Search Results (12,089)

Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often limit their effectiveness. As a primary traditional Chinese medicine (TCM) therapy, acupuncture treats CG through multi-target mechanisms. This review systematically outlines the classification and pathology of CG. It also comprehensively analyzes animal and clinical studies on acupuncture for CG from the past decade. The study summarizes the mechanisms of acupuncture and related therapies for CG, covering gastric mucosal function, metabolism, intestinal flora, gastrointestinal hormones, apoptosis, inflammation, and oxidative stress. It further explores the relationships among diseases, interventions, acupoints, and molecular pathways. Additionally, it compares the therapeutic profiles of different external therapies. The review also examines the current state of clinical research, including the selection of acupoints, treatment duration, and outcome assessment. The results demonstrate that external therapies effectively alleviate common CG symptoms such as abdominal distension, acid reflux, and stomach pain. These treatments also improve gastric mucosal health and modulate serum levels of inflammatory factors, oxidative stress markers, and gastrointestinal hormones. In vivo experiments using chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG) models confirm these benefits, showing changes in key biomarkers and elucidating potential mechanisms. Nevertheless, future high-quality, large-sample clinical trials are still needed to firmly establish efficacy. Further mechanistic studies are also needed to validate the interconnections among relevant signaling pathways. Full article

Background: Fluoroquinolone (FQ) resistance in Escherichia coli (E. coli) undermines empiric therapy and often coincides with multidrug resistance (MDR). Because sequencing is not routinely available in many laboratories, we evaluated a phenotype-first, sequencing-independent diagnostic framework deployable on standard platforms. Methods: We profiled 45 archived E. coli isolates for susceptibility (Clinical and Laboratory Standards Institute [CLSI]-guided), extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC) phenotypes, MDR, and multiple-antibiotic resistance (MAR) indices. Ten founders (five FQ-susceptible [FQ-S], five low-level resistant [LLR]) seeded 20 parallel lineages exposed to stepwise ciprofloxacin. We tracked minimum inhibitory concentrations (MICs), collateral resistance, growth kinetics, and biofilm biomass using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification, automated and reference antimicrobial susceptibility testing (AST), growth-curve analysis, and crystal violet microtiter assays. The intended use is a sequencing-independent workflow for routine laboratories—especially where whole-genome sequencing is not readily available—working with archived or prospective clinical E. coli. This workflow is best applied when local FQ nonsusceptibility threatens empiric reliability; inputs include standard ID/AST with simple growth and biofilm assays. Primary outputs include: (i) MIC trajectories with time to high-level resistance (HLR), (ii) ΔMAR-summarized collateral resistance with class-level susceptible-to-resistant conversions, and (iii) concise fitness/biofilm summaries to guide empiric-policy refresh and early de-escalation. Results: At baseline, ciprofloxacin nonsusceptibility was 40.0%; ESBL and AmpC phenotypes were confirmed in 28.9% and 15.6%, respectively; 46.7% met the MDR definition; and the median MAR index was 0.29. During evolution, 70% of lineages reached HLR (MIC ≥ 4 μg/mL), with earlier conversion from LLR versus FQ-S founders (median 7 vs. 11 passages). Collateral resistance emerged most often to third-generation cephalosporins (3GCs), trimethoprim–sulfamethoxazole, and tetracyclines, while carbapenem activity was preserved. MAR increased in parallel with rising MICs. Resistance acquisition imposed modest fitness costs (slightly reduced growth rates and longer lag phases) that were partly offset under subinhibitory ciprofloxacin, whereas biofilm biomass changed little. Conclusions: this phenotype-first, routine-laboratory workflow rapidly maps FQ resistance and clinically relevant co-selection in E. coli. In high-resistance settings, empiric FQ use is difficult to justify, and MAR trends provide practical co-selection signals for stewardship. This reproducible framework complements genomic surveillance and is directly applicable where sequencing is unavailable. Full article

