Distinct Affinities Research Articles

DEREGulated pathways: unraveling the role of epiregulin in skin, kidney, and lung fibrosis.

The epidermal growth factor receptor (EGFR) signaling pathway is an evolutionary conserved mechanism to control cell behavior during tissue development and homeostasis. Deregulation of this pathway has been associated with abnormal cell behavior, including hyperproliferation, senescence, and an inflammatory cell phenotype, thereby contributing to pathologies across a variety of organs, including the kidneys, skin, and lungs. To date, there are seven distinct EGFR ligands described. Although binding of these ligands to the receptor is cell type-specific and spatio-temporally controlled with distinct affinities and kinetics, epiregulin (EREG) stands out as a long-acting EGFR ligand that emerges under pathological conditions, particularly in tissue fibrosis. Although EREG has been extensively studied in cancer, its contribution to the maladaptive remodeling of tissue is elusive. The aim of this review is to highlight the role of EREG in skin, kidney, and lung fibrosis and to discuss opportunities for therapeutic intervention.

Response of beetle communities and functional groups to changes in structural and compositional biodiversity of cork oak forest and agricultural landscapes in the northwest of Morocco

The geographical location of Morocco provides an exceptionally biodiverse environment. This study aims to fill knowledge gaps regarding the biodiversity of beetles in the northwest of Morocco. We explored cork oak forests Quercus suber L. in Larache and the Gharb plain over two consecutive years (2021 and 2022) and performed an inventory of beetles. We captured and identified 5,405 specimens belonging to 246 species and 39 families. Three trends were evident in this study: 1) the most diverse family was Tenebrionidae, a family with a distinct affinity to Mediterranean climates; 2) we found few sapro–xylophagous, xylophagous, and coprophagous beetles in the study; and 3) our findings indicate that the Larache cork oak forest plays a vital ecological role in the area as beetle biodiversity and functional groups were much higher in the forested sectors than in nearby agricultural areas.

An Ion Pair Receptor for Selective Solid-Liquid Extraction of LiCl.

We have synthesized a new ion pair receptor (2) consisting of a cone-calix[4]arene bearing a combination of ethyl esters and ethers as a cation binding site and a calix[4]pyrrole subunit acting as an anion binding site. Ion pair receptor 2 complexes LiCl, NaCl, and CsCl among alkali metal chloride salts with distinct complexation modes and affinities in 10 % methanol-d4 in chloroform-d. For instance, relatively small Li+ and Na+ cations are bound to the oxygen atoms of the functionalized calix[4]arene lower rim with Cl- being hydrogen bonded to the calix[4]pyrrole NHs while the larger Cs+ cation is bound to the cone-shaped calix[4]pyrrole cavity via a π-cation interaction. By contrast, in the co-presence of all MCl salts (M=Li, Na, K, Rb, and Cs), receptor 2 binds LiCl with complete selectivity. Besides, receptor 2 is capable of extracting LiCl selectively into a chloroform or a dichloromethane organic phase from its solid source containing all other MCl salts.

Clinicopathological Characteristics of Extranodal Marginal Zone Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT-Lymphoma) of the Intestine: A Single Center Analysis.

Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT-lymphoma) is an indolent B-cell lymphoma with a distinct affinity for mucosal structures. Most commonly arising in the stomach, only roughly 2% of MALT-lymphomas occur in the colon or the intestine. In view of this, we have retrospectively assessed all patients with MALT-lymphoma involving the intestine for clinicopathological characteristics. Data of all patients with MALT-lymphoma and intestinal involvement (i.e. both primary and secondary), treated and followed at the Medical University of Vienna between 1999 and 2021 were retrospectively collected from hospital records and analyzed. Differences in baseline and therapy characteristics, as well as survival between primary and secondary, and between intestinal and gastric MALT-lymphoma (as the most common subgroup of patients) were investigated. In total, 42 patients were identified; 24/484 (5%) were classified as primary and 18 (3.7%) as secondary intestinal MALT-lymphomas. The most common primary intestinal location was the colon (10/24) and the most frequent primary site in the 18 cases with secondary intestinal MALT-lymphomas was the stomach (14/18). A total of 28/42 (66.7%) patients presented with LUGANO stage I, 7/42 (16.7%) with stage II/IIE and 7/42 (16.7%) with stage IV disease. Translocation t (11; 18) (q21; q21) was positive in 47% of patients with secondary and 25% of primary intestinal MALT-lymphomas. Median OS in for intestinal MALT-lymphoma was 301months (95% CI n.a.) with 89.1% alive at 5years and 77.2% alive at 10years. Median PFS in the entire cohort was 50.4months (95% CI 38.4-62.4months), with an overall response rate and disease control rate of 73% and 97.3%, respectively. No difference in OS and PFS between primary and secondary intestinal, as well as between intestinal and gastric MALT-lymphoma was detected. Our data suggest that dissemination within the GI tract does not seem to be an adverse prognostic feature and highlights the preferred use of the Lugano staging system in such patients, which also summarizes multiple lesions within the GI-tract as Stage I.

