Search Results (733)

The increasing complexity of cyber–physical manufacturing systems demands simulation architectures that scale with the physical plant without a proportional growth in engineering effort. This paper introduces a formal, symmetry-based framework for behavioral reuse in arbitrary cyber–physical manufacturing systems, implemented within the Siemens NX Mechatronic Concept Designer (MCD), version NX 2506, environment. Symmetry is treated rigorously, as an equivalence relation induced by a symmetry-group action over the set of plant components, and three exploitable classes are defined on this basis: structural symmetry, arising from replicated kinematic configurations; functional symmetry, arising from shared behavioral specifications across instances of a common component class; and temporal symmetry, arising from synchronized cyclic behavior across concurrent actors. From these definitions, a four-condition behavioral inheritance protocol is derived, specifying the prerequisites under which a single behavioral library template is correctly instantiated across an arbitrary number of interchangeable components. The framework is demonstrated on a production cell comprising ten conveyor sections, nine CNC machining centers (5-axis, X/Y/Z/A/B/SP), and two COMAU NJ420-3.0 manipulators—each a 6-axis articulated arm extended by an external linear rail to seven controlled axes—governed through Siemens Sinumerik RunMyRobot/Direct Control and exercised in a co-simulation environment that integrates a Create MyVirtual Machine (CMVM) Software-in-the-Loop (SiL) controller, a Simit Model-in-the-Loop (MiL) communication layer, and MCD for kinematic and behavioral emulation. Using the number of independent behavioral configuration operations as the effort metric, the symmetry-driven approach reduces machining-center configuration effort by 88.9% (from nine independent configurations to one template instantiated nine times) and robot behavioral configuration effort by 100% (both manipulators inherit from a single seven-axis library entry), while preserving full kinematic and signal-level fidelity. The inheritance mechanism is shown to tolerate heterogeneous kinematic substitution: a COMAU NJ420-3.0 may be replaced by any kinematically equivalent 6-axis manipulator in the RunMyRobot database without behavioral reconfiguration. The component and capability mapping matrix (CCMM) introduced in prior work is extended with a symmetry-annotation layer that explicitly encodes instance relationships and inheritance chains, providing a structured input to automated behavioral-deployment workflows. The results establish symmetry-based modular simulation as a principled and scalable methodology for industrial digital-twin development in multi-robot manufacturing environments. Full article

Chronic diseases and aging-related disorders are driven by interconnected mechanisms, including oxidative stress, low-grade inflammation, metabolic dysregulation, and glycation. Targeting these overlapping pathways remains a major challenge for conventional single-target therapeutics. In this context, endophytic fungi have emerged as a promising source of bioactive metabolites with multi-target pharmacological potential. This review provides a mechanistic overview of endophyte-derived metabolites, including alkaloids, terpenoids, polyketides, and phenolic compounds, with a focus on their ability to modulate key signaling pathways such as NF-κB, Nrf2, PI3K/Akt, AMPK, and the AGE–RAGE axis. Evidence from experimental studies suggests that these metabolites exhibit anticancer, anti-inflammatory, antioxidant, and metabolic regulatory effects through coordinated modulation of cellular signaling networks. Several endophyte-derived metabolites also possess antimicrobial activity against bacterial and fungal pathogens and may represent a promising source of novel anti-infective agents. Their ability to modulate host immune responses and microbial-associated signaling pathways further highlights their relevance for antimicrobial discovery and microbiome-based therapeutic strategies. Particular attention is given to pathway-level convergence in chronic diseases, including cancer, diabetes, and inflammation-associated disorders, as well as their relevance to aging and health span. The pharmacological potential of these compounds is discussed alongside key limitations, including issues related to bioavailability, reproducibility, and translation into clinical applications. Overall, endophytic fungal metabolites represent a structurally diverse and mechanistically rich resource for the development of multi-target therapeutic strategies. Future integration of metabolomics, genome mining, and advanced disease models will be essential to bridge the gap between experimental findings and clinical application. Full article

