Susceptibility To Infection Research Articles

Obesity impairs ciliary function and mucociliary clearance in the murine airway epithelium.

Obesity is a risk factor for increased morbidity and mortality in viral respiratory infection. Mucociliary clearance (MCC) in the airway is the primary host defense against viral infections. However, the impact of obesity on MCC is unclear, prompting this study. Using murine tracheal tissue culture and in vitro influenza A virus (IAV) infection models, we analyzed cilia-driven flow and ciliary beat frequency (CBF) in the airway epithelium to evaluate MCC. Short-term IAV infection increased cilia-driven flow and CBF in control mice, but not in high-fat diet-induced obese mice. Basal cilia-driven flow and CBF were also lower in obese mice than in control mice. Mechanistically, the increase of extracellular adenosine triphosphate (ATP) release during IAV infection, which was observed in the control mice, was abolished in the obese mice; however, the addition of ATP increased cilia-driven flow and CBF both in control and obese mice to a similar extent. In addition, RNA sequencing and reverse transcription-polymerase chain reaction revealed the downregulation of several cilia-related genes, including Dnah1, Dnal1, Armc4, and Ttc12 (the dynein-related genes); Ulk4 (the polychaete differentiation gene); Cep164 (the ciliogenesis and intraflagellar transport gene); Rsph4a, Cfap206, and Ppil6 (the radial spoke structure and assembly gene); and Drc3(the nexin-dynein regulatory complex genes) in obese murine tracheal tissues compared with their control levels. In conclusion, our studies demonstrate that obesity attenuates MCC under basal conditions and during IAV infection by downregulating the expression of cilia-related genes and suppressing the release of extracellular ATP, thereby increasing the susceptibility and severity of IAV infection.NEW & NOTEWORTHY Our study shows that obesity impairs airway mucociliary clearance (MCC), an essential physical innate defense mechanism for viral infection. Mechanically, this is likely due to the obesity-induced downregulation of cilia-related genes and attenuation of extracellular ATP release. This study provides novel insights into the mechanisms driving the higher susceptibility and severity of viral respiratory infections in individuals with obesity.

Teratogenic effects of voriconazole (anti-fungal drug) on Swiss albino mice

Antifungals are a class of drugs that target the treatment of invasive fungal infections. This includes polyenes, triazoles, and echinocadins. Among these, azoles are being extensively used nowadays. Triazoles have become standard for the azoles and have replaced amphotericin B as the first line of defence for fungal infections. With the increased cases of fungal infection, which affect a majority of the population at different stages and situations, one such section of the population is pregnant females. The rate and susceptibility of fungal infections are particularly higher in pregnant females, as the immunity of the mother is highly compromised. Systemic fungal infections like invasive aspergillosis, esophageal candidiasis, and candidemia are being treated with new age triazole antifungals like voriconazole. Prolonged and high concentrations of this drug are associated with various developmental anomalies. With this aim, teratogenic studies were performed on pregnant female mice during gestation and the weaning/lactation period to observe the effects of voriconazole at different dosages (8 mg/kg b.w., 10 mg/kg b.w., and 20 mg/kg b.w.). Pregnant dams were subjected to 20 mg/kg b.w. Voriconazole had a small litter size and a high number of resorptions. Craniofacial defects in the form of reduced ossification and widely open sutures, the presence of the 14th rib, asymmetry in the sternebrae, and the absence of ossified distal phalanges were some of the skeletal anomalies which were significant in the foetus and pups subjected to both 10 mg/kg b.w. and 20 mg/kg b.w. doses of voriconazole.

Cerium dioxide nanozyme doped hybrid hydrogel with antioxidant and antibacterial abilities for promoting diabetic wound healing

Diabetic wounds are among the most severe chronic complications in patients with diabetes. Owing to the detrimental effects of high glucose and high levels of reactive oxygen species (ROS) in the wound microenvironment, diabetic wound healing is significantly challenging. To address the issues of elevated ROS levels and infection susceptibility in diabetic wounds, we designed a composite hydrogel system loaded with cerium dioxide nanoparticles (CeO2 NPs) and vancomycin. This hydrogel aimed to reshape the wound microenvironment by continuously consuming ROS and inhibiting infection. Experimental results demonstrated that the CeO2 NPs-loaded hydrogel demonstrated an 85.40% clearance rate of hydroxyl radicals (·OH) and achieved over 90% inhibition against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and effectively promoted the healing of diabetic mouse wounds. This cerium dioxide nanozyme hybrid hydrogel system can exert antioxidative and antibacterial effects and serve as a wound dressing to promote the healing of infected diabetic wounds.

Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention.

Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients. We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n=10, mean age: 10.7±6.6 years) and after a 6-month oral hygiene intervention (n=9,mean age: 11.6±5.27 years), and from 12 healthy controls. We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins. SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.

Untangling the memory and inhibitory effects on SIS-epidemic model with Beddington–DeAngelis infection rate

The dynamical behaviors of an epidemic model based on the susceptible–infected–susceptible (SIS) model are investigated. The Beddington–DeAngelis functional response is used for the infection rate to present the dependence of the transmission of the infection on the ratio of both susceptible and infected populations. A Caputo fractional derivative is applied to show the existence of memory in nature affects population dynamics. The disease-free and endemic equilibrium points are obtained as the equilibrium points that describe the condition when the population is free from the disease or the disease exists in the population throughout time. The existence, uniqueness, non-negativity, and boundedness are proven which state the biological validity of the mathematical model. The local and global stability of each equilibrium point is studied including the basic reproduction number and its influence on the dynamical behaviors. Some numerical simulations are portrayed to explore more about the dynamics of the model which are relevant to the analytical findings. The partial rank correlation coefficient is presented to investigate the dominant parameter with respect to the basic reproduction number and the density of susceptible and infected populations. The parameter continuations are demonstrated to show the impact of infection rate and the inhibitory effect which lead to the occurrence of forward bifurcations. The memory effect is also demonstrated numerically to show the changes in convergence rate due to the changes in memory strength.

Epidemiology, clinical profiles, and antimicrobial susceptibility of Elizabethkingia meningoseptica infections: Insights from a tertiary care hospital in Saudi Arabia.

To investigate the incidence rate, clinical characteristics across different age groups, antimicrobial susceptibility, and outcomes of Elizabethkingia meningoseptica (E. meningoseptica) infections. A retrospective analysis was carried out to include 66 cases with confirmed E. meningoseptica cultures from sterile samples between January 2014 and June 2022 at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. A total of 66 cases were identified, with an incidence rate of 0.3 per 1000 admissions. Most cases were hospital-acquired (80.3%), primarily in critical care areas. All patients had underlying diseases, with respiratory (40.9%) and cardiovascular (39.4%) diseases being the most common. Minocycline showed the highest susceptibility (96.0%), followed by trimethoprim/sulfamethoxazole (77.0%), whereas tobramycin and colistin were fully resistant. The in-hospital mortality rate was 34.8%, whereas the 28-day mortality rate was 22.7%. Clinical characteristics across age groups showed a higher prevalence of cardiovascular disease in pediatrics than in adults, whereas exposure to mechanical ventilation, immunosuppressive therapy, previous infection, anemia, and in-hospital mortality were reported more frequently in adults (p<0.05). Our study provides valuable insights into E. meningoseptica infection in Saudi Arabia, emphasizing the importance of robust infection control measures. Incidence and mortality rates align with global trends. Variations in clinical characteristics across age groups highlight the importance of tailored treatments based on patient demographics and underlying comorbidities.

The Closed-Form Solutions of an SIS Epidemic Reaction–Diffusion Model with Advection in a One-Dimensional Space Domain

This work investigates a class of susceptible–infected–susceptible (SIS) epidemic model with reaction–diffusion–advection (RDA) by utilizing the Lie group methods. The Lie symmetries are computed for the three widely used incidence functions: standard incidence, mass action incidence, and saturated incidence. The Lie algebra for the SIS-RDA epidemic model is four-dimensional for the standard incidence function, three-dimensional for mass action incidence, and two-dimensional for saturated incidence. The reductions and closed-form solutions for the SIS-RDA epidemic model for the standard incidence infection mechanism are established. The transmission dynamics of an infectious disease utilizing closed-form solutions is presented. To illustrate the paths of susceptible and infected populations, we consider the Cauchy problem. Moreover, a sensitivity analysis is conducted to provide insights into potential policy recommendations for disease control.

