A case report of IgG4-related hepatic inflammatory pseudotumor in a 3-year old boy.

Background: Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition. Case Presentation: A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies. Conclusion: This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.

Exploring the Link Between Autophagy-Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons.

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.

Identification of a novel ANK1 gene variant c.1504-9G>A and its mechanism of intron retention in hereditary spherocytosis.

Objective: The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. Methods: We utilized whole-exome sequencing (WES) for individual analysis (case 1) and family-based trio analysis (case 2). The significance of the intronic mutation was validated through a Minigene splicing assay and supported by subsequent in vitro experiments. Results: Both probands received a diagnosis of hereditary spherocytosis. WES identified a novel ANK1 c.1504-9G>A mutation in both patients, causing the retention of seven nucleotides at the 5' end of intron 13, as substantiated by the Minigene assay. This variant results in a premature stop codon and the production of a truncated protein. In vitro studies indicated a reduced expression of the ANK1 gene. Conclusion: The novel ANK1 c.1504-9G>A variant is established as the causative factor for hereditary spherocytosis, with the c.1504-9G site functioning as a splicing receptor.

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma.

The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

Enhancing simultaneous nitrogen and phosphorus availability through biochar addition during Chinese medicinal herbal residues composting: Synergism of microbes and humus.

The disposal of Chinese medicinal herbal residues (CMHRs) derived from Chinese medicine extraction poses a significant environmental challenge. Aerobic composting presents a sustainable treatment method, yet optimizing nutrient conversion remains a critical concern. This study investigated the effect and mechanism of biochar addition on nitrogen and phosphorus transformation to enhance the efficacy and quality of compost products. The findings reveal that incorporating biochar considerably enhanced the process of nutrient conversion. Specifically, biochar addition promoted the retention of bioavailable organic nitrogen and reduced nitrogen loss by 28.1 %. Meanwhile, adding biochar inhibited the conversion of available phosphorus to non-available phosphorus while enhancing its conversion to moderately available phosphorus, thereby preserving phosphorus availability post-composting. Furthermore, the inclusion of biochar altered microbial community structure and fostered organic matter retention and humus formation, ultimately affecting the modification of nitrogen and phosphorus forms. Structural equation modeling revealed that microbial community had a more pronounced impact on bioavailable organic nitrogen, while humic acid exerted a more significant effect on phosphorus availability. This research provides a viable approach and foundation for regulating the levels of nitrogen and phosphorus nutrients during composting, serving as a valuable reference for the development of sustainable utilization technologies pertaining to CMHRs.

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

Impulsive consensus algorithms for vector second-order Lipschitz nonlinear multi-agent systems using only velocity regulation.

The existing impulsive consensus algorithms for second-order Lipschitz nonlinear multi-agent systems require to apply the impulsive control to both position and velocity vectors at the same time. Such a requirement cannot be met in most of the real-world applications. To overcome the limitations of these impulsive algorithms, two kinds of new second-order impulsive consensus algorithms using only velocity regulation are proposed. Through developing a weighted discontinuous Lyapunov function-based approach that is able to leverage the spectral property of Laplacian matrix, impulse-dwell-time-dependent sufficient conditions for solving second-order impulsive consensus are derived in the form of linear matrix inequalities. Further, it is shown that if the impulsively controlled velocity subsystems are globally exponentially stable, the impulsive static consensus algorithm is able to ensure that all agents tend to an agreed position. Based on the consensus conditions, two convex optimization problems are formulated, by which the impulsive gain matrices for ensuring a prescribed exponential convergence rate can be designed. Finally, the effectiveness of the proposed distributed impulsive consensus algorithms is certified through numerical simulations.

How hetero-single-atom dispersion reconstructed electronic structure of carbon materials and regulated Fenton-like oxidation pathways.

