This study profiled morphological and laboratory-derived performance biomechanics by position of American style football players training for the National Football League draft. Fifty-five players were categorized into Big (e.g., lineman; n=17), Big-skill (e.g., tight end; n=11), and Skill (e.g., receiver; n=27) groups. Body fat (BF%), lean body mass (LBM), total body mass, running force and ground contact time (GCT), countermovement jump height (CMJ-JH), CMJ normalized peak power (CMJ-NPP), and reactive strength were measured in a laboratory. Asymmetry was calculated for running force, GCT, and CMJ eccentric and concentric impulse (IMP). MANOVA determined between-group differences, and radar plots for morphological and performance characteristics were created using Z-scores. There was a significant between-group difference, F(26,80)=5.70, p<0.001;Wilk’s Λ=0.123, partial η2=0.649. Fisher’s least squares difference post-hocs showed Skill had greater JH, CMJ-NPP, reactive strength, and running force versus Big but not Big-skill, p<0.05. Big had greater BF%, LBM, total body mass, and GCT than Skill and Big-Skill, p<0.05. Big-skill had greater GCT asymmetry than Skill and Big, p<0.05. Asymmetries in running forces, and CMJ eccentric and concentric IMP were not different, p>0.05. Morphological and performance biomechanics differences are pronounced between Skill and Big. Big-skill possess characteristics from both groups. Laboratory-derived results provide specialized profiles of draft trainees.

Background/Aims: Obstructive sleep apnea syndrome (OSAS) affects a large part of the aging population. It is characterized by chronic intermittent hypoxia and associated with neurocognitive dysfunction. One hypothesis is that the blood-brain barrier (BBB) functions could be altered by exosomes. Exosomes are nanovesicles found in biological fluids. Through the study of exosomes and their content in tau and amyloid beta (A), the aim of this study was to show how exosomes could be used as biomarkers of OSAS and of their cognitive disorders. Methods: Two groups of 15 volunteers from the PROOF cohort were selected: severe apnea (AHI >30) and control (AHI

Human osteosarcoma (OS) is a rare tumor predominantly affecting long bones and characterized by a poor prognosis. Currently, the first line of intervention consists of surgical resection of primary tumors combined with radiotherapy and chemotherapy, with a profound impact on patient’s life. Since surgical removal of OS frequently results in large resection of bones the use of biomaterials to sustain the stability of remaining tissue and to stimulate bone regeneration is challenging. Moreover, residual neoplastic cells might be responsible for tumor recurrence. Here we explored the potential of doped-bioactive glass as novel therapeutic intervention to both eradicate residual malignant cells and promote bone regeneration. Bioactive glass (BAG) has been extensively studied and employed in the field of regenerative medicine, due to its osseointegration properties and ability to improve bone tissue regeneration. We found that the incorporation of tellurium in BAG selectively kills OS cells through ferroptosis while preserving the viability of hBMSCs, and stimulating their osteodifferentiation. Although the mechanism of Te toxicity is still unclear: i) Te-BAG generates lipid-ROS through LOXs activity but not iron overload; ii) Te-dependent ferroptosis is mediated by GPX4 down-regulation, and iv) abrogates the anti-ferroptotic activity of FSP1, which expression confers resistance of OS to canonical induction of ferroptosis.

Mesenchymal Stem Cells (MSCs) secretions, usually containing growth factors, cytokines, and chemokines, have improved wound healing via a paracrine mechanism. This makes them particularly valuable as potential cell therapeutics. Similarly, wound healing is mainly regulated via paracrine signaling of growth factors, cytokines, and chemokines. Chronic wound healing has prolonged inflammatory, proliferative, or remodeling phases, resulting in tissue fibrosis and non-healing ulcers. The growth factors, cytokines, and chemokines secreted by MSCs can be applied to wounds by transplanting cells or using the secretome/conditioned medium (CM) of MSCs, which contains these secreted bioactive molecules. For their success in increasing the wound healing rate, MSCs offer a promising option for treating chronic wounds. This review provides a concise summary of current knowledge of the biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role of MSCs in wound healing by increasing wound healing rate with the secretion of growth factors, cytokines, and chemokines. In addition, the function and type of MSCs also have been discussed.

Primary themes in intergenerational justice are a healthy environment, the perpetuation of Earth’s biodiversity, and the sustainable management of the biosphere. However, the current rate of species declines globally, ecosystem collapses driven by accelerating and catastrophic global heating and a plethora of other threats, preclude the ability of habitat protection alone to prevent a cascade of amphibian and other species mass extinctions. Reproduction biotechnologies, biobanking, and conservation breeding programs (RBCs), enabling species restoration, offer a critical transformative change that can economically and reliably perpetuate species irrespective of environmental targets. These capacities extend indefinitely into the future and satisfy humanities needs as the biosphere expands into space. Currently applied RBCs include the hormonal stimulation of reproduction, the collection and refrigerated storage of sperm and oocytes, sperm cryopreservation, in vitro fertilisation, along biobanking. Advanced biotechnologies such as assisted evolution and cloning for species adaptation or restoration have yet to be fully realised. We broaden our discussion to include genetic management, broad political and cultural engagement, and future applications. The development and application of RBCs, and particularly assisted evolution and species restoration, raise intriguing ethical, theological, and philosophical issues. We address these themes with amphibian models to introduce the MDPI Special Issue, The Sixth Mass Extinction and Species Sustainability through Reproduction Biotechnologies, Biobanking, and Conservation Breeding Programs.

Solanum indicum Linn, is commonly known as Indian Nightshade or Poison Berry belongs to the family Solanaceae. This review studied the botanical description, traditional uses of its seeds, its chemical composition, pharmacological properties and modern applications in medicinal system. The plant is rich in alkaloids, steroidal saponins, flavonoids and phenolic acids having diverse pharmacological activities and phytochemical profile. It is used in treatment of various respiratory disorders, inflammation, skin problems and gastrointestinal disease since ancient times. Scientific research in modern times also tested many of the traditional uses revealing anti-inflammatory, antioxidant, antimicrobial activities as well as some cytotoxic and even antidiabetic effects. These pharmacological activities show potential future as uses for organic drugs, natural health products, skincare formulations and agricultural advancements.

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder, caused by pathogenic variants in the CYP27B1 gene, typically characterized by growth failure, rickets, leg bowing, fracture, seizures, hyperparathyroidism, hypocalcemia, high alkaline phosphatase, high or normal 25(OH)D3, and low 1,25(OH)2D3. We studied two siblings in a Mexican family with an atypical form of VDDR1A. In addition to the typical features of VDDR1A, the proband showed cafe au lait spots, small teeth and grayish sclera, with hypophosphatemia, normocalcemia and normal 25(OH)D3, the proband´s brother showed grayish sclera. Proband underwent Next Generation Sequencing. Sanger sequencing was performed in the proband, his brother, the parents and 100 healthy controls for validation of detected variant. Both brothers presented a recurrent variant NM_000785.3; c.1319_1325dupCCCACCC and a novel nonsense variant NM_000785.3; c.227G>A in the CYP27B1 gene. Calcitriol treatment had better response in proband´s younger brother. We describe the first Mexican family with an atypical form of VDDR1A associated with novel nonsense variant, the results contribute to the phenotypic spectrum and increases the pool of pathogenic variants in CYP27B1. Data suggesting that nonsense-truncating variants play a significant role in the severity of VDDR1A.

CpG islands typically occur at or near the transcription start site of genes, particularly housekeeping genes, invertebrates. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the cytosines in such an arrangement tend to be methylated. Described DNA methylation mediated gene silencing occurs by direct inhibition of transcription factor binding to their relative sites and by recruitment of methyl binding domain proteins. The present study aims at predicting the CpG islands using Perl and R environment codes. The results indicated that the average length of the CpG islands in the X-chromosomes is comparable, however, the number of CpG islands is three times in swine (13539), as compared to that of rats (4465). The average CpG percent and the Average Guanine+Cytosine percent are also similar in the X-Chromosomes of both species. Similar results were evident for Y-Chromosome. The results obtained need validation through wet-lab experimentation.

Cellular therapies exhibit immense potential in treating complex diseases with sustained response. Manufacture of cell therapies involves purification and engineering of specific cells from a donor or patient to achieve a therapeutic response upon injection. Magnetic cell sorting targeting the presence or absence of surface markers is commonly used for upfront purification. However, emerging research is showing that optimal therapeutic phenotypes are characterized not only by the presence or absence of specific antigens but also on antigen density. Unfortunately, current cell purification tools like magnetic or fluorescence activated cell sorting lack the resolution to differentiate populations based on antigen density while maintaining scalability. Utilizing a technique known as Digital Magnetic Sorting (DMS) we demonstrate proof of concept for a scalable, magnetic based approach to fractionate cell populations based on antigen density level. Targeting CD4 on human leukocytes, DMS demonstrated fractionation into CD4High T cells and CD4Low monocytes/neutrophils as quantified by flow cytometry and single cell RNA sequencing. DMS also demonstrated high throughput processing at throughputs 5-10X faster than flow cytometry. We believe DMS can be leveraged and scaled to enable antigen density-based sorting in cell therapy manufacturing, leading to the production of more potent and sustainable cellular therapies.

The global landscape of health and disease has undergone significant transformations over the past several decades. While infectious diseases once dominated the morbidity and mortality statistics, non-communicable diseases (NCDs) have emerged as the leading cause of death and disability worldwide. This shift has profound implications for public health systems, healthcare delivery, and global health policies. This introduction aims to explore the main tendencies of disease burden, morbidity, and mortality in the world, with a special emphasis on NCDs and the Implications of Emerging AI Technologies. By examining the current trends and underlying factors, we can better understand the challenges and opportunities for improving global health outcomes.

Aural rehabilitation with hearing aids can decrease the attentional requirements of cognitive resources by amplifying the deteriorated-frequency sound in hearing loss patients and improve the auditory discrimination ability like speech-in-noise perception. As aural rehabilitation with an intelligible-hearing sound also can be hopeful, the aim of this study was to evaluate the effectiveness of the aural rehabilitation with intelligible-hearing sound for hearing loss patients. Adult native Japanese speakers (17 males and 23 females, 68.43±9.23 years) showed over 30 dB at 125, 250, 500, 1000, 2000, 3000, 4000, 8000, 10000, and 12000Hz on any side, were recruited and underwent Mini-Mental State Examination Japanese. we conducted self-evaluation questionnaire for hearing problems of voice, gap detection test, fast speech test, and speech-in-noise test, pure tone audiogram, speech perception test using Japanese 67-S, cortical auditory evoked fields, and magnetic mismatch negativity before and after the non-intelligible-hearing (N=20) and intelligible-hearing (N=20) sound therapy with listening to music for one hour a day for 35 days. Better hearing ear was defined using a four-frequency pure-tone average at the thresholds of 500, 1000, 2000 and 4000 Hz. After the sound therapy, speech-in-noise test with signal to noise ratio +10 in better hearing ear showed significant improvement (p<0.05), and N1m-P2m amplitudes showed the significant increase in Lt superior temporal gyrus at the stimulus from better hearing ear (p<0.05). The significant enhancement of the magnetic mismatch negativity amplitude at Lt superior temporal gyrus was exhibited after the sound therapy (p<0.01). Intelligible-hearing sound therapy can improve the ability of speech-in-noise perception in better hearing ear and the enhancement of central cortex response, which reflect the ability of working memory, was proved by cortical auditory evoked fields and magnetic mismatch negativity. Intelligible-hearing sound therapy can be a valuable aural rehabilitation method for sensory neural hearing loss as same as hearing aids.

Almost fifty years after the introduction of antibiotics as an antimicrobial agent, we are facing an increasing number of multi-resistant microbials. The search for new antimicrobial compounds emerged as a promising alternative to treatments for diseases caused by microorganisms such as fungi and bacteria. Thus, endophytic fungi are gaining recognition for their varied metabolites that may possess antimicrobial properties. In our research, we isolated, from Calea pinnatifida, six endophytic fungi identified as Colletotrichum siamense, Colletotrichum karstii, Hypomontagnella barbarensis, Neopestalotiopsis clavispora, Nigrospora sacchari-officinarum and Annulohypoxylon moriforme. Analyses of microbial secondary metabolites by utilizing UHPLC-HR-ESI-MS/MS in conjunction with molecular networking, allowed the annotation of 9 compounds, 5 of them from GNPS spectral library match, and 4 from prediction-based on the molecular network, and allowed the isolation of two pairs of Acyl-tetronic acid derivatives distereoisomeric identified by NMR spectrum. In this sense, the present study underlines the value of endophytic fungi as a reservoir of potentially new antimicrobial agents.

