Clinical and pathological features of cerebrospinal meningitis caused by Pantoea agglomerans : a case report.

BACKGROUND: Pantoea agglomerans (P. agglomerans) is a gram-negative bacterium that is commonly isolated from plant surfaces, seeds, and the environment. As an opportunistic pathogen, it can cause blood, urinary and soft tissue infections in immunocompromised patients. In central nervous system, P. agglomerans infection has been report in children and immune-compromised patients, however, infection by such bacterium in nontraumatized immune competent adults has not been reported. Here, we report a case of P. agglomerans cerebrospinal meningitis accompanied by positive anti-myeloperoxidase (MPO) antibody in a 49-year-old female who has a history of black fungus planting. CASE PRESENTATION: The patient manifested with repeated fever, headache, generalized muscle pain, and neurological defects. Cerebrospinal fluid (CSF) tests revealed a moderately elevated number of polymorphonuclear leukocytes (50-193 × 106/L), low glucose levels (0.54-2.44 mmo1/L), and extremely high protein content (2.42-25.42 g/L). Blood tests showed positive anti-myeloperoxidase antibodies lasting for 1.5 year before turning negative. Spine MRI showed thickening and enhancement of the whole spinal meninges. CSF metagenomic next-generation sequencing (mNGS) revealed 75,189 specific DNA reads of P. agglomerans. The patient underwent spinal laminectomy due to meningeal adhesions. Pathological results revealed fibrous tissue proliferation, inflammatory infiltration with focal necrosis and calcification in the dura mater. The patient was successfully treated with sufficient antibiotics at 1-year follow-up. CONCLUSIONS: People should be alert to CNS infections caused by P. agglomerans which presented with relatively mild clinical symptoms at onset, especially for those who contucts relevant agricultural and forestry work. The CSF characterization of P. agglomerans meningitis is elevated multiple nuclei white blood cells, significantly reduced glucose content, and markedly increased protein level which may be related to the secondary spinal membrane adhesions.

Activatable molecular probes for fluorescence-guided surgery, endoscopy and tissue biopsy.

The real-time, dynamic optical visualization of lesions and margins ensures not only complete resection of the malignant tissues but also better preservation of the vital organs/tissues during surgical procedures. Most imaging probes with an "always-on" signal encounter high background noise due to their non-specific accumulation in normal tissues. By contrast, activatable molecular probes only "turn on" their signals upon reaction with the targeted biomolecules that are overexpressed in malignant cells, offering high target-to-background ratios with high specificity and sensitivity. This review summarizes the recent progress of activatable molecular probes in surgical imaging and diagnosis. The design principle and mechanism of activatable molecular probes are discussed, followed by specific emphasis on applications ranging from fluorescence-guided surgery to endoscopy and tissue biopsy. Finally, potential challenges and perspectives in the field of activatable molecular probe-enabled surgical imaging are discussed.

State-of-the-art self-luminescence: a win-win situation.

Self-luminescence, which eliminates the real-time external optical excitation, can effectively avoid background autofluorescence in photoluminescence, endowing with ultrahigh signal-to-noise ratio and sensitivity in bioassay. Furthermore, in situ generated and emitted photons have been applied to develop excitation-free diagnostics and therapeutic agents against deeply seated diseases. "Enhanced" self-luminescence, referring to the aggregation-induced emission (AIE)-integrated self-luminescence systems, is endowed with not only the above merits but also other superiorities including stronger luminous brightness and longer half-life compared with "traditional" self-luminescence platforms. As an emerging and booming hotspot, the "enhanced" self-luminescence facilitated by the win-win cooperation of the aggregation-induced emission and self-luminescent techniques has become a powerful tool for interdisciplinary research. This tutorial review summarizes the advancements of AIE-assisted self-luminescence including chemiluminescence and afterglow imaging, starting from the discussion on the design and working principles, luminescent mechanisms of self-luminescence fuels, versatile integrated approaches and advantages, and a broad range of representative examples in biosensors and oncotherapy. Finally, the current challenges and perspectives are discussed to further actuate the development of "enhanced" self-luminescence agents for biomedical diagnosis and treatment.

