Search Results (383)

Tobacco use disorder remains a leading cause of preventable mortality, with nicotine playing a central role in the development and maintenance of dependence, mainly through its action on α4β2 nicotinic acetylcholine receptors (nAChRs). Smoking cessation treatments must address both physiological withdrawal and the affective disturbances (such as anxiety, irritability, and mood lability) which often facilitate relapses. This review compares two pharmacotherapies used in smoking cessation, varenicline and cytisinicline (cytisine), with particular focus on their impact on emotional regulation, psychological symptoms, and neuropsychiatric safety. Varenicline, a high-affinity partial agonist at α4β2 nAChRs, has demonstrated superior efficacy in maintaining abstinence and is well-supported by robust clinical data, including in psychiatric populations. However, its use may be limited by adverse effects such as nausea and sleep disorders. Cytisinicline, a structurally similar but less potent partial agonist, has recently gained renewed interest due to its lower cost, favorable tolerability profile, and comparable effectiveness in the general population. Although less extensively studied in patients with serious mental illness, preliminary data suggest cytisinicline may offer a better side effect profile, particularly regarding sleep disturbances and emotional reactivity. Both agents appear to ameliorate withdrawal-related affective symptoms without significantly increasing psychiatric risk. Ultimately, pharmacotherapy choice should be guided by individual clinical features, mental health status, treatment tolerability, and resource availability. Further research is needed to establish cytisinicline’s efficacy and safety across diverse clinical contexts, particularly among individuals with severe psychiatric comorbidities. Full article

Acute lymphoblastic leukemia (ALL) is the most common cancer affecting children, making up about 80% of all acute leukemia cases in the pediatric population. While treatment with L-asparaginase (ASNase) has greatly improved survival rates, its bacterial origin often causes immune reactions in some patients, which can reduce how well the therapy works. To overcome this challenge, previous in silico studies designed a humanized chimeric ASNase by swapping out the predicted immunogenic parts of the bacterial enzyme with similar, less immunogenic segments from the human version—while keeping the enzyme’s active site intact. In this study, the chimeric L-asparaginase designed was successfully cloned, expressed, and purified using the Escherichia coli Rosetta strain. The production conditions (37 °C, 0.01 mM IPTG, 2–4 h) were optimized, and we purified the enzyme in a single step with nickel-affinity chromatography. The enzyme’s activity was confirmed in vitro, showing that it is possible to produce a functional humanized variant in a bacterial system. These results lay important groundwork for future research to assess the immune response and therapeutic potential of this novel chimeric enzyme. Full article

Stink bugs are widespread agricultural pests that damage crops and reduce yield. Their impact is influenced by host plant selection and interactions with natural enemies, particularly egg parasitoids. Understanding these relationships is crucial for improving biological control strategies. This paper investigates the seasonal host plant use and parasitism of Halyomorpha halys, Palomena prasina, and Pentatoma rufipes in South Tyrol, Italy. Over two years, we conducted field surveys at 27 sites, recording stink bug presence across 85 plant species and analyzing egg parasitism rates. Results show that stink bugs exhibit distinct host plant preferences, with H. halys utilizing the broadest range of host plants while P. prasina and P. rufipes showed stronger affinities for specific families such as Sapindaceae and Rosaceae. Parasitism rates varied across species and plant families: Trissolcus japonicus predominantly parasitized H. halys while T. cultratus and two Telenomus species targeted P. rufipes and P. prasina, respectively. Spatial–temporal features and host plant associations significantly influenced species distributions and parasitoid occurrence. These findings emphasize the role of plant–insect interactions in shaping pest and parasitoid dynamics. Integrating plant diversity into pest management strategies could enhance parasitoid effectiveness and reduce stink bug populations, contributing to more sustainable agricultural practices. Full article

