Search Results (2,861)

Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to insulin resistance remain largely unknown. Although the Janus Kinase (Jak)/signal transducer and activator of transcription 3 (Stat3) signaling in myeloid cells are known to promote the M2 phenotype in tumors, we demonstrate here that the Jak2/Stat3 pathway amplifies M1-mediated adipose tissue inflammation and insulin resistance under metabolic challenges. Ablating Jak2 in the myeloid compartment reduces insulin resistance in obese mice, which is associated with a decrease in infiltration of adipose tissue macrophages (ATMs). We show that the adoptive transfer of Jak2-deficient myeloid cells improves insulin sensitivity in obese mice. Furthermore, the protection of obese mice with myeloid-specific Stat3 deficiency against insulin resistance is also associated with reduced tissue infiltration by macrophages. Jak2/Stat3 in the macrophage is required for the production of pro-inflammatory cytokines that promote M1 macrophage polarization in the adipose tissues of obese mice. Moreover, free fatty acids (FFAs) activate Stat3 in macrophages, leading to the induction of M1 cytokines. Silencing the myeloid cell Stat3 with an in vivo siRNA targeted delivery approach reduces metabolically activated pro-inflammatory ATMs, thereby alleviating obesity-induced insulin resistance. These results demonstrate Jak2/Stat3 in myeloid cells is required for obesity-induced insulin resistance and inflammation. Moreover, targeting Stat3 in myeloid cells may be a novel approach to ameliorate obesity-induced insulin resistance. Full article

The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular cloning revealed that the barbel chub DF (ScDF) gene encodes a 1251-bp cDNA sequence translating into a 250-amino acid protein. Crucially, bioinformatic characterization identified a unique N-glycosylation site at Asn¹³⁹ in ScDF, representing a structural divergence absent in grass carp (Ctenopharyngodon idella) DF (CiDF). While retaining a conserved Tryp_SPc domain harboring the catalytic triad (His⁶¹, Asp¹⁰⁹, and Ser²⁰⁴) and substrate-binding residues (Asp¹⁹⁸, Ser²¹⁹, and Gly²²¹), sequence and phylogenetic analyses confirmed ScDF’s evolutionary conservation, displaying 94.4% amino acid identity with CiDF and clustering within the Cyprinidae. Expression profiling revealed constitutive ScDF dominance in the liver, and secondary prominence was observed in the heart. Upon GCRV challenge in S. curriculus kidney (SCK) cells, ScDF transcription surged to a 438-fold increase versus uninfected controls at 6 h post-infection (hpi; p < 0.001)—significantly preceding the 168-hpi response peak documented for CiDF in grass carp. Functional validation showed that ScDF overexpression suppressed key viral capsid genes (VP2, VP5, and VP7) and upregulated the interferon regulator IRF9. Moreover, recombinant ScDF protein incubation induced interferon pathway genes and complement C3 expression. Collectively, ScDF’s rapid early induction (peaking at 6 hpi) and multi-pathway coordination may contribute to barbel chub’s GCRV resistance. These findings may provide molecular insights into the barbel chub’s high GCRV resistance compared to grass carp and novel perspectives for anti-GCRV breeding strategies in fish. Full article

Electromagnetic and magnetic devices are increasingly prevalent in sectors such as transportation, industry, and renewable energy due to the ongoing electrification trend. These devices exhibit nonlinear behavior, particularly under signals rich in harmonics. They require precise and appropriate modeling for accurate sizing. Identifying model-specific parameters, which depend on frequency, is crucial. This article focuses on a specific frequency range where a circuit model with series resistance and inductance, along with a parallel resistance to account for iron losses (${\mathrm{R}}_{\mathrm{iron}}$), is applicable. While the determination of series elements is well documented, the determination of ${\mathrm{R}}_{\mathrm{iron}}$ remains complex and debated, with traditional methods neglecting operating conditions such as magnetic saturation. To address these limitations, an innovative experimental method is proposed, comprising two main steps: determining the complex impedance of the magnetic device and extracting ${\mathrm{R}}_{\mathrm{iron}}$ from the model. This method aims to provide a more precise and representative estimation of ${\mathrm{R}}_{\mathrm{iron}}$, improving the reliability and accuracy of electromagnetic and magnetic device simulations and designs. The obtained values of the iron loss equivalent resistance are different by at least 300% than those obtained by an impedance analyzer. The proposed method is expected to advance the understanding and modeling of losses in electromagnetic and magnetic devices, offering more robust tools for engineers and researchers in optimizing device performance and efficiency. Full article