Background and Objectives: Endometriosis is associated with chronic inflammation, immune dysregulation, oestrogen-dependent growth, oxidative stress, altered steroid hormone metabolism, compromised epithelial barrier integrity, and the production of bioactive microbial metabolites. These interconnected alterations have been proposed to create, in principle, a permissive local microenvironment for malignant transformation. This narrative review examines whether endometriosis-associated dysregulation of the gut and reproductive tract microbiota may act as a hypothetical biological modulator linking these multi-axis changes to endometrial carcinogenesis, with attention to immunological, endocrine, metabolic, microbial–metabolite, oxidative, and barrier-related pathways. Material and Methods: We narratively integrated current evidence on gut and reproductive tract microbiota alterations relevant to endometrial homeostasis, with emphasis on the estrobolome, low-biomass uterine microbial communities, inflammatory and immune signaling, microbial metabolites, and pathways implicated in carcinogenesis. Results: Available data suggest that dysbiosis may influence endometrial carcinogenesis through interconnected endocrine, inflammatory, metabolic, and immune mechanisms. Attention has been given to loss of Lactobacillus dominance, enrichment of anaerobic and pro-inflammatory taxa, altered estrogen recirculation, progesterone resistance, Toll-like receptor activation, NF-κB/STAT3 signaling, COX-2/PGE2 activity, PI3K/AKT/mTOR pathway activation, oxidative stress, macrophage polarization, and impaired natural killer cell surveillance. These alterations may contribute to a permissive microenvironment characterized by persistent inflammation, defective immune control, and disrupted endometrial homeostasis. However, the current literature remains limited by small and heterogeneous cohorts, predominantly cross-sectional designs, contamination risk, and marked methodological variability, particularly in low-biomass uterine samples. Conclusions: Current evidence supports the view that microbiome dysregulation is a context-dependent biological modulator that intersects with endocrine, inflammatory, metabolic, immune, oxidative, and barrier-related pathways relevant to endometrial carcinogenesis. Microbiome dysbiosis should be regarded as a hypothetical contributory factor rather than as an established causal driver. Its near-term translational relevance appears greater for biomarker development and risk stratification than for immediate microbiome-directed therapy. Longitudinal, standardized, and functionally integrated studies are needed to clarify whether microbiome-associated signatures can be translated into clinically meaningful prevention and management strategies in endometrial cancer. Full article

Ginkgo biloba extract (GBe) attenuates the transition of cisplatin (CDDP)-induced acute kidney injury to chronic kidney disease (AKI-to-CKD). Purpose: This study aimed to reveal the mechanism by which GBe inhibits CDDP-induced AKI-to-CKD. The potential targets of GBe in alleviating CDDP-induced renal interstitial fibrosis (Cis-RIF) were predicted through network pharmacology. Transcriptomics and metabolomics were used to detect differentially expressed genes (DEGs) and metabolites (DEMs) in renal tissues from Cis-RIF rats. Integrated multi-omics analysis was performed to determine the potential mechanism underlying GBe inhibiting AKI-to-CKD, and experimental verification was conducted in vivo, in vitro, and using siRNA. We identified 100 targets of GBe that could inhibit Cis-RIF using network pharmacology, and these targets were enriched in 194 signaling pathways. Transcriptomics and metabolomics revealed 8907 DEGs (enriched in 51 pathways) and 424 DEMs (enriched in 16 pathways), respectively. Collectively, the phosphatidylinositol signaling pathway was a co-enriched pathway, which may be the key pathway through which GBe inhibits AKI-to-CKD. This was verified experimentally. The related apoptosis and fibrosis indicators, and the key targets of the phosphatidylinositol signaling pathway (PLC, PKC, PIP2, IP3, DAG, Ca²⁺), in rat renal tissues and renal tubular epithelial cells (RTECs) with CDDP-induced AKI-to-CKD were significantly increased. Inhibition of HIF-1α and knockdown of HIF-1α in RTECs reversed the changes the phosphatidylinositol pathway targets. Moreover, both GBe and the HIF-1α inhibitor could inhibit HIF-1α and the phosphatidylinositol pathway targets, as well as the apoptosis and EMT of RTECs. Conclusion: This study reveals for the first time that GBe may inhibit AKI-to-CKD by downregulating apoptosis and EMT in RTECs through the HIF-1α/phosphatidylinositol signaling axis. Full article