Novel Pyrimidine Tethered Benzamide Derivatives as Potential Anticancer Agents: Synthesis, Characterization, Molecular Docking and In vitro Cytotoxicity Evaluation

Current research work presents the synthesis, characterization, molecular docking study and in vitro cytotoxicity evaluation of novel pyrimidine-tethered benzamide derivatives as potential anticancer agents. The synthesis involved multi-steps procedure, including the synthesis of various chalcones (3a-t) with corresponding ketones (1 and 2) and substituted aldehydes (a-j), followed by pyrimidine amines (5a-t) with condensation of chalcones and guanidine and finally pyrimidinyl benzamide derivatives (8a-t) from compounds 5a-t coupling with acid chloride (7) using DIBAL-H. Synthesized compounds characterized by NMR spectroscopy and HRMS. The molecular docking studies were conducted against EGFR (6LUD) and CDK-4 (7SJ3) receptors, revealing distinct binding affinities influenced by substituent groups. Additionally, the cytotoxicity of the synthesized compounds was evaluated using the MTT assay against various cancer cell lines, including A-549 (non-small cell lung cancer), HCT-116 (colorectal cancer), PANC-1 (pancreatic cancer) and HaLa (cervical cancer), along with one normal human embryonic kidney cell line (HEK-293). Among the synthesized compounds, derivatives 8f and 8j exhibited the best anticancer activity against A-549 cells, compounds 8j and 8e showed exceptional potency against HCT-116 cells, compounds 8f and 8j demonstrated high efficacy against PANC-1 cells and compound 8h displayed remarkable potency against HaLa cells. The findings highlight the potential of these pyrimidinyl benzamide derivatives as targeted anticancer agents.

A structural analysis of the splice-specific functional impact of the pathogenic familial hemiplegic migraine type 1 S218L mutation on Cav2.1 P/Q-type channel gating

P/Q-type (Cav2.1) calcium channels mediate Ca2+ influx essential for neuronal excitability and synaptic transmission. The CACNA1A gene, encoding the Cav2.1 pore forming subunit, is highly expressed throughout the mammalian central nervous system. Alternative splicing of Cav2.1 pre-mRNA generates diverse channel isoforms with distinct biophysical properties and drug affinities, which are differentially expressed in nerve tissues. Splicing variants can also affect channel function under pathological conditions although their phenotypic implication concerning inherited neurological disorders linked to CACNA1A mutations remains unknown. Here, we quantified the expression of Cav2.1 exon 24 (e24) spliced transcripts in human nervous system samples, finding different levels of expression within discrete regions. The corresponding Cav2.1 variants, differing by the presence (+) or absence (Δ) of Ser-Ser-Thr-Arg residues (SSTR) in the domain III S3-S4 linker, were functionally characterized using patch clamp recordings. Further, the + /ΔSSTR isoforms were used to demonstrate the differential impact of the Familial Hemiplegic Migraine Type 1 (FHM-1) S218L mutation, located in the domain I S4-S5 linker, on the molecular structure and electrophysiological properties of Cav2.1 isoforms. S218L has a prominent effect on the voltage-dependence of activation of +SSTR channels when compared to ΔSSTR, indicating a differential effect of the mutation depending on splice-variant context. Structural modeling based upon Cav2.1 cryo-EM data provided further insight reflecting independent contributions of amino acids in distant regions of the channel on gating properties. Our modelling indicates that by increasing hydrophobicity the Leu218 mutation contributes to stabilizing a structural conformation in which the domain I S4-S5 linker is oriented alongside the inner plasma membrane, similar to that occurring when S4 is translocated upon activation.The SSTR insertion appears to exert an influence in the local electric field of domain III due to an change in the distribution of positively charged regions surrounding the voltage sensing domain, which we hypothesize impacts its movement during the transition to the open state. In summary, we reveal molecular changes correlated with distinct functional effects provoked by S218L FHM-1 mutation in hCav2.1 splice isoforms whose differential expression could impact the manifestation of the neurological disorder.

