Infratemporal Fossa Schwannoma Surgery via a Combined Prelacrimal Recess, Caldwell-Luc, and Distal Intraoral Approach.

BACKGROUND: The deep location of infratemporal fossa (ITF) combined with the abundant vascular plexus in it increased the difficulty of removing the mass in ITF through endoscope surgery approach. However, under appropriate circumstances, the excision of ITF tumors through a combined prelacrimal recess, Caldwell-Luc, and distal intraoral approach can be safely performed with minimal impact on the surrounding tissues. CASE PRESENTATION: The Department of Neurology received a 69-year-old male patient who had been experiencing headache, dizziness, and numbness from the mastoid region of his left ear to the corner of his mouth for a duration of 22 days. Cranial magnetic resonance imaging revealed the presence of a tumor located in the ITF. Following transfer to our department, surgical intervention was performed using a combined approach involving the prelacrimal recess, the anterior wall of maxillary sinus, and lateral ITF to successfully remove the tumor. Postoperative pathologic examination confirmed schwannoma as its nature. The patient was discharged in excellent condition without any functional impairment. CONCLUSIONS: On the basis of this case, the authors believe that this combined approach can offer a distinct endoscopic perspective and adequate surgical workspace, which is crucial for tumor removal while preserving the integrity of surrounding normal tissues. Moreover, the utilization of multiple small incisions has minimal impact on postoperative recovery.

Analysis of Diagnosis and Treatment Strategies for Primary Juvenile Psammomatoid Ossifying Fibroma Complicated With Primary Aneurysmal Bone Cyst.

BACKGROUND: Juvenile Psammomatoid Ossifying Fibroma (JPOF) is a type of noncancerous bone tumor that usually affects adolescents in the craniomaxillofacial area. Clinical manifestations are usually symptoms caused by the tumor's invasive compression of surrounding tissues. Aneurysmal Bone Cyst (ABC) is also a benign bone tumor, and it typically occurs in long bones and the spine. Only 2% to 3% of cases occur in the head and neck. Due to the rarity of this combination of clinical cases, clinicians face difficulties in comprehensively understanding this complex lesion. Therefore, a comprehensive review of the clinical manifestations and characteristic imaging findings is necessary for surgeons. CASE PRESENTATIONS: On April 6, 2019, a 13-year-old boy presented with left maxillofacial bulge and pain for 1 month. Magnetic resonance imaging of the paranasal sinuses showed an irregular hive-like mass signal in the left maxillary sinus, and cystic changes with fluid levels were seen in the lesion. After the initial diagnosis of JPOF with primary ABC, we decided to perform a facial mid-facial resection of maxillary sinus tumor to remove the tumor tissue. Finally, after 3 recurrences and 4 operations, there was no tumor recurrence for 20 months after the last operation, and the patient was still under continuous follow-up. CONCLUSIONS: This case provided a reference for the diagnosis and treatment of JPOF combined with ABC. In particular, a new understanding of the association between the two diseases and the management of recurrence were proposed, which had the potential to improve clinical understanding of this complicated condition.

In Situ Polymerization of Antibacterial Modification Polyamide 66 with Au@Cu2O-ZnO Ternary Heterojunction.

In situ polymerization has proven to be an effective route through which to introduce function materials into polyamide materials. In this work, a nano-heterojunction material was evenly dispersed in PA66 via in situ polymerization methods to yield the antimicrobial PA66. The composites showed excellent antibacterial activity against Staphylococcus aureus and Escherichia coli, with strong mechanical properties. Fourier transform infrared spectroscopy (FTIR) showed that metal ions reacted with oxygen-containing functional groups. In addition, the shift of oxygen peaks in XPS spectra confirmed the occurrence of a complexation reaction. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) confirmed the effect of nano-heterojunction, which induced crystallization. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed uniform dispersion of heterojunctions in PA66. Tensile testing revealed decreased toughness with higher loadings. The nanocomposite polyamide material has good processing properties which can be processed into thin films, molds, and wires without changing the morphology, and can be widely used in a variety of fields.

Bacteroides methylmalonyl-CoA mutase produces propionate that promotes intestinal goblet cell differentiation and homeostasis.