Background/Objectives: Congenital Radioulnar Synostosis (CRS) is a rare elbow joint disorder resulting from abnormal fusion of the radius and ulna during fetal development. Methods: Although predominantly sporadic, familial cases exist with autosomal dominant inheritance. Diagnosis relies on clinical evaluation and radiological findings, showcasing synostosis. Surgical decisions hinge on factors like age and symptom severity. Results: Multiple surgical treatments have been described but derotation osteotomy offers predictable results. Challenges include potential complications and cultural considerations influencing final forearm positioning. Conclusions: A nuanced approach is crucial for optimal management, highlighting the need for ongoing research to refine diagnostic and therapeutic strategies for improved outcomes in CRS patients.

Objective: A 1964 study challenged the consensus that saturated fat consumption increased the risk for myocardial infarction (MI). Roseto Pennsylvania, an Italian-American enclave of 1600 people, had similar rates of cigarette smoking, obesity and higher saturated fat consumption as neighboring towns, but far lower MI death rates. More than 50 years later, it remains uncertain if Roseto’s residents had better heart health than the average American and if so, what factors were responsible. Methods: We compared MI deaths in Roseto and neighboring towns to the Framingham Heart Study cohort matched for age and sex. Results: We found no evidence that MI deaths were lower in Roseto, PA than in Framingham, MA when controlling for age and sex. While the role of social support in health is uncontested, methodological issues, confounding factors and biases challenge the validity of the Roseto study. Conclusions: The dramatically lower MI and MI mortality rates among males in Roseto reflects biases in sampling and comparison populations, which also impacted the contrasting Diet-Heart hypothesis that saturated fats cause heart disease. Although social support enhances health outcomes, the Roseto study neither supported nor refuted this connection.

Estrogen receptor α (ERα) is a nuclear hormone receptor that mediates the biological effects of estrogen and is known to be phosphorylated at multiple sites. Despite several reports highlighting serine-167 (S167) of ERα as a common phosphorylation site for various kinases, there have been contradictory data regarding its relevance in the context of ERα-expressing luminal A breast cancer. In this study, we show that S167 is targeted by the oncogenic PIM family kinases in these cells. Loss of PIM expression or catalytic activity reduces S167 phosphorylation and restricts ERα signaling, while PIM overexpression has the opposite effect. Nonetheless, we found no evidence that PIMs protect breast cancer cells from ERα blockade, as both PIM protein levels and ERα S167 phosphorylation levels were substantially lower in populations of cells that had developed tamoxifen resistance as compared to untreated cells. However, this does not rule out the possibility that PIMs provide protection against ERα-targeting therapies in such breast cancer cells in which they are overexpressed, warranting further investigations.

Objectives: Epidemiologic and experimental animal studies have shown that stress can alter tumor growth and that adrenergic fibers from the sympathetic nervous system, acting through stromal β2-adrenergic receptors, promote tumor cell survival during the initial phases of cancer development. Recent epidemiological data suggest that beta blocker intake improves survival of prostate cancer patients. Methods: Signaling mediated by β-adrenergic receptors promotes neuroendocrine differentiation in prostate cancer cell line. Although neuroendocrine cells are a minor population in the epithelial compartment of normal prostate glands, the population of neuroendocrine-like cells that express markers such as SYN, Bcl-2, Dll-3, and AMACR correlates with cancer progression, androgen-independent state, and poor prognosis in prostate cancer patients. As recent studies show that an increase in neuroendocrine cell density occurs before development of benign prostatic hyperplasia (BPH), a non-lethal disease affecting the transition zone, in hypertensive rats, we investigated whether neuroendocrine differentiation is associated with BPH. Results: Our results showed that isobutyl-methyl-xanthine and forskolin leading to sustained activation of the cAMP/PKA pathway led to an increase in neuroendocrine differentiation markers in BPH-1 cell line. Similar results were observed by combining the β-adrenergic receptors agonist isoproterenol with forskolin. These treatments reduced BPH-1 cell proliferation rates by 40% and 60%, respectively. Effects on neuroendocrine markers expression and cell proliferation were fully reversed by the β2 blocker carvedilol. Conclusion: These data suggest that β-adrenergic receptors are linked to the development of neuroendocrine-like cells in BPH. As 20% of the prostate cancer tumors occur in this zone, this observation warrants further investigation.

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium brevis BBr60 group or a placebo group. Both groups received diet guidance and took either BBr60 (1×1010 CFU/day) or a placebo for 12 weeks. Re-searchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pre-treatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group (p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister, Klebsiella, and Bacteroides, which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulating BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.

Glioblastoma (GBM) is an incurable primary brain cancer characterized by increased reactive oxygen species (ROS) production. The redox-sensitive tumor suppressor gene TP53, wildtype (wt) for 70% of patients, regulates redox homeostasis. Glioblastoma stem cells (GSCs) increase thioredoxin (Trx) and glutathione (GSH) antioxidant systems as survival redox-adaptive mechanisms to maintain ROS below the cytotoxic threshold. Auranofin, an FDA-approved anti-rheumatoid drug, inhibits thioredoxin reductase 1 (TrxR1). L-buthionine sulfoximine (L-BSO) and the natural product piperlongumine (PPL) inhibit the GSH system. We evaluated the cytotoxic effects of Auranofin alone and in combination with L-BSO or PPL in GBM cell lines and GSCs with known TP53 status. The Cancer Genome Atlas/GBM analysis revealed a significant positive correlation between wtp53 and TrxR1 expression in GBM. Auranofin induced ROS-dependent cytotoxicity within a micromolar range in GSCs. Auranofin decreased TrxR1 expression, AKT(Ser-473) phosphorylation, increased p53, p21 and PARP-1 apoptotic cleavage in wtp53-GSCs, while mutant-p53 was decreased in a mutant-p53 GSC line. p53-knockdown in a wtp53-GSC line decreased TrxR1 expression and significantly increased sensitivity to auranofin, suggesting the role of wtp53 as a negative redox-sensitive mechanism in response to auranofin in GSCs. Auranofin and L-BSO combination synergistically increased ROS, decreased IC50s and induced long-term cytotoxicity irrespective of p53 in GBM cell lines and GSCs. Intriguingly, Auranofin increased expression of glutathione S-transferase pi-1 (GSTP-1), a target of PPL. Combination of auranofin with PPL synergistically decreased IC50s to a nanomolar range in GSCs, supporting the potential to repurpose auranofin and PPL in GBM.

Background: Dengue virus (DENV) infection is a significant public health concern in many trop-ical and subtropical regions, where early and rapid detection is crucial for effective patient man-agement and controlling the spread of the disease. Particularly in resource-limited, rural healthcare settings where dengue is endemic, there is a need for diagnostic methods that are both easy to perform and highly sensitive. Objective: This study focuses on the development and validation of a single-tube reverse tran-scription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of DENV. Methodology: The RT-LAMP assay designed in this work combines two sets of primers targeting the 5' and 3'-UTR regions of the dengue virus, aiming to increase the sensitivity of detection. Results: The clinical validation of this COMB-RT-LAMP in samples from febrile individuals with a serological or antigenic diagnosis showed a sensitivity of over 95%. The assay's perfor-mance was statistically compared to standard diagnostic method quantitative reverse transcrip-tion-polymerase chain reaction (qRT-PCR). Conclusions: The findings support the potential of RT-LAMP as a rapid, sensitive, and specific tool for dengue diagnosis and surveillance, particularly suitable for field use in low-resource set-tings.

Circadian rhythm (CR) influences various physiological functions, including physical and cognitive performance, which fluctuate throughout the day. The present study aimed to investigate the combined and separate effects of CR and physical fatigue on cognitive and physical performance. A sample of 18 amateur athletes was subjected to a series of tests at three different times of the day: morning, afternoon, and evening. Fatigue was induced following isokinetic concentric exercise combined with a 20-minute treadmill run, followed by assessments of selected physical and cognitive tasks. Repeated measures ANOVA did not reveal an interaction between CR and fatigue in cognitive performance (p &gt; 0.05). However, a significant main effect of fatigue was observed in visual reaction time (VisRT) across all three time points. Moreover, peak torque (PT) and peak torque fatigue index (PTFI) showed significant differences between the three times of the day, peaking in the evening. Although we found no interaction between CR and physical fatigue state on selected cognitive parameters at the three times of day, a separate effect of fatigue on cognitive performance was identified. Additionally, physical parameters exhibited peak values occurring in the evening hours. Future research should further explore underlying mechanisms that potentially influence cognitive performance at different times of the day.

Duchenne Muscular Dystrophy (DMD) is a pediatric disorder characterized by progressive muscle degeneration and premature death, with no cure at the moment. The currently most promising therapeutic avenue is based on gene replacement mediated by adeno-associated viruses (AAVs) using a shortened, but still functional, version of Dystrophin, known as microdystrophin (µDys), to fit AAV capacity. The limited improvements observed in clinical trials suggest a sub-optimal performance of µDys in the human context, that could be due to the lack of key domains in the protein. Therefore, expressing larger dystrophin proteins may be necessary for a more complete correction of the disease phenotype. In this study, we developed three novel Midi-Dystrophin constructs using a dual-AAV approach, leveraging split intein-based protein trans-splicing. The midi-dystrophins include additional domains compared to µDys, such as the central cytoskeleton-binding domain, nNOS and Par1b interacting domains, and a complete C-terminal region. Given the limited capacity of each AAV vector, we strategically partially reduced hinge regions while ensuring that the structural stability of the protein remains intact. We predicted the interactions between the two halves of the split Midi-Dys proteins thanks to the deep-learning algorithm AphaFold3. We observed strong associations between the N- and C-termini in Midi-Dys 1 and 2, while a weaker interaction in Midi-Dys 3 was revealed. Our subsequent experiments confirmed the efficient protein trans-splicing both in vitro and in vivo in DBA2/mdx mice of the Midi-Dys 1 and 2 and not in Midi-Dy3 as expected from the structural prediction. Additionally, we demonstrated that Midi-Dys 1 and 2 exhibit significant therapeutic efficacy in DBA2/mdx mice, highlighting their potential as therapeutic agents for DMD. Overall, these findings highlight the potential of deep learning-based structural modeling for the generation of intein-based dystrophin versions and pose the basis for further investigation of these new midi-dystrophins versions for clinical studies.

Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Besides, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in subjects post-COVID-19. The study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. On the other hand, those subjects who have a psychiatric diagnosis are considered. Besides, the MoCA and MMSE scales were applied. Telomere length was determined using a Polymerase Chain Reaction, and statistical analysis was employed ANOVA and X2 tests. We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p≤0.05). However, no association was found between LTL and cognitive impairment in subjects post-COVID-19. The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition.

Amuyo Ponds (AP) are a group of three hydrothermal lagoons located at 3,700 m above sea level, in a pre-Andean setting at the Atacama Desert. Each pond shows a conspicuous green, red, or yellow coloration, and discharge waters rich in arsenic and boron into the Caritaya River (Camarones Basin, Arica and Parinacota Region, in northern Chile). Microorganisms at these ponds are subjected to harsh environmental conditions, and microbial composition and diversity in Amuyo Ponds sediments are unknown. Then, microbial life colonizing AP sediments was explored by metagenomics analyses. This approach showed a highly diverse microbial life dominated by members of the Bacterial Domain (nearly 800 bacterial genome sequences) and includes sequences associated to Archaea, Eukarya, and viruses. We also report putative functional capabilities related to virulence and defense genes, and biosynthesis of secondary metabolites. Thirteen bacterial and fourteen virus metagenome-assembled genomes were reconstructed and are here informed. This work expands our knowledge on the richness of microorganisms in AP and open further studies on the ecology and genomics of this striking Andean geosite.

Living processes are integral to open systems for multiple reasons. From a thermodynamic perspective, they reduce local entropy at the cost of increasing environmental entropy. Furthermore, these processes are inherently nonlinear owing to their feedback interactions with the environment. Nonlinear systems exhibit diverse behaviours: some stabilize at a constant value, whereas others display bifurcations and chaotic dynamics. This study introduces a model that describes living processes as the dynamics of nonlinear single-value diverging maps, whereas chaotic evolution is associated with the increasing entropy environment. This model enables us to describe the lifetime of different species simply by varying the model parameters. This model also simplifies explaining the transition from life to death.

Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to the innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids(GPLs), and sterols, in Rhizopus delemar 99-880, a well-characterized reference strain among Mucorales. Through high-throughput analysis involving the identification and quantification of intermediates, we have elucidated the biosynthetic pathways of SLs, PGLs, and sterols. Notably, the acidic SLs were not found probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of R. delemar 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms.

