Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders.

Peroxiredoxin 6 (Prdx6), a unique 1-Cys member of the peroxiredoxin family, exhibits peroxidase activity, phospholipase activity, and lysophosphatidylcholine acyltransferase (LPCAT) activity. Prdx6 has been known to be an important enzyme for the maintenance of lipid peroxidation repair, cellular metabolism, inflammatory signaling, and antioxidant damage. Growing research has demonstrated that the altered activity of this enzyme is linked with various pathological processes including central nervous system (CNS) disorders. This review discusses the distinctive structure, enzyme activity, and function of Prdx6 in different CNS disorders, as well as emphasizing the significance of Prdx6 in neurological disorders.

Associations of global biomarkers of oxidative stress with osteoporosis, bone microstructure and bone turnover: Evidence from human and animal studies.

PURPOSE: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. RESULTS: In humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. CONCLUSION: In conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

Investigating product innovation pathway from a modular standpoint: A case study of large aircraft assembly line.

Product innovation is a robust approach for enterprises to acquire and maintain a competitive edge. In order to support the development of enterprise product innovation, it is essential to establish an innovation pathway. Grounded in a modular perspective and considering the product innovation process, this study segments the process into product demand analysis, product module partitioning, product innovation opportunity recognition, and product innovation design. Consequently, an integrated product innovation pathway is constructed by incorporating relevant innovation theories and methodologies, encompassing the innovation process, theory, and methods. The feasibility and efficacy of this research are validated through a case study of a large aircraft assembly line, indicating that this approach effectively bolsters product innovation development and holds practical significance.

Innovation technology opportunity identification of civil aircraft mechanical connections based on generative topographic mapping.

In order to advance civil aircraft manufacturing to higher levels, there is an urgent need to identify technological innovation opportunities to help new technology development. This paper first analyses the current state of the research field and determines the topic. It preprocesses papers and patents within the research topic to obtain a base database. Then, the database is analyzed using the LDA (Latent Dirichlet Analysis) cluster analysis method. The TF-IDF (Term Frequency-Inverse Document Frequency) algorithm processes the data to obtain critical technical words. The abstracts of patents and papers are processed to construct a binary-based vector of technical keywords. The papers and patents are visualized in a two-dimensional space technology map by generative topographic mapping (GTM) to create a technology map to identify technology blank dots. The combination of technologies characterized by each technology blank dot is obtained by GTM inverse mapping. Finally, technology opportunities with a high probability of development are identified to achieve innovation opportunity identification. It also provides countermeasures for the research institution, enterprise, sector, and industry. After research and analysis, the future in the mechanical connection technology of civil aircraft is necessary to strengthen basic technology development and improve the study of intelligence, integration, and flexibility. Technology such as sensors and lasers can improve the precision and efficiency of mechanical connections.

Global biomarkers of oxidative stress and fractures: a matched case-control study.

Background: Evidence for a relationship between oxidative stress and osteoporotic fractures in humans is limited. Fluorescent oxidation products (FlOPs, excitation/emission wavelengths 320/420nm denoted FlOP_320; 360/420nm [FlOP_360]; and 400/475nm [FlOP_400]) are global biomarkers of oxidative stress, and reflect oxidative damage to proteins, phospholipids, and nucleic acids. We investigated the association between FlOPs and a recent osteoporotic fracture. Methods: We conducted a case-control study in a Chinese population aged 50 years or older. A recent osteoporotic fracture in the cases was confirmed by x-ray. Cases were matched with community-based non-fracture controls (1:2 ratio) for age (± 4 years) and sex. In addition, we conducted a sensitivity unmatched case-control study which included all fracture cases and all eligible non-fracture controls prior to matching. Plasma FlOPs were measured with a fluorescent microplate reader. We used unconditional logistic regression to analyze the association between FlOPs (per 1-SD increase in logarithmic scale) and fracture; odds ratios (OR) and 95% confidence intervals (95% CI) were reported. Results: Forty-four cases and 88 matched controls (mean age: 68.2 years) were included. After covariate adjustment (i.e., body mass index, physical activity, and smoking), higher FlOP_360 (OR = 1.85; 95% CI = 1.03 - 3.34) and FlOP_400 (OR = 13.29; 95% CI = 3.48 - 50.69) levels, but not FlOP_320 (OR = 0.56; 95% CI = 0.27 - 1.15), were associated with increased fracture risk. Subgroup analyses by fracture site and unmatched case-control study found comparable associations of FlOP_360 and FlOP_400 with hip and non-hip fractures. Conclusions: Higher FlOP_360 and FlOP_400 levels were associated with increased risk of fracture, and this association was comparable for hip and non-hip fractures. Prospective studies are warranted to confirm this finding.