Pine wilt disease, a devastating disease severely impacting pine ecosystems, is caused by the pinewood nematode Bursaphelenchus xylophilus (Steiner & Bührer, 1934) Nickle, 1970 (Nematoda: Parasitaphelenchidae). Controlling B. xylophilus is crucial for preventing and managing pine wilt disease. Recently discovered novel nematocidal lectins could provide more advantageous materials for utilizing genetically engineered bacteria to control this pathogen. Therefore, this study focuses on identifying novel nematocidal toxins within B. xylophilus lectins. Overall, we obtained twenty-one galectin, one L-type lectin (LTL), and three chitin-binding domain (CBD) genes by screening the B. xylophilus genome database; these genes were successfully expressed proteins. The bioassay results indicated that Bxgalectin2, Bxgalectin3, Bxgalectin4, Bxgalectin9, and BxLTL1 induced mortality rates exceeding 50% in B. xylophilus. Notably, Bxgalectin4 showed the strongest nematocidal activity, causing 88% mortality in the treated nematode population. The enzyme-linked immunosorbent assays further demonstrated that Bxgalectin3 (K_d = 8.992 nM) and Bxgalectin4 (K_d = 9.634 nM) had a higher binding affinity to GPI-anchored proteins from B. xylophilus. Additionally, Bxgalectin2 (K_d = 16.50 nM), Bxgalectin9 (K_d = 16.48 nM), and BxLTL1 (K_d = 24.34 nM) can bind to the GPI-anchored protein. This study reports, for the first time, that lectins endogenous to B. xylophilus exhibit nematocidal activity against their own species. These findings open up the possibility of using nematode lectins as potent control agents in the biological control of B. xylophilus. Full article

The development of new cell separation technologies has continued as the demand for sorted cell populations for molecular testing increases. The goal is to increase through-put potential and reduce the manual handling of samples required whilst ensuring that cells are sorted efficiently with high purity. Herein, we review two affinity-based methods utilising magnetic beads to isolate cells: one is currently used within a clinical laboratory as standard of care and the other is a newly developed larger platform using the same principle. Cells were sorted simultaneously on both platforms and assessments were made of the purity, cell recovery, and hands-on time, indicating that the new larger platform is sufficient for use in a clinical laboratory as it not only increased cell sorting capacity and reduced manual processing but was also able to isolate cells with sufficient purity levels for downstream molecular testing. Full article

Chronic pain affects a significant portion of the population, with fewer than 30% achieving adequate relief from existing treatments. This study describes the humanization methodology and characterization of an effective non-opioid single-chain fragment variable (scFv) biologic that reverses pain-related behaviors, in this case by targeting P2X4. After nerve injury, ATP release activates/upregulates P2X4 receptors (P2X4R) sequestered in late endosomes, triggering a cascade of chronic pain-related events. Nine humanized scFv (hscFv) variants targeting a specific extracellular 13-amino-acid peptide fragment of human P2X4R were generated via CDR grafting. ELISA analysis revealed nanomolar binding affinities, with most humanized molecules exhibiting comparable or superior affinity compared to the original murine antibody. Octet measurements confirmed that the lead, HC3-LC3, exhibited nanomolar binding kinetics (KD = 2.5 × 10⁻⁹ M). In vivo functional validation with P2X4R hscFv reversed nerve injury-induced chronic pain-related behaviors with a single dose (0.4 mg/kg, intraperitoneal) within two weeks. The return to naïve baseline remained durably reduced > 100 days. In independent confirmation, the spared nerve injury (SNI) model was similarly reduced. This constitutes an original method whereby durable reversals of chronic nerve injury pain, anxiety and depression measures are accomplished. Full article

