Search

To investigate the substrate recognition mechanism of trypsin-like protease cocoonase (CCN), mutational analyses were conducted at key substrate recognition sites, Asp187 and Ser188, and their effects on substrate specificity and enzymatic activity were evaluated. Mutants with the Asp187 substitution exhibited a significant reduction in catalytic activity compared with the wild-type enzyme, whereas the Ser188 mutants displayed a comparatively minor effect on activity. This indicates that Asp187 plays a crucial role in catalytic function, whereas Ser188 serves a complementary role in substrate recognition. Interestingly, the substitution of the Asp187 to Glu or Ser caused novel substrate specificities, resulting in the recognition of Orn and His residues. In addition, when Asp187 and Ser188 were substituted with acidic residues (Glu or Asp), both the precursor proCCN and mature CCN proteins retained highly similar secondary and tertiary structures. This reveals that the structural characteristics of precursor proteins are maintained in the mature proteins, potentially influencing substrate recognition and catalytic function. These findings suggest that the pro-regions of these mutants interact much more tightly with the mature enzyme than in the wild-type CCN. These results provide fruitful insights into the structural determinants governing substrate recognition in enzyme variants. [ABSTRACT FROM AUTHOR]

The analysis of nucleic acid structures, topologies, nano-mechanics and interactions with ligands and other biomacromolecules (most notably proteins) at the single molecule level has become a fundamental topic in molecular biophysics over the last two decades. Techniques such as molecular tweezers, single-molecule fluorescence resonance energy transfer, and atomic force microscopy have enabled us to disclose an unprecedented insight into the mechanisms governing gene replication, transcription and regulation. In this minireview, we survey the main working principles and discuss technical caveats of the above techniques, using as a fil-rouge the history of their achievements in dissecting G-quadruplexes. The revised literature offers a clear example of the superior ability of single-molecule techniques with respect to ensemble techniques to unveil the structural and functional diversity of the several polymorphs corresponding to a single G-quadruplex folding sequence, thus shedding new light on the extreme complexity of these fascinating non-Watson–Crick structures. [ABSTRACT FROM AUTHOR]

This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT's ability to improve therapeutic outcomes through combination strategies is examined. In cancers such as lung, breast, cholangiocarcinoma, and cervical, PDT shows promise in enhancing response rates, reducing recurrence, and minimizing adverse effects when used alongside standard modalities. This study highlights current findings on PDT's mechanisms in complementing chemotherapy, augmenting surgical precision, and enhancing radiotherapeutic effects, thus offering a multi-faceted approach to cancer treatment. Additionally, insights into the clinical application of PDT in these cancers emphasize its potential for reducing tumor resistance and supporting more effective, personalized care. By providing an overview of PDT's synergistic applications across diverse cancer types, this review underscores its emerging significance in oncology as a tool to address traditional treatment limitations. Ultimately, this review aims to inform and inspire researchers and clinicians seeking to refine and innovate cancer therapy strategies through PDT integration, contributing to the advancement of more effective, synergistic cancer treatments. [ABSTRACT FROM AUTHOR]

Deionized water is replacing fluorinated liquids as the preferred choice for two-phase immersion cooling in data centers. Yet, insufficient bubble removal capability at low saturated pressure is a key challenge hindering the widespread application. To solve this issue, this study employs non-ionic surfactant (Tween 20) and asymmetric structures (expanding microchannel) to enhance the boiling performances of deionized water under sub-atmospheric pressure. The research examines the effects of pressure (8.8~38.5 kPa), surfactant concentration (0.1~0.5 mL/L), and heat flux density (10~180 W/cm2) on the boiling heat transfer characteristics and analyzes the mechanism of unusual temperature oscillations induced by surfactants. It was found that the trade-off between the sub-atmospheric pressure, surface tension coefficient, and reduced static contact angle results in pronounced intermittent boiling on the heated surface. Even with the addition of surfactants, the improvement in heat transfer requires demanding conditions. Boiling enhancement throughout all heat flux conditions was achieved when the surfactant concentration was higher than 0.2 mL/L for the expanding microchanneled surface. The heat transfer coefficient reached 6.89 W·cm−2·K−1 under 8.8 kPa, which was 45% higher than without the surfactant. Under the same heat flux and sub-atmospheric pressure, as the concentration increased from 0.1 to 0.5 mL/L, the amplitudes of temperature fluctuation of the plane surface and expanding microchanneled surface decreased from 10 K to 2 K and 18 K to 1 K, respectively. The onset of nucleate boiling and wall superheat of the expanding microchanneled surface gradually decreased with the increase in surfactant concentration, where the onset of nucleate boiling decreased by 10.54 K. When the heat flux is 160 W/cm2, the wall superheat is reduced by 12.8 K. [ABSTRACT FROM AUTHOR]

Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over the years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline the DLBCL tumor biology behind the actual and potential drug targets and address the challenges and drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody–drug conjugates, chimeric antigen receptors, bispecific antibodies and T-cell engagers, and immune checkpoint inhibitors. Candidate drugs explored in ongoing clinical trials are coupled with diverse toxicity issues and refractoriness to drugs. According to the literature on DLBCL, the promise for new therapeutic targets lies in epigenetic alterations, B-cell receptor and NF-κB pathways. Herein, we present putative targets hiding in lipid pathways, ferroptosis, and the gut microbiome that could be used in addition to immuno-chemotherapy to improve the general health status of DLBCL patients, thus increasing the chance of being cured. It may be time to devote more effort to exploring DLBCL metabolism to discover novel druggable targets. We also performed a bibliometric and knowledge-map analysis of the literature on DLBCL published from 2014–2023. [ABSTRACT FROM AUTHOR]

