Malicious Tumor? Pathological Fracture of the Femur in Children Caused by Myelolipoma: A Case Report and Review of Literatures.

Myelolipoma is a kind of benign lipoma containing myeloid cells. It is a rare type of tumor that typically presents as an occasional adrenal tumor, generally manifesting as a nonfunctional adrenal mass. Although it can occur in extra-adrenal tissues, its occurrence in bone tissue is extremely rare. Most cases are discovered accidentally during physical examinations of adults, and there are currently no reports of cases with pathological fractures as the main symptoms. We present a case of a 15-year-old teenager who developed a pathological fracture caused by femoral myelolipoma. The diagnosis of the specific type of bone tumor of the patient was determined through pathology and imaging. To treat the condition, we utilized a technique known as the "soft drill" to fully access the tumor space, remove the bone septum, and scrape away the diseased tissue. The fracture was then stabilized using a hybrid external fixation. After a 2-year follow-up period, there was no recurrence of the bone tumor. This case is the first case of intraosseous myelolipoma that occurred in a minor with the initial symptom of pathological fracture, filling the gap in our existing body of knowledge and providing a reference for the treatment of this type of intraosseous myelolipoma.

PLIN5 Suppresses Lipotoxicity and Ferroptosis in Cardiomyocyte via Modulating PIR/NF-κB Axis.

Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL)-1ß/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.

The mechanism of Xihuang pills' intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. AIM OF THE STUDY: Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. MATERIALS AND METHODS: Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. RESULTS: Xihuang Pill has a regulatory effect on the tumor immune microenvironment. CONCLUSIONS: The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein.

108 m Underwater Wireless Optical Communication Using a 490 nm Blue VECSEL and an AOM.

Advanced light sources in the blue-green band are crucial for underwater wireless optical communication (UWOC) systems. Vertical-external-cavity surface-emitting lasers (VECSELs) can produce high output power and good beam quality, making them suitable for UWOC. This paper presents a 108 m distance UWOC based on a 100 mW 490 nm blue VECSEL and an acousto-optic modulator (AOM). The high-quality beam, which is near diffraction-limited, undergoes relatively small optical attenuation when using a conventional avalanche photodiode (APD) as the detector and employing 64-pulse position modulation (PPM). At the time-slot frequency of 50 MHz, the bit error rate (BER) of the UWOC was 2.7 × 10-5. This is the first reported AOM-based UWOC system with a transmission distance over 100 m. The estimated maximum transmission distance may be improved to about 180 m by fully utilizing the detection accuracy of the APD according to the measured attenuation coefficient of the blue VECSEL used. This type of UWOC system, composed of a high-beam-quality light source and a conventional detector, make it more closely suited to practical applications.

Diaphorobacter nitroreducens synergize with oxaliplatin to reduce tumor burden in mice with lung adenocarcinoma.

Lung adenocarcinoma (LADC) is the most common lung cancer and the leading cause of cancer-related deaths globally. Accumulating evidence suggests that the gut microbiota regulates the host response to chemotherapeutic drugs and can be targeted to reduce the toxicity of current chemotherapeutic agents. However, the effect of Diaphorobacter nitroreducens synergized with oxaliplatin on the gut microbiota and their impact on LADC have never been explored. This study aimed to evaluate the anti-cancer effects of D. nitroreducens, oxaliplatin, and their combined treatment on tumor growth in tumor-bearing mice. The composition of gut microbiota and the immune infiltration of tumors were evaluated by using 16S rRNA gene high-throughput sequencing and immunofluorescence, respectively. The inhibitory effect of the combination treatment with D. nitroreducens and oxaliplatin was significantly stronger than that of oxaliplatin alone in tumor-bearing mice. Furthermore, we observed that the combination treatment significantly increased the relative abundance of Lactobacillus and Akkermansia in the gut microbiota. Meanwhile, the combination treatment significantly increased the proportions of macrophage but decreased the proportion of regulatory T cells in the LADC tumor tissues of mice. These findings underscored the relationship between D. nitroreducens and the gut microbiota-immune cell-LADC axis, highlighting potential therapeutic avenues for LADC treatment. IMPORTANCE: Oxaliplatin is widely used as an effective chemotherapeutic agent in cancer treatment, but its side effects and response rate still need to be improved. Conventional probiotics potentially benefit cancer chemotherapy by regulating gut microbiota and tumor immune infiltration. This study was novel in reporting a more significant inhibitory effect of Diaphorobacter nitroreducens on lung adenocarcinoma (LADC) cells compared with common traditional probiotics and validating its potential as an adjuvant therapy for LADC chemotherapy in mice. This study investigated the impact of D. nitroreducens combined with oxaliplatin on the gut microbiota and immune infiltration of tumors as a potential mechanism to improve anticancer effects.

