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Background: Central venous catheterization (CVC) is a critical clinical procedure. To avoid complications, possessing good knowledge regarding the CVC care bundle and skills for the proper insertion and maintenance of CVC are important. Objectives: To evaluate the effectiveness of an educational intervention and the use of an interactive response system in enhancing the CVC bundle care and insertion skills of medical students undergoing critical care medicine training. Materials and Methods: Sixth-year medical students (equivalent to fourth-year students in the United States) engaged in didactic lessons, interactive demonstrations, and simulator training facilitated by a CVC team comprising three thoracic and two vascular surgeons (all with a minimum 5 years of experience in central venous access) during their intensive care unit (ICU) rotation. Self-reported knowledge and confidence levels were assessed using pre-and posttests administered through the Zuvio App, an interactive response system. Results: A total of 60 students underwent the educational intervention, of which 54 completed the pretest and 40 completed the posttest. In the posttest, significant improvement was found in the CVC bundle care competency and understanding (P = 0.002), preprocedural preparation (P = 0.002), insertion procedures (P = 0.004), complications (P = 0.003), and insertion depth decisions (P = 0.001). Staff and students reported that assessment and interaction via the Zuvio App were valuable, practical, and feasible in a clinical setting, providing trainees with an individual competency portfolio of receiving precise medical education. Conclusions: Integrating the training provided by a specialized team with an interactive response system enhanced the knowledge and competency level in CVC insertion among medical students in this study.
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OBJECTIVES: To investigate prevalence, risk factors, and in-hospital outcomes of comatose extracorporeal membrane oxygenation (ECMO) patients. DESIGN: Retrospective observational. SETTING: Tertiary academic hospital. PARTICIPANTS: Adults received venoarterial (VA) or venovenous (VV) ECMO support between November 2017 and April 022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined 24-hour off sedation as no sedative infusion (except dexmedetomidine) or paralytics administration over a continuous 24-hour period while on ECMO. Off-sedation coma (comaoff) was defined as a Glasgow Coma Scale score of ≤8 after achieving 24-hour off sedation. On-sedation coma (comaon) was defined as a Glasgow Coma Scale score of ≤8 during the entire ECMO course without off sedation for 24 hours. Neurological outcomes were assessed at discharge using the modified Rankin scale (good, 0-3; poor, 4-6). We included 230 patients (VA-ECMO 143, 65% male); 24-hour off sedation was achieved in 32.2% VA-ECMO and 26.4% VV-ECMO patients. Among all patients off sedation for 24 hours (n = 69), 56.5% VA-ECMO and 52.2% VV-ECMO patients experienced comaoff. Among those unable to be sedation free for 24 hours (n = 161), 50.5% VA-ECMO and 17.2% VV-ECMO had comaon. Comaoff was associated with poor outcomes (p < 0.05) in VA-ECMO and VV-ECMO groups, whereas comaon only impacted the VA-ECMO group outcomes. In a multivariable analysis, requirement of renal replacement therapy was an independent risk factor for comaoff after adjusting for ECMO configuration, after adjusting for ECMO configuration, acute brain injury, pre-ECMO partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, and bicarbonate level (worst value within 24 hours before cannulation). CONCLUSIONS: Comaoff was common and associated with poor outcomes at discharge. Requirement of renal replacement therapy was an independent risk factor.
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Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
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Macroalgae play crucial roles as major habitat-forming organisms in marine ecosystems, having significant impacts on coral recruitment and reef recovery. However, the interactions between marine macroalgae and coral larvae remain poorly understood. Furthermore, little is known whether differences in bacterial assemblages associated with macroalgae may play roles in this process. Here, we comprehensively investigated the impacts of different macroalgae and their associated microbiomes on larval settlement and survival of coral Pocillopora damicornis. The results revealed significant variations in larval settlement and survival rates when exposed to different macroalgal species. The highest settlement rate, reaching 90%, was observed in the presence of the red alga Hypnea pannosa, followed by green algae Caulerpa serrulata, C. racemosa, and brown algae Turbinaria gracilis, Sargassum polycystum. Correspondingly, similarities in bacterial compositions were observed between H. pannosa and C. racemosa, as well as between T. gracilis and S. polycystum, implying associated bacterial may be related with the algal functions. Furthermore, macroalgae that facilitate larval settlement exhibited higher abundances of amplicon sequence variants (ASVs) associated with the metabolism of dimethylsulfoniopropionate or the antagonism of known coral pathogens. However, the brown alga Padina boryana failed to induce larval settlement with survival rate of zero after 120 h. The algal species harbored more abundances of ASVs related to Rhizobiaceae. These findings highlight the significant impact of macroalgae and their associated microbiomes on coral recruitment, as they influence both larval settlement and survival rates.
