Cytokines are pivotal mediators of intercellular communication in immunity and inflammation, exerting their effects through tightly regulated signaling cascades that shape both innate and adaptive responses. Among them, interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) represent key biomarkers that orchestrate distinct yet interconnected phases of the inflammatory process. This review synthesizes current evidence on the molecular mechanisms, functional roles, and clinical significance of these four cytokines. IL-1β and TNF-α act as early pro-inflammatory mediators, initiating vascular activation, leukocyte recruitment, and febrile responses. IL-6 sustains acute-phase reactions and bridges innate and adaptive immunity, while IFN-γ enhances antimicrobial defenses and antigen presentation, shaping T-cell polarization. Advances in detection methods—including ELISA, multiplex immunoassays, high-sensitivity biosensors, and IFN-γ release assays—have enabled precise quantification, improving diagnostic accuracy, disease monitoring, and therapeutic decision-making across a broad spectrum of autoimmune, infectious, cardiovascular, and neoplastic disorders. Clinically, elevated cytokine levels serve as diagnostic discriminators, prognostic markers, and guides for targeted therapies such as anti-TNF and anti-IL-6 biologics. Conclusion: IL-1β, IL-6, TNF-α, and IFN-γ emerge as indispensable biomarkers whose measurement provides critical insights into disease pathogenesis and underpins the advancement of personalized medicine in inflammatory conditions.
Abstract Background Compelling evidence has established a strong link between the gut microbiota and host reproductive health. However, the specific regulatory roles of individual bacterial species on reproductive performance are not well-understood. In the present study, Jinhua sows with varying reproductive performances under the same diet and management conditions were selected to explore potential mechanisms on the intricate relationship between the gut microbiome and host reproductive performance using 16S rRNA sequencing, metagenomics and serum metabolomics. Results Our findings revealed that the KEGG pathways for base excision repair and DNA replication were enriched, along with gene-level enhancements in spore formation, in sows with higher reproductive performance, indicating that the gut microbiome experiences stress. Further analysis showed a positive correlation between these changes and litter size, indicating that the host acts as a stressor, reshaping the microbiome. This adaptation allows the intestinal microbes in sows with high reproductive performance to enrich specific serotonin-related bacteria, such as Oxalobacter formigenes, Ruminococcus sp. CAG 382, Clostridium leptum, and Clostridium botulinum. Subsequently, the enriched microbiota may promote host serotonin production, which is positively correlated with reproductive performance in our study, known to regulate follicle survival and oocyte maturation. Conclusion Our study provides a theoretical basis for understanding the interactions between gut microbes and the host. It highlights new insights into reassembling gut microbiota in sows with higher litter sizes and the role of serotonin-related microbiota and serotonin in fertility. Graphical Abstract
<i>Yersinia enterocolitica</i> is a foodborne pathogen capable of biofilm formation and virulence modulation in response to environmental signals. Among these, glucose—present at physiologically relevant concentrations in the human body—may serve as a regulatory cue affecting infection-associated pathways, including those governed by the pYV virulence plasmid. Although the role of glucose has been investigated under host-mimicking conditions, its impact in non-host environments remains poorly understood. This study was designed to evaluate the glucose-dependent physiological responses of two isogenic <i>Y. enterocolitica</i> strains, KT0001 (pYV-negative) and KT0003 (pYV-positive), under non-host conditions (26 °C). Both strains were cultured in TYE medium containing 0–3% glucose. Comparative analyses were conducted under identical in vitro conditions to elucidate plasmid-associated phenotypic differences. Glucose elicited markedly divergent responses. In KT0001, growth remained unaffected; however, biofilm formation declined by 77.7%, accompanied by a 90% reduction in surface hydrophobicity, a 40% decrease in motility, and a 59% drop in intracellular cyclic AMP—suggesting classical carbon catabolite repression. Conversely, KT0003 exhibited 86% growth inhibition but maintained biofilm levels. This was associated with substantial extracellular polymeric substance induction (~20-fold increase in polysaccharides and ~4.7-fold in extracellular DNA) and nearly fivefold elevation in cyclic AMP levels, despite concurrent decreases in motility (64%) and hydrophobicity (40%). These findings indicate that glucose functions as a strain-specific modulator in <i>Y. enterocolitica</i>. In particular, KT0003’s response suggests that the pYV plasmid enables the bacterium to interpret glucose as a host-associated cue, even under non-host conditions, potentially initiating virulence-related adaptations prior to host contact.
