Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in acti-vating the perforin/granzyme cytotoxic pathways. It is targeted to the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CtsF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, we revealed a strong upregulation of CstF during infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA si-lencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. Here, we investigate the impact of CstF depletion during coinfection of Mtb-infected mac-rophages with lymphocytes infected with HIV. Our results indicate that decreasing CstF released by phagocytes impacts the major pro-granzyme convertase cathepsin C of cytotoxic immune cells. Consequently, an observed increase of the granzyme B apoptotic effects leads to a significant re-duction in viral replication in HIV-infected lymphocytes. Overall, our results indicate a mecha-nism of Mtb/HIV evasion of the cytotoxic mediated pathogen killing driven by the ax-is CstF/ catC/granzymes contributing to this syndemic interaction. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF.

Disease transmission in wildlife is linked to ecosystem and human health, and host community structure can mediate pathogen spread. Here, we decompose the well-known susceptible-infected (SI) compartmental models of disease transmission for multi-host communities to explore the disease-biodiversity relationship. We examine the parameters involved in interspecific transmission and link them to the multi-host outbreak potential, R0. We partition R0 into its separate elements that can be associated with either the recipient or donating host, and show how this allows us to identify maintenance versus spillover hosts, allowing us to quantify separate stages of spillover into a novel, recipient host. We further suggest that the evolutionary relatedness between donating and recipient host may play a role in the probability a pathogen establishes in a novel species, as illustrated by the observed phylogenetic signal in the host-breadth of multi-host pathogens. We discuss how anthropogenic changes to the environment and wildlife communities, such as the reduction and fragmentation of wildlife habitat, might alter the mode and dynamics of disease transmission. This discussion contributes to the ongoing debate on the relationship between disease incidence and biodiversity. Through a synthesis of classic ecological theory, we illustrate how pathogens can affect host populations through phenomena such as in/direct symbioses, that can save a pathogen from extinction or suppress competing host species, but we highlight how host diversity can simultaneosuly influence the survival and success of the pathogen, suggesting a complex feedback between hosts and parasites in multi-host communities. Our review provides a guide to common derivations of interspecific transmission, and underscores the critical connections between community and disease-ecology.

Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified factors important for the intracellular survival of 10GEN C. neoformans, such as urease activity, capsule synthesis, and DNA content using flow cytometry and fluorescent microscopy techniques. Real-time visualization of time-lapse imaging was applied to determine the phagosomal acidity, membrane permeability, and vomocytosis (non-lytic exocytosis) rate in J774 macrophages that phagocytosed C. neoformans of different generational ages. Our results showed that old C. neoformans exhibited higher urease activity, and enhanced capsule formation, which was supported by an increased Golgi complex. In addition, old C. neoformans were more likely to be arrested in the G2 phase, resulting in the occasional formation of aberrant trimera-like cells. To finish, the advanced generational age of the yeast cells slightly reduced vomocytosis events within host cells, which might be associated with increased phagolysosomal pH and membrane permeability. Altogether our results contribute to a better understanding of the strategies used by old C. neoformans to resist phagosomal killing and suggest that old generation C. neoformans intracellular behavior may be driving cryptococcosis pathogenesis.

Proteases are integral enzymes of the plant immune system. Multiple aspects of defence are regulated by proteases, including the hypersensitive response, pathogen recognition, priming and peptide hormone release. These processes are regulated by unrelated proteases residing at different subcellular locations. In this review we discuss ten prominent plant proteases contributing to the plant immune system, highlighting the diversity of roles they perform in plant defence.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

By providing useful tools to study host-pathogen interactions, next-generation omics has recently enabled the study of gene expression changes in both pathogen and infected host simultaneously. However, since great discriminative power is required to study pathogen and host simultaneously throughout the infection process, the depth of quantitative gene expression profiling has proven to be unsatisfactory when focusing on bacterial pathogens, thus preferentially requiring specific strategies or the development of novel methodologies based on complementary omics approaches. In this review, we focus on the difficulties encountered when making use of omics approaches to study bacterial pathogenesis. Besides, we review different omics strategies (i.e. transcriptomics, proteomics and secretomics) and their applications for studying interactions of pathogens with their host.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

Tomato (Solanum lycopersicum L.) is a valuable horticultural crop grown and consumed worldwide. Optimum production is hindered by several factors of which Verticillium dahliae, the cause of Verticillium wilt, is one of the major biological constraints in temperate production regions. V. dahliae is difficult to manage because it is a vascular pathogen, has a broad host range and worldwide distribution, and can persist in soil for years. Understanding the pathogen virulence and genetic diversity, host resistance, and plant-pathogen interactions can ultimately inform the development of integrated strategies to manage the disease. In recent years, considerable research has focused on providing new insight into these processes as well as the development and integration of environment-friendly management approaches. In this review, we discuss and summarize the recent findings on the race and population structure of V. dahliae; pathogenicity factors; host genes, proteins, and enzymes involved in defense; the emergent management strategies, and recent approaches to managing Verticillium wilt in tomatoes.

Shiga toxin-producing Escherichia coli (STEC) is a significant public health threat due to its ability to cause severe gastrointestinal diseases in humans, ranging from diarrhea to life-threatening conditions such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). As the primary reservoir of STEC, cattle play a crucial role in its transmission through contaminated food and water, posing a considerable risk to human health. This comprehensive review explores host-pathogen interactions during STEC colonization of the bovine gut, focusing on the role of gut microbiota in modulating these interactions and influencing disease outcomes. We integrated findings from published transcriptomics, proteomics, and genomics studies to provide a thorough understanding of how STEC adheres to and colonizes the bovine gastrointestinal tract. The insights from this review offer potential avenues for the development of novel preventative and therapeutic strategies aimed at controlling STEC colonization in cattle threby reducing the risk of zoonotic transmission.

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019 and has since spread worldwide, is the latest human pandemic, and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.

Dietary protein quality plays a key role in maintaining intestinal mucosal integrity, but also modulates the growth of luminal microorganisms. This work assessed the effect of dietary protein sources on the performance, gut morphology, and microbiome in Nile tilapia. Four isonitrogenous and isolipidic diets comprising equivalent amounts of the protein supply derived from either PLANT, ANIMAL, INSECT, or MICROBIAL (bacterial biomass) sources were fed to triplicate groups of fish (IBW: 12 g) during 46 days. Fish fed ANIMAL and MICROBIAL diets showed significantly higher growth than those fed the PLANT and INSECT diets (P < 0.05). Relative abundance at the phylum level shows Bacteroidetes, Fusobacteria and Proteobacteria as more abundant phyla in tilapia’s intestine, while Cetobacterium is the most representative genera in all treatments. Interesting patterns were observed in the correlation between amino acid intake and genus and species abundance. Metabolism prediction analysis showed that microbial amine and polyamine degradation pathways are modulated depending on diets. In conclusion, different protein sources interfere directly with the cross-talk of bacteria pathways and amino acid intake.

Dengue virus (DENV), being one of the lethal pathogens in the hot climatic regions of the world, have been extensively studied to decipher its mechanism of pathogenesis and missing links of its life cycle. With respect to the entry of DENV, multiple receptors have been recognised in different cells of the human body. However, scientists still argue whether these identified receptors are the exclusive entry mediators for the virus. Adding to the complexity, DENV has been reported to be infecting multiple organ types in its human host. Also, more than one receptor in a particular cell has been discerned to take part in mediating the ingress of DENV. In this review, we aim to discuss about the different cells of the human immune system that support DENV infection and their corresponding receptors that DENV deploy to gain access to the cells.

Nicotiana benthamiana plants infected with a potato virus Y isolate (PVYO) under ambient conditions of 25 °C and ~405 parts-per-million (ppm) ambient CO2 display symptoms of chlorosis, leaf curling, and stunting. However, under elevated temperature and CO2 levels (30 °C, 970 ppm), systemic viral titers decrease several-fold, and plants appear asymptomatic. Under the latter conditions we have studied how infection, drought, or both combined affect infection, drought-driven loss of leaf turgor, plant water content, stomatal conductance, metabolome, and hormone (ABA, SA, and JA) levels. We found that drought did not affect viral titers. As expected, drought decreased plant water content and stomatal conductance. Under drought conditions, infection did not alter significantly final water content or loss of leaf turgor progression, but it increased the levels of some sugars and other osmo-protectants. Infection and drought altered the levels of many components of the metabolome. Some components altered by infection were not altered by drought, but most of those altered by drought were also altered by infection. Drought increased the levels of ABA, infection increased the levels of ABA, SA, and JA, and altered their relative balance. The effects of drought and of infection on hormone levels were cumulative when combined. Thus, under ambient conditions that turn a severe infection into an asymptomatic one both, plant physiology parameters and the interplay with drought are affected.

This study presents extended Immunity Agent-Based Model (IABM) simulations to evaluate vaccination strategies in controlling the spread of infectious diseases. The application of IABM in the analysis of vaccination configurations is innovative, as a vaccinated individual can be infected depending on how their immune system acts against the invading pathogen, without a pre-established infection rate. Analysis at the microscopic level demonstrates the impact of vaccination on individual immune responses and infection outcomes, providing a more realistic representation of how the humoral response caused by vaccination affects the individual’s immune defense. At the macroscopic level, the effects of different population-wide vaccination strategies are explored, including random vaccination, targeted vaccination of specific demographic groups, and spatially focused vaccination. The results indicate that increased vaccination rates are correlated with decreased infection and mortality rates, highlighting the importance of achieving herd immunity. Furthermore, strategies focused on vulnerable populations or densely populated regions prove to be more effective in reducing disease transmission compared to randomly distributed vaccination. The results presented in this work show that vaccination strategies focused on highly crowded regions are more efficient in controlling epidemics and outbreaks. Results suggest that applying vaccination only in the densest region resulted in the suppression of infection in that region, with less intense viral spread in areas with lower population densities. Strategies focused on specific regions, in addition to being more efficient in reducing the number of infected and dead people, reduce costs related to transportation, storage, and distribution of doses compared to the random vaccination strategy. Considering that, despite scientific efforts to consolidate the use of mass vaccination, the accessibility, affordability, and acceptability of vaccines are problems that persist, investing in the study of strategies that mitigate such issues is crucial in the development and application of government policies that make immunization systems more efficient and robust.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing Human African Trypanosomosis (HAT - sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal Trypanosomosis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Sahara Africa. Trough mechanical transmission, T. vivax has however been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical Human Trypanosomosis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasite, but this is the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies allowing trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.