Ultrasound examination for developmental dysplasia of the hip (DDH) in infants is highly dependent on operator experience, leading to inconsistent imaging quality and poor reproducibility between sonographers. This study proposes an autonomous robotic ultrasound system to improve the standardization and automation of hip ultrasound examinations. The system consists of a robotic arm, a six-axis force/torque sensor, an RGB-D camera and an ultrasound probe, integrating multiple functions including contact force control, visual localization, deep-learning-based segmentation and ultrasound image screening. To ensure stability and safety during scanning, an admittance-based hybrid force/position control strategy is adopted to achieve constant contact force control. For Graf standard plane acquisition, a stage-wise search strategy is designed, in which the search space is progressively narrowed through femoral head searching and multi-angle scanning. The optimal Graf standard plane is then automatically selected by combining image segmentation with a scoring mechanism. A customized hip phantom was used for validation. Experimental results show that the Dice coefficient for femoral head segmentation reaches 0.872, while the average Dice coefficient for multi-structure segmentation reaches 0.866. In 30 autonomous scanning trials, the success rate of Graf standard plane acquisition is 90.0%. Meanwhile, the system can maintain the contact force stably within the target range during scanning, validating the effectiveness of the force control strategy. These results indicate that the proposed robotic system, image recognition algorithm and visual servo control strategy exhibit favorable safety and feasibility, providing an innovative solution for automated infant hip ultrasound examination of DDH. Full article

Background: Noise-induced hearing loss (NIHL) is a pervasive occupational health challenge, yet the individual susceptibility mechanisms remain unclear. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in cochlear hair cell damage. This study aims to elucidate the regulatory role of the transcription factor FOXA2 and the deacetylase SIRT1 in ferroptosis and to investigate the association between SIRT1 genetic polymorphisms and NIHL susceptibility in occupational populations. Methods: We employed a multi-level study design combining epidemiological investigation, animal models, and cellular experiments. First, a case–control study was conducted involving 1314 noise-exposed workers (639 cases vs. 675 controls) from a chemical fiber enterprise in Jiangsu Province to analyze the association between SIRT1 single nucleotide polymorphisms (SNPs) and NIHL risk. Second, a C57BL/6J mouse model exposed to 120 dB white noise was established to assess cochlear morphology and protein expression. Third, in HEI-OC1 cochlear hair cells, we performed siRNA-mediated knockdown of Foxa2 and dual-luciferase reporter assays to verify the transcriptional regulation of SIRT1 and its downstream effects on the ferroptosis pathway. Results: Population analysis revealed that the SIRT1 rs12778366 C allele was significantly associated with increased NIHL risk (OR = 1.386, 95% CI: 1.084–1.772, p = 0.009), and this association remained significant after adjustment (p = 0.041). Stratified analysis further revealed a significant gene–environment interaction in workers with >15 years of noise exposure (OR = 2.126, 95% CI: 1.401–3.226, p < 0.001). In vivo, noise exposure led to significant downregulation of Sirt1 and Foxa2 in cochlear tissues, accompanied by elevated ferroptosis markers (Fe²⁺, MDA) and depleted antioxidant defenses (GSH, xCT, and GPX4). Mechanistically, we demonstrate that FOXA2 transcriptionally activates SIRT1 by binding to its promoter. Knockdown of FOXA2 in vitro suppressed SIRT1 expression, suppressed xCT, a key component of the System Xc⁻/GPX4 antioxidant axis, and promoted ferroptosis-related cellular changes. Conclusions: This study identifies a novel protective axis where FOXA2 prevents noise-induced ferroptosis in cochlear hair cells by transcriptionally upregulating SIRT1 and maintaining xCT-mediated antioxidant defense. Furthermore, the SIRT1 rs12778366 polymorphism is identified as a candidate variant warranting further investigation in independent cohorts before clinical translation. Full article

