Discovery and Manipulation of van der Waals Polarons in Sb2O3 Ultrathin Molecular Crystal.

Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.

Smartphone-Based Free-to-Total Prostate Specific Antigen Ratio Detection System Using a Colorimetric Reaction Integrated with Proximity-Induced Bio-Barcode and CRISPR/Cas12a Assay.

The free-to-total prostate-specific antigen (f/t-PSA) ratio is of great significance in the accurate diagnosis of prostate cancer. Herein, a smartphone-based detection system is reported using a colorimetric reaction integrated with proximity-induced bio-barcode and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a assay for f/t-PSA ratio detection. DNA/antibody recognition probes are designed to bind f-PSA or t-PSA and induce the release of the DNA bio-barcode. The CRISPR/Cas12a system is activated by the DNA bio-barcode to release Ag+ from the C-Ag+-C structure of the hairpin DNA. The released Ag+ is used to affect the tetramethylbenzidine (TMB)-H2O2-based colorimetric reaction catalyzed by Pt nanoparticles (NPs), as the peroxidase-like activity of the Pt NPs can be efficiently inhibited by Ag+. A smartphone with a self-developed app is used as an image reader and analyzer to analyze the colorimetric reaction and provide the results. A limit of detection of 0.06 and 0.04 ng mL-1 is achieved for t-PSA and f-PSA, respectively. The smartphone-based method showed a linear response between 0.1 and 100 ng mL-1 of t-PSA or f-PSA. In tests with clinical samples, the smartphone-based method successfully diagnosed prostate cancer patients from benign prostatic hyperplasia patients and healthy cases with high sensitivity and specificity.

The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

Advances in metal-organic framework-based nanozymes in ROS scavenging medicine.

Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.

Policies and Practices Regarding Preparative Fasting for Contrast-Enhanced Computed Tomography: A Nationwide Survey.

OBJECTIVES: To evaluate current policies and practices regarding preparative fasting before contrast-enhanced computed tomography (CECT) and the knowledge and attitudes of radiology head nurses. METHODS: Radiology head nurses in 499 Chinese hospitals participated in an online survey on preparative fasting for CECT, which mainly included current departmental policies and practices and their knowledge and attitudes. RESULTS: Response rate was 89.8% (448/499). All surveyed hospitals established preparative fasting protocols, mainly based on guidelines for iodinated contrast media (ICM) usage (68.8%). For the nongastrointestinal CECT scan, the most frequent fasting duration for solid food, semiliquid diet, liquid diet, and clear liquids was 4 to 6 hours (215/422 [50.9%]), less than 6 hours (332/396 [83.8%]), less than 6 hours (275/320, 85.9%), and less than 6 hours (151/189 [79.9%]), respectively. Forty-six percent of the respondents confirmed that unnecessary excessive fasting existed in practice, and the related patient discomfort occurred in 60.3% of the hospitals, mainly manifested as hypoglycemia (86.7%). Expert consensus and guidelines for iodinated contrast media usage (75%) were the leading approach to gain knowledge about preparative fasting; 90.6% of the respondents believed that the clinical scenarios requiring preparative fasting were the upper abdominal examinations. A majority of respondents (72.1%) believed that the current preparative fasting policies needed improvement. CONCLUSION: Preparative fasting policies varied among hospitals in terms of the fasting content and duration. Respondents' opinions differed on fasting requirements based on various CECT examination sites and patients. The latest guideline regarding no fasting before CECT has not been fully adopted. Further research is required to promote the transformation of guideline evidence.

A Case Report of Neonatal Lupus Erythematosus with Liver Function Damage and Cytomegalovirus Colonization.