Sunflower is one of the oil crops and its planting areas was listed behind Soybean, peanut and rapeseeds in China. It will encounter different kind of diseases during planting, thus limited the seeds yield. Fusarium species are the major threat to different crops nowadays, it is very important to identify the species caused diseases on different hosts, so that the potential control measures may be explored. In Inner mongolia, Sunflower Disk Rot (SDR) was found in different sunflower planting field, the average infection ratio around 8.50%, typically in some verieties, its infection ratio reach to 11.67%. The diseased receptacle were collected from different locations and Koch’s postulate was conducted. The results showed that Fusarium verticillioides was the main causal agent caused SDR. Fungicide toxicity tests shown that Fludioxonil and Flutolanil were screened out from six fungicides for controlling F. verticillioides, with EC50 values of 0.05 µg/mL (R = 0.9825) and 0.96 µg/mL (R = 0.9964) , respectively. This is the first report of SDR caused by F. verticillioides, and it will alert sunflower reseachers to include SDR in the disease list, so as to control sunflower diseases with integrated management strategy successfully.

The endocannabinoid system (ECS) is a complex neuromodulatory network in the human body that have enormous impact in developing the central nervous system, as well as modulates various physiological processes. The ECS is made up of anandamide, 2-arachidonoylglycerol (2-AG), which are responsible for the synthesis and degradation of endocannabinoids, and enzymes such as FAAH and MAGL ensures the precise control over endocannabinoid levels. The ECS relies on CB1 receptors found in the central nervous system (CNS), and CB2 receptors found in the peripheral nervous system and immune cells. Dysregulation of the ECS has been associated with several health conditions, prompting investigations into its association with phytocannabinoids to harness their therapeutic potential. The ECS is intricately linked with the nervous system, and it is known to modulate neuronal activities in the CNS, influencing pain and mood modulation. The ECS is also associated with neuropathies-peripheral nerve damage leading to symptoms such as weakness, numbness and pain as evidenced in diabetic neuropathy, Guillain-Barré Syndrome, carpal tunnel syndrome, peripheral neuropathy, and postherpetic neuralgia. The focus of this review is on the interplay between 2-arachidonoylglycerol and anandamide amidohydrolase in neuropathy, elucidating their roles in pain regulation, inflammation, and specific neuropathies. The knowledge generated is expected to have broad implications, providing comprehensive insights into neuropathic conditions and how to improve on them. Ultimately, this understanding may lead to more effective treatments and improved quality of life for individuals affected by these conditions.

Emerging infectious disease threats are becoming more frequent due to various social, political and geographical pressures including increased human-animal contact, global trade, transportation and changing climate conditions. As a result, the threat that emerging agents can be spread by blood contact or transfusion of blood products also becomes increasingly problematic. Blood transfusion is essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving components can become a vector for spreading diseases, particularly to vulnerable populations. New methods have been implemented on a global basis for prevention of transfusion transmission via plasma, platelet, and whole blood products. Implementing proactive pathogen reduction methods can significantly reduce the likelihood of disease transmission via blood transfusion, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety which is based on a photochemical method involving Riboflavin and UV light. We provide examples of how emerging threats such as Ebola, SARS-CoV-2, Hepatitis E, monkeypox and other agents have been evaluated in real time regarding effectiveness of this method for reducing the likelihood of disease transmission via transfusion. Keywords: transfusion; blood; pathogen reduction; emerging infectious diseases.

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

Key genes needed for maintenance and growth for the two pathogens, Fusarium graminearum and Magnaporthe oryzae, were identified. These are genes that are induced in response to maintenance requirements (stress) and growth requirements. The processes involved are synthesizing arginine, synthesis of DNA-bases, nitric oxide synthesis needing arginine, autophagy, DNA synthesis, and DNA repair. A simplified regulatory network for these key genes for both organisms was constructed as a hypothesis for the work, and procedures previously developed to use sets of downloaded transcriptomic data were used to test hypotheses concerning what time under the course of infection of plants the key genes are expressed. The analysis shows that the transcription efforts (costs) to maintain the fungal cells (maintenance) are high before infection and during early infection. During the following biotrophic stage, maintenance activities drop, followed by a dramatic increase in the necrotrophic stage transition. Finally, in the necrotrophic stage, maintenance is again lower despite the high growth rate that can also cause stress. All identified genes' expressions behaved almost similar with an increased expression in the biotrophy-necrotrophy transition for both fungi except the DNA repair genes PARP/PARG that was not responding or absent (PARG) in the mainly clonal M. oryzae. This PARG expression pattern might indicate that M. oryzae is more subject to evolution by point mutations than F. graminearum, where sexual reproduction is frequent. The potential consequences of this in the development and the accelerated breakage of host species resistance in a Red Queen dynamics scenario are discussed. The analysis demonstrates the possibility of using large transcriptome datasets and co-regulations between key genes to test hypotheses. This technique's advantages complement molecular techniques that employ knockouts and over-expression of target genes to suggest that genes' roles are discussed.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD remains poorly understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

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.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

In the contemporary accelerated pace of life, emphasizing the importance of sleep quality is essential for enhancing overall well-being and health. This study investigates the link between poor sleep quality and key factors affecting wellness, such as mental health and eating disorders. Through a cross-sectional analysis involving 407 participants, utilizing established measures including the Depression Anxiety Stress Scale (DASS-21), the Eating Disorder Examination Questionnaire Short (EDE-QS), and the single-item Sleep Quality Scale (SQS), data was collected and analyzed using SPSS v28 and R-Statistics. The findings reveal a significant correlation (p&lt;0.05) between DASS-21, EDE-QS, and SQS, indicating that individuals experiencing poor sleep quality exhibit higher levels of depression, anxiety, and stress. Furthermore, multinomial logistic regression analysis highlights low sleep quality as a risk factor for both mental health (OR: 1.071, 95% CI: 1.042, 1.102, p&lt;0.05, low vs. high sleep quality), and eating disorders (OR: 1.047, 95% CI: 1.004, 1.092, p&lt;0.05, low vs. high sleep quality). Overall, these results underscore the critical role of sleep quality in mental health and suggest insomnia as a predictive factor for both poor mental well-being and disordered eating habits. Further research through randomized controlled trials is warranted to validate the findings of this cross-sectional study.

The rise in precocious puberty cases can be attributed to a combination of genetic and environmental factors. Genetic factors play a significant role, with studies identifying genetic abnormalities in genes such as KISS1, KISS1R, MKRN3, DLK1, GABRA1, LIN28B, NPYR, TAC3, and TACR3, which are associated with central precocious puberty (CPP). Epigenetic factors like DNA methylation and histone modifications may mediate the relationship between genetic and environmental influences on CPP development. Environmental factors such as exposure to secondhand smoke, cesarean section, and BMI have also been linked to precocious puberty, particularly in girls, highlighting the multifactorial nature of this phenomenon. Understanding the interplay between these genetic and environmental factors is crucial in addressing the increasing prevalence of precocious puberty in children. The published literature in the past five years was systematically reviewed and summarized highlighting the interplay of genetic and environmental factors for the rise in the precocious puberty.

This article aims to analyze the relationship between non-obstructive coronary artery disease (NOCAD) and atrial fibrillation (AF), exploring the underlying pathophysiological mechanisms and implications for clinical management. NOCAD and AF are prevalent cardiovascular conditions that often coexist, yet their interrelation is not well understood. NOCAD, characterized by the presence of atherosclerotic plaques without significant luminal stenosis, can lead to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. Atrial fibrillation, on the other hand, is the most common sustained cardiac arrhythmia, associated with an increased risk of stroke and heart failure, which may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Therefore, NOCAD and AF seems to be a complex Interplay with one begets another.

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth by targeting multiple iron/heme-dependent biological processes and suppressing the development of drug resistance. The aim of this review is to highlight recent findings on the mechanisms of action of gallium and provide further insights into the development of gallium-based compounds. Understanding the mechanisms underlying gallium’s biological activities will enhance its therapeutic application across various medical fields, offering promising avenues for the treatment of infectious diseases, cancer, and inflammatory conditions.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field.

the close phylogenetic relationship between ascidians (Tunicata) and vertebrates makes them a powerful model for studying the innate immune system. To better understand the nature and dynamics of immune responses and the mechanisms through which bacterial infections are detected and translated into inflammation in Ciona robusta, we applied an approach combining in vivo lipopolysaccharide (LPS) stimulation, immune-labelling and functional enzymatic analyses. The immunohistochemistry showed that toll-like receptor 4 (TLR4) and nuclear factor kappa B (NFκB) were expressed during the inflammatory pharynx response 4 hours post-LPS, with formation of immune-stained haemocyte nodules in the vessel lumen. Pharynx vessel endothelium also took part in the inflammatory response. Observations of histological sections from naive and MS-inoculated ascidians confirmed immuno-positive tissue response. Enzyme immune parameters – which included the activity of phenoloxidase, glutathione peroxidase, lysozyme, alkaline phosphatase and esterase – showed up-modulation 4 hours after LPS injection, confirming their involvement during ascidian inflammatory response. These findings provide new insights into the mechanisms involved in LPS-induced C. robusta response and suggest that a broad innate immune mechanism is involved in the regulation of tunicate inflammatory responses.