Single-atom catalysts (SACs) have emerged as competitive candidates for Fenton-like oxidation of micro-pollutants in water. However, the impact of metal insertion on the intrinsic catalytic activity of carrier materials has been commonly overlooked, and the environmental risk due to metal leaching still requires attention. In contrast to previous reports, where metal sites were conventionally considered as catalytic centers, our study investigates, for the first time, the crucial catalytic role of the carbon carrier modulated through hetero-single-atom dispersion and the regulation of Fenton-like oxidation pathways. The inherent differences in electronic properties between Fe and Co can effectively trigger long-range electron rearrangement in the sp2-carbon-conjugated structure, creating more electron-rich regions for peroxymonosulfate (PMS) complexation and initiating the electron transfer process (ETP) for pollutant degradation, which imparts the synthesized catalyst (FeCo-NCB) with exceptional catalytic efficiency despite its relatively low metal content. Moreover, the FeCo-NCB/PMS system exhibits enduring decontamination efficiency in complex water matrices, satisfactory catalytic stability, and low metal leaching, signifying promising practical applications. More impressively, the spatial relationship between metal sites and electron density clouds is revealed to determine whether high-valent metal-oxo species (HVMO) are involved during the decomposition of surface complexes. Unlike single-type single-atom dispersion, where metal sites are situated within electron-rich regions, hetero-single-atom dispersion can cause the deviation of electron density clouds from the metal sites, thus hindering the in-situ oxidation of metal within the complexes and minimizing the contribution of HVMO. These findings provide new insights into the development of carbon-based SACs and advance the understanding of nonradical mechanisms underpinning Fenton-like treatments.

Ability of dynamic gadoxetic acid-enhanced magnetic resonance imaging combined with water-specific T1 mapping to reflect inflammation in a rat model of early-stage nonalcoholic steatohepatitis.

Background: Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) has shown potential in reflecting the hepatic function alterations in nonalcoholic steatohepatitis (NASH). The purpose of this study was to evaluate whether Gd-EOB-DTPA combined with water-specific T1 (wT1) mapping can be used to detect liver inflammation in the early-stage of NASH in rats. Methods: In this study, 54 rats with methionine- and choline-deficient (MCD) diet-induced NASH and 10 normal control rats were examined. A multiecho variable flip angle gradient echo (VFA-GRE) sequence was performed and repeated 40 times after the injection of Gd-EOB-DTPA. The wT1 of the liver and the reduction rate of wT1 (rrT1) were calculated. All rats were histologically evaluated and grouped according to the NASH Clinical Research Network scoring system. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of Gd-EOB-DTPA transport genes. Analysis of variance and least significant difference tests were used for multiple comparisons of quantitative results between all groups. Multiple regression analysis was applied to identify variables associated with precontrast wT1 (wT1pre), and receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance. Results: The rats were grouped according to inflammatory stage (G0 =4, G1 =15, G2 =12, G3 =23) and fibrosis stage (F0 =26, F1 =19, F2 =9). After the infusion of Gd-EOB-DTPA, the rrT1 showed significant differences between the control and NASH groups (P<0.05) but no difference between the different inflammation and fibrosis groups at any time points. The areas under curve (AUCs) of rrT1 at 10, 20, and 30 minutes were only 0.53, 0.58, and 0.61, respectively, for differentiating between low inflammation grade (G0 + G1) and high inflammation grade (G2 + G3). The MRI findings were verified by qRT-PCR examination, in which the Gd-EOB-DTPA transporter expressions showed no significant differences between any inflammation groups. Conclusions: The wT1 mapping quantitative method combined with Gd-EOB-DTPA was not capable of discerning the inflammation grade in a rat model of early-stage NASH.

Biomimetic Self-Maturation Mineralization System for Enamel Repair.

Enamel repair is crucial for restoring tooth function and halting dental caries. However, contemporary research often overlooks the retention of organic residues within the repair layer, which hinders the growth of dense crystals and compromises the properties of the repaired enamel. During the maturation of natural enamel, the organic matrix undergoes enzymatic processing to facilitate further crystal growth, resulting in a highly mineralized tissue. Inspired by this process, a biomimetic self-maturation mineralization system is developed, comprising ribonucleic acid-stabilized amorphous calcium phosphate (RNA-ACP) and ribonuclease (RNase). The RNA-ACP induces initial mineralization in the form of epitaxial crystal growth, while the RNase present in saliva automatically triggers a biomimetic self-maturation process. The mechanistic study further indicates that RNA degradation prompts conformational rearrangement of the RNA-ACP, effectively excluding the organic matter introduced earlier. This exclusion process promotes lateral crystal growth, resulting in the generation of denser enamel-like apatite crystals that are devoid of organic residues. This strategy of eliminating organic residues from enamel crystals enhances the mechanical and physiochemical properties of the repaired enamel. The present study introduces a conceptual biomimetic mineralization strategy for effective enamel repair in clinical practice and offers potential insights into the mechanisms of biomineral formation.

Automatic segmentation of the interscapular brown adipose tissue in rats based on deep learning using the dynamic magnetic resonance fat fraction images.