Background/Objectives: T cell bispecific antibodies (TCBs) result in the activation of T cell receptor signaling upon binding to tumor antigens providing signal 1 to T cells. To enhance and sustain their activity, a co-stimulatory signal 2 is required. Here CEACAM5-targeted 4-1BBL antibody fusion proteins for combination with CEA-TCB (cibisatamab, RG7802) are described in an investigation of the relationship between the CEACAM5 epitope and T cell activity. Methods: CEACAM5-targeted bispecific 4-1BBL antibody fusion proteins (CEA-4-1BBLs) were generated based on different CEACAM5 antibodies and characterized in vitro in Jurkat-4-1BB reporter and PBMC cell assays. The impact of shed CEA on in vitro activity and cynomolgus cross-reactivity was studied. In vivo efficacy was assessed in human stem cell humanized NSG mice xenograft models bearing MKN-45 and HPAFII tumors. Results: MFE23-4-1BBL and Sm9b-4-1BBL showed superior functional activity in Jurkat-4-1BB reporter and primary T cell assays when combined with the CD3 antibody V9, whereas T84.66-LCHA-4-1BBL and A5B7-4-1BBL performed better when combined with CEA-TCB. In humanized NSG mice MKN-45 and HPAFII xenograft models, T84.66-LCHA-4-1BBL mediated the best anti-tumor efficacy. Conclusions: For the assessment of the combination of CEA-TCB with CEA-4-1BBL, co-stimulatory antibody fusion protein in vitro assays are not sufficient to fully capture the complex relationships affecting efficacy. Thus, screening with different cell assays and in vivo efficacy studies in combination with CEA-TCB are essential to select the best candidate. Based on the totality of data on the T84.66-LCHA-4-1BBL antibody fusion protein comprising the CEACAM5 antibody, T84.66-LCHA was selected as the optimal combination partner for CEA-TCB. Full article

Aiming at the problem of low signal-to-noise ratio of the projectile signal output by the sky screen sensor, the symmetrical characteristics of the projectile signal and the noise sources were analyzed, and a joint denoising method of variational mode decomposition (VMD) and wavelet threshold based on the whale optimization algorithm (WOA) was proposed. This method employs the whale optimization algorithm (WOA) to globally optimize the key parameters of variational mode decomposition (VMD), namely the number of modes $K$ and the penalty factor $\alpha$, to obtain the optimal parameter combination that minimizes the envelope entropy. The original projectile signal is adaptively decomposed through the optimal VMD parameters. The variance contribution rate is used to screen the decomposed intrinsic mode function to retain the IMF component containing the projectile signal information and improve the signal-to-noise ratio of the projectile signal. Then, a wavelet threshold function is introduced to conduct secondary denoising processing on the selected modal components, further improving the signal-to-noise ratio of the projectile signal. Through noise reduction experiments on the measured projectile signals, it is proved that the signal-to-noise ratio of the signals has been significantly improved, indicating that this method can suppress noise while retaining the effective signal of the projectile to the greatest extent, laying a foundation for the recognition of projectile signals of the sky screen target. Full article

Melanoma is an aggressive form of skin cancer marked by unique genetic alterations that promote tumor growth and resistance to therapy. Advances in targeted therapy have markedly improved clinical outcomes by selectively inhibiting key oncogenic pathways. This review focuses on three clinically relevant agents—vemurafenib, trametinib, and imatinib—analyzing their mechanisms of action, clinical applications, efficacy, and limitations. Vemurafenib, a selective BRAFV600E inhibitor, significantly extends progression-free and overall survival in BRAF-mutant melanoma but is limited by acquired resistance and frequent cutaneous toxicities. Trametinib, a MEK1/2 inhibitor, acts downstream in the MAPK pathway and is typically combined with BRAF inhibitors to enhance efficacy and delay resistance. Imatinib, targeting c-KIT and PDGFR mutations, demonstrates therapeutic benefit primarily in acral and mucosal melanoma subtypes, though with lower response rates than BRAF-directed therapies. Adverse events associated with these drugs are generally manageable with appropriate monitoring. Despite substantial advances, secondary mutations and reactivation of oncogenic signaling remain major challenges. This narrative review integrates data from clinical, preclinical, and real-world studies to update the current understanding of targeted therapies in cutaneous melanoma and highlight ongoing research aimed at overcoming resistance and optimizing personalized treatment strategies. Full article