BACKGROUND: Neonatal lupus erythematosus (NLE) is an acquired autoimmune disease. NLE with liver function damage and cytomegalovirus colonization is rarely reported. METHODS: This case describes a newborn male's laboratory testing found sustained liver function damage when he came to see the doctor due to oral candidiasis. The cause was identified through clinical symptoms, laboratory tests, auxiliary examinations, and family history of the patient. RESULTS: The final diagnosis of the child was NLE with liver function damage and cytomegalovirus colonization according to comprehensive analysis and follow-up observation. CONCLUSIONS: NLE and cytomegalovirus colonization can both lead to liver function damage. When the organ function of newborns is abnormal, it is necessary to promptly investigate the cause and determine whether it is NLE.

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OBJECTIVES: To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS). METHODS: A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared. RESULTS: Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor (P<0.05). There was no significant difference in treatment protocols between the two groups (P>0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement (P<0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups (P>0.05). CONCLUSIONS: Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.

Bidirectional crosstalk of the cAMP/ROS-dependent signaling pathways in inflammatory macrophage: An activation of formononetin.

Bacterial lipopolysaccharide (LPS) is a toxic stimulant to macrophage inflammation. Inflammation intersects cell metabolism and often directs host immunopathogenesis stress. We aim here at pharmacological discovering of formononetin (FMN) action, to which anti-inflammatory signaling spans across immune membrane receptors and second messenger metabolites. In ANA-1 macrophage stimulated by LPS, and simultaneous treatment with FMN, results show the Toll-like receptor 4 (TLR4) and estrogen receptor (ER) signals, in concert with reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP), respectively. LPS stimulates inactivation of the ROS-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) by upregulating TLR4, but it does not affect cAMP. However, FMN treatment not only activates Nrf2 signaling by TLR4 inhibition, but also it activates cAMP-dependent protein kinase activities by upregulating ER. The cAMP activity gives rise to phosphorylation (p-) of protein kinase A, liver kinase B1 and 5'-AMP activated protein kinase (AMPK). Moreover, bidirectional signal crosstalk is amplified between p-AMPK and ROS, as FMN combinational validation with AMPK activator/inhibitor/target small-interfering RNA or ROS scavenger. The signal crosstalk is well positioned serving as the 'plug-in' knot for rather long signaling axis, and the immune-to-metabolic circuit via ER/TLR4 signal transduction. Collectively, convergence of the FMN-activated signals drives significant reduction of cyclooxygenase-2, interleukin-6 and NLR family pyrin domain-containing protein 3, in LPS-stimulated cell. Although anti-inflammatory signaling is specifically related to the immune-type macrophage, the p-AMPK antagonizing effect arises from FMN combination with ROS scavenger H-bond donors. Information of our work assists in predictive traits against macrophage inflammatory challenges, using phytoestrogen discoveries.

Smart Phototheranostics based on Carbon Nanohorns for Precise Imaging-Guided Post-PDT toward Residual Tumor Cells after Initial Phototherapy.

As promising photonic material, phototheranostics can be activated in the laser irradiation range of tumor with sensitivity and spatiotemporal precision. However, it is difficult to completely eradicate solid tumors due to their irregularity and limited laser irradiation area. Herein, multi-stimulus responsive HA-Ce6@SWNHs were constructed with single-walled carbon nanohorns (SWNHs) and chlorine e6 (Ce6) modified hyaluronic acid (HA) via non-covalent binding. This SWNHs-based phototheranostics not only exhibited water dispersion but also could target tumor and be activated by near-infrared light for photodynamic therapy (PDT) and photothermal therapy (PTT). Additionally, HA-Ce6@SWNHs could be degraded by hyaluronidase in residual tumor cells, causing HA-Ce6 to fall off the SWNHs surfaces to restore autofluorescence, thus precisely guiding the programmed photodynamic treatments for residual tumor cells after the initial phototherapy. Thus, this work provides a rationally designed multiple-stimulus-response strategy to develop smart SWNHs-based phototheranostics for precise PDT/PTT and post-treatment imaging-guided PDT of residual tumor cells.

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer's Disease from 2004 to 2022.