Propionate is a short-chain fatty acid that is generated upon microbiome-mediated fiber fermentation in the intestine. By modulating immune and metabolic pathways, propionate exerts many health benefits. Key bacterial species, such as Bacteroides thetaiotaomicron, generate propionate, but the biochemical pathways and specific functions remain undetermined. We identified a gene operon-encoding methylmalonyl-CoA mutase (MCM) that contributes to propionate biosynthesis in B. thetaiotaomicron. Colonization of germ-free mice with wild-type or MCM-deficient strains as well as in vitro examination demonstrated that MCM-mediated propionate production promotes goblet cell differentiation and mucus-related gene expression. Intestinal organoids lacking the propionate receptor, GPR41, showed reduced goblet cell differentiation upon MCM-mediated propionate production. Furthermore, although wild-type B. thetaiotaomicron alleviated DSS-induced intestinal inflammation, this effect was abolished in mice receiving the MCM-deficient strain but restored upon propionate supplementation. These data emphasize the critical role of MCM-mediated propionate biosynthesis in goblet cell differentiation, offering potential pathways to ameliorate colitis.

Strictosamide ameliorates LPS-induced acute lung injury by targeting ERK2 and mediating NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects. AIM OF THE STUDY: This study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Biotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments. RESULTS: Biotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF-κB) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF-κB signaling pathway in LPS-induced ALI. CONCLUSIONS: Our findings indicate that STR can inhibit the NF-κB signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI.

Bioinformatics-led discovery of liver-specific genes and macrophage infiltration in acute liver injury.

Background: Acute liver injury (ALI) is an important global health concern, primarily caused by widespread hepatocyte cell death, coupled with a complex immune response and a lack of effective remedies. This study explores the underlying mechanisms, immune infiltration patterns, and potential targets for intervention and treatment ALI. Methods: The datasets of acetaminophen (APAP), carbon tetrachloride (CCl4), and lipopolysaccharide (LPS)-induced ALI were obtained from the GEO database. Differentially expressed genes (DEGs) were individually identified using the limma packages. Functional enrichment analysis was performed using KEGG, GO, and GSEA methods. The overlapping genes were extracted from the three datasets, and hub genes were identified using MCODE and CytoHubba algorithms. Additionally, PPI networks were constructed based on the String database. Immune cell infiltration analysis was conducted using ImmuCellAI, and the correlation between hub genes and immune cells was determined using the Spearman method. The relationship between hub genes, immune cells, and biochemical indicators of liver function (ALT, AST) was validated using APAP and triptolide (TP) -induced ALI mouse models. Results: Functional enrichment analysis indicated that all three ALI models were enriched in pathways linked to fatty acid metabolism, drug metabolism, inflammatory response, and immune regulation. Immune analysis revealed a significant rise in macrophage infiltration. A total of 79 overlapping genes were obtained, and 10 hub genes were identified that were consistent with the results of the biological information analysis after screening and validation. Among them, Clec4n, Ms4a6d, and Lilrb4 exhibited strong associations with macrophage infiltration and ALI.

Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.

The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ileal cells in response to stimulators in vitro, but dramatically changed the postprandial dynamics of endogenous bile acids, particularly ω-muricholic acid (ωMCA) and hyocholic acid (HCA). The bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) but not farnesoid X receptor (FXR), participated in the regulation of postprandial GLP-1 response in the circulation and ileum, and ωMCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or ωMCA and HCA supplementation restored postprandial GLP-1 response. In conclusion, gut microbiota is indispensable for maintaining the postprandial GLP-1 response specifically in the ileum, and bile acid (ωMCA and HCA)-TGR5 signaling is involved in this process. This study helps to understand the essential interplay between the gut microbiota and host in regulating postprandial GLP-1 response and opens the foundation for new therapeutic targets.

Fecal short chain fatty acids modify therapeutic effects of sleeve gastrectomy.

Aims: We aimed to investigate changes of fecal short chain fatty acids (SCFAs) and their association with metabolic benefits after sleeve gastrectomy (SG). Specifically, whether pre-surgery SCFAs modify surgical therapeutic effects was determined. Methods: 62 participants with measurements of fecal SCFAs and metabolic indices before and 1, 3, 6 months after SG were included. Changes of fecal SCFAs and their association with post-surgery metabolic benefits were calculated. Then, participants were stratified by medians of pre-surgery fecal SCFAs and modification effects of pre-surgery fecal SCFAs on surgical therapeutic effects were investigated, through calculating interaction of group by surgery. Results: Fecal SCFAs were markedly changed by SG. Changes of propionate and acetate were positively correlated with serum triglycerides and total cholesterol, respectively. Notably, high pre-surgery fecal hexanoate group showed a better effect of SG treatment on lowering body weight (P=0.01), BMI (P=0.041) and serum triglycerides (P=0.031), and low pre-surgery fecal butyrate had a better effect of SG on lowering ALT (P=0.003) and AST (P=0.019). Conclusion: Fecal SCFAs were changed and correlated with lipid profiles improvement after SG. Pre-surgery fecal hexanoate and butyrate were potential modifiers impacting metabolic benefits of SG.

