The DEAD-box RNA helicase DDX3X is a multifunctional protein involved in RNA metabolism and stress responses. In this study, we investigated the role of RG/RGG motifs in the dynamic process of liquid-liquid phase separation (LLPS) of DDX3X using cell-free assays and explored their potential link to cancer development through bioinformatic analysis. Our results demonstrate that the number, location, and composition of RG/RGG motifs significantly influence the ability of DDX3X to undergo phase separation and form self-aggregates. Mutational analysis revealed that the spacing between RG/RGG motifs and the number of glycine residues within each motif are critical factors in determining the extent of phase separation. Bioinformatic analysis of cancer genomic datasets uncovered a significant enrichment of DDX3X mutations in RG/RGG motifs across multiple cancer types, particularly in the N-terminal region of the protein. Furthermore, we found that DDX3X is co-expressed with the stress granule protein G3BP1 in several cancer types and can undergo co-phase separation with G3BP1 in a cell-free system, suggesting a potential functional interaction between these proteins in phase-separated structures. DDX3X and G3BP1 may interact through their RG/RGG domains and subsequently exert important cellular functions under stress situation. Collectively, our findings provide novel insights into the role of RG/RGG motifs in modulating DDX3X phase separation and their potential contribution to cancer pathogenesis.

This study investigated the adaptability of Dunaliella salina to different salinity levels, with emphasis on growth, pigment concentration, and desalination potential. It was found that among the 21 salinity levels (0-20%), 75‰ salinity produced consistently favorable results in cell count (13.08 x 103 ± 1.41 x 103 cells/mL), dry biomass (2.46 ± 0.06 g/L), pigment content (chlorophyll a = 9.75 ± 0.01 µg/L, chlorophyll b = 12.36 ± 0.03 µg/L), and desalination (9.32 ± 0.47 % reduction). Therefore, 75‰ salinity level was selected for the final trial (scale-up), which revealed unanticipatedly high cell counts (58.96 x 103 ± 535.22 cells/mL), with dry biomass weight being statistically extremely different (higher) than the expected (4.21 ± 0.02 g/L) (p<0.0001), most likely due to high cell count and energy reserve storage for high salinity adaption in the form of bio-compounds. Pigment growth continued (chlorophyll a = 9.54 ± 0.2 µg/L, chlorophyll b = 12.81 ± 0.51 µg/L), indicating pigment production under salt stress. Notably, desalination did not occur in this stage, possibly due to the necessity for a bigger initial inoculate, prolonged exposure or bioaccumulation becoming the prevailing mechanism over desalination. Despite this, the microalgae thrived in high salinity conditions. These findings point to further study into the mechanics of salt build-up within cells, which might lead to successful desalination technologies. Dunaliella salina adaptation to high salinity settings suggests its possible usage in natural pools or soils that are normally inappropriate for traditional production, giving a chance for enterprises to function in rough extreme salinity conditions.

Galectins are a family of beta-galactoside-binding proteins that are characterised by their carbohydrate recognition domain (CRD) and include galectin-1 and galectin-3. These galectins have been implicated in numerous diseases due to their pleiotropic nature, including cancer and fibrosis, with therapeutic inhibitors being clinically developed to block the CRD. One of the early methods developed to characterise these galectins was hemagglutination of red blood cells. Although insightful this approach has been hampered by a lack of sensitivity and accurate quantification of the agglutination observed. In this study we aimed to validate a more precise and quantitative method to enable further investigation of differences between galectins in respect to agglutination induction in different blood groups as well as characterisation of small molecule inhibitors. Quantification of hemagglutination was shown to be optimal using U-bottom plates imaged and analysed with FIJI ImageJ rather than flat bottom plates read for absorbance on an optical density plate reader. Galectin-3-induced red blood cell agglutination efficacy increased significantly from blood group O to A to B. However, for both the galectin-1 monomer and concatemer a more comparable effect was observed between blood group B and O but with more potent effects than in blood group A. Inhibition assays for both galectin-3 and galectin-1 induced-hemagglutination were able to demonstrate clear concentration-responses and expected selectivity profiles for a set of small molecule glycomimetics, confirming historical profiles obtained in biochemical binding and functional cellular assays.

Rapidly digestible starch can be obtained by gelatinization (cooking), cooking extrusion, use of small granule starch, breaking down starch granules, or by hydrolysis to maltodextrins. Resistant starch includes five groups: the first group is physically encapsulated starch within a food/polymer matrix, the second one is some native starch, the third one is recrystallized starch, the fourth one is chemically modified starch, and the fifth one is starch-lipid complexes. Starch digestion in the human body is also influenced by the degree of chewing, activity of α-amylase in the intestine, and transit time through the stomach and small intestine. Resistant starch or dietary fiber (DF) enriches specific bacterial groups located in the large intes-tine. They produce short chain fatty acids (SCFAs) and gases, causes the lowering of the pH, and inhibits pathogens. SCFAs are considered endogenous signaling molecules, acting through their free fatty-acid receptors 2 and 3 which can trigger the secretion of glucagon-like peptide-1 and peptide PYY, being released together following a meal to mediate postprandial satiety. A sufficient intake of DF reduces the risk of cardiovascular disease, coronary heart disease, stroke, hyperten-sion, colorectal cancer, and type 2 diabetes. Gluten matrix or phenolic compounds can lead to a low digestion rate of starch.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Our study explores the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the rpt5a mutant characterized by persistent reddish-brown leaf spots from seedling stage to maturity, leading to extensive leaf necrosis. Through map-based cloning, we localized the responsible locus to a 330Kb region on chromosome 2 and identified LOC_Os02g56000 (named OsRPT5A) as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and generation of knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. Our study also revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by mutations. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in rpt5a mutants, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the rpt5a mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice's pathogen resistance mechanisms. These findings elucidate the genetic basis of the spotted leaf phenotype and emphasize the intricate interplay between plant defense responses and developmental pathways.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

Whole cell biosensors could serve as eco-friendly and cost-effective alternatives for detecting potentially toxic bioavailable heavy metals in aquatic environments. However, they often fail to meet practical requirements due to an insufficient limit of detection (LOD) and high background noise. In this study, we designed a synthetic genetic circuit specifically tailored for detecting ionic mercury, which we applied to environmental samples collected from artisanal gold mining sites in Peru. We developed two distinct versions of the biosensor, each utilizing a different reporter protein: a fluorescent biosensor (Mer-RFP) and a colorimetric biosensor (Mer-Blue). Mer-RFP enabled real-time monitoring of the culture’s response to mercury samples using a plate reader, whereas Mer-Blue was analysed for colour accumulation at the endpoint using a specially designed, low-cost camera set up for harvested cell pellets. Both biosensors exhibited negligible baseline expression of their respective reporter proteins and responded specifically to HgBr2 in pure water. Mer-RFP demonstrated a linear detection range from 1 nM to 1 μM, whereas Mer-Blue showed a linear range from 2 nM to 125 nM. Our biosensors successfully detected a high concentration of ionic mercury in the reaction bucket where artisanal miners produce a mercury-gold amalgam. However, they did not detect ionic mercury in the water from active mining ponds, indicating a concentration lower than 3.2 nM Hg2+ -a result consistent with chemical analysis quantitation. Furthermore, we discuss the potential of Mer-Blue as a practical and affordable monitoring tool, highlighting its stability, reliance on simple visual colorimetry, and the possibility of sensitivity expansion to organic mercury.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