INTRODUCTION: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer's disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. METHODS: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. RESULTS: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer's Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. CONCLUSION: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

ABO blood groups and nosocomial infection.

The timely identification of the high-risk groups for nosocomial infections (NIs) plays a vital role in its prevention and control. Therefore, it is crucial to investigate whether the ABO blood group is a risk factor for NI. In this study, patients with NI and non-infection were matched by the propensity score matching method and a logistic regression model was used to analyse the matched datasets. The study found that patients with the B&AB blood group were susceptible to Escherichia coli (OR = 1.783, p = 0.039); the A blood group were susceptible to Staphylococcus aureus (OR = 2.539, p = 0.019) and Pseudomonas aeruginosa (OR = 5.724, p = 0.003); the A&AB blood group were susceptible to Pseudomonas aeruginosa (OR = 4.061, p = 0.008); the AB blood group were vulnerable to urinary tract infection (OR = 13.672, p = 0.019); the B blood group were susceptible to skin and soft tissue infection (OR = 2.418, p = 0.016); and the B&AB blood group were vulnerable to deep incision infection (OR = 4.243, p = 0.043). Summarily, the patient's blood group is vital for identifying high-risk groups for NIs and developing targeted prevention and control measures for NIs.

Complete Genome Sequence of Streptomyces sp. HP-A2021, a Promising Bacterium for Natural Product Discovery.

Streptomyces are one of the most prolific sources of bioactive and structurally diverse secondary metabolites for natural product drug discovery. Genome sequencing and bioinformatics analysis revealed that the genomes of Streptomyces harbor a wealth of cryptic secondary metabolite biosynthetic gene clusters that could encode novel compounds. In this work, a genome mining approach was employed to investigate the biosynthetic potential of Streptomyces sp. HP-A2021, isolated from rhizosphere soil of Ginkgo biloba L. The complete genome of HP-A2021 was sequenced and contained the 9,607,552 base pair linear chromosome with a GC content of 71.07%. The annotation results revealed the presence of 8534 CDSs, 76 tRNA genes, and 18 rRNA genes in HP-A2021. The highest dDDH and ANI values based on genome sequences between HP-A2021 and the most closely related type strain, Streptomyces coeruleorubidus JCM 4359, were 64.2% and 92.41%, respectively. In total, 33 secondary metabolite biosynthetic gene clusters with an average length of 105,594 bp were identified, including the putative thiotetroamide, alkylresorcinol, coelichelin, and geosmin. The antibacterial activity assay confirmed that the crude extracts of HP-A2021 showed potent antimicrobial activity against human pathogenic bacteria. Our study demonstrated that Streptomyces sp. HP-A2021 will propose a potential use in biotechnological and novel bioactive secondary metabolite biosynthetic applications.

Shared decision-making for renal replacement treatment and illness perception in patients with advanced chronic kidney disease.

