Search Results (607)

Coronaviruses are worldwide-distributed RNA viruses with zoonotic potential and the ability to jump from one host species to another, including humans. Even after the COVID-19 pandemic, the search for new, biologically active substances with anti-coronavirus activity continues to be a critical milestone for human health protection. In the framework of a complex engineering strategy, we cultivated the microalgal species Scenedesmus acutus in two different innovative types of flat-plate photobioreactors (PBR1 and K1) for CO₂ utilization and biomass production with special features. Isolated extracts from the microalgal biomass of each one were compared for their anti-coronavirus potential. The design of both PBRs allows a hydrodynamic regime to achieve best fluid flow distribution in their sections, therefore providing the optimal so-called flashing light effect. Of course, this is achieved under well-controlled operational conditions. A strain of beta coronavirus 1 (BCoV, bovine coronavirus) replicated in MDBK cells was used as an in vitro model for the evaluation of the antiviral activity of both extracts. The cell viability, number of survived BCoV particles, and cytopathic effect were evaluated after pre-incubation of the virus with the extracts or direct treatment. The extracts’ samples exhibited evident antiviral activity—extract 1 (from PBR1) in concentrations ≥ 200 µg/mL and extract 2 (from K1) in concentrations ≥150 µg/mL. The ddPCR result revealed significant diminishment of the BCoV particles in samples treated with higher concentrations of the extracts. The phytochemical analysis for certain main groups of compounds (flavonoids, polyphenols, carotenoids, and lipids) showed some differences for both extracts, which could be a possible reason for the observed difference in the antiviral activity. In conclusion, the innovative PBRs are a good platform for studying microalgal growth kinetics by applying different stress conditions from hydrodynamics and mass transfer subsystems. Both extracts showed promising potential for the isolation of metabolites with antiviral activity against BCoV and could be an object for future pharmacological investigations. Full article

Background/Objectives: The high prevalence of fluoroquinolone-resistant E. coli in healthy children represents a significant public-health risk, facilitating the spread of antimicrobial resistance and increasing the potential for difficult-to-treat extraintestinal infections with severe clinical outcomes. This study aimed to investigate the prevalence of fluoroquinolone resistance in multidrug-resistant E. coli isolated from presumptively healthy children in St. Petersburg, Russia, with a particular focus on fluoroquinolone resistance determinants. Methods: Phenotypic AST was performed on 307 E. coli isolates from fecal pediatric samples, comprising 230 isolates from 2012 to 2013 and 77 isolates from 2021 to 2022. A subset (n = 47) of MDR isolates underwent whole-genome sequencing. Results: The frequency of MDR E. coli strains rose significantly from 15.7% to 32.5% over the study period. The most significant increases in resistance among E. coli strains were to third-generation cephalosporins (CTX, CTZ) and fluoroquinolones (CIP), rising fourfold over a decade. Based on phenotypic resistance profiles of MDR E. coli to quinolones, the highest resistance rates were observed for MFX (80.9%) followed by NAL (74.5%), LVX (44.7%) and CIP (40.4%). Genotypic analysis revealed distinct pathways: low-level NAL resistance required only an S83 mutation in gyrA, whereas low-level MFX resistance was predominantly conferred by a plasmid-borne qnr gene. In contrast, resistance to CIP and LVX involved at least three QRDR mutations: S83L and D87N/Y in gyrA, and S80I in parC. Notably, our study showed the predominance of the ST131 and ST38 clones in E. coli isolated from pediatric samples. Conclusions: Our findings suggest that the efficacy of moxifloxacin for empirical treatment of infections caused by MDR E. coli might be severely compromised. Overall, the current study highlights that the pediatric gut microbiota serves as a reservoir for resistant E. coli with the expansion of multidrug-resistant clones independently of direct antibiotic selection pressure. Full article