(1) Background: Learning and training in variable conditions favors adapting to unstable or changing environments. The aim of the study was to test the effect of variable practice on the accuracy of the forehand net approach shot in tennis.; (2) Methods: Thirty (n=30) first-class national players (12.9 ± 1.1 years old) participated, divided into three groups: i) induced variability training (n=10) (varying court surfaces and balls), ii) specific training (n=10) and iii) usual training -control group- (n=10). All groups trained for a month: 12 sessions of 20 minutes -3 per week-. The accuracy of the shots were analyzed through a 2D capture and digitization process of the ball bounce on the court; (3) Results: The variability group presented better accuracy values after the period without practice than the stable training group (p = 0.041; ES= 0.51).; (4) Conclusions: the application of variability in the game conditions during tennis training seems to have a favorable effect on the retention of accuracy in the forehand down the line approach to the net.

The new hybrid composite materials for PEM fuel cell were synthesized by UV-polymerization of acrylic monomers (acrylonitrile (AN), acrylic acid (AA), ethylene glycol dimethacrylate (EGDMA)) and sulfo aromatic monomer – sodium styrene sulfonate (SSS), and tetraethoxysilane/3-methacryloxypropyltrimethoxysilane (TEOS/MAPTMS)-based sol-gel system. By means of X-ray spectroscopy fractal structure of the obtained materials was characterized. Proton conductivity and viscoelastic properties of the materials were investigated depending on the content of inorganic component in nanocomposites. On the basis of impedance studies, an equivalent scheme is proposed that successfully describes the proton conductivity in the synthesized composite electrolyte membranes.

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p<0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P<0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

Nuclear DNA mutations, mitochondrial DNA mutations, combined nuclear and mitochondrial DNA defects, and random occurrences are the main causes of mitochondrial disease. Black pigmentation loss is a major sign of Parkinsonism. Because of the loss of dopaminergic neurons in the substantia nigra, it drops to less than 80%. The degree of motor impairment was correlated with the amount of black pigmentation loss. After RNA extraction, reverse transcription is carried out because reverse transcriptase was used to create cDNA. One microliter of total RNA supplemented with IORT Buffer, dNTPs, random hexamers, Multi-Scribe Reverse Transcriptase, and nuclease-free was used to create cDNA. The following was how the reaction was carried out in a thermal cycler: 10 minutes at 25°C, 120 minutes at 37°C, 5 seconds at 85°C, and lastly 4°C. The data was expressed as a v-value, which shows how much the target gene is enriched in comparison to the reference gene. Earlier research using mice injected with functional HtrA2/Omi protease activity revealed similar outcomes, including induced up-regulation of CHOP, decreased mitochondrial function, and early brain cell aging because of an increase in mtDNA deletions. The cell viability of the genotypes exhibits a dmg concentration-dependent effect in these results, suggesting that high content ratios of drug treatment with 6-OHDA may be the cause of cellular content depletion. After 6-OHDA neurotoxin treatment, CHOP is up-regulated. Prior in vitro research has shown that treatment with a model based on 6-OHDA neurotoxin causes the activation of mitochondrial stress pathways, which in turn promotes the death of neurons. 6-OHDA reversibly inhibited complexes I and IV's activities in rat brain cells, which led to dopaminergic neurodegeneration, a defining feature of PD pathogens. As a result, the number of living cells will directly correlate with the dmg concentration, supporting the results of the current study. Real-time PCR can generally demonstrate that the removal of HtrA 2 results in a significant up-regulation of Hsp60 expression when compared to WT cells. This could be linked to a decreased threshold for mitochondrial stress in HtrA2 KO cells, which would explain why, following ADEP4 and ACP5 treatment, Hsp60 is significantly up-regulated in HtrA2 KO cells compared to WT cells.

B-cell lymphomas (BCL) is the most frequent hematological cancer in dogs. Treatment typically consists of chemotherapy, with CHOP-based protocols. However, outcome remains generally poor, urging the exploration of new therapeutic strategies with a targeted approach. Myc tran-scription factor plays a crucial role in regulating cellular processes and its dysregulation is im-plicated in numerous human and canine malignancies, including canine BCL (cBCL). This study aims to evaluate the efficacy of indirectly inhibiting Myc in cBCL using BI2536 and MZ1 com-pounds in two in vitro models (CLBL-1 and KLR-1201). Both BI2536 and MZ1, alone and com-bined, affected cell viability in a significant concentration and time-dependent manner. Western Blot revealed an upregulation of PLK1 expression in both cell lines upon treatment with BI2536, in association with a reduction in c-Myc protein levels. Conversely, MZ1 led to a decrease in its primary target, BRD4, along with a reduction in c-Myc. Furthermore, BI2536, both alone and in combination with MZ1, induced larger transcriptomic changes in cells compared to MZ1 alone, primarily affecting MYC target genes and genes involved in cell cycle regulation. These data un-derscore the potential role of Myc as therapeutic target in cBCL, providing a novel approach to indirectly modulate this molecule.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

The potential of metallic lithium to become the anode material for next-generation batteries is hampered by significant challenges, chief among which is dendrite growth during battery charging. These dendritic structures not only impair battery performance but also pose safety risks. Among the non-destructive analytical techniques in battery research, Magnetic Resonance Imaging (MRI) stands out as a promising tool. However, the direct imaging of lithium by 7Li MRI is hindered by its low sensitivity and spatial resolution, making its use for of dendritic growth imaging very difficult. Instead, a recently introduced indirect imaging approach based on 1H MRI of the electrolyte was used in this study. This method was used for sequential 3D imaging to monitor the charging process of lithium metal symmetric cells in three different electrical circuits: single cell, four cells in parallel, four cells in series. The measured sequential images allowed measurement of dendrite growth in each cell using volumetric analysis. The growth results confirmed the theoretical expectation that growth across cells is uneven in a parallel circuit and even in a series circuit. The methods presented in this study can be applied also to many other dendrite-related issues in batteries.

Background: The accurate diagnosis of regional lymph node metastasis is critical for guiding treatment decisions in head and neck cancer patients. Despite advances in imaging techniques, detecting nodal metastasis remains challenging, leading to potential undertreatment or overtreatment. This systematic review aims to identify molecular markers associated with occult metastasis in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. Methods: The present research was conducted following PRISMA guidelines. Prospero registration nr. CRD42024522985. Results: Through a comprehensive literature search and review process, 634 articles were considered, 103 of them were finally included. Conclusions: Several promising markers were identified, including miR-205, DSG3, pan-CK AE1/AE3, HPV-16, Activin-A, Cyclin D1, and NPL that demonstrated effectiveness across multiple studies. Future research should focus on exploring combination scoring systems to improve diagnostic precision and optimize treatment selection in HNSCC patients.