Mastitis is a common mammary gland disease in mammals that severely impairs lactation function, with Staphylococcus aureus (S. aureus) being the primary pathogenic bacterium. However, the molecular mechanisms underlying S. aureus-induced mastitis in sheep remain incompletely elucidated. This study employed RNA sequencing (RNA-SEq) technology to systematically analyze the dynamic transcriptomic characteristics of mammary tissue in small-tailed sheep (SHT) after S. aureus infection, aiming to clarify the molecular regulatory mechanism of the host immune response and its relationship with the occurrence of mastitis. Twelve lactating STH were selected to establish an S. aureus-induced mastitis model. Blood, milk, and tissue samples were collected at 0, 24, 48, and 72 h post-infection (hpi). The infected sheep exhibited typical mastitis symptoms, including exacerbated breast swelling, reduced milk yield, elevated udder temperature, and darker, more viscous milk. Hematoxylin–eosin (HE) staining revealed significant pathological changes over time, such as stromal hyperplasia, extensive inflammatory cell infiltration, severe necrosis and sloughing of mammary epithelial cells, and compromised tissue integrity. RNA-Seq analysis identified 1299 differentially expressed genes (DEGs), among which 75 core genes maintained stable expression throughout the infection time (24 hpi, 48 hpi, and 72 hpi). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were associated with metabolic processes, protein binding, Toll-like receptor signaling, and the NF-κB pathway. The PPI network analysis identified core hub genes including PTK2B, STAT3, and JAK1/3, providing critical evidence for therapeutic target screening. Furthermore, qPCR verification indicated that the expressions of innate immune receptors TLR2, TLR4, TLR7, and TLR10, as well as pro-inflammatory factors IL-1β, IL-16, TNF-α, type I interferon (IFN-α), and nuclear transcription factor NF-κB were significantly upregulated in a time-dependent manner (p < 0.05). In conclusion, this study delineated the dynamic response of ovine mammary tissue to S. aureus infection, systematically elucidated temporal gene expression patterns, and revealed the molecular mechanisms underlying the tissue’s initial defense against inflammatory challenges. Full article

Eleven novel asymmetric pyrimidine derivatives were synthesized. The pyrimidine core was functionalized with a coumarin chromophore and a pro-mesogenic fragment bearing either chiral or linear alkyl chains of variable length and substitution patterns. The thermal properties were investigated using polarized optical microscopy, differential scanning calorimetry, and small-angle X-ray scattering, revealing that only selected derivatives exhibited liquid crystalline phases with ordered columnar or smectic organizations. Linear and nonlinear optical properties were characterized by UV–Vis absorption, fluorescence spectroscopy, two-photon absorption, and second-harmonic generation. Optical responses were found to be highly sensitive to the substitution pattern: derivatives functionalized at the 4 and 3,4,5 positions exhibited enhanced 2PA cross-sections and pronounced SHG signals, whereas variations in alkyl chain length exerted only a minor influence. Notably, compounds forming highly ordered non-centrosymmetric mesophases produced robust SHG-active thin films. Importantly, strong SHG responses were obtained without the need for a chiral center, as the inherent asymmetry of the linear alkyl chain derivatives was sufficient to drive self-organization into non-centrosymmetric materials. These results demonstrate that asymmetric pyrimidine-based architectures combining π-conjugation and controlled supramolecular organization are promising candidates for nonlinear optical applications such as photonic devices, multiphoton imaging, and optical data storage. Full article