Simple Summary: Systemic therapy is the primary treatment option for patients diagnosed with unresectable hepatocellular carcinoma. The aim of our retrospective study is to assess the comparative effectiveness and safety of two treatment regimens in the first-line setting: lenvatinib plus pembrolizumab and atezolizumab plus bevacizumab. Our findings indicate that both regimens show similar overall survival, progression-free survival, and acceptable safety profiles in real-world conditions. Background: The combination of anti-angiogenic therapy and immune checkpoint inhibitors has revolutionized the management of unresectable hepatocellular carcinoma (uHCC). While an early-phase study demonstrated promising outcomes for lenvatinib plus pembrolizumab (L+P) in treating uHCC, the LEAP-002 trial did not meet its primary endpoint. However, the comparative efficacy between L+P and atezolizumab plus bevacizumab (A+B) as first-line treatment remains a topic of uncertainty. This study aimed to assess the effectiveness and safety of L+P in contrast to A+B among patients diagnosed with uHCC. Methods: We conducted a retrospective analysis of enrolled patients with uHCC who received L+P or A+B as initial systemic treatment at Chang Gung Memorial Hospital from June 2019 to December 2022. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by modified RECIST were compared. Results: 121 patients were recruited, with 37 receiving L+P and 84 receiving A+B. Among them, 95 (78.5%) patients were BCLC stage C, and 99 (81.8%) patients had viral etiology for HCC, predominantly chronic HBV (68.6%). Both the L+P and the A+B groups demonstrated comparable OS (18.2 months versus 14.6 months, p = 0.35) and PFS (7.3 months versus 8.9 months, p = 0.75). The ORR and DCR were similar. After propensity score matching, the results remained consistent between the matched patients. Treatment-related adverse events of any grade occurred in 30 (81.1%) in the L+P group and 62 (73.8%) in the A+B group. Conclusions: Our findings suggest that L+P and A+B exhibit comparable efficacy and safety profiles in real-world settings. [ABSTRACT FROM AUTHOR]

The ecological conservation of nature reserves has garnered considerable attention and is subject to stringent management in China. However, the majority of these areas have a history of underdeveloped economies and require urgent improvements in the well-being of local communities. Effectively coupling and harmonizing the dynamic relationship between ecosystem services and socio-economic development has emerged as a crucial concern for nature reserves. Therefore, further exploration is needed to achieve a spatio-temporal balance and alignment between the supply and demand of ESs in nature reserves in China. Utilizing multiple datasets, RULSE, and bivariate autocorrelation methods, this study investigated the spatio-temporal evolution of the ecosystem services supply–demand ratio (ESDR) and supply–demand spatial matches for soil conservation services (SCSs) in the Qinling Mountains (QMs) from 2000 to 2020. The results indicated the following: (1) Over the years, the supply of SCSs exhibited a consistently high level, with an upward trend observed in 63.10% of the QMs, while the demand for SCSs is generally low, with a decreasing trend observed in 82.68% of the QMs. (2) The supply and demand of SCSs remained favorable, with a positive ESDR reaching 82.19% of the QMs. From 2000 to 2010, there was a significant decline in ESDR; however, a substantial rebound was observed in the ESDR across the region from 2010 to 2020. (3) Over years, the majority of counties and districts exhibited positive values in ESDR. When examining cities, Weinan, Xi'an, and Ankang demonstrated relatively consistent patterns with higher ESDR values over time. In 2000, the ESDR on the northern slope exhibited lower values than that on the southern slope; however, this situation subsequently underwent a reversal. (4) The spatial distribution of SCS supply and demand was predominantly characterized by matching regions exhibiting either High Supply–High Demand or Low Supply–Low Demand for years. This study suggests that the supply and demand dynamics of SCSs in the Qinling Mountains have been favorable in recent years, with consistent spatial supply–demand matches. These findings can provide valuable insights for similar nature reserves aiming to implement ecological environmental protection and achieve sustainable development. The future research endeavors, however, should strive to expand upon these findings by exploring the supply and demand patterns associated with other ESs across diverse nature reserves, while considering their unique geographical characteristics, in order to promote more rational ecological management strategies. [ABSTRACT FROM AUTHOR]

Stator faults are one of the common issues in pumped storage generators, significantly impacting their performance and safety. To ensure the safe and stable operation of pumped storage generators, a stator fault diagnosis method based on an improved short-time Fourier transform (STFT)-support vector data description (SVDD) hybrid algorithm is proposed. This method establishes a fault model for inter-turn short circuits in the stator windings of pumped storage generators and analyzes the electrical and magnetic states associated with such faults. Based on the three-phase current signals observed during an inter-turn short circuit fault in the stator windings, the three-phase currents are first converted into two-phase currents using the principle of equal magnetic potential. Then, the STFT is applied to transform the time-domain signals of the stator's two-phase currents into frequency-domain signals, and the resulting fault current spectrum is input into the improved SVDD network for processing. This ultimately outputs the diagnosis result for inter-turn short circuit faults in the stator windings of the pumped storage generator. Experimental results demonstrate that this method can effectively distinguish between normal and faulty states in pumped storage generators, enabling the diagnosis of inter-turn short circuit faults in stator windings with low cross-entropy loss. Through analysis, under small data sample conditions, the accuracy of the proposed method in this paper can be improved by up to 7.2%. In the presence of strong noise interference, the fault diagnosis accuracy of the proposed method remains above 90%, and compared to conventional methods, the fault diagnosis accuracy can be improved by up to 6.9%. This demonstrates that the proposed method possesses excellent noise robustness and small sample learning ability, making it effective in complex, dynamic, and noisy environments. [ABSTRACT FROM AUTHOR]

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4+ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions. [ABSTRACT FROM AUTHOR]

Background: Hypoxia plays a crucial role in regulating various cellular functions, including ion-transport mechanisms in the kidney. The sodium-chloride co-transporter (NCC) is essential for sodium reabsorption in the distal convoluted tubule (DCT). However, the effects of hypoxia on NCC expression and its regulatory pathways remain unclear. We aimed to explore the effects and potential mechanisms of hypoxia on NCC in vitro. Methods: mDCT15 cells were treated with cobalt chloride (CoCl2) at a concentration of 300 μmol/L to induce hypoxia. The cells were harvested at different time points, namely 30 min, 1 h, 6 h, and 24 h, and the expression of NCC and CaMKII-β was analyzed using Western blot. Results: A time-dependent upregulation of NCC and CaMKII-β expression in response to CoCl2-induced hypoxia. KN93 reversed the effect of CoCl2 on NCC and phosphorylated NCC expression. Conclusions: Hypoxia, mediated through cobalt chloride treatment, upregulates NCC expression via the CaMKII-β pathway in mDCT15 cells. [ABSTRACT FROM AUTHOR]