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and high-risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. Particularly, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, where many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed association with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.

Currently, the textile industry is among the most rapidly expanding areas of the economy and is an important source of water pollution. There are many efficient chemical and physical methods for treating textile effluent, but they produce secondary pollutants. Therefore, there is a need to manage the textile waste wastewater. The potential EPS-producing and plant growth-promoting rhizobacteria Lysinibacillus capsici PB300 (T) bacteria strain has been isolated from the bark borer-affected Peltophorum pterocarpum plant and has been determined to be effective in > 95 decolorizing Reactive Red 120, and other azo dyes such as AB11385%, orange II 94.62%, Congo red 94.62%, phenol red 94.54%, and mixtures of azo dyes 81.66%. Physico-chemical factors were optimized manually, including Taguchi design. EPS production, PGPR strain, and fabric discoloration of L. capsici were qualitatively studied. The FTIR, GC-MS, and UV absorbance studies also confirmed that the dye had been broken into its amines. Research findings using enzyme assays have shown that the bacteria Lysinibacillus capsici PB300 (T) can utilize laccase and manganese peroxidase and are capable of degrading dyes significantly. According to this work, immobilised L. capsici cells and the studied four bacterial consortiums, Lysinibacillus capsici PB300 (T), Alcaligenes faecalis subsp. Phenolicus DSM 16503 (T), Acinetobacterbaumanni ATCC 19606 (T), and Pseudomonasaeruginosa JCM 5962 may be employed to degrade RR120 effectively, and it is concluded that L. capsici PB300 (T) bacteria is significantly efficient in textile effluent treatment.

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

Adult neurogenesis involves generation of functional neurons from neural progenitor cells, which have the potential to complement and restore damaged neurons and neural circuits. Therefore, the development of drugs that stimulate neurogenesis represents a promising strategy in stem cell therapy and neural regeneration, greatly facilitating the reconstruction of neural circuits in cases of neurodegeneration and brain injury. Our study reveals that compound A5, previously designed and synthesized by our team, exhibits remarkable neuritogenic activities, effectively inducing neurogenesis in neural stem/progenitor cells (NSPCs). Subsequently, transcriptome analysis using high-throughput Illumina RNA-seq technology was performed to further elucidate the underlying molecular mechanisms by which compound A5 promotes neurogenesis. Notably, comparative transcriptome analysis showed that the up-regulated genes were mainly associated with neurogenesis and the down-regulated genes were mainly concerned with cell cycle progression. Furthermore, we confirmed that compound A5 significantly affected the expression of transcription factors related to neurogenesis and cell cycle regulatory proteins. Collectively, these findings identify a new compound with neurogenic activity and may provide insights into drug discovery for neural repair and regeneration.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Let BT4l denotes a subclass of bounded turning functions connected with a four-leaf-type domain. The goal of the study is to probe into coefficients of |b6|, |b7|, |b8|, the bounds of the logarithmic coefficients and the third-order determinants of H3,1, H3,2, H3,3 for functions in this class.

GCTs are developmental tumors and likely to reflect ontogenetic and teratogenetic determinants. The objective was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were used. According to Teilum's holistic concept malignant and benign teratomas were registered. We used a case control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 17 isolated cases of eGCT with a wide range of syndromes, however not significantly associated following Bonferroni correction. All these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.

The refractive index of a liquid serves as a fundamental parameter reflecting its composition, thereby enabling the determination of component concentrations in various fields such as chemical research, food industry, and environmental monitoring. Traditional methods for refractive index (RI) measurement rely on light deflection angles at interfaces between the liquid and a material of known refractive index. In this paper, the authors present a new differential refractometer for highly sensitive measurement of RI differences between two liquid samples. Using a configuration with two cells equipped with flat parallel plates as measuring elements, the instrument facilitates accurate analysis. Namely, the sensor signals from both the solution and the solvent cuvette are generated simultaneously with one laser pulse, reducing the possible fluctuations of the laser radiation intensity. Our evaluation shows the high sensitivity of RI measurements (< 7 · 106), so this differential refractometer can be proposed not only as a high-sensitivity sensing tool that can be used for mobile detection of nanoparticles in solution samples, but also to determine the level of environmental nano-pollution using water (including rain, snow) samples from various natural as well as industrial sources, thus helping to solve some important environmental problems.

Aims: This study aims to evaluate the impact of family-centered empowerment on Jordanian adolescents with type 1 diabetes (T1DM), focusing on their HbA1c levels, self-efficacy, and quality of life (QOL). Background: Poor glycemic management in adolescents with type 1 diabetes increases complications. Improved control is linked to various variables, but few studies focus on Middle Eastern populations. Methods: An experimental study involved 68 adolescents with T1DM visiting Jordanian Royal Medical Services' clinics. Two sets of participants were created: control (n = 34) and intervention (n = 34). Data was collected through face-to-face interviews and medical records. Results: The study found significant differences in self-efficacy scores between the intervention and control groups, with the intervention group experiencing a significant decrease in HbA1c readings and a significant difference in QOL between pre-program and post-program phases. Discussion: Family empowerment can significantly improve the lives of Jordanian teenagers with type 1 diabetes. This strategy leads to improved glycemic management, increased self-efficacy, and improved quality of life. Future treatments and health policies should recognize and value the critical role families play in the care of this population. Conclusion: The study suggests that patients with T1DM should receive continuous care education sessions, including self-care training, to improve their health. Nurses should also incorporate these training into treatment plans and educational programs for adolescents to enhance their QOL.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