Left ventricular reverse remodeling after transcatheter aortic valve replacement for predominant aortic stenosis and mixed aortic valve disease.

BACKGROUND: Mixed aortic valve disease (MAVD) is a frequent concomitant valve disease with unique cardiac pathological changes compared to predominant aortic stenosis (PAS). The previous studies about the MAVD are contradictory. Therefore, a new perspective is needed to assess the value of TAVR for this cohort of patients. METHODS: From January 2018 to December 2021, 90 MAVD patients and 72 PAS patients who underwent TAVR in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The dynamic changes in left ventricular morphology and hemodynamics were compared by generalized estimating equations. Univariate or multivariate logistic regression analysis was used to screen for independent risk factors for the non-occurrence of left ventricular reverse remodeling (non-LVRR). RESULTS: After the matching procedure, 112 patients were included in the analysis (56 in each group). Baseline characteristics were similar between the two groups. LVRR occurred in both groups, but MAVD had greater left ventricular end-diastolic volume index and left ventricular mass index, a higher incidence of mitral regurgitation (MR), and a more pronounced transformation of ventricular geometry patterns. Post-operative MR (odd ratio [OR]: 10.05; 95% confidence interval [CI]: 2.08-48.57; p < .001) and coronary artery disease (OR: 2.82; 95% CI: 1.08-7.34; p = .034) were independent risk factors for non-LVRR. CONCLUSION: LVRR also occurs in patients with MAVD, post-operative MR and coronary artery disease were independent risk factors for non-LVRR.

[Discussion on discipline of herbalism].

Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional Chinese medicines, or medical books, or traditional pharmacology. Due to the differences in the concept of materia medica, scholars also have controversies about the concept of herbalism. Herbalism is usually understood as traditional Chinese pharmacology. After years of evolution, the term "herbalism" has now possessed the characteristics of an independent discipline, which can be defined as an applied basic discipline that comprehensively utilizes traditional and modern technological methods to study the formation, development, and changes of traditional pharmacology and reveal the basic theories and application laws of traditional medicine. At present, the research content of herbalism mainly includes three aspects: materia medica history, materia medica literature, and traditional pharmacology. This study explores the disciplinary concepts and main research content of herbalism based on a systematic review of the literature about the concepts of materia medica and herbalism, with the aim of attracting more attention to promote the establishment and development of the discipline of herbalism.

A Polymeric Extracellular Matrix Nanoremodeler for Activatable Cancer Photo-Immunotherapy.

Cancer immunotherapy has shown tremendous potential to train the intrinsic immune system against malignancy in the clinic. However, the extracellular matrix (ECM) in tumor microenvironment is a formidable barrier that not only restricts the penetration of therapeutic drugs but also prevents the infiltration of antitumor immune cells. We herein report a semiconducting polymer-based ECM nanoremodeler (SPNcb) to combine photodynamic antitumor activity with cancer-specific inhibition of collagen-crosslinking enzymes (lysyl oxidase (LOX) family) for activatable cancer photo-immunotherapy. SPNcb is self-assembled from an amphiphilic semiconducting polymer conjugated with a LOX inhibitor (ß-aminopropionitrile, BAPN) via a cancer biomarker (cathepsin B, CatB)-cleavable segment. BAPN can be exclusively activated to inhibit LOX activity in the presence of the tumor-overexpressed CatB, thus blocking collagen crosslinking and decreasing ECM stiffness. Such an ECM nanoremodeler synergizes immunogenic phototherapy and checkpoint blockade immunotherapy to improve the tumor infiltration of cytotoxic T cells, inhibiting tumor growth and metastasis.

Smart Nano-PROTACs Reprogram Tumor Microenvironment for Activatable Photo-metabolic Cancer Immunotherapy.