OBJECTIVE: The study aims to propose an accurate labelling method of interscapular BAT (iBAT) in rats using dynamic MR fat fraction (FF) images with noradrenaline (NE) stimulation and then develop an automatic iBAT segmentation method using a U-Net model. MATERIALS AND METHODS: Thirty-four rats fed different diets or housed at different temperatures underwent successive MR scans before and after NE injection. The iBAT were labelled automatically by identifying the regions with obvious FF change in response to the NE stimulation. Further, these FF images along with the recognized iBAT mask images were used to develop a deep learning network to accomplish the robust segmentation of iBAT in various rat models, even without NE stimulation. The trained model was then validated in rats fed with high-fat diet (HFD) in comparison with normal diet (ND). RESULT: A total of 6510 FF images were collected using a clinical 3.0 T MR scanner. The dice similarity coefficient (DSC) between the automatic and manual labelled results was 0.895 ± 0.022. For the network training, the DSC, precision rate, and recall rate were found to be 0.897 ± 0.061, 0.901 ± 0.068 and 0.899 ± 0.086, respectively. The volumes and FF values of iBAT in HFD rats were higher than ND rats, while the FF decrease was larger in ND rats after NE injection. CONCLUSION: An automatic iBAT segmentation method for rats was successfully developed using the dynamic labelled FF images of activated BAT and deep learning network.

Screening and identification of hub genes of scar physique via weighted gene co-expression network analysis.

Scar physique refers to the abnormal repair of skin injury in some people, which may easily lead to keloid or hypertrophic scar. However, the mechanism of scar physique is still unclear. GSE108110 was obtained from the gene expression omnibus database. Differently expression genes (DEGs) between normal skin tissue of non-scar physique individuals and normal skin tissue of scar physique individuals were screened by R package "limma". Weighted gene co-expression network analysis was performed to find highly relevant gene modules. Functional annotation of DEGs was made. Protein-protein interaction network was constructed, and the identification and analysis of hub DEGs were performed, including identification of hub DEGs associated with scar diseases, MiRNA of hub DEGs prediction, and functional annotation of miRNA. A total of 1389 up-regulate DEGs and 1672 down-regulate DEGs were screened. weighted gene co-expression network analysis analysis showed that the dendrogram and heatmap were used to quantify module similarity by correlation. The associations between clinic traits and the modules were identified based on the correlation between module and scar physique. Eight common hub genes were obtained. The comparative toxicogenomics database shows common hub genes associated with scar tissue. Gene ontology and Kyoto encyclopedia of genes and genomes analysis were significantly enriched in "fibroblast growth factor receptor signaling pathway", "epidermal growth factor receptor signaling pathway", "G1/S transition of mitotic cell cycle", protein polyubiquitination", and others. The 8 hub genes might be involved in the development of scarring and used as early diagnosis, prevention and treatment of scar physique.

Enhanced Oxidation of Organic Compounds by the Ferrihydrite-Ferrate System: The Role of Intramolecular Electron Transfer and Intermediate Iron Species.

Previous studies mostly held that the oxidation capacity of ferrate depends on the involvement of intermediate iron species (i.e., FeIV/FeV), however, the potential role of the metastable complex was disregarded in ferrate-based heterogeneous catalytic oxidation processes. Herein, we reported a complexation-mediated electron transfer mechanism in the ferrihydrite-ferrate system toward sulfamethoxazole (SMX) degradation. A synergy between intermediate FeIV/FeV oxidation and the intramolecular electron transfer step was proposed. Specifically, the conversion of phenyl methyl sulfoxide (PMSO) to methyl phenyl sulfone (PMSO2) suggested that FeIV/FeV was involved in the oxidation of SMX. Moreover, based on the in situ Raman test and chronopotentiometry analysis, the formation of the metastable complex of ferrihydrite/ferrate was found, which possesses higher oxidation potential than free ferrate and could achieve the preliminary oxidation of organics via the electron transfer step. In addition, the amino group of SMX could complex with ferrate, and the resulting metastable complex of ferrihydrite/ferrate would combine further with SMX molecules, leading to intramolecular electron transfer and SMX degradation. The ferrate loss experiments suggested that ferrihydrite could accelerate the decomposition of ferrate. Finally, the effects of pH value, anions, humic acid, and actual water on the degradation of SMX by ferrihydrite-ferrate were also revealed. Overall, ferrihydrite demonstrated high catalytic capacity, good reusability, and nontoxic performance for ferrate activation. The ferrihydrite-ferrate process may be a green and promising method for organic removal in wastewater treatment.