Multilayer monolithic zirconia, which incorporates polychromatic layers that mimic natural tooth gradients, offers enhanced aesthetics and functionality while reducing debonding risks and improving fabrication efficiency. However, uncertainties remain regarding the fracture characteristics of multilayer monolithic zirconia crowns under occlusal loading, whether composed of uniform or combined yttria levels. The current study investigated how variations in yttria levels and thicknesses affected the optical properties and fracture loads of multilayer monolithic zirconia. Samples of multilayer monolithic zirconia in the Vita A1 shade were used, while employing 3Y (SZ) and 4Y + 5Y (AZ) yttria levels. The optical properties, including the color difference (Δ<i>E<sub>WS</sub></i>) and translucency parameters (<i>TP</i><sub>00</sub>), were measured using a digital colorimeter. The fracture loads were analyzed using a universal testing machine, and fractured surfaces were examined under a stereomicroscope. Statistical analyses assessed the impacts of the yttria levels and sample thicknesses on the optical properties. The Δ<i>E<sub>WS</sub></i> values of SZ ranged 3.6 to 4.0, while for AZ, Δ<i>E<sub>WS</sub></i> at 0.5 mm was 3.9 and <2.6 for other thicknesses. The <i>TP</i><sub>00</sub> values decreased with an increased thickness, with AZ generally exhibiting greater translucency than SZ. In the fracture load investigations, SZ (>1600 N) generally exceeded AZ (>1260 N), with fracture loads notably increasing with thickness, particularly for premolars (SZ > 3270 N, AZ > 2257 N). SZ predominantly exhibited partial and complete fractures, whereas AZ showed fewer non-fracture categorizations. Complete fractures began with dense, irregular cracks that extended outward to reveal smooth surfaces, while premolars subjected to higher loads exhibited concentric ripple-like structures. Partial fractures revealed radial textures indicative of areas of stress concentration. In summary, higher yttria levels were correlated with increased translucency, while variations in the fracture loads primarily stemmed from differences in the tooth position or thickness. Overall, multilayer monolithic zirconia incorporating combined yttria levels of 4Y + 5Y (AZ) offered high translucency, precise color matching, and substantial fracture resistance, rendering it highly suitable for aesthetic and functional dental applications.
Abstract Background Polyhydroxyalkanoates (PHAs) are naturally produced biopolymers with significant scientific and biotechnological potential. This study aimed to investigate the diversity of the PHA-producing bacterial community and PhaC genes in soil samples collected from a municipal solid waste disposal site known as “Qoshe” in Addis Ababa, Ethiopia, using a shotgun metagenomics approach. The SqueezeMeta pipeline was used to analyze the microbial community in the waste samples. A CD search against the TIGRFAM protein family database was performed to identify the complete-length multidomain sequences of PhaC genes and classify them into their respective classes. Statistical analysis and data visualization were performed using RStudio with R version 4.2.3. Results The findings of this study suggest that known and unknown taxa likely contribute to the phaC genes of municipal solid waste. Taxonomic profiling of the metagenomic data revealed that the majority of the PHA-producing taxa belonged to the phylum Proteobacteria (80%), followed by Actinomycetota (16.5%). Furthermore, this study identified Thiomonas and unclassified Mycobacterium as the main contributors to class I PhaC genes. Class II PhaC genes are predominantly associated with the Pseudomonadaceae family, followed by unclassified Hyphomicrobials and Acidimicrobiales. Class III PhaC genes are abundantly related to the Methylococcaceae family, specifically the Methylocaldum genus. The analysis of PhaC gene sequences revealed high level of diversity, with a significant proportion of putative PhaC genes exhibiting low sequence identity with each other and PhaC gene in the database. Notably, the sequence variation observed within the same PhaC gene classes suggests the potential presence of previously unidentified PhaC gene variants. Conclusions Overall, this research improves our understanding of the diversity of PHA-producing taxa and PhaC genes in municipal solid waste environments, providing opportunities for sustainable PHA production and waste management strategies. However, additional studies, including the isolation and characterization of specific strains, are necessary to confirm the PHA production capabilities of these strains and explore their biotechnological potential.