Protease inhibitors can modulate intratumoral metabolic processes to reprogram the immunosuppressive tumor microenvironment (TME), which however suffer from the limited efficacy and off-targeted side effects. We report smart nano-proteolysis targeting chimeras (nano-PROTACs) with phototherapeutic ablation and cancer-specific protein degradation to reprogram the TME for photo-metabolic cancer immunotherapy. This nano-PROTAC has a semiconducting polymer backbone linked with a cyclooxygenase 1/2 (COX-1/2)-targeting PROTAC peptide (CPP) via a cathepsin B (CatB)-cleavable segment. CPP can be activated by the tumor-overexpressed CatB to induce the degradation of COX-1/2 via the ubiquitin-proteasome system. The persistent degradation of COX-1/2 depletes their metabolite prostaglandin E2 which is responsible for activation of immune suppressor cells. Such a smart PROTAC strategy synergized with phototherapy specifically reprograms the immunosuppressive TME and reinvigorates antitumor immunity.

A Dual-Locked Activatable Phototheranostic Probe for Biomarker-Regulated Photodynamic and Photothermal Cancer Therapy.

Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal therapy (PTT), which suffer from poor therapeutic efficacy due to deficient cellular oxygen and complex tumor microenvironment. We herein report a dual-locked activatable phototheranostic probe that activates near-infrared fluorescence (NIRF) signals in tumor, triggers PDT in response to a tumor-periphery biomarker, and switches from PDT to PTT upon detecting a tumor-core-hypoxia biomarker. This PDT-PTT auto-regulated probe exhibits complete tumor ablation under the photoirradiation of a single laser source by producing cytotoxic singlet oxygen at the tumor periphery and generating hyperthermia at tumor-core where is too hypoxic for PDT. This dual-locked probe represents a promising molecular design approach toward precise cancer phototheranostics.

Renal-Clearable Molecular Probe for Near-Infrared Fluorescence Imaging and Urinalysis of SARS-CoV-2.

Despite the importance of rapid and accurate detection of SARS-CoV-2 in controlling the COVID-19 pandemic, current diagnostic methods are static and unable to distinguish between viable/nonviable virus or directly reflect viral replication activity. Real-time imaging of protease activity specific to SARS-CoV-2 can overcome these issues but remains lacking. Herein, we report a near-infrared fluorescence (NIRF) activatable molecular probe (SARS-CyCD) for detection of SARS-CoV-2 protease in living mice. The probe comprises a hemicyanine fluorophore caged with a protease peptide substrate and a cyclodextrin unit, which function as an NIRF signaling moiety and a renal-clearable enabler, respectively. The peptide substrate of SARS-CyCD can be specifically cleaved by SARS-CoV-2 main protease (Mpro), resulting in NIRF signal activation and liberation of the renal-clearable fluorescent fragment (CyCD). Such a design not only allows sensitive detection of Mpro in the lungs of living mice after intratracheal administration but also permits optical urinalysis of SARS-CoV-2 infection. Thus, this study presents an in vivo sensor that holds potential in preclinical high-throughput drug screening and clinical diagnostics for respiratory viral infections.

[Hotspots and trends of Ophiopogonis Radix based on CiteSpace knowledge map].

Ophiopogonis Radix is an important Yin-nourishing drug in traditional Chinese medicine(TCM), with the effects of nourishing Yin, promoting fluid production, clearing away heart-fire, and relieving restlessness. It is widely used in clinical practice due to its multiple chemical components and pharmacological effects. The technique "mapping knowledge domains" is an effective tool to quantitatively and objectively visualize the development frontiers and trends of certain disciplines. In this study, TCM research papers related to Ophiopogonis Radix were retrieved from Web of Science(WoS) and CNKI, and the research institutions, journals, and keywords involved were visualized and analyzed using the scientometric software CiteSpace. The co-occurrence network of related research on Ophiopogonis Radix was constructed, and the Ophiopogonis Radix-disease-target network was plotted using Cytoscape 3.8.2. The hot topics in Chinese and English papers were analyzed and the shortcomings in the research on Ophiopogonis Radix were summed up. Furthermore, the development trends were discussed. A total of 1 403 Chinese papers and 292 English papers were included in this study. The analysis of research institutions showed that Beijing University of Chinese Medicine and China Pharmaceutical University were the two research institutions with the largest numbers of papers published. The analysis of journals showed that Hebei Journal of Traditional Chinese Medicine and Journal of Asian Natural Products Research were the two journals with the highest numbers of papers concerning Ophiopogonis Radix. The keyword analysis showed that the research contents of Chinese papers focused on the analysis of medication regularity and clinical observation trials, while the English papers focused on component analysis and pharmacological investigation. Data mining and apoptosis-based pharmacological mechanism might be the research trends in the future.