Diagnostic Significance of Targeted Next-Generation Sequencing in Central Nervous System Infections in Neurosurgery of Pediatrics.

Background: Cerebrospinal fluid (CSF) pathogen culture suffers from the drawbacks of prolonged cycle time and a low positivity rate in diagnosing intracranial infections in children. This study aims to investigate the diagnostic potential of targeted next-generation sequencing (tNGS) in pediatric neurosurgery for central nervous system (CNS) infections. Methods: A retrospective study was conducted on children under 14 with suspected intracranial infections following craniocerebral trauma or surgery between November 2018 and August 2020. Routine, biochemical, smear, and pathogen culture tests were performed on CSF during treatment. The main parameters of CSF analysis encompassed white blood cells (WBC, ×106/L) count, percentage of multinucleated cells (%), protein levels (g/L), glucose concentration (GLU, mmol/L), chloride levels (mmol/L), and pressure (mmH2O). The outcomes of tNGS were assessed through the Receiver Operating Characteristic (ROC) curve and pertinent diagnostic parameters. Results: Among the 35 included pediatric patients, 22 were clinically diagnosed with CNS infection in neurosurgery, tNGS was confirmed in 18 cases. The sensitivity and specificity of tNGS were 81.8% and 76.9%, respectively, while the traditional method of CSF cultures and smears exhibited a sensitivity of 13.6% and a specificity of 100%. ROC curve analysis indicated an area under the curve (AUC) of 0.794 for tNGS and 0.568 for the CSF cultures and smears. CSF analysis indicated that the two groups exhibited statistically significant differences in terms of WBC count [330.0 (110.00-2639.75) vs 14.00 (4.50-26.50), P<0.001] and percentage of multinuclear cells (%) [87.50 (39.75-90.00) vs 0 (0-10.00), P<0.001]. However, the remaining parameters did not statistically significant differences between the groups (all P>0.05). Conclusion: tNGS demonstrates a high degree of diagnostic accuracy when detecting infections within the CNS of pediatric neurosurgery patients. tNGS can effectively establish for diagnosing CNS infections by detecting pathogenic microorganisms and their corresponding virulence and/or resistance genes within the test samples.

Obstructive sleep apnea is related to alterations in fecal microbiome and impaired intestinal barrier function.

Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect fecal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers-intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Plasma D-LA and I-FABP were significantly elevated in patients with OSA. The severity of OSA was related to differences in the structure and composition of the fecal microbiome. Enriched Fusobacterium, Megamonas, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the fecal microbiome, intestinal barrier biomarkers, and AHI. The study confirms that changes in the intestinal microbiota are associated with intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.

Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway.

Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a significant antitumor role in several malignant tumors. In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time- and concentration-dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K-Akt-mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin-mediated pro-apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K-mTOR inhibitor NVP-BEZ235. Taken together, these findings indicate that anti-proliferation and pro-apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K-Akt-mTOR pathway, suggesting a potential therapeutic strategy against glioma.

Data-Driven Technology Roadmaps to Identify Potential Technology Opportunities for Hyperuricemia Drugs.