Simple Summary: With advances in radiological imaging and its increased use, small nodules are being detected more frequently. Surgical resection is often the final option for diagnosis and treatment; however, small nodules may be too small to be detected during surgery. The lungs are soft, deformable organs that can change shape during respiratory phases and surgical procedures. Thus, surgeons rely on preoperative or intraoperative markings for nodule identification and precise resection. Furthermore, two randomized clinical trials found that sublobar resection could be an alternative treatment for early-stage non-small-cell lung cancer. Therefore, the demand for preoperative or intraoperative marking techniques is increasing, particularly for wedge resection or segmentectomy. In this study, we provide a narrative review of the current status and future perspectives of preoperative and intraoperative markings in thoracic surgery. The widespread implementation of lung cancer screening and thin-slice computed tomography (CT) has led to the more frequent detection of small nodules, which are commonly referred to thoracic surgeons. Surgical resection is the final diagnostic and treatment option for such nodules; however, surgeons must perform preoperative or intraoperative markings for the identification of such nodules and their precise resection. Historically, hook-wire marking has been performed more frequently worldwide; however, lethal complications, such as air embolism, have been reported. Therefore, several surgeons have recently attempted to develop novel preoperative and intraoperative markers. For example, transbronchial markings, such as virtual-assisted lung mapping and intraoperative markings using cone-beam computed tomography, have been developed. This review explores various marking methods that have been practically applied for a better understanding of preoperative and intraoperative markings in thoracic surgery. Recently, several attempts have been made to perform intraoperative molecular imaging and dynamic virtual three-dimensional computed tomography for the localization, diagnosis, and margin assessment of small nodules. In this narrative review, the current status and future perspectives of preoperative and intraoperative markings in thoracic surgery are examined for a better understanding of these techniques. [ABSTRACT FROM AUTHOR]

The mechanical properties of proteins/peptides play an essential role in their functionalities and implications, as well as their structure and dynamic properties. Understanding mechanical properties is pivotal to our knowledge of protein folding and the molecular basis of diverse cellular processes. Herein, we present a computational approach using ab initio quantum mechanical calculations to determine the mechanical properties—such as bulk modulus, shear modulus, Young's modulus, and Poisson's ratio—of a solvated Arg-Gly-Asp (RGD) peptide model. Since this peptide serves as the RGD-directed integrin recognition site and may participate in cellular adhesion, it is considered a promising small peptide for medicinal applications. This successful approach paves the way for investigating larger and more complex biomolecules. [ABSTRACT FROM AUTHOR]

The application of binary gas mixtures consisting of heptafluorobutyronitrile (C4F7N) and carbon dioxide (CO2) in AC GIS is currently attracting much attention. Therefore, the evaluation of the gas–solid interface charge distribution characteristics of epoxy resin is indispensable. Additionally, the phase-dependency of the charging behavior remains not fully understood. We simulated coaxial electrode structure in GIS and investigated the surface charge distribution on a down-scaled epoxy insulator. The influence of the truncated phase angle and duration of AC voltage on charge behavior were analyzed, and the charge transport mechanism under AC voltage was theoretically analyzed. The results showed that there was a noticeable negative charge speckle with the presence of the metal particle and the accumulated negative charge on the insulator surface far exceeded that of the positive charge. The maximum surface charge density and the amount of surface charge accumulated first increased and then decreased over time. It was found that the phase angle has a negligible influence on the surface charge distribution at the cut-off moment. [ABSTRACT FROM AUTHOR]

An atmospheric pressure plasma source of the microwave plasma pencil type utilizing a coaxial line is presented. The generated plasma takes the form of a cylinder up to about 30 mm long and up to 5 mm in diameter. It is suitable for surface sterilization, surface treatment, and material processing. This study numerically analyzes the electromagnetic radiation emitted by the plasma pencil, which compromises performance and poses safety risks. Electric field distributions, radiation patterns, the ratio of the power entering the discharge to the incident wave power, and the ratio of radiated power to entering power were numerically investigated for different plasma parameters and pencil lengths. Results indicate that increasing electron density, gas temperature, plasma length, and pencil length increases the radiated power by up to more than 60% of the entering power, and the radiation patterns can be highly non-uniform with strong backward lobe. The numerical finding were qualitatively confirmed experimentally. It was also found that it is possible to reduce radiation from the device by using appropriately designed cones, the presence of which does not impede its performance. [ABSTRACT FROM AUTHOR]

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare but aggressive malignancy associated with the human T-cell lymphotropic virus type 1 (HTLV-1). ATLL is a challenging malignancy characterized by its aggressive nature and poor prognosis. Despite advancements in treatment, relapse rates remain high. Donor lymphocyte infusion (DLI) is a promising therapeutic option post-hematopoietic stem cell transplantation (HSCT) to prevent relapse. However, the prophylactic use of DLI in ATLL patients remains underexplored. We report the case of a 45-year-old female diagnosed with ATLL. Following induction chemotherapy and successful HSCT, a modified prophylactic DLI regimen was administered, consisting of gradually increasing doses of donor lymphocytes. The patient demonstrated a favorable response with no significant graft-versus-host disease (GVHD) and maintained remission over a 40-month follow-up period, suggesting a potential benefit of this approach. This case highlights the potential efficacy and safety of modified prophylactic DLI in ATLL patients, warranting further investigation. Our findings suggest that modified prophylactic DLI is a viable option for ATLL patients post-HSCT, offering a balance between efficacy and safety. Future research should focus on optimizing DLI protocols and exploring biomarkers for response prediction. [ABSTRACT FROM AUTHOR]

The incidence of breast implant illness (BII) and BII-related explant procedures has not decreased with current surgical and treatment techniques. It is speculated the main underlying cause of BII complications is the result of chronic, sub-clinical infections residing on and around the implant. The infection, and subsequent biofilm, produce antagonistic compounds that drive chronic inflammation and immune responses. In this study, the microbial communities in over 600 consecutive samples of infected explant capsules and tissues were identified via next-generation sequencing to identify any commonality between samples. The majority of the bacteria identified were Gram-positive, with Cutibacterium acnes and Staphylococcus epidermidis being the dominant organisms. No correlation between sample richness and implant filling was found. However, there was a significant correlation between sample richness and patient age. Due to the complex nature, breast augmentation failures may be better addressed from a holistic approach than one of limited scope. [ABSTRACT FROM AUTHOR]

