Associations between blood nickel and lung function in young Chinese: An observational study combining epidemiology and metabolomics.

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.

Glycosylation in aging and neurodegenerative diseases.

Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.

Prenatal LPS leads to increases in RAS expression within the PVN and overactivation of sympathetic outflow in offspring rats.

The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) are two major blood pressure-regulating systems. The link between the renal and cerebral RAS axes was provided by reflex activation of renal afferents and efferent sympathetic nerves. There is a self-sustaining enhancement of the brain and the intrarenal RAS. In this study, prenatal exposure to lipopolysaccharide (LPS) led to increased RAS activity in the paraventricular nucleus (PVN) and overactivation of sympathetic outflow, accompanied by increased production of reactive oxygen species (ROS) and disturbances between inhibitory and excitatory neurons in PVN. The AT1 receptor blocker losartan and α2 adrenergic receptor agonist clonidine in the PVN significantly decreased renal sympathetic nerve activity (RSNA) and synchronously reduced systolic blood pressure. Prenatal LPS stimulation caused H3 acetylation at H3K9 and H3K14 in the PVN, which suggested that epigenetic changes are involved in transmitting the prenatal adverse stimulative information to the next generation. Additionally, melatonin treatment during pregnancy reduced RAS activity and ROS levels in the PVN; balanced the activity of inhibitory and excitatory neurons in the PVN; increased urine sodium secretion; reduced RSNA and blood pressure. In conclusion, prenatal LPS leads to increased RAS expression within the PVN and overactivation of the sympathetic outflow, thereby contributing to hypertension in offspring rats. Melatonin is expected to be a promising agent for preventing prenatal LPS exposure-induced hypertension.

Evaluation of the clinical efficacy of ultra-fast track anesthesia for endoscopic thoracic sympathectomy of palmar hyperhidrosis.

OBJECTIVE: In this study, we investigated the safety and practicability of ultra-fast track anesthesia (UFTA) for endoscopic thoracic sympathectomy (ETS). METHODS: A total of 72 patients with palmar hyperhidrosis undergoing ETS were randomly divided into three groups: the UFTA group (group I), the group undergoing single-lumen tracheal intubation with local infiltration anesthesia technique (group II), and the group undergoing single-lumen tracheal intubation with routine anesthesia (group III). Mean arterial pressure (MAP) and heart rate (HR) were recorded for all three groups at the following six time points: Before anesthetics administration (T0), the time of intubating or inserting laryngeal mask airway (T1), the time of incising skin (T2), the time of disconnecting of the right sympathetic nerve (T3), the time of disconnecting of the left sympathetic nerve (T4), the time of withdrawing the tracheal tube or laryngeal mask airway (T5), and the time of transferring the patient to a post-anesthesia care unit (PACU) (T6). The three groups were compared from the following perspectives: surgery duration; anesthesia recovery duration, that is, the duration from discontinuation of anesthesia to extubating the tracheal tube; the dose of propofol and remifentanil per kilogram body mass per unit time interval (the time at the end of the procedure, which lasted from anesthesia induction to incision suturing); and the visual analog scale (VAS) in the resting state in the PACU. RESULTS: Based on pairwise comparisons, the average HR and average MAP values of the three groups differed significantly from T2 to T6 (p < 0.05). As demonstrated by the correlation analysis between remifentanil and propofol with HR and MAP, the doses of the total amount of remifentanil and propofol were lower, and group I used less remifentanil and propofol than group II. No patient in group I experienced throat discomfort following surgery. Patients in groups II and III experienced a range of postoperative discomfort. The VAS scores of groups I and II were significantly lower than those of group III, with group I lower than group II. CONCLUSION: When utilized in ETS, UFTA can provide effective anesthesia for minor traumas. It is safe, effective, and consistent with the enhanced recovery philosophy of fast-track surgery departments.

Multi-mode resonance of bound states in the continuum in dielectric metasurfaces.

Bound states in the continuum (BIC) represent distinct non-radiative states endowed with infinite lifetime and vanishing resonance linewidth. Introducing asymmetric perturbation to the system can convert true BICs into high quality leaky modes which is useful in many photonic applications. Previously, such perturbation and resonance of interest is only limited to a single factor. However, different perturbations by unit cell gap, geometry and rotation angle result distinctive resonance modes. The combination of two perturbation factors can excite multi-mode resonance contributed from each asymmetric factor which coexist simultaneously; thus, the number of reflectance peaks can be controlled. In addition, we have carefully analyzed the electric field variations under different perturbation factors, followed by a multipolar decomposition of resonances to reveal underlying mechanisms of distinct resonance modes. Through simulations, we find that the introduction of multiple asymmetric perturbations also influences the metasurface sensitivity in refractive index sensing and compare the performance of different resonance modes. These observations provide structural design insights for achieving high quality resonance with multiple modes and ultra-sensitive sensing.

