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OBJECTIVES: To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC). MATERIALS AND METHODS: The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders. RESULTS: Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p = 0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p = 0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p = 0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p = 0.008). CONCLUSION: In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB.
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Objectives: Sinonasal squamous cell carcinoma (SqCC) often invades the orbit. Treatment of sinonasal cancer invading orbit can vary depending on the medical center and the extent of the invasion. The definitive treatment strategy, whether it involves preserving the orbit or not, varies on a case-by-case basis and leads to different outcomes. Currently, a multimodal treatment approach, which includes surgery, chemotherapy (CTx), radiotherapy (RT), or concurrent chemoradiotherapy (CCRT), is frequently employed for sinonasal cancers. This study aims to evaluate the prognosis of sinonasal SqCC with orbit invasion in various perspectives. Methods: We conducted a retrospective review of patients with primary sinonasal SqCC invading the orbit who were treated at between 2009 and 2018. We examined factors such as the extent of tumor, orbit invasion, treatment strategies, recurrence rates, and survival rates. Results: Overall survival (OS) and disease-free survival (DFS) rates did not significantly differ based on the grade of orbit invasion. When tumor resection with orbit preservation was performed as definitive treatment, DFS was significantly longer compared to cases where surgery was not the definitive treatment (RT, CCRT). There was no significant difference in DFS between those who underwent orbit exenteration and those who underwent tumor resection with orbit preservation as the definitive treatment. Conclusion: Tumor resection with orbit preservation as the definitive treatment appears to be the preferred approach, leading to prolonged DFS while ensuring survival in cases of SqCC with orbit invasion.
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BACKGROUND: Recent human and animal studies have demonstrated that Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is closely involved in the development of allergic diseases. OBJECTIVE: To identify the mechanism underlying the activation of NLRP3 inflammasome signaling pathway in an ovalbumin (OVA)-induced allergic rhinitis (AR) mice model and to validate the effect of a specific inhibitor of the NLRP3, MCC950. METHODS: Mice were divided into three groups and each group consisted of ten mice (saline group, the negative control group; OVA group, the OVA-induced AR model group; and OVA+MCC group, treated with 10 mg/kg MCC950). MCC950 was administered intraperitoneally every second day. Multiple parameters of AR, including NLRP3, caspase-1, interleukin (IL)-1ß, and IL-18 were evaluated by using ELISA, RT-qPCR, histopathology, and immunohistochemistry. RESULTS: The mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 were upregulated in the OVA group compared with those of the saline group. MCC950 significantly inhibited the mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 in nasal tissue. Further, AR symptoms and eosinophil count were normalized after MCC950 treatment. However, OVA-specific IgE was not restored in the OVA+MCC group. CONCLUSION: NLRP3 inflammasome signaling pathway may be an alternative pathway to induce AR symptoms in OVA-induced AR model. MCC950 is a specific inhibitor of NLRP3 cascade, which attenuates AR symptoms regardless of IgE.
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The mechanism and predictive biomarkers of sinonasal inverted papilloma (IP) transformation into squamous cell carcinoma (SCC) are still unclear. We investigated the genetic mutations involved and the predictive biomarkers. Fourteen patients with SCC arising from IP and six patients with IPs without malignant transformation (sIP) were included. DNA was extracted separately from areas of normal tissue, IP, dysplasia, and SCC. Whole exome sequencing and immunohistochemistry was performed. Major oncogenic mutations were observed in the progression from IP to SCC. The most frequently mutated genes were TP53 (39%) and CDKN2A (27%). Mutations in TP53 and/or CDKN2A were observed in three of six IPs with malignant transformation (cIP); none were observed in sIPs. Tumor mutational burden (TMB) increased from IP to SCC (0.64/Mb, 1.11/Mb, and 1.25 for IP, dysplasia, and SCC, respectively). TMB was higher in the cIPs than in the sIPs (0.64/Mb vs 0.3/Mb). Three cIPs showed a diffuse strong or null pattern in p53, and one showed a total loss of p16, a distinct pattern from sIPs. Our result suggests that TP53 and CDKN2A status can be predictive markers of malignant transformation of IP. Furthermore, immunohistochemistry of p53 and p16 expression can be surrogate markers for TP53 and CDKN2A status.
