TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Investigating the Effects and Mechanisms of Cyclomorusin on Osteoclasts in a High Glucose Environment.

Diabetes mellitus is an endocrine disease characterized by prolonged hyperglycemia. Prolonged high blood sugar levels interfere with the differentiation and maturation process of OBs and OCs, leading to the onset of osteoporosis. However, OCs differentiation and maturation is a complex regulatory process. In this study, we used a co-culture system of RAW264.7 and MC3T3-E1 cells under HG concentration to explore the effect of CYM on OCs in a HG environment. The effects of CYM on the formation and function of OCs were observed using TRAP-positive cell counts and bone resorption pits. Then, mRNA and protein expression levels of OCs-related genes were detected by real-time qPCR and western blotting. The results showed that CYM had an inhibitory effect on OCs differentiation and bone resorption, reduced mRNAs expression of OCs-associated genes, and downregulated RANKL/RANK/TRAF6 pathway that mediates OCs differentiation. CYM could be a promising natural compound against diabetic osteoporosis.

Spatial distribution, source identification, and transportation paths of plutonium in the Beibu Gulf, South China Sea.

To investigate the spatial distribution and source of plutonium isotopes in the Beibu Gulf, surface sediments were collected and analyzed using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). The activities of 239+240Pu in surface sediments ranged from 0.012 to 0.451 mBq/g (mean: 0.171 ± 0.138 mBq/g, n = 36), indicating a decreasing trend in a counterclockwise direction from the southern bay mouth. The counterclockwise decreasing trend in the south of the bay mouth is similar to the current in the Beibu Gulf. The 240Pu/239Pu atom ratios in surface sediments ranged from 0.156 to 0.283 (mean: 0.236 ± 0.031, n = 36), slightly higher than that of the global fallout value of 0.18. This suggests that the Pu in the Beibu Gulf was a combination of global fallout and Pacific Proving Ground (PPG). The average contribution of the plutonium (Pu) derived from the PPG in the sediment was estimated to be 52 % ± 24 %.

Engineering High-Spin State Cobalt Cations in Sulfide Spinel for Enhancing Water Oxidation.

The spin states of active sites have a significant impact on the adsorption/desorption ability of the reaction intermediates during the oxygen evolution reaction (OER). Sulfide spinel is not generally considered a highly efficient OER catalyst owing to the low spin state of Co3+ and the lack of unpaired electrons available for adsorption of reaction intermediates. Herein, it is proposed a novel Nd-evoked valence electronic adjustment strategy to engineer the spin state of Co ions. The unique f-p-d orbital electronic coupling effect stimulates the rearrangement of Co d orbital electrons and increases the eg electron filling to achieve high-spin state Co ions, which promotes charge transport by propagating a spin channel and generates a high number of active sites for intermediate adsorption. The optimized CuCo1.75 Nd0.25 S4 catalyst exhibits outstanding electrocatalytic properties with a low overpotential of 320 mV at 500 mA cm-2 and a 48 h stability at 300 mA cm-2 . In situ synchrotron radiation infrared spectra confirm the quick accumulation of key *OOH and *O intermediates. This work deepens the comprehensive understanding of the relationship between OER activity and spin configurations of Co ions and offers a new design strategy for spinel compound catalysts.

Multicomponent Synthesis of Imidazole-Linked Fully Conjugated 3D Covalent Organic Framework for Efficient Electrochemical Hydrogen Peroxide Production.

The semiconducting properties and applications of three dimensional (3D) covalent organic frameworks (COFs) are greatly hampered because of their long-ranged non-conjugated skeletons and relatively unstable linkages. Here, a robust imidazole-linked fully conjugated 3D covalent organic framework (BUCT-COF-7) is synthesized through the one-pot multicomponent Debus-Radziszewski reaction of the saddle-shaped aldehyde-substituted cyclooctatetrathiophene, pyrene-4,5,9,10-tetraone, and ammonium acetate. The semiconducting BUCT-COF-7, as a metal-free catalyst, shows excellent two electron oxygen reduction reaction (ORR) activity in alkaline medium with high hydrogen peroxide (H2 O2 ) selectivity of 83.4 %. When the BUCT-COF-7 as cathode catalyst is assembled into the electrolyzer, the devices showed high electrochemical production rate of H2 O2 up to 326.9 mmol g-1 h-1 . The accumulative amount of H2 O2 could totally degrade the dye methylene blue via Fenton reaction for wastewater treatment. This is the first report about intrinsic 3D COFs for efficient electrochemical synthesis of H2 O2 , revealing the promising applications of fully conjugated 3D COFs in the environment-related field.