In the context of the minimally extended varying speed of light (meVSL) model, both the absolute magnitude and the luminosity distance of type Ia supernovae (SNe Ia) differ from those predicted by general relativity (GR). Utilizing the Pantheon+ data, we examine the plausibility of various dark energy models under meVSL. Both ωCDM and CPL parameterization dark energy (DE) models exhibit indications of cosmic variations in the speed of light at the 1-σ level. For Ωm0=0.30,0.31, and 0.32 with (ω0,ωa)=(−1,0), the 1-σ range of c˜˙0/c˜0(10−13yr−1) is (-8.76 , -0.89), (-11.8 , 3.93), and (-14.8 , -6.98), respectively. Meanwhile, the 1-σ range of c˜˙0/c˜0(10−12yr−1) for CPL dark energy models with −1.05≤ω0≤−0.95 and 0.28≤Ωm0≤0.32, is (-6.31 , -2.98). The value of c˜ at z=3 can exceed that of the present by 0.2∼3 % for ωCDM models and 5∼13 % for CPL models. Additionally, for viable models except for the CPL model with Ωm0=0.28, we find −25.6≤G˜˙0/G˜0(10−12yr−1)≤−0.36. For this particular model, we obtain an increasing rate of the gravitational constant within the range 1.65≤G˜˙0/G˜0(10−12yr−1)≤3.79.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Buildings’ thermal energy needs are inherently linked to climate conditions. Consequently, it is crucial to evaluate how climate changes affect these energy demands. Despite extensive analysis, a comprehensive assessment involving a diverse range of building types has not been consistently conducted. The primary objective of this research is to perform a coherent evaluation of the influence of climate changes, construction element properties, and the Heating, Ventilation, and Air Conditioning (HVAC) system type of control on the energy requirements of six buildings (residential, services, and commercial). The buildings are considered located in a temperate Mediterranean climate. Our focus is on the year 2070, considering three distinct climatic scenarios: (i) maintaining the current climate without further changes, (ii) moderate climate changes, and (iii) extreme climate changes. The buildings are distributed across three different locations, each characterized by unique climatic conditions. Buildings’ envelope features a traditional External Thermal Insulation Composite System (ETICS) and expanded polystyrene (EPS) serves as thermal insulation material. Two critical design factors are explored: EPS thickness ranging from 0 (no insulation) to 12 cm; and horizontal external fixed shading elements varying lengths from 0 (absence) to 150 cm. Six alternative setpoint ranges are assessed for the HVAC system control: three based on the Predicted Mean Vote (PMV) and three based on indoor air temperature (Tair). Results were obtained with a validated in-home software tool. They show that, even under extreme climate conditions, the application of thermal insulation remains energetically favorable, however its relative importance diminishes as climate severity increases. Then, proper insulation design remains important for energy efficiency. The use of external shading elements for glazing (e.g., overhangs, louvers) proves beneficial in specific cases. As climate changes intensify, the significance of shading elements grows. Thus, strategic placement and design are necessary for good results. The HVAC system’s energy consumption depends on the level of thermal comfort requirements, on the climate characteristics and on the building’s type of use. As climate change severity intensifies, energy demands for cooling increase, while energy needs for heating decrease. However, it’s essential to recognize that the impact of climate changes on HVAC system energy consumption significantly depends on the type of building.

This study explores the use of remote ultrasound vibration to enhance welding strength. It examines the effects of 20 kHz, and 40 kHz High Power Ultrasound Transducers (HPUT) in contact and contactless modes during ultrasonic assistance laser welding. Employing shear tests and microscopy for assessment, the research evaluates ultrasound's impact on welding strength and identifies the optimal transducer. Theoretical and numerical analyses investigate vibration transmission into the welding area, particularly examining the vibration distribution and cavitation initiation within the molten pool area. Results indicate that ultrasound-assisted welding increases pull test performance, including the resistance force and strain, and improves microscopic structural integrity. Numerical simulations suggest that narrow-band vibration intensifies pressure in specific welding zones. Contactless ultrasound application also shows enhanced welding quality, offering a promising alternative to current methods. This work contributes to electric car technology by suggesting improvements in welding techniques for power battery systems.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Members of the SOX (SRY-related HMG-box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular models. By providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

We have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

The article studies and analyzes a hybrid power source system, lithium battery, and fuel cell assisted by flexible photovoltaic panels for hybrid electric vehicles (HEVs). The new configuration operates based on optimizing the performance of the dual power source to maximize the available energy and operating time. The operational mode simulates specific driving conditions in urban, peripheral, and intercity routes under variable driving patterns and traffic conditions. The simulation results show that the new configuration increases the hybrid electric vehicle performance, providing higher reliability despite the more complex design. The proposed system reduces the external power supply dependence and avoids unexpected sudden stops due to energy exhaustion. The new configuration also extends the vehicle driving range depending on driving mode and route conditions. The vehicle driving range extension may reach up to 276.3 km. The hybridization of fuel cells with lithium battery and PV panel assistance enhances battery management, reducing battery servicing and increasing lifespan. The proposed topology is cheaper than a single fuel cell power system by 17.2%, reducing the total cost related to the single battery power system if we consider the battery recharge for its entire lifespan. The cost saving is 2.6% for the American market and 14.8% for the European one.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Yeast, crucial in beer production, holds promise as a valuable by-product resource, known as brewer's spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer's spent yeast with those of pure cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of BSY residue (641.90 μg/mg) was higher than that of SC (553.52 μg/mg) and SB (591.56 μg/mg). The yields of alkali-extracted water-soluble polysaccharides were 40%, 30%, and 35% for BSY, SC, and SB, respectively, with BSY comprising a higher proportion of water-soluble saccharides than SC and SB, including 49.3% mannan and 20.1% β-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential as an effective functional food material.

Chronic conditions like type 2 diabetes mellitus (T2DM), arterial hypertension (HTN), and obesity are major global health issues, causing significant morbidity and mortality. In Latin America, these conditions contribute to millions of premature deaths annually, posing challenges exacerbated by limited healthcare access and poor primary care quality, particularly in Mexico. Complementary medicine presents a potential solution, offering minimally invasive techniques to improve physical, mental, and spiritual well-being. Effective treatment adherence, crucial for positive outcomes, is influenced by self-efficacy, the ability to manage one's behavior in response to medical conditions. However, treatment adherence rates remain low, indicating a pressing public health concern. This study aimed to explore how perception of complementary medicine and treatment adherence predict self-efficacy among individuals with chronic conditions in Mexico. Analyzing data from 113 participants revealed significant correlations between variables, with treatment adherence positively associated with self-efficacy and perception of holistic medicine negatively correlated with self-efficacy. Regression analysis showed that incorporating perception of complementary medicine and treatment adherence significantly explained self-efficacy levels, suggesting the potential of complementary therapies in holistic healthcare approaches. However, collinearity between variables highlights the need for further research to better understand these relationships and their implications for improving healthcare outcomes in Mexico. Integrating complementary therapies with conventional treatments could enhance overall well-being and treatment adherence, offering promising avenues for addressing chronic conditions in the region. These findings underscore the importance of comprehensive healthcare approaches that integrate both conventional and complementary modalities to optimize health outcomes and quality of life for individuals with chronic conditions in Mexico and beyond.

Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies has performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations — specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to ATG-G (7.5% vs. 38.3%, p=0.001). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p&lt;0.001), with a shorter time between transplant and CMV (&lt;61 days, 77.8% vs. 33.3%, p=0.008) and a higher median CMV copy number (1000 vs. 0, p=0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p=0.005). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year probability of relapse while comparing ATG-T and ATG-G (32.0% vs 40.3%, p=0.423; 63.9% vs 55.7%, p=0.438, respectively).

The evolutionary cancer cell biology ECCB explains the deep homology existent between the life cycle of cancer and protists. Due to their origin and sensitivity to oxygen, all non-gametogenic germ lines and germ stem cells (GSCs), including human adult stem cells (ASCs) and cancer stem cells (CSCs), suffer severe DNADSB damage when exposed to stress oxygen content above 6.0% O2 (Urgermline hyperoxia) as occurring in tissue and bloodstream. As a result, GSCs/ASCs/ CSCs lose their stemness potential and convert from a functional asymmetric cyclic phenotype (ACD phenotype) to a dysfunctional symmetric phenotype capable of defective symmetric proliferation (DSCD) that is, however, unable to repair genomic degradation. Genome reconstruction occurs through evolutionary mechanisms evolved by the common ancestor of amoebozoans, metazoans, and fungi. They complete the cycle by removing the damage, reconstructing the functional genome, and reinstating the ASC phenotype. The stemness life cycle acts not only during carcinogenesis, tumorigenesis, and recurrence but also in the life cycle of protists.