A pH-responsive phase-transition bi-affinity nanopolymer-assisted exosome metabolomics for early screening of osteoarthritis

Exosomes, emerging as ideal non-invasive biomarkers for disease diagnosis and monitoring, have seldom been explored based on metabolite levels. In this study, we designed and synthesized a pH-responsive phase-transition bifunctional affinity nanopolymer (pH-BiAN) that could efficiently and homogeneously separate exosomes from urine. Specifically, poly-4-vinylpyridine (P4VP) was chosen as the pH-responsive polymer and simultaneously modified with two exosome-affinity components CD63 aptamer and distearoyl phosphoethanolamine (DSPE) through a one-step amide reaction at room temperature. By utilizing two distinct but synergistic affinity mechanisms—the immune affinity between CD63 aptamer and exosomal CD63 proteins, and hydrophobic interactions between the DSPE and the exosomal lipids—pH-BiAN can enable efficient and specific exosome separation. Moreover, during the urine exosome capture procedure, the pH-BiAN outperforms conventional solid exosome separation materials by remaining soluble in the urine sample, significantly enhancing mass transfer and contact efficiency. After exosome capture, pH-BiAN can quickly aggregate and convert to solid upon pH adjustment, allowing for easy centrifugation separation. Afterwards, multiple machine learning models were established by combining liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) untargeted metabolomics for isolated exosomes, and the clinical accuracy of the training and test sets was more than 0.919, which could well distinguish early osteoarthritis patients from healthy people.

Phytochemical Associes of Fungal Endophytes in Nigeria Riverine Mangrove Ecosystem

The interaction between endophytic fungi and phytochemicals in the dominant mangroves (Rhizophora mangle, Lacugularia racemosa, and Avicennia africana) of the Iko River Estuary in Nigeria was investigated. Standard analytical procedures were employed to measure antioxidant levels, while endophytic fungi were isolated, morphologically characterized, and identified using culture-dependent methods. The study identified various bioactive compounds, including alkaloids, saponins, tannins/phenols, flavonoids, deoxy-sugars, cardiac glycosides, and steroids, with their concentrations varying depending on the mangrove species and plant parts. Alkaloids were present in all mangrove samples, with particularly high concentrations in the leaves of white (5%) and red (4.2%) mangroves. Principal Component Analysis (PCA) was used to analyze the interaction between the endophytic fungi and phytochemicals, revealing a distinct affinity of certain fungal species for specific antioxidants in the mangroves. Fungal species such as Phoma sp., Rhizopus arrhizus, Aspergillus niger, and others exhibited a negative relationship with tannins, flavonoids, deoxysugars, and cardiac glycosides, but a positive affinity for saponins, alkaloids, and steroids. Conversely, Candida pseudotropicalis, Fusarium oxysporum, P. italicum, and others showed a positive affinity for tannins, flavonoids, cardiac glycosides, and deoxysugars, but a negative affinity for alkaloids, saponins, and steroids. Notably, Absidia sp. was the only frequently isolated species with a strong correlation (r value ≥75 at a 95% confidence limit) with deoxy-sugars, while Aspergillus niger, Aspergillus terreus, and Absidia sp. demonstrated significant relationships with alkaloids, saponins, and steroids. These phytochemicals, which serve as precursors to antioxidants with promising biotechnological applications, likely play a crucial role in determining the association of endophytic fungi with deltaic mangroves in Nigeria.