Obesity and chronic inflammation are well-known risk factors for cancer. Interleukin-33 (IL-33) functions in inflammatory diseases, particularly those related to obesity and cancer. However, the correlation and molecular mechanisms linking IL-33, obesity, and cancer remain unclear. IL-33 is a nuclear cytokine released as an alarm signal when cells are damaged or stressed. It is expressed in epithelial, endothelial, and fibroblast-like cells during normal conditions and in-flammation. When IL-33 is present, immune cells expressing the IL-1RL1/ST2 receptor are alerted in response to tissue damage or cell injury. Research on IL-33 and its correlation with obesity has revealed improvements in inflammatory and metabolic changes associated with obesity. IL-33 can have both pro-tumorigenic and antitumorigenic effects, depending on the cellular content, in-flammatory environment, expression levels, and bioactivity of IL-33. This review will discuss the various functions of IL-33 in obesity-driven inflammation and cancers and how they intersect.

Keywords: cranberry, exercise, proteomics, oxylipins, gut microbiome, metabolomics, immunity

Stem cell-derived therapies have shown substantial promise in regenerative medicine for the treatment of degenerative diseases and injuries. Mesenchymal Stem Cells (MSCs) exhibit a remarkable capacity to differentiate into diverse cell types, modulate immune responses, and facilitate tissue repair. Nevertheless, concerns regarding their potential to induce tumors arise from their intrinsic properties, environmental factors, and genetic mutations that occur during handling. This review explores the intricate challenges associated with the tumorigenic potential of stem cell-derived therapeutic products and examines the underlying mechanisms contributing to this risk, such as oncogene activation, suppression of tumor suppressor genes, and the influence of the microenvironment on stem cell behavior. Furthermore, it delves into the role of epigenetic modifications and chromosomal aberrations in cell culture and expansion. This article provides an overview of strategies to mitigate tumorigenic risks, encompassing rigorous quality control measures, refined differentiation protocols, and advanced screening techniques. It also highlights innovative approaches, such as gene editing technologies and small-molecule modulation of stem cell behavior, as promising avenues to enhance safety. Despite these challenges, ongoing research and technological advancements are actively addressing these concerns to ensure safer and more effective utilization of stem cell-based therapies in clinical settings.

Leucine is an essential amino acid that cannot be produced endogenously in the human body and therefore needs to be obtained from dietary sources. Leucine plays a pivotal role in stimulating muscle protein synthesis along with isoleucine and valine as the group of branched-chain amino acids making them as one of the most popular dietary supplements for athletes and gym-goers. Individual effects of leucine, however, are not fully clarified, as most of the studies focused on the grouped effects of branched-chain amino acids. In recent years, leucine and its metabolites have been shown to stimulate muscle protein synthesis mainly via mammalian target of rapamycin complex 1 signaling pathway, thereby improving muscle atrophy in cancer cachexia. Interestingly, cancer research suggests that leucine may have either anti-cancer or carcinogenic effects. In the current manuscript, we aim to review leucine's roles in muscle protein synthesis, tumor suppression, and tumor progression, specifically summarizing the molecular mechanisms of leucine's action. The role of leucine is controversial in hepatocellular carcinoma, whereas its carcinogenic effects have been demonstrated in breast and pancreatic cancers. In summary, leucine being used as nutritional supplement for athletes needs more attention, as its oncogenic effects may have been identified by recent studies. Anti-cancer or carcinogenic effects of leucine in various cancers should be further investigated to have clear conclusions.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by its aggressive progression and dismal prognosis. Advances in epigenetic profiling, specifically DNA methylation analysis, have significantly deepened our understanding of PDAC pathogenesis. This review synthesizes findings from recent genome-wide DNA methylation studies, notably those by Espinet et al. and Wang et al., which have delineated a complex DNA methylation landscape differentiating between normal and cancerous pancreatic tissues, as well as across various stages and molecular subtypes of PDAC. These studies identified specific differentially methylated regions (DMRs) that not only enhance our grasp of the epigenetic drivers of PDAC but also offer potential biomarkers for early diagnosis and prognosis, enabling the customization of therapeutic approaches. The review further explores how DNA methylation profiling could facilitate the development of subtype-tailored therapies, potentially improving treatment outcomes based on precise molecular characterizations. Overall, leveraging DNA methylation alterations as functional biomarkers holds promise for advancing our understanding of disease progression and refining PDAC management strategies, which could lead to improved patient outcomes and a deeper comprehension of the disease’s underlying biological mechanisms.

The present work offers a contemporary synthesis of the application of the Oxford Nanopore^® MinION^™ within the context of cultural heritage biodeterioration investigations, while also providing a comprehensive discussion of possible future perspectives for their utilization in this research field. Owing to the distinctive characteristics of this device, the past few years have witnessed the consistent increase on the application of this system in a variety of cultural heritage materials. In fact, the technique has been useful to understand microbial biodeteriogens diversity and some of their metabolic and biodeteriogenic features. Considering the immense potential for application of this system, this manuscript explores and discusses further possibilities of the technique, focusing on helping understand critical questions on the cultural heritage biodeterioration area. Its application in various differential contexts, has opened doors for prospective applications on other interesting sub-areas of research meriting future investigations, including: biodeteriogens genome and transcriptome analysis, metatranscriptomics, biodeteriorative metabolism studies, inter and intra kingdom interactions analysis, resistome profiling, object history and context studies, in situ applications, bioprospecting and biotechnology.

UVA1 phototherapy has been reported to mediate some of its effects via FICZ/AHR/MAPK signaling. A proof-of-concept study was performed to assess whether a topical solution of L tryptophan formulated to favor the generation 6-formylindolo[3,2-b] carbazole (FICZ) demonstrated activity at the aryl hydrocarbon receptor (AHR) as assessed by the intensity of cytochrome P450 1A2 staining. Ten participants applied a trial agent consisting of L- tryptophan, lecithin, polyvinyl alcohol and ethanol followed by 36 sessions of graduated sun exposure increasing to a total of 20 Joules per square centimetre. At the end of the trial, biopsies were taken from a treated site with photo-protected buttock skin used as a control. Assessment was via intensity of cytochrome P450 1A2 staining. An average baseline value of 53488923 units was obtained at the control site and 972214294 at the treatment site supporting the concept that this preparation displays activity at the AHR. As the components of this preparation are known to have UV absorbing properties and are potentially permissive of UVA-1 transmission, UV absorbance was assessed for natural sunlight and at 365 and 395nm confirming strong absorption in the UVB and UVA-2 spectra with partial transmission in the UVA-1 spectrum.

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different than the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method.

More than 90% of patients affected by mastocytosis are characterized by a somatic point mutation of c-KIT, which induces ligand-independent activation of the receptor and downstream signal triggering, ultimately leading to mast cell proliferation and survival. The most frequent mutation is c-KIT p.D816V, but other rarer mutations can also be found. These mutations often have a very low variant allele frequency (VAF), well below the sensitivity of common next-generation sequencing (NGS) methods used in routine diagnostic panels. Highly sensitive methods are developing for detecting mutations. This review summarizes the current indications on the recommended methods and on how to manage and interpret molecular data for the diagnosis and follow-up of patients with mastocytosis.

Rationale: Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknow. Methods: Our study included 9 patients with hepatocellular carcinoma (HCC) undergoing PHx: 3 patients with PHLF, 3 patients undergoing the Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) procedure and three matched controls without complications after PHx. Patient plasma was collected before (PRE), 1 and 5 days (POD1, POD5) after PHx. EVs were isolated by ultracentrifugation and extracted proteins subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell-lines. Results: We identified 2625 and quantified 2570 proteins in EVs in PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF compared to patients undergoing ALPPS. The EV-proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodeling, metabolic and cell cycle pathways, present already before PHx. Conclusion: Longitudinal proteomic analysis of EV´s circulating in human patient plasma undergoing PHx uncovers proteomic signatures associated with PHLF which reflect dying hepatocytes and endothelial cells and are present before PHx already. Our results support EVs as potential biomarkers and therapeutic targets for liver regeneration and failure.

This study explored the correlation between concentrations of phenolic compounds (phenols, tannins, and flavonoids) and the versatility of woody medicinal plants in the Caatinga, a seasonally dry forest region in Brazil. We examined whether these compounds influence the versatility of plants used by populations, given their known therapeutic properties. Plants were categorized as high or low versatility based on their relative importance (RI) values ​​at the regional level. Samples collected in Catimbau National Park, Pernambuco, were analyzed using colorimetric methods: Folin-Ciocalteu reagent for total phenols, casein precipitation for tannins, and aluminum chloride complexation for flavonoids. Contrary to expectations, no significant differences in phenolic compound concentrations were found between the high and low versatility groups. Higher levels of total phenols and tannins were observed in Myracrodruon urundeuva and Anadenanthera colubrina, both highly versatile species. However, less versatile species, such as Mimosa tenuiflora and Schinopsis brasiliensis, also showed high levels. Flavonoid content, notably lower than phenols and tannins, did not show significant variation between groups. Although phenolic compounds contribute to the therapeutic properties of medicinal plants, their concentration alone does not determine the versatility of plants in the Caatinga. Versatility is more likely influenced by ecological conditions, cultural practices, and species availability. This study highlights the need to integrate multiple perspectives in ethnopharmacological research.

Background: Ubiquitination is an important post-transcriptional modification crucial for maintaining cell homeostasis. As a deubiquitination enzyme, ubiquitin-specific protease 1 (USP1) is associated with tumor progression; however, its role in bladder cancer is unknown. This study was aimed to analyze USP1 expression and study its roles in bladder cancer. Methods: The web server GEPIA was used to analyze the USP1 expression. To explore USP1 function in bladder cancer, we constructed USP1-knockout cell lines in UMUC3 cells. A FLAG-USP1 (WT USP1) plasmid and a plasmid FLAG-USP1 C90S (catalytic-inactive mutant) used to overexpress USP1 in T24 cells. CCK8, colony formation, and transwell assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP1 and c-MYC. Xenograft mouse model was used to study the role of USP1 in bladder cancer. Results: USP1 expression is upregulated in human bladder cancer cells and correlated with poor patient prognosis. USP1 overexpression promoted cell proliferation, clone formation, and migration; this was attenuated by genetic ablation of USP1. Furthermore, we observed that USP1- deficiency inhibited tumor formation in vivo. Mechanistically, the c-MYC pathway was remarkably activated compared with the other pathways. Furthermore, USP1 could directly interact with c-MYC. and increase c-MYC stability depending on the catalytic activity of USP1. Conclusions: Our results suggest that high expression of USP1 promotes bladder cancer progression by stabilizing c-MYC; hence, USP1 it may serve as a novel therapeutic target for treating bladder cancer.

Type 2 Diabetes mellitus (T2DM) and cancer share common risk factors including obesity, in-flammation, hyperglycemia, and hyperinsulinemia. High insulin levels activate PI3K/Akt/mTOR signaling pathway promoting cancer cell growth, survival, proliferation, metastasis, and an-ti-apoptosis. The inhibition of PI3K/Akt/mTOR signaling pathway for cancer remains a promising therapy, however, the combination of therapeutic inhibitors may solve the resistance to such agents. Understanding the metabolic link between diabetes and cancer can assist in improving the therapeutic strategies used for the management of cancer patients with diabetes and vice versa. This review provides an overview of shared molecular mechanisms between diabetes and cancer as well as discusses established and emerging therapeutic anti-cancer agents targeting the PI3K/Akt/mTOR pathway in cancer management.

Mediterranean diet has been widely suggested to exert significant beneficial effects on endothelial oxida-tive status and cardiometabolic health. Greek Orthodox monasteries, due to their specific nutritionaland sartorial habits, comprise a population which strictly adheres to nutritional patterns with restricted eating and a plant-based subset of the Mediter-ranean diet, often accompanied by profound hypovitaminosis D. Time –restricted eating is also adopted from a large part of general lay Greek population for health promoting reasons, without restrictions on an-imal product consumption, as imposed by Orthodox religious fasting. However, comparative effects of these nutritional patterns on oxidative stress markers remain scarce. The present study attempted to evaluate the effects of Christian Orthodox fasting (COF) in a group of vitamin D –deficient and overweight Orthodox nuns from Central and Northern Greece, compared to the implementation of TRE, 16:8 dietary regimen in a cohort of adult women from the general population from the same region, with regard to markers of endothelial oxidative status. A group of 50 women from two Orthodox monasteries in Northern Greece and one group of 50 healthy lay women were included. During enrollment a detailed recording of dietary habits was performed, along with a scientific registry of demographic and anthropometric characteristics (via bioimped-ance).Orthodox nuns followed a typical Orthodox fasting regimen[daily feeding window (8 am–4 pm)] whereas lay women followed a TRE 16:8 regimen with the same feeding time-window with recommenda-tion to follow a low-fat diet, without characteristics of the Mediterranean diet. We included a complete biochemical analysis, as well as calciotropic profiles [Calcium-Ca, Albumin, Parathyroid hormone-PTH, 25-hydroxyvitamin D- 25(OH)D] as well as and markers of TAC (trichloroacetic acid), (glutathione) GSH and thiobarbituric acid reactive substances (TBARS) concentrations, as markers of oxidative status. All groups were comparable at baseline for calcium, PTH and 25(OH)D concentrations, with no significant differences between groups. Orthodox nuns manifested a lower median GSH compared to con-trols (6.0 vs. 7.2, p 0.04) and a higher median TAC (0.92 vs. 0.77, p <0.001). TBARS comparisons showed no significant difference between the two groups. No significant associations of oxidative status with 25(OH)D, PTH and markers of glucose homeostasis were evident. Results of this small pilot study indicate that both dietary regimens have advantages over oxidative markers compared to each other, with increased TAC in the groups of Orthodox Nuns after a 16th week period of COF compared to a 16:8 TRE and increased GSH concentrations in the lay women group. Future randomized trials are required to investigate superiority or non-inferiority between these dietary patterns, in the daily clinical setting.