This narrative review provides a comprehensive analysis of the several methods and technologies employed to measure handgrip strength (HGS), a significant indicator of neuromuscular strength and overall health. The document evaluates a range of devices, from traditional dynamometers to innovative sensor-based systems, and assesses their effectiveness and application in different demographic groups. Special attention is given to the methodological aspects of HGS estimation, including the influence of device design and measurement protocols. Endogenous factors such as hand dominance and size, body mass, age and gender, as well as exogenous factors including circadian influences and psychological factors, are examined. The review identifies significant variations in the implementation of HGS measurements and interpretation of the resultant data, emphasizing the need for careful consideration of these factors when using HGS as a diagnostic or research tool. It highlights the necessity of standardizing measurement protocols to establish universal guidelines that enhance the comparability and consistency of HGS assessments across various settings and populations. [ABSTRACT FROM AUTHOR]

With regard to the heating technology of small test specimens (D < 1 inch, i.e., 25.4 mm), only a limited amount of data and literature are available for making adequate technological decisions. Heating time of small geometric shapes is influenced by the technological parameters of the furnace, the temperature, the disposition technique in the furnace and the geometric characteristics of the workpiece. How to shorten heating time to achieve a suitable material structure is a vital question, while considerable energy is saved at the same time. Among the geometric characteristics, shape dependence is one of the important aspects that must be taken into account in terms of heating technology. Shape dependence is usually taken into account with empirically produced correction factors, which can result in significant oversizing of heating time, energy-wasting technology and material structure of insufficient fineness. In the course of our work, we investigated and compared the shape dependence of cylindrical and prismatic specimens with the same surface-to-volume ratios, which were combined with surface heat transfer analyses and geometric effect tests to formulate new approximate equations for determining heating time. As a result, we could mathematically derive a relationship between heating time, size and shape of the active surfaces, the correlation of which can shorten heating time by 20%. In addition, a shape factor (1.125) between cylinder and prismatic-shaped specimens was determined, which can be used with the new equation to calculate heating time for similar specimens. At last, a relationship is developed between the amount of heat that can be stored in the body during heat equalization and the complexity of the shape, which can be characterized through ratios depending on heating times and active surfaces in the function of total surface/volume ratio. Based on this relationship it can be determined more precisely when heat equalization occurs; therefore, shorter heating time can be achieved. In conclusion, with the help of this new method, optimal heating time for structural steel components, in the case of small cross-section and weight, can be determined. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a diverse malignancy originating from myeloid progenitor cells, with significant genetic and clinical variability. Modern classification systems like those from the World Health Organization (WHO) and European LeukemiaNet use immunophenotyping, molecular genetics, and clinical features to categorize AML subtypes. This classification highlights crucial genetic markers such as FLT3, NPM1 mutations, and MLL-AF9 fusion, which are essential for prognosis and directing targeted therapies. The MLL-AF9 fusion protein is often linked with therapy-resistant AML, highlighting the risk of relapse due to standard chemotherapeutic regimes. In this sense, factors like the ZEB, SNAI, and TWIST gene families, known for their roles in epithelial–mesenchymal transition (EMT) and cancer metastasis, also regulate hematopoiesis and may serve as effective therapeutic targets in AML. These genes contribute to cell proliferation, differentiation, and extramedullary hematopoiesis, suggesting new possibilities for treatment. Advancing our understanding of the molecular mechanisms that promote AML, especially how the bone marrow microenvironment affects invasion and drug resistance, is crucial. This comprehensive insight into the molecular and environmental interactions in AML emphasizes the need for ongoing research and more effective treatments. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of small regulatory RNA that are generated via core protein machinery. The miRNAs direct gene-silencing mechanisms to mediate an essential role in gene expression regulation. In mollusks, miRNAs have been demonstrated to be required to regulate gene expression in various biological processes, including normal development, immune responses, reproduction, and stress adaptation. In this study, we aimed to establishment the requirement of the miRNA pathway as part of the molecular response of exposure of Biomphalaria glabrata (snail host) to Schistosoma mansoni (trematode parasite). Initially, the core pieces of miRNA pathway protein machinery, i.e., Drosha, DGCR8, Exportin-5, Ran, and Dicer, together with the central RNA-induced silencing complex (RISC) effector protein Argonaute2 (Ago2) were elucidated from the B. glabrata genome. Following exposure of B. glabrata to S. mansoni miracidia, we identified significant expression up-regulation of all identified pieces of miRNA pathway protein machinery, except for Exportin-5, at 16 h post exposure. For Ago2, we went on to show that the Bgl-Ago2 protein was localized to regions surrounding the sporocysts in the digestive gland of infected snails 20 days post parasite exposure. In addition to documenting elevated miRNA pathway protein machinery expression at the early post-exposure time point, a total of 13 known B. glabrata miRNAs were significantly differentially expressed. Of these thirteen B. glabrata miRNAs responsive to S. mansoni miracidia exposure, five were significantly reduced in their abundance, and correspondingly, these five miRNAs were determined to putatively target six genes with significantly elevated expression and that have been previously associated with immune responses in other animal species, including humans. In conclusion, this study demonstrates the central importance of a functional miRNA pathway in snails, which potentially forms a critical component of the immune response of snails to parasite exposure. Further, the data reported in this study provide additional evidence of the complexity of the molecular response of B. glabrata to S. mansoni infection: a molecular response that could be targeted in the future to overcome parasite infection and, in turn, human schistosomiasis. [ABSTRACT FROM AUTHOR]

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative with notable psychoactive properties and emerging therapeutic potential, particularly for treating post-traumatic stress disorders (PTSD) and substance use disorders. However, its use remains controversial due to inter-individual variability influenced by both environmental and genetic factors. In this context, pharmacogenomics could play a crucial role in guiding MDMA treatment by identifying individuals with genetic predispositions affecting their response to MDMA. Tailoring treatment plans based on individual's genetic makeup may enhance therapeutic outcomes and minimize adverse effects, leading to safer and more effective use of MDMA in clinical settings. Literature analysis reveals that the influence of genetic variants within genes encoded for enzymes involved in MDMA metabolism and/or pharmacodynamics (PD) targets have been relatively under-investigated in humans. Some studies have pointed out associations between MDMA-induced effects and polymorphisms. For example, the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and cardiovascular MDMA-induced effects. Similarly, polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with several MDMA-induced adverse effects including mood disorders. However, despite these findings, only a few associations have been highlighted. Furthermore, some genes encoded for MDMA targets have been only poorly investigated, representing a significant research gap. These observations underscore the need for large-scale, controlled pharmacogenomics studies focusing on a broad panel of genes involved into MDMA pharmacokinetics and PD. Such studies could provide critical insights for optimizing MDMA's therapeutic use and minimizing its risks. [ABSTRACT FROM AUTHOR]

