Search Results (145)

Background/Objectives: Late-onset neonatal sepsis (LOS) remains a leading cause of morbidity and mortality in very low birth weight (VLBW) infants (<1500 g and/or gestational age <32 weeks), with limited preventive strategies. We evaluated whether early enteral bovine lactoferrin (bLf), given its antimicrobial, immunomodulatory, and antioxidant properties, reduces LOS and improves immunologic, antioxidant, and hematologic markers in these infants. Methods: In this randomized, double-blind, placebo-controlled trial, 103 VLBW infants received bLf (150 mg/kg/day; n = 50) or the placebo (n = 53) within 72 h of birth for four weeks or until discharge. Outcomes included culture-confirmed LOS, mortality, and major morbidities. Risk ratios (RRs) were calculated, adjusting for gestational age, human milk intake, and ventilatory support when ≥25 events occurred. Pre/post changes in cytokines, total antioxidant capacity (TAC), and hemoglobin (Hb) were analyzed for interaction effects (time x intervention). Results: bLf reduced LOS (adjusted RR 0.54; 95% CI 0.31–0.93; p = 0.028), without differences in other morbidities or mortality. bLf preserved MCP-1 levels, declining in the placebo group (interaction p = 0.022). Among LOS infants receiving bLf, IL-6 remained stable and MCP-1 increased, while both declined in other groups (interaction p = 0.007 for IL-6; p = 0.052 for MCP-1). Although TAC showed a non-significant interaction, the placebo group declined (p = 0.002), while bLf remained stable (p = 0.400) in the post hoc analysis. In non-transfused infants, bLf increased Hb by 0.9 g/dL vs. controls (p = 0.028). Conclusions: Early bLf supplementation safely reduces LOS in VLBW infants and may support immunologic, antioxidant, and hematologic stability. Full article

For multi-agent systems under Denial-of-Service (DoS) attacks, a relative threshold strategy for event triggering and a state-constrained control method with prescribed performance are proposed. Within the framework of combining graph theory with the leader–follower approach, coordinate transformation is utilized to decouple the multi-agent system. Inspired by the three-way handshake technology of TCP communication, a DoS detection system is designed based on event-triggering. This system is used to detect DoS attacks, prevent the impacts brought by DoS attacks, and reduce the update frequency of the controller. Fuzzy logic systems are employed to approximate the unknown nonlinear functions within the system. By using a first-order filter to approximate the derivative of the virtual controller, the computational complexity issue in the backstepping method is addressed. Furthermore, The Barrier Lyapunov Function (BLF) possesses unique mathematical properties. When the system state approaches the pre-set boundary, it can exhibit a special variation trend, thereby imposing a restrictive effect on the system state. The Prescribed Performance Function (PPF), on the other hand, defines the expected performance standards that the system aims to achieve in the tracking task, covering key indicators such as tracking accuracy and response speed. By organically integrating these two functions, the system can continuously monitor and adjust its own state during operation. When there is a tendency for the tracking error to deviate from the specified range, the combined function mechanism will promptly come into play. Through the reasonable adjustment of the system’s control input, it ensures that the tracking error always remains within the pre-specified range. Finally, through Lyapunov analysis, the proposed control protocol ensures that all closed-loop signals remain bounded under attacks, with the outputs of all followers synchronizing with the leader’s output in the communication graph. Full article

This paper refers to fast and accurate electric servo control in the presence of position and velocity constraints. This problem, one of the most common nowadays in industrial automation, is often addressed by controllers derived using barrier Lyapunov functions (BLFs). This popular and effective technique is burdened with several difficulties, such as complex feasibility conditions and the inapplicability of the derived controller because of control constraints. In this contribution, we propose a novel, BLF-based, adaptive controller for an electric servo (linear or rotational) with modeling uncertainties, solving a tracking problem. The controller derivation is completed by the tuning procedure, which enables safe system operation in the presence of active control constraints, measurement errors, and noise. The selection of the best combination of BLFs is a part of this procedure. Also, all feasibility issues are solved by the proposed approach. The derivation is completed by extensive numerical simulations and real-life implementation using two different servo systems—the first with a linear permanent magnet motor and the second with a rotational PMSM. Full article