Accuracy of discrete- and continuous-time mean-field theories for epidemic processes on complex networks.

Discrete- and continuous-time approaches are frequently used to model the role of heterogeneity on dynamical interacting agents on the top of complex networks. While, on the one hand, one does not expect drastic differences between these approaches, and the choice is usually based on one's expertise or methodological convenience, on the other hand, a detailed analysis of the differences is necessary to guide the proper choice of one or another approach. We tackle this problem by investigating both discrete- and continuous-time mean-field theories for the susceptible-infected-susceptible (SIS) epidemic model on random networks with power-law degree distributions. We compare the discrete epidemic link equations(ELE) and continuous pair quenched mean-field (PQMF) theories with the corresponding stochastic simulations, both theories that reckon pairwise interactions explicitly. We show that ELE converges to the PQMF theory when the time step goes to zero. We performed an epidemic localization analysis considering the inverse participation ratio (IPR). Both theories present the same localization dependence on network degree exponent γ: for γ<5/2 the epidemics are localized on the maximum k-core of networks with a vanishing IPR in the infinite-size limit while, for γ>5/2, the localization happens on hubs that do not form a densely connected set and leads to a finite value of the IPR. However, the IPR and epidemic threshold of ELE depend on the time-step discretization such that a larger time step leads to more localized epidemics. A remarkable difference between discrete- and continuous-time approaches is revealed in the epidemic prevalence near the epidemic threshold, in which the discrete-time stochastic simulations indicate a mean-field critical exponent θ=1 instead of the value θ=1/(3-γ) obtained rigorously and verified numerically for the continuous-time SIS on the same networks.

METABOLIC AND BIOENERGETIC ALTERATIONS ARE ASSOCIATED WITH INFECTION SUSCEPTIBILITY IN SURVIVORS OF SEVERE TRAUMA: AN EXPLORATORY STUDY.

Background : Trauma and blood loss are frequently associated with organ failure, immune dysfunction, and a high risk of secondary bacterial lung infections. We aim to test if plasma metabolomic flux and monocyte bioenergetics are altered in association with trauma and related secondary infections. Methods : Plasma samples were collected from trauma patients at three time points: days 0, 3, and 7 postadmission. Metabolites (140) were measured in plasma from trauma survivors ( n = 24) and healthy control individuals (HC, n = 10). Further analysis within the trauma cohort included subsets of trauma/infection-negative (TIneg, n = 12) and trauma/infection-positive patients (TIpos, n = 12). The bioenergetic profile in monocytes was determined using mitochondrial and glycolytic stress tests. Results : In the trauma cohort, significant alterations were observed in 29 metabolites directly affecting 11 major metabolic pathways, while 34 metabolite alterations affected 8 pathways in 9, versus TIneg patients. The most altered metabolic pathways included protein synthesis, the urea cycle/arginine metabolism, phenylalanine, tyrosine, tryptophan biosynthesis, and carnitine compound family. In monocytes from trauma patients, reduced mitochondrial indices and loss of glycolytic plasticity were consistent with an altered profile of plasma metabolites in the tricarboxylic acid cycle and glycolysis. Conclusions : Our study highlights that the metabolic profile is significantly and persistently affected by trauma and related infections. Among trauma survivors, metabolic alterations in plasma were associated with reduced monocyte bioenergetics. These exploratory findings establish a groundwork for future clinical studies aimed at enhancing our understanding of the interplay between metabolic/bioenergetic alterations associated with trauma and secondary bacterial infections.

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy

Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.