The medical care and welfare of domestic dogs are now respected worldwide at the same level as that of humans. We previously established a test method to determine whole mitochondrial DNA (mtDNA) using oral mucosal DNA that may be useful for the medical care and welfare of dogs. However, the sample types tested in dogs are not limited to those obtained from the oral mucosa. Therefore, in the present study, we attempted to establish a test method to determine whole mtDNA sequences using feces, which represents the least invasive specimen. Two Japanese domestic dogs were used in the present study. DNA was extracted from approximately 100 mg of fresh feces from each dog, and PCRs were performed using four primer-pairs that can amplify whole mtDNA. Following PCR, amplicons were pooled to create a DNA library using an experimental robot with an original program. Data were then acquired via NGS and data analysis was performed. The results showed that the whole mtDNA sequence of the two dogs was determined with high accuracy. Our results suggest that feces can be adapted for mitochondrial disease and individual identification testing and could serve as a useful testing method for the future medical care and welfare of domestic dogs.

This paper examines the utility and exploitation of non-obvious "alien" AI constructions, artificial intelligence solutions that significantly deviate from human intuition and traditional problem-solving approaches. It explores recent revelations, key characteristics, applications across various domains, and far-reaching implications for scientific research and innovation. Particular attention is given to developments in mathematical reasoning, drug discovery, and healthcare. The paper also discusses challenges in implementation, ethical considerations, and future directions, including meta-learning algorithms and human-AI collaboration frameworks. By synthesizing current research and identifying emerging trends, this paper aims to provide a basic understanding of the transformative potential of non-obvious AI solutions in reshaping scientific discovery and biomedical innovation.

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an Area Under the Curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6 - 40.8) with p&lt;0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

Obesity looms large in the contemporary health landscape, extending its impact beyond physical appearance to influencing overall well-being. This slow intruder subtly weaves its influence through society, affecting individual health and presenting a significant public health dilemma. Beyond the visible weight gain, a web of interconnected health issues emerges, from cardiovascular complications to metabolic disorders, casting a pervasive shadow over the pursuit of a healthy, fulfilling life. In response to the escalating prevalence of obesity and its associated health complexities, there is a growing interest in swift weight management medications. However, current pharmacotherapies targeting crucial weight management pathways often fall short due to substantial side effects outweighing their benefits. Recently, plant extracts have emerged as potential regulators of lipid metabolism and obesity by influencing gut microbiota composition and abundance. This comprehensive review takes deep dive into the potential roles of Salvia spp. phytochemicals as health-promoting agents, with a specific focus on the anti-obesity properties of Salvia spp. by compiling a wealth of in-vitro, in-vivo and clinical studies. Drawing from the latest research, we unravel the potential of Salvia spp. by shedding light on their underlying mechanisms intertwined with gut microbiota dynamics. As scientific inquiry progresses, unraveling the intricate interplay between plant extracts, gut microbiota, and metabolic health holds tremendous promise for addressing the escalating global burden of obesity. This review is a humble attempt to provide a valuable synthesis of current knowledge, so as to pave the way for future advancements in pursuit of effective anti-obesity strategies for clinical interventions.

As the number of publications is quickly growing in any area of science, the need to efficiently find relevant information amidst a large number of similarly themed articles becomes very important. Semantic searching through text documents has the potential to overcome the limits of keyword-based searches, especially since the introduction of attention-based transformers, which can capture contextual nuances of meaning in single words, sentences or whole documents. The deployment of these computational tools has been made simpler and accessible to investigators in every field of research thanks to a growing number of dedicated libraries, but a knowledge of how meaning representation strategies work is crucial to make the most out of these instruments. The present work aims at introducing the technical evolution of the meaning representation systems, from vectors to embeddings and transformers tailored to life science investigators with no previous knowledge of natural language processing.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

Decidualization of the uterine endometrium is a critical process for embryo implantation in mammals, primarily occurring on gestational day 8 in pregnant mice. However, the interplay between the maternal gut microbiome, metabolism, and the uterus at this specific time point remains poorly understood. This study employed a multi-omics approach to investigate the metabolic, gut microbiome, and transcriptomic changes associated with early pregnancy (gestational day 8 (E8)) in mice. Serum metabolomics revealed a distinct metabolic profile in E8 compared to controls, with differential metabolites primarily enriched in amino acid metabolism pathways. Gut microbial composition showed that E8 mice exhibited higher alpha-diversity and a significant shift of beta-diversity. Specifically, the E8 group displayed a decrease in pathogenic Proteobacteria and an increase in beneficial Bacteroidetes and S24-7 taxa. Transcriptomics identified myriads of distinct gene between E8 and control mice. The differentially expressed genes were enriched in pathways involved in Alanine, Aspartate and Glutamate metabolism, PI3K-Akt signaling, and PPAR signaling pathway. Integrative analysis of the multi-omics data uncovered potential mechanistic relationships among the differential metabolites, gut microbiota, and uterine gene expression changes. Notably, the gene Asns showed strong correlations with specific gut S24-7 and metabolite L-Aspartatic acid, suggesting its potential role in mediating the crosstalk between the maternal environment and embryo development during early pregnancy. These findings provide valuable insights into the complex interplay between the maternal metabolome, gut microbiome, and uterine transcriptome in the context of early pregnancy, which may contribute to our understanding of the underlying mechanisms of embryo implantation and development.

Cumulative evidence attests to the essential roles of commensal microbes in the physiology of the hosts. Although microbiome has been a major research subject since the time of Luis Pasteur and William Russell over 140 years ago, recent findings that certain intracellular bacteria contribute to the pathophysiology of healthy or diseased tissues have brought the field of microbiome to a new era of investigation. In particular, in the field of breast cancer research, breast-tumor resident bacteria are deemed to be the essential players of tumor initiation and progression. This is a resurrection of Russel’s bacterial cause of cancer theory abandoned over 100 years ago. This review will introduce some of the recent findings that exemplify the roles of breast tumor-resident microbes in breast carcinogenesis and metastasis and provide mechanistic explanations of these phenomena. Such information would be able to justify the utility of breast-tumor resident microbes as biomarkers for disease progression and therapeutic targets.

Introduction: Diagnosing and managing Borrelia miyamotoi disease (BMD) is challenging due to its symptom overlap with Lyme disease (LD) and the lack of reliable laboratory diagnostics for BMD. This case study demonstrates the use of phage-based PCR (phb-PCR) to identify B. miyamotoi in a patient who had been bitten by ticks. Case presentation: A female patient aged 46 presented with joint and muscle pain, myalgic encephalomyelitis/chronic fatigue syndrome, and cognitive impairment after multiple tick bites in Europe. The patient was assessed for LD at the National Reference Centre in Strasbourg using Enzyme-linked immunosorbent assay (ELISA) and immunoblot. Additional diagnostics involved screening for Bartonella and Anaplasma antibodies using indirect immunofluorescence, and tests for antinuclear antibodies to check for autoimmune conditions. All serological and immunological tests yielded negative results. However, the phb-PCR identified B. miyamotoi. Consequently, the patient received treatment for BMD with a regimen of intravenous ceftriaxone, oral azithromycin, and additional intravenous vitamin and mineral therapy. Post-treatment evaluations showed significant improvements in pain levels, cognitive abilities, and fatigue. Conclusion: This case highlights the importance of direct diagnostic methods like phb-PCR for identifying BMD when serological tests fail. Clinicians should consider B. miyamotoi testing for accurate and timely management of complex TBDs.

Due to its intriguing applications across a wide range of industries, nanotechnology is generating a lot of interest globally. Titanium dioxide (TiO2) nanoparticles are one type of nanoparticle (NP) that is commonly utilised in everyday use and can be produced using a variety of physical, chemical, and environmentally friendly techniques. Green synthesis is an economical, environmentally benign, and non-toxic method of synthesising NPs. Under normal circumstances, the application of TiO2 greatly enhanced the plants' shoot length, leaf area, and root dry weight. These growth-promoting factors coincided with elevated proline, soluble sugar, and chlorophyll B levels as well as improved antioxidant enzyme activity. Thus, higher levels of proline and other metabolites played a role in osmo-protection, while increased antioxidant enzyme activities helped to explain the observed decrease in hydrogen peroxide and malondialdehyde contents. Taken together, these factors significantly improved plant growth under salinity. TiO2 nanoparticles have demonstrated efficacy in treating contaminated water and have been shown to positively impact plant physiology, particularly in response to abiotic stresses. However, the reaction to these nanoparticles varies depending on characteristics such as metal species, type, size, shape, dose, duration of exposure, and other variables. One of the most popular nanomaterials in customer goods, agricultural, and energy industries is TiO2 NPs. Therefore, harm to ecosystems and living things will unavoidably result from high demand and widespread usage. Gaining more knowledge about the toxicity of TiO2 NP to living things could help with risk assessments and safe handling procedures for these nanoparticles. The synthesis of titanium oxide, its many uses, the toxicity of titanium dioxide nanoparticles, and their mode of toxicity are all summarised in this paper.

Background/Objectives: The latest WHO classification underscores the importance of the complete blood count (CBC) and cell morphology assessment in diagnosing lymphoid neoplasms. This study evaluated the diagnostic role of Research Use Only (RUO) parameters from the BC-6800 Plus Mindray analyzer in differentiating cell chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and other lymphoproliferative disorders. Methods: CBCs were performed on 90 patients (66% male, median age 67 years) with pathological blood counts (ALL, n=14; CLL, n=47; other lymphoproliferative disorders, n=29) at Novara’s University Hospital. Univariable and multivariable logistic regression assessed the association of basic (WBC, Hb, RDW, NE#, LY#, MO#, PLT) and research cell parameters (NLR, NMR, LMR, NeuX, NeuY, NeuZ, LymX, LymY, LymZ, MonX, MonY, MonZ). Results: In multivariable analysis, Hb (p=0.02), NeuY (p=0.04), and MonY (p=0.01) independently predicted CLL versus ALL, correctly classifying 93.4% of cases (AUC 0.91, 95% CI 0.81-1.0). MO# (p=0.003), LymY (p&lt;0.0001), and MonY (p=0.004) were independent predictors of CLL versus other lymphoproliferative disorders, classifying 77.6% of cases (AUC 0.86, 95% CI 0.78-0.95). NeuZ (p=0.01) and NeuY (p=0.04) independently predicted ALL versus other lymphoproliferative disorders, classifying 93% of cases (AUC 0.98, 95% CI 0.95-1.0). Conclusions: The use of RUO parameters offers valuable, cost-effective support in the early diagnosis of ALL, CLL, and other lymphoproliferative disorders.

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination. Traditional methods of sterilization (heat and irradiation) can denature collagen. This study addresses these issues by introducing a novel technique: double filtration and low-temperature steam sterilization of a collagen gel. In vitro tests document sterility and confirm that the collagen structure remained intact without modification. An in vivo study found no adverse effects in rats or significant lesions at the implantation site over 13 weeks. These results suggest that this novel method to process collagen gels is a safe and effective skin booster. Advanced processing methods are likely to mitigate safety risks associated with injectable collagen products, though further research is needed to validate their biological effectiveness and clinical benefits.