Cyanobacteria of the genus Tychonema are common inhabitants of freshwater bodies in a temperate zones. In Lake Baikal, Tychonema sp. was first reported in 2014. It grows excessively on the bottom on almost all substrates types, forming epiphytic and epizoic biofilms, and its role in the mass mortality events affecting of endemic Baikal sponges is discussed. The cyanobacterial strain BBK16 (=IPPAS B-2063^T), isolated from a biofilm on a log pier in the Bolshiye Koty settlement in 2016, was used for further taxonomic characterization. Key morphological features of strain BBK16 include its growth as a creeping mat, highly motile trichomes that are sometimes narrowed and hooked at the ends, and the presence of rounded-conical apical cells with a calyptra. Strain ultrastructure (fascicular parietal thylakoids and type D cell division) differs from Tychonema species with radial thylakoids but aligns with other genera in the Microcoleaceae family. A comprehensive analysis, including 16S rRNA gene phylogeny, conserved protein phylogeny, and whole-genome comparisons, confirmed its placement within the genus Tychonema. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between strain BBK16 and T. bourrellyi FEM GT703 were 90.7%, 91.1% and 43.3%, respectively, indicating values below the standard thresholds for species delineation. Based on combined morphological, genomic, and ecological evidence, we propose the name Tychonema litorale sp. nov. for strain BBK16, a novel species described in accordance with the International Code of Nomenclature for Algae, Fungi, and Plants. Full article

Background/Objectives: Pregnancy is characterized by complex immunological adaptations that may increase susceptibility to infections, including SARS-CoV-2. Interleukin-6 (IL-6), a key pro-inflammatory cytokine, plays a crucial role in the immune response and has been strongly implicated in the pathogenesis of COVID-19. Genetic variations in the IL6 gene, particularly single-nucleotide polymorphisms (SNPs) in the promoter region, can modulate IL-6 expression and potentially influence individual susceptibility to viral infections. This study aimed to evaluate the relationship between promoter region IL6 gene polymorphisms and COVID-19 susceptibility, as well as the inflammatory response, in pregnant women. Methods: We enrolled in this study 204 pregnant women with evidence of SARS-CoV-2 infection in pregnancy and 134 pregnant women with no evidence of SARS-CoV-2 infection in the past. Genotyping was conducted for the two functional SNPs in the IL6 promoter region, rs1800796 and rs1800797, via Sanger sequencing, and for associations with COVID-19 susceptibility and IL-6 levels were analyzed. Results: No significant association was found between IL6 polymorphisms and COVID-19, IL-6 levels, age, or immunization status. IL-6 levels > 5 pg/mL were more frequent in SARS-CoV-2-negative pregnant women than in SARS-CoV-2-positive pregnant women (p = 0.032). Among vaccinated participants, IL-6 levels were significantly higher in SARS-CoV-2-negative pregnant women (p = 0.044), while no difference was observed in the unvaccinated group. Conclusions:IL6 polymorphisms rs1800797 and rs1800796 were not associated with infection susceptibility or IL-6 levels. These results highlight the complex immunological interplay between pregnancy, infection, and genetic background and support the need for further research in larger cohorts. Full article

Visceral leishmaniasis (VL) is a serious vector-borne disease affecting humans and dogs, posing major public health challenges in endemic regions. Control efforts often target sandfly vectors, whose larvae and pupae develop in soil. Environmental management, such as removing organic matter, reducing moisture, and pruning vegetation, aims to limit breeding sites and reduce sandfly populations. This study evaluated the impact of integrated interventions on sandfly behavior in priority areas for VL control in Araçatuba, São Paulo, Brazil. The control strategy combined environmental management, canine surveys, and educational actions across seven local work areas (LWAs). Between 2019 and 2021, CDC-type light traps were installed in intra- and peridomiciliary settings at twelve properties in LWA 5. Spatial risk analysis for canine transmission was conducted in LWAs 3 and 5 using a Generalized Additive Model, with results presented as spatial odds ratios. Vector prevalence was analyzed using negative binomial regression compared to historical municipal data. Intervention coverage averaged 52.91% of visited properties (n = 15,905), ranging from 48% to 76.8% across LWAs. Adherence to environmental management exceeded 85%. Of the 150 sandflies collected, 98.67% were Lutzomyia longipalpis and 1.33% Nyssomyia neivai. A 6% reduction in vector density was observed compared with historical data, although this difference was not statistically significant. Spatial risk varied among LWAs, indicating heterogeneous transmission levels. These findings suggest that integrated environmental and educational interventions may contribute to reducing vector density and that identifying priority areas tends to support surveillance and the effectiveness of disease control actions. Full article