Chitosan coatings have been demonstrated to be a highly effective and safe approach to extending the shelf life of food. This study, for the first time, evaluates the effectiveness of bamboo-leaf flavonoids (BLFs) added to a chitosan coating to delay the spoilage of strawberries, blueberries, and bamboo shoots. The addition of BLFs improved the tensile strength of the coatings. Chitosan coating incorporated with 0.1% BLFs had the highest tensile strength (36.38 ± 2.69 MPa). BLFs conferred antioxidant properties to chitosan coatings as determined by DPPH radical scavenging activity. Key quality parameters were measured over the storage period of strawberries, blueberries, and bamboo shoots. The coating significantly affected the impact of storage time on some variables. Chitosan/BLF coatings were particularly effective in limiting changes over time in weight loss, spoilage percentage, and vitamin C content (strawberries and blueberries), as well as crude fiber content (bamboo shoots), although their effect on titratable acid, soluble solids, and soluble protein content was less pronounced. The chitosan/BLFs composite coating demonstrated superior efficacy over pure chitosan in delaying spoilage. In conclusion, the chitosan/BLF coating could be useful for maintaining the quality of strawberries, blueberries, and bamboo shoots. Full article

This paper resolves the predefined-time control problem for multi-agent systems under predefined performance metrics and state constraints, addressing critical limitations of traditional methods—notably their inability to enforce strict user-specified deadlines for mission-critical operations, coupled with difficulties in simultaneously guaranteeing transient performance bounds and state constraints while suffering prohibitive stability proof complexity. To overcome these challenges, we propose a predefined performance control methodology that integrates Barrier Lyapunov Functions command-filtered backstepping. The framework rigorously ensures exact convergence within user-defined time independent of initial conditions while enforcing strict state constraints through time-varying BLF boundaries and further delivers quantifiable performance such as overshoot below 5% and convergence within 10 s. By eliminating high-order derivative continuity proofs via command-filter design, stability analysis complexity is reduced by 40% versus conventional backstepping. Stability proofs and dual-case simulations (UAV formation/smart grid) demonstrate over 95% tracking accuracy under disturbances and constraints, validating broad applicability in safety-critical multi-agent systems. Full article

Background: Sepsis remains a significant cause of morbidity and mortality in preterm and low birth weight (LBW) neonates, especially in low- and middle-income countries (LMICs). Lactoferrin, a glycoprotein present in breast milk with antimicrobial activity, is a low-cost, readily available, and promising intervention currently under investigation. The available literature presents conflicting results on the impact of lactoferrin on the risk of late-onset sepsis (LOS). This study evaluated the effectiveness of two doses of bovine lactoferrin (bLF) supplementation in preventing LOS and necrotizing enterocolitis (NEC) in preterm and LBW neonates in Pakistan. Methods: A three-arm, double-blind, placebo-controlled, randomized clinical trial in the neonatal intensive care unit of Aga Khan University was conducted from July 2019 to August 2020. Preterm (28 to 36 + 5 weeks gestational age) and low birth weight (≥1000 g to <2500 g) neonates who established enteral feeding by 72 h were eligible. The exclusion criteria included sepsis before randomization, maternal history of chorioamnionitis or group B streptococcus colonization, and congenital anomalies. Enrolled neonates were randomly assigned in a 1:1:1 ratio using a computer-generated random allocation sequence to receive placebo (D-glucose), 150 mg bLF, or 300 mg bLF mixed with breast milk once daily for 28 days. The study staff, parents, and outcome assessors were blinded to the allocation. The primary outcome was late-onset sepsis from the trial entry to 28 days. The secondary outcome was NEC from the trial entry to 28 days. Neonates were followed weekly for 28 ± 2 days, and episodes of LOS and NEC were recorded. Results: Of 305 neonates enrolled, 102, 102, and 101, respectively, were randomized to receive a placebo (arm A), 150 mg bLF (arm B), and 300 mg bLF (arm C), respectively. Outcome data of 291 participants (99 in arm A, 95 in arm B, and 97 in arm C) were available for inclusion in the intention-to-treat analysis. The frequency of culture-proven sepsis was 8/102 (7.8%) in arm A compared to 1/102 (0.98%) (p = 0.020) in arm B and 5/101 (4.9%) in arm C (p = 0.390). We did not find any difference in episodes of NEC between arms A (n = 3, 3%) and B (n = 0, 0%) (p = 0.087) or between arms A and C (n = 2, 2%) (p = 0.650). We reported compliance rates of 79 (79.79%) in arm A, 78 (82.1%) in arm B, and 82 (84.53%) in arm C for investigational products. Arm C recorded two deaths, but neither was attributed to the intervention. Conclusions: Bovine lactoferrin supplementation did not prevent late-onset sepsis in neonates of preterm and low birth weight in our trial. However, given the small sample size, further trials with larger sample sizes are required to investigate its efficacy in these at-risk groups. Full article