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Biomarcadores Tumorais , Transformação Celular Neoplásica , Inibidor p16 de Quinase Dependente de Ciclina , Papiloma Invertido , Proteína Supressora de Tumor p53 , Humanos , Papiloma Invertido/genética , Papiloma Invertido/patologia , Papiloma Invertido/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Masculino , Feminino , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Idoso , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/metabolismo , Mutação , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Adulto , Idoso de 80 Anos ou mais , Sequenciamento do Exoma , Imuno-HistoquímicaRESUMO
BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. APPROACH AND RESULTS: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05). CONCLUSIONS: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.
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Objective: To analyze changes in olfactory function after endoscopic endonasal skull base surgery and compare performance of the olfactory questionnaire with those of conventional psychophysical tests. Methods: Patients were classified into 5 categories for olfactory function evaluation (normal, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia) based on a self-assessment. Patients also underwent the butanol threshold test (BTT), Cross-Cultural Smell Identification Test (CCSIT), and 11-item olfactory questionnaire. Subjects with normosmia preoperatively and who were followed up at least 6 months after surgery were analyzed. Receiver operating characteristic curves and confusion matrix analysis were performed for BTT, CCSIT, and olfactory questionnaire to compare their diagnostic abilities. The effects of age, preoperative olfaction, septal flap, tumor pathology, and tumor size on postoperative olfaction were evaluated using multivariate linear regression analysis. Results: Data from 108 patients were analyzed. Postoperative changes in the olfactory questionnaire were significantly associated with changes in the BTT and CCSIT. The area under the curve for postoperative self-olfactory function classification was highest for olfactory questionnaire (0.894), followed by BTT (0.767) and CCSIT (0.688). Patient age at the time of surgery and preoperative BTT score were significantly related to postoperative olfactory outcomes. Conclusion: The olfactory questionnaire correlated well with conventional psychosomatic olfactory function tests. In combination with clinical parameters and preoperative psychosomatic olfactory function tests, the olfactory questionnaire is suitable for assessing subjective olfactory function after endoscopic endonasal skull base surgery.
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OBJECTIVES: Inflammation is known as one of key pathophysiologic mechanisms of coronary artery disease. We aimed to investigate the relationship between white blood cell (WBC) count and long-term clinical outcomes of patients with vasospastic angina (VA). METHODS: A total of 823 patients who were diagnosed as VA without significant coronary lesion by coronary angiography with ergonovine provocation test were enrolled for analysis. Patients were divided according to WBC count tertile at the time of diagnosis: group I, tertile 1 and 2 (nâ =â 546, <7490/ml); group II, tertile 3 (nâ =â 277, ≥7490/ml). Primary outcome was defined as major adverse cardiovascular events (MACE), a composite outcome of all-cause death, cardiac death, myocardial infarction (MI), readmission due to cardiac symptoms, and revascularization. RESULTS: Median follow-up duration was 4.3 years. No significant difference of primary outcome was observed between group I and group II (14.7% vs. 20.2%, hazard ratio (HR) 1.29, confidence interval (CI) 0.90-1.83, P â =â 0.162), while incidence of cardiac death and MI was significantly higher in group II (1.5% vs. 4.3%, HR 2.86, CI 1.14-7.17), P â =â 0.025). In multivariate Cox regression model, elevated WBC count at the time of diagnosis of VA was an independent predictor of MI (HR 3.43, CI 1.02-11.59, P â =â 0.047). CONCLUSION: Elevated WBC count at the time of diagnosis was associated with a significantly increased risk of cardiac death and MI during long-term follow-up in VA patients.