Abstract: Student profiling on the use of technology for teaching, learning and assessment has a potential to enable educators to enhance their transformational teaching strategies. Therefore, this study explored the views of students on use of technology to facilitate online learning during COVID-19. The study employed a quantitative approach to collect data using a Google Form questionnaire. Nineteen conveniently sampled respondents (38%) were drawn from a population of 50 students registered for first year BSc Microbiology and BSc Environmental Biology in 2021. The collected data was analyzed through descriptive statistics using Microsoft Excel 2010. The findings revealed that during online learning students experienced challenges related to subject knowledge acquisition (63%). Hence; majority (84%) of the students preferred face-to-face or blended teaching learning and assessment to ensure pedagogic access. It is concluded that students’ exposure to online learning helped improve skills such as typing (79%), internet information searching (95%) and general computer skills (89%). Thus, it is recommended that academics and student should be capacitated with training, and higher education curricula should encourage the use of digital technology, which prepares students to be relevant in the digital society.
Ragab E. Abouzeid, Ahmed Salama, Esmail M. El-Fakharany
et al.
Bio sustainable hydrogels including tunable morphological and/or chemical cues currently offer a valid strategy of designing innovative systems to enhance healing/regeneration processes of damaged tissue areas. In this work, TEMPO-oxidized cellulose nanofibrils (T-CNFs) were embedded in alginate (Alg) and polyvinyl alcohol (PVA) solution to form a stable mineralized hydrogel. A calcium chloride reaction was optimized to trigger a crosslinking reaction of polymer chains and mutually promote in situ mineralization of calcium phosphates. FTIR, XRD, SEM/EDAX, and TEM were assessed to investigate the morphological, chemical, and physical properties of different mineralized hybrid hydrogels, confirming differences in the deposited crystalline nanostructures, i.e., dicalcium phosphate dehydrate (DCPDH) and hydroxyapatite, respectively, as a function of applied pH conditions (i.e., pH 4 or 8). Moreover, in vitro tests, in the presence of HFB-4 and HSF skin cells, confirmed a low cytotoxicity of the mineralized hybrid hydrogels, and also highlighted a significant increase in cell viability via MTT tests, preferentially, for the low concentration, crosslinked Alg/PVA/calcium phosphate hybrid materials (<1 mg/mL) in the presence of hydroxyapatite. These preliminary results suggest a promising use of mineralized hybrid hydrogels based on Alg/PVA/T-CNFs for bone and wound healing applications.
Shi Ting Lee, Thasaneeya Kuboki, Satoru Kidoaki
et al.
A plasmonic metasurface composed of self‐assembled gold nanoparticles enables high‐speed interfacial imaging with high axial and lateral resolution down to the theoretical limit under a widefield microscope. This high‐spatiotemporal resolution imaging method monitors “early molecular events” in the adhesion of 3T3 fibroblasts expressing Venus‐paxillin and LifeAct‐mScarlet, revealing unique transient cell dynamics. Upon attaching to the SiO2‐coated plasmonic metasurface, cells exhibit fibrous nascent adhesions spreading radially at the periphery, together with actively moving membrane blebs. These fibrous nascent structures exist transiently during passive spreading and disappear upon transition to active spreading with mature focal adhesions (FAs). The structure forms on a poor‐cell‐adhesive SiO2‐coated surface but not on a fibronectin‐preadsorbed cell‐adhesive surface, suggesting that it temporarily anchors cells to the interface but maintains freedom before active cell spreading. These momentary molecular‐level phenomena at the nanointerface are successfully captured by the herein described high‐spatiotemporal resolution live‐cell imaging method using a plasmonic metasurface.
Inflammatory bowel disease (IBD) is a chronic disease with multiple complications during its development, and it is difficult to cure. The aim of this study was to evaluate the alleviating effect of different concentrations of the bioactive peptide IQW (Ile-Gln-Trp) on dextran sodium sulfate (DSS)-induced colitis in mice. For this study, we randomly divided 56 ICR mice into seven groups: the (I) control (CON), (II) dextran sodium sulfate treatment (2.5% DSS), (III) IQW-DSS (20 μg/ml) treatment, (IV) IQW-DSS (40 μg/ml) treatment, (V) IQW-DSS (60 μg/ml) treatment, (VI) IQW-DSS (80 μg/ml) treatment, and (VII) IQW-DSS (100 μg/ml) groups. The results showed that IQW at 60 μg/ml alleviated body weight loss, improved the liver index (p < 0.05), and improved histomorphological and pathological changes in the colon compared to the DSS-treated group. IQW at 60 μg/ml and IQW at 80 μg/ml modified intestinal microbial disorders. In addition, IQW at 60 μg/ml significantly increased butyric acid levels and decreased valeric acid levels, while IQW at 80 μg/ml significantly increased isobutyric acid and isovaleric acid levels. Hence, IQW at a concentration of 60 μg/ml alleviates DSS-induced colitis by enhancing the body's anti-inflammatory ability and regulating intestinal flora and metabolic changes. In the above context, IQW at 60 μg/ml could be a potential candidate for IBD prevention and treatment.