Metabolic impairments associated with type 2 diabetes mellitus and the potential effects of exercise therapy: An exploratory randomized trial based on untargeted metabolomics.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles. METHODS: This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy. RESULTS: Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline. CONCLUSION: T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.

TiRobot-Assisted Percutaneous Cannulated Screw Fixation for Elderly Patients with Fragility Fractures of the Pelvis: A Retrospective Study.

OBJECTIVE: The incidence of fragility fractures of the pelvis (FFPs) is increasing in the elderly population, and FFPs that require fixation are a challenge for orthopedic surgeons. The insertion of implants is not risk free due to the complex anatomical and osteoporotic bones and requires a steep learning curve. This study aimed to investigate the clinical efficacy of TiRobot-assisted percutaneous cannulated screw fixation in the treatment of elderly FFP patients. METHOD: The clinical data of 46 elderly FFP patients who had been treated with percutaneous cannulated screw fixation from May 2020 to September 2022 were retrospectively analyzed. Twenty-four patients were treated with percutaneous cannulated screw fixation assisted by the TiRobot (TiRobot-assisted group) and 22 patients were treated with conventional freehand surgery (freehand group). Postoperative outcomes, including Matta value, excellent and good rate (EGR) of fracture reduction, and accuracy of screw placement (ASP), were compared. Changes in the Visual analog scale (VAS) pain score and the Majeed score were recorded and compared between groups before and after surgery and during the 24-week follow-up. Repeated-measures analysis of variance (ANOVA) and effect sizes were used as analysis methods. RESULTS: A total of 90 screws were implanted, 51 screws in the TiRobot-assisted group and 39 screws in the freehand group. The operation time of the two groups was 34.1 ± 2.67 min versus 64.5 ± 4.19 min (p < 0.001). There were no screw-related complications or revision surgeries in any group. The Matta value of the TiRobot-assisted group was 5.13 ± 3.52, which was significantly lower than that of the freehand group (9.00 ± 3.68, p < 0.001), while the EGR was 91.67% versus 72.73%, with statistical significance (p < 0.001). The ASP was 100% in the TiRobot-assisted group, better than that in the freehand group, where it was 85.7% (p = 0.043). At each timepoint in the early postoperative period, the VAS score of the TiRobot-assisted group was significantly lower than that of the freehand group and was close to consistent by the last follow-up; the Majeed score of the former was significantly higher than that of the latter at each timepoint of follow-up, with statistical significance (p < 0.001). CONCLUSION: TiRobot-assisted percutaneous cannulated screw fixation of elderly FFP patients is advantageous over conventional freehand surgery, with less invasion, more accurate screw placement, better fracture reduction, early pain relief, and rapid recovery, suggesting that Freehand method to stabilize FFP in the elderly population.

Response of fine particulate matter and ozone concentrations to meteorology and anthropogenic precursors over the "2+26" cities of northern China.