To addressthe challenge of attitude control in quad-ducted fan unmanned aerial vehicles (UAVs) under coupled disturbances comprising thrust lag, ground effect and a composite wind field during near-ground flight and to mitigate the inherent trade-off between disturbance rejection and noise suppression in fixed-bandwidth extended state observers (ESOs), this paper proposes a robust attitude control method based on a Sigmoid law adaptive-bandwidth extended state observer (AB-ESO). An attitude dynamic model covering the above multi-source disturbances is established, with all uncertainties uniformly treated as lumped disturbances. An adaptive-bandwidth mechanism with filtering and rate-limiting modules is designed for smooth continuous bandwidth tuning. A composite control framework integrating disturbance feedforward, lag compensation and attitude feedback is constructed, and the uniform ultimate boundedness of the closed-loop system is proved. Comparative simulations are conducted against six baseline controllers, including a cascade proportional–integral–derivative (PID) controller, fixed-bandwidth ESOs, incremental nonlinear dynamic inversion (INDI), fast terminal sliding mode control (FTSMC) and a time-varying bandwidth ESO, in a near-ground composite wind scenario. Results show that the proposed method achieves improved comprehensive performance: the three-axis average tracking root mean square error (RMSE) is approximately 72% lower than of the PID controller and 15.8% lower than that of the high-bandwidth ESO, and the control output total variation is reduced by about 27.8%. Monte Carlo verification with 100 random turbulence groups further validates the strong statistical robustness of the proposed method. All validations in this work are based on numerical simulations. This study provides a technical reference for high-precision control of ducted fan UAVs in near-ground environments. Full article

Modern aerospace vehicles operate under complex multiaxial dynamic environments throughout service, including multidirectional coupled shock, random vibration, harmonic vibration, and aeroelastic excitation. While conventional sequential uniaxial testing facilitates engineering implementation, it cannot replicate the spatial coherence, phase relationships, and nonlinear coupling effects of operational environments. This issue may bias the evaluation of structural response, fatigue damage, and onboard equipment functional degradation. This review summarizes recent advances in multiaxial shock/vibration environment simulation and damage evaluation for aerospace vehicles. It covers multiaxial load source classification, transmission paths and coupling mechanisms, dynamic response analysis, shock- and vibration-induced damage models, and updated experimental testing technologies. This work further identifies unresolved challenges in load-spectrum measurement, spectral-matrix reproduction, nonlinear path recognition, and coupled shock–vibration damage assessment. Future research directions are proposed, including multiaxial service-environment database construction, unified response and damage equivalence criteria, and integrated evaluation frameworks for structural, equipment and functional performance. This review provides technical references for the environmental design, structural qualification and reliability assessment of aerospace systems. Full article

To address the unstable detection of weak orbital maneuvers from publicly available Two-Line Element (TLE) data affected by natural perturbations, orbit-determination errors, outliers, and irregular update intervals, an adaptive multi-feature maneuver-detection method is proposed. The method incorporates a dominant $J_2$ perturbation correction into the computation of the mean semimajor axis and combines semimajor-axis variation, eccentricity variation rate, and local dispersion of mean motion. A two-stage outlier-processing scheme, iterative background-noise estimation, and an adaptive switching mechanism based on the sampling interval are further introduced. Multi-object simulations for low- and high-altitude satellites show that the average detection accuracies for along-track maneuvers are 94.47% and 93.95%, respectively, while those for radial maneuvers are 92.83% and 93.26%, respectively. The proposed method demonstrates stable detection performance and good applicability across different orbital altitudes and maneuver directions. Full article

Bone remodeling imbalance represents the fundamental pathological basis of osteoporosis. Exercise is broadly regarded as a valuable non-pharmacological strategy for preventing and managing osteoporosis; however, the precise molecular mechanisms through which exercise modulates bone metabolism remain incompletely understood. Mitophagy has recently been recognized as an important mediator linking exercise to the regulation of bone remodeling. This review centers on the “exercise–mitophagy–bone remodeling” axis, systematically outlining the biological processes and regulatory determinants of mitophagy within the bone microenvironment. Evidence suggests that mitophagy facilitates bone formation by preserving mitochondrial quality, attenuating oxidative stress, and optimizing cellular energy metabolism. Moreover, it exerts stage-specific inhibitory effects on bone resorption during osteoclast differentiation. Particular emphasis is placed on the mechanisms by which exercise activates mitophagy-related signaling pathways via metabolic, mechanical, and hypoxic stimuli. In addition, exercise may enhance the efficiency of this regulatory axis by maintaining vitamin D and calcium homeostasis and modulating estrogen signaling pathways. The differential effects of exercise modalities and durations on these processes are also critically evaluated. Finally, this review addresses current limitations in existing research and highlights future directions, including the optimization of exercise interventions targeting mitophagy and the integration of multi-omics approaches. These findings offer a theoretical basis for designing precise exercise regimens and combined therapeutic approaches in the management of osteoporosis. Full article

