[Prdx1 regulates macrophage polarization by maintaining mitochondrial homeostasis].

In order to investigate the role of Prdx1 in macrophage polarization, mouse leukemia cells of monocyte macrophage (RAW264.7) were treated with lipopolysaccharides (LPS)+ interferon gamma (IFNγ) or IL-4 to induce type 1 macrophage (M1) and type 1 macrophage (M2) macrophages, respectively. The Prdx1 gene knockout cells (Prdx1-/-) were used for the study. Flow cytometry was conducted to detect M1/M2 macrophage markers, and ELISA kits were used to measure M1/M2 cytokine levels. Inducible nitric-oxide synthase (iNOS) activity, arginase-1 (Arg-1) activity, and oxidative damage were also assessed. The Seahorse XFe24 Extracellular Flux Analyzer was employed to measure extracellular acidification rate and oxygen consumption rate. The mitochondrial membrane potential was analyzed using the mitochondrial membrane potential dye (JC-1) fluorescent probe, and mitochondrial superoxide was detected through fluorescence staining. Additionally, the impact of adding a mitochondrial reactive oxygen species (ROS) scavenger on RAW264.7 macrophage polarization was examined. The results demonstrated an increase in ROS, hydrogen peroxide, and 8-hydroxy-2 deoxyguanosine (8-OHDG). Cytotoxicity and mitochondrial toxic effects, including mitochondrial superoxide accumulation, decreased adenosine-triphosphate (ATP) production, reduced mitochondrial membrane potential, and decreased mitochondrial DNA copy number, were observed. Furthermore, down-regulation of translocase of inner mitochondrial membrane 23 (TIM23) mitochondrial protein and mitochondrial stress protein heat shock protein 60 (HSP60) was noted. The extra cellular acidification rate (ECAR) in M1 macrophage polarization in RAW264.7 cells was increased, while oxygen consumption rate (OCR) in M2 macrophages was reduced. These findings indicate that Prdx1 knockout in RAW264.7 cells can inhibit M2 macrophage polarization but promote M1 macrophage polarization by impairing mitochondrial function and reducing oxidative phosphorylation.

Capacity enhancement through entropy loading with probabilistically shaped signals in a frequency comb-based transmission system.

We demonstrate a multichannel entropy loading mechanism in an optical frequency comb-based coherent communication system. In high-capacity wavelength division multiplexing communications, the individual laser sources can be replaced by an optical frequency comb, thus reducing the complexity and energy consumption of the transmitter. However, the power variation among different comb lines will lead to performance discrepancies. Spectral flattening filters can be adopted to suppress the variation at the expense of an additional system loss. Alternatively, by applying probabilistic shaping, we have implemented multichannel entropy loading to facilitate a continuous adaptation of the source entropy. The data rate can be dynamically allocated according to the performance of each channel. Through the loading scheme, the non-uniform performances across the channels are effectively mitigated, achieving a capacity enhancement of 34.91 Gbit/s.

Strategies to enhance the ability of nerve guidance conduits to promote directional nerve growth.

Severely damaged peripheral nerves will regenerate incompletely due to lack of directionality in their regeneration, leading to loss of nerve function. To address this problem, various nerve guidance conduits (NGCs) have been developed to provide guidance for nerve repair. However, their clinical application is still limited, mainly because its effect in promoting nerve repair is not as good as autologous nerve transplantation. Therefore, it is necessary to enhance the ability of NGCs to promote directional nerve growth. Strategies include preparing various directional structures on NGCs to provide contact guidance, and loading various substances on them to provide electrical stimulation or neurotrophic factor concentration gradient to provide directional physical or biological signals.

The Impact of Valve Surgery on the Safety and Cardiac Function of Patients with Valvular Heart Disease Complicated by Pulmonary Arterial Hypertension.