Background/Objectives: Dry eye disease (DED), also known as “keratoconjunctivitis sicca”, is a common chronic ocular surface disease accompanied by inflammation and diminished tear production. Bovine Lactoferrin (BLF), a multi-functional iron-binding glycoprotein found in tears, decreased significantly in patients with DED, used for the treatment of dry eye, conjunctivitis, and ocular inflammation. BLF has limited therapeutic efficacy due to poor ocular bioavailability. Methods: This study developed and optimized a BLF-loaded nanosuspension (BLF-NS) using the Box–Behnken Design (BBD). Optimized BLF-NS was then incorporated with polyvinyl pyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) dissolving microneedles (MNs). The formulations were characterized by Scanning and transmission microscopy, DSC, FTIR, ex vivo studies in corneal tissue from sheep and tested for its antibacterial and antifungal efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Aspergillus niger, respectively. Moreover, they were tested for their Benzalkonium chloride (BCL) dry eye in a rabbit model. Results: The optimized nanosuspension showed a vesicle size of (215 ± 0.45) nm, a Z.P (zeta potential) of (−28 ± 0.34) mV, and an Entrapment Efficiency (EE%) of (90 ± 0.66) %. The MNs were fabricated using a ratio of biodegradable polymers, PVP/HPMC. The resulting BLF-NS-MNs exhibited sharp pyramidal geometry with high mechanical strength, ensuring ocular insertion. In vitro release showed 95% lactoferrin release over 24 h, while ex vivo permeation achieved 93% trans-corneal delivery. In vivo, BLF-NS-MNs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6, MMP-9, IL-1β, MCP-1) and upregulated antioxidant and anti-inflammatory genes (PPARA, SOD 1), restoring their levels to near-normal (p < 0.001). Conclusions: The nanosuspension combined with MNs has shown higher ocular tolerance against DED ensured by the Draize and Schirmer Tear Test. Full article

Burkholderia lethal factor 1 (BLF1), a toxin derived from Burkholderia pseudomallei, reacts with eukaryotic initiation factor (eIF) 4A to inhibit protein synthesis. eIF4A1 and eIF4A2 are involved in translation initiation and share over 90% sequence similarity. However, they exert distinct effects on cancer treatment outcomes. To understand the molecular mechanism by which BLF1 modulates eIF4A isoforms in cancer cells, we investigated its effects on eIF4A-mediated adenosine 5′-triphosphate (ATP) hydrolysis. We found that eIF4A1 has a higher ATP-binding affinity compared to eIF4A2 (K_m = 6.55 ± 0.78 μM vs. K_m = 11.61 ± 2.33 μM). Meanwhile, we also found that eIF4A1 is more sensitive to changes in temperature, pH, and Mg²⁺ concentration. Through N-terminal swapping and single amino acid mutations, we found that leucine 98 (L98) and alanine 100 (A100) play important roles in the ATPase activities of eIF4A isoforms. Moreover, BLF1 treatment significantly enhanced eIF4A2-mediated ATP hydrolysis at all tested ATP concentrations. These differences in BLF1-regulated eIF4A isoforms may explain its selective cytotoxicity against cancer cells. Our findings provide molecular insights into the functional difference between eIF4A isoforms and suggest that BLF1 might be of promising value for anticancer therapies. Full article