Interactions between nanobiochar and arsenic: Effects of biochar aging methods on arsenic binding capacity and mechanisms

Nano-biochar (nanoBC), produced from biochar aging, exhibits significant molecular heterogeneity that may affect the fate and toxicity of co-occurring pollutants. However, the interaction between nanoBC and arsenic (As) remains unclear. Herein, we simulated biochar aging through water erosion, photoaging, and thermal chemical decomposition to generate three types of nanoBC (nUBC, nPBC, and nHBC). We then investigated their distinct binding affinities and interaction mechanisms with arsenite (AsIII) and arsenate (AsV). Complementary analysis using optical spectrophotometer and high-resolution mass spectrometry revealed significant differences in properties and chemical compositions among the three nanoBCs at a size of 100 nm. Specifically, nHBC had higher yield, nPBC had higher aromaticity, and nUBC had more intricate molecular compositions and larger molecular weights. Binding experiments showed that nHBC and nUBC exhibited the highest conditional distribution coefficient (KD) for AsIII and AsV, respectively. In nHBC, a higher proportion of humic-like fluorescent component C3 enhanced its affinity for AsIII, attributed to lignin-like molecules with CHONS formulas where thiol acted as active binding sites. In contrast, the robust AsV binding capacity of nUBC stemmed from its richness in humic-like fluorescent component C1 and tryptophan-like fluorescent component C2. This is facilitated by lipid-like molecules and CHO formulas in C1 and aliphatic/peptide-like molecules and CHON formulas in C2, which provided oxygenic and nitrogen-containing groups for binding. All nanoBC had a significantly higher binding affinity for As than bulk BC. These findings provide a deeper understanding of As-nanoBC binding mechanisms at the molecular level, facilitating more accurate prediction of As fate in biochar-amended soil and associated ecosystem risks.

Cisuralian plant fossils from Khenifra (Central Morocco): Palaeoenvironmental and palaeobiogeographical reconstructions

This study focuses on newly collected plant fossils from the Cisuralian successions of the Khenifra Basin in Central Morocco, revealing a diverse assemblage dominated by conifers, pteridosperms, and sphenophytes. The assemblage includes eleven taxa of vegetative and reproductive organs preserved as compressions and impressions. Two pteridosperm species taxa (Neurodontopteris auriculata, Odontopteris subcrenulata) are recorded for the first time from Central Morocco, whereas other taxa are known from the early Permian deposits of Bou Achouch and Tiddas basins. Contrary to previous interpretations, the flora is does not exhibit a mixed character, but instead exhibits a distinct Euramerican affinity, despite the absence of the widespread callipterids Autunia conferta and A. naumannii. These similarities between this flora and coeval Euramerican floras highlight the significant biogeographical connections across Pangea during the Cisuralian. The plant fossil assemblage is dominated by meso- to xerophilous species adapted to drought, with rare hygrophilous elements adapted to humid habitats, reflecting a heterogeneous landscape with various vegetation types.

The costs and benefits of symbiotic interactions: variable effects of rhizobia and arbuscular mycorrhizae on Vigna radiata accessions

BackgroundThe symbiosis among plants, rhizobia, and arbuscular mycorrhizal fungi (AMF) is one of the most well-known symbiotic relationships in nature. However, it is still unclear how bilateral/tripartite symbiosis works under resource-limited conditions and the diverse genetic backgrounds of the host.ResultsUsing a full factorial design, we manipulated mungbean accessions/subspecies, rhizobia, and AMF to test their effects on each other. Rhizobia functions as a typical facilitator by increasing plant nitrogen content, plant weight, chlorophyll content, and AMF colonization. In contrast, AMF resulted in a tradeoff in plants (reducing biomass for phosphorus acquisition) and behaved as a competitor in reducing rhizobia fitness (nodule weight). Plant genotype did not have a significant effect on AMF fitness, but different mungbean accessions had distinct rhizobia affinities. In contrast to previous studies, the positive relationship between plant and rhizobia fitness was attenuated in the presence of AMF, with wild mungbean being more responsive to the beneficial effect of rhizobia and attenuation by AMF.ConclusionsWe showed that this complex tripartite relationship does not unconditionally benefit all parties. Moreover, rhizobia species and host genetic background affect the symbiotic relationship significantly. This study provides a new opportunity to re-evaluate the relationships between legume plants and their symbiotic partners.