Objective: This study evaluates the effects of valve surgery on safety and cardiac function in patients with valvular heart disease complicated by pulmonary arterial hypertension (PAH), focusing on postoperative outcomes influenced by age, heart function grade, and PAH severity. Methods: A retrospective analysis was conducted on 307 valve surgery patients from April 2017 to April 2022. The cohort had a mean age of 57.6 years, with 56.9% males, and was stratified by NYHA functional class II-IV. Outcomes assessed included mortality, complication rates, left ventricular ejection fraction (LVEF), and pulmonary artery systolic pressure (PASP), with statistical analysis performed using t-tests and chi-square tests for continuous and categorical data, respectively. Results: Postoperative outcomes varied significantly with age, NYHA class, and PASP grade. Patients aged ≤60 exhibited an average PASP reduction of 44.46% in the male group and 44.44% in the female group and an LVEF improvement of 5.28% in the male group and 5.80% in the female group. However, these patients showed a higher risk of postoperative complications, such as renal failure, arrhythmia, low cardiac output syndrome, respiratory insufficiency, (23.31%), and a higher mortality rate (13.53%)(P < .05). Higher NYHA classes correlated with increased postoperative risks of complications and mortality rates, and elevated PASP grades were associated with larger improvements in PASP and LVEF but also higher postoperative risks. Conclusion: Valve surgery in valvular heart disease with PAH is influenced by patient age, functional status, and PAH severity. Despite advances in surgical techniques, there remains a notable gap in understanding the nuanced interplay between these conditions and the variable outcomes of valve surgery. This study addresses this research gap, offering comprehensive insights into how age, heart function, and PAH severity influence postoperative outcomes. These findings are crucial for clinicians, providing a more informed basis for tailored treatment strategies, and ultimately enhancing patient care in this complex clinical scenario.Healthcare providers should consider the age-specific benefits and risks of valve surgery in patients with valvular heart disease and pulmonary arterial hypertension. Tailored decision-making, particularly for those aged ≤60, higher NYHA classes, or severe PAH, is essential for optimizing individual outcomes.

Integrating Machine Learning in Metabolomics: A Path to Enhanced Diagnostics and Data Interpretation.

Metabolomics, leveraging techniques like NMR and MS, is crucial for understanding biochemical processes in pathophysiological states. This field, however, faces challenges in metabolite sensitivity, data complexity, and omics data integration. Recent machine learning advancements have enhanced data analysis and disease classification in metabolomics. This study explores machine learning integration with metabolomics to improve metabolite identification, data efficiency, and diagnostic methods. Using deep learning and traditional machine learning, it presents advancements in metabolic data analysis, including novel algorithms for accurate peak identification, robust disease classification from metabolic profiles, and improved metabolite annotation. It also highlights multiomics integration, demonstrating machine learning's potential in elucidating biological phenomena and advancing disease diagnostics. This work contributes significantly to metabolomics by merging it with machine learning, offering innovative solutions to analytical challenges and setting new standards for omics data analysis.

Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway.

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1ß. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

Plasmonic Alloys Enhanced Metabolic Fingerprints for the Diagnosis of COPD and Exacerbations.

Accurate diagnosis of chronic obstructive pulmonary disease (COPD) and exacerbations by metabolic biomarkers enables individualized treatment. Advanced metabolic detection platforms rely on designed materials. Here, we design mesoporous PdPt alloys to characterize metabolic fingerprints for diagnosing COPD and exacerbations. As a result, the optimized PdPt alloys enable the acquisition of metabolic fingerprints within seconds, requiring only 0.5 µL of native plasma by laser desorption/ionization mass spectrometry owing to the enhanced electric field, photothermal conversion, and photocurrent response. Machine learning decodes metabolic profiles acquired from 431 individuals, achieving a precise diagnosis of COPD with an area under the curve (AUC) of 0.904 and an accurate distinction between stable COPD and acute exacerbations of COPD (AECOPD) with an AUC of 0.951. Notably, eight metabolic biomarkers identified accurately discriminate AECOPD from stable COPD while providing valuable information on disease progress. Our platform will offer an advanced nanoplatform for the management of COPD, complementing standard clinical techniques.

Failure of lipid control by PCSK9 inhibitors in compound heterozygous familial hypercholesterolemia complicated with premature myocardial infarction: A case report.

Key Clinical Message: A certain level of low-density lipoprotein receptor activity is crucial for the efficacy of PCSK9i. Therapeutic strategies for familial hypercholesterolemia patients should consider drug efficacy, and genetic testing will be helpful. Abstract: Familial hypercholesterolemia (FH) is a serious autosomal dominant disorder. Managing blood lipids in FH patients poses greater challenges for clinicians. Drug therapy may not always yield satisfactory results, particularly in individuals with low-density lipoprotein receptor (LDLR) negative mutations. Herein, we report a young female harboring an LDLR frameshift mutation. This patient developed xanthomas at 7 months old and underwent several years of treatment involving four classes of lipid-lowering drugs, including PCSK9i. However, the response to drug therapy was limited in this patient and eventually culminated in premature myocardial infarction. The efficacy of PCSK9i depends on the activity of LDLR. The inefficacy of PCSK9i may arise from the extensive mutations which leading to loss of LDLR activity. Therapy plans for these patients should take into account the efficacy of drug therapy. Early genetic testing is crucial for clinicians to make informed decisions regarding therapy options.

