Search Results (182)

Feline immunodeficiency virus (FIV) is a lentivirus that exhibits significant structural and pathological similarities to human immunodeficiency virus (HIV), establishing it as a valuable model for HIV vaccine development. In this study, artificial intelligence (AI) and immunoinformatics were employed to design a novel multi-epitope DNA vaccine targeting conserved regions of the FIV gag, pol, and env genes. Predicted B-cell and T-cell epitopes were evaluated for their capacity to induce strong immune responses while minimizing allergenic or toxic effects and were linked to the immune adjuvant PADRE. Structural analysis indicated that the vaccine construct is stable, soluble, and biocompatible, with a well-folded tertiary structure that binds Toll-like receptor 9 (TLR9) and elicits robust humoral and cellular immune responses. These findings identify a promising FIV vaccine candidate and provide insights for the development of next-generation HIV vaccines. Full article

Objective: Population mobility complicates the prevention and control of HIV. To address these challenges, this study explored the molecular epidemiology of HIV among migrant populations in Hangzhou. Methods: People newly diagnosed with HIV/AIDS from 2020 to 2023 were divided into permanent migrant population (PMP), temporary migrant population (TMP), and non-migrant population (NMP). HIV-1 pol gene sequencing was performed to calculate genetic distance. Sample pairs with genetic distances ≤0.005 were used to construct the molecular transmission network. Results: PMP comprised people living with HIV in Hangzhou, characterized by younger age, higher education, and predominantly homosexual transmission. This population forms multiple large molecular clusters together with NMP. TMP accounted for the highest proportion of females and people infected through heterosexual contact, but the education level was the lowest. NMP had the fewest people living with HIV. The main subtypes identified were CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B. Drug resistance prevalence did not differ significantly among the populations. The molecular transmission network included 833 cases forming 275 clusters, with an overall sample inclusion rate of 23.04%. PMP, TMP and NMP inclusion rates were 27.10%, 19.03% and 21.4%, respectively. All molecular clusters involved migrant populations. Factors associated with inclusion in the network for migrants included current residence, household registration, STD history, sample source, and stage at diagnosis. Conclusions: Migrant populations play a major role in ongoing HIV transmission. Prevention and control measures should be strengthened according to population-specific characteristics. Molecular transmission networks are useful tools for assisting precise control. Full article

Bovine leukemia virus (BLV) is an oncogenic deltaretrovirus that infects B cells, and its possible presence in humans has garnered increasing attention. This study included 58 participants: 11 with B-cell precursor acute lymphoblastic leukemia (B-ALL, cases) and 47 healthy individuals (controls). Researchers assessed anti-gp51 antibodies and BLV proviral DNA in bone marrow and blood samples. Seropositivity was observed only in the B-ALL group (18.2%; 2/11), while all controls were seronegative. Quantitative PCR targeting the pol gene detected proviral DNA in 74.1% of samples, with similar detection rates between cases and controls. Although proviral load was higher in controls, this difference did not reach statistical significance. Conventional and nested PCR for other viral genes revealed a differential pattern: amplification of the tax gene was significantly associated with B-ALL, whereas gag and env were not. Bayesian Chow–Liu network analyses identified dependencies among viral genes and suggested that contextual factors, such as fieldwork, may influence the association between molecular positivity and B-ALL. Sequence analyses showed that the detected BLV strains clustered with previously reported bovine and human sequences from Colombia, all within genotype 1. These findings support human exposure to BLV and raise important questions about its persistence and potential connections to hematological diseases in humans. Full article

In this work, we analyzed the ability to incorporate 8-oxo-dATP by several human DNA polymerases: replicative Pol ε (exo-) from Family B; base excision repair (BER) enzymes Pol β and Pol λ from Family X; and translesion Pol η, Pol ι, and Pol κ from Family Y. We demonstrated that human DNA polymerases differ in their abilities to discriminate against 8-oxo-dATP. Among the tested DNA polymerases, Pol λ exhibited the worst ability to discriminate against 8-oxo-dATP opposite template T on DNA substrates with a protruding single-stranded 5′-end and a double-stranded DNA with a 1 nt gap. Pol β and DNA polymerases of Family Y showed relatively high accuracy. Pol η demonstrated the most effective discrimination against 8-oxo-dATP on templates T and G. Pol ι exclusively incorporated 8-oxo-dATP opposite template G but not T. Unexpectedly, the catalytic subunit of high-fidelity Pol ε (exo-) incorporated 8-oxo-dATP opposite templates T and G with higher efficiency compared with the error-prone polymerases of Family Y and Pol β. While the structures of human polymerases with incoming 8-oxo-dATP are not available, we speculate on a possible mechanism of 8-oxo-dATP discrimination. Full article