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = −0.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = −0.58, p < 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events. Full article

Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus (CLas), is the most devastating disease threatening global citrus production. Although no commercial citrus varieties exhibit complete HLB resistance, genotype-specific tolerance variations remain underexplored. This study conducted a comparative transcriptomic profiling of six commercially citrus cultivars in South China, four susceptible cultivars (C. reticulata cv. Tankan, Gongkan, Shatangju, and C. sinensis Osbeck cv. Newhall), and two tolerant cultivars (C. limon cv. Eureka; C. maxima cv Guanxi Yu) to dissect molecular mechanisms underlying HLB responses. Comparative transcriptomic analyses revealed extensive transcriptional reprogramming, with tolerant cultivars exhibiting fewer differentially expressed genes (DEGs) and targeted defense activation compared to susceptible genotypes. The key findings highlighted the genotype-specific regulation of starch metabolism, where β-amylase 3 (BAM3) was uniquely upregulated in tolerant varieties, potentially mitigating starch accumulation. Immune signaling diverged significantly: tolerant cultivars activated pattern-triggered immunity (PTI) via receptor-like kinases (FLS2) and suppressed ROS-associated RBOH genes, while susceptible genotypes showed the hyperactivation of ethylene signaling and oxidative stress pathways. Cell wall remodeling in susceptible cultivars involved upregulated xyloglucan endotransglucosylases (XTH), contrasting with pectin methylesterase induction in tolerant Eureka lemon for structural reinforcement. Phytohormonal dynamics revealed SA-mediated defense and NPR3/4 suppression in Eureka lemon, whereas susceptible cultivars prioritized ethylene/JA pathways. These findings delineate genotype-specific strategies in citrus–CLas interactions, identifying BAM3, FLS2, and cell wall modifiers as critical targets for breeding HLB-resistant cultivars through molecular-assisted selection. This study provides a foundational framework for understanding host–pathogen dynamics and advancing citrus immunity engineering. Full article

This article utilises Max-Neef’s Human Scale Development (HSD) framework (1991) to answer two research questions: what impact does government and community-based social protection (SP) have on UK asylum-seeker wellbeing; how are interactions with all forms of SP, both as giver and receiver, supporting or harming the satisfaction of asylum-seekers’ fundamental human needs at this time? The research study utilised a mixed-methods, collaborative, case study design situated within a refugee and asylum-seeker (RAS) support charity in Southwest England. Methods included peer-led Qualitative Impact Protocol interviews, Photovoice, surveys, and staff interviews. Data were subjected to an inductive, bottom-up process on Causal Map software (version 2, Causal Map Ltd., 39 Apsley Rd., Bath BA1 3LP, UK) and the analysis used the HSD framework. We found eight over-arching themes. The four main needs-violators/destroyers of asylum-seeker wellbeing were dehumanisation, unfreedoms, enforced ignorance, and (re)traumatisation, and the four main needs-satisfiers were common humanity, autonomy and resistance, exerting agency through knowledge exchange, and healing. Five policy and practice-focused bridging satisfiers are recommended to help move individual and collective experience from a negative to a positive state in the research population. Policy and practice should be transparent and evidence-based, efficient and equitable, supportive of participation and productivity, trauma-informed, and multi-agency. Full article

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

In this study, a current vector pattern is analyzed for inter-turn fault (ITF) diagnosis of induction machines (IMs), and an ITF diagnosis algorithm is proposed. When an ITF occurs in IMs, a negative-sequence current is generated due to fault resistance, even though a positive-sequence voltage is applied to IMs. Based on the mathematical model of IMs with an ITF, the current vector patterns in the stationary coordinate frame are analyzed. The superposition of positive- and negative-sequence components results in an elliptical current vector trajectory, and its orientation varies depending on the fault conditions. The co-simulation using finite element analysis and circuit simulation is implemented to analyze the current vector pattern of IMs with an ITF. The ITF diagnosis is proposed based on the current vector pattern. A 12 kW, four-pole, three-phase IM and terminal box, which was used to implement an ITF, is manufactured, and an experiment setup is established to verify the ITF algorithm. The effectiveness of the proposed ITF algorithm is validated through experimental verification of the manufactured IM and terminal box. Full article