This review reappraises the anti-inflammatory potential of the contact activation system (CAS) in intensive care through an evolutionary lens. The authors propose that coagulation factor XII (FXII) and related components evolved in terrestrial animals as a “foreign-surface sensing–immunothrombosis” module, helping to explain the minimal bleeding phenotype of FXII deficiency and the secondary loss of F12 in marine mammals. CAS shares components with the kallikrein–kinin system (KKS): alpha-coagulation factor XIIa (α-FXIIa) drives coagulation factor XI (FXI) activation to amplify coagulation, whereas betacoagulation factor XIIa (β-FXIIa) activates the KKS to generate bradykinin, promoting vasodilation and vascular leak. Beyond proteolysis, zymogen FXII signals via urokinase-type plasminogen activator receptor (uPAR) to induce neutrophil extracellular trap formation (NETosis), thereby amplifying immunothrombosis. Clinically, the relevance spans sepsis and extracorporeal organ support: pathogens can hijack CAS/KKS to facilitate invasion, and artificial surfaces such as extracorporeal membrane oxygenation (ECMO) circuits chronically trigger contact activation. In animal models, selective inhibition of FXII/FXI prolongs circuit life and attenuates pulmonary edema and inflammation without materially increasing bleeding. The review also catalogs “non-coagulation” roles of CAS members: Activated coagulation factor XI (FXIa) modulates endothelial permeability and smooth-muscle migration, and the FXII heavy chain exhibits direct antimicrobial activity—underscoring CAS as a nexus for coagulation, inflammation, and host defense. Overall, CAS inhibitors may couple “safe anticoagulation” with “cascade-level anti-inflammation,” offering a testable translational path for organ protection in the ICU alongside infection control and informing combined, precision strategies for anticoagulation and anti-inflammatory therapy. Full article

Ultra-reliable low-latency communication (URLLC) presents significant challenges in simultaneously guaranteeing stringent latency bounds, ultra-high reliability, and efficient resource utilization under dynamic channel conditions. To address these joint constraints, a novel framework that integrates a reconfigurable intelligent surface (RIS) with cooperative non-orthogonal multiple access (NOMA) is proposed for short-packet communications. Two distinct phase configuration designs for the RIS are considered, i.e., a near-user priority strategy (NUPS) and a far-user priority strategy (FUPS). The NUPS configures the RIS to enhance the received signal power for the near user, while the FUPS optimizes the phase shifts to maximize the received power for the far user. Closed-form expressions that characterize the average block error rate (BLER) of the near and far users under the two proposed strategies in the presence of hardware impairments are derived. Specifically, the analysis for the far user considers both selection combining (SC) and maximum ratio combining (MRC) reception schemes. Based on the average BLER, we then derive a closed-form expression for the effective throughput. Simulation findings reveal the following: (1) The far user in the proposed cooperative NOMA achieves a lower average BLER than in the non-cooperative NOMA. (2) When the RIS is deployed in close proximity to the base station (BS), the NUPS can effectively leverage the RIS to enhance the far user’s signal quality through cooperation, without sacrificing the near user’s priority; and (3) SC serves as a low-complexity alternative that achieves near-optimal performance when inter-user channel conditions are favorable. Full article