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Angiografia Coronária , Vasoespasmo Coronário , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Contagem de Leucócitos , Vasoespasmo Coronário/fisiopatologia , Vasoespasmo Coronário/mortalidade , Vasoespasmo Coronário/diagnóstico , Angiografia Coronária/métodos , Idoso , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/sangue , Fatores de Risco , Fatores de Tempo , Estudos Retrospectivos , Prognóstico , Medição de Risco/métodos , Causas de MorteRESUMO
Objectives: This study aimed to evaluate the characteristics and treatment outcomes of inverted papillomas involving the frontal sinus. Methods: Patients treated for inverted papilloma involving the frontal sinus between 2003 and 2020 were reviewed. Tumors were classified based on their extent (Extent 1: partially encroaching on the frontal sinus; Extent 2: completely filling the frontal sinus; Extent 3: eroding bony borders beyond the frontal sinus) and site of origin (Origin 1: originating outside the frontal sinus and prolapsing into the frontal sinus; Origin 2: originating from the frontal sinus walls medial to the vertical plane of the lamina papyracea; Origin 3: originating from the frontal sinus walls lateral to the vertical plane of the lamina papyracea). Treatment outcomes including tumor recurrence and patency of the frontal recess were analyzed according to tumor characteristics and surgical treatment modalities. Results: A total of 49 surgical cases were analyzed. Extent 1 were the most common type (n = 27), followed by Extent 2 (n = 15), and Extent 3 (n = 7). The most common sites of origin were Origin 1 (n = 23), followed by Origin 2 (n = 15), and Origin 3 (n = 11). Overall, there were nine recurrences (18.4%). Recurrence was not associated with tumor extent, whereas tumor origin, particularly Origin 3 was associated with higher recurrence; 1/23 (4.3%) for Origin 1, 3/15 (20.0%) for Origin 2, and 5/11 (45.5%) for Origin 3 (Log-rank p < .001). Draf III frontal sinusotomy was associated with in the highest patency rate (84.6%) during the follow-up. Conclusion: The recurrence rate of frontal sinus inverted papilloma depends on tumor origin rather than the extent of the tumor. In particular, lesions originating from the frontal sinus lateral to the lamina papyracea recur frequently. Draf III frontal sinusotomy can achieve patent frontal recess allowing active surveillance. Level of Evidence: IV.
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OBJECTIVES: Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. METHODS: We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. RESULTS: In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. CONCLUSION: Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.
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Cerebral ischemia induces massive mitochondrial damage, leading to neuronal death. The elimination of damaged mitochondria via mitophagy is critical for neuroprotection. Here we show that the level of PA2G4/EBP1 (proliferation-associated 2G4) was notably increased early during transient middle cerebral artery occlusion and prevented neuronal death by eliciting cerebral ischemia-reperfusion (IR)-induced mitophagy. Neuron-specific knockout of Pa2g4 increased infarct volume and aggravated neuron loss with impaired mitophagy and was rescued by introduction of adeno-associated virus serotype 2 expressing PA2G4/EBP1. We determined that PA2G4/EBP1 is ubiquitinated on lysine 376 by PRKN/PARKIN on the damaged mitochondria and interacts with receptor protein SQSTM1/p62 for mitophagy induction. Thus, our study suggests that PA2G4/EBP1 ubiquitination following cerebral IR-injury promotes mitophagy induction, which may be implicated in neuroprotection.Abbreviations: AAV: adeno-associated virus; ACTB: actin beta; BNIP3L/NIX: BCL2 interacting protein 3 like; CA1: Cornu Ammonis 1; CASP3: caspase 3; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DMSO: dimethyl sulfoxide; PA2G4/EBP1: proliferation-associated 2G4; FUNDC1: FUN14 domain containing 1; IB: immunoblotting; ICC: immunocytochemistry; IHC: immunohistochemistry; IP: immunoprecipitation; MCAO: middle cerebral artery occlusion; MEF: mouse embryonic fibroblast; OGD: oxygen-glucose deprivation; PRKN/PARKIN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced kinase 1; RBFOX3/NeuN: RNA binding fox-1 homolog 3; SQSTM1/p62: sequestosome 1; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TUBB: tubulin beta class I; WT: wild-type.
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Isquemia Encefálica , Mitofagia , Animais , Camundongos , Mitofagia/genética , Proteína Sequestossoma-1/metabolismo , Infarto da Artéria Cerebral Média , Autofagia , Proteínas Quinases/metabolismo , Fibroblastos/metabolismo , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
PURPOSE: Snoring is the most common symptom of obstructive sleep apnea. Various objective methods of measuring snoring are available, and even if the measurement is performed the same way, communication is difficult because there are no common reference values between the researcher and clinician with regard to intensity and frequency, among other variables. In other words, no consensus regarding objective measurement has been reached. This study aimed to review the literature related to the objective measurement of snoring, such as measurement devices, definitions, and device locations. METHODS: A literature search based on the PubMed, Cochrane, and Embase databases was conducted from the date of inception to April 5, 2023. Twenty-nine articles were included in this study. Articles that mentioned only the equipment used for measurement and did not include individual details were excluded from the study. RESULTS: Three representative methods for measuring snoring emerged. These include (1) a microphone, which measures snoring sound; (2) piezoelectric sensor, which measures snoring vibration; and (3) nasal transducer, which measures airflow. In addition, recent attempts have been made to measure snoring using smartphones and applications. CONCLUSION: Numerous studies have investigated both obstructive sleep apnea and snoring. However, the objective methods of measuring snoring and snoring-related concepts vary across studies. Consensus in the academic and clinical communities on how to measure and define snoring is required.