Importance: Neuropsychiatric disorders like schizophrenia and bipolar disorder lack objective diagnostic markers, hindering accurate diagnosis and treatment. A novel approach using patient-derived cerebral organoids and digital analysis of electrophysiological recordings could provide much-needed objective biomarkers.Objective: To develop a digital analysis pipeline that can identify distinct electrophysiological signatures of schizophrenia and bipolar disorder using multi-electrode array recordings from patient-derived cerebral organoids.Design: This was an experimental study using previously published data. The study type can be classified as a case-control study, comparing cerebral organoids and 2D neuronal cultures derived from patients with schizophrenia, bipolar disorder, and healthy controls. The study utilized multi-electrode array recordings for analysis. Setting: The study was conducted in a laboratory setting using previously recorded data. Main Outcomes and Measures: The primary outcome was the accuracy of a support vector machine classifier in distinguishing between healthy control, schizophrenia, and bipolar disorder samples based on electrophysiological features extracted from the recordings. Key cellular-digital biomarkers were identified using minimum redundancy maximum relevance feature selection.Results:Our Support Vector Machine classifier achieved 95.8% accuracy in distinguishing SCZ from control samples in 2D neuronal cultures under both baseline and post-electrical stimulation (PES) conditions. For cerebral organoids, classification accuracy was 83.3% under baseline conditions, improving to 91.6% under PES when distinguishing between control, SCZ, and BPD samples. Key features for classification included channel-specific measures such as median, covariance, autocorrelation, and kurtosis of neural activity. Confusion matrices visualize classification performance, with most misclassifications occurring in the BPD class under baseline conditions. These results demonstrate that our digital analysis pipeline can effectively distinguish between healthy control and patient-derived samples using electrophysiological features from multi-electrode array recordings, particularly under PES conditions.Conclusions and Relevance: This digital analysis pipeline demonstrates the potential to identify objective electrophysiological signatures of schizophrenia and bipolar disorder using patient-derived cerebral organoids. This approach could lead to improved diagnostic accuracy and personalized treatment strategies for neuropsychiatric disorders.

I present the first complete theory of ADHD. ADHD occurs when the organism adapts to try to maintain higher glucose levels than normal. The main mechanism via which this is done is by faster opening of KATP channels, mainly Kir6.2/SUR1, which increases the cell's intrinsic \xtblty. I show that this induces all of the symptoms of ADHD. The optimal treatment for ADHD already exists, since drugs of the sulfonylurea family close KATP channels and have been used for safely treating people for dozens of years.

Butirosins are naturally occurring aminoglycoside (AG) antibiotics featuring a 4,5-disubstituted 2-deoxystreptamine (2-DOS) with a (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. This side chain has been shown to confer resistance against AG modifying enzymes, leading to ongoing studies on the butirosin biosynthetic pathway and the corresponding enzymes. Butirosin is produced by Niallia (formerly Bacillus) circulans and Bacillus vitellinus, with most research focused on the former strain. To date, no whole genome analysis has been performed on B. vitellinus. In this study, we sequenced the complete genome of B. vitellinus NBRC 13296 and performed a comparative analysis of different butirosin biosyntheric gene clusters (BGCs), including those from N. circulans. The complete genome of B. vitellinus NBRC 13296 comprises a 6,331,192 base circlular chromosome with a GC content of 52.68%. The annotation revealed the presence of 5,605 CDSs, 70 tRNA genes, 30 rRNA genes, and 3 ncRNA genes in NBRC 13296. The highest dDDH and ANI values between NBRC 13296 and the most closely related type strain, Paenibacillus chitinolyticus KCCM 41400, were 97.8% and 98.66%, respectively. Based on these genome-based comparative analyses, we propose reclassifying B. vitellinus NBRC 13296 as P. chitinolyticus. Genome mining revealed 18 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of B. vitellinus NBRC 13296, indicating the enormous biosynthetic potential of this strain. The predicted structural diversity of secondary metabolites includes aminoglycoside, PKS, NRPS, PKS-NRPS hybrids, metallophores, phosphonates, terpenes, β-lactones, and RiPP peptides. We then comparatively characterized butorosin BGCs previously studied in several N. circulans strains. Additionally, comparative genome analysis revealed complete butirosin BGCs identified from P. chitinolyticus KCCM 41400, P. chitinolyticus NRRL B-23119, P. chitinolyticus NRRL B-23120, P. chitinolyticus B-14908, P. chitinolyticus YSY-3.1, P. chitinolyticus JMW06, Paenibacillus sp. GbtcB18, Paenibacillus sp. HGH0039, Paenibacillus sp. MZ04-78.2. Finally, we identified the core region consisting of BtrS, BtrN, BtrM, BtrL, BtrA, BtrB, BtrC, BtrD, BtrD, BtrE, BtrF, BtrG, BtrH, BtrI, BtrI, BtrJ, BtrK, BtrO, BtrP, and BtrV, followed by an upstream region organizing BtrQ, BtrW, BtrX, BtrY, and BtrZ in the same transcriptional direction and sequential genetic arrangement, and a downstream region organizing various proteins based on BtrT, BtrR2, BtrU, and BtrR1. Our study provided insights into the reclassification of B. vitellinus NBRC 13296 to P. chitinolyticus and suggested the need for continued studies on butirosin biosynthesis from an enzymatic perspective.

Cardiovascular disease is a leading cause of morbidity and mortality. New research elucidates in-creasingly complex relationships between cardiac and metabolic health, giving rise to new possible therapeutic targets. Sphingolipids are a heterogenous class of bioactive lipids with critical roles in normal human physiology. They have also been shown to play both protective and deleterious roles in the pathogenesis of cardiovascular disease. This review will explore the roles of Sphingolipids in vascular, cardiac, and metabolic pathologies and will evaluate the therapeutic potential in targeting Sphingolipids with the aim of prevention and reversal of cardiovascular disease, in order to improve long-term cardiovascular outcomes.

Fungi inhabiting deep subseafloor sediments have been shown to possess anaerobic methane (CH₄) production capabilities under atmospheric conditions. However, their ability to produce CH₄ under in situ conditions with high hydrostatic pressure (HHP) remains unclear. Here, Schizophyllum commune 20R-7-F01, isolated from ~ 2 km below the seafloor, was cultured in Seawater Medium (SM) in culture bottles fitted with sterile syringes for pressure equilibration. Subsequently, these culture bottles were transferred into 1-liter stainless steel pressure vessels at 30 °C for 5 days to simulate in situ HHP and anaerobic environments. Our comprehensive analysis of bioactivity, biomass, transcriptomics revealed that S. commune not only survived but significantly enhanced CH₄ production, reaching approximately 2.5 times higher levels under 35 MPa HHP compared to 0.1 MPa standard atmospheric pressure. Pathways associated with carbohydrate metabolism, methylation, hydrolase activity, cysteine and methionine metabolism, and oxidoreductase activity were notably activated under HHP. Specifically, key genes involved in fungal anaerobic CH₄ synthesis, including methyltransferase mct1 and dehalogenase dh3, were upregulated 7.9- and 12.5-fold, respectively, under HHP. Enhanced CH₄ production under HHP was primarily attributed to oxidative stress induced by pressure, supported by intracellular Reactive Oxygen Species (ROS) levels and comparative treatments with cadmium chloride and hydrogen peroxide. These findings suggest that fungi persisting in deep-sea sediments over millions of years have the potential to significantly contribute to global CH₄ flux.

This literature review presents a comparative analysis of cranial morphology in Allosaurus, focusing on its implications for feeding mechanics. Allosaurus, a large theropod dinosaur from the Late Jurassic period, exhibits distinct cranial features that are pivotal for understanding its predatory behaviors and ecological role. By examining fossilized skulls and employing advanced imaging techniques, this research identifies key morphological traits such as tooth structure, jaw articulation, and cranial robusticity. The analysis reveals that Allosaurus had a specialized cranial architecture that supported a powerful bite force and efficient processing of prey. Comparative metrics are applied to assess similarities and differences with other theropods, such as Tyrannosaurus rex, to elucidate variations in feeding strategies among theropods. The findings suggest that Allosaurus possessed adaptations that allowed it to exploit a diverse range of prey, indicating a versatile feeding strategy. These results enhance our understanding of theropod evolution and ecological interactions, providing insights into the functional significance of cranial morphology in dinosaurian predation. This review underscores the importance of cranial features in reconstructing the behavior and diet of extinct species and contributes to the broader field of vertebrate functional morphology.

Oxidative stress and chronic inflammation create a perpetual cycle in the elderly, where impaired immune function amplifies susceptibility to oxidative damage, and oxidative stress further weakens the immune response. This cycle is particularly detrimental to the respiratory system of the elderly, which is an easy target for constant exogenous harmful attacks during cold/flu season or under heavy air pollution. Herbal medicines that protect respiratory function are seen as safer alternatives to conventional therapies; however, there is limited availability of scientifically validated, safe, and effective natural supplements for these conditions. In this study, we evaluated a standardized bioflavonoid composition, UP446, which contains bioactives from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, as a natural and nutritional supplement for its antioxidative and immunoregulatory effects in oxidative stress-accelerated aging and chemically induced immune suppression mouse models. Immunosenescence was induced by continual subcutaneous injection of D-galactose (D-Gal) at a dose of 500 mg/kg/day in CD-1 mice. UP446 was administered orally at doses of 100 mg/kg and 200 mg/kg starting in the fifth week of immunosenescence induction. The study lasted a total of ten weeks. All mice received a quadrivalent influenza vaccine 14 days before the end of the study. Whole blood, serum, spleen homogenate, and thymus tissues were used for analysis.Cyclophosphamide (Cy)-induced immunosuppression was triggered by three consecutive injections of cyclophosphamide at 80 mg/kg/day, followed by oral administration of UP446 for 18 days at doses of 100 mg/kg and 200 mg/kg. Blood was collected from each animal at necropsy, and serum was isolated for IgA and IgG ELISA analysis. UP446 was found to improve immune response, as evidenced by stimulation of innate (NK cells) and adaptive immune responses (T cells and cytotoxic T cells), an increase in antioxidant capacity (glutathione peroxidase), preservation of vital immune organs (the thymus), and a reduction in NFκB. UP446 also increased serum levels of IgA and IgG. The findings presented in this report demonstrate the antioxidative, anti-inflammatory, and immune-regulatory activities of UP446, suggesting its potential use in respiratory conditions involving immune stress due to aging, oxidative stress, and/or pathogenic challenges.

This study employed High-Performance Liquid Chromatography coupled with Diode Array De-tector and Mass Spectrometry (HPLC-DAD-MS) to characterize bioactive compounds in olive leaf extracts. The analysis revealed a diverse metabolic profile, predominantly composed of tyrosol, flavonoids, and hydroxycinnamic acid. The antioxidant activity of the extracts demonstrated their efficacy, with variations observed between neutral and acidic pH conditions. Encapsulation was explored as a preservation method, successfully maintaining the integrity of phenolic compounds in both liquid and powdered forms. All four extracts have an undeniable antimicrobial effect. Moreover, the antibacterial activity tested on E. coli ATCC 25922 and S. aureus ATCC 25923 strains significantly improved post-encapsulation, particularly for the acidic pH extract. The findings suggest that encapsulation can potentially conserve and/or enhance the antimicrobial activity of olive leaf extract, paving the way for developing functional products with improved shelf life and nutritional properties. Further investigations are recommended to elucidate underlying mecha-nisms and optimize encapsulation processes to maximize the benefits of olive leaf extract in di-verse applications.

Drug residues that contaminate food and water represent a serious concern for human health, since their irrational use is constantly increasing the amplitude of exposure. Multiple sources contribute to the overall exposure to contaminants, including agriculture, domestic use, personal, public, and veterinary healthcare, increasing the possible origin of contamination. In this review, we focus on crop pesticides and veterinary drug residues because of their extensive use in modern agriculture and farming, which ensures food production and security for the ever-growing population around the world. We discuss crop pesticides and veterinary drug residues with respect to their worldwide distribution and impacts, with special attention on their harmful effects on human reproduction and embryo development, as well as their link to epigenetic alterations, leading to intergenerational and transgenerational diseases. Among the contaminants, the most commonly implicated in causing such disorders are organophosphates, glyphosate and antibiotics, with tetracyclines being the most frequently reported. This review highlights the importance of finding new management strategies for pesticides and veterinary drugs. Moreover, due to the still limited knowledge on inter- and transgenerational effects of these contaminants, we underlie the need to strengthen research in this field, so as to better clarify the specific effects of each contaminant and their long-term impact.

Although metastasis-associated protein 1 (MTA1) is known to play a role in cancer invasion and metastasis of various cancers, the clinical significance of its expression in canine urothelial carcinoma (UC) has not been explored. We sought to evaluate the expression of MTA1, cyclooxygenase 2 (COX2) and E-cadherin (E-cad) in association with clinicopathological parameters in clinical samples of canine UC. Here, we show that MTA1 and COX2 are overexpressed in canine UC samples compared to normal canine bladder samples, whereas E-cad levels are higher in normal bladder. The results demonstrated that MTA1 expression correlated with aggressive clinicopathological features such as high tumor-grade, muscular/vascular invasion, and metastasis. The expression of MTA1 differed in tumors depending on their localization, with the highest being in the urethra adjoining the prostate. Unexpectedly, higher E-cad levels were detected in metastatic tumor cells compared to primary tumor cells. Overall, these findings suggest that MTA1 may represent a key upstream effector tightly associated with COX2 and E-cad-mediated events in canine UC. Accordingly, MTA1 may be considered a feasible interceptive and therapeutic target for canine UC treatment.