Hemicyanine-Based Near-Infrared Activatable Probes for Imaging and Diagnosis of Diseases.

Molecular activatable probes with near-infrared (NIR) fluorescence play a critical role in in vivo imaging of biomarkers for drug screening and disease diagnosis. With structural diversity and high fluorescence quantum yields, hemicyanine dyes have emerged as a versatile scaffold for the construction of activatable optical probes. This Review presents a survey of hemicyanine-based NIR activatable probes (HNAPs) for in vivo imaging and early diagnosis of diseases. The molecular design principles of HNAPs towards activatable optical signaling against various biomarkers are discussed with a focus on their broad applications in the detection of diseases including inflammation, acute organ failure, skin diseases, intestinal diseases, and cancer. This progress not only proves the unique value of HNAPs in preclinical research but also highlights their high translational potential in clinical diagnosis.

Charge-Reversal Polymer Nano-modulators for Photodynamic Immunotherapy of Cancer.

Nanomedicine can regulate the balance between cytotoxic T lymphocytes (CTLs) and suppressive regulatory T lymphocytes (Tregs), which however has been rarely exploited for cancer immunotherapy. We report a charge-reversal polymer nano-modulator (SPDMC N) activated by tumor microenvironment (TME) for photodynamic immunotherapy of cancer. SPDMC N is constructed by conjugating an immunomodulator (demethylcantharidin, DMC) to the side chains of a photodynamic polymer via an acid-liable linker. The negative charge of SPDMC N ensures its high stability in blood circulation and ideal tumor accumulation; exposure to acidic TME reverses its surface charge to positive, enhancing tumor penetration and locally releasing DMC. Upon near-infrared photoirradiation, SPDMC N generates singlet oxygen to ablate tumors and promote maturation of dendritic cells. Released DMC inhibits protein phosphatase 2 (PP2A) activity and decreases Tregs differentiation. Such combinational action induces a sharp increase in CTL/Treg ratio in TME and effectively inhibits both primary and distant tumors in living mice.

Genome-based analysis of SFTSV causing severe encephalitis with brain lesions.

Encephalitis is an infrequent manifestation in the various spectrums caused by severe fever with thrombocytopenia syndrome virus (SFTSV) infection. There are few data about the possible pathogenic mechanisms of SFTSV-associated encephalitis. Here, two SFTSV-infected patients with onset of encephalitis were enrolled. The whole genome of two SFTSV strains isolated from cerebrospinal fluid (CSF) was deeply sequenced by next-generation sequencing (NGS) and phylogenetic analysis was conducted. The specific mutations of M fragment were P98L and T665S respectively. The three-dimensional structure of glycoprotein Gn which was encoded by M fragment, an important virulence factor of SFTSV, was constructed by SWISS-MODEL. There was no significant variation in glycoprotein Gn of the two isolates comparing to other strains without encephalitis. Phylogenetic trees based on the complete sequences of M segment showed the two strains were highly identical to other local strains without encephalitis. Our study demonstrates that the virulence factors of SFTSV with encephalitis are not different from those without encephalitis. SFTSV itself is a neurotropic virus.

Organic Photodynamic Nanoinhibitor for Synergistic Cancer Therapy.

Despite its great potential in cancer treatment, photodynamic therapy (PDT) often exacerbates hypoxia and subsequently compromises its therapeutic efficacy. To overcome this issue, an organic photodynamic nanoinhibitor (OPNi) has been synthesized that has the additional ability to counteract carbonic anhydrase IX (CA-IX), a molecular target in the hypoxia-mediated signalling cascade. OPNi is composed of a metabolizable semiconducting polymer as the photosensitizer and a CA-IX antagonist conjugated amphiphilic polymer as the matrix. This molecular structure allows OPNi not only to selectively bind CA-IX positive cancer cells to facilitate its tumor accumulation but also to regulate the CA-IX-related pathway. The integration of CA-IX inhibition into the targeted PDT process eventually has a synergistic effect, leading to superior antitumor efficacy over that of PDT alone, as well as the reduced probability of hypoxia-induced cancer metastasis. This study thus proposes a molecular strategy to devise simple yet amplified photosensitizers to conquer the pitfalls of traditional PDT.