This paper presents a water-based reflect-transmit antenna (WBRTA) array for millimeter-wave (mm-wave) applications. The WBRTA array incorporates the low-permittivity polylactic acid (PLA)- and high-permittivity water-based unit cells. The low permittivity PLA unit cells provide better transmission, whereas the water-based unit cell offers good reflections due to a very high permittivity. Therefore, the WBRTA enables simultaneous beam splitting in reflection and transmission modes across a wider bandwidth. In addition, depending on the distribution and configuration of the water- and PLA-based unit cells, the WBRTA enables beam tilting of up to 45° in the reflection and transmission modes simultaneously. The proposed WBRTA offers peak gains of 25.2 dBi in transmission and 24 dBi in reflection at the central frequency. The corresponding sidelobe levels (SLLs) are −22 dB for transmission and −17 dB for reflection, while cross-polarization (x-pol) levels remain below −81 dB. In addition, the wide operational bandwidth, low sidelobe levels, and high polarization purity make the proposed WBRTA relevant as an enabling antenna structure for positioning-oriented sensing functions in future mmWave wireless systems. Full article

This work conducted a transcriptome analysis of canine intestinal epithelial cells (cIECs) treated with nicotinamide mononucleotide (NMN), a physiologically active nucleotide with a pyridine base known for its anti-aging and anti-inflammatory effects. In our experiment, cIECs were cultured and segregated into a control group (Ctrl) and an NMN-treated group. The finding demonstrated that NMN significantly affects cell proliferation in cIECs in comparison to the Ctrl. The transcriptome analysis indicated a high enrichment of genes associated with the cell cycle, proliferation, cellular senescence, and inflammatory pathways in NMN-treated cIECs, showing that NMN has the capacity to modify these biological processes. Compared to the Ctrl group, NMN treatment significantly increased ATP, SOD, CAT and GSH levels and decreased the activities of ROS and MDA. NMN treatment also significantly increased the activity of the relative complex I, III and V enzymes compared to the Ctrl group. Furthermore, the expression of MAPK13, EDN1, TNFAIP6, TNFSF15 and SLC7A11 were decreased significantly, while ACOX2, CPT1C, CCNA1 and CCNE1 were increased significantly in NMN-5μM treatment compared to Ctrl. NMN-treated significantly decreased the expression of Hdac2, Hdac6 and Hdac8, while increasing the expression of Kdm5a, Kdm5b and Kdm5c compared to the Ctrl group. Additionally, ChIP-qPCR use discovered that NMN-treatment significantly downregulated the enrichment of EDN-1 at target loci of NR4A1, SRC1, P300, Pol II and Ser5- Pol II compared to the Ctrl group. Expression of the NR4A1 gene suggests that its exert in biological activities by inhibiting inflammatory responses and anti-aging pathways. Then, we detected the transcriptional activation linked histone markers and found that H3K23ac and H3K27ac were significantly downregulated, while H3K27me3 was significantly upregulated in the NMN-treatment compared to the Ctrl group. We conclude that NMN regulates EDN-1 expression in cIECs through mechanisms involving NR4A1 and histone modifications, highlighting its potential role in canine intestinal health. Full article