EHD1 impaired decidualization of endometrial stromal cells in recurrent implantation failure: role of SENP1 in modulating progesterone receptor signalling.

Recurrent implantation failure (RIF) patients exhibit poor endometrial receptivity and abnormal decidualization with reduced effectiveness and exposure to progesterone, which is an intractable clinical problem. However, the associated molecular mechanisms remain elusive. We found that EH homeodomain 1 (EHD1) expression was abnormally elevated in RIF and linked to aberrant endometrial decidualization. Here we show that EHD1 overexpressed in human endometrial stromal cells (HESCs) significantly inhibited progesterone receptor (PGR) transcriptional activity and the responsiveness to progesterone. No significant changes were observed in PGR mRNA levels, while a significant decrease in PRB protein level. Indeed, EHD1 binds to the PRB protein, with the K388 site crucial for this interaction. Overexpression of EHD1 promotes the SUMOylation and ubiquitination of PRB, leading to the degradation of the PRB protein. Supplementation with the de-SUMOylated protease SENP1 ameliorated EHD1-repressed PRB transcriptional activity. To establish a functional link between EHD1 and the PGR signalling pathway, sg-EHD1 were utilized to suppress EHD1 expression in HESCs from RIF patients. A significant increase in the expression of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) was detected by interfering with the EHD1. In conclusion, we demonstrated that abnormally high expression of EHD1 in endometrial stromal cells attenuated the activity of PRB associated with progesterone resistance in a subset of women with RIF.

Insights into DNMT1 and programmed cell death in diseases.

DNMT1 (DNA methyltransferase 1) is the predominant member of the DNMT family and the most abundant DNMT in various cell types. It functions as a maintenance DNMT and is involved in various diseases, including cancer and nervous system diseases. Programmed cell death (PCD) is a fundamental mechanism that regulates cell proliferation and maintains the development and homeostasis of multicellular organisms. DNMT1 plays a regulatory role in various types of PCD, including apoptosis, autophagy, necroptosis, ferroptosis, and others. DNMT1 is closely associated with the development of various diseases by regulating key genes and pathways involved in PCD, including caspase 3/7 activities in apoptosis, Beclin 1, LC3, and some autophagy-related proteins in autophagy, glutathione peroxidase 4 (GPX4) and nuclear receptor coactivator 4 (NCOA4) in ferroptosis, and receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like protein (RIPK1-RIPK3-MLKL) in necroptosis. Our study summarizes the regulatory relationship between DNMT1 and different types of PCD in various diseases and discusses the potential of DNMT1 as a common regulatory hub in multiple types of PCD, offering a perspective for therapeutic approaches in disease.

Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Neurodegenerative diseases (NDs) have posed significant challenges to public health, and it is crucial to understand their mechanisms in order to develop effective therapeutic strategies. Recent studies have highlighted the potential role of selenium in ND pathogenesis, as it plays a vital role in maintaining cellular homeostasis and preventing oxidative damage. However, a comprehensive analysis of the association between selenium and NDs is still lacking. METHOD: Five public databases, namely PubMed, Web of Science, EMBASE, Cochrane and Clinical Trials, were searched in our research. Random model effects were chosen, and Higgins inconsistency analyses (I2), Cochrane's Q test and Tau2 were calculated to evaluate the heterogeneity. RESULT: The association of selenium in ND patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) was studied. A statistically significant relationship was only found for AD patients (SMD = -0.41, 95% CI (-0.64, -0.17), p < 0.001), especially for erythrocytes. However, no significant relationship was observed in the analysis of the other four diseases. CONCLUSION: Generally, this meta-analysis indicated that AD patients are strongly associated with lower selenium concentrations compared with healthy people, which may provide a clinical reference in the future. However, more studies are urgently needed for further study and treatment of neurodegenerative diseases.

