrates the detrimental effects of gadolinium exposure at the level of the cell membrane. Biophysical analysis using fluorescence spectroscopy and dynamic light scattering illustrates differential interactions of gadolinium ions with key classes of brain membrane lipids, including phosphatidylcholines and sphingomyelins, as well as brain polar extracts and biomimetic brain model membranes. Electrostatic attraction to negatively charged lipids like phosphatidylserine facilitates metal complexation but zwitterionic phosphatidylcholine and sphingomyelin interaction was also significant, leading to membrane rigidification and increases in liposome size. Effects were stronger for fully saturated over monounsaturated acyl chains. The metal targets key lipid classes of brain membranes and these biophysical changes could be very detrimental in biological membranes, suggesting that the potential negative impact of gadolinium contrast agents will require more scientific attention. [ABSTRACT FROM AUTHOR]