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Transition metal-nitrogen-carbon complexes, featuring single metal atoms embedded in a nitrogen-doped carbon matrix, emerge as promising alternatives to traditional platinum-based catalysts, offering cost-effectiveness, abundance, and enhanced catalytic performance. This work introduces a novel method for the etching and doping of zeolitic imidazolate frameworks (ZIFs) with transition metals, creating a uniform distribution of secondary metal centers on ZIF surfaces. By disrupting the crystalline symmetry of ZIFs through synthetic defect engineering, we gain access to their entire internal volume, creating multichannel pathways. The absorption of metal ions is theoretically simulated, demonstrating their thermodynamically spontaneous nature. The selective removal of defect channels under Lewis acidic conditions, induced by metal ion alcoholysis/hydrolysis, facilitates the introduction of metal atoms into ZIF cavities. The resulting single-atom catalyst, after pyrolysis, features a three-dimensional (3D) multichannel structure, high surface area, and uniformly dispersed metal atoms within the N-doped carbon matrix, establishing it as an exceptional catalyst for the oxygen reduction reaction (ORR). Our findings highlight the potential of using metal etching in defect-engineered metal-organic frameworks (MOFs) for single-atom catalyst preparation, paving the way for the next generation of high-performance, cost-effective ORR catalysts in sustainable energy systems.
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PURPOSE: Asthma, an airway inflammatory disease, involves multiple tumor necrosis factors (TNF). TNF ligand superfamily member 11 (TNFSF11) and its known receptor, TNF receptor superfamily 11A (TNFRSF11A), has been implicated in asthma; however, the related mechanisms remain unknown. METHODS: The serum and bronchial airway of patients with asthma and healthy subjects were examined. The air-liquid interface of primary human bronchial epithelial (HBE) cells, and Tnfsf11+/- mouse, Tnfrsf11a+/- mouse, and a humanized HSC-NOG-EXL mouse model were established. This study constructed short hairpin RNA (shRNA) of TNFSF11, TNFRSF11A, transforming growth factor ß1 (TGFß1), and transforming growth factor ß receptor type 1 (TGFßR1) using lentivirus to further examine the ability of TNFSF11 protein. RESULTS: This study was the first to uncover TNFSF11 overexpression in the airway and serum of asthmatic human subjects, and the TNFSF11 in serum was closely correlated with lung function. The TNFSF11/TNFRSF11A axis deficiency in Tnfsf11+/- or Tnfrsf11a+/- mice remarkably attenuated the house dust mite (HDM)-induced signal transducer and activator of transcription 3 (STAT3) action and remodeling protein expression. Similarly, the HDM-induced STAT3 action and remodeling protein expression in HBE cells decreased after pretreatment with TNFSF11 or TNFRSF11A shRNA. Meanwhile, the expression of the remodeling proteins induced by TNFSF11 significantly decreased after pretreatment with-stattic (inhibitor of STAT3 phosphorylation) in HBE cells. The STAT3 phosphorylation and remodeling protein expression induced by TNFSF11 obviously decreased after pretreatment with TGFß1 or TGFßR1 shRNA in HBE cells. The above results also verified that blocking TNFSF11 with denosumab alleviated airway remodeling via the TGFß1/STAT3 signaling in the humanized HSC-NOG-EXL mice with HDM-induced asthma. CONCLUSIONS: TGFß1/STAT3 action was closely correlated with TNFSF11/TNFRSF11A axis-mediated airway remodeling. This study presented a novel strategy that blocks the TNFSF11/TNFRSF11A axis to exert a protective effect against asthma.
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To enhance the reversible electrolytic conversion of oxygen in zinc-air batteries, a molten-salt-assisted method was demonstrated to synthesize highly porous carbon foams with in situ anchoring of metal sites. These electrocatalysts improved the electrolysis for oxygen reduction and evolution reactions, thus leading to the fabrication of advanced zinc-air batteries.