The SMART-P (Spectral Measurements for Atmospheric Radiative Transfer–Polarimeter) algorithm was developed to retrieve aerosol and ocean parameters from PolCube measurements. The PolCube is a multi-angular polarimeter (MAP) aboard the BusanSat-B CubeSat scheduled for launch in 2026, which measures polarized radiances at 410, 555, 670, and 865 nm from four viewing angles. This study presents the theoretical basis of the algorithm and conducts a sensitivity analysis of aerosol inversions over the ocean processed by SMART-P under the expected measurement conditions for PolCube observations. The results indicate that the degree of linear polarization (DoLP) significantly increases the information content of the real part of the refractive index and of the fine-mode particle-size parameters relative to radiance-only measurements. Enhanced measurement sensitivity enables more accurate retrieval of fine-dominated aerosol properties, such as smoke and sulfate. The sensitivity analysis also shows that the ocean surface reflectivity is the most critical forward-model parameter affecting aerosol-property retrievals. The SMART-P algorithm will support the BusanSat-B mission to understand the role of aerosol particles in the climate system and air quality. Full article

Cardinium endosymbionts are obligate intracellular bacteria found in a wide range of invertebrate hosts. In this study, we generated ten new Cardinium genomes from plant-parasitic nematodes of the genera Amplimerlinius, Bursaphelenchus, Cactodera, Ditylenchus, Globodera, Meloidoderita, and Rotylenchus, revealing their broad ecological and phylogenetic distribution. Using an expanded set of genes, we clarified the relationship between previously defined Cardinium groups B and F from nematodes, showing that they are closely related and likely share a single evolutionary origin within nematode-associated Cardinium. Among the newly assembled Cardinium genomes obtained in this study, two genomes originating from strains associated with wood-inhabiting Bursaphelenchus species exhibited remarkable genome reduction, with estimated sizes of approximately 695 kb. Functional annotation of Cardinium genomes indicated an absence of or a reduction in several central metabolic pathways, including the biotin biosynthetic pathway. A complete biotin pathway was found only in D. weischeri, and this pathway is only partially encoded in Cactodera sp. The polA gene, which encodes DNA polymerase I, showed partial loss in several Cardinium strains. Phylogenetic and comparative genomic analyses provided strong evidence that several carbohydrate, glycerophospholipid, and biotin metabolism genes in these endosymbionts have been acquired through horizontal gene transfer. Future research that integrates high-quality genome assemblies with functional analyses of host–symbiont interactions will be essential to elucidate how metabolic dependency, genome reduction, and horizontal gene transfer collectively shape the evolution and ecological diversification of Cardinium across nematode hosts. Full article

The global distribution of HIV-1 subtypes exhibits significant regional variations, with evolving epidemiological patterns over time. China currently experiences concurrent circulation of multiple HIV-1 subtypes, and the transmission landscape is becoming increasingly complex and diversified. We performed prospective molecular surveillance and drug-resistance profiling of HIV-1 in Wuhan City to delineate the local genotypic structure and to guide antiretroviral therapy. A total of 149 whole blood samples from HIV-1-infected individuals preserved in 2022 at a hospital in Wuhan were selected. Peripheral-blood mononuclear cells (PBMCs) were isolated, total RNA extracted, and the Gag, Pol, and Env regions were amplified by nested RT-PCR and sequenced. The sequencing and phylogenetic tree results revealed that subtype B constituted the predominant clade (73/149, 49.1%), followed by CRF07_BC (20, 13.4%), CRF01_AE (13, 8.7%), CRF55_01B (2, 1.3%), and subtype C (1, 0.7%). Drug resistance mutations were detected in 36 cases, involving 41 mutation sites across 21 distinct types. Resistance profiles included two protease inhibitor-associated mutation sites (2 types), seven nucleoside reverse transcriptase inhibitor (NRTI)-related mutation sites (6 types), and 32 non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation sites (13 types). Full article