Hyperuricemia is a metabolic disease with an increasing incidence in recent years. It is critical to identify potential technology opportunities for hyperuricemia drugs to assist drug innovation. A technology roadmap (TRM) can efficiently integrate data analysis tools to track recent technology trends and identify potential technology opportunities. Therefore, this paper proposes a systematic data-driven TRM approach to identify potential technology opportunities for hyperuricemia drugs. This data-driven TRM includes the following three aspects: layer mapping, content mapping and opportunity finding. First we deal with layer mapping.. The BERT model is used to map the collected literature, patents and commercial hyperuricemia drugs data into the technology layer and market layer in TRM. The SAO model is then used to analyze the semantics of technology and market layer for hyperuricemia drugs. We then deal with content mapping. The BTM model is used to identify the core SAO component topics of hyperuricemia in technology and market dimensions. Finally, we consider opportunity finding. The link prediction model is used to identify potential technological opportunities for hyperuricemia drugs. This data-driven TRM effectively identifies potential technology opportunities for hyperuricemia drugs and suggests pathways to realize these opportunities. The results indicate that resurrecting the pseudogene of human uric acid oxidase and reducing the toxicity of small molecule drugs will be potential opportunities for hyperuricemia drugs. Based on the identified potential opportunities, comparing the DNA sequences from different sources and discovering the critical amino acid site that affects enzyme activity will be helpful in realizing these opportunities. Therefore, this research provides an attractive option analysis technology opportunity for hyperuricemia drugs.

A Novel Epilepsy Detection Method Based on Feature Extraction by Deep Autoencoder on EEG Signal.

Electroencephalogram (EEG) signals are the gold standard tool for detecting epileptic seizures. Long-term EEG signal monitoring is a promising method to realize real-time and automatic epilepsy detection with the assistance of computer-aided techniques and the Internet of Medical Things (IoMT) devices. Machine learning (ML) algorithms combined with advanced feature extraction methods have been widely explored to precisely recognize EEG signals, while among which, little attention has been paid to high computing costs and severe information losses. The lack of model interpretability also impedes the wider application and deeper understanding of ML methods in epilepsy detection. In this research, a novel feature extraction method based on an autoencoder (AE) is proposed in the time domain. The architecture and mechanism are elaborated. In this method, specified features are defined and calculated on the basis of signal reconstruction quantification of the AE. The EEG recognition is performed to validate the effectiveness of the proposed detection method, and the prediction accuracy reached 97%. To further investigate the superiority of the proposed AE-based feature extraction method, a widely used feature extraction method, PCA, is allocated for comparison. In order to understand the underlying working mechanism, permutation importance and SHapley Additive exPlanations (SHAP) are conducted for model interpretability, and the results further confirm the reasonability and effectiveness of the extracted features by AE reconstruction. With high computing efficiency in the time domain and an extensively satisfactory accuracy, the proposed epilepsy detection method exhibits great superiority and potential in almost real-time and automatic epilepsy monitoring.

Re-discussion of servitization strategy and firm performance.

Servitization innovation is critical for manufacturing firms to strengthen their sustainable competitive advantage in a dynamic business environment. Current research on the relationship between servitization and firm performance has matured, but many conclusion remain divergent. That cannot only hinder the development of servitization theory, but also make manufacturers lack a scientific basis for deciding whether to develop servitization. Thus, this study aims to systematically analyze the quantitative research results in this field through Meta-analysis methods to reveal the reasons for the disagreement. After collecting 59 independent articles on servitization and firm performance, this study performed statistical analysis using Meta-analysis. Then, the relationship between servitization and firm performance was explored, as well as the effects of different potential moderating variables. The moderate positive relationship between servitization strategies and their different orientations and firm performance is found. For the moderating variables, the servitization strategy has a more significant effect on non-financial performance. And they are more correlated when there are mediator variables. The impact of firm servitization transformation in developing regions is better than in developed areas. A stable market environment is more beneficial to the servitization transformation. The transformation effect of high-tech manufacturing is better than that of traditional manufacturing. And the transformation effect of large companies is better than that of small and medium-sized companies.

A variety of simple and ultra-low-cost methods preparing SLiCE extracts and their application to DNA cloning.