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OBJECTIVE: Despite the high prevalence, mild traumatic brain injury (mTBI)-induced chronic headache and cognitive deficits are poorly understood and lack effective treatments. Low-dose interleukin-2 (LD-IL-2) treatment soon after mTBI or overexpressing IL-2 in brain astrocytes prior to injury protects mice from developing post-traumatic headache (PTH)-related behaviors and cognitive decline. The present study addresses a clinically relevant knowledge gap: whether LD-IL-2 treatment long after the initial injury is still effective for chronic PTH and cognitive deficits. METHODS: mTBI was induced by a noninvasive closed-head weight drop method. LD-IL-2 was administered 4-6 weeks post-mTBI to assess its effects on chronic PTH-related facial mechanical hypersensitivity as well as mTBI-induced impairment in novel object recognition and object location tests. Endogenous regulatory T (Treg) cells were depleted to investigate the mechanism of action of LD-IL-2. RESULTS: Delayed LD-IL-2 treatment abolished chronic PTH-related behaviors. It also completely reversed mTBI-induced cognitive impairment in both male and female mice. Treg cell depletion not only prolonged PTH-related behaviors but also abolished the effects of LD-IL-2. Interestingly, LD-IL-2 treatment significantly increased the number of Treg cells in dura but not in brain tissues. INTERPRETATION: These results suggest that the beneficial effects of LD-IL-2 treatment are mediated through the expansion of meningeal Treg cells. Collectively, our study identifies Treg as a cellular target and LD-IL-2 as a promising therapy for both chronic PTH and mTBI-induced cognitive impairment for both males and females, with a wide therapeutic time window and the potential of reducing polypharmacy in mTBI treatment. ANN NEUROL 2024;96:508-525.
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Conmoción Encefálica , Disfunción Cognitiva , Modelos Animales de Enfermedad , Interleucina-2 , Animales , Ratones , Masculino , Femenino , Disfunción Cognitiva/etiología , Disfunción Cognitiva/tratamiento farmacológico , Conmoción Encefálica/complicaciones , Conmoción Encefálica/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Ratones Endogámicos C57BL , Cefalea Postraumática/etiología , Cefalea Postraumática/tratamiento farmacológico , Dolor/etiología , Dolor/tratamiento farmacológicoRESUMEN
BACKGROUND: Airway epithelial cell (AEC) necroptosis contributes to airway allergic inflammation and asthma exacerbation. Targeting the tumor necrosis factor-like ligand 1 A (TL1A)/death receptor 3 (DR3) axis has a therapeutic effect on asthmatic airway inflammation. The role of TL1A in mediating necroptosis of AECs challenged with ovalbumin (OVA) and its contribution to airway inflammation remains unclear. METHODS: We evaluated the expression of the receptor-interacting serine/threonine-protein kinase 3(RIPK3) and the mixed lineage kinase domain-like protein (MLKL) in human serum and lung, and histologically verified the level of MLKL phosphorylation in lung tissue from asthmatics and OVA-induced mice. Next, using MLKL knockout mice and the RIPK3 inhibitor GSK872, we investigated the effects of TL1A on airway inflammation and airway barrier function through the activation of necroptosis in experimental asthma. RESULTS: High expression of necroptosis marker proteins was observed in the serum of asthmatics, and necroptosis was activated in the airway epithelium of both asthmatics and OVA-induced mice. Blocking necroptosis through MLKL knockout or RIPK3 inhibition effectively attenuated parabronchial inflammation, mucus hypersecretion, and airway collagen fiber accumulation, while also suppressing type 2 inflammatory factors secretion. In addition, TL1A/ DR3 was shown to act as a death trigger for necroptosis in the absence of caspases by silencing or overexpressing TL1A in HBE cells. Furthermore, the recombinant TL1A protein was found to induce necroptosis in vivo, and knockout of MLKL partially reversed the pathological changes induced by TL1A. The necroptosis induced by TL1A disrupted the airway barrier function by decreasing the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin, possibly through the activation of the NF-κB signaling pathway. CONCLUSIONS: TL1A-induced airway epithelial necroptosis plays a significant role in promoting airway inflammation and barrier dysfunction in asthma. Inhibition of the TL1A-induced necroptosis pathway could be a promising therapeutic strategy.
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Asma , Ratones Noqueados , Necroptosis , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Animales , Asma/metabolismo , Asma/patología , Necroptosis/fisiología , Humanos , Ratones , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Masculino , Femenino , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Ratones Endogámicos C57BL , Proteínas Quinasas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Ovalbúmina/toxicidadRESUMEN
BACKGROUND: Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary. AIM: To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis. METHODS: The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively. RESULTS: We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups. CONCLUSION: FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.