Mothers of children with a specific clinical condition such as type 1 diabetes mellitus (T1DM) may experience higher levels of stress predisposing them to a poorer perception of quality of life and alterations in nutritional status. The aim of this research was to evaluate the relationship between nutritional status and quality of life perception of mothers caring for children with Type 1 Diabetes Mellitus. This research was conducted from July to September 2022, with mothers of children aged 5 to 10 years with diabetes. Data were collected through an online questionnaire including soci-oeconomic information, anthropometric data, clinical data of the children, and the WHO-QOL-abbreviated quality of life questionnaire. For statistical analysis, Statistical Package for Social Science 24 was used. Fifty-five mothers of children with diabetes were evaluated. Over 33% of the mothers were overweight and reported a regular perception of quality of life. Higher BMI was associated with poorer perception of quality of life in the psychological and self-assessment domains, and longer diagnosis time was associated with better perception of quality of life in the physical, psychological, and environmental domains. Therefore, it is understood that actions aimed at improving the quality of life of these mothers are necessary.

Existing research indicates that mineralization of Carlin-type gold deposit is related to geological structures, but current studies mostly focus on the qualitative association, and lack quantitative analysis of the relationship between mineralization and structural features, which limits the potential for predictive mineral exploration. In this study, the Nibao Carlin-type gold deposit was selected as the research area to conduct three-dimensional geological modeling, spatial analysis, and three-dimensional prospectivity modeling. Spatial analysis revealed that the majority of gold ore bodies are situated near the main fault, with gold mineralization primarily occurring within a spatial range of approximately -80 meters to 20 meters from the main fault plane. This spatial distribution predominantly aligns in a SW-NE direction. Spatial characteristic extraction of fault slope indicators suggests that the slope angles are conducive to the migration and accumulation of ore-forming hydrothermal fluids, with ore body metal content rapidly increasing within an angle range of approximately 20° to 60°. The shape analysis of the mainfault indicates that the principal spaces of mineralization enrichment are within -10m to 20m of the fault plane undulations, where gold resources are concentrated in a relatively flat area. However, the degree of mineralization is more pronounced in the protruding sections than in the depressed areas. The areas with significant dip changes in faults display higher variations in orebody attitudes, with mineralization noticeably weaker in areas where the fault steepness changes markedly. Ore-bearing units exhibit significantly higher grades within the -17° to 3° interval of fault steepness transition. This interval also sees a rapid accumulation of gold resources. The Nibao gold mine's mineralization is derived from deep, ore-bearing hydrothermal fluids ascending along major fractures, precipitating, and accumulating in favorable ore-hosting spaces (faults, anticline cores) and lithological combinations (sedimentary tuffs, tuffs). Three deep potential gold targets were identified, highlighting the deep western edge of the F1 fault and the deep southeast-trending lower plate as prospective areas for future exploration. This study underscores the effectiveness of 3D prospective modeling as an indispensable tool for elucidating the spatial distribution of fault-controlled Carlin-type gold deposits and their tectonic determinants.

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes, yet they stand at the base of the Olfactores clade - which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among the 84 that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs’ quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, “ the fourth germ layer”, providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception tool-kits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.

Abstract Precision medicine is essentially based on reliable and non-invasive biomarkers. Aim of this review has been to describe the newest biomarkers in the field of kidney transplantation and the kidney rejection, one of the commonest and severe complications. Standard of care tools to identify acute rejection are largely full of errors and of drawbacks. In recent years new and reliable biomarkers have been found. They are avoid of risks, non-invasive and able to detect rejection even in those frequent cases in which acute rejection are clinically asymptomatic and not otherwise identifiable. In recent years several biomarkers have been identified. Very recently have been found new relevant biomarkers able to diagnose rejection with high positive predictive value and low negative predictive value. These are the donor derived cell free DNA found in the recipient, the gene expression profile of the donor found in the recipient and the urinary cytokines that express modification in the graft tissue. The aim of this study has been to find the most recent findings in the literature on this topic and to describe the utility and possible limitation of such new biomarkers on kidney rejection.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

Protein Kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement of PKCδ for preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ selectively deletes anti-dsDNA B cells in the germinal center (GC), disclosing a key B cell tolerance mechanism that prevents lupus autoimmunity. PKCδ’s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ’s tolerance activity, and discuss the potential significance of therapeutically targeting PKCδ’s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is the most prevalent form, accounting for nearly 95% of laryngeal cancer. This study evaluates the effectiveness of chemotherapy and radiation therapy combined for treating LSCC, along with exploring miR-449a as a potential biomarker for predicting treatment response and prognosis in LSCC patients. Patients and Methods: The study had 81 patients with advanced laryngeal cancer and 50 healthy controls. Chemotherapy was given for two cycles, followed by an evaluation of the response. Disease progression cases had surgical resection and radiation therapy. Positive responders had radiation therapy after a third cycle. The study also assessed miR-449a expression levels in tumor tissue, normal tissue, and serum samples from control subjects. Results: 31% achieved a complete response, and 49% showed a partial response. 31% of complete response participants maintained laryngeal integrity and vocal function. After radiation therapy, 74% of 65 patients responded completely and preserved laryngeal functions. Lower MiR-449a levels found in LSCC tissues and serum samples were correlated with aggressive tumor behavior, poor prognostic markers, and decreased survival. Conversely, elevated levels were seen in treatment responders. Conclusions: Combined chemo and radiotherapy preserve vocal function and improve outcomes in LSCC. MiR-449a is a promising indicator for diagnosis and treatment efficacy in LSCC.

In Indonesia, types of meat are still identified manually due to increasing prices for beef and buf-falo ahead of Idul Fitri. Traders mix beef with pork to thwart the beef scam. Haar wavelet and GLCM, GLCM with angles of 0°, 45°, 90°, and 135°, as well as matrices using contrast, correlation, energy, homogeneity, and entropy, are used in feature extraction. The following are the results of meat image classification testing using k-NN, Haar wavelet, and GLCM: The k-NN algorithm shows superiority in identifying fresh (99%), frozen (99%), and rotten (96%) meat texture images with the most fantastic accuracy results in every situation. Meanwhile, GLCM routinely provides good results, especially regarding the texture image of fresh meat (183.21) and rotten meat (115.79). However, despite delivering less throughput than k-NN and GLCM, Haar wavelets are still helpful, especially when dealing with fresh meat texture images (89,96).