Despite being the world’s third largest ocean, the Indian Ocean is one of the least studied and understood with respect to microbial diversity as well as biogeochemical and ecological functions. In this study, we investigated the microbial community and its metabolic potential for nitrogen (N) acquisition in the oligotrophic surface waters of the Indian Ocean using a metagenomic approach. Proteobacteria and Cyanobacteria dominated the microbial community with an average 37.85 and 23.56% of relative abundance, respectively, followed by Bacteroidetes (3.73%), Actinobacteria (1.69%), Firmicutes (0.76%), Verrucomicrobia (0.36%), and Planctomycetes (0.31%). Overall, only 24.3% of functional genes were common among all sampling stations indicating a high level of gene diversity. However, the presence of 82.6% common KEGG Orthology (KOs) in all samples showed high functional redundancy across the Indian Ocean. Temperature, phosphate, silicate and pH were important environmental factors regulating the microbial distribution in the Indian Ocean. The cyanobacterial genus Prochlorococcus was abundant with an average 17.4% of relative abundance in the surface waters, and while 54 Prochlorococcus genomes were detected, 53 were grouped mainly within HLII clade. In total, 179 of 234 Prochlorococcus sequences extracted from the global ocean dataset were clustered into HL clades and exhibited less divergence, but 55 sequences of LL clades presented more divergence exhibiting different branch length. The genes encoding enzymes related to ammonia metabolism, such as urease, glutamate dehydrogenase, ammonia transporter, and nitrilase presented higher abundances than the genes involved in inorganic N assimilation in both microbial community and metagenomic Prochlorococcus population. Furthermore, genes associated with dissimilatory nitrate reduction, denitrification, nitrogen fixation, nitrification and anammox were absent in metagenome Prochlorococcus population, i.e., nitrogenase and nitrate reductase. Notably, the de novo biosynthesis pathways of six different amino acids were incomplete in the metagenomic Prochlorococcus population and Prochlorococcus genomes, suggesting compensatory uptake of these amino acids from the environment. These results reveal the features of the taxonomic and functional structure of the Indian Ocean microbiome and their adaptive strategies to ambient N deficiency in the oligotrophic ocean.
Vitalii Balobanov, Rita Chertkova, Anna Egorova
et al.
Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.
Cancer immunotherapy has become an emerging strategy recently producing durable immune responses in patients with varieties of malignant tumors. However, the main limitation for the broad application of immunotherapies still to reduce side effects by controlling and regulating the immune system. In order to improve both efficacy and safety, biomaterials have been applied to immunotherapies for the specific modulation of immune cells and the immunosuppressive tumor microenvironment. Recently, researchers have constantly developed biomaterials with new structures, properties and functions. This review provides the most recent advances in the delivery strategies of immunotherapies based on localized biomaterials, focusing on the implantable and injectable biomaterial scaffolds. Finally, the challenges and prospects of applying implantable and injectable biomaterial scaffolds in the development of future cancer immunotherapies are discussed.
Abstract Background Transcription factor-based biosensors are useful tools for the detection of metabolites and industrially valuable molecules, and present many potential applications in biotechnology and biomedicine. However, the most common approach to develop biosensors relies on employing a limited set of naturally occurring allosteric transcription factors (aTFs). Therefore, altering the ligand specificity of aTFs towards the detection of new effectors is an important goal. Results Here, the PcaV repressor, a member of the MarR aTF family, was used to develop a biosensor for the detection of hydroxyl-substituted benzoic acids, including protocatechuic acid (PCA). The PCA biosensor was further subjected to directed evolution to alter its ligand specificity towards vanillin and other closely related aromatic aldehydes, to generate the Van2 biosensor. Ligand recognition of Van2 was explored in vitro using a range of biochemical and biophysical analyses, and extensive in vivo genetic-phenotypic analysis was performed to determine the role of each amino acid change upon biosensor performance. Conclusions This is the first study to report directed evolution of a member of the MarR aTF family, and demonstrates the plasticity of the PCA biosensor by altering its ligand specificity to generate a biosensor for aromatic aldehydes.