Enhancing osteoblast proliferation and bone regeneration by poly (amino acid)/selenium-doped hydroxyapatite.

Among various biomaterials employed for bone repair, composites with good biocompatibility and osteogenic ability had received increasing attention from biomedical applications. In this study, we doped selenium (Se) into hydroxyapatite (Se-HA) by the precipitation method, and prepared different amounts of Se-HA-loaded poly (amino acid)/Se-HA (PAA/Se-HA) composites (0, 10 wt%, 20 wt%, 30 wt%) byin-situmelting polycondensation. The physical and chemical properties of PAA/Se-HA composites were characterized by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and their mechanical properties. XRD and FT-IR results showed that PAA/Se-HA composites contained characteristic peaks of PAA and Se-HA with amide linkage and HA structures. DSC and TGA results specified the PAA/Se-HA30 composite crystallization, melting, and maximum weight loss temperatures at 203.33 °C, 162.54 °C, and 468.92 °C, respectively, which implied good thermal stability. SEM results showed that Se-HA was uniformly dispersed in PAA. The mechanical properties of PAA/Se-HA30 composites included bending, compressive, and yield strengths at 83.07 ± 0.57, 106.56 ± 0.46, and 99.17 ± 1.11 MPa, respectively. The cellular responses of PAA/Se-HA compositesin vitrowere studied using bone marrow mesenchymal stem cells (BMSCs) by cell counting kit-8 assay, and results showed that PAA/Se-HA30 composites significantly promoted the proliferation of BMSCs at the concentration of 2 mg ml-1. The alkaline phosphatase activity (ALP) and alizarin red staining results showed that the introduction of Se-HA into PAA enhanced ALP activity and formation of calcium nodule. Western blotting and Real-time polymerase chain reaction results showed that the introduction of Se-HA into PAA could promoted the expression of osteogenic-related proteins and mRNA (integrin-binding sialoprotein, osteopontin, runt-related transcription factor 2 and Osterix) in BMSCs. A muscle defect at the back and a bone defect at the femoral condyle of New Zealand white rabbits were introduced for evaluating the enhancement of bone regeneration of PAA and PAA/Se-HA30 composites. The implantation of muscle tissue revealed good biocompatibility of PAA and PAA/Se-HA30 composites. The implantation of bone defect showed that PAA/Se-HA30 composites enhanced bone formation at the defect site (8 weeks), exhibiting good bone conductivity. Therefore, the PAA-based composite was a promising candidate material for bone tissue regeneration.

Pollution characteristics, sources, and health risks of phthalate esters in ambient air: A daily continuous monitoring study in the central Chinese city of Nanchang.

In recent years, the atmospheric pollution caused by phthalate esters (PAEs) has been increasing due to the widespread use of PAE-containing materials. Existing research on atmospheric PAEs lacks long-term continuous observation and samples from cities in central China. To investigate the pollution characteristics, sources, and health risks of PAEs in the ambient air of a typical city in central China, daily PM2.5 samples were collected in Nanchang from November 2020 to October 2021. In this study, the detection and quantification of six significant PAE contaminants, namely diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), Di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DnOP), and diisodecyl phthalate (DIDP), were accomplished using gas chromatography and mass spectrometry. The results revealed that the concentrations of DEP, DnBP, DEHP, and DnOP were relatively high. Higher temperatures promote the volatilization of PAEs, leading to an increase in the gaseous and particulate PAE concentrations in warm seasons and winter pollution scenarios. The results of principal component analysis show that PAEs mainly come from volatile products and polyvinylchloride plastics. Using positive matrix factorization analysis, it is shown that these two sources contribute 67.0% and 33.0% in atmosphere PAEs, respectively. Seasonally, the contribution of volatile products to both gaseous and particulate PAEs substantially increases during warm seasons. The residents in Nanchang exposed to PAEs have a negligible non-cancer risk and a potential low cancer risk. During the warm seasons, more PAEs are emitted into the air, which will increase the toxicity of PAEs and their impact on human health.

Synthesis of High-Molecular-Weight Poly(ether-alt-ester) by Selective Double Ring-Opening Polymerization of Spiroorthoesters.

