Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

BACKGROUND: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS: In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS: Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS: Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Rational Conversion of Imine Linkages to Amide Linkages in Covalent Organic Frameworks for Photocatalytic Oxidation with Enhanced Photostability.

Covalent organic frameworks (COFs) and their applications in photocatalysis have been extensively studied, but the instability of imine-linked COFs is an important factor limiting their performance. In this work, two imine-linked COFs were successfully converted to amide-linked COFs through post synthetic modification (PSM). The oxidized COFs presented lower binding energy to O2, exhibited higher photocatalytic activity for oxidation of thioethers and coupling of benzylamines with excellent stability. The present work can serve as a reliable reference for the development of novel highly active and stable COF-based photocatalysts.

Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

Preliminary study of 3D printing technology for extracorporeal positioning guide assisted ultrasound-guided microwave ablation of the liver.

BACKGROUND: We designed a 3D-printed extracorporeal positioning guide for assisting ultrasound-guided microwave ablation of the liver and observed its effectiveness. RESEARCH DESIGN AND METHODS: 13 patients with liver cancer were selected, and their CT data were obtained. The CT data is reconstructed in 3D by computer software Mimics to create a 3D model. The 3D-printed in vitro positioning guides were designed by 3-Matic and fabricated using 3D printing technology. Finally, it is applied to the clinic, and its effect is observed. RESULTS: The preliminary design of a 3D printed extracorporeal positioning guide was applied to the clinic, and the efficiency of assisted ultrasound positioning was 76.92% (10/13), with three patients requiring repositioning. The efficiency of the 3D printed extracorporeal positioning guide technique was 76.92%, a CT examination was performed one month after surgery, and three patients had residual lesions. CONCLUSIONS: 3D-printed extracorporeal positioning guides can assist ultrasound in localizing tumors during liver microwave ablation and reduce repeated punctures. It makes percutaneous microwave ablation of the liver more precise and safe. However, the current study sample is small, there are still apparent shortcomings, and long-term clinical studies are needed to prove its effectiveness.

Combination of covalent organic frameworks (COFs) and polyoxometalates (POMs): the preparation strategy and potential application of COF-POM hybrids.

Both covalent organic frameworks (COFs) and polyoxometalates (POMs) show excellent properties and application potential in many fields, thus receiving widespread attention. In recent years, COF-POM hybrid materials were prepared by combining COFs and POMs through physical or chemical methods. COF-POM hybrids have shown high performance in many fields, such as catalysis, sensing, energy storage, and biomedicine. In this review, we introduced the preparation strategy and application of COF-POM hybrids in detail. We believe that the combination of COFs and POMs will provide more abundant functions and broad application prospects.

Vitamin E supplementation in the treatment on nonalcoholic fatty liver disease (NAFLD): Evidence from an umbrella review of meta-analysis on randomized controlled trials.

OBJECTIVE: We conducted this umbrella review of meta-analysis on randomized controlled trials to clarify the effects of vitamin E administration on alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), degrees of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: PubMed, MEDLINE, SCOPUS, EMBASE, and Web of Science were searched to identify pertinent articles published up to June 2023. To calculate the overall effect size (ES) and confidence intervals (CI), random-effects model was used. RESULTS: Six meta-analyses were included in the umbrella review. By pooling ES based on the random-effects model, we found that vitamin E supplementation significantly decreased ALT (ES -6.47, 95% CI -11.73 to -1.22, P = 0.01), AST (ES -5.35, 95% CI -9.78 to -0.93, P = 0.01), degrees of fibrosis (ES -0.24, 95% CI -0.36 to -0.12, P < 0.001) and steatosis (ES -0.67, 95% CI -0.88 to -0.45, P < 0.001) in NAFLD patients, but had no effect on GGT. In the subgroup analyses, we detected that fibrosis scores notably decreased when vitamin E dosage was >600 IU/day (ES -0.25, 95% CI -0.41 to -0.10, P = 0.002) and when the treatment duration was ≥12 months (ES -0.24, 95% CI -0.37 to -0.12, P < 0.001). CONCLUSION: Vitamin E administration improves ALT, AST, fibrosis, and steatosis in NAFLD subjects. Fibrosis scores were significantly reduced when vitamin E dosage exceeded 600 IU/day or with a treatment duration of at least 12 months.