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

For the first time, the effect of a significant change in the resistance of the aquatic environment of a population of protozoan microorganisms under the influence of radiofrequency electromagnetic radiation from cell phones has been experimentally studied. The results of the experiment demonstrate the biological nature of the changes occurring in the “water population of protozoa” system, which indicates that the impact of radiation directly affects the cell. This conclusion is confirmed by the same order of magnitude time of information exchange between individual individuals of the population in the calculation and in the experiment. An extremely low concentration of protozoa in the experiment was established, equal to 1000 pcs./liter, at which the indicated effect is observed.An unambiguous dependence of the biological effect in the “water – amoeba population” system on the average power of electromagnetic radiation of cell phones, both in standby mode and in talk mode, has been established. It is concluded that the presented method of changing the physical properties of the aquatic environment of a population of protozoa under the influence of electromagnetic fields can be a model experiment in identifying the mechanisms of interaction of biological systems with electromagnetic radiation, determining the response time of biological systems to external electromagnetic influence, and establishing the degree of influence of radiation in the 4G, 5G ranges.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

Cognitive impairment is a condition which affects aging patient populations and is becoming more prevalent as the geriatric population expands. It is categorized by the extent of cognitive decline, memory loss, functional abilities, and the capability to perform daily tasks. Based on the degree of impairment, it is classified as mild cognitive impairment or dementia. Considering the debilitating nature of cognitive decline and its impact on quality of life, prevention is key. In addition, given the gradual progression of the underlying causes of cognitive decline, early diagnosis and appropriate management has the potential to offer clinical advantages and better patient outcomes. Management options discussed vary from pharmaceutical regimens to neurosurgical interventions, with differing outcomes based on etiology of cognitive impairment.

Non-Small Cell Lung Cancer (NSCLC) is the most common pulmonary malignancy, most frequently diagnosed at an advanced stage (III/IV). Patients in the Locally-Advanced Stage Subgroup (IIIA) are relatively few, yet compose of heterogenic phenotypes posing a diagnostic and treating challenge, leading to lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, operable Stage IIIA NSCLC patients who underwent surgery between 2013-2020 were evaluated on several aspects, including initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, overall survival at 2-years and 5-years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with Stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 20 patients, of which 7 (25%) cases were defined as complete pathological response. The 2-years overall survival rate was 65% and the 5-years overall survival rate was 60%. The main pattern of disease recurrence was distant metastasis.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

Fiber-rich green river Aonori alga is mass-cultivated in Japan; it has been reported to reduce inflammation and improve metabolic health in humans. Peroxisome proliferation-activated receptor (PPARs) are associated with metabolic disorders such as obesity and type 2 diabetes (T2DM). We evaluated the effects of supplementation with NBF2, a formula made of algal and junos citrus biomaterials, on metabolic markers in obese and diabetic rats. An experimental study was performed using 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats randomly assigned to high dose NBF2 (20mg/kg; n=6), low dose (10mg/kg; n=6) NBF2 drink for 6 weeks, whereas OLETF control rats received similar amount of tap water (vehicle; n=6). LETO rats were used as normal controls (n=8). Biospecimens were taken for ELISA and real-time PCR. Both high dose and low dose NBF2 increased brown adipose tissue (BAT) mass and adiponectin (APN), improved insulin sensitivity, and significantly improved glycemic and lipid (TG, LDL-c) profiles in NBF2-supplemented OLETF rats after a 6-week supplementation with NBF2 (vs. OLETF controls), as well as LDL-c (p<0.05). During the glucose tolerance test (OGTT), both NBF2 groups and LETO rats had normal glycemia by 90-minute time-point (vs. OLETF controls; p<0.01). Furthermore, intake of NBF2 up-regulated PPARa/g-mRNA and Sirt2-mRNA gene expressions in BAT, and improved blood pressure profile in OLETF rats. Findings from this research suggest that intake of NBF2 formula induces dual PPAR-a/g and Sirt2 activation, providing insights on beneficial prophylactic and therapeutic effects of this NB2 formula on dyslipidemia and hyperglycemia in T2DM.

To develop peptide drugs targeting integrin receptors, synthetic peptide ligands endowed with well-defined selective binding motifs are necessary. The snake venom KTS-containing disintegrins, that selectively block collagen α1β1 integrin, were used as lead compounds for the synthesis and structure-activity relationship of a series of linear peptides containing the KTS-pharmacophore and alternating natural amino acids and 3-aminobenzoic acid (MABA). To ensure a better stiffness and metabolic stability, one, two and three MABA residues, were introduced around the KTS pharmacophore motif. Molecular dynamics simulations have determined that the solution conformation of MABA peptide 4 is more compact, underwent larger conformational changes until convergence, and spent most of the time in a single cluster. The peptides’ binding affinity has been characterized by enzyme linked immunosorbent assay in which the most potent peptide 4 inhibited with IC50 of 324±8 µM and 550±45 µM the binding of GST-α1-A domain to collagen IV fragment CB3, and the cell adhesion to collagen IV using α1-overexpressor cells, respectively. Docking studies and MM-GBSA calculations confirmed that peptide 4 binds a smaller region of the integrin near the collagen- binding site and penetrated deeper into the binding site near Trp1. Peptide 4, inhibited tube formation by endothelial cell migration in the Matrigel angiogenesis in vitro assay. Peptide 4 was acutely tolerated by mice, showed stability in human serum, decreased tumor volume and angiogenesis, and significantly increased the survival of mice injected with B16 melanoma cells. These findings propose that MABA-peptide 4 can further serve as an α1β1-integrin antagonist lead compound for further drug-optimization in angiogenesis and cancer therapy.

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

We report a novel dual-band barrier infrared detector (DBIRD) design using type-II superlattices (T2SLs). The DBIRD structure consists of back-to-back barrier diodes: a "blue channel" (BC) diode which has an nBp architecture, an n-type layer of larger bandgap for absorbing blue band infrared/barrier/p-type layer, and a "red channel" (RC) diode which has an pBn architecture, a p-type layer of smaller bandgap for absorbing red band infrared/barrier/n-type layer. Each has a unipolar barrier using a T2SL lattice matched to a GaSb substrate to impede the flow of majority carriers from the absorbing layer. Each channel in the DBIRD can be independently accessed with a low bias voltage, as is preferable for high-speed thermal imaging. Device modeling of DBIRDs and simulation results of the current-voltage characteristics under dark and illuminated conditions are also presented. They predict that dual-band operation of the DBIRD will produce low dark currents and 27-33% quantum efficiencies for the in-band photons in the BC with λc=5.58 μm, and a nearly-constant 33% in the RC with λc=8.05 μm. The spectral quantum efficiency of the BC for 500 K blackbody radiation is approximately 20% over the range of λ=3 − 4.2 μm, while that of the RC has a peak of 42% at 5.7 μm. The DBIRD may provide improved high-speed dual-band imaging in comparison with NBn dual-band detectors.