Bimetallic metal-organic framework aerogels supported by aramid nanofibers for efficient CO2 capture.

The excessive CO2 emission has gained global attentions due to its potential effects on climate change, plant nutrition deterioration, and human health and safety. Metal-organic frameworks (MOFs) featured with high specific surface area, adjustable pore size, and tailorable morphology have been widely applied for CO2 capture. However, some drawbacks of poor mechanical stability and uneven distribution of mesopores limit their further applications. Herein, we demonstrate a one-step synthesis of bimetallic center framework (OSSBCF) and pore reconstruction (PRC) strategy to prepare the hierarchical porous Zn/Co-ZIF@ANF aerogels. This unique design achieves the construction of efficient gas transfer channels and creates massive micropores with abundant Lewis basic adsorption sites. Benefiting from theses merits, the bimetallic Zn/Co-ZIF@ANF aerogels demonstrate high MOFs loading mass of 47.51 wt%, high specific surface area of 686.39 m2g-1, and large porosity of 99.31 %. Moreover, the bimetallic Zn/Co-ZIF@ANF aerogels exhibit an enhanced CO2 adsorption capacity of 5.99 mmol/g and CO2/N2 adsorption selectivity of 35 at 25 °C and 1 bar. The CO2 capacity of bimetallic Zn/Co-ZIF@ANF aerogels keep up to 95.19 % after ten cycles of CO2 adsorption, indicating the excellent long-term recycle stability. Therefore, this study provides a promising strategy to engineer hierarchical porous bimetallic MOF aerogels toward practical CO2 capture.

Antecedent configuration pathways for manufacturing-enterprise digital servitization: Based on a technology-organization-environment theoretical framework.

The expeditious advancement and elevation of the manufacturing industry's transformation and upgrading represent pivotal strides for China in its ascent toward the upper echelons of the global manufacturing value chain. Currently, China's manufacturing-industry transformation faces the dual-lag quandary of digitalization and servitization. The notion of digital servitization elucidates the interdependent relationship between digitalization and servitization, unveiling the mechanisms underlying the formation of digital servitization. This holds significant implications for advancing the comprehension of digitalization and servitization and, crucially, facilitates the acceleration of China's manufacturing sector transitioning from production-centric to service-centric paradigms. Harnessing the technology-organization-environment (TOE) theoretical framework, we constructed a model elucidating the driving factors underpinning manufacturing digital servitization. By employing the fuzzy-set qualitative comparative analysis (fsQCA), we explored strategic decisions and path dependencies in the transformation of manufacturing digital servitization, offering valuable insights to foster China's manufacturing sector in its digital-servitization journey. The following findings were obtained. (1) A singular condition was insufficient as a prerequisite for manufacturing digital servitization and necessitated the coordinated alignment of multiple variables. (2) Three pathways existed for achieving manufacturing digital servitization: TOE, organization-environment collaborative-oriented, and technology-organization collaborative-oriented. (3) The progression of manufacturing digital servitization resulted from the collective impact of numerous factors, exhibiting a characteristic of different paths leading to the same destination. Various manufacturing enterprises pursued distinct trajectories to achieve digital servitization, contingent upon their unique circumstances. These findings have the potential to provide valuable insights for effectively fostering manufacturing digital servitization.

Realizing dendrite-free lithium deposition with three-dimensional soft-rigid nanofiber interlayers.

Lithium (Li) metal is regarded as the most desirable anode candidates for high-energy-density batteries by virtue of its lowest redox potential and ultrahigh theoretical specific capacity. However, uncontrollable Li dendritic growth, infinite volume variation and unstable solid electrolyte interface (SEI) ineluctably plague its commercialization process. Herein, the three-dimensional (3D) nanofiber functional layers with synergistic soft-rigid feature, consisting of tin oxide (SnO2)-anchored polyvinylidene fluoride (PVDF) nanofibers, are directly electrospun on copper current collector. This strategy can effectively regulate uniform Li deposition and strengthen SEI stability through the dual effect of physical accommodation and chemical ionic intervention. On the one hand, the nanofiber interlayers with excellent electrolyte affinity and well-distributed Li+ transport pathways can promote uniform Li+ flux distribution and large-size Li deposition. On the other hand, the rigid SnO2 contributes to reducing Li nucleation overpotential and stabilizing SEI layer assisted by its spontaneous reaction with Li. As a result, the smooth and dense Li deposition is achieved by such soft-rigid nanofiber interlayers, thereby extending the cycling life and improving the safety application of Li metal batteries. This work offers a new route for efficient protection of Li metal anodes and brings a new inspiration for developing high-energy-density Li metal batteries.