This article examines air sampling as an environmental surveillance strategy for early pathogen detection and offers a preliminary comparison of air and wastewater surveillance. Air sampling involves collecting bioaerosols to analyze the microbial composition of the air, utilizing techniques like PCR and metagenomic sequencing. Air sampling appears especially promising for detecting respiratory pathogens and highly transmissible pandemic agents, as these spread primarily via aerosols and droplets. The article details various air sampling techniques, their efficiency, and practical considerations, categorizing them into filtration, impaction, impingement, electrostatic precipitation, and condensation methods. It also explores the composition of airborne microbes, emphasizing the low concentration of viral nucleic acids and the challenges this poses for metagenomic sequencing. The selection of sampling locations, including indoor environments and airplanes, is discussed as critical for effective pathogen detection. Finally, the article contrasts air and wastewater sampling, concluding that while both methods should ideally be explored as layered defenses, air sampling does not collectively appear more promising than wastewater sampling.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

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

The past few years have brought substantial progress toward understanding how human cytomegalovirus (HCMV) enters the remarkably wide spectrum of cell types and tissues that the virus infects. Neuropilin-2 and platelet-derived growth factor receptor alpha (PDGFRa) were identified as receptors, respectively, for the trimeric and pentameric glycoprotein H/glycoprotein L (gH/gL) complexes that in large part govern HCMV cell tropism, while CD90 and CD147 were also found to play roles during entry. X-ray crystal structures for the proximal viral fusogen, glycoprotein B (gB), and for the pentameric gH/gL complex (pentamer) have been solved. A novel virion gH complex consisting of gH bound to UL116 instead of gL was described, and findings supporting the existence of a stable complex between gH/gL and gB were reported. Additional work indicates that the pentamer promotes a mode of cell-associated spread that resists antibody neutralization, as opposed to the trimeric gH/gL complex (trimer), which appears to be broadly required for the infectivity of cell-free virions. Finally, viral factors such as UL148 and US16 were identified that can influence the incorporation of the alternative gH/gL complexes into virions. We will review these advances and their implications for understanding HCMV entry and cell tropism.

Lirianthe delavayi has valuable ornamental and medicinal value, is an important economic tree, and has a long history of cultivation. As important regulatory molecules, miRNAs are involved in important physiological processes, such as the plant stress response, organ morphogenesis, hormone secretion, and signaling. In this study, based on miRNA sequencing analysis of wild and cultivated Lirianthe delavayi, we explored the differences in posttranscriptional regulation during the cultivation of Lirianthe delavayi from the aspect of miRNA molecular regulation. The results revealed the following: 1. A total of 365 miRNAs were sequenced and identified, and their first bases had obvious uracil (U) base preferences. Among them, 242 miRNAs were classified into 32 miRNA families; 2. Analysis of miRNA expression differences revealed that 39 miRNAs had significant expression differences between wild and cultivated populations; 3. Bioinformatics target gene prediction and target gene enrichment analysis of significantly differentially expressed miRNAs revealed that the target genes were significantly enriched in plant‒pathogen interactions, sphingolipid metabolism, defense responses, and ADP binding. 4. The plant‒pathogen interaction pathway involves seven differentially expressed miRNAs and 30 miRNA‒target gene regulatory pairs, which are involved mainly in pathogen signature molecule recognition and binding, signal transduction, and the regulation of disease resistance molecules or gene expression; Ath-MIR169g-p3_2ss7AG19GA, ath-MIR169g-p5_2ss7AG19GA, and ath-miR408-3p_L-3 are expressed only in wild population, and it is hypothesized that the domestication process from wild to cultivation species may be accompanied by the loss of disease resistance-related miRNAs. This study provides a reference for exploring the posttranscriptional-level regulatory mechanisms of adaptive changes in Lirianthe delavayi from wild to cultivated.

This essay discusses the complicated relationship between ideology and faith, focusing on the importance of faith. It endeavors to enrich the critical examination of religion by providing a platform to analyze the multifaceted nature of ideologies and their profound influence on human geography. This study is particularly distinctive for its focus on the complex interplay of Marxism, religion, and modernity, deepening our understanding of how these dynamics shape contemporary societies.

Leishmania parasites present astonishing adaptative abilities that represent a matter of life or death within disparate environments during the heteroxenous parasite life cycle. From an evolutionary perspective, organisms develop methods of overcoming such challenges. Strategies that extend beyond the genetic diversity have been discussed and include variability between parasite cells during the infections of their hosts. The occurrence of Leishmania subpopulation fluctuations with variable structural genomic contents demonstrates that a single strain might shelter the variability required to overcome inconsistent environments. Such intrastrain variability provides parasites with an extraordinary ability to adapt and thus survive and propagate. However, different perspectives on this evolution have been proposed. Strains or species living in the same environment can cooperate but also compete. These interactions might increase the replication rate of some parasites but cause the loss of more aggressive competitors for others. Adaptive responses to intra- and interspecific competition can evolve as a fixed strategy (replication is adapted to the average genetic complexity of infections) or an optional strategy (replication varies according to the genetic complexity of the current infection). This review highlights the complexity of interspecies and intrastrain interactions among Leishmania parasites as well as the different factors that influence this interplay.

Vitamin D and iron deficiencies are the most prevalent micronutrient deficiencies among women of reproductive age (WRA) in Morocco. Recent studies suggest that Vitamin D deficiency (VDD) may reduce iron bioavailability necessary for erythropoiesis, potentially leading to iron deficiency (ID) and anemia. This study investigates the association between vitamin D status, iron levels, and anemia risk among Moroccan WRA aged 18-49 years. A cross-sectional study was conducted with 463 participants. Serum levels of 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine were measured. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were evaluated using validated questionnaires, and anthropometric data were collected. Linear and logistic regression models assessed the relationships between variables, while Receiver Operating Characteristic (ROC) curve analysis evaluated the predictive accuracy of VDD for ID and anemia. VDD (25(OH)D &lt; 20 ng/ml) was significantly associated with lower levels of hemoglobin, hematocrit, red blood cells, and ferritin (all p &lt; 0.01), suggesting a role of vitamin D in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19-19.28, p &lt; 0.001), ID (OR: 2.20, 95% CI: 1.32-3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73-12.08, p = 0.004). Dietary iron intake was inadequate among all participants, with minimal protective effect against anemia and ID (β(SE): -0.08(0.03), p = 0.030 and β(SE): -0.05(0.02), p=0.037 respectively). ROC analysis demonstrated moderate discriminative power for VDD in diagnosing IDA and anemia (AUC: 0.643 and 0.603) but reduced accuracy for ID (AUC: 0.575). This study identifies VDD as a significant risk factor for impaired iron status and anemia among Moroccan WRA, underscoring the need for targeted nutritional interventions and further research to explore effective prevention strategies.

Fall armyworm, Spodoptera frugiperda, is one of the major migratory polyphagous insect pests of various crops. The essential nutrient and mineral profile of host plants determines the feeding fitness of herbivorous insects. As a result, growth and development of insects is affected. To determine the effect of nutrient and mineral profile of different host plants (maize, castor bean, cotton, cabbage, okra and sugarcane) on the growth and development of S. frugiperda, biological parameters like larval weight, pupal weight (male/female), feeding and growth indices were calculated. The proximate compositions and mineral contents of the tested host plants showed a significant difference (p&lt;0.5). Better nutrients were observed in castor bean and maize host plants. The growth indices on these host plants also showed the statistical difference (p&lt;0.05) except efficiency of ingested food (p&gt;0.05). The maximum relative growth rate (RGR), relative consumption rate (RCR) and consumption index (CI) were recorded in S. frugiperda larvae that fed on maize and castor bean leaves. Larval, male and female pupal weights were the maximum in the larvae feeding on castor bean host plant. In case of fitness indices, the highest larval growth, pupal growth, standard growth and fitness indices were observed in S. frugiperda larvae that fed on maize. The findings of the present study highlight the dynamic growth and development of S. frugiperda larvae on maize plants and provide novel information based on nutritional ecology to develop sustainable integrated pest management strategies using selective crop rotation and limiting alternative host plants.

In the context of evolving perceptions of sexuality, particularly within the realm of health and disability, this study investigates the impact of multiple sclerosis (MS) on female sexual function and quality of life. A quantitative study involving 130 female MS patients aged 35 to 50 was conducted, employing measures such as The Female Sexual Function Index (FSFI), The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), and The Fatigue Severity Scale (FSS). Results indicate a significant association between greater sexual dysfunction and poorer quality of sex life, alongside the correlation of increased fatigue with diminished sexual satisfaction. Factors such as education level, time of diagnosis, and treatment regimen also influenced outcomes. Findings underscore the importance of supportive interventions, including counseling, to enhance the quality of sex life for women with disabilities, particularly those with MS.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

Enterococci are gastrointestinal commensals whose hardiness allowed them to colonize very diverse environments, including soils, water, food and feed. This ability to overcome adverse conditions makes enterococci problematic once they colonize hospital niches. Together with the malleability of their genomes, the capacity to acquire and disseminate determinants of antibiotic resistance have contributed to convert what was once just another opportunistic pathogen into a first-class clinical problem. This review discusses the dimension of the emergence of enterococcal resistance to key antimicrobial agents, the dissemination of this resistance and its significance in terms of public health, with the aim of raising the awareness to the need to devise and implement monitoring programmes and effective antibiotic usage guidelines.