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Anthozoa , Larva , Microbiota , Seaweed , Animals , Anthozoa/microbiology , Anthozoa/physiology , Seaweed/physiology , Larva/growth & development , Larva/microbiology , Coral Reefs , Bacteria/classification , Bacteria/geneticsABSTRACT
The ability to precisely engineer nanostructures underpins a wide range of applications in areas such as electronics, optics, and biomedical sciences. Here we present a novel approach for the growth of nanoparticle assemblies that leverages the unique properties of superfluid helium. Unlike viscous solvents at or near room temperature, superfluid helium provides an unperturbed and cold environment in which weak van der Waals interactions between molecular templates and metal atoms become significant and can define the spatial arrangement of nanoparticles. To demonstrate this concept, diol and porphyrin-based molecules are employed as templates to grow gold nanoparticle assemblies in superfluid helium droplets. After soft-landing on a solid surface to remove the helium, transmission electron microscopy (TEM) imaging shows the growth of gold nanoparticles at specific binding sites within the molecular templates where the interaction between gold atoms and the molecular template is at its strongest.
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BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.
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Frequency agility refers to the rapid variation of the carrier frequency of adjacent pulses, which is an effective radar active antijamming method against frequency spot jamming. Variation patterns of traditional pseudo-random frequency hopping methods are susceptible to analysis and decryption, rendering them ineffective against increasingly sophisticated jamming strategies. Although existing reinforcement learning-based methods can adaptively optimize frequency hopping strategies, they are limited in adapting to the diversity and dynamics of jamming strategies, resulting in poor performance in the face of complex unknown jamming strategies. This paper proposes an AK-MADDPG (Adaptive K-th order history-based Multi-Agent Deep Deterministic Policy Gradient) method for designing frequency hopping strategies in frequency agile radar. Signal pulses within a coherent processing interval are treated as agents, learning to optimize their hopping strategies in the case of unknown jamming strategies. Agents dynamically adjust their carrier frequencies to evade jamming and collaborate with others to enhance antijamming efficacy. This approach exploits cooperative relationships among the pulses, providing additional information for optimized frequency hopping strategies. In addition, an adaptive K-th order history method has been introduced into the algorithm to capture long-term dependencies in sequential data. Simulation results demonstrate the superior performance of the proposed method.
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BACKGROUND: Stiff skin syndrome (SSS) is a rare disease characterized by thickened, indurated skin and limited joint movement. Multiple diverse phenotypes have been reported, and the correlation of severity with the clinical heterogeneity and histopathological findings of SSS needs to be refined. OBJECTIVE: To define subtypes based on clinical features and predict the prognosis of a new SSS classification. METHODS: Eighty-three patients with SSS were retrospectively reviewed for clinicopathological manifestations and routine laboratory workup, including 59 cases obtained from a PubMed search between 1971 and 2022 and 24 cases diagnosed in our department between 2003 and 2022. RESULTS: Among the 83 patients, 27.7, 41, and 31.3% had classic widespread, generalized segmental, and localized SSS, respectively. Joint immobility was present in 100, 71, and 20% of classic, generalized, and localized cases, respectively. Histopathologic findings were common among the 3 groups, and based on that, we further found a difference in the distribution of proliferative collagen. 54.5% of classic and 50% of generalized cases occurred throughout the dermis or the subcutis, whereas 76% of localized cases were mainly involved in the reticular dermis or subcutis. In patients with incipient localized SSS, 42% (21/50) developed generalized SSS, and only 6% (3/50) progressed to classic SSS, whereas more than half of the incipient generalized SSS cases (60.6%, 20/33) developed classic SSS. LIMITATIONS: This retrospective study was limited to previously published cases with limited data. CONCLUSIONS: We propose a distinct clinical classification characterized by lesion distribution, including classic widespread, generalized segmental, and localized SSS, associated with disease severity and prognosis.