Genome-wide identification and analysis of the evolution and expression pattern of the SBP gene family in two Chimonanthus species.

BACKGROUND: Chimonanthus praecox and Chimonanthus salicifolius are closely related species that diverged approximately six million years ago. While both C. praecox and C. salicifolius could withstand brief periods of low temperatures of - 15 °C. Their flowering times are different, C. praecox blooms in early spring, whereas C. salicifolius blooms in autumn. The SBP-box (SQUAMOSA promoter-binding protein) is a plant-specific gene family that plays a crucial vital role in regulating plant flowering. Although extensively studied in various plants, the SBP gene family remains uncharacterized in Calycanthaceae. METHODS AND RESULTS: We conducted genome-wide identification of SBP genes in both C. praecox and C. salicifolius and comprehensively characterized the chromosomal localization, gene structure, conserved motifs, and domains of the identified SBP genes. In total, 15 and 18 SBP genes were identified in C. praecox and C. salicifolius, respectively. According to phylogenetic analysis, the SBP genes from Arabidopsis, C. praecox, and C. salicifolius were clustered into eight groups. Analysis of the gene structure and conserved protein motifs showed that SBP proteins of the same subfamily have similar motif structures. The expression patterns of SBP genes were analyzed using transcriptome data. The results revealed that more than half of the genes exhibited lower expression levels in leaves than in flowers, suggesting their potential involvement in the flower development process and may be linked to the winter and autumn flowering of C. praecox and C. salicifolius. CONCLUSION: Thirty-three SBPs were identified in C. praecox and C. salicifolius. The evolutionary characteristics and expression patterns were examined in this study. These results provide valuable information to elucidate the evolutionary relationships of the SBP family and help determine the functional characteristics of the SBP genes in subsequent studies.

Analysis of potential copy-number variations and genes associated with first-trimester missed abortion.

Background: Copy number variation sequencing (CNV-seq) was proven to be a highly effective tool in studying of chromosomal copy number variations (CNVs) in prenatal diagnosis and post-natal cases with developmental abnormalities. However, the overall characteristics of missed abortion (MA) CNVs were largely unexplored. Methods: We retrospectively analyzed the results of CNV-seq in first-trimester MA. The samples included were single pregnancy loss before 13 gestational weeks, and other potential factors affecting embryonic implantation and development had been excluded. Gene ontology and KEGG enrichment analysis was performed on the smallest overlapping regions (SORs) of high-frequency deletion/duplication. Result: On the basis of strict inclusion and exclusion criteria, only 152 samples were included in our study. 77 (50.7%) samples displayed chromosome number abnormalities, 32 (21%) showed isolated CNVs, and 43 (28.3%) showed no CNVs. A total of 45 CNVs, ranging in size between 300 Kb and 126.56 Mb were identified, comprising 13 segmental aneuploidies CNVs, and 32 submicroscopic CNVs. Among these CNVs, we screened out four SORs (5q31.3, 5p15.33-p15.2, 8p23.3-p23.2, and 8q22.2-24.3), which were potentially associated with first-term MA. 16 genes were identified as potential miscarriage candidate genes through gene-prioritization analysis, including three genes (MYOM2, SDHA and TPPP) critical for embryonic heart or brain development. Conclusion: We identified some potential candidate CNVs and genes associated with first-trimester MA. 5q31.3 duplications, 5p15.33-p15.2 deletions, 8p23.3-p23.2 deletions and 8p22.2-p24.3 duplications are four potential candidate CNVs. Additionally, MYOM2, SDHA and TPPP are potential genes associated with first-trimester MA.

LXA4 attenuates perioperative neurocognitive disorders by suppressing neuroinflammation and oxidative stress.

Perioperative neurocognitive disorder (PND) is a common complication that increases morbidity and mortality in elderly patients undergoing surgery. Abnormal microglia activation causes neuroinflammation and contributes to the development of PND. Growing evidence shows that lipoxin A4 (LXA4), a lipid mediator, possesses potent anti-inflammatory activities. In this study, we investigated whether LXA4 exerted a protective effect against surgery-induced neurocognitive deficits and explored the underlying mechanisms. Mice were subjected to laparotomy under sevoflurane anesthesia to establish an animal model of PND. LXA4 (15 µg/kg/d, ip) was administered three days prior surgery. We showed that LXA4 significantly alleviated surgery-induced cognitive impairments, attenuated neuroinflammation and microglial activation in hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of LXA4 (100 nΜ) significantly inhibited M1 polarization and promoted M2 polarization, and decreased the levels of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6) and increased the levels of anti-inflammatory cytokine (IL-10). LXA4 also mitigated LPS-regulated expression of HO-1, NOX2, and SOD1, elevated SOD activity, and attenuated ROS production. Furthermore, we revealed that LXA4 increased the expression of SIRT1 and decreased the protein level of acetylated NF-κB p65. SIRT1 inhibitor EX-527 abolished the anti-inflammatory and antioxidant response effects of LXA4 in BV2 microglial cells. Hence, LXA4 is a potential therapeutic agent for surgery-induced neuroinflammation, oxidative stress, and cognitive deficit, and the effect of LXA4 is probably mediated by the activation of the SIRT1/NF-κB signaling pathway in microglia.