Frontal sinus size in South African Later Stone Age Holocene Khoe-San.

Frontal size variation is comparatively poorly sampled among sub-Saharan African populations. This study assessed frontal sinus size in a sample of Khoe-San skeletal remains from South African Later Stone Age contexts. Volumes were determined from CT scans of 102 adult crania; individual sex could be estimated in 82 cases. Sinus volume is not sexually dimorphic in this sample. The lack of frontal sinus aplasia is concordant with the low incidences recorded for other sub-Saharan African and most other global populations save those that inhabit high latitudes. There is considerable variation in frontal sinus size among global populations, and the Khoe-San possess among the smallest. The Khoe-San have rather diminutive sinuses compared to sub-Saharan Bantu-speaking populations but resemble a northern African (Sudanese) population. Genetic studies indicate the earliest population divergence within Homo sapiens to have been between the Khoe-San and all other living groups, and that this likely occurred in Africa during the span of Marine Isotope Stages 8-6. There is scant information on frontal sinus development among Late Quaternary African fossils that are likely either closely related or attributable to Homo sapiens. Among these, the MIS 3 cranium from Hofmeyr, South Africa, exhibits distinct Khoe-San cranial affinities and despite its large size has a very small frontal sinus. This raises the possibility that the small frontal sinuses of the Holocene South African Khoe-San might be a feature retained from an earlier MIS 3 population.

Anti-tumor and anti-metastasis of water-soluble sulfated β-glucan derivatives from Saccharomyces cerevisiae

Traditional fungi β-glucan commonly possesses high molecular weight with poor water solubility, which remains significant challenge in the drug development and medical application. Water-soluble β-glucan with high molecular weight (dHSCG) of 560 kDa, low molecular weight (dLSCG) of 60 kDa, and sulfated derivative (SCGS) with a molecular weight of 146 kDa and sulfate degree at 2.04 were obtained through well-controlled degradation and sulfated modification from Saccharomyces cerevisiae in this study. The structural characteristics were confirmed as β-1,3/6-glucan by FT-IR and NMR spectroscopy. Carbohydrate microarrays and surface plasmon resonance revealed distinct and contrasting binding affinities between the natural β-glucans and sulfated derivatives. SCGS exhibited strong binding to FGF and VEGF, while natural β-glucan showed no response, suggesting its potential as a novel antitumor agent. Moreover, SCGS significantly inhibited the migration rate of the highly metastatic melanoma (B16F10) cells. The lung metastasis mouse model also demonstrated that SCGS significantly reduced and eliminated the nodules, achieving an inhibition rate of 86.7% in vivo, with a dramatic improvement in IFN-α, TNF-α, and IL-1β levels. Through analysis of protein content and distribution in lung tissues, the anti-tumor and anti-metastasis mechanism of SCGS involves the regulation of degrading enzymes to protect extracellular matrix (ECM), as well as the reduction of angiogenic factor release. These findings provide a foundation for exploring the potential of SCGS in the development of new anti-tumor and anti-metastasis drugs and open up a new field in cancer research.

Following the Evolutionary Paths of Dscam1 Proteins toward Highly Specific Homophilic Interactions.

Many adhesion proteins, evolutionarily related through gene duplication, exhibit distinct and precise interaction preferences and affinities crucial for cell patterning. Yet, the evolutionary paths by which these proteins acquire new specificities and prevent cross-interactions within their family members remain unknown. To bridge this gap, this study focuses on Drosophila Down syndrome cell adhesion molecule-1 (Dscam1) proteins, which are cell adhesion proteins that have undergone extensive gene duplication. Dscam1 evolved under strong selective pressure to achieve strict homophilic recognition, essential for neuronal self-avoidance and patterning. Through a combination of phylogenetic analyses, ancestral sequence reconstruction, and cell aggregation assays, we studied the evolutionary trajectory of Dscam1 exon 4 across various insect lineages. We demonstrated that recent Dscam1 duplications in the mosquito lineage bind with strict homophilic specificities without any cross-interactions. We found that ancestral and intermediate Dscam1 isoforms maintained their homophilic binding capabilities, with some intermediate isoforms also engaging in promiscuous interactions with other paralogs. Our results highlight the robust selective pressure for homophilic specificity integral to the Dscam1 function within the process of neuronal self-avoidance. Importantly, our study suggests that the path to achieving such selective specificity does not introduce disruptive mutations that prevent self-binding but includes evolutionary intermediates that demonstrate promiscuous heterophilic interactions. Overall, these results offer insights into evolutionary strategies that underlie adhesion protein interaction specificities.