Cell lysates from a laboratory strain of Escherichia coli can be exploited for seamless DNA cloning in vitro, which is named the seamless ligation cloning extract (SLiCE) cloning method. The SLiCE method can incorporate DNA fragments into a vector to achieve conventional DNA cloning and is more cost-effective than commercially seamless DNA cloning kits. In this study, we found that the SLiCE extracts could easily be prepared with different methods, such as 3% Triton X-100 lysis buffer, 3% SDS lysis buffer, or freeze-thaw cycles. At high E. coli transformation efficiency, the SLiCE extracts prepared using different simple and ultra-low cost methods did not affect the DNA cloning efficiency. These results further revealed that the SLiCE cloning method can be efficiently used for seamless DNA cloning in vitro.

Cold Plasma Irradiation Attenuates Atopic Dermatitis via Enhancing HIF-1α-Induced MANF Transcription Expression.

Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of manf gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression via HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment.

Start-Up's Road to Disruptive Innovation in the Digital Era: The Interplay Between Dynamic Capabilities and Business Model Innovation.

The emergence and infusion of digital technologies bring greater chances for start-ups to conduct disruptive innovation through digital entrepreneurship. Despite the existed business practices, the happening mechanism of start-up's disruptive innovation in the digital economy context remains unclear. This study aims to understand the evolutionary mechanism and fulfillment path start-ups' disruptive innovation in the digital era. The longitudinal case study is conducted for a Chinese Internet start-up that successfully launched disruptive innovation under the digital economy background. Adopting a process perspective, this study analyzes the evolutionary phases of digital disruptive innovation. Moreover, this study identifies the digital technologies adoption, dynamic capabilities deployment, and business model innovation as the key pillars, and their interactions. Finally, this study induces and proposes its evolution mechanism and fulfillment path models. This study enriches the research scope of disruptive innovation and digital entrepreneurship. This study can offer theoretical guidance for the start-ups' disruptive innovation in the digital era, and practical implications for implementing a digital catching-up strategy.

Time-resolved quantitative phosphoproteomics reveals cellular responses induced by caffeine and coumarin.

Protein phosphorylation is a critical way that cells respond to external signals and environmental stresses. However, the patterns of cellular response to chemicals at different times were largely unknown. Here, we used quantitative phosphoproteomics to analyze the cellular response of kinases and signaling pathways, as well as pattern change of phosphorylated substrates in HepG2 cells that were exposed to caffeine and coumarin for 10 min and 24 h. Comparing the 10 min and 24 h groups, 33 kinases were co-responded and 32 signaling pathways were co-enriched in caffeine treated samples, while 48 kinases and 34 signaling pathways were co-identified in coumarin treated samples. Instead, the percentage of co-identified phosphorylated substrates only accounted for 4.31% and 9.57% between 10 min and 24 h in caffeine and coumarin treated samples, respectively. The results showed that specific chemical exposure led to a bunch of the same kinases and signaling pathways changed in HepG2 cells, while the phosphorylated substrates were different. In addition, it was found that insulin signaling pathway was significantly enriched by both the caffeine and coumarin treatment. The pattern changes in phosphorylation of protein substrates, kinases and signaling pathways with varied chemicals and different time course shed light on the potential mechanism of cellular responses to endless chemical stimulation.

A Review of Technological Forecasting from the Perspective of Complex Systems.

Technology forecasting (TF) is an important way to address technological innovation in fast-changing market environments and enhance the competitiveness of organizations in dynamic and complex environments. However, few studies have investigated the complex process problem of how to select the most appropriate forecasts for organizational characteristics. This paper attempts to fill this research gap by reviewing the TF literature based on a complex systems perspective. We first identify four contexts (technology opportunity identification, technology assessment, technology trend and evolutionary analysis, and others) involved in the systems of TF to indicate the research boundary of the system. Secondly, the four types of agents (field of analysis, object of analysis, data source, and approach) are explored to reveal the basic elements of the systems. Finally, the visualization of the interaction between multiple agents in full context and specific contexts is realized in the form of a network. The interaction relationship network illustrates how the subjects coordinate and cooperate to realize the TF context. Accordingly, we illustrate suggest five trends for future research: (1) refinement of the context; (2) optimization and expansion of the analysis field; (3) extension of the analysis object; (4) convergence and diversification of the data source; and (5) combination and optimization of the approach.