Background and Objectives: Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. Although chemotherapy is an effective treatment for colorectal cancer (CRC), its effectiveness is frequently hindered by the emergence of resistant cancer cells. Studies have demonstrated a linkage between drug resistance and the pregnane X receptor (PXR), which influences the metabolism and the transport of chemotherapeutic agents. Likewise, autophagy is also a well-established mechanism that contributes to chemotherapy resistance, and it is closely tied to tumor progression. This pre-clinical study aims to investigate the role of mtKRAS-dependent autophagy with PXR expression after treatment with Irinotecan in colorectal cancer. Methods: CRC lines were treated with specific inhibitors, such as 3-methyladeninee, hydroxychloroquine PI-103, and irinotecan hydrochloride, and subjected to various assays, including MTT for cell viability, Western blot for protein expression, siRNA-mediated PXR knock-out, and confocal microscopy for autophagic vacuole visualization. Protein quantification, gene knockdown, and subcellular localization studies were performed under standardized conditions to investigate treatment effects on autophagy and apoptosis pathways. Conclusions: Our experiments showed that PXR knockdown does not alter autophagy levels following Irinotecan treatment, but it promotes apoptotic cell death despite elevated autophagy. Moreover, late-stage autophagy inhibition reduces PXR expression, whereas induction through PI3K/AKT/mTOR inhibition leads to increased expression of PXR. Our experiments uncover a mechanism by which autophagy facilitates the nuclear translocation of the PXR, thereby promoting resistance to Irinotecan across multiple cell lines. Full article

Elucidating the mechanisms of radioresistance in highly radiotolerant organisms can provide valuable insights into the adaptation and evolution of organisms. However, research has been limited on many naturally occurring radioresistant organisms due to a lack of information regarding their genetic and biochemical characteristics and the difficulty of handling them experimentally. To address this, we conducted an experiment on adaptive evolution using gamma radiation as the selection pressure to generate evolved Escherichia coli with gamma radiation resistance approximately one order of magnitude greater than that of wild-type E. coli. Gene expressions in all wild-type and evolved radioresistant E. coli in the presence or absence of gamma irradiation were analyzed and compared using RNA sequencing. Under steady-state conditions, the genes involved in survival, cell recovery, DNA repair, and response following stress exposure were upregulated in evolved E. coli compared with those in wild-type E. coli. Furthermore, the evolved E. coli induced these genes more efficiently following gamma irradiation and greater DNA repair activity than that in the wild-type E. coli. Our results indicate that an increased steady-state expression of various anti-stress genes, including DNA repair-related genes, and their highly efficient induction under irradiation are responsible for the remarkable radioresistance of evolved E. coli. Full article

Island microgrids are essential for the exploitation and utilization of offshore renewable energy resources. However, voltage regulation and accurate reactive power sharing remain significant technical challenges that need to be addressed. To tackle these issues, this paper proposes an algorithm that integrates a dynamic leader election (DLE) mechanism and model-free reinforcement learning (RL). The algorithm aims to address the issue of fixed leaders restricting reactive power flow between buses during heavy load variations in island microgrids, while also overcoming the challenge of obtaining model parameters such as resistance and inductance in practical microgrids. First, we establish a voltage containment control and reactive power error model for island alternating current (AC) microgrids and construct a corresponding value function based on this error model. Second, a dynamic leader election algorithm is designed to address the issue of fixed leaders restricting reactive power flow between buses due to preset voltage limits under unknown or heavy load conditions. The algorithm adaptively selects leaders based on bus load, allowing the voltage limits to adjust accordingly and regulating reactive power flow. Then, to address the difficulty of accurately acquiring parameters such as resistance and inductance in microgrid lines, a model-free reinforcement learning method is introduced. This method relies on real-time measurements of voltage and reactive power data, without requiring specific model parameters. Ultimately, simulation experiments on offshore island microgrids are conducted to validate the effectiveness of the proposed algorithm. Full article