Monitoring nitrogen dioxide (NO₂) in various scenarios is crucial due to its significant environmental impact as a hazardous gas which is emitted by several industrial sectors. This study reports the optimized synthesis of WO₃ flower-like structures using the microwave-assisted hydrothermal method under various experimental conditions, resulting in the optimized sample designated MF-WO₃-K2. Structural, morphological, and chemical characterizations revealed that WO₃ microflowers (MF-WO₃-K2) exhibit a hexagonal crystalline phase, a bandgap of 2.4 eV, and a high specific surface area of 61 m²/g. The gas-sensing performance of WO₃ microflowers was investigated by electrical measurements of six similarly fabricated MF-WO₃-K2 sensors. The MF-WO₃-K2 sensors demonstrated a remarkable sensor signal of 225 for 5 ppm NO₂ at 150 °C and response/recovery times of 14.5/2.4 min, coupled with outstanding selectivity against potential interfering gases such as CO, H₂, C₂H₂, and C₂H₄. Additionally, the sensors achieved a low detection limit of 65 ppb for NO₂ at 150 °C. The exceptional sensing properties of WO₃ microflowers are attributed to the abundance of active sites on the surface, large specific surface area, and the presence of pores in the material that facilitate the diffusion of NO₂ molecules into the structure. Overall, the WO₃ microflowers demonstrate a promising ability to be used as a sensitive layer in high-performance chemiresistive gas sensors due to their high sensor performance and good reproducibility for NO₂ detection. Full article

Phytochemicals are plant-derived bioactive compounds with antioxidant, anti-inflammatory, and epigenetic modulatory effects that may contribute to the prevention and management of chronic diseases. This review synthesizes recent evidence on the molecular mechanisms through which phytochemicals influence oxidative stress, inflammatory signaling, and epigenetic regulation. A targeted literature search of the PubMed and Web of Science databases (2015–2025) identified over 400 experimental and review studies investigating phytochemicals with documented antioxidant and epigenetic activities. Eligible articles were selected based on relevance to oxidative stress, inflammation, and DNA or histone modification pathways in chronic diseases. Data were qualitatively analyzed to highlight mechanistic links between redox balance, transcriptional regulation, and disease modulation. The results indicate that several phytochemicals, including hesperidin, phloretin, lycopene, and silybin, modulate signaling cascades—NF-κB, Nrf2, and PI3K/Akt—while also influencing DNA methylation and histone acetylation to restore gene expression homeostasis. Despite strong in vitro and in vivo evidence, translation to clinical practice remains limited by low bioavailability, lack of standardized formulations, and insufficient human trials. Future research should prioritize integrative study designs linking molecular mechanisms to clinical endpoints. Understanding the epigenetic actions of phytochemicals may guide the development of nutraceutical strategies for chronic disease prevention. Full article

This article describes a model for optimizing traffic flow control and generating traffic signal phases based on the stochastic dynamics of traffic and the percolation properties of transport networks. As input data (in SUMO), we use lane-level vehicle flow rates, treating them as random processes with unknown distributions. It is shown that the percolation threshold of the transport network can serve as a reliability criterion in a stochastic model of lane blockage and can be used to determine the control interval. To calculate the durations of permissive control signals and their sequence for different directions, vehicle queues are considered and the time required for them to reach the network’s percolation threshold is estimated. Subsequently, the lane with the largest queue (i.e., the shortest time to reach blockage) is selected, and a phase is formed for its signal control, as well as for other lanes that can be opened simultaneously. Simulation results show that when dynamic traffic signal control is used and a percolation-dynamic model for balancing road traffic is applied, lane occupancy indicators such as “congestion” decrease by 19–51% compared to a model with statically specified traffic signal phase cycles. The characteristics of flow dynamics obtained in the simulation make it possible to construct an overall control quality function and to assess, from the standpoint of traffic network management organization, an acceptable density of traffic signals and unsignalized intersections. Full article