Effects of Different Hypothermia on the Results of Cardiopulmonary Resuscitation in a Cardiac Arrest Rat Model.

Objective: To investigate the optimal temperature of hypothermia treatment in rats with cardiac arrest caused by ventricular fibrillation (VF) after the return of spontaneous circulation (ROSC). Methods: A total of forty-eight male Sprague-Dawley rats were induced by VF through the guidewire with a maximum of 5 mA current and untreated for 8 min. Cardiopulmonary resuscitation (CPR) was performed for 8 min followed by defibrillation (DF). Resuscitated rats were then randomized into the normothermia (37°C) group, milder (35°C) group, mild (33°C) group, or moderate (28°C) group. Hypothermia was immediately induced with surface cooling. The target temperature was maintained for 4 h before rewarming to 37 ± 0.5°C. Moreover, at the end of the 4 h, a rat in each group was randomly selected to be sacrificed for the cerebral cortex electron microscopy observation (n = 1). The other resuscitated animals were observed for up to 72 h after ROSC (n = 7). Left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) were measured. Survival time, survival rate, and neurological deficit score (NDS) were recorded for 72 h. Results: During hypothermia, higher LVEF was observed in the hypothermia groups when compared with normothermia group (35°C vs. 37°C, p < 0.05, 33°C and 28°C vs. 37°C, p < 0.01). Among the hypothermia groups, LVEF was higher in the 28°C group than that of 35°C (p < 0.05). However, both the heart rate (HR) (p < 0.01) and LVEDV (28°C vs. 35°C, p < 0.01, 28°C vs. 37°C and 33°C, p < 0.05) were lowest in the 28°C group when compared with the other groups. There were no significant differences of LVEF and LVEDV between the group 35°C and 33°C (p > 0.05). After rewarming, the LVEF of 35°C group was higher than that of group 37°C, 33°C, and 28°C (35°C vs. 37°C and 28°C, p < 0.01, 35°C vs. 33°C, p < 0.05). Group 35°C and 33°C resulted in longer survival (p < 0.01), higher survival rate (p < 0.01), and lower NDS (35°C vs. 37°C and 28°C, p < 0.01, 33°C vs. 37°C and 28°C, p < 0.05) compared with the group 37°C and 28°C. The extent of damage to cerebral cortex cells in group of 35°C and 33°C was lighter than that in group of 37°C and 28°C. The 35°C group spent less time in the process of cooling and rewarming than the group 33°C and 28°C (p < 0.01). Conclusions: An almost equal protective effect of milder hypothermia (35°C) and mild hypothermia (33°C) in cardiac arrest (CA) rats was achieved with more predominant effect than moderate hypothermia (28°C) and normothermia (37°C). More importantly, shorter time spent in cooling and rewarming was required in the 35°C group, indicating its potential clinical application. These findings support the possible use of milder hypothermia (35°C) as a therapeutic agent for postresuscitation.

Mesencephalic astrocyte-derived neurotrophic factor attenuates acute lung injury via inhibiting macrophages' activation.

Acute lung injury (ALI) is an urgent respiratory disease without effective treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF)has been demonstrated to play a suppressive role in some inflammatory conditions. However, the effect of MANF on ALI has not yet been reported. In this study, we collected bronchoalveolar lavage fluid (BALF) from the patients with or without pulmonary inflammation, and used lipopolysaccharide (LPS) to induce mice ALI model. Mono-macrophage-specific MANF knockout (MKO) mice were constructed and recombinant human MANF protein was used to ALI mice. We found that the endogenous MANF protein in both human BALF and mice lung tissues was increased in inflammatory conditions. MANF level in the macrophages of inflammatory lung was higher than that in normal controls in both human and mice. MANF deficiency in macrophages induced lung inflammation and aggravated LPS-induced lung injury. MANF lowered LPS-induced lung injury, inhibited macrophage polarization to M1 functional type. Meanwhile, MANF inhibited-LPS induced activation of NF-κB signal pathway by down regulating phosphorylated p65in lung tissue and macrophages. These results indicate that MANF acts as a suppressor in ALI via negatively regulating NF-κB activation and macrophages polarization, which may be a novel potential target and shed light on ALI therapy.