Synthetic Aperture Radar (SAR) has been widely applied for rice monitoring, especially in cloud-prone areas, due to its ability to penetrate clouds. However, only limited methods were developed to monitor separately irrigated rice and rainfed rice ecosystems. This study demonstrated the use of multi-temporal polarimetric dual-polarization (dual-pol) SAR (Sentinel-1B and ALOS PALSAR-2) data to monitor and discriminate the irrigated and favorable rainfed rice ecosystems in the province of Iloilo, Philippines. Key polarimetric parameters derived from H–A–α and model-based dual-pol decomposition were analyzed to characterize the rice phenology of both ecosystems. Segmented regression was performed to detect breakpoints corresponding to changes in rice phenology within each ecosystem and used to identify the parameters to use for classification. Based on the results, Sentinel-1B polarimetric parameters (entropy, anisotropy, and alpha) can capture the phenological dynamics, whereas ALOS2 polarimetric parameters were more sensitive to water conditions, as reflected in span and volume scattering. Furthermore, irrigated rice exhibited more stable and predictable scattering patterns than favorable rainfed rice. Using the Random Forest classifier, various combinations of backscatter and polarimetric parameters from Sentinel-1B and ALOS2 were tested to discriminate between the two ecosystems. The highest classification accuracy (81.81% overall accuracy; Kappa = 0.6345) was achieved using the combined backscatter (S1B VH, ALOS2 HH, and HV) and polarimetric parameters from both sensors. The results demonstrated that polarimetric parameters effectively capture phenological stages and associated scattering mechanisms, with the integration of Sentinel-1B and ALOS2 data improving the discrimination of irrigated and favorable rainfed rice systems. Full article

The extensive genetic diversity of HIV-1, also represented by the circulation of multiple subtypes and circulating recombinant forms (CRFs), poses significant challenges for accurate subtype classification, especially when sequencing is limited to partial genomic regions. This study evaluated the performance of four commonly used automated subtyping tools (Stanford HIVdb, COMET, REGA, and Geno2pheno) by comparing their outputs with molecular phylogenetic analysis (Mphy), considered the gold standard, using three NGS-derived sequence data sets: protease-reverse transcriptase (PR-RT), pol, and near full-length (NFL). One hundred plasma samples were processed to generate sequences of increasing length, which were analyzed to assess concordance, sensitivity, and specificity. NFL-based Mphy identified a higher proportion of circulating recombinant forms (51.6%) than PR-RT and pol (44.1%) and enabled the reclassification of 13 samples as more complex CRFs. Automated tools displayed good concordance with Mphy for PR-RT and pol, particularly for pure subtypes, whereas concordance decreased considerably for NFL sequences, especially among non-B subtypes and CRFs. Sensitivity varied substantially across tools and subtypes, while specificity remained consistently high. Overall, the findings indicate that whole genome or NFL sequencing enhances the detection of CRFs and that the accuracy of automated tools is strongly influenced by the completeness and updating of their reference databases. Full article

Background: Limited molecular surveillance continues to constrain Morocco’s HIV response, leaving subtype dynamics largely underreported. Once characterized by a predominance of subtype B, the Moroccan epidemic now appears to reflect shifting patterns shaped by regional and international connectivity. This study aimed to investigate HIV-1 molecular diversity, monitor circulating HIV-1 genetic variants, and inter-gene recombination in a cohort of people living with HIV in Morocco. Methods: We conducted an analysis of individuals diagnosed with HIV-1 infection or receiving follow-up care. Demographic and clinical data were extracted. Genotypic testing was performed on the protease/reverse transcriptase (PR/RT) and integrase (IN) regions of the pol gene using the HIV-1 Genotyping Kit with Integrase. Subtypes were assigned via Stanford HIVdb and HIV Blast, and phylogenetic relationships were analyzed using MEGA 12. Results: Of the 73 individuals enrolled, 64 were successfully sequenced. The median age was 43 years (IQR 35–51.3), with over half aged 25–44, and 85.9% were male. Heterosexual transmission was the main route (87.5%), and 59.4% were ART-naïve. Non-B subtypes predominated (87.5%), led by CRF02_AG (73.4%), followed by B (12.5%), C (7.8%), and A3 (3.1%). The cohort showed significant genetic diversity, including multiple CRFs such as CRF45_cpx (1.6%), CRF01_AE (1.6%), B/CRF02_AG (7.8%), G/CRF02_AG (3.1%), C/CRF02_AG (1.6%), CRF02_AG/CRF45_cpx (1.6%) and CRF02_AG/CRF22_01A1 (1.6%). Conclusions: This study provides updated insight into HIV-1 diversity in Morocco, showing a predominance of non-B subtypes, particularly CRF02_AG, and signals of increasing heterogeneity compared with reports from more than a decade ago that described subtype B predominance. These findings suggest a viral transition shaped in part by regional connectivity and highlight a gap in Morocco’s HIV strategy, underscoring the need to implement nationwide molecular surveillance to inform future HIV control efforts. Full article