We report the selective double ring-opening polymerization of presequenced spiroorthoester monomers to form high-molecular-weight (≈90 kDa) poly(ether-alt-ester)s with a simple cationic alkyl gallium catalyst. The selective formation of double ring-opened polymer units was confirmed by NMR and IR spectroscopies. Thermal and rheological properties of homo- and copolymers were further characterized by differential scanning calorimetry, thermogravimetric analysis, and stress-controlled rotational rheometry. Linear viscoelastic moduli show that these systems are well entangled (plateau modulus), thereby possessing nearly terminal relaxation at long time scales (low frequencies) and Rouse segmental dynamics at short time scales (high frequencies) with characteristic slopes. These are the highest-molecular-weight poly(ether-alt-ester)s reported to date.

Artesunate-Nanoliposome-TPP, a Novel Drug Delivery System That Targets the Mitochondria, Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Oxidative Stress and Inflammatory Effects.

Background: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy. Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored. Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1. Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI.

The relationship between triglyceride-glucose index and prospective key clinical outcomes in patients hospitalised for coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a dependable alternative for assessing insulin resistance (IR), given its simplicity, cost-effectiveness, and strong correlation with IR. The relationship between the TyG index and adverse outcomes in patients with coronary heart disease (CHD) is not well established. This study examines the association of the TyG index with long-term adverse outcomes in hospitalized CHD patients. METHODS: In this single-center prospective cohort study, 3321 patients hospitalized with CHD were included. Multivariate Cox regression models were employed to assess the associations between the TyG index and the incidence of all-cause mortality and major adverse cardiovascular events (MACEs). To examine potential nonlinear associations, restricted cubic splines and threshold analysis were utilized. RESULTS: During a follow-up period of 9.4 years, 759 patients (22.9%) succumbed to mortality, while 1291 (38.9%) experienced MACEs. Threshold analysis demonstrated a significant "U"-shaped nonlinear relationship with MACEs, with different hazard ratios observed below and above a TyG index of 8.62 (below: HR 0.71, 95% CI 0.50-0.99; above: HR 1.28, 95% CI 1.10-1.48). Notably, an increased risk of all-cause mortality was observed only when the TyG index exceeded 8.77 (HR 1.53, 95% CI 1.19-1.96). CONCLUSIONS: This study reveals a nonlinear association between the TyG index and both all-cause mortality and MACEs in hospitalized CHD patients with CHD. Assessing the TyG index, particularly focusing on individuals with extremely low or high TyG index values, may enhance risk stratification for adverse outcomes in this patient population.

Screening of Genes Related to Fat Deposition of Pekin Ducks Based on Transcriptome Analysis.

Subcutaneous fat deposition is an important index with which to evaluate meat-producing ducks, and affects their meat quality and feed conversion rate. Studying the differentially expressed genes in subcutaneous fat will help to comprehensively understand the potential mechanisms regulating fat deposition in ducks. In this study, 72 Nankou 1 Pekin Ducks and 72 Jingdian Pekin Ducks (half male and half female) at 42 days of age were selected for slaughter performance and transcriptome analysis. The results showed that the breast-muscle yield of Nankou 1 ducks was significantly higher than that of Jingdian ducks, but that the abdominal fat yield and subcutaneous fat yield were higher than that of Jingdian ducks. Thousands of DEGs, including many important genes involved in fat metabolism regulation, were detected by transcriptome. KEGG enrichment analysis showed that the DEGs were significantly enriched on pathways such as regulation of lipolysis in adipocytes, primary bile acid biosynthesis, and biosynthesis of unsaturated fatty acids. SCD, FGF7, LTBP1, PNPLA3, ADCY2, and ACOT8 were selected as candidate genes for regulating subcutaneous fat deposition. The results indicated that Nankou 1 had superior fat deposition ability compared to Jingdian ducks, and that the candidate genes regulated fat deposition by regulating fat synthesis and decomposition.

Sources and influences of atmospheric nonpolar organic compounds in Nanchang, central China: Full-year monitoring with a focus on winter pollution episodes.