The trillions of bacteria that live in and on our bodies make up the human microbiota, which is a very important part of keeping us healthy and protecting us from pathogenic infections. Dysbiosis is when there are changes in the composition and variety of the microbiota. This can upset the delicate balance between the host and its microbes, making the host more vulnerable to pathogens. Understanding the complicated link between microbiota and pathogens is important for coming up with effective ways to change microbiota and boost the body's defenses against infections. This study looks at how microbiota modulation affects the spread of pathogens and infections. It talks about how the makeup of microbiota affects how susceptible you are to pathogens. It shows how a healthy microbiota can protect you by making it hard for pathogens to grow and take over. The review also goes into detail about how the microbiota protects against pathogens, such as through competitive exclusion, the production of antimicrobial compounds, and the regulation of immune reactions. The study also looks at the idea of dysbiosis and how it is linked to pathogenic shifts. Disruptions in the microbiota can make it easier for pathogens to grow and make it harder for the host to fight off infections. It focuses on the need to recover microbial balance to improve the host's defenses and lower risks caused by pathogens. There is also talk about the use of probiotics, prebiotics, and fecal microbiota transplantation (FMT) as ways to change the microbiome. The goal of these interventions is to restore the diversity and function of microbes, improve the integrity of barriers, and boost the immune system's reaction to pathogens. The review shows how these methods could be used to change the microbiota and make it easier for the body to fight off infections. In conclusion, knowing how the microbiota and pathogens work together in a complicated way can help a lot when it comes to making specific interventions for microbiota modulation. Strategies that restore the balance of microbes and boost the host's defenses could stop pathogens from taking over and making people sick. More study needs to be done in this area to improve therapeutic approaches and use the microbiota to its fullest extent to fight infectious diseases.

Antimicrobial resistance (AMR) is a growing public health issue worldwide that affects the world economy. The concern associated with this issue increased during the COVID-19 pandemic. The misuse of antibiotics during the COVID-19 pandemic will have catastrophic implications for the control of AMR. In 2019, the coronavirus illness COVID-19 first appeared in China. COVID-19 infection is a surface-to-surface communicable disease. It is considered the most vital global health disaster of the century. It has rapidly spread around the world and is the greatest challenge for humankind. This chapter discusses the origin, symptoms, transmission, treatment, and recommendations of the COVID-19 disease.

The success of any tsetse control programs depends on the knowledge of their behaviour. This study assessed the host choice and feeding behaviours of Glossina morsitans’ siblings whose parents were bloodfed on Rabbits, Guinea pigs, Rodents and Squirrels. Individual host was placed in a screen cage which allowed flies to enter through openings on each side. The groups of flies (20 per replicate) colour-marked differently basing on their parents’ bloodmeal hosts, were released from the centre of large semi-field cage. Released flies were aspirated after 24 hours, then, sorted basing on the location, feeding status and parents’ bloodmeal. A total of 213 flies (72.95% of the recovered) were attracted to the hosts. The number of flies attracted to different hosts varied significantly (χ²4= 33.685, p= 0.0001); Rodent (n=80, p=0.006), Rabbit (n=59, p=0.331), Guinea pig (n=49, p=0.057) and squirrel (n=25, p=0.005). The number of flies attracted to their parent’s blood meal source varied significantly (χ²12 = 56.476, p&lt;0.001); rabbits (n= 35, 59.32%, p&lt;0.001), rodent (n=25, 31.25%, p=0.043) and guinea pig (n= 19, 38.78%, p=0.45). But, only 39 flies (18.31% of total attracted) bloodfed on the hosts; Guinea pigs (n=10, 25.64%), Rodents (n=23, 58.97%), Rabbits (n=6, 15.38%) and Squirrels (n=0,0.0%). There was significant variation in number of flies that fed successively across hosts (χ²4=49.478, p&lt;0.001). The findings from this study confirms the presence of the hosts’ differential attractiveness to flies but failed to explain observed behaviours with reference to genetic inheritance. Therefore, the study attracts the need for detailed investigation on the influence of bloodmeal sources on tsetsefly siblings’ behaviours across filial generations using small mammals.

Ovarian cancer is among the most common causes of female mortality. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1) was examined. Cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, both on cancer stem cells (CSCs), marked as CD49f+ and non-CSCs (CD49f-) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (P &lt; 0.001). The expression of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. Both cell lines showed a change in the glycophenotype of the cells, either up or down of its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment of Compound 1 resulted in a statistically significant increase in both early and late apoptosis (P&lt;0.001) suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The metabolic analysis revealed that the treated cancer cells showed reduced metabolic activity compared to the control group (P &lt; 0.001)

The onset of neurodegenerative diseases involves a complex interplay of pathological mecha-nisms, including protein aggregation, oxidative stress, impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disor-ders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox sig-naling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a criti-cal antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading al-tered cell components. The interaction between p62/SQSTM1, Nrf2 and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for thera-peutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, the review explores the potential synergy between the endocannabinoid system and Nrf2 signal-ing for neuroprotection. Further research is needed to elucidate the involved molecular mecha-nisms and develop effective therapeutic strategies against neurodegeneration.

The crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete Aphanomyces astaci (Ap. astaci), which was introduced to Europe around 1860. All European species of freshwater crayfish are susceptible to the disease, including the white-clawed crayfish Austropotamobius pallipes. The aquatic mould is primarily spread by North American crayfish species and can also disperse rapidly through contaminated wet gear moved between water bodies. This spread, coupled with competition from non-indigenous crayfish, has drastically reduced and fragmented native crayfish populations across Europe. Remarkably, the island of Ireland remained free from the crayfish plague pathogen for over 100 years, providing a refuge for A. pallipes. However, this changed in 1987 when a mass mortality event was linked to the pathogen marking the pathogen's introduction to the region. Fortunately, the plague did not establish and was not detected again in Ireland until 2015 when a molecular analysis linked a mass mortality event in the Erne catchment to Ap. astaci. Since then, the pathogen has appeared across the island. Between 2015 and 2023, Ap. astaci was detected in 18 Irish water catchments, revealing multiple genotypes. Intriguingly, the pathogen in Ireland exists without its natural host species. The uneven distribution of various genetic lineages strongly suggests human-mediated transport of zoospores via contaminated water equipment as a primary cause of spread. This review details the timeline of these events, Ap. astaci’s introductions into Ireland, its rapid spread, the genotypes documented, the issue of non-indigenous crayfish species in Ireland and management efforts.

The effects of ELICE16INDURES, a well-known plant conditioner developed by the Research Institute for Medicinal Plants and Herbs Ltd. Budakalasz, Hungary, were studied in a soybean population. The active ingredients of the compound have been selected to help elicit general immunity in plants without pathogenic damage, thereby roborizing the healthy plant population and preparing it for possible future biotic stressors. Here we have analyzed changes in the expression levels of genes encoding enzymes involved in the catalysis of metabolic pathways that induce and regulate PAMP-triggered immunity (PTI) at two different time points and treatments. Twenty-three different enzymes were analyzed that catalyze different metabolic pathways, such as the biosyntheses of jasmonic acid, salicylic acid, ethylene, phenylpropanoid, flavonoid, and phytoalexin biosynthesis and cellular detoxification processes. Bioinformatical softwares werw used to analyze the results. It has been found that some of the primary defense mechanisms (e.g., Mitogen-Activated-Protein Kinase (MAPK) cascade, jasmonic acid biosynthesis, flavonoid and phytoalexin biosynthesis, etc.) that intensify following the attack of pathogens can be activated without the intrusion of the actual pathogen by an immunochemical. Thus, we proved that plant resistance can be artificially conditioned.

Campylobacter is one of the major foodborne pathogens of concern in its growing trend of antimicrobial resistance. C. jejuni and C. coli are the major causative agents, with C. jejuni contributing to most of the cases in approximately 90% in the world. Infection is transmitted to humans due to consumption of contaminated food and water. Campylobacteriosis caused by C. jejuni is commonly presented with severe diarrhoea, abdominal pain, fever, headache, nausea, and vomiting with some extreme cases resulting in Guillain–Barré syndrome (GBS) and acute flaccid paralysis. Symptoms are severe in cases of children below 5 years, elderly and individuals who are immunocompromised. The infection is usually sporadic, and self-limiting and thus does not require antibiotics for treatment. Still, the antimicrobial resistance in Campylobacter is a major concern because of the transmission of resistance from animal sources to humans. This review highlights the recent epidemiology, geographical impact, resistance mechanisms, spread of Campylobacter spp. and the strategies to control the transmission of Campylobacter from veterinary sources and its antimicrobial resistance.

Predator-prey interactions present heightened opportunities for pathogen spillover, as predators are exposed to novel parasites through consumption of prey harboring potentially infectious agents. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events with significant conservation implications, particularly for sensitive species. However, relatively few virulent infections following prey consumption are reported, given the very large number of exposures that presumably occur. Further, many transmitted agents are infectious but clinically silent and thus go unrecognized. Mechanisms that determine outcome of predator exposure to prey-based pathogens therefore represent an important, understudied component of disease dynamics that should be considered in modeling approaches and empirical research to better understand disease risk and emergence, particularly in vulnerable or threatened species.