Analyzing the influencing factors of fine particulate matter and ozone formation and identifying the coupling relationship between the two are the basis for implementing the synergistic pollutants control. However, the current research on the synergistic relationship between the two still needs to be further explored. Using the Geodetector model, we analyzed the effects of meteorology and emissions on fine particulate matter and ozone concentrations over the "2 + 26" cities at multiple timescales, and also explored the coupling relationship between the two pollutants. Fine particulate matter concentrations showed overall decreasing trends on inter-season and inter-annual scale from 2015 to 2021, whereas ozone concentrations showed overall increasing trends. While ozone concentrations displayed an inverted U-shaped distribution from month to month, fine particulate matter concentrations displayed a U-shaped fluctuation. On inter-annual scale, climatic factors, with planet boundary layer height as the main determinant, have higher effects for both pollutants than human precursors. In summer and autumn, sunshine duration had the most influence on fine particulate matter, while planet boundary layer height was the greatest factor in winter. Fine particulate matter is the leading impacting factor on ozone concentrations in summer, and there were positive associations between them on both annual and seasonal scale. The impact of nitrogen oxides and volatile organic compounds for both pollutants concentrations varied significantly between seasons. The two pollutants concentration were enhanced by the interactions between the various components. On inter-annual scale, interactions between the planet boundary layer height and other factors dominated the concentrations of the two pollutants, whereas in summer, interactions between fine particulate matter and other factors dominated the concentrations of ozone. The study has implications for the treatment of atmospheric pollution in China and other nations and can serve as an important reference for the creation of integrated atmospheric pollution regulation policies over the "2 + 26" cities.

Synthesis of MnOOH and its application in a supporting hexagonal Pd/C catalyst for the oxygen reduction reaction.

With the expansion of global energy problems and the deepening of research on oxygen reduction reaction (ORR) in alkaline media, the development of low cost and high electrocatalytic performance catalysts has become a research hotspot. In this study, a hexagonal Pd-C-MnOOH composite catalyst was prepared by using the triblock copolymer P123 as the reducing agent and protective agent, sucrose as the carbon source and self-made MnOOH as the carrier under hydrothermal conditions. When the Pd load is 20% and the C/MnOOH ratio is 1 : 1, the 20% Pd-C-MnOOH-1 : 1 catalyst obtained by the one-step method has the highest ORR activity and stability in the alkaline system. At 1600 rpm, the limiting diffusion current density and half-wave potential of the 20% Pd-C-MnOOH-1 : 1 electrocatalyst are -4.78 mA cm-2 and 0.84 V, respectively, which are better than those of the commercial 20%Pd/C catalyst. According to the Koutecky-Levich (K-L) equation and the linear fitting results, the electron transfer number of the 20%Pd-C-MnOOH-1 : 1 electrocatalyst for the oxygen reduction reaction is 3.8, which is similar to that of a 4-electron process. After 1000 cycles, the limiting diffusion current density of the 20%Pd-C-MnOOH-1 : 1 catalyst is -4.61 mA cm-2, which only decreases by 3.7%, indicating that the 20%Pd-C-MnOOH-1 : 1 catalyst has good stability. The reason for the improvement of the ORR performance of the Pd-C-MnOOH composite catalyst is the improvement of the conductivity of the carbon layer formed by original carbonization, the regular hexagonal highly active Pd particles and the synergistic catalytic effect between Pd and MnOOH. The method of introducing triblock copolymers in the synthesis of oxides and metal-oxide composite catalysts is expected to be extended to other electrocatalysis fields.

The transcription activity of OTX2 on p16 expression is significantly blocked by methylation of CpG shore in non-promoter of lung cancer cell lines.

Background: The aberrant expression of the classical tumor suppressor gene p16 is a frequent event in lung cancer mainly due to the hypermethylation of its 5'-cytosine-phosphate-guanine-3' island (Cgi). However, whether methylation happens in other regions and how p16 expression and function are affected are largely unknown. Methods: Clustered Regularly Interspaced Short Palindromic Repeats/dCas9 (CRISPR/dCas9) technology was used for methylation editing at specific site of p16. The effects of methylation editing were detected by 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS), transwell migration and wound healing tests. Chromatin immnoprecipitation-quantitative polymerase chain reaction (CHIP-qPCR) was performed to explore the impact of Cgi shore methylation on the binding abilities of transcription factors (TFs) including YY1, SP1, ZNF148 and OTX2 to p16 gene. A rescue experiment was performed to verify the regulatory effect of OTX2 on p16. The negative relationship between p16 expression and the methylation level of Cgi shore in non-promoter region was further verified with datasets from The Cancer Genome Atlas (TCGA) program and lung adenocarcinoma (LUAD) patients' samples. Results: The suppressive effect of p16 Cgi shore methylation on its expression was demonstrated in both HEK293 and A549 cells using CRISPR/dCas9-mediated specific site methylation editing. Methylation of the Cgi shore in the p16 non-promoter region significantly decreased its expression and promoted cell growth and migration. The ability of OTX2 bound to p16 was significantly reduced by 19.35% after methylation modification. Over-expression of OTX2 in A549 cells partly reversed the inhibitory effect of methylation on p16 expression by 19.04%. The verification results with TCGA and LUAD patients' samples supported that the p16 Cgi shore is a key methylation regulatory region. Conclusions: Our findings suggested that methylation of the Cgi shore in the p16 non-promoter region can hamper the transcriptional activity of OTX2, leading to a reduction in the expression of p16, which might contribute to the development of lung cancer.