Quantifying the Health–Economy Trade-Offs: Mathematical Model of COVID-19 Pandemic Dynamics

The COVID-19 pandemic has presented a complex situation that requires a balance between control measures like lockdowns and easing restrictions. Control measures can limit the spread of the virus but can also cause economic and social issues. Easing restrictions can support economic recovery but may increase the risk of virus transmission. Mathematical approaches can help address these trade-offs by modeling the interactions between factors such as virus transmission rates, public health interventions, and economic and social impacts. A study using a susceptible-infected-susceptible (SIS) model with modified discrete time was conducted to determine the cost of handling COVID-19. The results showed that, without government intervention, the number of patients rejected by health facilities and the cost of handling a pandemic increased significantly. Lockdown intervention provided the least number of rejected patients compared to social distancing, but the costs of handling the pandemic in the lockdown scenario remained higher than those of social distancing. This research demonstrates that mathematical approaches can help identify critical junctures in a pandemic, such as limited health system capacity or high transmission rates, that require rapid response and appropriate action. By using mathematical analysis, decision-makers can develop more effective and responsive strategies, considering the various factors involved in the virus’s spread and its impact on society and the economy.

COVID-19 and the need for special care for women with polycystic ovary syndrome: A systematic review

Objective The study investigates the association between coronavirus disease 2019 (COVID-19) and polycystic ovary syndrome (PCOS) and assess whether women with PCOS are at a higher susceptibility and risk for COVID-19 complications. Methods This review analyzes articles indexed in PubMed, Scopus, Google Scholar, and the Cochrane Library, focusing on the onset of the COVID-19 pandemic in December 1, 2019, until November 1, 2022. The quality of the evidence was assessed using the NIH quality assessment tool. The study was registered on PROSPERO (CRD42023371956) on January 12, 2023. Results A total of 11 observational studies were identified, totaling 22,155 PCOS patients. Despite the heterogeneity of the included studies, the findings of most of the studies were similar in terms of increased susceptibility and severity of COVID-19 infection in PCOS patients. PCOS patients were reported to have a 51% higher risk of COVID-19 infection than non-PCOS women (HR =1.51). Many causes have been identified to play a role, most notably the overactivation of the renin-angiotensin system (RAS) and elevated levels of RAS-associated proteins, decreased serum levels of neuropilin-1 (sNRP1), elevated serum biomarkers such as platelet degranulation and coagulation cascade markers increased acute phase response, and lower levels of vitamin D could render PCOS patients susceptible to a chronic inflammatory state, which can also lead to difficulties and severe consequences, when impacted by COVID-19. Furthermore, the COVID-19 pandemic also influenced psychological well-being, with an increase in the incidence and severity of depression and anxiety among PCOS patients in the COVID-19 pandemic era compared to healthy individuals. Conclusions Patients with PCOS are more likely to get infected with COVID-19 and display a higher affinity to severe infections and complications due to overlapping and confounding factors. These findings suggest that PCOS patients may need more medical attention when infected with COVID-19.

Veno-Arterial Extracorporeal Membrane Oxygenation in Pregnancy: A Literature Review

Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a very important circulatory support system, and its use is increasing over the years especially in pregnancy and its related consequences on the mother and the fetus. This article is directed to review all the important aspects regarding VA-ECMO in pregnancy, addressing that it is less commonly used during pregnancy not disregarding maternal, neonatal, and long-term outcomes such as, the survival rate is relatively good compared to the general population adjusted to different causes mentioned in this article. A description of what VA-ECMO is, protocols, usual targeted goals, preferred sites of access especially peripheral cannulation, indications including multiple causes of cardiac failure, some contraindications majorly end-stage cardiac failure when recovery or transplant is not possible, the use of anticoagulation and its side effects, specific complications including bleeding from multiple sites, and the incidence of thromboembolic complications. Moreover, a good clarification and thorough discussion is intended for some of the special considerations and technical challenges in pregnancy due to uterine compression, maternal susceptibility for thrombosis and infections, the status of the fetus and the mode of delivery.

Mass Spectrometry Identifies Taenia solium Proteins in Sera of Patients With and Without Parenchymal Neurocysticercosis.