Highly stabilized and efficient thermoelectric copper selenide.

The liquid-like feature of thermoelectric superionic conductors is a double-edged sword: the long-range migration of ions hinders the phonon transport, but their directional segregation greatly impairs the service stability. We report the synergetic enhancement in figure of merit (ZT) and stability in Cu1.99Se-based superionic conductors enabled by ion confinement effects. Guided by density functional theory and nudged elastic band simulations, we elevated the activation energy to restrict ion migrations through a cation-anion co-doping strategy. We reduced the carrier concentration without sacrificing the low thermal conductivity, obtaining a ZT of ∼3.0 at 1,050 K. Notably, the fabricated device module maintained a high conversion efficiency of up to ∼13.4% for a temperature difference of 518 K without obvious degradation after 120 cycles. Our work could be generalized to develop electrically and thermally robust functional materials with ionic migration characteristics.

Research Progress on Quality Detection of Livestock and Poultry Meat Based on Machine Vision, Hyperspectral and Multi-Source Information Fusion Technologies.

Presently, the traditional methods employed for detecting livestock and poultry meat predominantly involve sensory evaluation conducted by humans, chemical index detection, and microbial detection. While these methods demonstrate commendable accuracy in detection, their application becomes more challenging when applied to large-scale production by enterprises. Compared with traditional detection methods, machine vision and hyperspectral technology can realize real-time online detection of large throughput because of their advantages of high efficiency, accuracy, and non-contact measurement, so they have been widely concerned by researchers. Based on this, in order to further enhance the accuracy of online quality detection for livestock and poultry meat, this article presents a comprehensive overview of methods based on machine vision, hyperspectral, and multi-sensor information fusion technologies. This review encompasses an examination of the current research status and the latest advancements in these methodologies while also deliberating on potential future development trends. The ultimate objective is to provide pertinent information and serve as a valuable research resource for the non-destructive online quality detection of livestock and poultry meat.

A retrospective study on adverse events of intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications in 83,778 patients.

OBJECTIVES: To investigate the rate of adverse events (AEs) caused by intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications retrospectively and to explore practical measures for prevention and treatment of them. MATERIALS AND METHODS: This study enrolled 83,778 contrast-enhanced ultrasound (CEUS) examinations using sulfur hexafluoride microbubbles intravenously performed during 11 years. Age, gender, and target organs of all CEUS patients were recorded. For cases of AEs, their medical history and laboratory results were also collected. The process of AEs was assessed and categorized. Besides, the management of AEs were recorded. RESULTS: Twenty patients had sulfur hexafluoride microbubbles-related AEs. The AE rate was 0.024%. No significant difference was observed between patients with AEs and the whole group for age and sex distribution. All AEs happened in liver examinations. Among them, 7 (35%) were mild, 8 (40%) were moderate, and 5 (25%) were severe. They were categorized into 15 allergic-like reactions and 5 physiologic reactions. The manifestations of mild and moderate AEs mainly include urticaria, chills, and mild hypoxia, which could be eased by simple management. Severe cases had anaphylactic shock, generalized convulsions, and diffuse erythema with hypotension respectively. They need close monitoring and oxygen inhalation with anti-shock and anti-anaphylactic treatment. Most cases started within 30 min and recovered within 1 day. CONCLUSIONS: Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications was safe with rare AEs. AEs were more likely to happen in abdominal applications than superficial ones. A well-designed emergency plan should be available for clinical use of sulfur hexafluoride microbubbles to reduce AEs and to deal with AEs properly. CRITICAL RELEVANCE STATEMENT: Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications reported few AEs and could be considered safe but severe AEs are life-threatening. We analyzed the influence factors of AEs and propose some methods for prevention and treatment of them, which can further improve the safety of sulfur hexafluoride microbubbles in clinical practice. KEY POINTS: • The AE rate of sulfur hexafluoride microbubbles in abdominal and superficial applications was 0.024%. • Patients were more likely to have AEs in abdominal applications than superficial ones. • Severe AEs are life-threatening and need prompt identification and treatment. • We summarized some detailed suggestions for clinical prevention and treatment of AEs.

Broadening horizons: ferroptosis as a new target for traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc-/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.

High fat diet-induced downregulation of TRPV2 mediates hepatic steatosis via p21 signalling.