Photoinduced Copper-Catalyzed 1,2-Difunctionalization of 1,3-Dienes with Aryl Diselenides.

Described herein is a photoinduced copper-catalyzed 1,2-difunctionalization of 1,3-dienes. The selenium atom radical was generated by the visible light irradiation of diselenides, triggering radical addition with 1,3-dienes to form allyl radical intermediate. Subsequent rapid Z/E isomerization allowed for thermodynamically favorable intermediate formation and enabled copper catalyzed stereoselective functionalization with various nucleophiles.

Protein acetylation and related potential therapeutic strategies in kidney disease.

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.

LncRNA MSTRG.22719.16 mediates the reduction of enoxaparin sodium high-viscosity bone cement-induced thrombosis by targeting the ocu-miR-326-5p/CD40 axis.

OBJECTIVE: Polymethylmethacrylate (PMMA) bone cement promotes the development of local thrombi. Our study found that a novel material, ES-PMMA bone cement, can reduce local thrombosis. We used a simple and reproducible animal model to confirm the reduction in local thrombosis and explored the associated molecular mechanism. METHODS: New Zealand rabbits, which were used to model thrombosis using extracorporeal carotid artery shunts, were divided into the following two groups, with 3 rabbits in each group: the PMMA bone cement group and the ES-PMMA bone cement group. Four hours after modelling, experimental samples, including thrombotic and vascular tissues, were collected. Thrombotic samples from the PMMA group and ES-PMMA group were subjected to lncRNA sequencing, and a lncRNA microarray was used to screen the differentially expressed lncRNAs. The expression of thrombomodulin in endothelial cells was quantified in vascular tissue samples. Differences in the lncRNA expression profiles between the thrombotic samples of the PMMA group and ES-PMMA group were assessed by base-to-base alignment in the intergenic regions of genomes. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. Thrombosis was observed in the PMMA group and ES-PMMA group. RESULTS: The thrombotic weight was 0.00706 ± 0.00136 g/cm in the PMMA group and 0.00551 ± 0.00115 g/cm in the ES-PMMA group. Quantitative real-time polymerase chain reaction (RT-q-CR) and Western blotting revealed that the expression of CD40, which can regulate thrombosis in vascular endothelial cells, was significantly lower in the ES-PMMA group than in the PMMA group. High-throughput sequencing was used to identify 111 lncRNAs with lower expression in the ES-PMMA group than in the PMMA group. Through bioinformatics investigation, lncRNA MSTRG22719.16/ocu-miR-326-5p/CD40 binding sites were selected. Fluorescent in situ RNA hybridization (FISH) was performed to verify the lower expression of lncRNA MSTRG.22719.16 in vascular tissues from the ES-PMMA group. A dual-luciferase reporter gene assay was applied to verify that ocu-miR-326-5p binds the CD40 3'-UTR and targets lncRNA MSTRG.22719.16. CONCLUSION: Compared with PMMA bone cement, ES-PMMA bone cement can reduce thrombosis through the lncRNA MSTRG.22719.16/ocu-miR-326-5p/CD40 axis.

Vanadium-catalyzed Hydration of 2-Cyanopyrazine to Pyrazinamide with Unique Substrate Specificity.