Photo-Controlled Nano-Supramolecular Size and Reversible Luminescent Behaviors Based on Cucurbit[7]uril Cascaded Assembly.

Supramolecular luminescent material with switchable behavior and photo-induced aggregation with emission enhancement is a current research hot spot. Herein, a size-tunable nano-supramolecular assembly with reversible photoluminescent behavior was constructed by noncovalent polymerization of diarylethene-bridged bis(coumarin) derivative (DAE-CO), cucurbit[7]uril (CB[7]), and ß-cyclodextrin-grafted hyaluronic acid (HACD). Benefiting from the macrocyclic confinement effect, the guest molecule DAE-CO was included into the cavity of CB[7] to give enhanced fluorescence emission of the resulting DAE-CO⊂CB[7]2 with longer lifetime at 432 nm to 1.43 ns, thereby further enhancing fluorescence output and lifetime (1.46 ns) when further assembled with HACD, compared with the free DAE-CO (0.95 ns). In addition, DAE-CO, DAE-CO⊂CB[7]2, and DAE-CO⊂CB[7]2&HACD all possessed characteristics of aggregation-induced emission and reversible photo-switched structural interconversion, exhibiting an obvious photophysical activation phenomenon of self-aggregation into larger nanoparticles with increase in fluorescence emission intensity, lifetime, and size after irradiation, which could be increased step by step with the alternating irradiation of 254 nm (5 min) or >600 nm (30 s) repeated 7 times. These supramolecular assemblies were successfully used in the tumor cells' targeted imaging and anti-counterfeiting because of the capability of HACD for recognizing specific receptors overexpressed on the surface of tumor cells and the excellent photo-regulated switch ability of DAE-CO, providing an approach of constructing photo-induced emission-enhanced luminescent materials.

Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1.

BACKGROUND: With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It's becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown. PURPOSE: The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI. METHODS: Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF. RESULTS: In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-ß1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice. CONCLUSION: EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.

Wulfenioidins D-N, Structurally Diverse Diterpenoids with Anti-Zika Virus Activity Isolated from Orthosiphon wulfenioides.

Eleven diterpenoids, wulfenioidins D-N (1-11), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides. The structures and absolute configurations were characterized by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC50 values of 8.07 and 8.50 µM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 µM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.

Conformationally confined three-armed supramolecular folding for boosting near-infrared biological imaging.

Herein, a triphenylamine derivative (TP-3PY) possessing 4-(4-bromophenyl)pyridine (PY) as an electron-accepting group and tris[p-(4-pyridylvinyl)phenyl]amine (TPA) with large two-photon absorption cross-sections as an electron-donating group was obtained, and showed intense absorption in the visible light region (λmax = 509 nm) and weak near-infrared (NIR) fluorescence emission at 750 nm. After complexation with cucurbit[8]uril (CB[8]), TP-3PY showed bright NIR fluorescence emission at 727 nm and phosphorescence emission at 800 nm. When the supramolecular assembly (TP-3PY⊂CB[8]) further interacted with dodecyl-modified sulfonatocalix[4]arene (SC4AD), the fluorescence and phosphorescence emissions were further enhanced at 710 and 734 nm, respectively. However, only the fluorescence emission of TP-3PY was enhanced in the presence of cucurbit[7]uril (CB[7]) and SC4AD. More interestingly, the photoluminescence of TP-3PY⊂CB[8]@SC4AD and TP-3PY⊂CB[7]@SC4AD assemblies could be excited by both visible (510 nm) and NIR light (930 nm). Finally, these ternary supramolecular assemblies with bright NIR light emission were applied to lysosome imaging of tumor cells and real-time biological imaging of mice.

Bimetallic Zn/Co telluride spinel with enhanced metal-tellurium covalency for efficient water oxidation.