In this paper, we report a comprehensive and consistent annotation of the locus encoding the horse T cell receptor b-chain (TRB), as inferred from the most recent genome assembly. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species stud-ied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV, belonging to 29 subgroups, 2 TRBD, 13 TRBJ and 2 TRBC genes, were iden-tified. The general genomic organization resembles that of other mammals, with a V-cluster of 135 TRBV genes, located upstream of two in-tandem aligned TRBD-J-C clusters, and an inverted TRBV gene at the 3’ end of the last TRBC gene. However, the horse b-chain repertoire would be affected by a high number of non-functional TRBV genes. Thus, we queried a transcriptomic da-taset derived from splenic tissue of a healthy adult horse, using each TRBJ gene as a probe to ana-lyse clonotypes encompassing the V(D)J junction. This analysis provided insights into the usage of the TRBV, TRBD and TRBJ genes and the variability of the juxtaposition region. Our results clearly demonstrated that the horse β-chain constitutes a complex level of variability broadly like that described in other mammalian species.

Gigantism in theropods represents one of the most intriguing phenomena in dinosaur evolution, showcasing extreme adaptations in body size and ecological roles. This literature review focuses on Giganotosaurus carolinii, one of the largest known theropods to have ever existed, to explore its unique aspects of gigantism and the subsequent ecological impacts. By analyzing features such as its skeletal morphology, comparative anatomy, and paleoenvironmental data, we assess the evolutionary pressures and biological constraints that shaped the gigantism observed in Giganotosaurus. We discover that the species exhibited a combination of physiological and ecological adaptations that allowed it to thrive as an apex predator in its Cretaceous environment. We will also further examine the implications of its size on prey dynamics, competition with other large theropods, and the overall ecosystem structure. Through a thorough, multidisciplinary approach, this research enhances our understanding of how gigantism influenced theropod behavior, interspecies interactions, and the broader paleoecological landscape.

The nematode Caenorhabditis elegans, with its highly sensitive olfactory system, has emerged as a promising tool for testing chemotaxis. In the field of cancer diagnostics, there is a growing interest in the development of non-invasive screening methods for the detection of volatile organic compounds in a patient's urine. The objective of this study was to contribute to the existing body of knowledge by evaluating the ability of a Caenorhabditis elegans-based chemotaxis assay to discriminate between urine samples from healthy individuals and patients diagnosed with breast or colon cancer. Following synchronization of the developmental stages of C. elegans, nematodes were exposed to the urine of cancer patients and healthy individuals. Subsequently, chemotactic indices were calculated for each urine sample. Our results demonstrated a statistically significant difference in the chemotactic response of C. elegans to urine samples from cancer patients compared to healthy volunteers (p < 0.001). Moreover, the test exhibited promising diagnostic utility, with a sensitivity of 98%, a specificity of 62%, and a detection rate of 78%. Our findings expand on previous observations, confirming the remarkable sensitivity of C. elegans hermaphrodites to discriminating cancer-related volatile organic compounds in urine samples.

This literature review examines the function and evolution of cranial crests in Dilophosaurus wetherilli, a notable theropod dinosaur from the Early Jurassic period. The review synthesizes morphological data and behavioral theories to provide a comprehensive analysis of the crests' roles in the dinosaur's life. Cranial crests, characterized by their distinctive, elongated structures extending from the skull, have intrigued paleontologists due to their unique appearance and apparent function. This review utilizes findings from recent fossil discoveries, comparative anatomy, and biomechanical studies to explore hypotheses regarding the crests' primary functions. Key theories suggest these structures may have served for display purposes, thermoregulation, or defensive mechanisms. Evidence from cranial and postcranial anatomy, as well as comparisons with extant analogs, provides insights into the possible evolutionary pressures influencing the development of crests in Dilophosaurus wetherilli. Additionally, the review considers the role of sexual dimorphism and social behavior in shaping these features. By integrating these diverse lines of evidence, the review aims to offer a nuanced understanding of how cranial crests might have contributed to the survival and social interactions of Dilophosaurus. This analysis not only advances our knowledge of Dilophosaurus wetherilli but also contributes to broader discussions on the evolution and functional morphology of early theropods.

This article reviews all the major stages in the origins of life. From the emergence of matter in the initial Big Bang to the modern, civilized human being. On an immaterial level, it is proposed and explained how consciousness necessarily takes precedence over matter. Next, we explain how consciousness, with its ability to process information, selected the water molecule to breathe life into the periodic table of elements. We also explain why the notion of entropy allows us to evolve: "Die Entropie der Welt strebt einem Maximum zu" (second principle) and, therefore, takes precedence over the notion of energy, which, on the contrary, encourages us to preserve what we have: "Die Energie der Welt bleibt konstant" (first principle). This is followed by a discussion of the importance of quantum coherence and the need to rely on a second quantization formalism for a proper understanding of the physical-biochemical properties of water. Moreover, throughout the argument developed on the best and most fundamental things science has to offer, care is taken to link this knowledge to the great philosophies of the West (Greece), the East (China, India) or even to practices of a shamanic nature (Africa, America). Hence, finally, the proposal to reconsider all musical practice within the framework of the diapason of water at a frequency of 429.62 Hz, as well as all therapeutic practice on the basis of seven clearly identified and established frameworks of thought.

Extremely low-frequency electromagnetic fields (ELF-EMF) are ubiquitous in industrial-11 ized environments due to the continuous use of electrical devices. Our previous studies demon-12 strated ELF-EMF affects muscle cells by modulating oxidative stress and enhancing myo-genesis. 13 This pilot study investigated these effects on skeletal muscles of sedentary adult mice, assessing 14 physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplemen-15 tation. Male C57BL/6 mice were exposed to ELF-EMF (0.1 or 1.0 mT) 1 hour/day up to 5 weeks, and 16 fed a standard diet without or with N-acetyl-cysteine (NAC). Results showed transient increases in 17 muscle strength (after 2-weeks’ exposure at 1.0 mT), potentially linked to muscle fiber recruitment 18 and activation, revealed by higher PAX7 and MyH expression levels. After ELF-EMF exposure, ox-19 idative status assessment revealed transient increases in expression levels of SOD1 and catalase en-20 zymes, in total antioxidant capacity and in protein carbonyl levels, marker of oxidative damage. 21 These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal 22 muscle physiology and NAC supplementation partially mitigates these effects, highlighting the 23 complex interactions between ELF-EMF and antioxidant pathways in vivo. Further investigations 24 on ELF-EMF as a therapeutic modality for muscle health are necessary.

This literature review provides a comprehensive analysis of the functional morphology and paleoecology of Pteranodon, a prominent genus of Pterosaur from the Late Cretaceous period. By synthesizing recent research findings with classic studies, this paper elucidates the aerodynamic and ecological adaptations of Pteranodon, which was one of the largest pterosaurs to ever soar the skies. The review examines the distinctive cranial features, including its elongated cranial crest and its implications for sexual dimorphism and species identification. Detailed analysis of wing morphology and limb proportions reveals insights into its flight mechanics, suggesting that Pteranodon was adapted for dynamic soaring, leveraging its expansive wingspan for efficient long-distance travel. Additionally, the paper explores Pteranodon's feeding habits and dietary preferences based on dental and jaw structure, indicating a diet primarily consisting of fish and other aquatic prey. The review also integrates fossil evidence with ecological models to reconstruct the paleoenvironment of the Late Cretaceous, highlighting the role of Pteranodon in its ecosystem as both a predator and a competitor. This synthesis not only enhances our understanding of Pteranodon’s physiological and ecological roles but also contributes to broader discussions on pterosaur evolution and behavior.

Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing resistance. Our research has focused on crotalicidin (Ctn), an AMP from a snake venom, and a fragment thereof, Ctn[15-34], with improved in vitro antimicrobial and anticancer activities and remarkable serum stability. As the retroenantio versions of both AMPs maintained favorable profiles, in this work we evaluate the in vivo efficacy of both the na-tive-sequence AMPs and their retroenantio counterparts in a murine infection model with Aci-netobacter baumannii. A significant reduction in bacterial levels is found in the mice treated with Ctn[15-34]. However, contrary to expectations, the retroenantio analogues either exhibit toxicity or lack efficacy when administered to mice.

The utilization of Artificial Intelligence (AI) in biotechnology is widespread, addressing challenges such as elucidating disease pathophysiology and novel therapeutic approaches. AI plays a critical role in tasks such as drug manufacturing, chemical analysis, RNA and DNA sequencing, and enzyme studies by automating processes and expediting data collection and analysis. AI has particularly transformed the analysis of omics data for researchers, providing tools to handle complex and multifaceted datasets effectively. Through AI, integrative analysis of multi-omics data can be conducted in efficient ways. This article discusses the application of multi-omics and AI technologies in studying various diseases related to infection (COVID-19), mutation (cancer), and senescence (alopecia) to understand their pathophysiology. The applications of AI were performed as the aspect of the diagnosis, prognosis, and treatment for each disease. We introduce AI-driven analysis of pathophysiology can overcome traditional limitations in pathology, with diverse features showing potential in defining the causes of diseases, and potentially enhancing primary omics data in the distinguish the subtype of diseases. In this context, integrated approaches using multi-omics data and AI technology could provide fresh biological insights by comprehending the molecular mechanism of diseases and is instrumental in advancing precision medicine. We anticipate that the rapidly advancing AI-based multi-omics data analysis will significantly contribute to promoting healthy longevity.

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, anti-ageing effects to protect normal tissues and can exert anti-angiogenic, and pro-apoptotic effects on cancer cells. Metabolites found in different parts of the olive tree, including leaves, also possess properties that might help in cancer prevention and promote wellness in aging. Olive mill wastewater (OMWW), a liquid residue produced during olive oil extraction, represents an environmental issue. However, it is enriched in phytochemicals with potential beneficial properties. Dietary supplements based on OMWW can be produced for nutritional supplementation with advantages to the ecology. Purpose: This work aims to measure hematochemical, anthropometric and metabolomic parameters in volunteers assuming an OMWW dietary supplement, OliphenoliaⓇ (OMWW-OL). Methods: The supplementation of OMWW-OL 25 mL twice daily for 30 days was tested on a pilot cohort of volunteers with characteristics close to metabolic syndrome. Hematochemical, anthropometric, and metabolomic parameters were analyzed before the intervention, at 30 days and 30 days after stopping consumption. Results: 29 volunteers were enrolled and 23 completed the study. The participants’ parameters at baseline were measured, and then twice daily at 30 days of treatment and 30 days after assumption discontinuation. Although treatment was with an olive derivative, weight and body mass index instead of increasing slightly decreased, particularly in women. Also, hydration increased, especially in women, while blood pressure, glycemia and insulin decreased. Cholesterol, low-density and high-density lipoproteins and triglycerides were stable while vitamin D levels, alongside calcium, sensibly increased. Albumin also increased and parameters related to sarcopenia displayed promising, although not statistically significant, trends toward positive effects. All the values were in support of an equilibrium with no damaging effects. By mass spectrometry analysis, we also found favorable changes in the vitamin D/histamine and homocysteine/methionine ratios, an increase in a new metabolite of unknown formula, and vitamin D/unknown metabolite ratio. Conclusions: Supplementation of OMWW-OL has no detrimental effects and, although with limited potency of a pilot study, might imply the beneficial modulation of several biological parameters, being potentially valuable for people at risk of metabolic syndrome. Some of these parameters could also be relevant as anti-ageing and in cancer prevention.

Background: The incidence of various types of cancer, for example papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diag-nostic biomarkers must be identified and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs sus-pected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis along with identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulat-ing blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, miR-1, miR-206, and miR-221, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG), and from the culture medium of a PTC cell line (MDAT32) and were duly characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes were associated to the molecular pathogenesis of PTC. Conclusions: Thus, our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.

Exosomes, nanoscale extracellular vesicles, are a hot area of investigation in the biomedical field, as they have been shown to play a crucial role in the physiology of numerous tissues, including bone. This study explores the landscape of exosome-based bone regeneration research using infometric techniques. By relying on BERTopic, an advanced topic modeling algorithm, we analyzed a comprehensive corpus of scientific literature to identify key themes and trends in exosome research in the bone regeneration field. We then extracted significant concepts from the abstracts of the corpus and we used them to create knowledge graphs using GPT 3.5 turbo Large Language Model, to map the distribution of information within this domain. The resulting ide-oscape highlights the key ideas that aggregate most of the recent research in the area, from mesenchymal stem cell-derived exosomes to engineered exosome-integrated biomaterials. This exploration provides a holistic view of the field and uncovers its emerging trends, providing useful insight to guide future research directions.