In vineyard mulching research, using biodegradable liquid mulch represents a novel and environmentally conscious approach to mulching. In comparison, grapevine branch return has been identified as the most effective mulching method. The effects of in-row mulching with two materials, biodegradable liquid film (BLF) and grapevine branches (GBM), on soil properties and microbial communities in the vineyard were assessed using a one-way horizontal block test with tillage as a control. The results indicated that the application of mulching resulted in a reduction in soil bulk weight; an increase in soil moisture; an enhancement in soil organic matter; and a notable elevation in soil nutrients content compared to the control treatment. Both mulching techniques increased the abundance and diversity of soil microorganisms, strongly correlated with soil physicochemical properties. The correlation analysis demonstrated that total organic carbon (TOC); total nitrogen (TN); total potassium (TK); nitrate nitrogen (NN); and available phosphorus (AP) had the most significant impact on shaping the microbial community, exhibiting a positive correlation with microbial diversity. Additionally, soil nutrients were identified to exert a more pronounced influence on the composition of the bacterial community. Full article

This study presents a novel finite-time robust control framework for quadrotor systems subjected to model uncertainties and unknown external disturbances. A fast terminal sliding mode (FTSM) manifold is first constructed to achieve finite-time convergence of tracking errors. To address the challenges posed by uncertain system dynamics, a radial basis function neural network (RBFNN) is integrated for real-time approximation of unknown nonlinearities. In addition, an adaptive gain regulation mechanism based on a barrier Lyapunov function (BLF) is developed to ensure boundedness of system trajectories while enhancing robustness without requiring prior knowledge of disturbance bounds. The proposed control scheme guarantees finite-time stability, strong robustness, and precise trajectory tracking. Numerical simulations substantiate the efficacy and superiority of the proposed method in comparison with existing control approaches. Full article

Lateral handling stability control is crucial for ensuring vehicle driving safety. To address this issue, this paper proposes a lateral handling stability control method that considers time-varying full-state constraints. By constructing a time-varying symmetric Barrier Lyapunov Function (TS-BLF), this method imposes time-varying nonlinear constraints on both the sideslip angle and yaw rate, thereby ensuring full-state constrained stability control of vehicles under complex operating conditions. Additionally, a second-order command filtering technique with an error compensation mechanism is introduced to reduce the computational complexity of control laws while mitigating filter-induced errors that may degrade system performance. To validate the effectiveness and robustness of the proposed method, the vehicle’s dynamic response is analyzed under different speeds on both dry asphalt pavement and dry gravel surfaces. The simulation results demonstrate that the proposed method effectively suppresses understeer and oversteer, enhances the dynamic stability margin under extreme operating conditions, and improves vehicle adaptability in complex environments. Full article

This study focuses on the distributed fixed-time fault-tolerant control problem for a network of six-degree-of-freedom (DOF) fixed-wing unmanned aerial vehicles (UAVs), which are subject to full-state constraints and actuator faults. The novelty of the proposed design lies in the incorporation of an enhanced asymmetric time-varying tan-type barrier Lyapunov function (BLF), which is applicable in both constrained and unconstrained scenarios. This function ensures that the UAV states remain within compact sets at all times while achieving fixed-time convergence. Additionally, a fixed-time performance function (FTPF) is developed to eliminate the dependency on exponential functions commonly used in traditional fixed-time control methods. The adverse effects of actuator faults, including lock-in-place and loss of effectiveness, are mitigated through a bounded uniform tracking control design. A rigorous Lyapunov function analysis demonstrates that all closed-loop signals are semi-globally uniformly ultimately bounded (SGUUB), with both velocity and attitude tracking errors converging to residual sets near the origin. Experimental validation tests are conducted to confirm the effectiveness of the theoretical findings. Full article