Background: Renal cancers are among the top ten causes of cancer-specific mortality, of which the ccRCC subtype is responsible for most cases. The grading of ccRCC is important in determining tumour aggressiveness and clinical management. Objectives: The objectives of this research were to predict the WHO/ISUP grade of ccRCC pre-operatively and characterise the heterogeneity of tumour sub-regions using radiomics and ML models, including comparison with pre-operative biopsy-determined grading in a sub-group. Methods: Data were obtained from multiple institutions across two countries, including 391 patients with pathologically proven ccRCC. For analysis, the data were separated into four cohorts. Cohorts 1 and 2 included data from the respective institutions from the two countries, cohort 3 was the combined data from both cohort 1 and 2, and cohort 4 was a subset of cohort 1, for which both the biopsy and subsequent histology from resection (partial or total nephrectomy) were available. 3D image segmentation was carried out to derive a voxel of interest (VOI) mask. Radiomics features were then extracted from the contrast-enhanced images, and the data were normalised. The Pearson correlation coefficient and the XGBoost model were used to reduce the dimensionality of the features. Thereafter, 11 ML algorithms were implemented for the purpose of predicting the ccRCC grade and characterising the heterogeneity of sub-regions in the tumours. Results: For cohort 1, the 50% tumour core and 25% tumour periphery exhibited the best performance, with an average AUC of 77.9% and 78.6%, respectively. The 50% tumour core presented the highest performance in cohorts 2 and 3, with average AUC values of 87.6% and 76.9%, respectively. With the 25% periphery, cohort 4 showed AUC values of 95.0% and 80.0% for grade prediction when using internal and external validation, respectively, while biopsy histology had an AUC of 31.0% for the classification with the final grade of resection histology as a reference standard. The CatBoost classifier was the best for each of the four cohorts with an average AUC of 80.0%, 86.5%, 77.0% and 90.3% for cohorts 1, 2, 3 and 4 respectively. Conclusion: Radiomics signatures combined with ML have the potential to predict the WHO/ISUP grade of ccRCC with superior performance, when compared to pre-operative biopsy. Moreover, tumour sub-regions contain useful information that should be analysed independently when determining the tumour grade. Therefore, it is possible to distinguish the grade of ccRCC pre-operatively to improve patient care and management.

Research on retinoid-based cancer prevention, spurred by the effects of vitamin A deficiency on gastric cancer and subsequent clinical studies on digestive tract cancer, unveils novel avenues for chemoprevention. Acyclic retinoids like 4,5-didehydrogeranylgeranoic acid (4,5-didehydroGGA) emerged as potent agents against hepatocellular carcinoma (HCC), distinct from natural retinoids such as all-trans retinoic acid (ATRA). Mechanistic studies reveal GGA's unique induction of pyroptosis, a rapid cell death pathway, in HCC cells. GGA triggers mitochondrial superoxide hyperproduction and ER stress responses through Toll-like receptor 4 (TLR4) signaling and modulates autophagy, ultimately activating pyroptotic cell death in HCC cells. Unlike ATRA-induced apoptosis, GGA and palmitic acid (PA) induce pyroptosis, underscoring their distinct mechanisms. While all three fatty acids evoke mitochondrial dysfunction and ER stress responses, GGA and PA inhibit autophagy, leading to incomplete autophagic responses and pyroptosis, whereas ATRA promotes autophagic flux. In vivo experiments demonstrate GGA's potential as an anti-oncometabolite, inducing cell death selectively in tumor cells and thus suppressing liver cancer development. This review provides a comprehensive overview of the molecular mechanisms underlying GGA's anti-HCC effects and underscores its promising role in cancer prevention, highlighting its importance in HCC prevention.

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), arise due to numerous causes like protein accumulation and autoimmunity, characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform a critical role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. MiRNA participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative diseases (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlighted miRNA as therapy.

Multiple sclerosis is an autoinflammatory condition that results in damage of myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing remittent disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting opportunity to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width - Coefficient of Variation)—in 117 glioblastoma patients. Data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in NLR, PLR, and RDW-CV across different treatment stages. NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p=0.007, η2p=0.06; PLR: p=0.001, η2p=0.23), while RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p &lt; 0.001, η2p=0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR=1.03, p=0.029; RDW-CV at progression: HR=1.14, p=0.004). We proposed specific marker cutoffs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line &lt; 5: p&lt;0.017; RDW-CV at progression &lt; 15: p=0.007). Elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

The mechanisms underlying the establishment of asymmetric structures during development remain elusive. The wing of Drosophila is asymmetric along the Anterior-Posterior (AP) axis, despite that its growth signals that drive its growth are presumably symmetric. Here, we investigated the contribution of cell recruitment, a process that drives wing fate differentiation in Drosophila, to the asymmetric shape and pattern of the adult wing. Genetic impairment of cell recruitment results in a significant reduction in adult wing asymmetry, primarily affecting the region between longitudinal vein 5 and the wing margin (L5-M). Morphometric analysis reveals that the lack of cell recruitment results in a more symmetric wing with respect to the AP, suggesting a contribution of cell recruitment to the establishment of asymmetry in the adult wing. A close examination of the expression of the wing selector gene vestigial (vg) in wing disc does not support this hypothesis. However, the circularity of the Vg pattern significantly increase in recruitment-impaired wing disc, suggesting that while the decrease of the L5-M region in the adult wing may not be attributed to cell recruitment, it could contribute to the overall asymmetry of the adult wing. We conclude that cell recruitment, a widespread mechanism that participates in growth and patterning of several developing systems, could drive, at least partially, the asymmetric shape of the Drosophila wing.

The therapeutic, attenuative, and morphological effects of proprietary neural stem cell-derived extracellular vesicles (NSC EVs, AB126) produced by Aruna Bio, Inc. were assessed in a range of in vitro and in vivo models of stroke. We emphasize that modulation of neuroinflammation is a key target and suggest further studies to advance our understanding of the mechanisms of action and ultimately how best to dose and monitor the benefits of AB126 in stroke patients.

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

This paper investigates an innovative photovoltaic cell configuration, denoted as “Au/CuSCN/RbGeI3/CdTe/ZnO/TiO2/FTO", using SCAPS-1D simulation. The research focuses on optimizing device performance by analyzing key components, including ZnO as the electron transport layer (ETL), RbGeI3 as the perovskite absorber layer, CuSCN as the hole transport layer (HTL), and CdTe as the active buffer layer. A comparison is made with the standard “Au/CuSCN/CH3NH3SnI3/CdTe/ZnO/TiO2/FTO" configuration under dark and illuminated conditions. Through an in-depth investigation involving temperature effects, generation rate analysis, RbGeI3 absorber layer thickness, Nd level, and interface defect levels, an optimized design for a unit area is achieved. The proposed solar cell demonstrates outstanding performance metrics, including an open circuit voltage (Voc) of 0.94V, a short circuit current density (Jsc) of 34.52mA/cm2, a fill factor (FF) of 77.77%, and an energy conversion efficiency (η) of 25.40%. These values significantly outperform the reference models with energy conversion efficiencies of 10.11% and 21.09%. Real-world applicability is validated by implementing these optimized characteristics in a photovoltaic system for Pakistan’s geographical location using PVSyst software. The suggested solar cell achieves a remarkable performance ratio (PR) of 85.6%, surpassing the PR of the reference basic solar cell model at 83%. The findings of this research offer a promising and superior solar cell design, incorporating innovative materials and optimization techniques to achieve exceptional energy conversion efficiency and overall performance. This study’s outcomes have the potential to advance photovoltaic technology and contribute to sustainable energy solutions worldwide.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

Organic solar cells are contributing extensively to the production of future large area and cost-effective sources of renewable energy with a compact environmental impact. Moreover, due to tunable optical properties of the active medium, the semi-transparent organic solar cell can be fabricated and become a promising nominee for building Integrated Photovoltaics (BIPV), vehicles, and mobile electronic devices. Therefore, three newly synthesized polymers used as were host materials for the active medium and blended with beetroot dye. Hence, based on BHJ structure two ternary systems have been constructed and utilized to fabricate semitransparent solar cells and characterized. The results show that the natural dye has a crucial impact on solar cell characteristic parameters. Consequently, large value of V_OC close to 1V were obtained for ternary systems and acceptor material named PINDOLE exhibits potentials for electron transport layer (ETL) and shows an improvement in both fill factor and device efficiency.