Nonpolar organic compounds (NPOCs) are found in atmospheric aerosols and have significant implications for environmental and human health. Although many studies have quantitatively estimated the sources of NPOCs in different cities, few have evaluated their main influencing factors (e.g., emissions and meteorological conditions) at relatively long (e.g., different seasons) and short timescales (e.g., several days during pollution episodes). A better understanding of this issue could optimise strategies for dealing with organic contamination in atmospheric particulate matter. NPOCs (including n-alkanes, PAHs and hopanes) in fine particulate matter (PM2.5) were sampled daily at Nanchang, China, from 1 November 2020 to 31 October 2021. Analyses of specific biomarkers and diagnostic ratios indicate that the NPOCs mainly had anthropogenic sources. The quantitative estimates of a positive matrix factorization model show that fossil fuel and biomass combustion were the main sources of n-alkanes (contributing 64.8 %), while vehicle exhaust was the main source of PAHs (47.0 %) and hopanes (52.3 %). Seasonally, the contributions from coal and/or biomass combustion were higher in autumn and winter (40.2-56.3 %) than in spring and summer (25.7-44.3 %), while contributions from natural plants, petroleum volatilization and vehicle exhaust were higher in spring and summer (14.7-63.5 %) than in autumn and winter (8.1-48.9 %). Redundancy analysis shows that increased emissions, especially from coal and/or biomass combustion, are the main cause of increases in NPOCs, during both annual sampling periods and winter pollution episodes. Over the year, higher temperature and longer sunshine hours correspond to lower NPOC concentrations. In winter pollution episodes, increases in temperature and relative humidity correspond to increases in NPOC concentrations. Our results suggest that controlling primary emissions, especially from coal and biomass combustion, may be an effective way to prevent increases in NPOC concentrations.

Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice.

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.

ß-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury.

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.

L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.

Mechanism of effects of electroacupuncture on memory and cognitive impairment in offspring rats with perinatal nicotine exposure. / ç”µé’ˆå¯¹å›´äº§æœŸå°¼å¤ä¸æš´éœ²å­ä»£å¤§é¼ è®°å¿†å’Œè®¤çŸ¥æŸä¼¤å½±å“çš„æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To observe the effects of electroacupuncture(EA) on memory, cognitive impairment, and the brain-derived neurotrophic factor(BDNF)/N-methyl-D-aspartate receptor subtype 1(NMDAR1) pathway in the brains of offspring rat with intrauterine growth restriction(IUGR) induced by perinatal nicotine exposure(PNE), so as to explore the underlying mechanism. METHODS: SD rats were randomly divided into normal, model, and EA groups, with 4 mothers and 10 offspring rats of each mother in each group. The IUGR model was established by subcutaneous injection of nicotine during pregnancy and lactation. From the 6th day of pregnancy in the mothers until the 21st day after birth of the offspring rats, EA (2 Hz/15 Hz, 1 mA) was administered bilaterally at the "Zusanli"(ST36) of mothers, once daily for 20 min. The brain organ coefficient was used to evaluate the brain development of the offspring rats. The Y-maze test and novel object recognition experiments were performed to assess memory and cognitive function. HE staining was used to observe the development and cellular morphology of the hippocampus and prefrontal cortex in the offspring rats. UV spectrophotometry was used to measure the glutamate(Glu) content in the hippocampus. ELISA was used to detect the BDNF content in the hippocampus. Western blot was performed to measure the protein expression of NMDAR1 in the hippocampus. Immunohistochemistry was used to count the number of BDNF-positive cells in the hippocampus and prefrontal cortex. RESULTS: Compared with the normal group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, contents of BDNF and expression of NMDAR1 proteins in the hippocampus, the number of BDNF-positive cells in the CA1 and CA3 regions of the hippocampus and prefrontal cortex were significantly reduced(P<0.01), while the Glu content in the hippocampus was significantly increased(P<0.01) in the model group of offspring rats；decreased cell number, scattered arrangement, and disrupted cellular structure were observed in the hippocampus and prefrontal cortex of offspring rats in the model group. Compared with the model group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, the BDNF contents and NMDAR1 protein expression in the hippocampus, the number of BDNF-positive cells in the hippocampal CA1 and CA3 regions and prefrontal cortex significantly increased(P<0.01, P<0.05), while the Glu content in the hippocampus was significantly decreased (P<0.01) in offspring rats of the EA group；increased cell number, neat arrangement, and reduced cellular damage were observed in the hippocampus and prefrontal cortex in the EA group. CONCLUSIONS: EA has an improving effect on memory and cognitive function impairment in offspring rats with IUGR induced by PNE, and this mechanism may be associated with the regulation of BDNF/NMDAR1 pathway, thereby improving the neuronal quantity and structure of the hippocampus and prefrontal cortex in offspring rats.

Tracking tumor evolution during the first-line treatment in brain glioma via serial profiling of cell-free tumor DNA from tumor in situ fluid.