Background: The Victorian era in Great Britain was a historical period that brought about profound changes for humanity. The confluence of various factors fostered the development of numerous scientific disciplines. In the field of health sciences, Florence Nightingale played a central role. Following her training as a nurse and her role as superintendent during the Crimean War, she made decisive contributions to establishing a public health network. Methods: This is a retrospective historical heuristic and hermeneutic study analyzing documentation of Nightingale's contributions to public health from around 1890 to 1900. The historical method was used to collect, classify, and analyze primary and secondary sources relevant to the study's objectives. Results: Nightingale supported the development of the concept of “health at home” by training women to implement healthy measures that contributed to the well-being of families and communities. Through the training and development of a formal “Health Missioners program”, she provided the necessary guidance to improve the health of rural communities across the English countryside. Conclusion: The role of Health Missioners has persisted, as health visitors continue to visit homes in the United Kingdom. Therefore, the contribution of Florence Nightingale to public health is unquestionable. This study was not registered.

Therizinosaurs, a unique clade of theropod dinosaurs, are characterized by their distinct morphological features and enigmatic ecological role. This review provides a comprehensive analysis of the functional morphology and ecological significance of these remarkable dinosaurs. Therizinosaurs are distinguished by their elongated, often curved claws, robust postcranial skeletons, and herbivorous diet, which starkly contrasts with their carnivorous theropod relatives. We explore the evolutionary implications of their morphology, focusing on adaptations such as their specialized feeding apparatus and limb structure. These features suggest a complex interplay between their herbivorous lifestyle and ecological niche. The review synthesizes recent findings from fossil evidence, including detailed studies of cranial and postcranial anatomy, to elucidate the functional mechanisms behind their unique adaptations. Additionally, we discuss the broader ecological role of therizinosaurs within their Mesozoic ecosystems, highlighting their interactions with contemporaneous flora and fauna. By integrating paleontological data with comparative anatomy and ecological modeling, this review aims to shed light on the evolutionary trajectory of therizinosaurs and their impact on our understanding of theropod diversity and adaptation. This focused review contributes to a more nuanced appreciation of therizinosaurs' place in dinosaur evolution and their adaptive strategies in prehistoric environments.

Many studies have demonstrated hydrogen's therapeutic and preventive effects on various diseases. Its selective antioxidant properties against hydroxyl radicals, which are responsible for the indirect effects of ionizing radiation, may make it worthy of attention as a new radio-protector. We recently developed new hydrogen water that is more stable and has higher antioxidant activity by using ultra-fine bubbles. In this study, female C57BL/6J mice given ad libitum access to ultra-fine bubble hydrogen water (UBHW) were subjected to whole-body irradiation (WBI) with X-rays, and the radio-protective effect of UBHW was evaluated. Sub-lethal WBI resulted in a 30-day survival rate of 100% in UBHW-fed mice, compared with 37% in control mice. In the case of lethal WBI, while the control mice died out in about 3 weeks, the 30-day survival rate improved to 40% by UBHW due to the high scavenging activity of hydroxy radicals. Twenty-six serum proteins involved in inflammatory and immune responses were significantly identified in UBHW-fed mice by proteomics, and UBHW may enhance and regulate these functions, resulting in reduced damage in mice exposed to WBI. We conclude that UBHW has good potential in radio-protection, with evidence that warrants further research efforts in this field.

In this very personal hunt for the meaning of the bacterial cell cycle, the snark, I briefly revisit and update some of the mechanisms we and many others have proposed to regulate the bacterial cell cycle. These mechanisms, which include the dynamics of calcium, membranes, hyperstructures and networks, are based on physical and physico-chemical concepts such as ion condensation, phase transition, crowding, liquid crystal immiscibility, collective vibrational modes, reptation, and water availability. I draw on ideas from subjects such as the ‘prebiotic ecology’ and phenotypic diversity to help with the hunt. Given the fundamental nature of the snark, I would expect that its capture would make sense of other parts of biology. The route therefore followed by the hunt has involved trying to answer questions like “why do cells replicate their DNA?”, “why is DNA replication semi-conservative?”, “why is DNA a double helix?”, “why do cells divide?”, “is cell division a spandrel?” and “how are catabolism and anabolism balanced?”. Here, I propose some relatively unexplored, experimental approaches to testing snark-related hypotheses and, finally, I propose some possibly original ideas about DNA packing, about phase separations, and about computing with populations of virtual bacteria.

JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasm (MPN): polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In MPNs this mutation is associated with the germline GGCC (46/1) haplotype. Most studies consider the association of the JAK2 haplotypeGGCC_46/1 with some MPNs clinical parameters but no one analyzed the association between JAK2 haplotypeGGCC_46/1 and the onset of onco-drug resistance. Thus, we assessed for JAK2 46/1 haplotype correlation with therapy response in JAK2 V617F positive patients. Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Most of them had PV (63%) or PMF (61%). Among patients that developed onco-drug resistance, 58% had C/G genotype and only 11% had the G/G allele. No correlation between onco-drug resistance and JAK2 haplotype 46/1 variants emerged. Nevertheless, we observed that G/G allele seems to be related to MPNs evolution to myelofibrosis and to the development of onco-drug resistance clinical parameters (p-value= 0.002449; odd ratio of 3.701209). Thus, although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

Ankylosaurus stands as a quintessential example of Cretaceous armored dinosaurs, renowned for its formidable defensive adaptations. This study explores the defensive mechanisms and paleoecology of Ankylosaurus, focusing on its unique armor and lifestyle. Through detailed morphological analysis of fossil specimens, we examine the structure and function of the robust osteoderms and the prominent tail club, evaluating their roles in defense against predators. The distribution and arrangement of these defensive features suggest a sophisticated strategy to deter and survive attacks from contemporary theropods. Additionally, we investigate the paleoenvironmental context of Ankylosaurus, assessing how its habitat and ecological interactions influenced its evolutionary adaptations. Comparative analysis with other ankylosaurids and contemporaneous species provides insights into the evolutionary pressures shaping its armor. Our findings highlight the balance between offensive and defensive strategies in the Late Cretaceous ecosystem, underscoring the role of Ankylosaurus as both a well-protected herbivore and a critical component of its ecological niche. This study contributes to a deeper understanding of the evolutionary dynamics of armored dinosaurs and their interaction with their environment, offering a comprehensive perspective on the adaptations that defined Ankylosaurus' survival strategy.

This narrative review challenges the recent World Workshop Consensus (WWC) conferences failure to classify aggressive periodontitis (AP) in young adults as distinct from adult periodontitis. Deficiencies in the consensus process, results of these deficiencies, and their impact on disease classification are presented. Support for retaining localized aggressive periodontitis (LAgP) in adolescents as a unique disease, focuses on the; 1) age of onset, 2) rate of bone loss in those affected, and 3) unique microbiological etiological associations. Examples of, 1) unique clinical signs and symptoms of LAgP are presented, and 2) the microbial subgingival consortia that precedes these clinical signs and symptoms are described. Tables show, 1) decreased publications for AP since publication of WWC guidelines and 2) Bradford-Hill guidelines that support the unique etiological consortia replicated in clinically well-defined longitudinal studies. The review describes major deficiencies in the WWC as compared to other medically-related well-run consensus conferences that, 1) set pre-conference standards for 70 – 80% agreement of expert participants, and 2) published the dissenting point of view. In contrast, the WWC conference was decided by a mere majority, and never presented the dissenting view. The review concludes that averaging of mean pocket depth reduction, or attachment gain can misrepresent disease and/or success of treatment in aggressive diseases. In contrast, clinical assessment of time to recurrence of subgingival re-infection with possible translocation of oral microbes to distant sites is presented as an alternative measurement of success. Other questions and future directions are presented.

Endolysin of bacteriophage T5 (EndoT5) is a Zn2+-dependent and Ca2+-activated L-alanyl-D-glutamate peptidase that hydrolyses peptidoglycans during the destruction of the cell wall of the phage host bacterium Escherichia coli. To elucidate the mechanism of calcium activation, the spatial solution structure of EndoT5 in a complex with two ions - catalytic Zn2+ and regulatory Ca2+ (EndoT5-Zn2+Ca2+, PDB ID: 8P3A) was determined by high-resolution NMR and deposited in the Protein Data Bank. We show that coordination of the Ca2+ ion fix the spatial position of polar amino acid residues D113, N115 and S117. As a result, the intramolecular mobility of extended protein loops (residues 40-70 and 111-132) is significantly reduced compared to the mobility of these loops in the structure of an enzyme containing only a catalytic a Zn2+ ion (EndoT5-Zn2+, PDB ID: 2MXZ). In the stabilized EF-like calcium-binding loop (residues 111-132), the number of van der Waals interactions with amino acid residues of the globular core of the protein increases. The binding of the Ca2+ ion is accompanied by the selection of the functional states of both extended loops of the enzyme (residues 40-70 and 111-132), because of which EndoT5-Zn2+Ca2+ acquires the structural integrity necessary for catalysis. Therefore, the mechanism of activation of L-alanyl-D-glutamate peptidase of bacteriophage T5 by Ca2+ ions involves stabilization of the enzyme molecule in a catalytically active “open” conformation. This work sheds light on the structural grounds of the ion-dependent functional proteoforms of this interesting protein.

Genetic similarity determines the extent to which two genotypes share common genetic material. It can be measured in various ways, such as comparing DNA sequences, proteins, or other genetic markers. The significance of genetic similarity is multifaceted and encompasses various fields, including evolutionary biology, medicine, forensic science, animal and plant breeding, and anthropology. Genetic similarity is an important concept with wide application across different scientific disciplines. In the presented study, six measures for calculating genetic similarity were compared: Euclidean, Jaccard, Kulczyński, Sokal and Michener, Nei, and Rogers. The research material included 21 rapeseed genotypes (ten interspecific Brassicaceae hybrids of F2 generation, and 11 of their parental forms) and 146 alleles, obtained using 21 ISSR molecular markers. The results indicate that the research material was divided into two identical groups using any of the proposed methods, despite differences in the values of genetic similarity coefficients. Two of the presented measures of genetic similarity (Sokal and Michener, and Euclidean) were the same.

Idiopathic pulmonary fibrosis, a chronic and fatal condition with no effective cure, is a challenging disease within the group of interstitial lung diseases. The pathogenic mechanisms of this disease are still not fully understood. In this context, the research on miRNAs, which are small non-coding RNAs that regulate messenger RNAs, is of utmost importance. These miRNAs, released into the circulation outside the cell through exosomes, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. The analysis of miRNAs in the serum/plasma of IPF patients has opened up new possibilities in the search for biomarkers. This review focuses on circulating miRNAs validated by real-time PCR in IPF and the evidence reported about the pulmonary fibrotic process.

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3^- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8^- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

This literature review investigates the role of plumage in the hunting tactics of Velociraptor, integrating anatomical analysis and biomechanical modeling. Velociraptor, a swift and agile theropod from the Late Cretaceous, exhibited advanced intelligence and sensory capabilities that contributed to its effective predatory strategies. Recent discoveries have confirmed that Velociraptor was covered in feathers, with quill knobs indicating well-developed plumage. This review explores the potential functions of feathers beyond flight, focusing on their impact on hunting behavior. Evidence suggests that Velociraptor’s plumage likely facilitated camouflage and enhanced aerodynamic control, improving its stealth and maneuverability during high-speed chases. Additionally, feathers might have contributed to stability during incline running, further supporting its adaptability in diverse environments. Velociraptor’s hunting strategies, characterized by agility and precision, were complemented by its feathered anatomy, which may have also played a role in pack hunting and social interactions. Overall, the integration of plumage with Velociraptor’s anatomical features and behavioral adaptations underscores its efficiency as a predator, demonstrating how feathers may have been a critical factor in its successful hunting tactics.

Based upon the latest molecular phylogenies of Gonyosoma sensu lato, which recovered five clades with robust support, we utilize morphological characters to demonstrate the distinctiveness of each clade, resulting in the resurrection of three genera (Gonyophis Boulenger, 1891 [1], Rhynchophis Mocquard, 1897 [2], and Rhadinophis Vogt, 1922 [3]) and proposal of a new genus and a new tribe. A synopsis of the group, with descriptions and diagnoses, is provided for the five genera and eight species in addition to distribution maps and illustrations of the head of each taxon. An artificial key to the species and genera in the new tribe is presented in addition to estimated origin times for each clade.