In this write-up, we provide an overview of the existing theoretical framework concerning rare kaon decays, with a particular emphasis on flavour-changing neutral current processes. These decays offer crucial indirect pathways for investigating short-distance new physics. Our discussion will encompass standard model predictions for relevant observables, alongside an assessment of their capacity to probe new physics through a comparison with experimental data. [ABSTRACT FROM AUTHOR]

Despite the sector's minor contribution (0.5%) to the Gross National Product, the fisheries sector in Cyprus is particularly important to the micro economy of coastal communities, offering direct and indirect employment and supporting small family businesses. Like any industry, the Cypriot fisheries sector faces its own challenges and opportunities. The current study aimed to identify the strengths, weaknesses, opportunities, and threats (SWOT) of the fisheries sector in Cyprus based on fishers' knowledge and to provide strategic recommendations based on the sector's identified needs. Following a participatory approach, a workshop with 30 small-scale fishers, six large pelagic longline fishers, and three scientists was conducted in November 2023. Fishers and scientists worked together to conduct the SWOT and the TOWS matrix (a reverse SWOT) analyses. Findings from the SWOT–TOWS analyses were used to develop strategic recommendations for the sector. Finally, using the Impact–Effort prioritisation method, the strategic recommendations were prioritised according to their potential impact on the sector and the effort required for their implementation. Based on the analyses, the study proposes 12 strategic recommendations that could significantly improve the sector's overall performance and sustainability, which if applied will give a light of hope for the future of the Cypriot fisheries sector. [ABSTRACT FROM AUTHOR]

Calcification plays a key role in biological processes, and breakdown of the regulatory mechanism results in a pathological state such as ectopic calcification. We hypothesized that ENPP1, the enzyme that produces the calcification inhibitor pyrophosphate, is transcriptionally regulated by Nrf2, and that Nrf2 activation augments ENPP1 expression to inhibit ectopic calcification. Cell culture experiments were performed using mouse osteoblastic cell line MC3T3-E1. Nrf2 was activated by 5-aminolevulinic acid and sodium ferrous citrate. Nrf2 overexpression was induced by the transient transfection of an Nrf2 expression plasmid. ENPP1 expression was monitored by real-time RT-PCR. Because the promoter region of ENPP1 contains several Nrf2-binding sites, chromatin immunoprecipitation using an anti-Nrf2 antibody followed by real-time PCR (ChIP-qPCR) was performed. The relationship between Nrf2 activation and osteoblastic differentiation was examined by alkaline phosphatase (ALP) and Alizarin red staining. We used mice with a hypomorphic mutation in ENPP1 (ttw mice) to analyze whether Nrf2 activation inhibits ectopic calcification. Nrf2 and Nrf2 overexpression augmented ENPP1 expression and inhibited osteoblastic differentiation, as indicated by ALP expression and calcium deposits. ChIP-qPCR showed that some putative Nrf2-binding sites in the ENPP1 promoter region were bound by Nrf2. Nrf2 activation inhibited ectopic calcification in mice. ENPP1 gene expression was transcriptionally regulated by Nrf2, and Nrf2 activation augmented ENPP1 expression, leading to the attenuation of osteoblastic differentiation and ectopic calcification in vitro and in vivo. Nrf2 activation has a therapeutic potential for preventing ectopic calcification. [ABSTRACT FROM AUTHOR]

The bulk and surface properties of materials based on nickel and aluminum oxides and hydroxides, as such or after reduction processes, are reviewed and discussed critically. The actual and potential industrial applications of these materials, both in reducing conditions and in oxidizing conditions, are summarized. Mechanisms for reactant molecule activation are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma with vascular invasion has a poor prognosis and inconsistent treatment evidence. Studies of portal vein tumor thrombus are relatively frequent; however, limited case studies of bile duct tumor thrombus and hepatic vein tumor thrombus exist. In this review, we also focus on bile duct tumor thrombus and hepatic vein tumor thrombus and review the current published studies. Vascular invasion of hepatocellular carcinoma involves tumor plugs in the main trunk of the portal vein, bile ducts, and veins, and it indicates poor prognosis. It is often associated with portal hypertension, which requires evaluation and management. Treatment includes hepatic resection, systemic pharmacotherapy, hepatic arterial infusion chemotherapy, and radiation therapy. Recurrence rates post-hepatic resection are high, and systemic drug therapy often has limited therapeutic potential in patients with a poor hepatic reserve. Single therapies are generally inadequate, necessitating combining multiple therapies with adjuvant and systemic pharmacotherapy before and after hepatectomy. This narrative review will provide an overview of the treatment of hepatocellular carcinoma with vascular invasion. [ABSTRACT FROM AUTHOR]

Cancer is one of the deadliest diseases to humanity. There is significant progress in treating this disease, but developing some drugs that can fight this disease remains a challenge in the field of medical research. Thirteen new 1,2,3-triazole linked tetrahydrocurcumin derivatives were synthesized by click reaction, including a 1,3-dipolar cycloaddition reaction of tetrahydrocurcumin baring monoalkyne with azides in good yields, and their in vitro anticancer activity against four cancer cell lines, including human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2), and human colon carcinoma (HCT-116) were investigated using MTT(3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyltetraz-olium bromide) assay. The newly synthesized compounds had their structures identified using NMR HRMS and IR techniques. Some of prepared compounds, including compounds 4g and 4k, showed potent cytotoxic activity against four cancer cell lines compared to the positive control of cisplatin and tetrahydrocurcumin. Compound 4g exhibited anticancer activity with a IC50 value of 1.09 ± 0.17 µM against human colon carcinoma HCT-116 and 45.16 ± 0.92 µM against A549 cell lines compared to the positive controls of tetrahydrocurcumin and cisplatin. Moreover, further biological examination in HCT-116 cells showed that compound 4g can arrest the cell cycle at the G1 phase. A docking study revealed that the potential mechanism by which 4g exerts its anti-colon cancer effect may be through inhabiting the binding of APC–Asef. Compound 4g can be used as a promising lead for further exploration of potential anticancer agents. [ABSTRACT FROM AUTHOR]