Neurocysticercosis (NCC), a major cause of global acquired epilepsy, results from Taenia solium larval brain infection. T. solium adult worms release large numbers of infective eggs into the environment contributing to high levels of exposure in endemic areas. This study identifies T. solium proteins in the sera of individuals with and without NCC using mass spectrometry to examine exposure in endemic regions. Forty-seven patients (18-51 years), 24 parenchymal NCC (pNCC), 8 epilepsy of unknown aetiology, 7 glioma, 8 brain tuberculoma, and 7 healthy volunteers were studied. Trypsin digested sera were subject to liquid chromatography-tandem mass spectrometry and spectra of 375-1700 m/z matched against T. solium WormBase ParaSite database with MaxQuant software to identify T. solium proteins. Three hundred and nineteen T. solium proteins were identified in 87.5% of pNCC and 56.6% of non-NCC subjects. Three hundred and four proteins were exclusive to pNCC sera, seven to non-NCC sera and eight in both. Ten percent, exhibiting immune-modulatory properties, originated from the oncosphere and cyst vesicular fluid. In conclusion, in endemic regions, T. solium proteins are detected in sera of individuals with and without pNCC. The immunomodulatory nature of these proteins may influence susceptibility and course of infection.

Bleeding Following Pediatric Liver Transplantation: A Brief Overview

End-stage liver disease (ESLD) occasionally needs liver transplantation (LT) as a life-saving treatment. In pediatric population, LT procedure is more complicated than adults, since they are mainly caused by extrahepatic cholestasis, has a variety of age groups, and has various infection susceptibilities. Furthermore, there is a complication related to LT, such as bleeding, which cannot be disregarded because it may aggravate patients’ conditions and necessitate reoperation. Moreover, in the case of hepatic artery thrombosis and portal vein thrombosis, which is caused by severe bleeding, patients and grafts’ survival may be significantly reduced. In this review, we are discussing bleeding following LT phenomena from the basic introduction, pathophysiology, prevention, monitoring, and treatment

The bacterial profile and antibiotic susceptibility in skin and soft tissue infections at a tertiary care hospital of Quetta, Pakistan.

To determine the bacterial profile and antibiotic susceptibility in skin and soft tissue infections among patients in a tertiary care setting. The cross-sectional cohort study was conducted at the Centre for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta, Pakistan, from June 2021 to May 2022, and comprised bacteriainfected skin samples that were collected from the Bolan Medical Complex Hospital, Quetta, and the Sandeman Provincial Hospital, Quetta. The swab samples were immediately cultured, and positive samples were evaluated for biochemical tests, antibiotic susceptibility test and polymerase chain reaction. Data was analysed using SPSS 22. Of the 800 samples, 598(74.7%) tested positive for pathogenic bacteria. Staphylococcus aureus accounted for 316(39.5%) infections, followed by clostridium perfringens 18.96(2.37%), escherichia coli 120(15.12%), pseudomonas aeruginosa 98(12.25%) and klebsiella pneumoniae 44(5.5%). Among all the infected samples, 380(47.5%) belonged to males, 218(27.25%) to patients aged 5-20 years, 448(56%) to the uneducated subjects, and 462(57.87%) to patients having lower socioeconomic status. Pseudomonas aeruginosa showed the highest level of resistance against all antibiotics. Regular surveillance and proper use of antibiotics should be encouraged in hospitals to limit the spread of antibiotic resistance against pathogenic bacteria.

Basic Susceptibility of Patients with Psoriasis under Systemic Therapy for Respiratory Infections: Data from the German Psoriasis Registry PsoBest.

Background: Patients with psoriasis under systemic treatments are in focus regarding their susceptibility to respiratory infections. To analyse real-world data for respiratory infections in patients with psoriasis under systemic treatments. Methods: We analysed data of the prospective, non-interventional German Psoriasis Registry PsoBest and compared rates for respiratory infections of 13,823 patients on systemic treatments for psoriasis and/or psoriatic arthritis in different therapy cohorts before the COVID-19 pandemic. Results: In total, 1415 respiratory infections were observed in 970 patients. Significant differences were observed between biologics and non-biologics, but not within these groups. The highest event rates (events/100 patient years) were identified for TNF-α inhibitors, 8.1, (CI 7.4-8.9), followed by 7.0 for IL-17 inhibitors (6.2-7.9), 5.7 for IL-12/23 and IL-23 inhibitors (5.1-6.5), 4.8 for methotrexate (4.3-5.4), 3.7 for small molecules (3.3-4.2), and 2.7 for retinoids (1.2-5.1). Conclusions: Overall, the susceptibility for respiratory infections in patients under systemic therapy for psoriasis is low compared to published study data and is sufficient as comparative data for COVID-19 studies.