The mortality rate of women during the gestation period or after delivery is very high worldwide. ToRCH pathogens [Toxoplasma gondii (T.gondii), Rubella Virus (RV), Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV)] are transmitted vertically and are associated with mortality and complications both in the mother and the fetus or children. Therefore, this study is designed to investigate the ToRCH pathogen-induced histopathological changes in placental tissues and associated post-obstetric complications in Pakistani women. Women (N = 68) included in this study were divided into Group A (women with current abortion and bad obstetric history-BOH) and Group B (women with normal delivery and BOH). The venous blood collected was analyzed for ToRCH antibodies through ELISA. A small piece of placenta tissue taken after delivery or abortion was subjected to nucleic acid (NA) detection through PCR using ToRCH pathogen-specific primers. The placental tissue was analyzed for histopathological changes under a microscope. The data obtained were analyzed using percentages and the Chi square test. Overall ToRCH antibody positivity was 64.70% (44/68). Of these, IgM (Immunoglobulin M) was found in 17.65% (12/68), IgG (Immunoglobulin G) in 45.59% (31/68), and one case (1.47%) was seropositive for both IgM and IgG. The NA was detected in 66.18% (45/68) of the placental tissues of the study population. The higher prevalence of antibodies for T.gondii and RV (23.53% each) and NA for RV, CMV, and HSV (17.99% each) was observed in the study population. The ToRCH infection (antibodies and NA) with BOH complications was statistically found to be non-significant (p> 0.05). Overall discrepancies in ToRCH antibodies and NA positivity were found in 86.76% (59/68) of cases, especially for RV (26.47%). Chorionic villitis (CV) in placental tissues was observed in 20.59% (14/68), i.e., 13.23% of Group A and 7.35% of Group B. Of the total, four women with T.gondii, six with RV, and three each with CMV and HSV infection were found with CV. The most common BOH complications observed were recurrent spontaneous abortions (RSAs) (47.05%, 32/68), stillbirth (22.05%, 15/68), congenital abnormalities (14.70%, 10/68), etc. It was observed that RSAs were associated with CV (10.29%) in the study population. The BOH complication and CV were found to be statistically non-significant (p> 0.05). It is concluded that ToRCH pathogens are prevalent in the study population, and CV was the only histopathological change found and associated with BOH complications.

Begomoviruses, which belong to the Geminiviridae family, are intracellular parasites transmitted by whiteflies to dicotyledonous plants, significantly damaging agronomically relevant crops. These nucleus-replicating DNA viruses need to move intracellularly from the nucleus to the cytoplasm and then, like other plant viruses, spread systemically throughout the plant to cause dis-ease. The transport proteins of begomoviruses play a crucial role in recruiting host components for the movement of viral DNA within and between cells while exhibiting functions that suppress the host's immune defense. Pioneering studies on species of the Begomovirus genus have identified specific viral transport proteins involved in intracellular transport, cell-to-cell movement, and systemic spread. Recent research has primarily focused on viral movement proteins and their interaction with the cellular host transport machinery, significantly expanding our understanding of viral infection pathways. This review focuses on three main aspects: (i) the role of viral transport proteins, specifically movement proteins (MPs) and nuclear shuttle proteins (NSPs), (ii) their ability to recruit host factors for intra- and intercellular viral movement, and (iii) suppress antiviral immunity, with a particular emphasis on bipartite begomoviral movement proteins.

In this brief review, the concepts of quantum tunneling and parity violation are introduced in the context of chiral molecules. A particle moving in a double well potential provides a good model to study the behavior of chiral molecules, where the left well and right well represent the L and R enantiomers, respectively. If the model considers the quantum behavior of matter, the concept of quantum tunneling emerges, giving place to a stereomutation dynamics between left- and right-handed chiral molecules. Parity-violating interactions, like the electroweak one, can be also considered, making possible the existence of an energy difference between the L and R enantiomers, the so-called parity-violating energy difference (PVED). Here we provide a brief account of some theoretical methods usually employed to calculate this PVED, also commenting on relevant experiments devoted to experimentally detect the aforementioned PVED in chiral molecules.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

The high transmissibility, rapid evolution, and immune escape of SARS-CoV-2 variants can influence the course of infection and, in turn, morbidity and mortality in COVID-19, posing a challenge in controlling transmission rates and contributing to the emergence and spread of new variants. The factors that shape viral genetic variation are consequently essential for understanding the evolution and transmission of SARS-CoV-2, especially in vaccinated individuals where immune response plays a role in the progression and spread of this disease. This study assessed. In this context, we evaluated the impact of immunity induced by the CoronaVac vaccine (Butantan/Sinovac) on intra-host genetic diversity, analyzing 118 whole-genome sequences of SARS-CoV-2 from unvaccinated and vaccinated patients infected with the Gamma variant. Vaccination with CoronaVac favors negative selection at the intra-host level in different genomic regions and prevent greater genetic diversity of SARS-CoV-2, which may help reduce the emergence of new mutations, reinforcing the importance of vaccination in reducing virus transmission.

When the zoonotic parasite of rodents that can cause human neuroangiostrongyliasis, i.e., Angiostrongylus cantonensis, is found in its natural definitive hosts, it is usually reported in isolation, as if the rat lungworm were the only component of the within-rat parasite community. In this study we report the coinfections found in rats naturally infected by A. cantonensis in urban populations of Rattus norvegicus and Rattus rattus in Valencia, Spain. In addition to the rat lungworms, which were found in 14 of the 125 rats studied (a prevalence of 11.20%), 18 other parasite infrapopulations (intestinal and tissular protists, microsporidia, and helminths) were found; some of them with high burdens. Fourteen of these 19 species found are potential zoonotic parasites, namely Blastocystis, Giardia duodenalis, Cryptosporidium spp., Enterocytozoon bieneusi, Encephalitozoon hellem, Toxoplasma gondii, Brachylaima spp., Hydatigera taeniaeformis larvae, Hymenolepis nana, Hymenolepis diminuta, Angiostrongylus cantonensis, Calodium hepaticum, Gongylonema neoplasticum and Moniliformis moniliformis. Despite the limited number of rats studied, the total predominance of coinfected rats as well as their high parasite loads seem to indicate a clear trend towards parasite tolerance.

Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV-host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 200 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the remaining 665 is unknown. Studying anti-influenza efficacy, immuno-modulating properties and potential resistance of these compounds or their combinations may lead to the discovery of novel modulators of IAV-host interactions, which might be more effective than the currently available anti-influenza therapeutics.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) is the Leishmania parasites carrying a viral endosymbiont Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable clinical outcomes. LRV1 has been observed in cultured strains of five L. (Viannia) species, and host specificity was suggested when studying LRV1 from L. braziliensis and L. guyanensis strains. The coevolution hypothesis of LRV1 and Leishmania was based on phylogenetic analyses, implying an association between LRV1 genotypes, Leishmania species, and their geographic origins. This study aimed to investigate LRV1 specificity to Leishmania (Viannia) species hosts by analyzing LRV1 from L. (Viannia) species. To this end, LRV1 was screened in L. (Viannia) species other than L. braziliensis or L. guyanensis, and it was detected in 11 out of 15 L. naiffi and in 2 out of 4 L. shawi. Phylogenetic analyses based on partial LRV1 genomic sequencing supported the hypothesis of host specificity, as LRV1 clustered according to their respective Leishmania species hosts. These findings underscore the importance of investigating Leishmania and LRV1 coevolution and its impact on Leishmania (Viannia) species dispersion and pathogenesis in the American Continent.

This review explores the complex interrelationships between emotion, attention, and behavior, drawing upon empirical evidence from psychological, neuroscientific, and clinical studies. It delves into the neural mechanisms that underlie these interactions, with a focus on key brain regions such as the prefrontal cortex and amygdala. Clinical cases involving stroke and attention-deficit/hyperactivity disorder (ADHD) are examined to illustrate the real-world implications of these cognitive interactions. The review also discusses the impact of effective emotion regulation strategies and the role of attention as a cognitive mechanism that influences both emotion and behavior. Neuroimaging studies, particularly functional MRI, are highlighted for their role in providing a deeper understanding of these intricate relationships. The review concludes by emphasizing the importance of this triadic relationship in adaptive functioning and its broader implications for mental health, interpersonal relationships, and quality of life.

Additive manufacturing (AM) has revolutionized the field of biopolymers by providing a range of opportunities to create complex and intricate structures. Here we provide an overview of developments in biopolymer AM, first in the context of how natural systems have impacted the synthetic processes of AM, and secondly in the context of how synthetically derived structures can be used for biomedical applications. In particular, we explore the range of biopolymers developed for AM, AM techniques for biopolymers, and potential biocompatible medical applications with a focus on four categories of tissue in the human body: skin, bone, heart, and nerve. Despite the current challenges of the technology, exciting results in tissue regeneration, synthetic replacements for natural grafts, and complex dynamic organoids have already come to pass - with many more possible in the future.

Financial stress can have significant implications for individuals, businesses, asset prices and the economy as a whole. This study examines the nonlinear structure and dynamic changes in the multifractal behavior of cross-correlation between the financial stress index (FSI) and four well-known commodity indices, namely Commodity Research Bureau Index (CRBI), Baltic Dry Index (BDI), London Metal Index (LME) and Brent Oil prices (BROIL), using multifractal detrended cross correlation analysis (MFDCCA). For analysis, we utilized daily values of FSI and commodity index prices from 16th June 2016 to 9th July 2023. The following are the most important empirical findings: (I) All of the chosen commodity market indices show cross correlations with the FSI and have notable multifractal characteristics. (II) The presence of power law cross-correlation implies that a noteworthy shift in FSI is likely to coincide with a considerable shift in the commodity indices. (III) The multifractal cross-correlation is highest between FSI and Brent Oil (BROIL) and lowest with LME. (IV) The rolling windows analysis reveals a varying degree of persistency between FSI and commodity markets. The findings of this study have a number of important implications for commodity market investors and policymakers.

Erectile dysfunction (ED) is the inability to achieve or maintain an erection during sexual performance. ED is one of the most common and neglected complications of diabetes. Almost 35-75% of diabetic men around the world suffer from ED. Although the exact mechanism by which diabetes causes ED is not well understood. However, several studies suggested it may be related to damage to the nerve and vessels that supply the penis.