The global prevalence and incidence of non-alcoholic fatty liver disease (NAFLD) are exhibiting an increasing trend. NAFLD is characterized by a significant accumulation of lipids, though its underlying mechanism is still unknown. Here we report that high-fat diet (HFD) feeding induced hepatic steatosis in mice, which was accompanied by a reduction in the expression and function of hepatic TRPV2. Moreover, conditional knockout of TRPV2 in hepatocytes exacerbated HFD-induced hepatic steatosis. In an in vitro model of NAFLD, TRPV2 regulated lipid accumulation in HepG2 cells, and TRPV2 activation inhibited the expression of the cellular senescence markers p21 and p16, all of which were mediated by AMPK phosphorylation. Finally, we found that administration of probenecid, a TRPV2 agonist, impaired HFD-induced hepatic steatosis and suppressed HFD-induced elevation in p21 and p16. Collectively, our findings imply that hepatic TRPV2 protects against the accumulation of lipids by modulating p21 signalling.

Harnessing multiplex crRNA enables an amplification-free/CRISPR-Cas12a-based diagnostic methodology for Nosema bombycis.

IMPORTANCE: The multiplex-crRNA CRISPR/Cas12a detection method saves hands-on time, reduces the risk of aerosol pollution, and can be directly applied to detecting silkworms infected with Nosema bombycis. This study provides a new approach for the inspection and quarantine of silkworm pébrine disease in sericulture and provides a new method for the detection of other pathogens.

Masson pine pollen aqueous extract ameliorates cadmium-induced kidney damage in rats.

Introduction: Cadmium (Cd) is a hazardous environmental pollutant present in soil, water, and food. Accumulation of Cd in organisms can cause systematic injury and damage to the kidney. The Masson pine pollen aqueous extract (MPPAE) has attracted increasing attention due to its antioxidant activity and ability to enhance immunity. Methods: In this study, we investigated the potential of MPPAE to protect against Cd-induced kidney damage in rats and the underlying mechanism. The transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, were explored. Results: The concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were both significantly altered after treatment with MPPAE. Furthermore, sequencing and analysis of the transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, revealed differential expression of numerous genes and metabolites compared with the untreated control rats. These differentially expressed genes (DEGs) included detoxification-related genes such as cytochrome P450 and the transporter. The differentially expressed metabolites (DEMs) included 4-hydroxybenzoic acid, L-ascorbate, and ciliatine. Conjoint transcriptome and metabolome analysis showed that several DEGs were correlated with DEMs. Conclusion: These preliminary findings indicate the potential of MPPAE for the treatment of toxic metal poisoning.

Directionally-Resolved Phononic Properties of Monolayer 2D Molybdenum Ditelluride (MoTe2) under Uniaxial Elastic Strain.

Understanding the phonon characteristics of two-dimensional (2D) molybdenum ditelluride (MoTe2) under strain is critical to manipulating its multiphysical properties. Although there have been numerous computational efforts to elucidate the strain-coupled phonon properties of monolayer MoTe2, empirical validation is still lacking. In this work, monolayer 1H-MoTe2 under uniaxial strain is studied via in situ micro-Raman spectroscopy. Directionally dependent monotonic softening of the doubly degenerate in-plane E2g1 phonon mode is observed with increasing uniaxial strain, where the E2g1 peak red-shifts -1.66 ± 0.04 cm-1/% along the armchair direction and -0.80 ± 0.07 cm-1/% along the zigzag direction. The corresponding Grüneisen parameters are calculated to be 1.09 and 0.52 along the armchair and zigzag directions, respectively. This work provides the first empirical quantification and validation of the orientation-dependent strain-coupled phonon response in monolayer 1H-MoTe2 and serves as a benchmark for other prototypical 2D transition-metal tellurides.

The presence of autoantibodies is associated with improved overall survival in lung cancer patients.

Objective: Autoantibodies have been reported to be associated with cancers. As a biomarker, autoantibodies have been widely used in the early screening of lung cancer. However, the correlation between autoantibodies and the prognosis of lung cancer patients is poorly understood, especially in the Asian population. This retrospective study investigated the association between the presence of autoantibodies and outcomes in patients with lung cancer. Methods: A total of 264 patients diagnosed with lung cancer were tested for autoantibodies in Henan Provincial People's Hospital from January 2017 to June 2022. The general clinical data of these patients were collected, and after screening out those who met the exclusion criteria, 151 patients were finally included in the study. The Cox proportional hazards model was used to analyze the effect of autoantibodies on the outcomes of patients with lung cancer. The Kaplan-Meier curve was used to analyze the relationship between autoantibodies and the overall survival of patients with lung cancer. Results: Compared to lung cancer patients without autoantibodies, those with autoantibodies had an associated reduced risk of death (HRs: 0.45, 95% CIs 0.27~0.77), independent of gender, age, smoking history, pathological type, and pathological stage of lung cancer. Additionally, the association was found to be more significant by subgroup analysis in male patients, younger patients, and patients with small cell lung cancer. Furthermore, lung cancer patients with autoantibodies had significantly longer survival time than those without autoantibodies. Conclusion: The presence of autoantibodies is an independent indicator of good prognosis in patients with lung cancer, providing a new biomarker for prognostic evaluation in patients with lung cancer.

Nanoscale goldbeating: Solid-state transformation of 0D and 1D gold nanoparticles to anisotropic 2D morphologies.

Goldbeating is the ancient craft of thinning bulk gold (Au) into gossamer leaves. Pioneered by ancient Egyptian craftsmen, modern mechanized iterations of this technique can fabricate sheets as thin as ∼100 nm. We take inspiration from this millennia-old craft and adapt it to the nanoscale regime, using colloidally synthesized 0D/1D Au nanoparticles (AuNPs) as highly ductile and malleable nanoscopic Au ingots and subjecting them to solid-state, uniaxial compression. The applied stress induces anisotropic morphological transformation of AuNPs into 2D leaf form and elucidates insights into metal nanocrystal deformation at the extreme length scales. The induced 2D morphology is found to be dependent on the precursor 0D/1D NP morphology, size (0D nanosphere diameter and 1D nanorod diameter and length), and their on-substrate arrangement (e.g., interparticle separation and packing order) prior to compression. Overall, this versatile and generalizable solid-state compression technique enables new pathways to synthesize and investigate the anisotropic morphological transformation of arbitrary NPs and their resultant emergent phenomena.

Phase transition in bilayer MoS2under tensile loading: a molecular dynamics study.

Molybdenum disulfide (MoS2), especially single-layer MoS2, has been experimentally and computationally discovered to exist in several different polymorphs exhibiting various electronic and mechanical properties. The morphology of MoS2can be tuned through strain engineering. Molecular dynamics simulations are conducted to systematically study the phase transition of single-layer MoS2and bilayer MoS2under the uniaxial tensile condition at room temperature. The roles of edge and S-line vacancy are investigated. Phase transitions are always triggered near the edge and vacancy sites. The initiation of the metastable T″ phase can release the tensile stress in the lattice, followed by I4/mmm phase initiation, regardless of the edge conditions. The growth of the I4/mmm phase can cause the local buckling of the MoS2plane. With a tilted S-line vacancy, I4/mmm phase is first initiated to reduce the local shear stress accumulated near the vacancy line. Overall, the phase transition mechanism of single layer and bilayer MoS2under the uniaxial tensile loading is provided, which guides the future strain engineering of MoS2in nanoelectronics applications.

Low-level Cu-fortification of bovine lactoferrin: Focus on its effect on in vitro anti-inflammatory activity in LPS-stimulated macrophages.

Bovine lactoferrin (LF) per 1 g was reacted with 0.16, 0.32, and 0.64 mg CuCl2 to reach 10%, 20%, and 40% copper-saturation, respectively, aiming to assess their anti-inflammatory activities to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The macrophages treated with CuCl2 at 0.051 µg/mL dose did not have obvious change in cell viability, lactate dehydrogenase (LDH) release, and intracellular reactive oxygen species (ROS) production. However, LF and Cu-fortified LF products (10-80 µg/mL doses) mostly showed inhibitory effects on the stimulated macrophages dose-dependently. Moreover, Cu-fortified LF products of lower Cu-fortifying levels at lower doses exerted weaker inhibition on the stimulated macrophages than LF, leading to higher cell viability but decreased LDH release. Meanwhile, LF and Cu-fortified LF products at 10 and 20 µg/mL doses showed different activities to the stimulated cells, via partly decreasing or increasing the production of inflammatory mediators namely prostaglandin E2 (PGE2), nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and ROS production, depending on the used Cu-fortifying and dose levels. Compared with LF, Cu-fortified LF product (Cu-fortifying level of 0.16 mg/g LF) at 10 µg/mL dose showed enhanced inhibition on the production of PGE2, ROS, IL-1ß, and TNF-α, evidencing increased anti-inflammatory activity. However, the inhibition of Cu-fortified LF product (Cu-fortifying level of 0.32 mg/g LF) at 20 µg/mL dose on the production of these inflammatory mediators was mostly reduced. It is thus proposed that both Cu-fortifying and dose levels could affect LF's anti-inflammatory activity in LPS-stimulated macrophages, while the Cu-fortifying level of LF could govern activity change.