Raspberry (Rubus idaeus L.) is a high-value horticultural crop recognized for its significant economic importance and exceptional nutritional profile. We analyzed 76 raspberry accessions (wild and cultivar) using simple sequence repeat (SSR) and sequence-related amplified polymorphism (SRAP) markers, and we established a standardized SRAP system for this species. Genetic similarity differed markedly between markers: SSR values spanned 0.47–0.98 (mean = 0.73), compared to the narrower range of 0.52–0.97 (mean = 0.75) for SRAP. Cultivar accessions exhibited higher intra-group homogeneity than wild accessions, and northeastern wild accessions showed more stable similarity metrics than Guizhou wild accessions. In hierarchical clustering, the resolution varied depending on the labeling marker. The cluster analysis by SSR markers identified two main clusters and further partitioned them into three clusters. In contrast, the SRAP system revealed two primary clusters, which subsequently diverged into five subclusters. SSR markers effectively captured population-level differentiation, whereas SRAP markers enabled precise discrimination of cultivars and ecotypes through non-coding region polymorphisms. Phylogenetic analyses confirmed closer genetic affinity between northeastern wild and cultivated accessions, which diverged significantly from Guizhou. This dual-marker approach revealed complementary information: SSR markers were used to survey genome-wide diversity, while SRAP markers were used to detect structural variations. Their integrated application enhances germplasm characterization efficiency and provides practical strategies for raspberry conservation and molecular breeding. Full article

The Affinity for Technology Interaction (ATI) scale has been widely used to assess the tendency to engage in technology. To enhance the scale’s applicability and facilitate cross-cultural research, it is essential to provide translations of the scale. A Chinese translation is still missing. Additionally, a validation is necessary as culture can affect the psychometrics of questionnaires, bearing the danger of applying inadequate measures. The aims of the present study are therefore providing a Chinese translation of the ATI scale and presenting non-parametric and parametric psychometric analyses of the translated version to examine the underlying factor structure. In contrast to the original scale, analyses of the Chinese version suggest a two-dimensional structure with one dimension describing a passive interest in technology and another describing an active engagement with technology. The findings enable researchers to use the scale in Chinese-speaking populations and thereby advancing the understanding of human-technology interaction across different cultures. Full article

This study employs molecular dynamics simulations to investigate counterion effects (Li⁺, Na⁺, K⁺) on the interfacial aggregation of mixed short-chain fluorocarbon, Perfluorohexanoic acid (PFH_XA), and Sodium dodecyl sulfate (SDS) surfactants. Motivated by the need for greener surfactant alternatives and a fundamental understanding of molecular interactions governing their behavior, we demonstrate that counterion hydration radius critically modulates system organization. K⁺ ions induce superior monolayer condensation and interfacial performance compared to Li⁺ and Na⁺ counterparts, as evidenced by threefold analysis: (1) RMSD/MSD-confirmed equilibrium attainment ensures data reliability; (2) 1D/2D density profiles and surface tension measurements reveal K⁺-enhanced packing density (lower solvent-accessible surface area versus Na⁺ and Li⁺ systems); (3) Electrostatic potential analysis identifies synergistic complementarity between SDS’s hydrophobic stabilization via dodecyl chain interactions and PFH_XA’s charge uniformity, optimizing molecular-level charge screening. Radial distribution function analysis demonstrates K⁺’s stronger affinity for SDS head groups, with preferential sulfate coordination reducing surfactant-water hydration interactions. This behavior correlates with hydrogen-bond population reduction, attributed to SDS groups functioning as multidentate ligands—their tetrahedral oxygen arrangement facilitates cooperative hydrogen-bond networks, while counterion-specific charge screening competitively modulates bond formation. The resultant interfacial restructuring enables ordered molecular arrangements with lower system curvature than those observed in Li⁺ and Na⁺-containing systems. These findings elucidate counterion-mediated interfacial modulation mechanisms and establish K⁺ as an optimal candidate for enhancing PFH_XA/SDS mixture performance through hydration-radius screening. The work provides molecular-level guidelines for designing eco-friendly surfactant systems with tailored interfacial properties. Full article

The COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evoked a worldwide pandemic. Even though vaccines have been developed on an enormous scale, but due to regular mutations in the viral gene and the emergence of new strains could pose a more significant problem for the population. Therefore, new treatments are always necessary to combat future pandemics. Utilizing an antiviral peptide as a model biomolecule, we trained a generative deep learning algorithm on a database of known antiviral peptides to design novel peptide sequences with antiviral activity. Using artificial intelligence (AI), specifically variational autoencoders (VAE) and Wasserstein autoencoders (WAE), we were able to generate a latent space plot that can be surveyed for peptides with known properties and interpolated across a predictive vector between two defined points to identify novel peptides that exhibit dose-responsive antiviral activity. Two hundred peptide sequences were generated from the trained latent space and the top peptides were subjected to a molecular docking study. The docking analysis revealed that the top four peptides (MSK-1, MSK-2, MSK-3, and MSK-4) exhibited the strongest binding affinity, with docking scores of −106.4, −126.2, −125.7, and −127.8, respectively. Molecular dynamics simulations lasting 500 ns were performed to assess their stability and binding interactions. Further analyses, including MMGBSA, RMSD, RMSF, and hydrogen bond analysis, confirmed the stability and strong binding interactions of the peptide–protein complexes, suggesting that MSK-4 is a promising therapeutic agent for further development. We believe that the peptides generated through AI and MD simulations in the current study could be potential inhibitors in natural systems that can be utilized in designing therapeutic strategies against SARS-CoV-2. Full article

The high variability of human leukocyte antigen (HLA) genes results in each molecule having distinct antigenic peptide binding capacities, potentially influencing the immune response to SARS-CoV-2. This study aimed to investigate associations between HLA class I (A, B) and class II (DRB1) polymorphisms and COVID-19 severity in a South Brazilian population, and to evaluate the binding affinity of alleles to viral peptides. A cross-sectional study included 503 unvaccinated patients with RT-qPCR-confirmed COVID-19: 145 non-severe, 129 severe, and 229 critical. HLA typing was performed using PCR-SSO and Luminex™ technology. The DRB1*11 allelic group was significantly associated with protection against severe and critical cases, while DRB1*15 was associated with increased risk; both remained significant after Bonferroni correction. Other allelic groups were associated with disease outcomes but lost significance after correction: B*49 and B*08 (risk); and B*37, B*50, and A*03 (protection). In silico analysis revealed that the DRB1*15 allele group showed a higher proportion of strong binders, mostly from non-structural proteins, while DRB1*11:01 binders, though fewer in number, were concentrated in the M protein. These results suggest functional differences in antigen presentation and reinforce the relevance of class II HLA, particularly DRB1, in modulating COVID-19 severity. Full article

Background: Yiqi Zengmian (YQZM) functions as an immunopotentiator by enhancing both cellular and humoral immunity. However, its pharmacodynamic active constituents, particularly those absorbed into the bloodstream, and mechanism of action remain unclear. This study aimed to investigate the immunopotentiating effects and mechanisms of YQZM in mice immunized with the BBIBP-CorV (Beijing Bio-Institute of Biological Products Coronavirus Vaccine). Methods: Serum pharmacochemistry and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) were employed to identify bioavailable components of YQZM. The mice received the BBIBP-CorV twice on days 1 and 14, while YQZM was orally administered for 28 days. Neutralization assays and ELISA quantified antigen-specific antibodies (abs), flow cytometry (FC) and intracellular cytokine staining (ICS) were used to assess immune cell populations and their cytokines, and an enzyme-linked immunospot assay (ELISpot) quantified memory T and B cells (MBs and MTs). To identify underlying mechanisms, network pharmacology, RNA sequencing (RNA-Seq), molecular docking, Western blotting (WB), and quantitative reverse transcription PCR (RT-qPCR) were performed. Results: YQZM significantly enhanced antigen-specific antibody titers, immune cell proportions, cytokine levels, and memory lymphocyte functions. UPLC-MS/MS analysis identified 31 bioactive compounds in YQZM. KEGG enrichment analysis based on RNA-Seq and network pharmacology implicated the TLR-JAK-STAT signaling pathway in YQZM’s immune-enhancing effects. WB and RT-PCR validated that YQZM upregulated the expression of critical nodes in the TLR-JAK-STAT signaling pathway. Furthermore, molecular docking indicated that YQZM’s primary active components exhibited strong binding affinity for critical proteins. Conclusions: YQZM effectively enhances vaccine-induced innate and adaptive immunity via a multi-component, multi-target mechanism, among which the TLR-JAK-STAT signaling pathway is a validated molecular target. Full article