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Purpose: The 68Ga/177Lu-FAP-2286 is a newly developed tumor imaging agent that shows potential for visualizing and treating tumor stroma. The objective of this research was to evaluate the effectiveness of 68Ga-FAP-2286 PET/CT and 18F-FDG PET/CT in diagnosing advanced lung cancer. Methods: In this prospective study, patients with lung cancer who underwent 68Ga-FAP-2286 and 18F-FDG PET/CT examinations between September 2022 and June 2023 were analyzed. Lesion uptake was converted to SUVmax. A paired T-test was used to compare the SUVmax, and the number of positive lesions detected by the two methods was recorded. Results: In total, 31 participants (median age: 56 years) were assessed. The uptake of 68Ga-FAP-2286 was significantly higher than that of 18F-FDG in primary lesions (9.90 ± 5.61 vs. 6.09 ± 2.84, respectively, P < 0.001), lymph nodes (7.95 ± 2.75 vs. 5.55 ± 1.59, respectively, P=0.01), and bone metastases (7.74 ± 3.72 vs. 5.66 ± 3.55, respectively, P=0.04). Furthermore, the detection sensitivity of lymph nodes using 68Ga-FAP-2286 PET/CT was superior to that with 18F-FDG PET/CT [100% (137/137) vs. 78.8% (108/137), respectively], as well as for bone metastases [100% (384/384) vs. 68.5% (263/384), respectively]. However, the detection sensitivity for primary tumors using both modalities was comparable [100% (13/13) for both]. Conclusion: Compared to 18F-FDG PET/CT, 68Ga-FAP-2286 PET/CT demonstrated better lesion detection capabilities for lung cancer, particularly in lymph nodes and bone metastases, providing compelling imaging evidence for the efficacy of 177Lu-FAP-2286 treatment.
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Purpose: This study aimed to analyze articles on the diagnosis and treatment of bone and soft tissue sarcoma using positron emission tomography (PET)/computed tomography (CT) published in the last 13 years. The objective was to conduct a bibliometric analysis and identify the research hotspots and emerging trends. Methods: Web of Science was used to search for articles on PET/CT diagnosis and treatment of bone and soft tissue sarcoma published from January 2010 to June 2023. CiteSpace was utilized to import data for bibliometric analysis. Results: In total, 425 relevant publications were identified. Publications have maintained a relatively stable growth rate for the past 13 years. The USA has the highest number of published articles (139) and the highest centrality (0.35). The UDICE-French Research Universities group is the most influential institution. BYUN BH is a prominent contributor to this field. The Journal of Clinical Oncology has the highest impact factor in the field. Conclusion: The clinical application of PET/CT is currently a research hotspot. Upcoming areas of study concentrate on the merging of PET/CT with advanced machine learning and/or alternative imaging methods, novel imaging substances, and the fusion of diagnosis and therapy. The use of PET/CT has progressively become a crucial element in the identification and management of sarcomas. To confirm its efficacy, there is a need for extensive, multicenter, prospective studies.
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Objective:To analyze the clinical features, treatment methods and prognosis of radiation-induced sarcomaï¼RISï¼ of the head and neck after radiotherapy for nasopharyngeal carcinomaï¼NPCï¼, and explore its treatment strategies. Methods:A retrospective analysis was conducted on RIS patients after radiotherapy for NPC in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2013 to October 2022. The time of onset, lesion location, pathological subtypes, imaging features and treatment outcomes were described, and the median survival time was statistically analyzed through follow-up. Results:This study included 10 patients with an interval of 2-27 years between NPC and RIS. The nasopharynx was the more common site of RIS, and osteosarcoma was the main pathological type. The median overall survival was 18 months. The median survival was 40 months in the surgery combined with the chemotherapy group, and 12 months in the surgery alone group. The 1-and 2-year cumulative survival rates were 48% and 36%, respectively. Prognostic analysis showed that gender, age of onset, time of sarcoma onset after radiotherapy and treatment methods might not be influencing factors for prognosis, and osteosarcomas presented a poorer prognosis than other pathological types. Conclusion:RIS is one of the most severe long-term adverse effects in patients with NPC. The prognosis of RIS is poor, and complete surgical resection of the tumor can improve patient survival rates. In cases where complete surgical resection is challenging, radiotherapy or chemotherapy may offer some improvement in tumor control.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Sarcoma , Humanos , Estudios Retrospectivos , Neoplasias Nasofaríngeas/radioterapia , Carcinoma Nasofaríngeo/radioterapia , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Sarcoma/radioterapia , Tasa de Supervivencia , Neoplasias Inducidas por Radiación/etiología , Adulto , Carcinoma/radioterapia , Osteosarcoma/radioterapiaRESUMEN
BACKGROUND: Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. METHODS: The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. RESULTS: Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-ß1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. CONCLUSIONS: Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.