Maternal and embryonic signals cause functional differentiation of luminal epithelial cells and receptivity establishment.

Embryo implantation requires temporospatial maternal-embryonic dialog. Using single-cell RNA sequencing for the uterus from 2.5 to 4.5 days post-coitum (DPC) and bulk sequencing for the corresponding embryos of 3.5 and 4.0 DPC pregnant mice, we found that estrogen-responsive luminal epithelial cells (EECs) functionally differentiated into adhesive epithelial cells (AECs) and supporting epithelial cells (SECs), promoted by progesterone. Along with maternal signals, embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, respectively, enhancing the attachment of embryos to the endometrium and furthering embryo development. This differentiation process was largely conserved between humans and mice. Notably, the developmental defects of SOX9-positive human endometrial epithelial cells (similar to mouse EEC) were related to thin endometrium, whereas functional defects of SEC-similar unciliated epithelial cells were related to recurrent implantation failure (RIF). Our findings provide insights into endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is crucial for endometrial receptivity.

Inappropriate treatment response to DMARDs: A pathway to difficult-to-treat rheumatoid arthritis.

In recent years, difficult-to-treat rheumatoid arthritis (D2T RA) has attracted significant attention from rheumatologists due to its poor treatment response and the persistent symptoms or signs experienced by patients. The therapeutic demands of patients with D2T RA are not properly met due to unclear pathogenic causes and a lack of high-quality data for current treatment options, creating considerable management difficulties with this patient population. This review describes the clinical challenges associated with disease-modifying antirheumatic drugs (DMARDs) and explores contributing factors associated with inappropriate response to DMARDs that may lead to D2T RA and related immunological dysregulation. It is now understood that D2T RA is a highly heterogeneous pathological status that involves multiple factors. These factors include but are not limited to genetics, environment, immunogenicity, comorbidities, adverse drug reactions, inappropriate drug application, poor adherence, and socioeconomic status. Besides, these factors may manifest in the selection and utilization of specific DMARDs, either individually or in combination, thereby contributing to inadequate treatment response. Finding these variables may offer hints for enhancing DMARD therapy plans and bettering the condition of D2T RA patients.

Ethnobotany, phytochemistry and pharmacological properties of Fagopyri Dibotryis Rhizoma: A review.

Fagopyri Dibotryis Rhizoma (FDR) is an effective Chinese herbal medicine with a long history of use in China. FDR is effective in heat clearing and detoxifying, promotion of blood circulation, relieving carbuncles, dispelling wind, and removing dampness. Its seeds also have high nutritional value, are rich in protein, and contain a variety of mineral elements and vitamins. Therefore, FDR is considered a natural product with medical and economic benefits, and its chemical composition and pharmacological activity are of interest to scientists. The current review provides an overview of the available scientific information on FDR, particularly its botany, chemical constituents, and pharmacological activities. Various sources of valid and comprehensive relevant information were consulted, including the China National Knowledge Infrastructure, Web of Science, and PubMed. Among the keywords used were "Fagopyri Dibotryis Rhizoma", "botanical features", "chemical composition", and "pharmacological activity" in combination. Various ailments are treated with FDR, such as diabetes, tumor, sore throat, headache, indigestion, abdominal distension, dysentery, boils, carbuncles, and rheumatism. FDR is rich in organic acids, tannins, flavonoids, steroids, and triterpenoids. Experiments performed in vitro and in vivo showed that FDR extracts or fractions had a wide range of pharmacological activities, including antitumor, anti-inflammatory, immunomodulatory, antioxidant, antimicrobial, and antidiabetic. The current review provides an integrative perspective on the botany, phytochemistry and pharmacological activities of FDR. FDR may be used as a medicine and food. Based on its chemical composition and pharmacological effects, the main active ingredients of FDR are organic acids, tannins, and flavonoids, and it has obvious antitumor pharmacological activity against a variety of malignant tumors. Therefore, FDR is worthy of further study and application as a potential antitumor drug.