Effect of Extracellular Ribonucleic Acids on Neurovascularization in Osteoarthritis.

Osteoarthritis is a degenerative disease characterized by abnormal neurovascularization at the osteochondral junctions, the regulatory mechanisms of which remain poorly understood. In the present study, a murine osteoarthritic model with augmented neurovascularization at the osteochondral junction is used to examine this under-evaluated facet of degenerative joint dysfunction. Increased extracellular RNA (exRNA) content is identified in neurovascularized osteoarthritic joints. It is found that the amount of exRNA is positively correlated with the extent of neurovascularization and the expression of vascular endothelial growth factor (VEGF). In vitro binding assay and molecular docking demonstrate that synthetic RNAs bind to VEGF via electrostatic interactions. The RNA-VEGF complex promotes the migration and function of endothelial progenitor cells and trigeminal ganglion cells. The use of VEGF and VEGFR2 inhibitors significantly inhibits the amplification of the RNA-VEGF complex. Disruption of the RNA-VEGF complex by RNase and polyethyleneimine reduces its in vitro activities, as well as prevents excessive neurovascularization and osteochondral deterioration in vivo. The results of the present study suggest that exRNAs may be potential targets for regulating nerve and blood vessel ingrowth under physiological and pathological joint conditions.

Alkaloids from Piper longum Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells.

Piper longum L. is widely cultivated for food, medicine, and other purposes in tropical and subtropical regions. Sixteen compounds including nine new amide alkaloids were isolated from the roots of P. longum. The structures of these compounds were determined by spectroscopic data. All compounds showed better anti-inflammatory activities (IC50 = 1.90 ± 0.68-40.22 ± 0.45 µM) compared to indomethacin (IC50 = 52.88 ± 3.56 µM). Among the isolated compounds, five dimeric amide alkaloids exhibited synergistic effects with three chemotherapeutic drugs (paclitaxel, adriamycin, or vincristine) against cervical cancer cells. Moreover, these dimeric amide alkaloids also enhanced the efficacy of paclitaxel in paclitaxel-resistant cervical cancer cells. The combination treatment of one of these dimeric amide alkaloids and paclitaxel promoted cancer cell apoptosis, which is related to the Src/ERK/STAT3 signaling pathway.

Terrace-Like 2D Hierarchically Porous Iron/Cobalt Metal-Organic Framework: Ambient Fast Synthesis and Efficient Oxygen Evolution Reaction Application.

It is urgent to design a low-cost electrocatalyst with high activity to enhance the efficiency of oxygen evolution reaction (OER), which is limited by the slow four-electron transfer kinetics process. Nevertheless, traditional synthetic methods, including calcination and solvothermal, of the electrocatalysts are high-cost, low-yield, and energy-hogging, which limits their industrial application. Herein, an ambient fast synthetic method is developed to prepare terrace-like Fe/Co bimetal-organic framework (TFC-MOF) electrocatalyst materials in gram scale in 1 h. The method in this paper is designable based on coordination chemistry. Fe and Co ions can coordinate with the carboxyl groups on benzene-1,3,5-tricarboxylic acid (H3 BTC) to form a 2D-MOF structure. Structural characterizations, including SEM, TEM, and XRD are conducted to verify that the TFC-MOF is a terrace-like layered structure with uniform-sized mesoporous, which reduces the adsorption steric hindrance and facilitates the mass and electron transfer efficiency of OER. The TFC-MOF shows low overpotential, 255 mV at a current density of 10 mA cm-2 , and a low Tafel slope of 49.9 mV dec-1 , in an alkaline solution. This work provides a planar coordination strategy to synthesize 2D-MOF OER electrocatalyst on a large scale with low cost and low energy consumption, which will promote its practical OER applications.