Recent advances in emerging application of functional materials in sample pretreatment methods for liquid chromatography-mass spectrometry analysis of plant growth regulators: A mini-review.

Plant growth regulators (PGRs) are a class of small molecular compounds, which can remarkably affect the physiological process of plants. The complex plant matrix along with a wide polarity range and unstable chemical properties of PGRs hinder their trace analysis. In order to obtain a reliable and accurate result, a sample pretreatment process must be carried out, including eliminating the interference of the matrix effect and pre-concentrating the analytes. In recent years, the research of functional materials in sample pretreatment has experienced rapid growth. This review comprehensively overviews recent development in functional materials covering one-dimensional materials, two-dimensional materials, and three-dimensional materials applied in the pretreatment of PGRs before liquid chromatography-mass spectrometry (LC-MS) analysis. Besides, the advantages and limitations of the above functionalized enrichment materials are discussed, and their future trends have been prospected. The work could be helpful to bring new insights for researchers engaged in functional materials in sample pretreatment of PGRs based on LC-MS.

Anti-hyperuricemia effect of hesperetin is mediated by inhibiting the activity of xanthine oxidase and promoting excretion of uric acid.

Hesperetin is a natural flavonoid with many biological activities. In view of hyperuricemia treatment, the effects of hesperetin in vivo and in vitro, and the underlying mechanisms, were explored. Hyperuricemia models induced by yeast extract (YE) or potassium oxonate (PO) in mice were created, as were models based on hypoxanthine and xanthine oxidase (XOD) in L-O2 cells and sodium urate in HEK293T cells. Serum level of uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) were reduced significantly after hesperetin treatment in vivo. Hesperetin provided hepatoprotective effects and inhibited xanthine oxidase activity markedly, altered the level of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and catalase (CAT), downregulated the XOD protein expression, toll-like receptor (TLR)4, nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, interleukin-18 (IL-18), upregulated forkhead box O3a (FOXO3a), manganese superoxide dismutase (MnSOD) in a uric acid-synthesis model in mice. Protein expression of organic anion transporter 1 (OAT1), OAT3, organic cationic transporter 1 (OCT1), and OCT2 was upregulated by hesperetin intervention in a uric acid excretion model in mice. Our results proposal that hesperetin exerts a uric acid-lowering effect through inhibiting xanthine oxidase activity and protein expression, intervening in the TLR4-NLRP3 inflammasome signaling pathway, and up-regulating expression of FOXO3a, MnSOD, OAT1, OAT3, OCT1, and OCT2 proteins. Thus, hesperetin could be a promising therapeutic agent against hyperuricemia.

Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), peculiarly nonalcoholic steatohepatitis (NASH), has become the main cause of liver transplantation and liver-related death. However, the US Food and Drug Administration has not approved a specific medication for treating NASH. Neferine (NEF), a natural bisbenzylisoquinoline alkaloid separated from the traditional Chinese medicine Nelumbinis plumula, has a variety of pharmacological properties, especially on metabolic diseases. Nevertheless, the anti-NASH effect and mechanisms of NEF remain unclear. PURPOSE: This study aimed to investigate the amelioration of NEF on NASH and the potential mechanisms. STUDY DESIGN: HepG2 cells, hepatic stellate cells (HSCs) and high-fat diet (HFD)+carbon tetrachloride (CCl4) induced C57BL/6 mice were used to observe the effect of NEF against NASH and investigate the engaged mechanism. METHODS: HSCs and HepG2 cells stimulated by oleic acid (OA) were treated with NEF. C57BL/6 mice were fed with HFD+CCl4 to induce NASH mouse model and treated with or without NEF (5 mg/kg or 10 mg/kg, once daily, i.p) for 4 weeks. RESULTS: NEF significantly attenuated the accumulation of lipid droplets, intracellular triglyceride (TG) levels and hepatocytes apoptosis in OA-exposed HepG2 cells. NEF not only enhanced the AMPK and ACC phosphorylation in OA-stimulated HepG2 cells, but also reduced inflammatory response and fibrosis in lipopolysaccharide (LPS)-stimulated HepG2 and in LX-2, respectively. In HFD+CCl4-induced NASH mice, pathological staining confirmed NEF treatment mitigated hepatic lipid deposition, inflammatory cell infiltration as well as hepatic fibrosis. Furthermore, the liver weight, serum and hepatic TG and total cholesterol (TC) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were decreased compared with the model group. HFD+CCl4 also induced the upregulation of specific proteins and genes associated to inflammation (ILs, TNF-α, NLRP3, ASC, CCL2 and CXCL10) and hepatic fibrosis (collagens, α-SMA, TGF-ß and TIPM1), which were also suppressed by NEF treatment. CONCLUSION: Our results demonstrated that NEF played a protective role in hepatic steatosis via the regulation of AMPK pathways, which may serve as an attractive candidate for a potential novel strategy on prevention and treatment of NASH.