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Remodelación de las Vías Aéreas (Respiratorias) , Aminoácido Oxidorreductasas , Asma , Ovalbúmina , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Aminoácido Oxidorreductasas/metabolismo , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/biosíntesis , Ovalbúmina/toxicidad , Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Humanos , Asma/patología , Asma/metabolismo , Asma/enzimología , Asma/genética , Transducción de Señal/fisiología , Femenino , Ratones Endogámicos BALB C , Masculino , Transición Epitelial-Mesenquimal/fisiologíaRESUMEN
BACKGROUND: Depression and suicidal ideation often co-occur in children and adolescents, yet they possess distinct characteristics. This study sought to identify the different related factors associated with depression and suicidal ideation. METHODS: A nationwide cross-sectional survey collected data from Chinese children and adolescents aged 8 to 18 (N = 160,962; 48.91 % girls). The survey included inquiries about demographics, depression, suicidal ideation, anxiety, perceived stress, academic burnout, internet addiction, non-suicidal self-injury, bullying, and being bullied. Fifteen machine learning algorithms were conducted to identify the different related factors associated with depression and suicidal ideation. Additionally, we conducted external validation on an independent sample of 1,812,889 children and adolescents. RESULTS: Our findings revealed seven related factors linked to depression and six associated with suicidal ideation, with average accuracy rates of 86.86 % and 85.82 %, respectively. For depression, the most influential factors were anxiety, perceived stress, academic burnout, internet addiction, non-suicidal self-injury, experience of bullying, and age. Similarly, anxiety, non-suicidal self-injury, perceived stress, internet addiction, academic burnout, and age emerged as paramount factors for suicidal ideation. Moreover, these related factors showed notable variations in their predictive capacities for depression and suicidal ideation across different subgroups. CONCLUSION: Anxiety emerged as the predominant shared factor for both depression and suicidal ideation, whereas the other related factors displayed distinct predictive patterns for each condition. These findings highlight the critical need for tailored strategies from public mental health service providers and policymakers to address the pressing concerns of depression and suicidal ideation.
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Acoso Escolar , Depresión , Aprendizaje Automático , Ideación Suicida , Humanos , Adolescente , Femenino , Masculino , Niño , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , China/epidemiología , Acoso Escolar/estadística & datos numéricos , Acoso Escolar/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Factores de Riesgo , Trastorno de Adicción a Internet/epidemiología , Trastorno de Adicción a Internet/psicología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Pueblos del Este de AsiaRESUMEN
Background: Hepatocellular carcinoma (HCC) is a highly aggressive cancer. This study aims to elucidate the role of Glyoxylate reductase/hydroxypyruvate reductase (GRHPR) in HCC proliferation and metastasis, along with its molecular mechanism, and to identify miRNAs targeting GRHPR. Materials and Methods: Expression levels of GRHPR and miR-138-5p were assessed using real-time fluorescent quantitative polymerase chain reaction and Western blot techniques. Bioinformatic analysis was employed to identify miRNAs targeting GRHPR, and the results were confirmed via dual-luciferase reporter assays. HCC cell lines overexpressing GRHPR were established to investigate its roles in cell proliferation, migration, and invasion. The biological function of miR-138-5p targeting GRHPR in HCC cells was also evaluated. Furthermore, a xenograft mouse model was utilized to examine the in vivo functions of GRHPR. Results: GRHPR expression was downregulated in HCC, whereas miR-138-5p was upregulated. Overexpression of GRHPR suppressed HCC cell proliferation, migration, and invasion. Conversely, inhibition of GRHPR by miR-138-5p promoted HCC cell proliferation and invasive properties. MiR-138-5p was found to regulate Phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) phosphorylation levels by inhibiting GRHPR expression. Conclusion: This study highlights GRHPR's role as a tumor suppressor in HCC, with its function being regulated by miR-138-5p.
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The adsorption and desorption of phosphorus (P) in soil constitute a crucial internal cycle that is closely associated with soil fertility, exerting direct influence on the quantity, form, and availability of P within the soil. The vertical spatial variation characteristics of soil adsorption and desorption were investigated for the 0-100 cm soil layer in the northeast black soil region in this study. The maximum adsorption capacity (Qmax) and maximum adsorption buffer capacity (MBC) of black soil in the study area ranged from 313.8 to 411.9 mg kg-1 and from 3.1 to 28.8 L kg-1, respectively, within the soil layer of 0-100 cm depth, exhibiting an increasing trend with greater soil depth. The degree of P adsorption saturation (DPS) exhibited a contrasting trend with the variations in Qmax and MBC, ranging from 3.8% to 21.6%. The maximum desorption capacity (Dmax) and desorption rate (Dr) of soil P ranged from 112.8 to 215.7 mg kg-1 and 32.1% to 52.5%, respectively, while the readily desorbable P (RDP) in soil was within the range of 1.02 to 3.35 mg kg-1. Both Dmax, Dr, and RDP exhibited a decreasing trend with increasing soil depth before showing an upward trend. These research findings not only provide essential background data for the systematic investigation of soil P in the black soil region but also serve as a valuable reference for assessing soil quality in this area.