Intestinal Escherichia coli and related dysfunction as potential targets of Traditional Chinese Medicine for respiratory infectious diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has saved countless lives and maintained human health over its long history, especially in respiratory infectious diseases. The relationship between the intestinal flora and the respiratory system has been a popular research topic in recent years. According to the theory of the "gut-lung axis" in modern medicine and the idea that "the lung stands in an interior-exterior relationship with the large intestine" in TCM, gut microbiota dysbiosis is a contributing factor to respiratory infectious diseases, and there is potential means for manipulation of the gut microbiota in the treatment of lung diseases. Emerging studies have indicated intestinal Escherichia coli (E. coli) overgrowth in multiple respiratory infectious diseases, which could exacerbate respiratory infectious diseases by disrupting immune homeostasis, the gut barrier and metabolic balance. TCM is an effective microecological regulator, that can regulate the intestinal flora including E. coli, and restore the balance of the immune system, gut barrier, and metabolism. AIM OF THE REVIEW: This review discusses the changes and effects of intestinal E. coli in respiratory infection, as well as the role of TCM in the intestinal flora, E. coli and related immunity, the gut barrier and the metabolism, thereby suggesting the possibility of TCM therapy regulating intestinal E. coli and related immunity, the gut barrier and the metabolism to alleviate respiratory infectious diseases. We aimed to make a modest contribution to the research and development of new therapies for intestinal flora in respiratory infectious diseases and the full utilization of TCM resources. Relevant information about the therapeutic potential of TCM to regulate intestinal E. coli against diseases was collected from PubMed, China National Knowledge Infrastructure (CNKI), and so on. The Plants of the World Online (https://wcsp.science.kew.org) and the Plant List (www.theplantlist.org) databases were used to provide the scientific names and species of plants. RESULTS: Intestinal E. coli is a very important bacterium in respiratory infectious diseases that affects the respiratory system through immunity, the gut barrier and the metabolism. Many TCMs can inhibit the abundance of E. coli and regulate related immunity, the gut barrier and the metabolism to promote lung health. CONCLUSION: TCM targeting intestinal E. coli and related immune, gut barrier, and metabolic dysfunction could be a potential therapy to promote the treatment and prognosis of respiratory infectious diseases.

Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway.

PURPOSE: This study aims to identify the mechanism of Inhibin Subunit Beta B (INHBB), a member of the transforming growth factor-ß (TGF-ß) family involved in the regulation of human endometrial stromal cells (HESCs) decidualization in recurrent implantation failure (RIF). METHODS: RNA-seq was conducted to identify the differentially expressed genes in the endometria from control and RIF patients. RT-qPCR, WB, and immunohistochemistry were performed to analyse the expression levels of INHBB in endometrium and decidualised HESCs. RT-qPCR and immunofluorescence were used to detect changes in the decidual marker genes and cytoskeleton after knockdown INHBB. Then, RNA-seq was used to dig out the mechanism of INHBB regulating decidualization. The cAMP analogue (forskolin) and si-INHBB were used to investigate the involvement of INHBB in the cAMP signalling pathway. The correlation of INHBB and ADCY expression was analysed by Pearson's correlation analysis. RESULTS: Our results showed significantly reduced expression of INHBB in endometrial stromal cells of women with RIF. In addition, INHBB was increased in the endometrium of the secretory phase and significantly induced in in-vitro decidualization of HESCs. Notably, with RNA-seq and siRNA-mediated knockdown approaches, we demonstrated that the INHBB-ADCY1-mediated cAMP signalling pathway regulates the reduction of decidualization. We found a positive association between the expression of INHBB and ADCY1 in endometria with RIF (R2 = 0.3785, P = 0.0005). CONCLUSIONS: The decline of INHBB in HESCs suppressed ADCY1-induced cAMP production and cAMP-mediated signalling, which attenuated decidualization in RIF patients, indicating that INHBB is an essential component in the decidualization process.

Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice.