Pyrazinamide is an important medicine used for the treatment of tuberculosis(TB). The preparation of pyrazinamide via catalytic hydration of 2-cyanopyrazine is of great economic interest with high atomic economy. Heterogeneous non-precious transition metal-catalyzed hydration of nitriles under neutral reaction conditions would be rather attractive. Herein vanadium-nitrogen-carbon materials were fabricated and employed for selective hydration of nitriles using water as both the solvent and reactant. 2-Cyanopyrazine could be smoothly converted into to pyrazinamide with unique substrate specificity. Additives with different N and O atoms could significantly affect hydration of 2-cyanopyrazine due to competitive adsorption/coordination in the reaction system. This work provides a new approach for non-precious metal catalyzed hydration of nitriles.

ATF2-driven osteogenic activity of enoxaparin sodium-loaded polymethylmethacrylate bone cement in femoral defect regeneration.

BACKGROUND: Polymethylmethacrylate (PMMA) bone cement loaded with enoxaparin sodium (PMMA@ES) has been increasingly highlighted to affect the bone repair of bone defects, but the molecular mechanisms remain unclear. We addressed this issue by identifying possible molecular mechanisms of PMMA@ES involved in femoral defect regeneration based on bioinformatics analysis and network pharmacology analysis. METHODS: The upregulated genes affecting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were selected through bioinformatics analysis, followed by intersection with the genes of ES-induced differentiation of BMSCs identified by network pharmacology analysis. PMMA@ES was constructed. Rat primary BMSCs were isolated and cultured in vitro in the proliferation medium (PM) and osteogenic medium (OM) to measure alkaline phosphatase (ALP) activity, mineralization of the extracellular matrix, and the expression of RUNX2 and OCN using gain- or loss-of-function experiments. A rat femoral bone defect model was constructed to detect the new bone formation in rats. RESULTS: ATF2 may be a key gene in differentiating BMSCs into osteoblasts. In vitro cell assays showed that PMMA@ES promoted the osteogenic differentiation of BMSCs by increasing ALP activity, extracellular matrix mineralization, and RUNX2 and OCN expression in PM and OM. In addition, ATF2 activated the transcription of miR-335-5p to target ERK1/2 and downregulate the expression of ERK1/2. PMMA@ES induced femoral defect regeneration and the repair of femoral defects in rats by regulating the ATF2/miR-335-5p/ERK1/2 axis. CONCLUSION: The evidence provided by our study highlighted the ATF2-mediated mechanism of PMMA@ES in the facilitation of the osteogenic differentiation of BMSCs and femoral defect regeneration.

Costunolide alleviated DDC induced ductular reaction and inflammatory response in murine model of cholestatic liver disease.

Purpose: Cholestatic liver diseases are groups of hepatobiliary diseases without curative drug-based therapy options. Regulation of bile acid (BA) metabolism, hepatoperiductal fibrosis, and inflammatory response indicated present novel methods for the treatment of cholestatic liver disease. Costunolide (COS) from herb Saussurea lappa exerts a pharmacological effect of regulation of BA metabolism, liver fbrosis and inflammatory response. The present study aimed to clarify the pharmacodynamic effects of COS against the murine model of cholestatic liver disease. Methods: We established a murine model of cholestatic liver disease through chronic feeding of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 28 days. Two independent in vivo experiments were designed to reveal the pharmacological effect of COS against cholestatic liver disease. In the first experiment, two dosages of COS (10 and 30 mg/kg) were intraperitoneally injected into model mice daily for 14 days. In the second experiment, high dosage of COS (30 mg/kg) was intraperitoneally injected into control and model mice daily for 28 days. Results: In the evaluation of the hepatoprotective effect of COS, COS showed dosage-dependent improvement of cholestatic liver disease, including ductular reaction, hepatoperiductal fibrosis, and inflammatory response. The mechanism of COS-mediated hepatoprotective effects mainly relies on the regulation of BA metabolism, and the inflammatory response. DDC diet feed induced hepatic BA metabolism, transport and circulation dysfunction. COS treatment not only regulated the BA metabolism and transport gene, but also reprogrammed hepatic primary and secondary BA concentrations. DDC induced hepatic infiltrated monocytes derived macrophages and lymphocytes were inhibited, while Kupffer cells were preserved by COS treatment. The liver elevating inflammatory cytokines of DDC diet feed were alleviated by COS. Moreover, high dosage of 30 mg/kg COS treatment for 28 days resulted in no significant serological changes and no obvious hepatic histopathological changes when compared with control mice. Conclusion: COS protected against DDC diet feeding-induced cholestatic liver disease since COS regulated BA metabolism, ductular reaction, hepatoperiductal fibrosis and inflammatory response. COS is suggested as a potential natural product for the treatment of cholestatic liver disease.