A comprehensive understanding of the genetic diversity among strains of Xanthomonas citri pv. citri (Xcc), the causative agent of citrus bacterial canker, is crucial for unraveling the pathological nature, structure, and evolution of populations, thereby facilitating the adoption of sustainable control measures. In a collection of 48 strains isolated in 2012, 2020, and 2021 from citrus production areas in Burkina Faso, polymerase chain reaction (PCR) tests utilizing specific primers were conducted to investigate the distribution of type 3 effectors (T3E) and the structuring of strains based on their geographical origins. The analysis of the distribution of type 3 non-transcription activate like effectors (TALE) reveals a more extensive repertoire in strains isolated in 2020 and 2021 compared to those isolated in 2012. Nevertheless, all strains share a common repertoire of three genes, namely XopE2, XopN, and AvrBs2. Additionally, all screened effectors were observed in the Bobo-Dioulasso locality. Concerning the characterization of TALEs, two profiles consisting of two to three TALEs were identified. Profile 1, with two TALEs, was present in 37 Xcc strains, while Profile 2, with three TALEs, was identified in 11 strains. Among the three TALEs (A, B, and C) identified, TALEs B and C were common to all strains. The correlation matrix revealed a positive correlation between the T3E content of strains and the years of their isolation. Multiple component analysis indicated a weak structuring of the tested strains.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

The shortage of physicians in rural communities contributes to increased mortality rates among Medicare beneficiaries. This increase in mortality risk is commonly due to diseases such as heart disease and cancer, including melanoma and non-melanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is considered the gold-standard treatment for NMSC tumors, however, due to a shortage of dermatologists and Mohs surgeons in rural areas, access to MMS is limited. In these areas, image guided superficial radiation therapy (IGSRT) serves as a viable option for the treatment of NMSC lesions, with fewer recurrences and 99% cure rates, which are comparable to MMS cure rates. IGSRT is performed in dermatology clinics with support from a multidisciplinary team, including radiation therapists, medical physicists, radiation oncologists, and dermatologists. As IGSRT is able to be performed by general dermatologists, Medicare beneficiaries in rural communities will have an increase in access to treatment options and a decrease in delayed skin cancer treatment.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

Abstract: The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes isolated from cattle farms, cattle abattoirs, and retail outlets in Gauteng province, South Africa. The isolates' sequence types (STs), clonal complexes (CCs), and lineages were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were 7 STs, 6 CCs, 44 putative virulence factors, 2 resistance genes, 1 plasmid with AMR genes and 3 with conjugative genes, 1 CRISPR gene, and all 60 isolates were positive for proviruses. Among the 7 STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p&lt;0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (P&lt;0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in 3 (5%) isolates. A CRISPR-Cas system was detected in 6 (10%), and all the isolates carried proviruses. Significant differences were detected in the frequencies of STs and virulence factors regarding the source and sample type of the L. monocytogenes isolates. The presence of both fosX and vga(G) genes in all the isolates from the three industries (cattle farms, abattoirs, and retail outlets) can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain in the country, provides the first evidence of the distribution of the pathogen with potential food safety and therapeutic implications.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic-dysfunction associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The efficacy of the model was assessed through the evaluation of the Out-of-Bag (OOB) error estimate. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using 3 models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest), the AUCs were 0.882, 0.972 and 0.96 respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS&gt;50%; n=10) or low (TPS&lt;1%; n=10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and low PD-L1 expression. After analyzing the correlation between methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with low PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

Background and objectives: sickle cell disease is the most common hemoglobinopathy in the world. It is considered to be a real public health problem. Sickle cell patients are subjected to several factors causing inflammation such as iron metabolism. The study aimed to look for inflammation in children with sickle cell disease in Cameroon, identify the factors associated with inflammation, and raise the consequences for the patient including the iron profile and the profile of the hemogram. Materials and methods: We conducted an analytical cross-sectional study for 03 months. The sickle cell disease patients coming and/or followed at the Hematology Department of the Regional Hospital of Bafoussam and the Central Hospital of Yaoundé have been recruited. The exploration of inflammation was made by determining CRP, IL6, and ferritin concentrations. The hematological parameters and iron profile were evaluated using standard methods. Statistical analysis of the data was performed; Univariate and multivariate logistic regression analyses allowed to identification of factors associated with inflammation in patients, using the statistical tool R version 4.1.1.. The proportions were compared with the chi-square test when the expected numbers were greater than 5 and the Fisher test when not. Results: The frequency of inflammation in the population was 42.3%. Hyperferritinemia was significantly greater (p<0.001) in patients with inflammation compared to the non-inflammatory patients (96.8% and 76.7% respectively). Patients with inflammation showed a significant elevation of iron parameters (p<0.05). In addition, ferritin and IL6 elevation were associated with inflammation during sickle cell disease respectively (Or = 4.96; 95% CI [1.15-36.42]; p=0.056) and (Or =6.23; 95% CI [1.43-45.96]; p=0.030). Conclusions: The elevated iron in plasma is an effect of inflammation in sickle cell patients. Hence the need of controlling inflammation and iron in the latter is necessary.

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenols, fiber, protein and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes ANGPTL8, CCNP, ETV4, and TRIB3, associated with adipose deposition. Pathway analysis highlighted enrichment in adipose-deposition-related pathways, including PPAR, Insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as PER2 and PTGES. Single-cell transcriptome data pointed to the specific expression of CD248 and PTGES in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake's potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Over the last several years, large-scale cancer genomics studies involving multi region, multi-sample sequencing indicate that most or at least many cancer patients may have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. They can be identified via multiregion, multisample biopsies - or circulating tumor cells/cell-free DNA. Achilles Therapeutics is currently the only company targeting patient-specific, clonal mutations. They have opted to utilize an immunotherapy approach. However, I recently devised another approach for exploiting clonal mutations called “Oncolytic Vector Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). It is based on the identification of patient-specific, clonal mutations and targeting them using a bioengineered facultative intracellular bacterium. It would be initially non-replicating, but transiently regain the ability to replicate (and also transiently become hyper-virulent) upon mutation detection via molecular switches.

Background: Fibonacci patterns and tubular forms both arose early in the phylogeny of multicellular organisms. Tubular forms offer the advantage of a regulated internal milieu, and Fibonacci forms may offer packing efficiencies. The underlying mechanisms behind the cellular genesis of Fibonacci and tubular forms remain unknown.