Microcystis viridis NIES-102 Cyanobacteria Lectin (MVL) Interacts with SARS-CoV-2 Spike Protein Receptor Binding Domains (RBDs) via Protein-Protein Interaction.

The emergence of coronavirus disease 2019 (COVID-19) posed a major challenge to healthcare systems worldwide, especially as mutations in the culprit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) complicated the development of vaccines and antiviral drugs. Therefore, the search for natural products with broad anti-SARS-CoV-2 capabilities is an important option for the prevention and treatment of similar infectious diseases. Lectins, which are widely recognized as antiviral agents, could contribute to the development of anti-SARS-CoV-2 drugs. This study evaluated the binding affinity of six lectins (including the cyanobacterial lectin from Microcystis viridis NIES-102 (MVL), and Jacalin, a lectin from the breadfruit, Artocarpus altilis) to the receptor binding domain (RBD) of the spike protein on the original (wild) SARS-CoV-2 and three of its mutants: Alpha, Delta, and Omicron. MVL and Jacalin showed distinct binding affinity to the RBDs of the four SARS-CoV-2 strains. The remaining four lectins (DB1, ConA, PHA-M and CSL3) showed no such binding affinity. Although the glycan specificities of MVL and Jacalin were different, they showed the same affinity for the spike protein RBDs of the four SARS-CoV-2 strains, in the order of effectiveness Alpha > Delta > original > Omicron. The verification of glycan-specific inhibition revealed that both lectins bind to RBDs by glycan-specific recognition, but, in addition, MVL binds to RBDs through protein-protein interactions.

Deciphering TCR-pMHC Interactions in Human Memory T Cells: Biophysical Insights into SARS-CoV-2 Antigen Recognition

Abstract Precise antigen recognition by T cell receptors (TCRs) is key for initiating cellular immune responses. This study investigates the biophysical characteristics of TCR-antigen interactions, emphasizing 2-dimentioanl (2D) TCR affinity and catch bond dynamics in human memory T cell subsets, particularly in their response to specific SARS-CoV-2 epitopes. Utilizing DNA-barcoded pMHC tetramers, our research profiles TCRs interacting with selected SARS-CoV-2 epitopes, identifying antigen-specific memory T cells in lung tissue, peripheral blood mononuclear cells (PBMCs), and antigen-specific precursor T cells from the spleen. Through micropipette adhesion assays and biomembrane force probe, we quantified 2D TCR affinity and examined catch bond formation dynamics at the single-cell level. Our findings indicate a broader range of 2D TCR affinities in spleen precursor T cells compared to memory T cell subsets in tissue and blood. Notably, tissue-resident and circulating memory T cells exhibit distinct 2D TCR affinity and catch bond properties. The differential biophysical properties, particularly in 2D affinity and catch bond force lifespan, underscore the unique role of tissue-resident memory T cells, influencing memory formation and tissue-specific immune responses. This detailed characterization of TCR-pMHC interactions in human tissue-resident memory T cells contributes significantly to our understanding of memory generation during viral infections.

Differential Solvent DEEP-STD NMR and MD Simulations Enable the Determinants of the Molecular Recognition of Heparin Oligosaccharides by Antithrombin to Be Disentangled.

The interaction of heparin with antithrombin (AT) involves a specific sequence corresponding to the pentasaccharide GlcNAc/NS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA). Recent studies have revealed that two AGA*IA-containing hexasaccharides, which differ in the sulfation degree of the iduronic acid unit, exhibit similar binding to AT, albeit with different affinities. However, the lack of experimental data concerning the molecular contacts between these ligands and the amino acids within the protein-binding site prevents a detailed description of the complexes. Differential epitope mapping (DEEP)-STD NMR, in combination with MD simulations, enables the experimental observation and comparison of two heparin pentasaccharides interacting with AT, revealing slightly different bound orientations and distinct affinities of both glycans for AT. We demonstrate the effectiveness of the differential solvent DEEP-STD NMR approach in determining the presence of polar residues in the recognition sites of glycosaminoglycan-binding proteins.