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Apneia Obstrutiva do Sono , Ronco , Humanos , Polissonografia/métodos , Som , VibraçãoRESUMO
Importance: Consumer-level sleep analysis technologies have the potential to revolutionize the screening for obstructive sleep apnea (OSA). However, assessment of OSA prediction models based on in-home recording data is usually performed concurrently with level 1 in-laboratory polysomnography (PSG). Establishing the predictability of OSA using sound data recorded from smartphones based on level 2 PSG at home is important. Objective: To validate the performance of a prediction model for OSA using breathing sound recorded from smartphones in conjunction with level 2 PSG at home. Design, Setting, and Participants: This diagnostic study followed a prospective design, involving participants who underwent unattended level 2 home PSG. Breathing sounds were recorded during sleep using 2 smartphones, one with an iOS operating system and the other with an Android operating system, simultaneously with home PSG in participants' own home environment. Participants were 19 years and older, slept alone, and had either been diagnosed with OSA or had no previous diagnosis. The study was performed between February 2022 and February 2023. Main Outcomes and Measures: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the predictive model based on the recorded breathing sounds. Results: Of the 101 participants included during the study duration, the mean (SD) age was 48.3 (14.9) years, and 51 (50.5%) were female. For the iOS smartphone, the sensitivity values at apnea-hypopnea index (AHI) levels of 5, 15, and 30 per hour were 92.6%, 90.9%, and 93.3%, respectively, with specificities of 84.3%, 94.4%, and 94.4%, respectively. Similarly, for the Android smartphone, the sensitivity values at AHI levels of 5, 15, and 30 per hour were 92.2%, 90.0%, and 92.9%, respectively, with specificities of 84.0%, 94.4%, and 94.3%, respectively. The accuracy for the iOS smartphone was 88.6%, 93.3%, and 94.3%, respectively, and for the Android smartphone was 88.1%, 93.1%, and 94.1% at AHI levels of 5, 15, and 30 per hour, respectively. Conclusions and Relevance: This diagnostic study demonstrated the feasibility of predicting OSA with a reasonable level of accuracy using breathing sounds obtained by smartphones during sleep at home.
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Apneia Obstrutiva do Sono , Smartphone , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Polissonografia , Sons Respiratórios , Apneia Obstrutiva do Sono/diagnóstico , SonoRESUMO
OBJECTIVES: Several criteria exist for classifying chronic rhinosinusitis with nasal polyps (CRSwNP) as eosinophilic or non-eosinophilic. This study attempted to evaluate several criteria for defining eosinophilic CRSwNP from clinical and immunological perspectives. METHODS: A cohort of 84 patients (73 patients with CRSwNP and 11 control patients) was retrospectively analyzed. Patients were divided into eosinophilic and non-eosinophilic CRSwNP based on four different criteria: eosinophils (EOS) accounting for more than 20% of the total inflammatory cells; ≥70 EOS per high-power field (HPF); >55 EOS/HPF; and ≥10 EOS/HPF. Preoperative clinical characteristics, the immunological profiles of 14 cytokines from nasal tissue, and postoperative outcomes were compared between eosinophilic and non-eosinophilic CRSwNP based on each criterion. These criteria were immunologically validated by using 14 cytokines to predict the performance of tissue eosinophilia with a random forest model. RESULTS: Patients with eosinophilic CRSwNP were significantly older when the criterion of ≥10 EOS/HPF or EOS >20% was used. The number of patients with aspirin intolerance was significantly higher in eosinophilic CRSwNP based on the criterion of EOS >20%. From an immunological perspective, non-type 2 inflammatory cytokines were significantly higher in non-eosinophilic CRSwNP with the criterion of EOS >20% of the total inflammatory cells. In addition, the criterion of EOS >20% of the total inflammatory cells resulted in the best prediction of eosinophilic CRSwNP, with an accuracy of 88.10% and area under the curve of 0.94. CONCLUSION: Clinical and immunological characteristics were different between eosinophilic and non-eosinophilic CRSwNP depending on a variety of criteria, and the. RESULTS: of this study should be taken into account when choosing the criterion for defining eosinophilic CRSwNP and interpreting the data accordingly.