Vietnam faces a hyperendemic burden of hepatitis B virus (HBV) infection, but the prevalence of occult HBV infection (OBI) and its underlying molecular mechanisms in healthy populations remain poorly understood. This study aimed to characterize the serological and molecular HBV profile of a healthy Vietnamese adult cohort in Southern Vietnam. We assessed the prevalence of occult HBV infection (OBI) and HBsAg-positivity (serving as a proxy for probable chronic infection). In this cross-sectional study, 397 healthy adults from Southern Vietnam underwent serological screening for HBsAg, anti-HBs, and anti-HBc. All participants were screened for HBV DNA using a high-sensitivity PCR assay (LOD ≥ 5 IU/mL). For all viremic cases, the full Pre-S/S region was sequenced to determine genotype and characterize escape mutations. We uncovered a high prevalence of both HBsAg-positivity (17.6%) and OBI (9.3% HBsAg-negative, HBV DNA-positive). Serological analysis revealed a massive, age-dependent reservoir of past exposure (63.7% anti-HBc) characterized by a high and increasing prevalence of the anti-HBc only profile (31.5%), a key serological marker for OBI. This trend contrasted sharply with a steep age-related decline in protective anti-HBs. The viral landscape was dominated by genotypes B (73.8%) and C (26.2%), with sub-genotypes B4 and C1 being the most prevalent. Critically, individuals with OBI carried a significantly higher burden of S gene escape mutations compared to those with HBsAg-positivity (p < 0.001). Canonical escape variants, including sG145R (21.6%), sK141R/T/E/Q (24.3%), and sT116N/A/I/S (18.9%), were exclusively or highly enriched in the OBI group. A LASSO-logistic model based on this mutational profile successfully predicted occult infection with high accuracy (AUC = 0.83). A substantial hidden reservoir of occult HBV infection exists within the healthy adult population of Vietnam, driven by a high burden of S gene escape mutations. These findings highlight the significant limitations of conventional HBsAg-only screening. They also underscore the need for comprehensive molecular surveillance to address the true scope of HBV viremia, hopefully enabling a reduction in hidden transmission of clinically significant viral variants. Full article

Tick-borne diseases are rising across Europe, yet human-biting tick data from the central Balkans remain limited. We analysed ticks removed from patients seeking care after tick bites at centers in Skopje (North Macedonia) and Novi Sad (Serbia) between January 2022 and December 2024, recording species, developmental stage, month of removal, and anatomical attachment site. A total of 1641 ticks were collected (North Macedonia, n = 157; Serbia, n = 1484) and identified morphologically. Six tick species were detected in North Macedonia and eight in Serbia. Ixodes ricinus was dominant in both countries, comprising ~69% of ticks in North Macedonia and >90% in Serbia, while Hyalomma marginatum was found in North Macedonia. Adult females predominated among ticks in North Macedonia (75.8%), whereas nymphs were most frequent among ticks in Serbia (55.6%); between-center comparisons of developmental stage should be interpreted cautiously given the marked sampling imbalance. In both settings, collections peaked in May–June (~64% of annual ticks), indicating highest bite pressure in late spring/early summer. Attachment sites were most commonly the torso and lower extremities, with significant between-country differences and species-/stage-specific patterns most evident in Serbia. These data refine the epidemiology of human tick exposure in two Balkan countries and support targeted seasonal prevention messaging and strengthened regional surveillance. Full article