Helicobacter pylori infects the human stomach and causes various gastrointestinal diseases. Saucerneol D is a type of lignan, which is a polyphenol compound that exists naturally in plants, and it is abundant in flaxseed, sesame seeds, whole grains, vegetables, and fruits. Saucerneol D is found in Saurus chinensis extract and has been reported to exert a variety of effects, such as antioxidant and anti-inflammatory abilities. However, its antibacterial effect against H. pylori has not been reported; therefore, we analyzed the effect of saucerneol D on H. pylori in the present study. Changes in the expression of pathogenic factors and gene transcription in H. pylori were observed after treatment with saucerneol D using Western blotting and RT-PCR. It was confirmed that saucerneol D suppressed the growth of H. pylori by decreasing the expression of the genes dnaN and polA, which are required for bacterial replication. Saucerneol D also reduced the secretion of the major pathogenic toxin protein, CagA, by downregulating the expression of type IV secretion system-composing proteins. Furthermore, saucerneol D reduced ammonia production by inhibiting the expression of urease proteins, which are essential for the survival of H. pylori in the acidic gastric environment. Additionally, saucerneol D decreased the expression of flaB, potentially reducing motility. Finally, it was confirmed that the expression of the sabA gene, associated with cell adhesion, was reduced. These results suggest that saucerneol D inhibits the growth of H. pylori and the expression of several pathogenic factors, indicating that saucerneol D has an antimicrobial effect against H. pylori. Full article

Replication timing (RT), the temporal order of DNA replication during S phase, influences regional mutation rates, yet the mechanistic basis for RT-associated mutagenesis remains incompletely defined. To identify drivers of RT-dependent mutation biases, we analyzed whole-genome sequencing data from cells with disruptions in DNA replication/repair genes or exposed to mutagenic compounds. Mutation distributions between early- and late-replicating regions were compared using bootstrapping and statistical modeling. We identified 14 genes that exhibit differential effects in early- or late-replicating regions, encompassing multiple DNA repair pathways, including mismatch repair (MLH1, MSH2, MSH6, PMS1, and PMS2), trans-lesion DNA synthesis (REV1) and double-strand break repair (DCLRE1A and PRKDC), DNA polymerases (POLB, POLE3, and POLE4), and other genes central to genomic instability (PARP1 and TP53). Similar analyses of mutagenic compounds revealed 19 compounds with differential effects on replication timing. These results establish replication timing as a critical modulator of mutagenesis, with distinct DNA repair pathways and exogenous agents exhibiting replication timing-specific effects on genomic instability. Our systematic bioinformatics approach identifies new DNA repair genes and mutagens that exhibit differential activity during the S phase. These findings pave the way for further investigation of factors that contribute to genome instability during cancer transformation. Full article

This study aimed to investigate the potential mechanisms of action of total alkaloids from Portulaca oleracea L. (POL) on ulcerative colitis (UC) using a network pharmacology approach. Network pharmacology analysis identified two bioactive alkaloids within POL as primary anti-UC constituents, targeting 16 core therapeutic proteins and 113 UC-associated signaling pathways. To further explore the therapeutic effects, in vitro cell assays and in vivo animal experiments were conducted. In vitro, high concentrations of Portulaca oleracea total alkaloids (POAs) demonstrated dose-dependent cytotoxicity, significantly reducing Caco-2 cell viability and impairing migration. In a murine model of UC, disease induction led to substantial weight loss, elevated disease activity index (DAI) scores, colon shortening, and severe colonic tissue damage compared to controls. Furthermore, the UC group displayed significantly upregulated serum levels of pro-inflammatory cytokines, TNF-α and IL-1β, as well as increased protein and mRNA expression of TLR4 and NF-κB in colon tissues. Crucially, POAs treatment effectively ameliorated UC symptoms in mice, significantly reducing DAI scores, mitigating colon shortening, and markedly suppressing TLR4/NF-κB pathway activation. These findings strongly suggest that the therapeutic effects of POAs in UC are, at least in part, mediated by the inhibition of the TLR4/NF-κB signaling pathway, leading to a reduction in colonic inflammation. Full article