The Myc gene, widely studied in numerous cancer types, serves as a pivotal regulator of crucial cellular processes implicated in tumorigenesis, such as cell growth, proliferation, invasion, metastasis, and therapy resistance. LncRNAs have been identified as relevant partners of Myc. LncRNAs modulate chromatin structure and function, transcription, splicing, stability, and translation of mRNAs, thereby emerging as pivotal regulators in cell differentiation, metabolism, signaling. An intricate crosstalk exists between Myc and lncRNAs in a wide range of cancers, wherein they can physically and functionally interact through direct and indirect mechanisms. Some lncRNAs can regulate Myc activity at post-transcriptional level, affecting its stability, translation, or interactions with other proteins, thus acting as oncogenes, while others act as tumor suppressors. On the other hand, Myc can target numerous lncRNA genes and modulate their expression, affecting the expression of downstream targets involved in tumorigenesis. Given the significant role of the Myc-lncRNA network in various cancer types, exploring therapeutic strategies targeting these crucial cellular regulators is of utmost importance. This review article focuses on breast cancer, analyzing those lncRNAs influencing Myc as well as the Myc-regulated lncRNAs.

Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to his-tone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively investigated in the context of cancer research, its association with histone modifiers has received limited attention. This review ex-plores the interplay between histone modifiers and p53 in regulating gene expression. We discussed how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This study provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

Solid tumours are characterized by an altered microenvironment (TME) from the physi-cochemical point of view, displaying a highly hypoxic and acidic interstitial fluid. Hy-poxia results from uncontrolled proliferation, aberrant vascularization and altered can-cer cell metabolism. Tumour cellular apparatus adapt to hypoxia by altering its metab-olism and behaviour, increasing its migratory and metastatic abilities by acquisition of a mesenchymal phenotype and selection of aggressive tumour cell clones. Extracellular acidosis is considered a cancer hallmark, acting as a driver of cancer aggressiveness by promoting tumour metastasis and chemoresistance by selecting for more aggressive cell phenotypes, although the underlying mechanism is still not clear. In this context, Ca2+ channels represent good target candidates due to their ability to integrate signals from the TME. Ca2+ channels are pH and hypoxia sensors and alterations in Ca2+ homeostasis in cancer progression and vascularization have been extensively reported. The present review will focus on Ca2+ permeable ion channels, with a major focus on TRP, SOC and PIEZO channels, that are modulated by tumour hypoxia and acidosis as well as the role of the resulted altered Ca2+ signals on cancer progression hallmarks. A deeper compre-hension of the Ca2+ signaling and acidic pH/hypoxia interplay will break new ground for the discovery of alternative and attractive therapeutics targets.

A topological quantum interplay between the magnetic flux and the mass has been investigated, for the case of an electron, by evaluating a gauge-invariant phase factor (a Wilson loop) linked to the electromagnetic gauge field of the particle. In particular, from this phase factor and the quantization of the magnetic flux variations, a relationship between the mass at rest of the electron and its self-energy , arising from radiative corrections, has been obtained also within a QED approach. Besides, a formulation of an energy scale comparable to the energy at rest of an electron-positron pair is proposed. Remarkably, a reckoning of the Bohr energy of a W⁺ W^- pair is compatible with constants and parameters usually employed within the electroweak theory and comparable to the energy at rest of an electron-positron pair.

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterized the diversity of these Carnivore protoparvovirus 1 variants in 18 faecal samples collected from domestic cats with FPL during an outbreak, using targeted parvoviral DNA metagenomics to a mean depth of >10,000 X coverage per site. All samples comprised FPV alone. Compared to the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were non-synonymous, including 9 in non-structural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit inter-host diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intra-host diversity at all polymorphic positions was low with sub-consensus variant frequencies (SVF) of >1% except for two positions (2108 and 3208) in two samples with SVF of 1.1 – 1.3%. Intra-host nucleotide diversity was measured across the whole genome (0.7 - 1.5%) and for each gene, and was highest in the NS2 gene of four samples (1.2 – 1.9%). Overall, intra-host viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.

The DNA Damage Response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is a crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway, as well as abnormalities in the DDR-MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers, as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

The spread of viral pathogens both between and within hosts is inherently a spatial process. While the spatial aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread within infected hosts are still understudied. Recent experimental studies, however, have started to shed more light on the mechanisms and spatial dynamics of viral spread within hosts. Here, we review these experimental studies as well as the limited number of computational modeling efforts that have begun to integrate spatial considerations for understanding within-host viral spread. We limit our review to influenza virus to highlight key mechanisms affecting spatial aspects of viral spread for pathogens of the respiratory tract. There is considerable empirical evidence for highly spatial within-host spread of influenza virus, yet few computational modeling studies that shed light on possible factors that structure the dynamics of this spatial spread. In existing modeling studies, there is also a striking absence of theoretical expectations of how spatial dynamics may impact the dynamics of viral populations. To mitigate this, we turn to the extensive ecological and evolutionary literature to provide informed theoretical expectations for what viral and host factors may impact the spatial patterns of within-host viral dynamics and for how spatial spread will affect the genetic composition of within-host viral populations. We end by discussing current knowledge gaps related to the spatial component of within-host influenza virus spread and the potential for within-host spatial considerations to inform the development of disease control strategies.

The impacts of spice (sumac, cumin, black pepper, and red pepper) extract on Gram-positive (S. aureus and E. faecalis) and Gram-negative (K. pneumonia, P. aureginosa, C. jejuni, A. hydrophila, S. Paratyphi A, and Y. enterocolitica) food-borne pathogen bacterial strains (FBP) for their antibacterial activity and accumulation of ammonia (AMN), trimethylamine (TMA), and biogenic amines (BAs) in tyrosine decarboxylase broth (TDB) were investigated. Sumac extract exhibited the highest an-tibacterial potential against all FBP followed by cumin and peppers. Ammonia (AMN) production (844.24-543 mg/L) was strongly inhibited by sumac extract (55.10 mg/L), whilst suppression of trimethylamine (TMA) production (53.66-3.21 mg/L) was observed by sumac (1.28 mg/L), followed by red pepper (0.91 mg/L) extract. Cumin extracts stimulated the production of cadaverine, spermidine, tryptamine, and 2-phenylethylamine. Furthermore, sumac extracts inhibited hista-mine and tyramine production in the majority of FBP. This research suggests the application of sumac extracts as natural preservatives for inhibiting the growth of FBP and inhibiting the pro-duction of AMN, TMA, and BAs.

This comprehensive review delves into the intricate relationship between Sodium-GlucoseCo-Transporter 2 (SGLT2) inhibitors and AF, highlighting the multifaceted actions of thesedrugs and their significant cardiovascular benefits. Mechanisms: SGLT2 inhibitors inducesubstantial hemodynamic changes, impacting blood pressure, adipose tissue function, andinflammation. They enhance glycemic control while potentially reducing oxidative stress andinflammation, and they modulate atrial electrophysiology, collectively contributing to the reductionof AF risk. Clinical Evidence: This review synthesizes a wealth of clinical evidence,drawing from observational studies and randomized controlled trials, consistently demonstratinga correlation between SGLT2 inhibitors, particularly dapagliflozin and empagliflozin, anda decreased risk of AF. This protective effect is most pronounced in patients with type 2 diabetesand heart failure, underscoring their potential as therapeutic agents for high-risk populations.Potential Benefits: SGLT2 inhibitors offer a spectrum of potential benefits, includingsubstantial reductions in AF risk, particularly in patients with type 2 diabetes and heart failure.These drugs have consistently demonstrated benefits in reducing heart failure hospitalizations,cardiovascular mortality, and stroke risk, which indirectly contribute to better AF management.Furthermore, SGLT2 inhibitors exhibit renoprotective properties by slowing theprogression of chronic kidney disease and reducing albuminuria, offering substantial benefitsfor AF patients with comorbid kidney disease. Metabolic improvements involving weight loss,blood pressure reduction, and favorable changes in lipid profiles contribute to enhanced cardiovascular health and reduced AF risk. Originally designed for diabetes management, thesemedications offer a holistic approach to AF risk reduction, particularly in patients with type 2diabetes and heart failure.

Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring of pathogen levels in aquaculture facilities. This paper describes a photonic biosensing platform based on silicon nitride waveguide technology with integrated active components, which could be used for such applications. Compared to the state of the art, the current system presents improvements in terms of miniaturization of the Photonic Integrated Circuit (PIC), and the development of wafer level processes for hybrid integration of active components and for material-selective chemical and biological surface modification. Furthermore, scalable processes for integrating the PIC in a microfluidic cartridge have been developed, as well as a prototype desktop readout instrument. Three bacterial aquaculture pathogens (Aeromonas salmonicida, Vagococcus salmoninarum, and Yersinia ruckeri) were selected for assay development. DNA biomarkers were identified, corresponding primer-probe sets designed, and qPCR assays developed. The biomarker for Aeromonas was also detected using the hybrid PIC platform. This is the first successful demonstration of biosensing on the hybrid PIC platform.

Biotic stressors pose serious threats to crop yield, jeopardizing food security and resulting in over US$220 billion per year losses to the agriculture industry. Plants activate innate defense mechanisms upon pathogen perception and invasion. The plant immune response comprises numerous concerted steps, including the recognition of invading pathogens, signal transduction, and activation of defensive pathways. However, pathogens have evolved various structures to evade plant immunity. Given these facts, genetic improvements of plants are required for sustainable disease management to ensure global food security. Advanced genetic technologies have provided new opportunities to revolutionize and boost plant disease resistance against devastating pathogens. Furthermore, targeting susceptibility (S) genes, such as OsERF922 and BnWRKY70, through CRISPR methodologies offers novel frontiers to disrupt the molecular compatibility of pathogens and introduce durable resistance against them in plants. Here, we provide a critical overview of advances in understanding disease resistance mechanisms. The review also critically examines management strategies under challenging environmental conditions and R gene-based plant genome engineering systems intending to enhance plant responses against emerging pathogens. This work underscores the transformative potential of modern genetic engineering practices in revolutionizing plant health and crop disease management while emphasizing the importance of responsible application to ensure sustainable and resilient agricultural systems.

Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant since some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, and drug resistance profile of K. ohmeri. To contribute to the knowledge of this yeast, this study aimed to describe in depth three isolates of K. ohmeri associated with fungemia in Honduras. The identification of the isolates was carried out by sequencing the ribosomal ITS region. In addition, the sensitivity profile to antifungals was determined, and some properties associated with virulence were evaluated (exoenzyme production, biofilm formation, cell adhesion, and invasion). The isolates showed strong protease, phospholipase, and hemolysin activity, in addition to being biofilm producers. Adherence and invasion capacity were evident in the HeLa and Raw 264.7 cell lines respectively. This study expands the understanding of the underlying biological traits associated with virulence in K. ohmeri and is the first report of the detection and identification of K. ohmeri in Honduras as a cause of human infection.

Fusarium circinatum is an important global pathogen of pine trees. Genome plasticity has been observed in different isolates of the fungus, but no genome comparisons are available. To address this gap, we sequenced and assembled to chromosome level five isolates of F. circinatum. These genomes were analysed together with previously published genomes of F. circinatum isolates FSP34 and KS17. Multi-sample variant calling identified a total of 461683 micro variants (SNPs and small indels) and a total of 1828 macro structural variants of which 1717 were copy number variants and 111 were inversions. Variant density was higher on sub-telomeric regions of chromosomes. Variant annotation revealed that genes involved in transcription, transport, metabolism and transmembrane proteins were overrepresented in gene sets affected by high impact variants. A core genome representing genomic elements conserved in all the isolates and a non-redundant pangenome representing all genomic elements is presented. Whole genome alignments showed that an average of 93% of the genomic elements are present in all isolates. The results of this study reveal that some genomic elements are not conserved within the isolates and some variants are high impact. The described genome-scale variations will help inform novel disease management strategies against the pathogen.

Black Knot (BK) is a deadly disease of European (Prunus domestics) and Japanese (Prunus salicina) plums caused by the hemibiotrophic fungus Apiosporina morbosa. After infection, the appearance of warty black knots indicates a phytohormonal imbalance in infected tissues. Based on this hypothesis, we quantified phytohormones such as indole-3-acetic acid, tryptophan, indoleamines (N-acetylserotonin, serotonin, and melatonin), and cytokinins (zeatin, 6-benzyladenine, and 2-isopentenyladenine) in temporally collected tissues of susceptible and resistant genotypes belonging to European and Japanese plums during of BK progression. The results suggested auxin-cytokinins interplay driven by A. morbosa appears to be vital in disease progression by hampering the plant defense system. Taken together, our results indicate the possibility of using the phytohormone profile as a biomarker for BK resistance in plums.

Recent years have seen an explosion of interest in the topic of gut health and food, revealing a complex interplay that affects many facets of human health beyond just digestion. This in-depth overview investigates crucial aspects of this connection, illuminating issues including the effects of processed meals, the advantages of fermented foods, individualized diets, and the harmonious relationship between gut bacteria and dietary components. In this article, we'll take a look at how processed foods affect your digestive system, and how their convenience might backfire by upsetting your body's delicate microbial balance. The effects of these diets have been studied, and the results suggest that there may be disruptions in microbial diversity, inflammation, and metabolic health. Instead, fermented foods are explored as potential allies in the fight for gut health. These foods' high probiotic content not only improves digestion and nutrition absorption, but may also have an effect on one's state of mind. There is growing evidence that eating fermented foods can help you maintain a healthy and robust gut microbiome. Recognizing that everyone has a different gut microbiota composition, the idea of individualized nutrition has come to the forefront. One novel strategy for improving digestive health is to provide nutritional advice based on a person's unique microbial profile. This paper looks at how microbiome testing can be combined with professional advice to create food programs that feed specific bacteria communities, improving both diversity and health. In conclusion, this review emphasizes the reciprocal interaction between dietary choices and the gut microbiota, and the significant impact that gut health has on numerous aspects of human health. The more we learn about the complexities of this interplay, the more we can take a holistic approach to nutrition, one that respects the uniqueness of each person's gut microbiome and encourages healthy eating habits. By taking a more all-encompassing view, we are reminded of the critical function of the gut microbiota in determining our health and of the significance of fostering this nuanced symbiotic connection.

Recent studies supported a clinical association between Parkinson’s Disease (PD) and periodontitis. Hence, investigating possible protein interactions between these two conditions is of interest. In this study, we conducted a protein-protein network interaction analysis with recognized genes encoding proteins for PD and periodontitis. Genes of interest were collected via GWAS database. Then, we conducted a protein interaction analysis using STRING database, with a highest confidence cut-off of 0.9. Our protein network casted a comprehensive analysis of potential protein-protein interactions between PD and periodontitis. This analysis may underpin valuable information for new candidate molecular mechanisms between PD and periodontitis and may serve new potential targets for research purposes. These results should be carefully interpreted giving the limitations of this approach.

The information about the BCoV receptors, co/receptors that might be involved in the BCoV entry to the host cells is inconceivable. In addition to that, the roles of other host cell proteases, such as Furin and TMPRSS2, have not yet been well studied during BCoV replication. The current study’s main objectives are to identify some novel BCoV receptors and host cell proteases that might fine-tune the BCoV replication, tissue tropism, and molecular pathogenesis. We used a combination of some in silico prediction, molecular docking, and gene expression profile tools to predict some new BCoV receptors out of some known other coronavirus receptors and some host cell enzymes that are potentially involved in BCoV replication. To achieve these goals, we applied the in-silico prediction tools to check the potential interactions between eh BCoV/S glycoprotein and some known coronaviruses receptors (ACE2, APN1, NPR1, CECAM-1, AXL, and DPP4). We also established some potential models for the interaction between the BCoV/S and some common host cell proteases proved to play important roles in other coronavirus replication cycle (Furin, TMPRRS2, and Cathepsin-L). To confirm our prediction models, we assessed the gene expression profiles of these potential receptors and proteases in some bovine cell lines infected with BCoV using the next generation sequencing and the qRT-PCR assay. Our results show that the NPR1, AXL1 and the ACE2 have the strongest and firm binding affinities to the BCoV-S protein. Our prediction models and gene expression profiles show the potential bindings of the Furin and TMPRSS2 to the BCoV-S polybasic cleavage site (RRSRR|A). Notably, high expression of the host cell Furin was observed in response to both BCoV/Ent and BCoV/Resp infection, whereas TMPRSS2 expression was upregulated in the case of the BCoV/Ent infection, positioning Furin as a common receptor for different BCoV isolates. Further research is needed to study the roles of these top-ranked receptors and host cell proteases in molecular pathogenesis, and tissue tropism.

Introduction: Leptin and ghrelin are two hormones that play a role in weight homeostasis. Leptin, which is produced primarily by adipocytes and is dependent on body fat mass, suppresses appetite and increases energy expenditure. Conversely, ghrelin is the “hunger hormone”, it stimulates appetite and promotes fat storage. Bariatric surgery significantly alters the levels and activity of these hormones, contributing to weight loss and metabolic improvements. Clarifying the interplay between bariatric surgery, weight loss, physical exercise, leptin, and ghrelin is essential for developing comprehensive strategies for optimizing long-term outcomes for candidates for bariatric surgery, especially sarcopenic patients. Methods: This was a randomized controlled study with two groups (n=22). The patients in both groups have obesity and sarcopenia. A Roux-en-Y-gastric bypass (RYGB) procedure was performed in all patients. The intervention group participated in a structured exercise program three times per week beginning one month after surgery and lasting 16 weeks. Patient assessment was performed before surgery (baseline) and after completion of the exercise program. The control group received the usual standard of care and was assessed similarly. Results: After surgery, weight, BMI and lean mass decreased significantly in both groups from baseline to the second assessment. Leptin was not significantly different from baseline to the second assessment in the physical exercise group but was significantly lower in the control group (p=0.05). Ghrelin increased over time in both groups, but the differences were not significant. When we associated leptin (the dependent variable) with weight (the independent variable), we found that lower weight was associated with lower leptin levels. A similar relationship was also observed between leptin and sarcopenia parameters (muscle strength and mass), as well as with bone health parameters (bone mineral density and t-score). Higher ghrelin levels were significantly associated with higher t-scores and z-score (p

Oncomelania Hupensis is the exclusive intermediary host of Schistosoma japonicum in China. The alteration of its habitat and population distribution directly affects the safety of millions of individuals residing in the Yangtze River Economic Belt (YREB), and the ecological stability. Therefore, it is crucial to analyse the influence of climate change on the distribution of O. Hupensis in order to achieve accurate control over its population. This study utilised the MaxENT model to forecast possible snail habitats by utilising snail distribution data obtained from historical literature. The subsequent outcomes were achieved: The primary ecological factors influencing the distribution of O. Hupensis are elevation, minimum temperature of coldest month, and precipitation of wettest month; Furthermore, future climate scenarios indicate a decrease in the distribution area and a northward shift of the distribution centre for O. hupensis; Specifically, those in the upstream will move northeast, while those in the midstream and downstream will move northwest; These changes in suitable habitat area, the average migration distance of distribution centers across different climate scenarios, time periods, and sub-basins within the YREB, resulting in uncertainty. This study offers theoretical justification for the prevention and control of O. hupensis along the YREB.