Novel insights into STAT3 in renal diseases.

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.

Solvent Engineering of Oxygen-Enriched Carbon Dots for Efficient Electrochemical Hydrogen Peroxide Production.

The development of cost-effective and reliable metal-free carbon-based electrocatalysts has gained significant attention for electrochemical hydrogen peroxide (H2 O2 ) generation through a two-electron oxygen reduction reaction. In this study, a scalable solvent engineering strategy is employed to fabricate oxygen-doped carbon dots (O-CDs) that exhibit excellent performance as electrocatalysts. By adjusting the ratio of ethanol and acetone solvents during the synthesis, the surface electronic structure of the resulting O-CDs can be systematically tuned. The amount of edge active CO group was strongly correlated with the selectivity and activity of the O-CDs. The optimum O-CDs-3 exhibited extraordinary H2 O2 selectivity of up to 96.55% (n = 2.06) at 0.65 V (vs RHE) and achieved a remarkably low Tafel plot of 64.8 mV dec-1 . Furthermore, the realistic H2 O2 productivity yield of flow cell is measured to be as high as 111.18 mg h-1  cm-2 for a duration of 10 h. The findings highlight the potential of universal solvent engineering approach for enabling the development of carbon-based electrocatalytic materials with improved performance. Further studies will be undertaken to explore the practical implications of the findings for advancing the field of carbon-based electrocatalysis.

Enoxaparin sodium bone cement displays local anti-inflammatory effects by regulating the expression of IL-6 and TNF-α.

Objective: To explore the roles of Enoxaparin Sodium-Polymethyl methacrylate bone cement on inflammatory factors Interleukin-6 and Tumour Necrosis Factor-α in a rabbit knee replacement model. As well as the mechanisms underlying its potential effects on lipopolysaccharide-induced endothelial cell injury. Methods: A knee replacement model was established using New Zealand rabbits. Forty rabbits were randomly divided into four groups: PMMA, ES-PMMA, sham-operated, and blank control groups (n = 10 in each group). Local tissues around the incision were taken at the 30th, 60th, and 90th minute after the surgical implantation of the corresponding bone cement. Immunohistochemistry in the surgical field was used to measure the expression of local inflammatory factors IL-6 and TNF-α. In the in vitro experiments, 1 cm3 of bone cement was immersed in 3 mL of the medium for 24 h. The bone cement was discarded and diluted to 25% with normal medium. Pre-experiments were screened for the best LPS-inducing concentration of 100 mg/mL, and the most compatible LPS concentration was used for subsequent experiments simulating the primary cultures of rats' Inferior Vena Cava Endothelial Cells. The experiments were divided into four groups: blank control group, LPS induction group, PMMA + LPS group, and ES-PMMA + LPS group. The apoptosis rate was detected by flow cytometry, and the expression levels of TNF-α and IL-6 in the cells and supernatant were measured by ELISA, western blotting, and immunofluorescence. Results: According to immunohistochemical results, IL-6-positive cells were concentrated in the tissue interstitial space. In the PMMA and sham-operated groups, the number of IL-6-positive cells gradually increased over time. At all time points, IL-6 expression in the ES-PMMA group was much lower than in the PMMA and sham-operated groups. At 30 min, TNF-α positive cells in the ES-PMMA group expressed less than those in the PMMA and sham-operated groups, with no discernible difference between the PMMA and ES-PMMA groups at 60 or 90 min. Using ELISA and flow cytometry, the expression levels of IL-6 and TNF-α were improved and the apoptosis rate was magnified in the LPS-induced group (***P < 0.001) in contrast with the blank control group. Additionally, the expression levels of IL-6 and TNF-α were reduced in the ES-PMMA + LPS group compared with the LPS-induced group (*P < 0.05) and the apoptosis rate was reduced (***P < 0.001), with statistically significant variations. Western blotting and immunofluorescence analysis confirmed that IL-6 and TNF-α protein expression in cells was upregulated in the LPS-induced group compared to the blank control group (***P < 0.001), and the mean fluorescence intensity was enlarged (***P < 0.001). Meanwhile, IL-6 and TNF-α expression in the ES-PMMA + LPS group were down-regulated (**P < 0.01 or *P < 0.05) compared with the LPS-induced group and PMMA + LPS crew protein expression, and the average fluorescence intensity of IL-6 and TNF-α was lowered in the ES-PMMA + LPS group compared to the LPS-induced group (***P < 0.001). Conclusions: ES-PMMA bone cement reduced the expression levels of local inflammatory factors IL-6 and TNF-α in a rabbit knee model. ES-PMMA bone cement reduced the rate of LPS-induced endothelial cell apoptosis and diminished local inflammatory damage by regulating the secretion of inflammatory factors TNF-α and IL-6.