This literature review investigates how the diverse habitats of Baryonyx walkeri influenced its hunting strategies, with a focus on adaptations for piscivory and generalist predation. The spinosaurid theropod Baryonyx walkeri, known for its distinctive elongated snout and conical teeth, inhabited a variety of environments during the Early Cretaceous period. Fossil evidence suggests that Baryonyx frequented fluvial and lacustrine environments, leading to the hypothesis that its primary diet consisted of fish and other aquatic organisms. Detailed analysis of its cranial morphology reveals a suite of adaptations, including robust forelimbs with a large, sickle-shaped claw, ideal for catching slippery prey. Isotopic analysis of oxygen in Baryonyx indicates a significant reliance on fish and other similar organisms. Comparisons with modern analogs, such as crocodilians, provide further insight into the behavioral ecology of Baryonyx. This review integrates paleontological data with modern ecological analogs to reconstruct the hunting strategies of Baryonyx walkeri. The findings underscore the importance of habitat diversity in shaping the evolutionary pathways of predatory dinosaurs and contribute to a broader understanding of spinosaurid ecology and behavior.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

This literature review investigates the morphological and behavioral significance of the horns of Carnotaurus sastrei, a theropod dinosaur from the Late Cretaceous period. Through a comprehensive analysis of fossil specimens, comparative anatomy, and biomechanical modeling, this review explores the evolutionary adaptations and potential functions of these distinctive cranial structures. The horns of Carnotaurus are hypothesized to serve multiple roles, including species recognition, thermoregulation, and intraspecific combat. Our findings suggest that its cranial horns likely served a primary role in species recognition, intimidating rivals and signaling mating readiness. It also could have been used occasionally in head-butting contests, potentially as a display of dominance, but likely did not play a role in thermoregulation. Additionally, we examine the ecological context in which Carnotaurus lived, assessing how environmental factors could have influenced the development of such features. The implications of this study extend to broader discussions on the functional morphology and adaptive strategies of theropod dinosaurs, highlighting the complex relationship between form and function in the evolutionary history of predatory dinosaurs like Carnotaurus sastrei.

Periodontal disease, a multifactorial inflammatory condition affecting the supporting structures of the teeth, has been increasingly recognized for its association with various systemic diseases. Understanding the molecular comorbidities of periodontal disease is crucial for elucidating shared pathogenic mechanisms and potential therapeutic targets. In this study, we conducted comprehensive literature and biological database mining utilizing tools such as DisGeNET2R, Romin, and Rentrez R libraries to identify diseases sharing associated genes, proteins, or molecular pathways with periodontitis. Our analysis revealed significant molecular overlaps between periodontal disease and several systemic conditions, including cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and inflammatory bowel diseases. Shared molecular mechanisms implicated in the pathogenesis of these diseases and periodontitis encompassed dysregulation of inflammatory mediators, immune response pathways, oxidative stress pathways, and alterations in the extracellular matrix. Furthermore, network analysis unveiled key hub genes and proteins that play pivotal roles in the crosstalk between periodontal disease and its comorbidities, offering potential targets for therapeutic intervention. Insights gained from this integrative approach shed light on the intricate interplay between periodontal health and systemic well-being, emphasizing the importance of interdisciplinary collaboration in developing personalized treatment strategies for patients with periodontal disease and associated comorbidities.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

PURPOSE: To investigate the oxylipin profiles in aqueous humor of primary open angle glaucoma (POAG) patients. METHODS: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to the liquid chromatography-mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. RESULTS: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified 5 differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The 5 oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk ratio in the POAG patients. In addition, 15-kPGF2α was positively correlated with visual field defect, and LTB4 was negatively correlated with macular thickness.  CONCLUSIONS: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in arachidonic acid metabolism pathway could play a role in POAG and anti-inflammatory therapies could be potential treatment strategies for POAG.

This literature review aims to gain a deeper understanding of the anatomy behind the jaw strength of Tyrannosaurus rex and analyze how these features contribute to its predatory behavior. This review will examine various studies and fossil excavations, exploring ideas such as the bite force of T. rex and its variations across different life stages. This will be obtained from numerous biomechanical models of both juvenile and adult Tyrannosaurus rex, as well as reference animals and dinosaurs for comparison. To provide additional information behind T. rex’s hunting techniques, we will also discuss the fauna of herbivorous dinosaurs that were part of T. rex’s diet. Furthermore, we will explore how mandibular stress concentration can vary between ages, a crucial topic in determining what T. rex could consume at certain stages of its life. Finally, we obtain a well-evidenced analysis of the various aspects of Tyrannosaurus rex’s hunting strategies throughout its lifetime.

BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) encode for tumor suppressor proteins which are critical regulators of the homologous recombination (HR) pathway, the most precise and important DNA damage response mechanism. Dysfunctional HR proteins cannot repair double-stranded DNA breaks in mammalian cells, a situation called HR deficiency. Since their identification, pathogenic variants and other alterations of BRCA1 and BRCA2 genes have been associated with an increased risk of developing mainly breast and ovarian cancer. Interestingly, HR deficiency is also detected in tumors not carrying BRCA1/2 mutations, a condition termed “BRCAness”. One of the main mechanisms causing the BRCAness phenotype is the methylation of the BRCA1/2 promoters and this epigenetic modification is associated with carcinogenesis and poor prognosis mainly among patients with breast and ovarian cancer. BRCA1 promoter methylation has been suggested as an emerging biomarker of great predictive significance, especially concerning Poly (ADP-ribose) Polymerase inhibitors (PARP inhibitor-PARPi) responsiveness, along with or beyond BRCA1/2 mutations. However, as its clinical exploitation is still insufficient, the impact of BRCA1/2 promoter methylation status needs to be further evaluated. The current review aims to gather the latest findings about the mechanisms that underline BRCA1/2 function as well as the molecular characteristics of tumors associated with BRCA1/2 defects, by focusing on DNA methylation. Furthermore, we critically analyze their translational meaning and the validity of BRCA methylation biomarkers in predicting treatment response and we suggest a diagnostic pipeline that could be implemented in liquid biopsy to aid precision pharmacotherapy in BRCA-associated tumors.

This literature review aims to gain a deeper understanding of Spinosaurus aegyptiacus’s dorsal sail regarding its function as thermoregulation, display, or hydrodynamic. The function of S. aegyptiacus’s dorsal sail has been widely debated for many years. The three most popular hypotheses are that it was used as a biological mechanism of thermoregulation, display, or hydrodynamic. The display hypothesis includes attracting mates, intimidating rivals, and social communication with other members. This literature review delves into each of the three hypotheses using past studies and excavation sites to analyze their validity. For the hydrodynamic aspect, the lifestyle of S. aegyptiacus must first be established. Based on existing research, we cannot conclude that there is a definitive primary function of Spinosaurus aegyptiacus’s dorsal sail. However, it is likely that its sail served the crucial function of display, since it would have a large surface area and could thus be a distinguishable characteristic of S. aegyptiacus that could determine mating success. Additionally, it is probable that the sail had supplementary roles in thermoregulation and hydrodynamics.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure (AHF) and LVAD as destination therapy are an option in non-HT candidates. Most patients with AHF never receive a HT or a LVAD, so alternative strategies are needed. Intermittent levosimendan can reduce HF hospitalizations in AHF patients in the short term. It is uncertain whether the results of the comparison of inotropes with older generation LVAD would have the same outcomes in the current era of less sick but older, AHF treated with levosimendan patients. In this paper we compare the use of two therapeutic strategies for end-stage HF in patients not candidates for HT: Repetitive intermittent Levosimendan vs. LVAD as destination therapy. To do so we compare two multicentre cohorts of real-life patients from Spain: the LEVO-D Registry and the REGALAD registry. 715 patients coming from the 2 registries where found, 403 from the LEVO-D and 312 from the REGALAD. Non-adjusted median survival was shorter for LEVO-D patients; with the benefit for the LVAD seen only after the first year of therapy. The survival advantage for the LVAD cohort was also true after analysis of the matched cohort but, as in the non-matched analysis, the survival benefit was mainly shown after one year of follow up. We conclude that in elderly AHF non-HT-candidates, LVAD therapy offers significantly better long-term outcomes when compared to intermittent levosimendan; thus, it should be considered in carefully selected candidates. On the other hand, in poor LVAD candidates or highly comorbid patients, intermit-tent inotropic support with levosimendan could be a reasonable alternative to LVAD as 1-year outcomes are similar.

Vitamin D receptor (VDR) is an important candidate gene in musculoskeletal phenotypes. Polymorphisms in VDR have been previously associated with several pathologies and muscular strength in athletes and elderly people, however literature reported contradictory results. The object of this research is to verify the association between the most studied VDR variants (rs2228570, rs7975232, and rs1544410) and the increase of muscle mass in elite young soccer players. A sample of 55 soccer players (15-18 years old) form a professional team was selected for this study. DNA was extracted by salting out method and polymorphisms were genotyped by PCR-RFLP, followed by 2% agarose gel electrophoresis. To test the effect of the three SNPs, logistic regression analysis was applied. Body composition was carried out through skinfold thickness method, and muscular area of arm and lower limb were calculated using Frisancho formulas. All three polymorphisms met Hardy-Weinberg equilibrium (p &gt; 0.05) and their frequencies fell within the worldwide variability. A significant correlation between rs1544410 and increase of calf muscle mass was observed. Individuals carrying A allele showed higher calf muscular mass than those carrying the G allele (p = 0.034). Moreover, haplotype analysis applied to the two SNPs in linkage disequilibrium (rs7975232 and rs1544410), showed that AG haplotype resulted negatively correlated to calf muscle area. In conclusion, we confirm an association between VDR polymorphisms and muscular mass that could encourage the genetic screening of VDR gene to identify a potential risk of injury and for individual nutritional interventions.

The World Health Organization (WHO) cancer agency predicts that more than 35 mil-lion cases of will be experienced in 2050, a 77 % increase over the 2022 estimate. Cur-rently, the leading cancer diagnosed cancer are breast, lung and colorectal. There is no standardized tool for cancer diagnosis; initially clinical procedures are guided by the patient´s symptoms and generally involve biochemical blood tests, imaging and biopsy. Label-free nonlinear optical approaches are promising tool for tumor imaging, due to their inherent non-invasive biosafe contrast mechanisms and the ability to monitor collagen-related disorders and metabolic changes during cancer progression. Last ad-vances in nonlinear modalities for tumor imaging are reviewed here. In addition, an application of a blind deconvolution procedure to improve the quality of two-photon images of breast tumor tissues is shown.

Gelsolin is an actin-binding protein that is competitively bound by lysophosphatidic acid (LPA), a possible biomarker for the early detection of ovarian cancer. Our group has previously shown the usage of gelsolin 1-3 (a fragment of gelsolin composed of the first three of its six subdomains) along with actin to detect the presence of lysophosphatidic acid. This histidine-tagged gelsolin 1-3 fragment is synthesized in our lab using bl21 Rosetta cells but required further characterization. This study aims to provide sufficient characterization of gelsolin 1-3 synthesized in our lab via both sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry using a Fourier-transform ion cyclotron resonance mass spectrometer (FTICR-MS). Both techniques show the presence of protein at the expected mass of approximately 41 kDa. Additionally, the dissociation of a smaller fragment of the complex when introduced into the gas phase which was equivalent to the approximate mass of one subdomain of gelsolin 1-3 further supports this conclusion.

We utilized camera traps to assess animal diversity, relative abundance, and anthropogenic activities in the Jhalana Reserve Forest (JRF), located amidst Jaipur, with a population of 3.9 million people. Between November 2017 and November 2019, camera traps were strategically deployed in both the tourist zone and peripheral areas, capturing 16,328 photos. This study represents the first comprehensive baseline assessment of animal diversity in JRF, documenting a total of 39 species, including 18 bird species, 14 mammals, and six domestic species, alongside human activity. Among the 14 mammal species, seven were carnivores. Notably, we identified 25 individual Indian leopards (Panthera pardus fusca) during 2017-2018, comprising 8 males and 17 females, highlighting the leopard as the apex predator in JRF. Concurrently, domestic animals accompanied by humans were observed within JRF. However, rigorous conservation efforts and patrols by the Rajasthan Forest Department resulted in a notable decline in human intrusion, reducing from 28.0% in 2017-18 to 3.9% in 2018-2019, with domestic animal activity reaching zero in the latter period. Consequently, the relative abundance of wildlife species increased during the study period of 2018-2019, underscoring the positive impact of conservation strategies implemented by authorities. Our findings affirm that camera traps effectively establish baseline data, assess animal diversity, and evaluate relative abundance in reserve forests situated within human-dominated landscapes. This study provides critical insights to inform the development and implementation of conservation strategies in similar protected areas.