Objective: Tumor in situ fluid (TISF) refers to the fluid within surgical cavities of glioma. Several studies preliminarily proved the value of cell-free tumor DNA (cf-tDNA) from TISF in the dynamic characterization of the glioma genome. Here, we assessed the potential utility of TISF cf-tDNA in broad aspects of tumor evolution under therapeutic pressure. Methods: This study was conducted under an Institutional Review Board-approved protocol at Henan Provincial People's Hospital (China). Cf-tDNA samples were sequenced with a designed 68-gene panel. A total of 205 cf-tDNA samples from 107 patients were studied. The clinical relevance of serial cf-tDNA profiling during the postoperative course was analyzed. Results: At least one tumor mutations were detected in 179/205 (87.3%) TISF cf-tDNA samples. Serial cf-tDNA was complementary to molecular residual disease and to initial tumors. Serial cf-tDNA revealed the selection of pre-existing mismatch repair-deficient cells by temozolomide as a resistant mechanism. Cf-tDNA parameters during treatment were predictive of recurrence, and serial cf-tDNA monitoring had diagnostic value for early recurrence. A total of 223 potentially actionable genomic alterations were assessed in cf-tDNA samples, wherein 78% were not found in any tumor tissue. Conclusions: In conclusion, serial TISF cf-tDNA profiling is valuable in tracking the tumor evolution of glioma during treatment and may be a feasible non-invasive option for monitoring glioma in future prospective studies and clinical practice.

Evidence for Wnt signaling's central involvement in perinatal nicotine exposure-induced offspring lung pathology and its modulation by electroacupuncture.

OBJECTIVE: Many factors during pregnancy can induce intrauterine growth restriction (IUGR), resulting in various adverse perinatal outcomes such as low birth weight and multiple organ disorders. Among these factors, prenatal smoke/nicotine exposure is a common cause of IUGR, often associated with altered fetal lung development. The classical Wnt signaling pathway plays a vital role in lung development, and its alterations are commonly associated with developmental lung pathologies. The purpose of this study was to determine whether electroacupuncture (EA) at "Zusanli" (ST 36) points protects perinatal nicotine exposure (PNE)-induced offspring lung dysplasia through Wnt/ß-catenin signaling pathway and to identify specific Wnt signaling pathway targets of EA. METHODS: Following a well-established protocol, nicotine (1 mg/kg/ body weight) was administered subcutaneously to pregnant Sprague Dawley rat dams from gestational day 6 to postnatal day 21. In the EA group, dams were treated with EA at both ST 36 acupoints, while in another experimental group, Wnt/ß-catenin signaling pathway agonist was injected subcutaneously (2 mg/kg/ body weight). Offspring body weight (PND 1, 7, 14, and 21), lung weight, Wnt signaling markers, pulmonary function, and lung morphology were determined at sacrifice on PND 21. Specifically, Western blotting and Real-time PCR were used to detect the protein and mRNA levels of critical Wnt signaling markers Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the offspring lung. The protein levels of ß-catenin in lung tissue of offspring rats were detected by ELISA that of LEF-1 by Western blotting. RESULTS: Compared to the control group, the body and lung weights of the offspring rats were significantly decreased in the nicotine-only exposed group. The pulmonary function determined as FVC, PEF, TV, and Cdyn was also significantly decreased, while PIF was significantly increased. The protein levels and mRNA expression of Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the lung tissue of the PNE offspring rats were significantly increased. With EA administration at ST 36 acupoints concomitant with nicotine administration, the body and lung weights, pulmonary function (FVC, PEF, PIF, TV, and Cdyn), protein and mRNA levels Wnt signaling pathway markers (Wnt2, Wnt7b, FZD4, FZD7, LRP5, LRP6, ß-catenin, and LEF-1) normalized and were not different from the control group. Notably, Wnt agonists agonist administration blocked the protective effects of EA against PNE-induced lung morphological, molecular, and function changes, highlighting the central significance of Wnt pathway signaling in PNE-induced offspring pulmonary pathology and its modulation by EA at ST 36 acupoints. CONCLUSION: Concomitant maternal EA at ST 36 acupoints from gestational day 6 to PND 21 protects against offspring PNE-induced lung phenotype. The protective effect is achieved by regulating the expression of Wnt ligand proteins (Wnt2 and Wnt7b) and receptor proteins (FZD4, FZD7, LRP5, and LRP6) upstream of the Wnt/ß-catenin signaling pathway intermediates ß-catenin, and LEF-1.