BACKGROUND: Current healthcare trends emphasize the use of shared decision-making (SDM) for renal replacement treatment (RRT) in patients with chronic kidney disease (CKD). This is crucial to understand the relationship between SDM and illness perception of CKD patients. Few studies have focused on SDM and illness perception status of CKD patients and the impact of illness perception on RRT after SDM. METHODS: In this cross-sectional study, we used a questionnaire with purposive sampling from March 2019 to February 2020 at the nephrology outpatient department of a medical center in southern Taiwan. The nephrology medical team in this study used the SHARE five-step model of SDM to communicate with the patients about RRT and Brief Illness Perception Questionnaire (BIPQ) was applied to evaluate illness perception of these patients at the beginning of SDM. According to the SDM decision time, the study participants were classified general and delayed SDM groups. The distribution between SDM groups was estimated using independent two sample t-test, chi-squared test or Fisher's exact test. The correlation between illness perception and SDM decision time were illustrated and evaluated using Spearman's correlation test. A p-value less than 0.05 is statistically significant. RESULTS: A total of 75 patients were enrolled in this study. The average time to make a dialysis decision after initiating SDM was 166.2 ± 178.1 days. 51 patients were classified as general group, and 24 patients were classified as delayed group. The median SDM decision time of delayed group were significantly longer than general group (56 vs. 361 days, P < 0.001). Our findings revealed that delayed group was significantly characterized with not created early surgical assess (delayed vs. general: 66.7% vs. 27.5%, p = 0.001) compared to general group. The average BIPQ score was 54.0 ± 8.1 in our study. We classified the patients into high and low illness perception group according to the median score of BIPQ. The total score of BIPQ in overall participants might increase by the SDM decision time (rho = 0.83, p = 0.830) and the linear regression line also showed consistent trends between BIPQ and SDM decision time in correspond cohorts. However, no statistically significant findings were found. CONCLUSIONS: The patients with advanced chronic kidney disease took an average of five and a half months to make a RRT decision after undergoing SDM. Although there is no statistical significance, the trend of illness perception seems correlated with decision-making time. The stronger the illness perception, the longer the decision-making time. Furthermore, shorter decision times may be associated with earlier establishment of surgical access. We need more research exploring the relationship between illness perception and SDM for RRT in CKD patients.

Conventional IVF is feasible in preimplantation genetic testing for aneuploidy.

PURPOSE: To investigate the feasibility of the application of conventional in vitro fertilization (cIVF) for couples undergoing preimplantation genetic testing for aneuploidies (PGT-A) with non-male factor infertility. METHODS: To evaluate the efficiency of sperm whole-genome amplification (WGA), spermatozoa were subjected to three WGA protocols: Picoplex, ChromInst, and multiple displacement amplification (MDA). In the clinical studies, 641 couples who underwent PGT-A treatment for frozen embryos between January 2016 and December 2021 were included to retrospectively compare the chromosomal and clinical outcomes of cIVF and intracytoplasmic sperm injection (ICSI). Twenty-six couples were prospectively recruited for cIVF and PGT-A treatment between April 2021 and April 2022; parental contamination was analyzed in biopsied samples; and 12 aneuploid embryos were donated to validate the PGT-A results. RESULTS: Sperm DNA failed to amplify under Picoplex and ChromInst conditions but could be amplified using MDA. In frozen PGT-A cycles, no significant differences in the average rates of euploid, mosaic, and aneuploid embryos per cycle between the cIVF-PGT-A and ICSI-PGT-A groups were observed. The results of the prospective study that recruited couples for cIVF-PGT-A treatment showed no paternal contamination and one case of maternal contamination in 150 biopsied trophectoderm samples. Among the 12 donated embryos with whole-chromosome aneuploidy, 11 (91.7%) presented uniform chromosomal aberrations, which were in agreement with the original biopsy results. CONCLUSIONS: Under the Picoplex and ChromInst WGA protocols, the risk of parental contamination in the cIVF-PGT-A cycles was low. Therefore, applying cIVF to couples with non-male factor infertility who are undergoing PGT-A is feasible.

Ultrasensitive DNA Methylation Ratio Detection Based on the Target-Induced Nanoparticle-Coupling and Site-Specific Base Oxidation Damage for Colorectal Cancer.

DNA methylation analysis holds great promise in the whole process management of cancer early screening, diagnosis, and prognosis monitoring. Nevertheless, accurate detection of target methylated DNA, especially its methylation ratio in the genome, remains challenging. Herein, we report for the first time an integrated strategy of target-induced nanoparticle-coupling and site-specific base oxidation damage for DNA methylation analysis with the assistance of well-designed nanosensors. The ultrahigh sensitivity for detecting target methylated DNA as low as 32 × 10-17 M and high specificity for distinguishing 0.001% methylation ratio are achieved by this proposed strategy without amplification operations. Notably, the precise quantification of target DNA methylation ratio has been achieved for the first time. Through quantitative detection of target methylated DNA and methylation ratio, this proposed strategy could reliably diagnose and monitor cancer progression and treatment responses for colorectal cancer, which is superior to the clinical Septin 9 kit. It is anticipated that the proposed strategy has attractive application prospects in early diagnosis and monitoring for colorectal cancer and other various diseases.