Enoxaparin sodium bone cement plays an anti-inflammatory immunomodulatory role by inducing the polarization of M2 macrophages.

OBJECTIVE: The implantation of PMMA bone cement results in an immune response and the release of PMMA bone cement particles causes an inflammatory cascade. Our study discovered that ES-PMMA bone cement can induce M2 polarization of macrophages, which has an anti-inflammatory immunomodulatory effect. We also delved into the molecular mechanisms that underlie this process. METHODS: In this study, we designed and prepared samples of bone cement. These included PMMA bone cement samples and ES-PMMA bone cement samples, which were implanted into the back muscles of rats. At 3, 7, and 14 days after the operation, we removed the bone cement and a small amount of surrounding tissue. We then performed immunohistochemistry and immunofluorescence to observe the polarization of macrophages and the expression of related inflammatory factors in the surrounding tissues. The RAW264.7 cells were exposed to lipopolysaccharide (LPS) for 24 h to establish the macrophage inflammation model. Then, each group was treated with enoxaparin sodium medium, PMMA bone cement extract medium, and ES-PMMA bone cement extract medium, respectively, and cultured for another 24 h. We collected cells from each group and used flow cytometry to detect the expressions of CD86 and CD206 in macrophages. Additionally, we performed RT-qPCR to determine the mRNA levels of three markers of M1 macrophages (TNF-α, IL-6, iNOS) and two M2 macrophage markers (Arg-1, IL-10). Furthermore, we analyzed the expression of TLR4, p-NF-κB p65, and NF-κB p65 through Western blotting. RESULTS: The immunofluorescence results indicate that the ES-PMMA group exhibited an upregulation of CD206, an M2 marker, and a downregulation of CD86, an M1 marker, in comparison to the PMMA group. Additionally, the immunohistochemistry results revealed that the levels of IL-6 and TNF-α expression were lower in the ES-PMMA group than in the PMMA group, while the expression level of IL-10 was higher in the ES-PMMA group. Flow cytometry and RT-qPCR analyses revealed that the expression of M1-type macrophage marker CD86 was significantly elevated in the LPS group compared to the NC group. Additionally, M1-type macrophage-related cytokines TNF-α, IL-6, and iNOS were also found to be increased. However, in the LPS + ES group, the expression levels of CD86, TNF-α, IL-6, and iNOS were decreased, while the expression of M2-type macrophage markers CD206 and M2-type macrophage-related cytokines (IL-10, Arg-1) were increased compared to the LPS group. In comparison to the LPS + PMMA group, the LPS + ES-PMMA group demonstrated a down-regulation of CD86, TNF-α, IL-6, and iNOS expression levels, while increasing the expression levels of CD206, IL-10, and Arg-1. Western blotting results revealed a significant decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 in the LPS + ES group when compared to the LPS group. Additionally, the LPS + ES-PMMA group exhibited a decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 levels when compared to the LPS + PMMA group. CONCLUSION: ES-PMMA bone cement is more effective than PMMA bone cement in down-regulating the expression of the TLR4/NF-κB signaling pathway. Additionally, it induces macrophages to polarize towards the M2 phenotype, making it a crucial player in anti-inflammatory immune regulation.