Requirements for novel effective antiviral agents against SARS-CoV-2 emphasizes the importance of robust in vitro screening platforms. We developed a test system based on spike-pseudotyped lentiviruses, carrying either luc+ or EGFP reporter genes as a payload, and a human non-small cell lung carcinoma (NSCLC) cell line, overexpressing ACE2 (H1299-hACE2). The cell origin makes our system resemble lung epithelium infection. Transmission electron microscopy confirmed that the spike glycoproteins on the pseudotyped lentiviral particles resemble native SARS-CoV-2 spike glycoproteins, thus validating their use in inhibitor screening. H1299-hACE2 cells showed significantly higher infection rate (p < 0.005) with spike-pseudotyped lentiviruses compared to parental H1299 cells, as determined by luciferase and fluorescence assays. The susceptibility of the stable H1299-hACE2 cell line to a broad panel of SARS-CoV-2 variants (Wuhan, Beta, Delta, Omicron) was assessed here for the first time in a unified experimental setting. Infection of H1299-hACE2 cells with SARS-CoV-2 induced cell fusion and syncytium formation with subsequent cell death. The developed pseudovirus-based assay was further used for assessment of the antiviral properties of derivatives of 1,7,7-trimethyl-[2.2.1]-bicycloheptane-potential spike protein inhibitors, which possess moderate activity against lentiviral particles. The H1299-hACE2/spike-pseudotyped lentivirus assay is, therefore, a reliable, high-efficiency platform for screening spike-mediated entry inhibitors. The cell line obtained during the development of the platform can be used to isolate and study new variants of SARS-CoV-2. Full article

This work describes the lead optimization of a promising class of antibacterial compounds, derived from a previously reported N-[4-(4-fluorophenoxy)phenyl]-6-(methylsulfonyl)-2,6-diazaspiro [3.4]octane-8-carboxamide (LK1819), through systematic scaffold simplification. A novel series of amide derivatives were designed and synthesized, exploring key structural variations, including the replacement of the diphenyl ether core with a biphenyl system. All compounds were evaluated for in vitro antibacterial activity against the ESKAPE panel of pathogens. The most potent simplified analogs demonstrated exceptional, broad-spectrum activity, with minimum inhibitory concentrations (MICs) that were 10 to 100 times lower than the control antibiotic ciprofloxacin against many strains. Mechanistic studies using a reporter system and enzymatic assays revealed that the compounds do not inhibit protein synthesis but disrupt DNA replication, exhibiting a dose-dependent inhibitory effect on bacterial topoisomerase I and DNA gyrase. The compounds showed moderate toxicity against human cell lines, consistent with their DNA-targeting mechanism, but cytotoxicity assays indicated a sufficient selectivity window. We conclude that scaffold simplification successfully yielded highly potent antibacterial agents with a defined mechanism of action, presenting a promising foundation for further development as antibiotics and potentially as anticancer agents. Full article

Wastewater treatment is fundamental to sustainable urban development, and recent European legislation now requires quaternary treatment of final effluent at wastewater treatment plants. Among the technologies evaluated for this purpose, adsorption and Advanced Oxidation Processes (AOPs) have demonstrated the highest removal efficiencies, and the ongoing shift toward more circular and sustainable urban wastewater management, positioning them as two of the most strategically significant technologies in the field. Quaternary treatments with ozonation and activated carbon adsorption (PAC/GAC) achieve median micropollutant removal above 80%. GAC is generally associated with the highest costs, followed by PAC and ozonation, typically in the range of approximately 0.035 to 0.3 € per cubic meter in European settings. This review presents a systematic comparison of adsorption and AOPs for the removal of urban wastewater pollutants, with emphasis on removal efficiency, energy requirements, carbon footprint, and operational limitations. It delineates the conditions under which each technology demonstrates superior performance and highlights its complementary strengths across different contaminant groups and treatment objectives. Beyond conventional performance indicators, the review frames these technologies as key enablers of circular wastewater treatment through material regeneration, resource recovery, and process integration. Full article