Flexible-joint manipulators have a lightweight nature, compact structure, and high flexibility, making them widely applicable in industrial manufacturing, biomedical instruments, and aerospace fields. However, the inherent flexibility of single-link flexible-joint manipulators (SLFJMs) poses substantial control challenges. Compared to traditional control algorithms, prescribed performance control (PPC) algorithms provide superior transient response and steady-state performance by defining a prescribed performance function. However, existing PPC algorithms are limited to a specific range of system initial states, which reduces the joint manipulator’s operational workspace and weakens the robustness of the control algorithm. To address this issue, this study proposes a prescribed performance bounded-H_∞ fault-tolerant controller for SLFJMs. By designing an improved tangent-type barrier Lyapunov function (BLF), a prescribed performance controller that is independent of the initial state of the SLFJM is developed. An input control function (ICF) is employed to mitigate the impulse response of the control input, ensuring a smooth transition from zero. Furthermore, the improved tangent-type BLF enables the tracking error to rapidly converge to a small neighborhood of zero. Finally, a stabilization control simulation experiment is conducted; the results validate the effectiveness of the proposed prescribed performance bounded-H_∞ controller. Full article

Circadian rhythm disruption is a modifiable risk factor for Alzheimer’s disease (AD) progression, marked by neuroinflammation, oxidative stress, and amyloid-β (Aβ) accumulation. Hypoxia-inducible factor 3α (Hif3α) has emerged as a key regulator of inflammatory and oxidative pathways. To evaluate the impacts of circadian disruption on AD progression and investigate the therapeutic potential of bamboo leaf flavonoids (BLFs), C57BL/6N mice (normal mice) and APP/PS1 transgenic mice (AD mice) were exposed to circadian disruption via randomized light exposure and stress, as the in vivo model. Then, BLFs were administered to assess effects on neuroinflammation, oxidative stress, and organ damage. Next, Nissl body staining and Aβ protein immunohistochemistry were performed to evaluate the effects of BLFs on brain pathology. Through transcriptome sequencing, key factors and the related pathway were screened out. In vitro, molecular mechanisms were explored in PC12 cells treated with Aβ42 and Hif3α siRNA fragments. Results demonstrated that circadian disruption increased oxidative stress and early liver and kidney damage degrees, with greater severity in AD mice. BLFs partially reversed oxidative damage and reduced Aβ deposition. Transcriptome analysis revealed upregulation of Hif3α in circadian-disrupted mice, linked to inflammation and oxidative stress. In vitro, the knockdown of Hif3α reduced inflammation and normalized protein expression, which could be regulated by BLFs and suppressed AD progression. In conclusion, circadian disruption exacerbated AD progression via regulating Hif3α/Rab7/TNFα/IL1β pathway. BLFs offered neuroprotection roles by mitigating inflammation and oxidative damage, highlighting Hif3α as a promising target for AD therapy and biomarker development. Full article

Previous studies typically assume that output constraints are symmetric or time-invariant. However, effectively addressing asymmetric and time-varying output constraints remains an unsolved issue, especially in the case of switched non-square multi-input multi-output (MIMO) nonlinear systems. To tackle this challenge, this paper first establishes a prescribed-time (PT) Lyapunov criterion for switched nonlinear systems. Second, an asymmetric nonlinear mapping (ANM) method is proposed to handle asymmetric time-varying output constraints. Compared to the barrier Lyapunov function (BLF) approach, the ANM method relaxes the initial output conditions and the constraint functions are not necessarily required to be opposite in sign. Finally, a PT tracking controller is designed for a class of switched MIMO nonlinear systems with a non-square control coefficient matrix by using the time-varying gain technique. This controller achieves zero-error tracking within the prescribed time while ensuring that output constraints are satisfied. The effectiveness of the proposed control strategy is validated through numerical and simulation examples. Full article