A telluride-spinel ZnCo2Te4/NF catalyst delivered an overpotential (η) of only 370 mV to achieve a current density of 100 mA cm-2 and displayed no significant degradation of performance during 50 h of operation. By virtue of in situ synchrotron infrared spectroscopic detection, an accumulation of key OOH* intermediates over the active site was observed, suggesting that the reaction followed the efficient adsorbate evolution mechanism (AEM) for water oxidation.

Synthesis of pendant fullerene dimers by an aminomethylation reaction of fulleropyrrolidines bearing ketone moieties.

An aminomethylation reaction of fulleropyrrolidines bearing ketone moieties in the presence of N-unsubstituted fulleropyrrolidines and paraformaldehyde with the aid of p-toluenesulfonic acid afforded a series of scarce pendant fullerene dimers. A simple change of reaction substrates from ketone to ketone-containing fulleropyrrolidines successfully realized the synthesis of a variety of novel pendant fullerene dimers, including those from methyl ketone-containing fulleropyrrolidines, which were considered to produce the known bridged fullerene dimers. It should be noted that pendant fullerene dimers are usually difficult to prepare by other methods and may have promising applications in perovskite solar cells. Density functional theory (DFT) has been employed to elucidate the regioselectivity of methyl ketone-containing fulleropyrrolidines to yield exclusively pendant fullerene dimers by investigating the Gibbs free energy profile of the reaction starting from methyl ketone-containing fulleropyrrolidines and iminium intermediates.

Highly Enhanced Chloride Adsorption Mediates Efficient Neutral CO2 Electroreduction over a Dual-Phase Copper Catalyst.

Electrocatalytic carbon dioxide reduction (CO2R) in neutral electrolytes can mitigate the energy and carbon losses caused by carbonate formation but often experiences unsatisfied multicarbon selectivity and reaction rates because of the kinetic limitation to the critical carbon monoxide (CO)-CO coupling step. Here, we describe that a dual-phase copper-based catalyst with abundant Cu(I) sites at the amorphous-nanocrystalline interfaces, which is electrochemically robust in reducing environments, can enhance chloride-specific adsorption and consequently mediate local *CO coverage for improved CO-CO coupling kinetics. Using this catalyst design strategy, we demonstrate efficient multicarbon production from CO2R in a neutral potassium chloride electrolyte (pH ∼6.6) with a high Faradaic efficiency of 81% and a partial current density of 322 milliamperes per square centimeter. This catalyst is stable after 45 h of operation at current densities relevant to commercial CO2 electrolysis (300 mA per square centimeter).

Concentrations, seasonal trends, sources, health risk and subchronic toxicity to the respiratory and immune system of PAHs in PM2.5 in Xi'an.

PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) have been proved to be hazardous to health. Previous studies have focused on the distribution and sources of PAHs, whereas there is little knowledge of the damage to organs. Here we sought to investigate the pollution level and seasonal variation characteristics of PAHs in PM2.5 in Xi'an and assess the health risk, to establish a PAHs exposure model, and investigate the toxicological effects of PAHs on the respiratory and immune functions. A sub-chronic exposure model of PAHs was established by inhalation. The pathological changes of lung tissues were observed with a light microscope. Inflammatory reactions in alveolar lavage fluid were determined using the corresponding kit. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with enzyme linked immunosorbent assay (ELISA) kit; the proliferation of lymphocytes in spleen was detected with methyl tetrazolium (MTT); DNA immune damage was determined with DNA gel electrophoresis. The results showed that (1) the total concentration of 16 PAHs ranged from 41.1 to 387 ng/m3, with a mean value of 170 ng/m3, and the concentration of PAHs in PM2.5 was higher in winter than in other seasons. (2) The sources of PAHs in the atmosphere of Xi'an urban area were mainly coal combustion, and the equivalent carcinogenic concentration of PAHs in PM2.5 was 3.9 ng/m3. (3) Foreign body granuloma formation and inflammatory cell damage were observed in the lungs of rats infected with toxin; the levels of reactive oxygen species (ROS) and mobile device assistant (MDA) increased while nitric oxide synthase (NOS) decreased with the increase of dose; the expression levels of IL-6 and IL-8 elevated with the increase of toxin dose, showing an obvious dose-effect relationship; the level of PAHs damage to cells showed a dose-effect relationship. Sub-chronic exposure to PAHs could cause sustained inflammatory injury to the organism. Measures should be taken to counter the problems of PAHs in PM2.5 in Xi'an and relevant health promotion strategies should be developed.