Pseudomembranous necrotizing laryngotracheobronchitis due to Mycoplasma pneumoniae: a case report and literature review.

BACKGROUND: Pseudomembranous necrotizing laryngotracheobronchitis refers to an acute diffuse necrotizing inflammation in the mucosa of the larynx, trachea, and bronchus. It often occurs in infants and children having viral infections secondary to bacterial infections. Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen that causes pneumonia in children. In recent years, serious complications due to M. pneumoniae infection, including necrotizing pneumonia, pulmonary embolism, and pleural effusion, have been increasingly reported. CASE PRESENTATION: An 11-year-old girl was admitted to our unit with cough, fever, and hoarseness persistent for a week. The results of the M. pneumoniae serological test, PCR examination with bronchial aspirate and bronchoalveolar lavage fluid (BALF), next-generation sequencing (mNGS) for BALF, all suggested the presence of M. pneumoniae infection. High-resolution CT scanning of the chest showed inflammation of the middle and lower lobes of the right lung. By bronchoscopy, the necrosis of the vocal cords, trachea, and bronchial mucosa was observed; each bronchial lumen contained a large amount of white viscous sputum. Pathological findings for bronchial mucosa suggested inflammatory necrosis. After administration of azithromycin and glucocorticoids, the symptoms of the patients were ameliorated. After 2 weeks post-discharge, the X-ray scan of her chest indicated the pneumonia resolution in the right lung. CONCLUSIONS: In patients with pneumonia due to M. pneumoniae infection, which causes obvious hoarseness, bronchoscopy is necessary even if the lung lesions are not massively consolidated. When necrotizing lesions of the larynx, trachea, and bronchi are detected by bronchoscopy, the necrotic tissues in the corresponding parts should be conducted tissue biopsy for pathological examination. Apart from macrolide antibiotics, the administration of small doses of glucocorticoids is necessary.

Identification of NLRP3 as a covalent target of 1,6-O,O-diacetylbritannilactone against neuroinflammation by quantitative thiol reactivity profiling (QTRP).

Neuroinflammation plays a key etiological role in the progressive neuronal damage of neurodegenerative diseases. Our phenotypic-based screening discovered 1,6-O,O-diacetylbritannilactone (OABL, 1) from Inula britannica exhibited the potential anti-neuroinflammatory activity as well as a favorable blood-brain barrier penetration. 1 and its active derivative Br-OABL (2) with insert of Br at the C-14 position both modulated TLR4/NF-kB/MAPK pathways. However, proteome-wide identification of 1 binding proteins remains unclear. Here, we employed an adapted isoTOP-ABPP, quantitative thiol reactivity profiling (QTRP) approach, to identify and quantify thiol reactivity binding proteins in murine microglia BV-2 cells. We screened out 15 proteins co-targeted by 1 and 2, which are involved in cellular response to oxidative stress and negative regulation NF-κB transcription factor in biological processes. In site-specific profiling, NLRP3 was identified as a covalent target of 1 and 2 for the first time, and the Cys483 of NLRP3 NACHT domain was identified as one active-site of NLRP3 cysteine residues that can be covalently modified by the α-methylene-γ-lactone moiety. Furthermore, NLRP3 was validated to be directly binded by 1 and 2 by cellular thermo shift assay (CETSA) and activity-based protein profiling (ABPP), and NLRP3 functions were also verified by small interfering RNA approach. Notably, OABL treatment (i.p., 20 mg/kg/day) for 21 days reduced inflammation in 5XFAD mice brain. Together, we applied the QTRP to uncover the binding proteins of OABL in BV-2 cells, among which NLRP3 was revealed as a new covalent target of 1 and 2 against neuroinflammation.