The induction and suppression of type I and type III interferons by human group H rotavirus.

Group H Rotavirus (RVH) is associated with human diarrhea gastroenteritis. The interferon (IFN) response induced by RVH remains unclear. In this study, we first studied the characteristic feature of RVH and found J19 strain of RVH grew less efficiently compared with the G6P1 strain of RVA. Next, we found that infection with the J19 virus resulted in the secretion of IFN-λ1, but not IFN-ß, while both IFN-ß and IFN-λ1 could inhibit J19 replication significantly in Caco-2 cells. NSP1 played an important role in the suppression of type I and type III IFN response, and NSP5 protein significantly inhibited activation of IFN-λ1. J19 NSP1 suppressed the induction of IFN-ß obviously than G6P1 NSP1, while G6P1 NSP1 reduced IFN-λ1 induction to the greatest extent compared with G9P8, Wa, and J19 NSP1s. Our studies reveal the propagation feature of RVH and interferon induction and suppression by group H rotavirus.

Effect of oral Xiao-xian decoction combined with acupoint application therapy on pediatric adenoid hypertrophy: A randomized trial.

BACKGROUND: This study aimed to observe the clinical effects of Xiao-xian decoction combined with acupoint application therapy (AAT) for treating pediatric adenoid hypertrophy (AH). METHODS: We randomly divided 93 AH children into 3 groups: AAT alone; Xiao-xian decoction + AAT; control: Montelukast oral therapy. All participants were treated for a month. We used the traditional Chinese medicine syndrome score to evaluate the clinical efficacy and the obstructive sleep apnea-18 scale to evaluate the quality of life. RESULTS: The major symptoms (nasal congestion, open mouth breathing, snoring, and tongue image) and secondary symptoms of patients treated with Xiao-xian decoction + AAT significantly improved compared to before treatment. The pairwise comparison between groups showed that snoring, tongue, secondary symptoms, and total effective rate of the combined treatment group were better than the control and AAT alone. Additionally, the open-mouth breathing, quality of life, and recurrence rate did not differ after treatment. CONCLUSION: Oral Xiao-xian decoction combined with AAT significantly improved the symptoms and signs of nasal congestion, open-mouth breathing, snoring, tongue, and quality of life of AH children and may be used as a long-term treatment for AH.

Electrochemiluminescence detection of miRNA-21 based on dual signal amplification strategies: Duplex-specific nuclease -mediated target recycle and nicking endonuclease-driven 3D DNA nanomachine.

DNA nanomachines have shown potential application in the construction of various biosensors. Here, an electrochemiluminescence biosensor for the sensitive detection of miRNA-21 were reported based on three-dimensional (3D) DNA nanomachine and duplex-specific nuclease (DSN)-mediated target recycle amplification strategy. First, the bipedal DNA walkers were obtained by DSN-mediated digestion reaction initiated by target miRNA-21.3D DNA tracks were prepared by modifying Fe3O4 magnetic beads (MBs) with ferrocene-labeled DNA (Fc-DNA). The produced DNA walkers autonomously moved along 3D DNA tracks powered by nicking endonuclease. During the movement, ferrocene-labeled DNA was cleaved, resulting in large amounts of Fc-labeled DNA fragments away from the MBs surface. Finally, the liberated Fc-labeled DNA fragments were dropped on the C-g-C3N4 modified electrode surface, leading to the quenching of C-g-C3N4 electrochemiluminescence (ECL). Benefiting from the dual amplification strategy of 3D DNA nanomachine and DSN-mediated target recycling, the developed ECL biosensor exhibited an excellent performance for miRNA-21 detection with a wide linear range of 10 fM to 10 nM and a low detection limit of 1.0 fM. This work offers a new thought for the application of DNA walkers in the construction of various biosensors.