ABCG1 is Expressed in an LXR-Independent Manner in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus have a high cardiovascular risk due, in part, to abnormalities of high-density lipoprotein mediated cholesterol efflux. The ATP-binding cassette A1 and G1 play a pivotal role in the regulation of cholesterol efflux. However, the regulation of these transporters in type 2 diabetes mellitus remains obscure. OBJECTIVES: This study aimed to investigate the expression of ATP-binding cassette A1 and G1 and their regulation by Liver X receptors in monocyte-derived macrophages in type 2 diabetes mellitus, and to determine whether the alteration of these transporters might affect cholesterol efflux from macrophages. METHODS: Blood was collected from type 2 diabetic patients and healthy controls. Peripheral monocytes were differentiated into macrophages. Quantitative real-time PCR, western blots, and cholesterol efflux assays were performed. The Liver X receptor and Liver X receptor element complex in the ATP-binding cassette G1 gene promoter were detected by electrophoretic mobility supershift assay. RESULTS: Macrophage ATP-binding cassette G1 expression and high density lipoproteininduced cholesterol efflux were significantly reduced in type 2 diabetic patients. However, the mRNA expression of ATP-binding cassette G1 in type 2 diabetic patients was not inhibited by Liver X receptor siRNA and the Liver X receptor- Liver X receptor element complexes remain unchanged similarly. CONCLUSION: The study suggested that the expression of ATP-binding cassette G1 and high density lipoprotein-induced cholesterol efflux in macrophages were reduced in type 2 diabetes mellitus. Impairment of cholesterol efflux and ATP-binding cassette G1 gene expression in type 2 diabetes mellitus might be regulated by a Liver X receptorindependent pathway.

Vitamin A status and its hematological correlates among preschool children in Beijing, China.

BACKGROUND AND OBJECTIVES: Vitamin A is vital for the growth and health of children. This study aimed to estimate the current vitamin A status and the prevalence of vitamin A deficiency (VAD) among preschool children and explore the correlation between serum vitamin A concentration and changes in hematological parameters. METHODS AND STUDY DESIGN: The study included 697 children aged 1-6 years, presenting for routine checkups at the Department of Pediatrics, Peking University Shougang Hospital, Beijing, from April 2017 to December 2020. We obtained the complete laboratory test data of 630 children. RESULTS: The mean serum vitamin A concentration among preschool children was 0.29±0.08 mg/L, with a median of 0.29 mg/L. The proportion of children with VAD and marginal VAD (MVAD) was 9.84% and 43.49%, respectively. The highest prevalence of VAD and MVAD was in the 3- to 4-year age group. Compared with the normal vitamin A serum concentration group, other groups had lower mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and higher red blood cell distribution width. The mean serum vitamin A concentration among anemic children was significantly lower (0.27±0.07 mg/L) than among those children who were not anemic (p<0.05). CONCLUSIONS: VAD constitutes a public health problem in northern China. The prevalence of VAD is highest, and the serum vitamin A concentration was the lowest among preschool children aged 3-4 years. Vitamin A serum concentration was associated with red blood cell indices. We should attach more importance to those children aged 3-4 years.

Case report: A compound heterozygous mutations in ARSA associated with adult-onset metachromatic leukodystrophy.