BACKGROUND: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial ß3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure. METHODS: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with LC-MS/MS were used to identify the phosphorylation site of Nur77 activated by Mst1. The phosphorylated Nur77 was detected by phos-tag SDS-PAGE assay and specific antibody against phospho-Nur77-Thr366. The effect of embryo-epithelium interaction was determined in the BeWo spheroid or mouse embryo adhesion assay, and delayed implantation mouse model. RNA-seq was used to explore the mechanism by which Nur77 derived peptide promotes endometrial receptivity. FINDINGS: Endometrial Mammalian sterile 20 (STE20)-like kinase 1 (Mst1) expression level was decreased in the women with RIF than that in the fertile control group, while Mst1 activation in the epithelial cells promoted trophoblast-uterine epithelium adhesion. The effect of Nur77 mediated trophoblast-uterine epithelium adhesion was facilitated by active Mst1. Mechanistically, mst1 promotes the transcription activity of Nur77 by phosphorylating Nur77 at threonine 366 (T366), and consequently increased downstream target ß3-integrin expression. Furthermore, a Nur77-derived peptide containing phosphorylated T366 markedly promoted mouse embryo attachment to Ishikawa cells ([4 (2-4)] vs [3 (2-4)]) and increased the embryo implantation rate (4 vs 1.4) in a delayed implantation mouse model by regulating integrin signalling. Finally, it is observed that the endometrial phospho-Nur77 (T366) level is decreased by 80% in the women with RIF. INTERPRETATION: In addition to uncovering a potential regulatory mechanism of Mst1/Nur77/ß3-integrin signal axis involved in the regulation of embryo-epithelium interaction, our finding provides a novel marker of endometrial receptivity and a potential therapeutic agent for embryo implantation failure. FUNDING: National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (82171653, 82271698, 82030040, 81971387 and 30900727), and National Institutes of Health grants (R01HL103869).

MTX-PEG-modified CG/DMMA polymeric micelles for targeted delivery of doxorubicin to induce synergistic autophagic death against triple-negative breast cancer.

The chemotherapy of triple-negative breast cancer based on doxorubicin (DOX) regimens suffers from great challenges on toxicity and autophagy raised off-target. In this study, a conjugate methotrexate-polyethylene glycol (shorten as MTX-PEG)-modified CG/DMMA polymeric micelles were prepared to endue DOX tumor selectivity and synergistic autophagic flux interference to reduce systematic toxicity and to improve anti-tumor capacity. The micelles could effectively promote the accumulation of autophagosomes in tumor cells and interfere with the degradation process of autophagic flux, collectively inducing autophagic death of tumor cells. In vivo and in vitro experiments showed that the micelles could exert improved anti-tumor effect and specificity, as well as reduced accumulation and damage of chemotherapeutic drugs in normal organs. The potential mechanism of synergistic autophagic death exerted by the synthesized micelles in MDA-MB-231 cells has been performed by autophagic flux-related pathway.

Synthesis and Characterization of a New Copolymer Consisting of Polyamide 1210 and Reactive Phosphorus-Nitrogen Flame-Retardant.

The thermal stability and reactivity of organophosphorus flame-retardants play a critical role in synthesizing copolymerized flame-retardant polyamides. Herein, this work successfully synthesizes a flame-retardant CEPPA-DDA salt (CDS) with both good thermal stability and high reactivity by reacting 2-carboxyethyl phenyl phosphonic acid (CEPPA) with 1,12-dodecanediamine (DDA). Flame-retardant polyamide 1210 (FRPA) is further prepared by copolymerizing the CDS, DDA, and sebacic acid (SEA). The test results show that the introduction of CDS can significantly improve the flame-retardant properties of FRPA. Specifically, the flame-retardant polyamide 1210 (FRPA-7) with 7 wt% CDS addition can reach V-0 grade according to UL-94 standard, accompanying limiting oxygen index value of 30.2% and tensile strength of 38.62 MPa. Compared with pure polyamide 1210, the peak heat release rate and total heat release rate of FRPA-7 reduce by 24.11% and 9.40%, respectively. This study provides a simple strategy to prepare flame-retardant polyamides with high flame retardancy and good mechanical properties, which are expected to show great potentials in future industrial applications.

Nauclea officinalis: A Chinese medicinal herb with phytochemical, biological, and pharmacological effects.

Nauclea officinalis (N. officinalis), a medicinal plant of the genus Nauclea in the family Rubiaceae, is used in the treatment of fever, pneumonia, pharyngolaryngitis, and enteritis in China. Extracts of N. officinalis include alkaloids, phenolic acids, pentacyclic triterpenoids, and flavonoids, which exert all kinds of pharmacological effects, for instance anti-inflammatory, anti-tumor, antibacterial, and antiviral and therefore show good effectiveness. To gain a comprehensive and deep understanding, the medicinal chemistry and chemical biology of N. officinalis are summarized in this review to provide a theoretical basis. The pharmacological effects were reviewed to provide evidence or insights into potential opportunities for further studies and medicinal exploitation of N. officinalis.