Cancer stem cells (CSCs) represent a small but critical subpopulation of tumor cells that drive therapy resistance, relapse and metastasis. Gastric cancer stem cells (GCSCs) have been identified through surface markers and transcriptional signatures, revealing their central role in tumor progression. Recently, N⁶-methyladenosine (m⁶A) RNA modification has emerged as a crucial epitranscriptomic regulator of CSC biology. The m⁶A machinery, including “writers” (METTL3, METTL14, WTAP, VIRMA), “erasers” (FTO, ALKBH5) and “readers” (YTHDFs/ YTHDCs, IGF2BPs, hnRNPA2B1), orchestrates RNA stability, splicing, translation and decay, thereby influencing self-renewal and oncogenic signaling. In GCSCs, m⁶A controls pluripotency factors, oncogenic transcripts and non-coding RNAs, collectively reinforcing stemness and malignant potential. Mounting evidence implicates dysregulated m⁶A effectors as not only key drivers of GCSC biology but also as promising biomarkers for patient stratification and therapeutic targets capable of selectively eliminating CSCs. Harnessing this knowledge could enable earlier diagnosis, more accurate patient stratification and more precise treatments. However, challenges remain regarding the resolution of m⁶A profiling, therapeutic selectivity to avoid unwanted toxicity and biomarker validation for clinical use. This review summarizes the discovery and features of CSCs, highlights the functional role of m⁶A in GCSCs, and explores diagnostic and therapeutic opportunities while outlining key difficulties for clinical translation. Full article

Background: Gastric cancer (GC) remains a leading cause of cancer mortality. E3 ubiquitin ligases, as central regulators of protein stability and signaling within the ubiquitin–proteasome system, have been implicated in tumor progression, but their functional roles in GC are not well established. Methods: We integrated bioinformatics analysis of TCGA and GEO datasets, in vitro experiments (including cell proliferation, migration, and apoptosis assays), and computational modeling to identify key prognostic factors in GC. Results: We established two molecular subtypes (E3GC1/E3GC2) with distinct clinical outcomes and developed a 10-gene prognostic signature. The model showed moderate predictive accuracy (AUC: 0.61–0.71) and was validated externally. MMRN1 was upregulated in GC cells and its knockdown significantly inhibited malignant phenotypes. Critically, drug sensitivity analysis revealed high-risk patients were more sensitive to proteasome inhibitors (bortezomib), while low-risk patients responded better to taxane-based chemotherapy (docetaxel). Molecular docking predicted a high-confidence interaction between MMRN1 and NEDD4L, suggesting potential ubiquitination regulation. Conclusions: MMRN1 drives GC cell proliferation and migration in vitro and may be regulated by NEDD4L-mediated ubiquitination. Our study provides a foundation for E3 ligase-based patient stratification and personalized therapy selection in GC. While this study provides comprehensive multi-omics evidence supporting the role of MMRN1 in GC progression, its clinical translation is limited by the lack of in vivo validation and direct experimental evidence of NEDD4L-MMRN1 physical interaction. Further studies using animal models and clinical specimens are warranted to confirm these findings. Full article

Background: FDA-approved artificial sweeteners (ASs) are widely used in food products due to their low-calorie content and high sweetness. However, growing evidence links them to adverse metabolic effects, including stroke and coronary heart disease. The musculoskeletal system, as a key metabolic target organ, has gradually gained attention, but the potential impact of ASs on its health remains unclear. Objective: This systematic review aims to assess the effects of ASs on bone and muscle, explore the underlying biological mechanisms and provide guidance for future research. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science using relevant keywords from inception to 25 June 2025. Studies written in English, available in full text, and investigating FDA-approved ASs in relation to the musculoskeletal system were included. Two independent reviewers screened and selected the eligible studies. The findings were summarized using a narrative synthesis approach. Results: A total of 15 studies (12 preclinical, 3 clinical), covering aspartame, acesulfame potassium, sucralose, and saccharin were included from an initial pool of 662 articles identified across PubMed (168), Embase (368), and Web of Science (126). Among them, twelve studies focused on skeletal effects, four on muscles, and two on joints; three studies reported multiple outcomes. No studies investigated ligaments or tendons. Conclusions: Based on our search, this review provides a narrative synthesis of the available evidence on ASs influencing skeletal structure, development, biomechanical strength, and skeletal muscle metabolism. Potential mechanisms involve gut microbiota, oxidative stress, and signaling pathways such as SIRT1/FOXO3a and PGC-1α/UCP3. Further research is warranted to clarify these mechanisms and to assess the chronic health effects of long-term AS exposure on the musculoskeletal system in human populations. Full article