Listeria ivanovii and L. monocytogenes, are the only pathogenic species of the genus Listeria and share many virulence factors and mechanisms of pathogenicity. L. ivanovii shows host tropism towards small ruminants and rodents and much lower virulence for humans compared to L. monocytogenes. However, severe infections caused by L. ivanovii, resulting in bacteremia, abortion and stillbirth, occasionally occurred in immunocompromised persons and in pregnant women, while in immunocompetent hosts L. ivanovii can cause gastroenteritis. In this review the updated knowledge on virulence aspects and distribution of L. ivanovii in the environment and in food are summarized. Recent research on its virulence characters at genome level gave indications on how pathogenicity evolved in this bacterial species. As for L. monocytogenes, L. ivanovii infections occur after the ingestion of contaminated food, so an overview of reports regarding its distribution in the food products was carried out to obtain indications on the categories of foods exposed to contamination by L. ivanovii. It was found that a wide variety of food products can be a source of this microorganism and that, like L. monocytogenes, L. ivanovii is able to persist in the food production environment. Studies on its ability to grow in enrichment and isolation media suggested that its occurrence in nature might be underestimated. Moreover, virulence varies among strains for differences in virulence character regulation, presence/absence of genetic regions and the possible instability of a Listeria pathogenicity genomic island, LIPI-2, which is unique to L. ivanovii. We can conclude that L. ivanovii, as a possible pathogen for animals and humans, requires more focused investigations regarding its occurrence in the environment and in food and on intra-species variability of pathogenic potential.

Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

The bacterial wilt pathogen, first known as Bacillus solanacearum, has undergone numerous taxonomic changes since its first description in 1896. The history and significance of this pathogen is covered in this review with an emphasis on the advances in technology that were used to support each reclassification that finally led to the current separation of Ralstonia solanacearum into three genomic species. Frequent name changes occurred as methodology transitioned from phenotypic, biochemical, and molecular studies, to genomics and functional genomics. The diversity, wide host range and geographical distribution of R. solanacearum has resulted in its inclusion in a “species complex” as genomic analyses of elucidated phylogenetic relationships among strains. Current advances in phylogenetics and functional genomics now open new avenues for research into the epidemiology and control of the devastating bacterial wilt disease.

Little phylogeographic structure is presumed for highly mobile species in pelagic zones. Lake Tanganyika is a unique ecosystem with a speciose and largely endemic fauna famous for its remarkable evolutionary history. In bathybatine cichlid fishes, the pattern of lake-wide population differentiation differs among species. We tested the magnifying glass hypothesis for their parasitic flatworm Cichlidogyrus casuarinus. Lake-wide population structure of C. casuarinus ex Hemibates stenosoma was assessed based on a portion of the mtCOI gene combined with morphological characterisation. Additionally, intraspecific mitogenomic variation among 80 individuals within one spatially constrained parasite metapopulation sample was assessed using shotgun NGS. While no clear geographic genetic structure was detected in parasites, both geographic and host-related phenotypic variation was apparent. The incongruence with the genetic north-south gradient observed in the host may be explained by the broad host range of this flatworm as some of its other host species previously showed no lake-wide restriction of gene flow. Our results are consistent with host driven morphological variation without genetic differentiation of the parasite, and highlight the importance of integratively approaching parasites` potential as “tags” for their hosts. We present the first parasite mitogenome from Lake Tanganyika and propose a methodological framework for studying intraspecific mitogenomic variation of dactylogyrid monogeneans.

This study investigates the intricate relationships between happiness, sustainability, and cultural values across 74 countries. Utilizing a multidimensional scaling (MDS) and K-means clustering approach, we analyze six happiness indices alongside the Sustainable Development Goals Index (SDGI). Our findings indicate a positive correlation between economic development, social progress, and elevated levels of both happiness and sustainability. Nevertheless, instances like the United States highlight the necessity of alternative methodologies, highlining classification of nonlinear models. The MDS analysis identifies four distinct clusters of countries, each demonstrating similar profiles in terms of happiness, sustainability, and cultural values, as per Inglehart's framework. This clustering underscores the necessity for a comprehensive perspective that integrates economic, social, and cultural dimensions to produce robust results and mitigate disparities or contradictions in subjective measures like the World Happiness Score. Future research should explore the impact of institutional frameworks, governance models, and social capital. Additionally, longitudinal studies are needed to examine how these relationships evolve in response to global challenges. We acknowledge the limitations related to data heterogeneity, the subjectivity of cluster analysis, and the exclusion of outliers, emphasizing the need for further research to enhance the generalizability and robustness of these findings.

Bile acids (BAs) play a crucial role in the human body's defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolases (BSHs) activity but also directly combat infections. Building upon our research group's previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and microbiota. Leveraging existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile, Staphylococcus aureus, Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Bacteroides, Clostridium scindens, Streptococcus thermophilus, Saccharomyces boulardii, Clostridium butyricum, Lactic Acid Bacteria), fungi (e.g., Candida albicans), and viruses (e.g., Coronavirus SARS-CoV-2, influenza virus, norovirus). Our research underscores the critical role of the interplay between BAs and intestinal microbiota, including Bacteroides, Clostridium scindens, Streptococcus thermophilus, Saccharomyces boulardii, Clostridium butyricum, and Lactic Acid Bacteria, in maintaining intestinal homeostasis and combating infections. It is imperative to note that Primary bile acid (PBA) and Secondary bile acid (SBA) often exhibit distinct roles in the anti-infection process. In the antimicrobial action of BAs, SBA demonstrate antagonistic properties against a wide range of microbiota, with the exception of Norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating intestinal microbial infections.

Biliary tract cancer, encompassing intrahepatic and extrahepatic cholangiocarcinoma, as well as gallbladder carcinoma, stands as a prevalent malignancy characterized by escalating incidence rates and unfavorable prognoses. The onset of cholangiocarcinoma involves a multitude of risk factors and could potentially be influenced by microbial exposure. The human microbiome, encompassing the entirety of human microbial genetic information, assumes a pivotal role in regulating key aspects such as host digestion, absorption, immune responses, and metabolism. The widespread application of next-generation sequencing technology has notably propelled investigations into the intricate relationship between the microbiome and diseases. An accumulating body of evidence strongly suggests a profound interconnection between biliary tract cancer and the human microbiome. This article critically appraises the existing evidence pertaining to the microbiome milieu within patients afflicted by biliary tract cancer. Furthermore, it delves into potential mechanisms through which dysregulation of the human microbiome could contribute to the advancement of biliary tract cancer. Additionally, the article expounds on its role in the context of chemotherapy and immunotherapy for biliary tract cancer.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

The global prevalence of cancer is on the rise, and while targeted therapies, early diagnosis, im-munotherapies, and conventional personalized chemotherapy have significantly upgraded out-comes for cancer patients, there is still a significant likelihood that cancer cannot be fully eradi-cated. Cancer stem-like cells (CSCs) and Epithelial-mesenchymal transition (EMT) exhibit pivotal roles in cancer cell metastasis, tumor recurrence, chemotherapy resistance, and cancer cell death, among other processes. This review aims to elucidate the molecular mechanisms underlying EMT and CSCs, their interplay, associated signaling pathways, and regulation of the EMT process and the initiation of CSCs. EMT induction confers mesenchymal properties and the potential of cancer cells to adopt the CSC state. These processes are intricately associated with the regulation of Notch and Wnt signaling pathways, transforming growth factor-β (TGF-β), as well as the expres-sion of miRNAs. Further exploring the relationship between EMT and CSCs is essential for the development of new chemotherapeutic strategies and the identification of novel therapeutic tar-gets, and hence, the development of therapeutic strategies targeting EMT, or CSCs holds promise for improving cancer therapy.

This study explores the dynamic interplay between supply chain integration and marketing strategies in achieving customer satisfaction. Through a qualitative approach involving semi-structured interviews with supply chain and marketing professionals, the research delves into how these traditionally distinct functions can be aligned to enhance operational efficiency and deliver superior customer experiences. Findings reveal that strategic alignment between supply chain management (SCM) and marketing fosters better coordination of product availability and service delivery, thereby meeting customer expectations consistently and enhancing brand loyalty. Information sharing and technological integration emerge as critical enablers, facilitating real-time data exchange and collaborative decision-making. The study also identifies challenges such as organizational silos, cultural resistance, and technological constraints that impede seamless integration, highlighting the need for proactive strategies to foster cross-functional collaboration. Additionally, the evolving roles of sustainability and customer-centricity are emphasized as key drivers for differentiating brands and achieving competitive advantage. By integrating sustainable practices and adopting a customer-centric approach, organizations can build stronger customer relationships and enhance their market position. The research underscores the importance of leadership support, investment in technology, and a collaborative organizational culture in overcoming integration barriers. The study’s findings provide actionable insights for organizations aiming to optimize their SCM and marketing strategies, drive innovation, and sustain growth in an increasingly complex and competitive business environment. This research contributes to the growing body of knowledge on supply chain and marketing integration, offering practical recommendations for achieving customer satisfaction and long-term success.

Acoustic focusing of particle flow in microfluidics has been shown to be an efficient tool for particle separation for various chemical and biomedical applications. The mechanism behind the method is the selective effect of the acoustic radiation force on distinct particles. In this way, they can be selectively focused and separated. The technique can also be applied under stationary conditions, i.e., in the absence of fluid flows. In this study, the manipulation of self-propelled particles, such as Janus particles, in an acoustofluidic setup is investigated. In experiments with self-propelled Janus particles and passive beads, we explore the interplay between self-propulsion and the acoustic radiation force. Our results demonstrate unusual and potentially useful effects such as selective trapping, escape and assisted escape in binary mixtures of active and passive particles. We also analyze various aspects related to the behavior of Janus particles in acoustic traps in the presence and absence of flows.