Differences in Salmonella Typhimurium infection and excretion among laboratory and field strains of the German cockroach suggest a genomic basis for vector competence

The German cockroach, Blattella germanica, can be a vector of human enteric bacterial pathogens, including Salmonella enterica serovar Typhimurium (S. Typhimurium). Transmission of such pathogens by cockroaches has largely been considered a passive mechanical process, but recent studies have argued against this dogma by demonstrating bacterial proliferation within the cockroach gut and the necessity of specific bacterial genes for successful transmission in the feces, revealing unappreciated biological complexity in the vector-pathogen relationship between cockroaches and S. Typhimurium. However, the influence of naturally occurring variation among cockroach populations on pathogen infection and dissemination has not been investigated. Thus, this study aimed to examine whether distinct strains of B. germanica exhibit differences in their ability to become infected by and disseminate S. Typhimurium. We performed controlled infections of one long-term laboratory strain and three recently field-collected strains reared under identical conditions, then compared bacterial loads in the body and excreta of individual insects. Separately, we also compared rates of necrophagy, a behavior known to contribute to the horizontal spread of S. Typhimurium among cockroaches. Our data show significant differences in infection susceptibility, pathogen shedding in the excreta, and necrophagy between laboratory and field strains as well as between some field strains. These observations represent the first evidence that genomic variation among cockroach populations may influence their ability to become infected by and disseminate pathogens, providing further support for the hypothesis that German cockroaches are active biological vectors rather than passive mechanical vectors of S. Typhimurium. Additional studies are needed to identify the genomic drivers of vector competence for S. Typhimurium in B. germanica.

Exploitation of multiple host-derived nutrients by the yellow catfish epidermal environment facilitates Vibrio mimicus to sustain infection potency and susceptibility

Infection with Vibrio mimicus in the Siluriformes has demonstrated a rapid and high infectivity and mortality rate, distinct from other hosts. Our earlier investigations identified necrosis, an inflammatory storm, and tissue remodeling as crucial pathological responses in yellow catfish (Pelteobagrus fulvidraco) infected with V. mimicus. The objective of this study was to further elucidate the impact linking these pathological responses within the host during V. mimicus infection. Employing metabolomics and transcriptomics, we uncovered infection-induced dense vacuolization of perimysium; Several genes related to nucleosidase and peptidase activities were significantly upregulated in the skin and muscles of infected fish. Concurrently, the translation processes of host cells were impaired. Further investigation revealed that V. mimicus completes its infection process by enhancing its metabolism, including the utilization of oligopeptides and nucleotides. The high susceptibility of yellow catfish to V. mimicus infection was associated with the composition of its body surface, which provided a microenvironment rich in various nucleotides such as dIMP, dAMP, deoxyguanosine, and ADP, in addition to several amino acids and peptides. Some of these metabolites significantly boost V. mimicus growth and motility, thus influencing its biological functions. Furthermore, we uncovered an elevated expression of gangliosides on the surface of yellow catfish, aiding V. mimicus adhesion and increasing its infection risk. Notably, we observed that the skin and muscles of yellow catfish were deficient in over 25 polyunsaturated fatty acids, such as Eicosapentaenoic acid, 12-oxo-ETE, and 13-Oxo-ODE. These substances play a role in anti-inflammatory mechanisms, possibly contributing to the immune dysregulation observed in yellow catfish. In summary, our study reveals a host immune deviation phenomenon that promotes bacterial colonization by increasing nutrient supply. It underscores the crucial factors rendering yellow catfish highly susceptible to V. mimicus, indicating that host nutritional sources not only enable the establishment and maintenance of infection within the host but also aid bacterial survival under immune pressure, ultimately completing its lifecycle.

SLC10A1 rs2296651 variant (S267F mutation) predicts biochemical traits, hepatitis B virus infection susceptibility and the risk of gallstone disease.

Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1's versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.