Sinomenine Hydrochloride Can Ameliorate Benign Prostatic Hyperplasia by Lowering the 5α-Reductase 2 Level and Regulating the Balance between the Proliferation and Apoptosis of Cells.

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.

Inhalation of 4% and 67% hydrogen ameliorates oxidative stress, inflammation, apoptosis, and necroptosis in a rat model of glycerol-induced acute kidney injury.

Acute kidney injury (AKI) is the major complication of rhabdomyolysis (RM) clinically, which is usually mimicked by glycerol injection in basic research. Oxidative stress, inflammatory response and apoptosis are recognized to play important roles in development of this disease. Recently, numerous studies have reported the therapeutic effects of molecular hydrogen (H2) on oxidative stress and inflammation-related diseases. Here, the effects of H2 against glycerol-induced AKI and the underlying mechanisms were explored in rats. Low (4%) and high (67%) concentrations of H2 were prepared using a self-made device to investigate the dose-response. After 72 hours of glycerol injection (8 mL/kg), we found that glycerol triggered oxidative stress, inflammatory reactions, and apoptotic events. These caused subsequent renal damage, evidenced by a significant reduction of antioxidases and up-regulation of the relevant damaged biomarkers. H2 inhalation reversed the above alterations and exerted renoprotective effects. Interestingly, for RM/AKI-related factors, no consistent dose-response benefits of H2 were observed. However, higher concentration of H2 inhalation improved histological and morphological changes better. This study suggests that H2 is a potential alternative therapy to prevent or minimize RM induced AKI possibly via its antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic properties.

[3 + 2] cycloaddition of nonstabilized azomethine ylides and 2-benzothiazolamines to access imidazolidine derivatives.

A simple and practical method for the construction of 1,3,5-trisubstituted imidazolidine derivatives via [3 + 2] cycloaddition reaction has been developed. This reaction could smoothly proceed between nonstabilized azomethine ylides generated in situ and 2-benzothiazolamines to deliver a wide scope of differently substituted imidazolidines in high yields (up to 98%). The structure of one example was confirmed by X-ray single-crystal structure analysis.

Supramolecular hybrids of chiral Waugh polyoxometalate with cyclodextrins.

The development of novel systems for chiral polyoxometalates (POMs) is an attractive research field because of their fascinating topological structures and well-defined functions. Herein, we have developed a new reaction route for the synthesis of two unprecedented chiral Waugh POM-based supramolecular architectures. Single-crystal X-ray diffraction reveals that the architectures exhibit a wavy three-dimensional framework and bamboo-rod-connected framework upon regulating the size of the cyclodextrin and the stacking pattern of the D3 symmetric Waugh {MnMo9}. Solution studies using NMR, circular dichroism and isothermal titration calorimetry corroborate nicely the very weak interactions between the components. The intricate chiral microenvironment originating from the hybrid frameworks may be responsible for the selective recognition of the Λ-{MnMo9} enantiomer. This study highlights the importance of the asymmetric configuration of the POM for designing CD/POM assemblies and understanding their chirality.

Retrospective validation of ultrasound characteristics at 19-24 weeks as predictive tools for selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies: a diagnostic study.