mTOR inhibitors (mTOR-Is) may induce proteinuria in kidney transplant recipients through podocyte damage. However, the mechanism has only been partially defined. Total cell lysates and supernatants of immortalized human podocytes treated with different doses of everolimus (EVE) (10, 100, 200, and 500 nM) for 24 h were subjected to mass spectrometry-based proteomics. Support vector machine and partial least squares discriminant analysis were used for data analysis. The results were validated in urine samples from 28 kidney transplant recipients receiving EVE as part of their immunosuppressive therapy. We identified more than 7000 differentially expressed proteins involved in several pathways, including kinases, cell cycle regulation, epithelial–mesenchymal transition, and protein synthesis, according to gene ontology. Among these, after statistical analysis, 65 showed an expression level significantly and directly correlated with EVE dosage. Polo-Like Kinase 1 (PLK1) content was increased, whereas osteopontin (SPP1) content was reduced in podocytes and supernatants in a dose-dependent manner and significantly correlated with EVE dose (p < 0.0001, FDR < 5%). Similar results were obtained in the urine of kidney transplant patients. This study analyzed the impact of different doses of mTOR-Is on podocytes, helping to understand not only the biological basis of their therapeutic effects but also the possible mechanisms underlying proteinuria. [ABSTRACT FROM AUTHOR]

QCD with the isospin chemical potential μ I is a useful laboratory to delineate the microphysics in dense QCD. To study the quark–hadron continuity, we use a quark–meson model that interpolates hadronic and quark matter physics at microscopic level. The equation of state is dominated by mesons at low density but taken over by quarks at high density. We extend our previous studies with two flavors to the three-flavor case to study the impact of the strangeness, which may be brought by kaons (K + , K 0) = (u s ¯ , s d ¯) and the UA(1) anomaly. In the normal phase, the excitation energies of kaons are reduced by μ I in the same way as hyperons in nuclear matter at the finite baryon chemical potential. Once pions condense, kaon excitation energies increase as μ I does. Moreover, strange quarks become more massive through the UA(1) coupling to the condensed pions. Hence, at zero and low temperature, the strange hadrons and quarks are highly suppressed. The previous findings in two-flavor models, sound speed peak, negative trace anomaly, gaps insensitive to μ I , persist in our three-flavor model and remain consistent with the lattice results to μ I ∼ 1 GeV. We discuss the non-perturbative power corrections and quark saturation effects as important ingredients to understand the crossover equations of state measured on the lattice. [ABSTRACT FROM AUTHOR]

Air pollution is one of the greatest environmental risks to health, with 99% of the world's population living where the World Health Organization's air quality guidelines were not met. In addition to the respiratory and cardiovascular systems, the brain is another potential target of air pollution. Population- and experiment-based studies have shown that air pollution may affect mental health through direct or indirect biological pathways. The evidence for mental hazards associated with air pollution has been well documented. However, previous reviews mainly focused on epidemiological associations of air pollution with some specific mental disorders or possible biological mechanisms. A systematic review is absent for early effect biomarkers for characterizing mental health hazards associated with ambient air pollution, which can be used for early warning of related mental disorders and identifying susceptible populations at high risk. This review summarizes possible biomarkers involved in oxidative stress, inflammation, and epigenetic changes linking air pollution and mental disorders, as well as genetic susceptibility biomarkers. These biomarkers may provide a better understanding of air pollution's adverse effects on mental disorders and provide future research direction in this arena. [ABSTRACT FROM AUTHOR]

Around 30–60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case–control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models. [ABSTRACT FROM AUTHOR]

Within flowers, the style channel receives pollen and transmits male gametes inside elongating pollen tubes to ovules. The styles of maize/corn are called silks. Fertilization-stage silks possess complex microbiomes, which may partially derive from pollen. These microbiomes lack functional analysis. We hypothesize that fertilization-stage silk microbiomes promote host fertilization to ensure their own vertical transmission. We further hypothesize that these microbes encode traits to survive stresses within the silk (water/nitrogen limitation) and pollen (dehydration/aluminum) habitats. Here, bacteria cultured from fertilization-stage silks of 14 North American maize genotypes underwent genome mining and functional testing, which revealed osmoprotection, nitrogen-fixation, and aluminum-tolerance traits. Bacteria contained auxin biosynthesis genes, and testing confirmed indole compound secretion, which is relevant, since pollen delivers auxin to silks to stimulate egg cell maturation. Some isolates encoded biosynthetic/transport compounds known to regulate pollen tube guidance/growth. The isolates encoded ACC deaminase, which degrades the precursor for ethylene that otherwise accelerates silk senescence. The findings suggest that members of the microbiome of fertilization-stage silks encode adaptations to survive the stress conditions of silk/pollen and have the potential to express signaling compounds known to impact reproduction. Overall, whereas these microbial traits have traditionally been assumed to primarily promote vegetative plant growth, this study proposes they may also play selfish roles during host reproduction. [ABSTRACT FROM AUTHOR]

cis-1-amino-2-indanol is an important building block in many areas of chemistry. Indeed, this molecule is currently used as skeleton in many ligands (BOX, PyBOX...), catalysts and chiral auxiliaries. Moreover, it has been incorporated in numerous bioactive structures. The major issues during its synthesis are the control of cis-selectivity, for which various strategies have been devised, and the enantioselectivity of the reaction. This review highlights the various methodologies implemented over the last few decades to access cis-1-amino-2-indanol in racemic and enantioselective manners. In addition, the various substitution patterns on the aromatic ring and their preparations are listed. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC. [ABSTRACT FROM AUTHOR]