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[This corrects the article DOI: 10.3389/fimmu.2023.1138112.].
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Background: Oxidative stress is considered as one of the main causes of Parkinson's disease (PD), however the exact etiology of PD is still unknown. Although it is known that Proviral Integration Moloney-2 (PIM2) promotes cell survival by its ability to inhibit formation of reactive oxygen species (ROS) in the brain, the precise functional role of PIM2 in PD has not been fully studied yet. Objective: We investigated the protective effect of PIM2 against apoptosis of dopaminergic neuronal cells caused by oxidative stress-induced ROS damage by using the cell permeable Tat-PIM2 fusion protein in vitro and in vivo. Methods: Transduction of Tat-PIM2 into SH-SY5Y cells and apoptotic signaling pathways were determined by Western blot analysis. Intracellular ROS production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. PD animal model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and protective effects were examined using immunohistochemistry. Results: Transduced Tat-PIM2 inhibited the apoptotic caspase signaling and reduced the production of ROS induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Furthermore, we confirmed that Tat-PIM2 transduced into the substantia nigra (SN) region through the blood-brain barrier and this protein protected the Tyrosine hydroxylase-positive cells by observation of immunohistostaining. Tat-PIM2 also regulated antioxidant biomolecules such as SOD1, catalase, 4-HNE, and 8-OHdG which reduce the formation of ROS in the MPTP-induced PD mouse model. Conclusion: These results indicated that Tat-PIM2 markedly inhibited the loss of dopaminergic neurons by reducing ROS damage, suggesting that Tat-PIM2 might be a suitable therapeutic agent for PD.
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HYPOTHESIS: The introduction of functional interlayers for efficient anchoring of lithium polysulfides has received significant attention worldwide. EXPERIMENTS: A facile wet-chemical method was adopted to obtain hollow porous carbon nanospheres (HPCNSs) impregnated with metallic and polar cobalt sulfide (Co9S8) nanocrystals (abbreviated as "Co9S8@HPCNS"). The prepared nanocrystals were employed as electrocatalytic interlayers via separator coating for the efficient capture and reutilization of polysulfide species in Li-S batteries. The HPCNSs were synthesized via the polymerization method followed by carbonization and template removal. The Co9S8 nanocrystals were impregnated inside the HPCNSs, followed by heat treatment in a reducing atmosphere. FINDINGS: The porous structure of the CNS enables the efficient percolation of the electrolyte, in addition to accommodating unwanted volume fluctuations during redox processes. Furthermore, the metallic Co9S8 nanocrystals improve the electronic conductivity and enhance the polarity of the CNS towards the polysulfide. Correspondingly, the Li-S cells featuring Co9S8@HPCNS as electrocatalytic interlayers and regular sulfur (S) electrodes display improved electrochemical performance such as reasonable rate performance and prolonged cycling stability at different current rates (0.1, 0.5, and 1.0 C). Therefore, we anticipate that the rational design strategy proposed herein will provide significant insights into the synthesis of advanced materials for various energy storage applications.
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BACKGRUOUND: Diabetes mellitus is one of the most common chronic diseases worldwide, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy (DCM) is a phenomenon characterized by a deterioration in cardiac function and structure, independent of vascular complications. Among many possible causes, the renin-angiotensin-aldosterone system and angiotensin II have been proposed as major drivers of DCM development. In the current study, we aimed to investigate the effects of pharmacological activation of angiotensin-converting enzyme 2 (ACE2) on DCM. METHODS: The ACE2 activator diminazene aceturate (DIZE) was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM. RESULTS: Echocardiography revealed that in DCM, the administration of DIZE significantly improved cardiac function as well as reduced cardiac hypertrophy and fibrosis. Transcriptome analysis revealed that DIZE treatment suppresses oxidative stress and several pathways related to cardiac hypertrophy. CONCLUSION: DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse hearts. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM.