Search Results (86)

Background: The Human Papillomavirus (HPV) vaccine generates high antibody titers against targeted HPV types. This study investigated vaccine-induced anti-HPV18 immunoglobulin (IgG) antibody titers and subsequent HPV18/45 infections. Methods: We performed a nested matched case-control study leveraging a prospective longitudinal cohort of adolescent and young adult women (AYW) vaccinated with the quadrivalent HPV vaccine (4vHPV) attending the Mount Sinai Adolescent Health Center (MSAHC) in Manhattan, NY. The case individuals included AYW who had an incident detection of cervical HPV18 (n = 3) or HPV45 (n = 34) DNA after vaccination and were compared to two vaccinated control individuals (HPV18/45-negative); one random control (RC, n = 37) and one high-risk control (HRC, n = 37) selected from the upper quartile of a sexual risk behavior score. Serological titers against HPV18 were measured by end-point dilution and enzyme-linked immunosorbent assay (ELISA) in serum collected before the incident detection of HPV. Matching was performed based on age at first dose, follow-up time, and sexual risk behavior score. Conditional logistic regression was used to assess the association between case-control status and anti-HPV antibody titers, consistent with the matched-pair design. Results: Antibody titers for HPV18 were most different between AYW who developed an HPV18/45 infection compared to high-risk controls OR = 1.66, 95% CI: 0.96–2.85 (p = 0.1629). Analyses of pooled data from vaccinated recipients including who developed HPV16/31 or HPV18/45 infections demonstrated that the odds of a one-log unit increase in anti-HPV16 or 18 antibody titers, respectively, were 40% higher in the combined control groups (RC + HRC, n = 160) (OR = 1.40, 95% CI: 1.09–1.79, p = 0.0135) and 73% higher in the HRC (n = 80) (OR 1.73, 95% CI: 1.34, 2.52, p = 0.0117) compared to HPV16/18/31/45 cases (n = 80). Conclusions: Overall, these findings suggest that higher IgG antibodies to HPV16/18 after vaccination represent an increased likelihood of protection from homologous and cross-reactive HPV types (HPV16/18/31/45). These results show that differences in antibody titers are associated with breakthrough infection after vaccination, suggesting that further study of long-term antibody titers and infection should be pursued. Full article

Background: The primary objective of this study was to evaluate the cytotoxic and genotoxic effects of calcium silicate-based sealers (BioRoot RCS and MTA Fillapex) compared to an epoxy-based sealer (AH Plus). Materials and methods: The study was conducted in vitro with the cell lines HepG2 and V79 to evaluate cytotoxicity and genotoxicity using the comet and micronucleus assays. Eluates of the materials were tested at two different concentrations (3 cm²/mL and 0.5 cm²/mL) after an exposure time of 72 h. Data were analyzed using the Mann–Whitney and Kruskal–Wallis tests (p < 0.05). Results: At lower concentrations in both cell lines, MTA Fillapex showed no significant difference in the measured comet assay parameters compared to the negative control (p > 0.05). In addition, it showed significantly lower genotoxic effects compared to AH Plus for all comet assay parameters, concentrations, and cell lines (p ≤ 0.001). BioRoot RCS showed lower primary DNA damage (p ≤ 0.001) than AH Plus, only at higher concentrations and in the HepG2 cell line. Concerning the two tested bioceramic sealers, BioRoot RCS showed higher tail intensity values compared to MTA Fillapex (p < 0.05). In contrast to the results of the comet assay, BioRoot RCS significantly reduced the number of nuclear buds and nucleoplasmic bridges in the HepG2 cell line compared to MTA Fillapex, whereas reduction in the V79 cell line was only observed for nuclear buds (p < 0.05). Both materials increased the number of apoptotic cells compared to the negative control (p < 0.05). In comparison to AH Plus, BioRoot RCS and MTA Fillapex significantly reduced the number of cells with micronuclei and increased the number of cells with undamaged chromatin (p < 0.05). Conclusions: The findings suggest that MTA Fillapex and BioRoot RCS exhibit superior biocompatibility over AH Plus, as evidenced by their lower cytotoxic and genotoxic effects in vitro. These results support the use of calcium silicate-based sealers in clinical practice, highlighting the need for further studies to evaluate their performance in vivo and their implications for patient safety. Full article

(1) The link between periodontal disease (PD) and acute coronary syndromes (ACSs) is predominantly attributed to the atherosclerotic process, mediated by systemic inflammation. However, the correlation between the severity of PD, characterized by the presence of periodontal pathogens, and systemic inflammation in patients with ACS remains inadequately clarified. (2) This study aims to assess the association between the severity of PD and systemic inflammatory biomarkers, along with lipid profiles, in patients with ACS. (3) In total, 42 patients with ACS and concomitant PD were divided into two groups based on the presence of periodontal pathogens belonging to the red or red-orange complexes. Group 1–29 patients displayed pathogens from the red complex (RC) and group 2–13 patients displayed pathogens from the red-orange complex (ROC). All participants underwent a comprehensive dental examination, including DNA sampling from the periodontal pockets for pathogen detection. Systemic inflammation was evaluated alongside assessments of lipid profiles. (4) Inflammatory markers were more pronounced in the RC group compared with the ROC group. Moreover, patients in the RC group showed significantly higher monocyte-to-lymphocyte ratios (0.41 ± 0.20 vs. 0.28 ± 0.12; p = 0.002), platelet-to-lymphocyte ratios (139.50 ± 33.85 vs. 100.90 ± 8.84; p = 0.02), serum C-reactive protein levels (9.34 ± 1.08 mg/L vs. 5.46 ± 1.03 mg/L; p = 0.03), and serum uric acid levels (6.9 ± 0.49 mg/dL vs. 5.4 ± 0.26 mg/dL; p = 0.006). Concerning lipid profiles, the RC group exhibited significantly higher low-density lipoprotein cholesterol (LDL) levels (169.60 ± 12.63 mg/dL vs. 106.70 ± 9.34 mg/dL; p = 0.0007) and significantly lower high-density lipoprotein cholesterol (HDL) levels (29.29 ± 3.50 mg/dL vs. 39.56 ± 2.07 mg/dL; p = 0.002). (5) The severity of PD, indicated by the concomitant presence of pathogens from the red and orange complexes, is associated with an unfavorable lipid profile and elevated inflammatory biomarkers. These findings highlight the potential importance of periodontal intervention in the prevention of ACS. Full article

As IoT devices proliferate in critical areas like healthcare or nuclear safety, it necessitates the provision of cryptographic solutions with security and computational efficiency. Very well-established encryption mechanisms such as AES, RC4, and XOR cannot strike a balance between speed, energy consumption, and robustness. Moreover, most DNA-based solutions are not cognizant of the hardware limitations of IoT platforms such as Arduino R3. This paper proposes an improved encryption technique incorporating stochastic DNA-inspired processing with optical computing in a resource-constrained environment. The proposed algorithm employs stochastic pixel selection with DNA-encoded key generation and is further enhanced by parallel optical processing to overcome the trade-offs of conventional techniques during implementation. Experimental trials performed on Arduino R3 established superior performance in terms of an encryption time of 3956 μs and memory usage of 773 bytes, placing it ahead of AES and XOR-based approaches. Apart from the tests performed, security analyses have revealed a strong resistant position upon differential cryptanalysis (DP = 0.051) and linear cryptanalysis (LP = 0.045), with an almost-ideal key entropy (7.99 bits/key) and minimal autocorrelation (0.018). This research offers practical applications in real-time medical monitoring and nuclear radiation detection systems by closing the existing gap in hardware-aware DNA cryptography. Full article

The aim of this study was to investigate the effects of storage temperature and preservation time on the microbial diversity and community composition of rumen fluid. Rumen fluid samples were collected from six Hu sheep fed on a high-forage diet and stored at −80 °C and −20 °C for intervals of 0, 7, 14, 30, 60, 120, and 240 days. DNA was extracted at each time point for 16S rRNA gene sequencing to evaluate the rumen microbial diversity and community composition. The results showed that storage temperature affected only the relative abundance of Proteobacteria, with no substantial impact on alpha-diversity or other microbial groups (p > 0.05), and no significant interaction effects were observed between storage temperature and preservation time (p > 0.05). Alpha-diversity indices such as Chao1, observed species, and PD whole tree showed dynamic changes after 7 days of storage, while the relative abundances of Verrucomicrobiota and Christensenellaceae R-7 group, as well as the energy metabolism metabolic pathway, exhibited significant alterations after 14 days of storage (p < 0.05). Notably, Patescibacteria, Rikenellaceae RC9 gut group, and Veillonellaceae UCG-001 abundances demonstrated significant changes after 240 days of storage (p < 0.05). Both principal coordinates analysis (PCoA) and non-metric multidimensional scaling (NMDS) showed distinct overlaps. This study suggests that storing rumen fluid at −80 °C and −20 °C does not influence rumen microbial diversity and community composition, whereas the storage time significantly impacts these factors, with most differences emerging after 14 days of preservation. Consequently, it is advised that the analysis of microbial diversity and community composition in rumen fluid samples be conducted within 14 days post-collection. Full article

The growing demand for viral vectors as nanoscale therapeutic agents in gene therapy necessitates efficient and scalable purification methods. This study examined the role of nanoscale biomaterials in optimizing viral vector clarification through a model system mimicking real AAV2 crude harvest material. Using lysed HEK293 cells and silica nanoparticles (20 nm) as surrogates for AAV2 crude harvest, we evaluated primary (depth filters) and secondary (membrane-based) filtration processes under different process parameters and solution conditions. These filtration systems were then assessed for their ability to recover nanoscale viral vectors while reducing DNA (without the need for endonuclease treatment), protein, and turbidity. Primary clarification demonstrated that high flux rates (600 LMH) reduced the depth filter’s ability to leverage adsorptive and electrostatic interactions, resulting in a lower DNA removal. Conversely, lower flux rates (150 LMH) enabled >90% DNA reduction by maintaining these interactions. Solution conductivity significantly influenced performance, with high conductivity screening electrostatic interactions, and the model system closely matching real system outcomes under these conditions. Secondary clarification highlighted material-dependent trade-offs. The PES membranes achieved exceptional AAV2 recovery rates exceeding 90%, while RC membranes excelled in DNA reduction (>80%) due to their respective surface charge and hydrophilic properties. The integration of the primary clarification step dramatically improved PES membrane performance, increasing the final flux from ~60 LMH to ~600 LMH. Fouling analysis revealed that real AAV2 systems experienced more severe and complex fouling compared to the model system, transitioning from intermediate blocking to irreversible cake layer formation, which was exacerbated by nanoscale impurities (~10–600 nm). This work bridges nanomaterial science and biomanufacturing, advancing scalable viral vector purification for gene therapy. Full article

DNA replication is a crucial biological process that ensures the accurate transmission of genetic information, underpinning the growth, development, and reproduction of organisms. Abnormalities in DNA replication are a primary source of genomic instability and tumorigenesis. During DNA replication, the assembly of the pre-RC at the G1-G1/S transition is a crucial licensing step that ensures the successful initiation of replication. Although many pre-replication complex (pre-RC) proteins have been identified, technical limitations hinder the detection of transiently interacting proteins. The APEX system employs peroxidase-mediated rapid labeling with high catalytic efficiency, enabling protein labeling within one minute and detection of transient protein interactions. MCM2 is a key component of the eukaryotic replication initiation complex, which is essential for DNA replication. In this study, we fused MCM2 with enhanced APEX2 to perform in situ biotinylation. By combining this approach with mass spectrometry, we identified proteins proximal to the replication initiation complex in synchronized mouse ESCs and NIH/3T3. Through a comparison of the results from both cell types, we identified some candidate proteins. Interactions between MCM2 and the candidate proteins CD2BP2, VRK1, and GTSE1 were confirmed by bimolecular fluorescence complementation. This research establishes a basis for further study of the component proteins of the conserved DNA replication initiation complex and the transient regulatory network involving its proximal proteins. Full article

The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to the activation of the DNA damage response (DDR) system. Dysfunctional DNA replication and DDR are a source of genomic instability, causing heritable mutations that drive cancer evolutions. The family of minichromosome maintenance (MCM) proteins plays an important role not only in DNA replication but also in DDR. Here, we will review the current strides of MCM proteins in these integrated processes as well as the acetylation/deacetylation of MCM proteins and the value of MCMs as biomarkers in cancer. Full article

Paratuberculosis (PTB), primarily caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic infection that affects ruminants and is difficult to prevent, diagnose, and treat. Investigating how MAP infections affect the gut microbiota in sheep can aid in the prevention and treatment of ovine PTB. This study examined fecal samples from eight small-tail Han sheep (STHS) at various stages of infection and from three different field areas. All samples underwent DNA extraction and 16S rRNA sequencing. Among all samples, the phyla p. Firmicutes and p. Bacteroidota exhibited the highest relative abundance. The dominant genera in groups M1–M6 were UCG-005, Christensenellaceae_R-7_group, Rikenellaceae_RC9_gut_group, Akkermansia, UCG-005, and Bacteroides, whereas those in groups A–C were Christensenellaceae_R-7_group, Escherichia–Shigella, and Acinetobacter, respectively. The microbial community structure varied significantly among groups M1–M6. Specifically, 56 microbiota consortia with different taxonomic levels, including the order Clostridiales, were significantly enriched in groups M1–M6, whereas 96 microbiota consortia at different taxonomic levels, including the family Oscillospiraceae, were significantly enriched in groups A–C. To the best of our knowledge, this is the first study to report that MAP infection alters the intestinal microbiota of STHS. Changes in p. Firmicutes abundance can serve as a potential biomarker to distinguish MAP infection and determine the infection stage for its early diagnosis. Our study provides a theoretical basis for the treatment of PTB by regulating the intestinal microbiota, including p. Firmicutes. Full article

Soil salinity is considered a serious problem that limits agricultural productivity. Currently, solutions are being sought to mitigate the negative impact of salt on economically important crops. The aim of the study was to evaluate the effect of foliar application of silicon (Si) on the physiological and epigenetic responses of wheat grown under salt stress conditions. The experiment with wheat seedlings was established in pots with 200 mM NaCl added. After 7 days, foliar fertilizer (200 g L⁻¹ SiO₂) was used at concentrations of 0.05, 0.1 and 0.2%. Physiological parameters were measured three times. The addition of salt caused a significant decrease in the values of the measured parameters in plants of all variants. In plants sprayed with Si fertilizer under salinity conditions, a significant increase in CCI and selected gas exchange parameters (P_N, C_i, E, g_s) and chlorophyll fluorescence (PI, RC/ABS, F_V/F_m, Fv/F₀) was observed. Si doses of 0.1 and 0.2% showed a better mitigating effect compared to the dose of 0.05%. The observed effect was maintained over time. The results obtained indicate a positive role for foliar silicon fertilization in mitigating salinity stress in wheat. Epigenetic mechanisms play an important role in regulating gene expression in response to stress. Changes in the status of methylation of the 5′CCGG3′ sequence of the nuclear genome of wheat plants exposed to salinity and treated with Si at different doses were determined by the MSAP approach. The obtained results showed a clear alteration of DNA methylation in plants as a response to experimental factors. The methylation changes were silicon dose-dependent. These modifications may suggest a mechanism for plant adaptation under salt stress after silicon application. Full article

This study evaluated the gut microbiota and meat quality traits in 11 healthy female cattle from the Huaral region of Peru, including 5 Angus, 3 Braunvieh, and 3 F1 Simmental × Braunvieh. All cattle were 18 months old and maintained on a consistent lifelong diet. Meat quality traits, including loin area, fat thickness, muscle depth, and marbling, were assessed in vivo using ultrasonography. Fecal samples were collected for microbiota analysis, and DNA was extracted for 16S and 18S rRNA sequencing to characterize bacterial, fungal, and protist communities. Significant correlations were observed between microbial genera and meat traits: Christensenellaceae R-7 and Alistipes were positively associated with marbling and muscle area, while Rikenellaceae RC9 showed a negative correlation with fat thickness. Among fungi, Candida positively correlated with marbling, while Trichosporon was negatively associated with muscle depth. For protists, Entodinium negatively correlated with fat thickness and marbling. Alpha diversity varied by breed, with Angus showing greater bacterial diversity, and beta diversity analyses indicated a strong breed influence on microbial composition. These findings suggest that microbial composition, shaped by breed and dietary consistency, could serve as an indicator of meat quality, offering insights into gut microbiota’s role in optimizing cattle production. Full article

A joint analysis of dendrochronological and genomic data was performed to identify genetic mechanisms of adaptation and assess the adaptive genetic potential of Siberian stone pine (Pinus sibirica Du Tour) populations. The data obtained are necessary for predicting the effect of climate change and mitigating its negative consequences. Presented are the results of an association analysis of the variation of 84,853 genetic markers (single nucleotide polymorphisms—SNPs) obtained by double digest restriction-site associated DNA sequencing (ddRADseq) and 110 individual phenotypic traits, including dendrophenotypes based on the dynamics of tree-ring widths (TRWs) of 234 individual trees in six natural populations of Siberian stone pine, which have a history of extreme climatic stresses (e.g., droughts) and outbreaks of defoliators (e.g., pine sawfly [Neodiprion sertifer Geoff.]). The genetic structure of studied populations was relatively weak; samples are poorly differentiated and belong to genetically similar populations. Genotype–dendrophenotype associations were analyzed using three different approaches and corresponding models: General Linear Model (GLM), Bayesian Sparse Linear Mixed Model (BSLMM), and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK), respectively. Thirty SNPs were detected by at least two different approaches, and two SNPs by all three. In addition, three SNPs associated with mean values of recovery dendrophenotype (Rc) averaged across multiple years of climatic stresses were also found by all three methods. The sequences containing these SNPs were annotated using genome annotation of a very closely related species, whitebark pine (P. albicaulis Engelm.). We found that most of the SNPs with supposedly adaptive variation were located in intergenic regions. Three dendrophenotype-associated SNPs were located within the 10 Kbp regions and one in the intron of the genes encoding proteins that play a crucial role in ensuring the integrity of the plant’s genetic information, particularly under environmental stress conditions that can induce DNA damage. In addition, we found a correlation of individual heterozygosity with some dendrophenotypes. Heterosis was observed in most of these statistically significant cases; signs of homeostasis were also detected. Although most of the identified SNPs were not assigned to a particular gene, their high polymorphism and association with adaptive traits likely indicate high adaptive potential that can facilitate adaptation of Siberian stone pine populations to the climatic stresses and climate change. Full article

Understanding the relationship between Raramuri Criollo cattle (RC) and their microbial ruminal ecosystem will help identify advantageous characteristics of adapted cattle as alternatives to achieve sustainable beef production systems. Our objective was to characterize the rumen microbiome of RC in comparison to Angus and Hereford breeds (European, E) and the cross between them (E × RC). Ruminal fluid was collected from 63 cows in their second productive cycle after grazing in the same paddock for 45 d, in the dry (n = 28) and rain (n = 35) seasons. DNA from ruminal fluid was isolated for 16s rRNA gene next-generation sequencing. The data were analyzed with QIIME2 and compared against the SILVA 16s rRNA database. Beta diversity was different (p < 0.05) between RC and E in both seasons. A microbial core was represented by the most abundant phyla. Planctomycetes and Spirochaetes represented above 1% in the rain season and below 1% in the dry one, whereas Euryarchaeota was below 1% and around 3%, respectively. LEfSe analysis identified differentiated (p < 0.05) key microbial groups that explain the differences between lineages at different taxonomic levels, reflecting the ability of the rumen ecosystem of RC cattle to adapt to hostile environmental conditions by having microbial groups specialized in the degradation of highly fibrous content. Full article

Background: We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. Materials and methods: In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2^−∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene). Results: We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR −0.27; CI −0.504 to −0.032; p = 0.036]; osteoblastic subtype [OR −0.36; CI −0.652 to −0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR −2.5; CI −3.616 to −1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR −1.04; CI −1.592 to −0.487; p = 0.035]; chondroblastic subtype [OR −0.83; CI −1.106 to −0.520; p = 0.012]; and osteoblastic subtype [OR −1.28; CI −1.664 to −0.901; p = 0.007]. Conclusions: In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent. Full article

In ruminants, supplementing appropriate amounts of amino acids improves growth, feed utilization efficiency, and productivity. This study aimed to assess the effects of different Lys/Met ratios on the ruminal microbial community and the metabolic profiling in Tibetan sheep using 16S rDNA sequencing and non-target metabolomics. Ninety-two-month-old Tibetan rams (initial weight = 15.37 ± 0.92 kg) were divided into three groups and fed lysine/methionine (Lys/Met) of 1:1 (LP-L), 2:1 (LP-M), and 3:1 (LP-H) in low-protein diet, respectively. Results: The T-AOC, GSH-Px, and SOD were significantly higher in the LP-L group than in LP-H and LP-M groups (p < 0.05). Cellulase activity was significantly higher in the LP-L group than in the LP-H group (p < 0.05). In the fermentation parameters, acetic acid concentration was significantly higher in the LP-L group than in the LP-H group (p < 0.05). Microbial sequencing analysis showed that Ace and Chao1 indicators were significantly higher in LP-L than in LP-H and LP-M (p < 0.05). At the genus level, the abundance of Rikenellaceae RC9 gut group flora and Succiniclasticum were significantly higher in LP-L than in LP-M group (p < 0.05). Non-target metabolomics analyses revealed that the levels of phosphoric acid, pyrocatechol, hydrocinnamic acid, banzamide, l-gulono-1,4-lactone, cis-jasmone, Val-Asp-Arg, and tropinone content were higher in LP-L. However, l-citrulline and purine levels were lower in the LP-L group than in the LP-M and LP-H groups. Banzamide, cis-jasmone, and Val-Asp-Arg contents were positively correlated with the phenotypic contents, including T-AOC, SOD, and cellulase. Phosphoric acid content was positively correlated with cellulase and lipase activities. In conclusion, the Met/Lys ratio of 1:1 in low-protein diets showed superior antioxidant status and cellulase activity in the rumen by modulating the microbiota and metabolism of Tibetan sheep. Full article