Liver cancer ranks among the most prevalent malignancies globally and stands as a leading cause of cancer-related mortality. Numerous isothiazolone derivatives and analogues have been synthesized and investigated for their potential as anticancer agents; however, limited data exist regarding their efficacy against liver cancer. In the present study, two nitrophenyl-isothiazolones, the 5-benzoyl-2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoA) and the 2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoB), were preliminarily investigated for their cytotoxicity against hepatoma human (Huh7) cells as a liver cancer model and Immortalized Human Hepatocytes (IHHs) as a model of non-cancerous hepatocytes. IsoB, derived from IsoA after removal of the benzoyl moiety, demonstrated the highest cytotoxic effect against Huh7 cells with CC50 values of 19.3 μΜ at 24 h, 16.4 μΜ at 48 h, and 16.2 μΜ at 72 h of incubation, respectively. IsoB also exhibited selective toxicity against the liver cancerous Huh7 cells compared to IHH cells, reinforcing its role as a potent and selective anticancer agent. Remarkably, the cytotoxicity of IsoB was higher when compared with the standard chemotherapeutical agent 5-fluorouracil (5-FU), which also failed to exhibit higher toxicity against the liver cancerous cell lines. Moreover, IsoB-treated Huh7 cells presented a noteworthy reduction in mitochondrial membrane potential (ΔΨm) after 48 and 72 h, while mitochondrial superoxide levels showed an increase after 24 h of incubation. The molecular mechanism of the IsoB cytotoxic effect was also investigated using RT-qPCR, revealing an apoptosis-mediated cell death along with tumor suppressor TP53 overexpression and key-oncogene MYCN downregulation. [ABSTRACT FROM AUTHOR]

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages and presents a novel, efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses, from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. The best practices and rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls, and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwhile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of these multivalent soft-matter nanorods. [ABSTRACT FROM AUTHOR]

Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis. [ABSTRACT FROM AUTHOR]

Simple Summary: Anti-cancer treatments often entail a spectrum of adverse effects, and among these, skin cancers have been under significant scrutiny. From traditional immunosuppressants such as methotrexate to chemotherapeutic agents such as fludarabine and hydroxyurea, as well as from new targeted therapies such as ibrutinib and JAK inhibitors to MAP kinase pathway inhibitors and sonic hedgehog pathway inhibitors, each treatment modality poses unique mechanisms of action and associated risks of skin cancer. In addition, the role of radiotherapy in inducing secondary skin cancers underscores the long-term consequences of therapeutic interventions. It is crucial to ascertain whether a specific therapy increases the risk of skin cancer so that appropriate screening measures can be implemented before and during treatment. Our comprehensive review not only investigates various medications and treatment modalities linked with heightened skin cancer risks, elucidating their mechanisms of action and relevant properties, but also proposes effective strategies for managing patients undergoing such therapies. Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased risk of skin cancers linked to different anti-cancer treatments, including classic immunosuppressants such as methotrexate (MTX), chemotherapeutic agents such as fludarabine and hydroxyurea (HU), targeted therapies like ibrutinib and Janus Kinase inhibitors (JAKi), mitogen-activated protein kinase pathway (MAPKP) inhibitors, sonic hedgehog pathway (SHHP) inhibitors, and radiotherapy. MTX, a widely used immunosuppressant in different fields, is associated with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM), particularly at higher dosages. Fludarabine, HU, and other chemotherapeutic agents increase the risk of non-melanoma skin cancers (NMSCs), including cSCC and BCC. Targeted therapies like ibrutinib and JAKi have been linked to an elevated incidence of NMSCs and CM. MAPKP inhibitors, particularly BRAF inhibitors like vemurafenib, are associated with the development of cSCCs and second primary melanomas (SPMs). SHHP inhibitors like vismodegib have been linked to the emergence of cSCCs following treatment for BCC. Additionally, radiotherapy carries carcinogenic risks, especially for BCCs, with increased risks, especially with younger age at the moment of exposure. Understanding these risks and implementing appropriate screening is crucial for effectively managing patients undergoing anti-cancer therapies. [ABSTRACT FROM AUTHOR]

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Expanding possibilities for foreign gene expression in cucurbits, we present a novel approach utilising a bipartite vector system based on the cucumber green mottle mosaic virus (CGMMV) genome. Traditional full-length CGMMV vectors face limitations such as a restricted cargo capacity and unstable foreign gene expression. To address these challenges, we developed two 'deconstructed' CGMMV genomes, DG-1 and DG-2. DG-1 features a major internal deletion, resulting in the loss of crucial replicase enzyme domains, rendering it incapable of self-replication. However, a staggered infiltration of DG-1 in CGMMV-infected plants enabled successful replication and movement, facilitating gene-silencing experiments. Conversely, DG-2 was engineered to enhance replication rates and provide multiple cloning sites. Although it exhibited higher replication rates, DG-2 remained localised within infiltrated tissue, displaying trans-replication and restricted movement. Notably, DG-2 demonstrated utility in expressing GFP, with a peak expression observed between 6 and 10 days post-infiltration. Overall, our bipartite system represents a significant advancement in functional genomics, offering a robust tool for foreign gene expression in Nicotiana benthamiana. [ABSTRACT FROM AUTHOR]

Regional lung ventilation assessment is a critical tool for the early detection of lung diseases and postoperative evaluation. Biosensor-based impedance measurements, known for their non-invasive nature, among other benefits, have garnered significant attention compared to traditional detection methods that utilize pressure sensors. However, solely utilizing overall thoracic impedance fails to accurately capture changes in regional lung air volume. This study introduces an assessment method for lung ventilation that utilizes impedance data from the five lobes, develops a nonlinear model correlating regional impedance with lung air volume, and formulates an approach to identify regional ventilation obstructions based on impedance variations in affected areas. The electrode configuration for the five lung lobes was established through numerical simulations, revealing a power–function nonlinear relationship between regional impedance and air volume changes. An analysis of 389 pulmonary function tests refined the equations for calculating pulmonary function parameters, taking into account individual differences. Validation tests on 30 cases indicated maximum relative errors of 0.82% for FVC and 0.98% for FEV1, all within the 95% confidence intervals. The index for assessing regional ventilation impairment was corroborated by CT scans in 50 critical care cases, with 10 validation trials showing agreement with CT lesion localization results. [ABSTRACT FROM AUTHOR]