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Skin , Humans , Female , Male , Retrospective Studies , Adult , Middle Aged , Adolescent , Skin/pathology , Young Adult , Child , Prognosis , Skin Diseases, Genetic/diagnosis , Skin Diseases, Genetic/classification , Skin Diseases, Genetic/pathology , Aged , Severity of Illness Index , Child, Preschool , Collagen/metabolism , ContractureABSTRACT
BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.
Subject(s)
Colonic Neoplasms , Microsatellite Instability , Neoadjuvant Therapy , Humans , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Male , Female , Middle Aged , Neoadjuvant Therapy/methods , Aged , Retrospective Studies , Adult , DNA Mismatch Repair , Injections, SubcutaneousABSTRACT
Arbuscular mycorrhizal fungi (AMF) increase the ability of plants to obtain nitrogen (N) from the soil, and thus can affect emissions of nitrous oxide (N2O), a long-lived potent greenhouse gas. However, the mechanisms underlying the effects of AMF on N2O emissions are still poorly understood, particularly in agroecosystems with different forms of N fertilizer inputs. Utilizing a mesocosm experiment in field, we examined the effects of AMF on N2O emissions via their influence on maize root traits and denitrifying microorganisms under ammonia and nitrate fertilizer input using 15N isotope tracer. Here we show that the presence of AMF alone or both maize roots and AMF increased maize biomass and their 15N uptake, root length, root surface area, and root volume, but led to a reduction in N2O emissions under both N input forms. Random forest model showed that root length and surface area were the most important predictors of N2O emissions. Additionally, the presence of AMF reduced the (nirK + nirS)/nosZ ratio by increasing the relative abundance of nirS-Bradyrhizobium and Rubrivivax with ammonia input, but reducing nosZ-Azospirillum, Cupriavidus and Rhodopseudomonas under both fertilizer input. Further, N2O emissions were significantly and positively correlated with the nosZ-type Azospirillum, Cupriavidus and Rhodopseudomonas, but negatively correlated with the nirS-type Bradyrhizobium and Rubrivivax. These results indicate that AMF reduce N2O emissions by increasing root length to explore N nutrients and altering the community composition of denitrifiers, suggesting that effective management of N fertilizer forms interacting with the rhizosphere microbiome may help mitigate N2O emissions under future N input scenarios.
Subject(s)
Denitrification , Mycorrhizae , Nitrous Oxide , Plant Roots , Soil Microbiology , Soil , Mycorrhizae/physiology , Nitrous Oxide/analysis , Plant Roots/microbiology , Soil/chemistry , Zea mays , Fertilizers , Air Pollutants/analysisABSTRACT
BACKGROUND/AIM: Progressive fibrosing interstitial lung disease (PF-ILD) refers to a group of chronic lung conditions commonly associated with immunoglobulin G4-related disorders. It is characterized by progressive scarring (fibrosis) within the pulmonary interstitium, resulting in respiratory failure and early mortality. Some patients do not respond to standard therapeutic interventions. Numerous studies have confirmed the anti-inflammatory and antioxidant properties of molecular hydrogen in various disease models. CASE REPORT: In this report, we present a case study of an 85-year-old female diagnosed with suspected IgG4-related PF-ILD complicated by hospital-acquired pneumonia. On the fourth day of hydrogen-assisted therapy, a noticeable improvement in lung infiltrations was observed in chest X-rays as the patient gradually progressed towards weaning off mechanical ventilation. To assess treatment responses, we compared immune phenotypes before and after hydrogen treatment. A marked increase was observed in resting regulatory T cell levels after treatment, accompanied by a notable decrease in Fas+ helper T cell and cytotoxic T cell subtypes. CONCLUSION: This case study highlights the effectiveness of hydrogen-assisted therapy in managing PF-ILD complicated by pneumonia, warranting further research in the future.
Subject(s)
Hydrogen , Immunoglobulin G , Lung Diseases, Interstitial , T-Lymphocytes, Regulatory , Humans , Female , Aged, 80 and over , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , T-Lymphocytes, Regulatory/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , fas Receptor/metabolism , Treatment OutcomeABSTRACT
INTRODUCTION: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival. METHODS: Using data (2002-2018) from Taiwan's National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation. RESULTS: In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation. CONCLUSION: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR.
Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve , Humans , Retrospective Studies , Male , Female , Middle Aged , Aged , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis/adverse effects , Taiwan/epidemiology , Mitral Valve/surgery , Adult , Heart Valve Diseases/surgery , Bioprosthesis , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/etiology , Treatment OutcomeABSTRACT
Objective: Acute myeloid leukemia (AML) is a malignant hematologic cancer with poor prognosis. Emerging evidence suggests a close association between AML progression and hypoxia. The purpose of this study was to establish a new risk prognostic model for AML based on hypoxia-related genes, and to explore the mechanisms by which hypoxia-related genes affect the prognosis of AML based on tumor immune microenvironment (TIME) and drug resistance. Methods: The AML patient samples obtained from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were classified into C1 and C2 based on hypoxia-related genes, followed by analysis utilizing Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Through univariate and LASSO Cox regression analysis, the hypoxia-related hub genes 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) were identified to construct the model. AML patient samples were obtained from the TARGET and The Cancer Genome Atlas (TCGA) databases, serving as the training and the validation sets, and were stratified into high-risk and low-risk group according to the median risk score. The correlations between the model and TIME and anti-tumor drugs were analysed using CIBERSORT and Genomics of Drug Sensitivity in Cancer (GDSC) databases. The expressions of PSMD11/PSMD14 in clinical samples and AML sensitive and drug-resistant cell lines were detected by Western blot and real-time PCR. Results: The C1 group with high expression of hypoxia-related genes had lower overall survival (OS). Immune-related signaling pathways were different between C1/C2, and hypoxia was positively correlated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. The model had good accuracy in both the training and the validation sets. The high-risk group exhibited lower OS and TIME activity, and was more sensitive to several anti-tumor drugs. PSMD11/PSMD14 were highly expressed in relapsed patients and AML drug-resistant cell lines. Conclusion: The established novel risk prognostic model and experiment results offer valuable insights for predicting AML prognosis and guiding drug selection. It also provides a fundamental framework for the mechanisms through which hypoxia impacts AML prognosis by modulating TIME and drug resistance.
Subject(s)
Cytomegalovirus Infections , Lupus Erythematosus, Systemic , Male , Humans , Dysgeusia , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapyABSTRACT
The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1+ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , B7-H1 Antigen/metabolism , Neutrophils/metabolism , Serum Amyloid A Protein/metabolism , Programmed Cell Death 1 Receptor , GlycolysisABSTRACT
An efficient intermolecular annulation of indazole aldehydes with propargylic amines has been developed for the synthesis of pyrazinoindazoles under catalyst- and additive-free conditions. This straightforward methodology was found to feature a wide substrate scope, high atom economy and environmental advantages. The bioactivity results of these new pyrazino[1,2-b]indazoles showed that some of them exhibited significant antifungal activity.
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Although aqueous zinc batteries have attracted extensive interest, they are limited by relatively low rate capabilities and poor cyclic stability of cathodes. The crystal orientation of the cathode is one important factor influencing electrochemical properties. However, it has rarely been investigated. Herein, VO2 cathodes with different crystal orientations are developed via tuning the number of hydroxyl groups in polyol, such as using glycerol, erythritol, xylitol, or mannitol. The polyols serve as a reductant as well as a structure-directing agent through a hydrothermal reaction. Xylitol-derived VO2 shows a (110)-orientated crystalline structure and ultrathin nanosheet morphology. Such features greatly enhance the pseudocapacitance to 76.1% at a scan rate of 1.0 mV s-1, which is significantly larger than that (61.6%) of the (001)-oriented VO2 derived from glycerol. The corresponding aqueous zinc batteries exhibit a high energy storage performance with a reversible specific capacity of 317 mAh g-1 at 0.5 A g-1, rate ability of 220 mAh g-1 at 10 A g-1, and capacity retention of 81.0% at 10 A g-1 over 2000 cycles. This work demonstrates a facile method for tailoring VO2 crystal orientations, offers an understanding of the Zn2+ storage mechanism upon different VO2 facets, and provides a novel method to develop cathode materials toward advanced aqueous zinc batteries.
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Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10⯵M significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1ß, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.