Metachromatic Leukodystrophy (MLD) is a rare autosomal recessive disease, which is caused by mutations in the arylsulfatase A (ARSA) gene. The ARSA gene is located on chromosome 22q13, containing eight exons. According to the age of onset, MLD can be divided into late infantile type, juvenile type, and adult type. Adult MLD has an insidious onset after the age of 16 years. Additionally, intellectual as well as behavioral changes, such as memory deficits or emotional instability, are commonly the first presenting symptoms. There is a study that reported an adult-onset MLD manifested cognitive impairment progressively due to compound heterozygous mutations of NM_000487: c.[185_186dupCA], p.(Asp63GlnfsTer18), and NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271 in the ARSA gene, finding that the c.[154G>T], p.(Gly172Cys) is a novel missense mutation. Brain magnetic resonance imaging (MRI) revealed symmetrical demyelination of white matter. The activity of ARSA enzymatic in leukocytes decreased. Nerve conduction studies displayed that evidence of polyneuropathy was superimposed upon diffuse, uniform demyelinating, and sensorimotor polyneuropathy. Family genes revealed that each family member carried one of two heterozygous mutant genes. She has been discharged and is currently being followed up. This study found a compound heterozygous mutation in the ARSA gene associated with MLD and identified a novel missense mutation NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271. This will provide a critical clue for prenatal diagnosis of the offspring in this family, and expand the mutation spectrum of MLD-related ARSA.

Evaluation of the diagnostic value of serum-based proteomics for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly malignant cancer with a high incidence and mortality in China. It is urgent to find a diagnostic marker with higher sensitivity and specificity than the traditional approaches for CRC diagnosis. AIM: To provide new ideas for the diagnosis of CRC based on serum proteomics. METHODS: Specimens from 83 healthy people, 62 colon polyp (CRP) patients, and 101 CRC patients were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The diagnostic value of the profiles of differentially expressed proteins was then analyzed. RESULTS: Compared with the healthy control group, CRC patients had elevated expression of 5 proteins and reduced expression of 14 proteins. The area under the curve (AUC) for a differentially expressed protein with a mass-to-charge ratio of 2022.34 was the largest; the AUC was 0.843, which was higher than the AUC of 0.717 observed with carcinoembryonic antigen (CEA), and the sensitivity and specificity of this identified marker were 75.3% and 79.5%, respectively. After cross-validation, the accuracy of diagnosis using levels of this differentially expressed protein was 82.37%. Compared with the CRP group, the expression of 3 proteins in the serum of CRC patients was elevated and 11 proteins were expressed at reduced levels. Proteins possessing mass-to-charge ratio values of 2899.38 and 877.3 were selected to establish a classification tree model. The results showed that the accuracy of CRC diagnosis was 89.5%, the accuracy of CRP diagnosis was 81.6%, and the overall accuracy of this approach was 86.3%. The overall sensitivity and specificity of diagnosis using the proteomics approach were 81.8% and 66.75%, respectively. The sensitivities and specificities of diagnoses based on CEA and carbohydrate antigen 19-9 expression were 55.6% and 91.3% and 65.4% and 65.2%, respectively. CONCLUSION: We demonstrated that serum proteomics may be helpful for the detection of CRC, and it may assist clinical practice for CRC diagnosis.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Advances in chromone-based reactants in the ring opening and skeletal reconstruction reaction: access to skeletally diverse salicyloylbenzene/heterocycle derivatives.

Salicyloylbenzene/heterocycles are privileged scaffolds found in many natural products and bioactive molecules. Numerous useful approaches for the preparation of these privileged scaffolds have been developed in recent years. Among these approaches, chromone-based reactants have demonstrated their importance in the synthesis of these salicyloylbenzene/heterocycle scaffolds with structural complexity and potential biological appeal. In this review, the recent advances in the synthesis of salicyloylbenzene/heterocycles are summarized and discussed according to the chromone-based reactants which could be achieved in one step via ring-opening and skeletal reconstruction reactions. Both the mechanisms and the applications of the corresponding products in organic and medicinal chemistry are also described.

Hyperoside suppresses osteoclasts differentiation and function through downregulating TRAF6/p38 MAPK signaling pathway.

Hyperoside (HP), as a natural product, can promote proliferation and differentiation of osteoblasts and presents a protective effect on ovariectomized (OVX) mice. However, the inhibitory effect of HP on osteoclasts (OCs) and the potential mechanism remain to be elucidated. In this study, it was found that HP could effectively inhibit the differentiation and bone resorption of OCs, and its intrinsic molecular mechanism was related to the inhibition of TRAF6/p38 MAPK signaling pathway. Therefore, HP could be a promising natural compound for lytic bone diseases.