Cervical auscultation is a simple, noninvasive method for diagnosing dysphagia, although the reliability of the method largely depends on the subjectivity and experience of the evaluator. Recently developed methods for the automatic detection of swallowing sounds facilitate a rough automatic diagnosis of dysphagia, although a reliable method of detection specialized in the peculiar feature patterns of swallowing sounds in actual clinical conditions has not been established. We investigated a novel approach for automatically detecting swallowing sounds by a method wherein basic statistics and dynamic features were extracted based on acoustic features: Mel Frequency Cepstral Coefficients and Mel Frequency Magnitude Coefficients, and an ensemble learning model combining Support Vector Machine and Multi-Layer Perceptron were applied. The evaluation of the effectiveness of the proposed method, based on a swallowing-sounds database synchronized to a video fluorographic swallowing study compiled from 74 advanced-age patients with dysphagia, demonstrated an outstanding performance. It achieved an F1-micro average of approximately 0.92 and an accuracy of 95.20%. The method, proven effective in the current clinical recording database, suggests a significant advancement in the objectivity of cervical auscultation. However, validating its efficacy in other databases is crucial for confirming its broad applicability and potential impact. [ABSTRACT FROM AUTHOR]

Simple Summary: We developed an attention-based whole slide image (WSI)-level classification deep learning model employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The area under the curve of our model was 0.781–0.824, higher than that of previous artificial intelligence (AI) studies with only WSIs. Our AI model, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current JSCCR guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC. According to the current guidelines, additional surgery is performed for endoscopically resected specimens of early colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM). However, the rate of LNM is 2.1–25.0% in cases treated endoscopically followed by surgery, indicating a high rate of unnecessary surgeries. Therefore, this study aimed to develop an artificial intelligence (AI) model using H&E-stained whole slide images (WSIs) without handcrafted features employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. To validate with an independent cohort, we developed a model with four versions comprising various combinations of training and test sets using H&E-stained WSIs from endoscopically (400 patients) and surgically resected specimens (881 patients): Version 1, Train and Test: surgical specimens; Version 2, Train and Test: endoscopic and surgically resected specimens; Version 3, Train: endoscopic and surgical specimens and Test: surgical specimens; Version 4, Train: endoscopic and surgical specimens and Test: endoscopic specimens. The area under the curve (AUC) of the receiver operating characteristic curve was used to determine the accuracy of the AI model for predicting LNM with a 5-fold cross-validation in the training set. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The AUC of our model was 0.758–0.830 in the training set and 0.781–0.824 in the test set, higher than that of previous AI studies with only WSI. Moreover, the AI model with Version 4, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire–Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores. [ABSTRACT FROM AUTHOR]

The phenomenon of bone metastases presents a significant challenge within the context of advanced cancer treatments, particularly pertaining to breast, prostate, and lung cancers. These metastatic occurrences stem from the dissemination of cancerous cells into the bone, thereby interrupting the equilibrium between osteoblasts and osteoclasts. Such disruption results in skeletal complications, adversely affecting patient morbidity and quality of life. This review discusses the intricate interplay between cancer cells and the bone microenvironment, positing the bone not merely as a passive recipient of metastatic cells but as an active contributor to cancer progression through its distinctive biochemical and cellular makeup. A thorough examination of bone structure and the dynamics of bone remodeling is undertaken, elucidating how metastatic cancer cells exploit these processes. This review explores the genetic and molecular pathways that underpin the onset and development of bone metastases. Particular emphasis is placed on the roles of cytokines and growth factors in facilitating osteoclastogenesis and influencing osteoblast activity. Additionally, this paper offers a meticulous critique of current diagnostic methodologies, ranging from conventional radiography to advanced molecular imaging techniques, and discusses the implications of a nuanced understanding of bone metastasis biology for therapeutic intervention. This includes the development of targeted therapies and strategies for managing bone pain and other skeletal-related events. Moreover, this review underscores the imperative of ongoing research efforts aimed at identifying novel therapeutic targets and refining management approaches for bone metastases. It advocates for a multidisciplinary strategy that integrates advancements in medical oncology and radiology with insights derived from molecular biology and genetics, to enhance prognostic outcomes and the quality of life for patients afflicted by this debilitating condition. In summary, bone metastases constitute a complex issue that demands a comprehensive and informed approach to treatment. This article contributes to the ongoing discourse by consolidating existing knowledge and identifying avenues for future investigation, with the overarching objective of ameliorating patient care in the domain of oncology. [ABSTRACT FROM AUTHOR]

It is now widely recognized that gut microbiota plays a critical role not only in the development and progression of diseases, but also in its susceptibility to dietary patterns, food composition, and nutritional intake. In this comprehensive review, we have compiled the latest findings on the effects of food nutrients and bioactive compounds on the gut microbiota. The research indicates that certain components, such as unsaturated fatty acids, dietary fiber, and protein have a significant impact on the composition of bile salts and short-chain fatty acids through catabolic processes, thereby influencing the gut microbiota. Additionally, these compounds also have an effect on the ratio of Firmicutes to Bacteroides, as well as the abundance of specific species like Akkermansia muciniphila. The gut microbiota has been found to play a role in altering the absorption and metabolism of nutrients, bioactive compounds, and drugs, adding another layer of complexity to the interaction between food and gut microbiota, which often requires long-term adaptation to yield substantial outcomes. In conclusion, understanding the relationship between food compounds and gut microbiota can offer valuable insights into the potential therapeutic applications of food and dietary interventions in various diseases and health conditions. [ABSTRACT FROM AUTHOR]

The adsorption of ethanol and ammonia changes the basic properties of alumina, and new basic sites are created. Ethanol reacts with surface Al-OH groups, forming ethoxy group Al-O-C2H5. The substitution of Al-OH by Al-O-C2H5 increases the negative charge of neighbouring oxygen atoms, and they became sufficiently basic to react with adsorbed CO2 forming carbonate species CO32−. These carbonates were found to be monodentate and bidentate species. Preadsorption of ammonia also increases the basicity of alumina, but the mechanism is different than for ethanol adsorption. Adsorbed ammonia interacts with surface Lewis acid sites being three-coordinated aluminium atoms. This interaction is accompanied by an electron transfer from ammonia molecules to surface sites, and increases the basicity of the neighbouring oxygens, which can react with the absorbed CO2. The carbonate species formed are polydentate ones. [ABSTRACT FROM AUTHOR]