This paper presents a structured and experimentally validated approach to the parameter identification, modeling, and real-time speed control of a brushless DC (BLDC) motor. Electrical parameters, including resistance and inductance, were measured through DC and AC testing under controlled conditions, respectively, while mechanical and electromagnetic parameters such as the back electromotive force (EMF) constant and rotor inertia were determined experimentally using an AVL dynamometer. The back EMF was obtained by operating the motor as a generator under varying speeds, and inertia was identified using a deceleration method based on the relationship between angular acceleration and torque. The identified parameters were used to construct a transfer function model of the motor, which was implemented in MATLAB/Simulink R2024b and validated against real-time experimental data using sinusoidal and exponential input signals. The comparison between simulated and measured speed responses showed strong agreement, confirming the accuracy of the model. A proportional–integral (PI) controller was developed and implemented for speed regulation, using a low-cost National Instruments (NI) USB-6009 data acquisition (DAQ) and a Kelly controller. A first-order low-pass filter was integrated into the control loop to suppress high-frequency disturbances and improve transient performance. Experimental tests using a stepwise reference speed profile demonstrated accurate tracking, minimal overshoot, and robust operation. Although the modeling and control techniques applied are well known, the novelty of this work lies in its integration of experimental parameter identification, real-time validation, and practical hardware implementation within a unified and replicable framework. This approach provides a solid foundation for further studies involving more advanced or adaptive control strategies for BLDC motors. Full article

To enhance the mechanical properties of NbMoTaW refractory high-entropy alloys (RHEAs), Si was added at varying concentrations (x = 0, 0.25, and 0.5) via vacuum induction levitation melting (re-melted six times for homogeneity). The microstructure and mechanical properties of NbMoTaWSi_x (x = 0, 0.25, and 0.5) RHEAs were characterized using scanning electron microscopy (SEM), universal testing, microhardness testing, and tribological equipment. Experimental results manifested that Si addition induces the formation of the (Nb,Ta)₅Si₃ phase, and the volume fraction of the silicide phase increases with higher Si content, which significantly improves the alloy’s strength and hardness but deteriorates its plasticity. Enhanced wear resistance with Si addition is attributed to improved hardness and oxidation resistance. Tribological tests confirm that Si₃N₄ counterfaces are optimal for evaluating RHEA wear mechanisms. This work can provide guidance for the fabrication of RHEAs with excellent performance. Full article

Background/Objectives: Cisplatin remains a cornerstone chemotherapeutic agent for non-small-cell lung cancer (NSCLC) treatment, yet its clinical utility is substantially limited by acquired resistance and the inadequate suppression of tumor metastasis. Emerging evidence implicates interleukin 6 (IL-6) as a critical mediator of chemoresistance through cancer stem cell (CSC) enrichment and metastasis promotion via epithelial–mesenchymal transition (EMT) induction, ultimately contributing to cisplatin therapy failure. This study sought to address these challenges by designing a nanoplatform with two innovative aims: (1) to achieve active tumor targeting through binding to the IL-6 receptor (IL-6R), and (2) to concurrently inhibit IL-6-mediated chemoresistance signaling pathways. Methods: A lipid–polymer hybrid nanoparticle (LPC) encapsulating cisplatin was synthesized and subsequently surface-functionalized with tocilizumab (TCZ), a monoclonal antibody that targets IL-6R. The therapeutic efficacy of this TCZ-modified nanoparticle (LPC-TCZ) was assessed through a series of in vitro and in vivo experiments, focusing on the inhibition of EMT, expression of CSC markers, tumor growth, and metastasis. Results: Systematic in vitro and in vivo evaluations revealed that LPC-TCZ synergistically attenuated both EMT progression and CSC marker expression through the targeted blockade of IL-6/STAT3 signaling. This multimodal therapeutic strategy demonstrated superior tumor growth inhibition and metastatic suppression compared to conventional cisplatin monotherapy. Conclusions: Our findings establish a nanotechnology-enabled approach to potentiate cisplatin efficacy by simultaneously countering chemoresistance mechanisms and metastatic pathways in NSCLC management. Full article