Lonicera japonica Thunb. (honeysuckle), a traditional herb with “food-medicine homology” status in Chinese medicine, is valued for its antipyretic and detoxifying properties. This review systematically summarizes its chemical composition—over 507 identified compounds, including phenylpropanoids, flavonoids, triterpenoids, saponins, and the plant-specific miR2911—as well as its multi-target pharmacological mechanisms and emerging translational applications, with particular emphasis on the gut–brain axis-mediated neuroprotective effects. Despite low oral bioavailability, honeysuckle polysaccharides and chlorogenic acid have been shown to exert significant neuroprotection in Alzheimer’s disease models by modulating gut microbiota composition, increasing short-chain fatty acid production, and restoring intestinal barrier integrity—a mechanism that challenges conventional direct-action paradigms. We also outline the applications of honeysuckle in functional foods, pharmaceuticals, animal husbandry, and cosmetics, and propose future directions including precision fermentation and mechanism-driven clinical trials. By integrating phytochemistry, pharmacology, and biotechnology, this review provides a roadmap for the evidence-based development of honeysuckle as a precise medicinal and edible resource. Full article

The estrobolome, defined as the collection of gut microbial genes encoding enzymes that metabolize estrogens and, by extension, the taxa that harbor them, has emerged as a central node of the new concept of “microbial endocrinology” within the gut–vagina axis. By regulating enterohepatic recirculation of conjugated estrogens, the estrobolome may modulate systemic estrogen availability and thereby may influence the estrogen-dependent biology of gynecological organs and tissues, including ovaries, endometrium, and the vaginal mucosa with its Lactobacillus-dominated ecosystem. In this narrative review, we synthesize current evidence on how gut microbial β-glucuronidases, sulfatases, and related enzymes shape circulating estrogen pools and, in turn, gynecological health. We outline the enzymatic and taxonomic architecture of the estrobolome, describe its major ecological determinants, and integrate these with mechanisms of the gut–vagina axis. We then examine how estrobolome function varies across a woman’s lifespan and how these dynamics intersect with vaginal health, dysbiosis, and conditions such as recurrent vaginitis, endometriosis, and polycystic ovary syndrome. We also review emerging strategies that may modulate the estrobolome as a microbial endocrine organ and discuss their potential downstream effects on gynecological health. Finally, we highlight major research gaps, particularly the need for causal, longitudinal, multi-omics studies explicitly linking estrobolome activity, systemic estrogens, and gynecological outcomes. Overall, available data support a mechanistically plausible but incompletely defined role for the estrobolome as a key microbial endocrine player in the gut–vagina axis and point toward microbiome-informed strategies to preserve and restore gynecological health across a woman’s lifespan. Full article

Mechanical speed sensors increase cost and may reduce the reliability of permanent magnet synchronous motor (PMSM) drives under harsh conditions. This paper proposes a validation-protected physics-consistent probabilistic neural estimator for sensorless PMSM speed estimation using only online-deployable signals: the previous estimated speed, measured d/q-axis currents, and commanded d/q-axis voltages. A multi-output probabilistic network predicts the speed distribution and auxiliary residual-compensation variables. Mechanical consistency, electrical consistency, and regularization losses are imposed during training, while a validation-protected rule selects, for each random seed, the checkpoint with the lower validation RMSE from the paired baseline and physics-trained candidates. Experiments use a frozen multi-seed protocol covering locked holdout evaluation, independent comparison, and disturbance tests. Across Datasets 8–11, the frozen predictive distributions yielded Gaussian NLL values from 3.190 to 3.239, 100% empirical coverage of the nominal 95% prediction intervals, and mean interval widths of approximately 35.9 rad/s, indicating conservative rather than well-calibrated uncertainty. On locked Dataset 7, Physics-safe reduced the mean RMSE from 3.415 to 3.277 and the inter-seed standard deviation from 0.290 to 0.052. Results on Datasets 8–11 show that the method is not universally mean-error optimal; its recurring advantage is lower inter-seed variability and more reproducible training outcomes. A local sensitivity analysis on Dataset 4 confirmed seed- and loss-weight-dependent physics-training outcomes, supporting the need for validation protection without implying globally optimal loss weights. On the specified desktop CPU using ONNX Runtime, the complete recursive estimator step required 40.154 microseconds, below the adopted 100-microsecond sampling interval, supporting estimator-level computational feasibility. Full article