Ecological determinants of avian population dynamics are essential for effective wildlife management and conservation. Black and grey francolins are classified as being of least concern by the IUCN and are an ecologically significant bird in the northern regions of Pakistan. Although habitat degradation and overhunting have adversely affected their populations, research on the population structure and habitat preferences of the Totali Game Reserve, Buner District, Pakistan, remains limited. The present study applied distance sampling via the line transect method to estimate population densities and the quadrat method to assess vegetation characteristics across three distinct habitats. A statistical analysis revealed significant variations in densities across the three habitat types—agricultural lands, agroforests, and pasturelands—with both species exhibiting distinct preferences for pastureland ecosystems. Seasonal trends indicated that autumn represented the peak period for the population, driven by post-breeding surges and optimal habitat conditions. Moreover, both species demonstrated a strong affinity for habitats dominated by specific plant species, including hopbush, raspberry, barberry, and blackberry, which provide a critical resource for food, foraging, nesting, and shelter. These findings highlight the ecological importance of pasturelands and specific vegetation types for supporting the survival of these species. Furthermore, conservation efforts should prioritize the preservation and restoration of pastureland ecosystems and incorporate rigorous monitoring programs to guide adaptive management strategies aimed at mitigating population declines. Full article

Background/Objectives: The Carpathian Basin is a genetically and culturally diverse region shaped by complex historical migrations and various ethnic groups. While studies based on Y-chromosomal and mitochondrial DNA have provided valuable insights into the genetic diversity of these populations, genome-wide autosomal SNP data remain underutilized in understanding the genetic structure of these groups. This study presents the first genome-wide autosomal SNP-based analysis of key Hungarian-speaking ethnic groups in the region, focusing on admixture patterns and the extent of preserved historical genetic components. Methods: We analyzed genome-wide autosomal SNP data from 597 individuals representing several ethnic groups in the Carpathian Basin. Standard population genetic methods were applied to assess genetic structure, admixture and differentiation, with comparisons to broader European reference populations. Results: Most ethnic groups displayed genetic affinities with Eastern European populations, consistent with historical and geographical proximity. The Swabian group, of German descent, exhibited a distinct Western European genetic component, likely due to historical isolation. Transylvanian populations appeared relatively homogeneous, indicating a shared ancestral background. In contrast, Csangos showed distinct sub-clusters, suggesting population isolation and distinct histories. Overall, genetic homogeneity characterizes the region, though certain isolated groups retain distinct ancestral signatures. Conclusions: Autosomal SNP analysis revealed mild overall genetic structuring among Carpathian Basin ethnic groups. However, historical isolation has preserved unique genetic components in specific groups, highlighting the value of genome-wide data in uncovering fine-scale population structure. These findings contribute to a deeper understanding of regional genetic diversity, which has implications for both population history and health-related genetic research. Full article

The smooth snake (Coronella austriaca) has a wide but fragmented distribution across the Western Palearctic, with limited records in Kazakhstan. This study aims to provide an updated distribution map and to explore the phylogenetic affinities of C. austriaca in Kazakhstan. The species had not been documented for over 60 years until its recent rediscovery in the region. Field surveys conducted between 2019 and 2024 in the West Kazakhstan and Aktobe regions have yielded novel records, including the southernmost observation in the Mugodzhar mountain range. Mitochondrial DNA analysis confirmed that the Kazakh populations belong to the Eastern lineage, sharing haplotypes with specimens from the northwestern Caucasus and Crimea. Habitat assessment revealed that the species’ distribution is restricted to open habitats of petrophytic and calciphyte steppe communities on chalks and rocky steppes. Of particular interest is that 70% of the observed individuals exhibited patternless coloration, suggesting the potential for regional morphological variation. These findings offer the first evidence for the phylogenetic affiliation of the smooth snake in Kazakhstan and reflect its rarity in the country, highlighting the need for local conservation efforts, including habitat protection and population monitoring. Full article