Background: Seeking an optimal time point for ultrasound examination is important for the diagnosis of late selective intrauterine growth restriction (sIUGR) at birth in monochorionic diamniotic (MCDA) twin pregnancies. We aimed to assess the role of ultrasound characteristics at 19-24 weeks as predictive tools for late sIUGR at birth in MCDA twin pregnancies. Methods: We retrospectively recruited 32 sIUGR and 56 normal patients with MCDA twin pregnancies. Ultrasound indexes of these included subjects at 19-24 weeks, including the middle cerebral artery peak systolic velocity (MCA-PSV), umbilical artery pulsatility index (UA-PI), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR) were assessed. Receiver operating characteristic (ROC) curves were used to ascertain the predictive value of ultrasound characteristics discrepancy for such complications, and the relationship between the ultrasound characteristics and sIUGR was assessed by a logistic regression analysis. Results: Differences were found in the MCA-PI, UA-PI, and CPR discordances between the normal MCDA and sIUGR subjects. CPR discordance was the most effective characteristic for predicting sIUGR [area under the ROC curve (AUC) =0.883; 95% CI: 0.795-0.948], followed by UA-PI discordance (AUC =0.772; 95% CI: 0.685-0.829), and MCA-PI discordance (AUC =0.746; 95% CI: 0.681-0.823), respectively. Additionally, the optimal cutoff value of CPR discordance was 21.65, and the corresponding sensitivity and specificity were 0.750 and 0.929, respectively. The correlation analysis revealed that gestational age (GA) at ultrasound scan but not at delivery was significantly correlated with the MCA-PSV (r=0.55, P<0.01), UA-PI (r=0.55, P<0.01), MCA-PI (r=0.49, P<0.01), and CPR (r=0.55, P<0.01) in sIUGR, while GA at both ultrasound scan and birth was significantly correlated with MCA-PSV (r=0.65, P<0.01), UA-PI (r=0.49, P<0.01), MCA-PI (r=0.48, P<0.01), and CPR (r=0.63, P<0.01) in normal MCDA. Conclusions: Increased MCA-PI, UA-PI, and CPR discordances were found in fetuses with sIUGR. CPR discordance could serve as a predictive index for sIUGR. An early ultrasound examination may be more accurate than biochemical modality for sIUGR prediction.

Synthesis of 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition of nitrile imines with ninhydrin-derived Morita-Baylis-Hillman carbonates.

An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived Morita-Baylis-Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.

FAEE exerts a protective effect against osteoporosis by regulating the MAPK signalling pathway.

CONTEXT: Ferulic acid ethyl ester (FAEE) is abundant in Ligusticum chuanxiong Hort. (Apiaceae) and grains, and possesses diverse biological activities; but the effects of FAEE on osteoporosis has not been reported. OBJECTIVE: This study investigated whether FAEE can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating mitogen-activated protein kinase (MAPK). MATERIALS AND METHODS: We stimulated RAW 264.7 cells with receptor activator of NF-κB ligand (RANKL) followed by FAEE. The roles of FAEE in osteoclast production and osteogenic resorption of mature osteoclasts were evaluated by tartrate resistant acid phosphatase (TRAP) staining, expression of osteoclast-specific genes, proteins and MAPK. Ovariectomized (OVX) female Sprague-Dawley rats were administered FAEE (20 mg/kg/day) for 12 weeks to explore its potential in vivo, and then histology was undertaken in combination with cytokines analyses. RESULTS: FAEE suppressed RANKL-induced osteoclast formation (96 ± 0.88 vs. 15 ± 1.68) by suppressing the expression of osteoclast-specific genes, proteins and MAPK signalling pathway related proteins (p-ERK/ERK, p-JNK/JNK and p-P38/P38) in vitro. In addition, OVX rats exposed to FAEE maintained their normal calcium (Ca) (2.72 ± 0.02 vs. 2.63 ± 0.03, p < 0.05) balance, increased oestradiol levels (498.3 ± 9.43 vs. 398.7 ± 22.06, p < 0.05), simultaneously reduced levels of bone mineral density (BMD) (0.159 ± 0.0016 vs. 0.153 ± 0.0025, p < 0.05) and bone mineral content (BMC) (0.8 ± 0.0158 vs. 0.68 ± 0.0291, p < 0.01). DISCUSSION AND CONCLUSIONS: These findings suggested that FAEE could be used to ameliorate osteoporosis by the MAPK signalling pathway, suggesting that FAEE could be a potential therapeutic candidate for osteoporosis.