Thyroid Function and Autoimmune Indications in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

OBJECTIVE: Previous studies have shown that functional abnormalities of the thyroid are associated with the pathogenesis of several neurological diseases. However, their relationship in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis remains to be defined. METHODS: Forty-three patients with anti-NMDAR encephalitis were examined for thyroid function and autoimmune indications, in comparison with 225 healthy controls (CTL). Patients were further classified into 2 subgroups based on their free tri-iodothyronine (fT3) levels. Moreover, fT3 levels were also investigated after at least three months of follow-up. The clinical characteristics of the patients and CTL were described in detail. RESULTS: Serum levels of fT3 and thyroid-stimulating hormone (TSH) were found to be relatively lower in patients with anti-NMDAR encephalitis than in CTL (both p < 0.001). Low T3 syndrome also occurred more frequently in anti- NMDAR encephalitis (25.6 vs. 0.4%, p < 0.001). However, no statistical differences were detected between patients and CTL in terms of the positive rate of thyroid antibodies and other types of thyroid dysfunction. Patients with low T3 levels tended to have a longer hospital stay (p = 0.006), a higher rate of abnormal brain magnetic resonance imaging (MRI) findings (p = 0.033), a higher frequency of consciousness declination (p = 0.029), and a higher modified Rankin scale (mRS) score during hospitalization. Low fT3 levels were also associated with abnormal MRI findings, a decline in consciousness, and the mRS score on admission. In addition, fT3 seemed to gradually return to normal levels upon improvement of the mRS score (r = -0.649, p = 0.002). CONCLUSIONS: Low T3 syndrome often copresents in anti-NMDAR encephalitis and indicates a longer hospitalization, abnormal MRI findings, consciousness declination, and a higher clinical severity. However, fT3 levels do not seem to influence the prognosis of anti-NMDAR encephalitis.

RAGE-Specific Inhibitor FPS-ZM1 Attenuates AGEs-Induced Neuroinflammation and Oxidative Stress in Rat Primary Microglia.

Advanced glycation end products (AGEs) enhance microglial activation and intensify the inflammatory response and oxidative stress in the brain. This process may occur due to direct cytotoxicity or interacting with AGEs receptors (RAGE), which are expressed on the surface of microglia. FPS-ZM1 is a high-affinity but nontoxic RAGE-specific inhibitor that has been recently shown to attenuate the Aß-induced inflammatory response by blocking the ligation of Aß to RAGE. In this study, we further investigated the effect of FPS-ZM1 on the AGEs/RAGE interaction and downstream elevation of neuroinflammation and oxidative stress in primary microglia cells. The results suggested that FPS-ZM1 significantly suppressed AGEs-induced RAGE overexpression, RAGE-dependent microglial activation, nuclear translocation of nuclear factor kappaB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO). Furthermore, FPS-ZM1 attenuated AGEs-stimulated NADPH oxidase (NOX) activation and reactive oxygen species (ROS) expression. Finally, FPS-ZM1 elevated the levels of transcription factors nuclear-factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1), as well as decreased antioxidant capacity and increased production of oxidative species. Our results suggest that FPS-ZM1 may be neuroprotective through attenuating microglial activation, oxidative stress and inflammation by blocking RAGE.

Ingestible Artificial Urinary Biomarker Probes for Urine Test of Gastrointestinal Cancer.