Background: Evidence on HAIs in Africa is fairly common. Objectives: The main objective was to identify the surveillance tools used for healthcare–associated infections (HAIs) in countries in the WHO African Region. Secondary objectives focused on the organization of surveillance, the pathogens involved, and the frequency of multidrug–resistant species. Inclusion and exclusion criteria: Observational or interventional studies on healthcare–associated infections in humans, published between January 2011 and December 2024, in French or English, were included. However, the following publications were not included: animal studies, healthcare–associated infections not related to healthcare, literature reviews, studies outside the period or geographical area, and studies in languages other than French or English. Sources of information and search date: The databases consulted were PubMed, Web of Science, EMBASE, Cochrane, African Index Medicus, Google Scholar, and AJOL. The search was conducted between January and March 2025. Risk of bias assessment: The risk of bias was assessed using a specific grid (eleven criteria), scored from one (low) to three (high). The studies were classified into three levels of methodological quality. The results of the bias assessment showed that the publications were excellent (strong and moderate) with a cumulative rate of 99.9%. Methods of synthesizing results: Data were extracted using a standardized grid and synthesized narratively. No meta–analysis was performed. Number of studies and characteristics: 95 studies were included, mostly cross–sectional studies (82.1%), cohorts (10.4%), and a few case reports. Most were from West Africa (60.0%), particularly Nigeria (16.8%) and South Africa (14.7%). Main results: • Most common pathogens: Staphylococcus aureus (53.7%), Escherichia coli (43.2%), Klebsiella pneumoniae (32.6%). • Resistance profile: ESBL (27.4%), MRSA (21.1%), multidrug resistance (13.7%). • Sources of HAIs: mainly exogenous (83.2%). • Laboratory methods: phenotypic (70.5%), genotypic or genomic rare (3.1%). • Scope of studies: local (96.8%), national (3.2%). Limitations of evidence: Risk of bias due to underreporting of HAIs, methodological heterogeneity, predominance of cross–sectional studies, low use of molecular methods, lack of modeling, and uneven geographical coverage. Overall interpretation and implications: surveillance of HAIs in Africa remains fragmented and poorly standardized. There is a need to strengthen national systems, integrate molecular methods, train professionals, and promote interventional research. The WHO GLASS program can serve as a framework for harmonizing surveillance. Full article

Bats are vital parts of ecosystems but also act as important reservoirs of viruses that can infect humans. Studying bat-borne viruses is essential for preventing spillover events, and passive surveillance offers a promising, bat-friendly approach. Among these viruses, lyssaviruses are a major public health concern because infection in humans is almost always fatal. In Europe, the European bat lyssavirus type 1 (EBLV-1) is the most widespread. We aimed to expand the Hungarian rabies surveillance system into a One Health-based passive surveillance framework for multiple bat viruses, using lyssaviruses and filoviruses as examples. Dead-found or injured bats that died despite care were collected for examination. In total, 208 bats from 15 species were tested for lyssaviruses and Lloviu virus. Three serotine bats (Cnephaeus serotinus, formerly Eptesicus) tested positive for EBLV-1, and complete viral genomes were obtained. All sequences belonged to the EBLV-1a lineage, closely related to previously described Hungarian strains. All bats tested negative for Lloviu virus. These results confirm the feasibility of passive surveillance for detecting bat-borne viruses and highlight the importance of collaborative monitoring systems for future zoonotic outbreak preparedness. Full article