Mesencephalic astrocyte-derived neurotrophic factor reprograms macrophages to ameliorate acetaminophen-induced acute liver injury via p38 MAPK pathway.

Acetaminophen (APAP)-induced liver injury (AILI) is the most frequent cause of acute liver failure; but the underlying mechanisms still remain obscure. Macrophages and endoplasmic reticulum (ER) stress play an important role in the pathogenesis of AILI. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly identified 18-kDa soluble protein, whose expression and secretion are stimulated by ER stress. To investigate the role of myeloid cell MANF in the pathogenesis of AILI, we assayed serum and liver samples from AILI model mice and patients with drug-induced liver injury (DILI). We demonstrated that the levels of MANF were elevated in patients with DILI and in mice with AILI. Moreover, myeloid-specific MANF knockout mice were generated and used. It was observed that a delayed liver recovery from myeloid-specific MANF gene knockout mice following APAP overdose compared to that from wild-type mice. MANF deficiency in myeloid cells resulted in increased infiltrating monocyte-derived macrophages (MoMFs) but reduced restorative Ly6Clow macrophages after APAP treatment. MANF supplementation increased restorative Ly6Clow macrophages and subsequently alleviated liver injury. Moreover, MANF could enhance IL-10 expression and phagocytosis in macrophages via p38 MAPK pathway. Altogether, MANF seems to be a critical immune modulator in promoting liver repair via reducing and reprogramming MoMFs. MANF perhaps promoted the phenotype conversion of pro-inflammatory MoMFs to pro-restorative Ly6Clow MoMFs via p38 MAPK pathway, particularly through enhancing IL-10 and phagocytosis.

Dietary carotenoid intake and osteoporosis: the National Health and Nutrition Examination Survey, 2005-2018.

Higher intake of ß-carotene and ß-cryptoxanthin were associated with lower risk of osteoporosis. A very high intake of lutein + zeaxanthin was also associated with lower risk of osteoporosis. These results support the beneficial role of carotenoids on bone health. PURPOSE: To examine the associations of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin intake with the risk of osteoporosis based on the cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 2005-2018. METHODS: This study identified individuals ≥ 50 years old with valid and complete data on carotenoid intake and bone mineral density (BMD). Intake of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin was averaged from two 24-h recall interviews. BMD was measured by dual-energy X-ray absorptiometry (DXA) and converted to T-scores; osteoporosis was defined as a T-score ≤ - 2.5. We used logistic regression models to test the associations between carotenoids and osteoporosis, adjusting for factors such as age, sex, race, and education. RESULTS: Participants were on average 61.9 years of age, with 57.5% identifying as females. Higher quintiles of ß-carotene (odds ratio [OR] for quintile 5 vs. 1:0.33; 95% CI: 0.19-0.59; P for trend = 0.010) and ß-cryptoxanthin intake (OR for quintile 5 vs. 1:0.61; 95% CI: 0.39-0.97; P for trend = 0.037) were associated with reduced risk of osteoporosis. Similar and marginally significant results for lutein + zeaxanthin intake was found (OR for quintile 5 vs. 1:0.53; 95% CI: 0.30-0.94; P for trend = 0.076). There was no association of α-carotene and lycopene intake with osteoporosis. These associations did not differ by sex (all P_interaction > 0.05). CONCLUSIONS: Higher ß-carotene and ß-cryptoxanthin intake was associated with decreased osteoporosis risk. A very high intake of lutein + zeaxanthin was also associated with lower risk of osteoporosis.