Background/Objectives: Microsatellite-stable colorectal cancer (MSS CRC) accounts for the vast majority of CRC cases and remains largely resistant to immune checkpoint inhibitors. Emerging evidence suggests that the gut microbiome is an important regulator of antitumor immunity and may contribute to immunotherapy resistance through multiple mechanisms involving the tumor microenvironment. This review aims to summarize current knowledge of the microbiome–immunity–therapy axis in MSS CRC and to explore microbiome-based strategies to enhance immunotherapy responsiveness. Methods: A narrative review of the recent literature was conducted, focusing on studies published within the last five years that investigated gut microbiota composition, microbial metabolites, tumor immune regulation, immunotherapy response, and microbiome-targeted therapeutic interventions in CRC. Evidence from mechanistic studies, translational research, clinical investigations, and multi-omics analyses was integrated. Results: Current evidence indicates that gut dysbiosis contributes to immune resistance in MSS CRC through immune exclusion, myeloid-driven immunosuppression, T-cell dysfunction, chronic inflammation, and altered microbial metabolite signaling. Specific microorganisms, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks-positive Escherichia coli, and other CRC-associated pathobionts, have been implicated in tumor progression and modulation of antitumor immunity. Microbial metabolites such as short-chain fatty acids, tryptophan-derived compounds, bile acids, succinate, and inosine represent key functional mediators linking microbial communities to host immune responses. Emerging microbiome-targeted interventions, including fecal microbiota transplantation, next-generation probiotics, postbiotics, selective microbial depletion, and engineered bacterial therapeutics, have shown promising results in preclinical models and early translational or clinical studies, although robust clinical evidence remains limited. In parallel, advances in metagenomics, metabolomics, spatial transcriptomics, and artificial intelligence are facilitating the development of precision immuno-microbiome oncology approaches. Conclusions: The gut microbiome functions as a critical regulator of immune resistance in MSS CRC through coordinated effects on microbial composition, metabolite production, and tumor immune remodeling. Microbiome-targeted interventions, combined with multi-omics-based patient stratification, may provide new opportunities to overcome immunotherapy resistance and expand the clinical benefits of immune checkpoint blockade in this traditionally refractory disease. Full article

Ovarian cancer treatment remains challenging due to aggressive metastasis and the complex tumor microenvironment (TME). Solanum nigrum L. (SN), a berry-bearing plant rich in bioactive phytochemicals, offers promising multi-target anticancer potential. This study elucidated the systemic molecular mechanisms of SN fractions against ovarian cancer by integrating network pharmacology, molecular docking, and in vitro models. In silico analyses and molecular docking identified apoptosis, metastasis-related pathways, and NF-κB (RELA) as core targets. For in vitro validation, butanol (SNBT) and methylene chloride (SNMC) fractions of SN were evaluated in SKOV3 cells. SNBT significantly induced caspase-3-dependent apoptosis, while SNMC effectively suppressed cancer cell migration and invasion without cytotoxicity. Furthermore, both fractions markedly downregulated phosphorylated AKT and NF-κB, experimentally confirming the suppression of the AKT/NF-κB signaling axis. Crucially, in a tumor-associated macrophage co-culture model, SNMC attenuated the pro-metastatic TME by reducing MMP2, MMP9, and VEGF secretion. Conclusively, SN exerts potent anticancer effects through distinct fractional activities, such as driving apoptosis and blocking metastasis, mediated via AKT/NF-κB inhibition and TME remodeling. These findings highlight SN-derived fractions as promising multi-target therapeutic candidates against ovarian cancer. Full article