Background/Objectives: The global emergence of carbapenem resistance is a major public health concern. Campylobacter jejuni and Campylobacter coli, key zoonotic agents causing human campylobacteriosis, are mainly isolated from poultry, their primary host. Their increasing resistance in animals and humans highlights the risk of gene transfer. This study investigates the molecular mechanisms of carbapenem resistance in 287 avian Campylobacter spp. isolates from Tunisia within a One Health approach. Methods: Antibiotic susceptibility of 287 carbapenem-resistant isolates, including 147 C. jejuni and 140 C. coli, was determined according to CLSI. All isolates were screened by PCR for genes encoding the most reported carbapenemases, including VIM, IMP, NDM and OXA-48. Eleven multidrug-resistant (MDR)/carbapenem-resistant C. coli isolates were selected to determine their clonal lineage by Multilocus sequence typing (MLST). Results: All isolates were susceptible to imipenem, but resistance to meropenem and ertapenem were observed in 60.71% and 35.71% of C. coli isolates, respectively, versus 13.6% in C. jejuni for each antibiotic. The bla_VIM, bla_NDM and bla_OXA-48 genes were detected in 15, 8, and 19 of the 20 C. jejuni isolates, respectively. However, for C. coli, 53, 12, and 15 isolates harbored bla_VIM, bla_NDM and bla_OXA-48 genes, respectively. The eleven (MDR)/carbapenem-resistant C. coli isolates belonged to a unique ST sequence type ST13450. Conclusions: We report for the first time the emergence of bla_VIM, bla_NDM, and bla_OXA-48 genes in Campylobacter spp. isolates of poultry origin highlighting possible horizontal transfer of these genes to pathogenic Gram-negative bacteria of the poultry’s microbiota. Full article

Despite the progressive extension of CFTR variant eligibility to the triple combination of elexacaftor/tezacaftor/ivacaftor (ETI), most rare CFTR pathogenic variants remain ineligible for CFTR modulators. It is crucial to determine whether unexplored variants are rescuable by clinical modulators and to identify innovative therapeutic strategies for rescuing non-responder variants. The approach known as “theratyping” (in vitro testing of genotypes) has been accepted by the Food and Drug Administration (FDA) for the extension of clinical modulators’ approval for in vitro responding genotypes. We used one of the most advanced models for theratyping: organoids derived from nasal epithelia of people with cystic fibrosis (pwCF). We optimized the forskolin-induced swelling (FIS) of organoids to assess CFTR basal or modulator-restored function. Nasal organoids mimicked the original epithelial tissue, CFTR residual activity, and modulator response. We set up the FIS assay using nasal organoids with reference genotypes and theratyped 38 rare (non-F508del) CFTR genotypes, either eligible or non-eligible for FDA approval, for treatment with ETI or ivacaftor. We found strong correspondence between the in vitro response of CFTR variants to modulators and their FDA approval status. Additionally, some previously uncharacterized CFTR variants have proven responsive to clinical modulators, with significant therapeutic implications. These results suggest that the nasal organoid FIS assay, pending confirmation of the prediction in the corresponding pwCF, might be considered as a powerful in vitro tool to predict modulator efficacy in each pwCF, guiding out-of-label prescription in CF, and to identify uncharacterized variants responsive to modulators. This approach may allow comparison of the efficacy of different therapeutics or the identification of innovative strategies for non-responding genotypes, improving personalized therapy and quality of life for pwCF. Full article

Bile acids provide a versatile platform for the design of biologically active compounds due to their amphiphilic structure, biocompatibility, and capacity for diverse chemical modifications. Among them, lithocholic acid is a promising scaffold for designing and revealing new antiviral agents. A novel lithocholic acid-based 3-spiro-1,2,4-trioxolane was synthesized by Griesbaum co-ozonolysis of methyl 3-O-methyl-oximino-lithocholate and 4-(trifluoromethyl)-cyclohexanone, and its structure was confirmed by 2D NMR and X-ray crystallographic analysis. Lithocholic acid derivatives were evaluated for cytotoxicity and anti-influenza activity against A/Puerto Rico/8/34 (H1N1), showing that steroid 1,2,4-trioxolane 3 exhibited the highest potency (IC₅₀ 4.3 µM, SI 11) compared to the parent methyl-3-oxo-lithocholate 1 (IC₅₀ > 84 µM, SI 1). In silico ADME predictions revealed several favorable drug-like properties, including a highly three-dimensional structure (Fsp³ = 0.97), significant lipophilicity (LogP = 7.54), and the presence of key pharmacophores such as a peroxide moiety and a trifluoromethyl group. Taken together, a stereospecific synthesis of a lithocholic acid 3-spiro-1,2,4-trioxolane by Griesbaum co-ozonolysis was realized and the first evidence of anti-influenza activity in the steroid-1,2,4-trioxolane series was found. Full article