Synthesis of metal ion-tolerant Mn-doped fluorescence silicon quantum dots with green emission and its application for selective imaging of ·OH in living cells.

Monitoring hydroxyl radical (·OH) in living cells remains a big challenge on account of its high reactivity and short half-life. In this work, we designed a fluorescent probe based on manganese-doped silicon quantum dots (Mn-SiQDs) for detecting and imaging of ·OH with good water solubility. The manganese was doped in its ethylene diamine tetra-acetic acid (EDTA) complex form and effectively improved the metal ion tolerance of fluorescence of SiQDs. And m-dihydroxybenzene was used as the reductant to extend the emission of SiQDs to the green region at 515 nm when the excitation wavelength was 424 nm. Basing on the fluorescence quenching of Mn-SiQDs, a linear response of ·OH was observed in the range 0.8-50 µM with a limit of detection (LOD) of 88.4 nM, which is lower than those reported with SiQDs. The interference from other ROS or RNS has been assessed and no impact was found. In fully aqueous systems, the Mn-SiQDs have been applied to monitor and image the endogenous ·OH in HeLa cells. Our work provided a new strategy for designing SiQDs with good biocompatibility, high selectivity and long monitoring wavelength. Synthesis of green-emitting silicon quantum dots with N-[3 -(trimethoxysilyl) propyl] ethylenediamine (DAMO), Ethylenediamine tetraacetic acid disodium salt dehydrate (EDTA-2Na·2H2O), manganese acetate tetrahydrate (Mn(CH3COO)2·4H20) and m-dihydroxybenzene. The green fluorescence of the silicon quantum dots can be selectively quenched by hydroxyl radicals.

The Preventive Effect of A Magnetic Nanoparticle-Modified Root Canal Sealer on Persistent Apical Periodontitis.

Persistent apical periodontitis is a critical challenge for endodontists. Developing root canal filling materials with continuous antibacterial effects and tightly sealed root canals are essential strategies to avoid the failure of root canal therapy and prevent persistent apical periodontitis. We modified the EndoREZ root canal sealer with the antibacterial material dimethylaminododecyl methacrylate (DMADDM) and magnetic nanoparticles (MNPs). The mechanical properties of the modified root canal sealer were tested. The biocompatibility of this sealer was verified in vitro and in vivo. Multispecies biofilms were constructed to assess the antibacterial effects of the modified root canal sealer. We applied magnetic fields and examined the extent of root canal sealer penetration in vitro and in vivo. The results showed that EndoREZ sealer containing 2.5% DMADDM and 1% MNP had biological safety and apical sealing ability. In addition, the modified sealer could increase the sealer penetration range and exert significant antibacterial effects on multispecies biofilms under an external magnetic field. According to the in vivo study, the apices of the root canals with the sealer containing 2.5% DMADDM and 1% MNP showed no significant resorption and exhibited only a slight increase in the periodontal ligament space, with a good inhibitory effect on persistent apical periodontitis.

An Insight into Antihyperlipidemic Effects of Polysaccharides from Natural Resources.

Hyperlipidemia is a chronic metabolic disease caused by the abnormal metabolism of lipoproteins in the human body. Its main hazard is to accelerate systemic atherosclerosis, which causes cerebrovascular diseases such as coronary heart disease and thrombosis. At the same time, although the current hypolipidemic drugs have a certain therapeutic effect, they have side effects such as liver damage and digestive tract discomfort. Many kinds of polysaccharides from natural resources possess therapeutic effects on hyperlipidemia but still lack a comprehensive understanding. In this paper, the research progress of natural polysaccharides on reducing blood lipids in recent years is reviewed. The pharmacological mechanisms and targets of natural polysaccharides are mainly introduced. The relationship between structure and hypolipidemic activity is also discussed in detail. This review will help to understand the value of polysaccharides in lowering blood lipids and provide guidance for the development and clinical application of new hypolipidemic drugs.