Determining environmental drivers of global mud snail invasions using climate and hydroclimate models

Climate change and invasive species represent two intertwined global environmental challenges profoundly affecting freshwater ecosystems. This study uses Ecological Niche Modeling along with risk screening to delve into the preferences and potential distribution of Potamopyrgus antipodarum, an invasive species, in relation to climate zones and habitat types, shedding light on the critical importance of coastal wetlands and high soil organic carbon content in shaping habitat suitability. Our findings underscore that P. antipodarum exhibits a distinct affinity for cool temperate, moist climates, as well as temperate floodplain rivers, wetlands, and coastal areas. Notably, coastal wetlands, endowed with elevated soil organic carbon levels, emerged as pivotal habitats for this species. Projections indicated a significant expansion in North America, potentially extending into South America. Türkiye reveals an intriguing alignment between its habitat and the natural distribution areas of P. antipodarum, presenting potential for habitat contraction while still retaining a broader range compared to other regions. These potential expansions were predominantly driven by climate suitability, playing a pivotal role in the invasiveness of P. antipodarum, with anticipated future climate regimes exerting substantial influence on its dispersal capabilities.

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Oncogenic microRNA (miRNA), especially miRNA-21 upregulation in triple-negative breast cancer (TNBC), suggests a new class of therapeutic targets. In this study, we aimed to create GE11 peptide-conjugated small interfering RNA-loaded chitosan nanoparticles (GE11-siRNA-CSNPs) for the targeting of EGFR overexpressed TNBC and selectively inhibit miRNA-21 expression. A variety of in-silico and in vitro cellular and molecular studies were conducted to investigate the binding affinities of specific targets used as well as the anticancer efficacies and mechanisms of GE11-siRNA-CSNPs in TNBC cells. An in-silico assessment reveals a distinct binding affinity of miRNA-21 with siRNA as well as between the extracellular domain of EGFR and synthesized peptides. Notably, the in vitro results showed that GE11-siRNA-CSNPs were revealed to have better cytotoxicity against TNBC cells. It significantly inhibits miRNA-21 expression, cell migration, and colony formation. The results also indicated that GE11-siRNA-CSNPs impeded cell cycle progression. It induces cell death by reducing the expression of the antiapoptotic gene Bcl-2 and increasing the expression of the proapoptotic genes Bax, Caspase 3, and Caspase 9. Additionally, the docking analysis and immunoblot investigations verified that GE1-siRNA-CSNPs, which specifically target TNBC cells and suppress miRNA-21, can prevent the effects of miRNA-21 on the proliferation of TNBC cells via controlling EGFR and subsequently inhibiting the PI3K/AKT and ERK1/2 signaling axis. The GE11-siRNA-CSNPs design, which specifically targets TNBC cells, offers a novel approach for the treatment of breast cancer with improved effectiveness. This study suggests that GE11-siRNA-CSNPs could be a promising candidate for further assessment as an additional strategy in the treatment of TNBC.Graphical

Development of Optical Differential Sensing Based on Nanomaterials for Biological Analysis

The discrimination and recognition of biological targets, such as proteins, cells, and bacteria, are of utmost importance in various fields of biological research and production. These include areas like biological medicine, clinical diagnosis, and microbiology analysis. In order to efficiently and cost-effectively identify a specific target from a wide range of possibilities, researchers have developed a technique called differential sensing. Unlike traditional “lock-and-key” sensors that rely on specific interactions between receptors and analytes, differential sensing makes use of cross-reactive receptors. These sensors offer less specificity but can cross-react with a wide range of analytes to produce a large amount of data. Many pattern recognition strategies have been developed and have shown promising results in identifying complex analytes. To create advanced sensor arrays for higher analysis efficiency and larger recognizing range, various nanomaterials have been utilized as sensing probes. These nanomaterials possess distinct molecular affinities, optical/electrical properties, and biological compatibility, and are conveniently functionalized. In this review, our focus is on recently reported optical sensor arrays that utilize nanomaterials to discriminate bioanalytes, including proteins, cells, and bacteria.