Although colorectal cancer diagnosed at an early stage shows high curability, methods simultaneously possessing point-of-care testing ability and high sensitivity are limited. Here, an orally deliverable biomarker-activatable probe (termed as HATS) for early detection of orthotopic tumors via remote urinalysis is presented. To enable its oral delivery to the colon, HATS is designed to have remarkable resistance to acidity and digestive enzymes in the stomach and small intestine and negligible intestinal absorption. Upon reaction with a cancer biomarker in the colon segment, HATS releases a small fragment of tetrazine that can transverse the intestinal barrier, enter blood circulation, and ultimately undergo renal clearance to urine. Subsequently, the urinary tetrazine fragment is detected by bioorthogonal reaction with trans-cyclooctene-caged resorufin (TCO-Reso) to afford a rapid and specific fluorescence enhancement of TCO-Reso. Such signal readout is correlated with the urinary tetrazine concentration and thus measures the level of cancer biomarkers in the colon. HATS-based optical urinalysis detects orthotopic colon tumors two weeks earlier than clinical serological tests and can be developed to a point-of-care paper test. Thereby, HATS-based urinalysis provides a non-invasive and sensitive approach to cancer screening at low-resource settings.

Comparable clinical advantages identification of three formulae on rheumatic disease using a modular-based network proximity approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue. AIM OF THIS STUDY: To develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae. MATERIALS AND METHODS: In this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments. RESULTS: 32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = -20.26); YXB was significantly associated with AS (Z = -4.532), MI (Z = -29.11), RhFv (Z = -6.945), OA (Z = -39.97), and GA (Z = -13.03); and WBFK was significantly associated with MI (Z = -205.5), SLE (Z = -37.65), RhFv (Z = -42.45), and GA (Z = -17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments. CONCLUSIONS: The modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment.

Neferine Attenuates HDM-Induced Allergic Inflammation by Inhibiting the Activation of Dendritic Cell.

House dust mite (HDM) acts as an environmental antigen that might cause chronic allergic diseases. Neferine (NEF) shows anti-inflammation therapeutic effects. This study is to explore the protection role of NEF against HDM-induced allergic inflammation. HDM-induced allergic asthmatic C57BL/6J mice models were established. Differential histological staining was used to analyze lung tissue pathological scores. Flow cytometry was used to analyze subtypes and biomarker expression of immune cells. RT-PCR and ELISA were used to test cytokines-related gene and/or protein expression levels. Western blot was performed to investigate the signaling pathway that mediates allergic inflammation from mice lung tissue and bone marrow-derived dendritic cells (BMDCs). H&E and PAS staining results indicate NEF significantly attenuated inflammatory index and the percentage of goblet cells in the lung tissue induced by HDM. The HDM-elevated TH2 and TH17 cells were significantly decreased by NEF; inflammatory cytokines Il-4, Il-13 and Il-17 were dramatically downregulated in the NEF plus HDM group compared with HDM alone. CD40+ and CD86+ DCs, eosinophils and mast cells, and ILC2 cells were decreased by NEF which was elevated under HDM stimulation. In vivo and ex vivo investigations indicated NEF can attenuate the activated NF-κB signaling induced by HDM is involved in allergic inflammatory immune response and regulates cytokines-related gene expression. HDM-activated DCs promoted differentiation of TH2 and TH17 cells but were attenuated by NEF. This study suggests NEF interrupts the overexpression of some cytokines released by DCs, TH2, and TH17 cells; NEF attenuates HDM-induced allergic inflammation via inhibiting NF-κB signaling of DCs.

Direct Visualization of CO Interaction on Oxygen Poisoned Co(0001).

The poisoning of catalysts has always been a vital issue in catalytic reactions. In this study, direct observation of the interaction of CO and oxygen-poisoned Co(0001) has been achieved with scanning tunneling microscopy (STM), temperature-programmed desorption (TPD), and density functional theory calculation. A two-stage adsorption process of CO on a well-prepared p(2×2)-O layer covered Co(0001) was directly visualized. With increasing annealing time at a certain temperature after the CO dosage, the ordered (2 × 2) pattern formed in the first stage can be recovered, suggesting the weak interaction of CO with the O-covered Co(0001) surface in the latter stage. Compared to the clean Co(0001) surface, on an oxygen-poisoned surface, no further reaction was observed, illustrating the poisoning of the catalyst. Moreover, TPD results are in good agreement with the STM observation; a desorption energy of 0.35 eV is evaluated with a simple but accurate scheme.