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Fósforo , Suelo , Fósforo/química , Fósforo/análisis , Suelo/química , Adsorción , ChinaRESUMEN
Emerging evidence demonstrates that pyroptosis has been implicated in the pathogenesis of asthma. Gasdermin D (GSDMD) is the pyroptosis executioner. The mechanism of GSDMD in asthma remains unclear. The aim of this study was to elucidate the potential role of GSDMD in asthmatic airway inflammation and remodeling. Immunofluorescence staining was conducted on airway epithelial tissues obtained from both asthma patients and healthy controls (HCs) to evaluate the expression level of N-GSDMD. ELISA was used to measure concentrations of cytokines (IL-1ß, IL-18, IL-17A, and IL-10) in serum samples collected from asthma patients and healthy individuals. We demonstrated that N-GSDMD, IL-18, and IL-1ß were significantly increased in samples with mild asthma compared with those from the controls. Then, wild type and Gsdmd-knockout (Gsdmd-/-) mice were used to establish asthma model. We performed histopathological staining, ELISA, and flow cytometry to explore the function of GSDMD in allergic airway inflammation and tissue remodeling in vivo. We observed that the expression of N-GSDMD, IL-18, and IL-1ß was enhanced in OVA-induced asthma mouse model. Gsdmd knockout resulted in attenuated IL-18, and IL-1ß production in both bronchoalveolar lavage fluid (BALF) and lung tissue in asthmatic mice. In addition, Gsdmd-/- mice exhibit a significant reduction in airway inflammation and remodeling, which might be associated with reduced Th17 inflammatory response and M2 polarization of macrophages. Further, we found that GSDMD knockout may improve asthmatic airway inflammation and remodeling through regulating macrophage adhesion, migration, and macrophage M2 polarization by targeting Notch signaling pathway. These findings demonstrate that GSDMD deficiency profoundly alleviates allergic inflammation and tissue remodeling. Therefore, GSDMD may serve as a potential therapeutic target against asthma.
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Asma , Modelos Animales de Enfermedad , Péptidos y Proteínas de Señalización Intracelular , Ratones Noqueados , Ovalbúmina , Proteínas de Unión a Fosfato , Animales , Asma/genética , Asma/patología , Asma/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , Ratones , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Humanos , Remodelación de las Vías Aéreas (Respiratorias) , Femenino , Inflamación/patología , Inflamación/metabolismo , Inflamación/genética , Ratones Endogámicos C57BL , Masculino , Citocinas/metabolismo , Piroptosis , Pulmón/patología , Pulmón/metabolismo , GasderminasRESUMEN
The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.
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Adenosina Trifosfato , Adenilato Quinasa , Axonema , Ratones Noqueados , Motilidad Espermática , Cola del Espermatozoide , Animales , Adenilato Quinasa/metabolismo , Masculino , Ratones , Axonema/metabolismo , Motilidad Espermática/fisiología , Cola del Espermatozoide/metabolismo , Adenosina Trifosfato/metabolismo , Humanos , Metabolismo Energético , Espermatozoides/metabolismo , Flagelos/metabolismo , Creatina Quinasa/metabolismo , Infertilidad Masculina/metabolismo , Infertilidad Masculina/genéticaRESUMEN
Herein, we investigate the temperature compensation for a dual-mass MEMS gyroscope. After introducing and simulating the dual-mass MEMS gyroscope's working modes, we propose a hybrid algorithm for temperature compensation relying on improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN), sample entropy, time-frequency peak filtering, non-dominated sorting genetic algorithm-II (NSGA II) and extreme learning machine. Firstly, we use ICEEMDAN to decompose the gyroscope's output signal, and then we use sample entropy to classify the decomposed signals. For noise segments and mixed segments with different levels of noise, we use time-frequency peak filtering with different window lengths to achieve a trade-off between noise removal and signal retention. For the feature segment with temperature drift, we build a compensation model using extreme learning machine. To improve the compensation accuracy, NSGA II is used to optimize extreme learning machine, with the prediction error and the 2-norm of the output-layer connection weight as the optimization objectives. Enormous simulation experiments prove the excellent performance of our proposed scheme, which can achieve trade-offs in signal decomposition, classification, denoising and compensation. The improvement in the compensated gyroscope's output signal is analyzed based on Allen variance; its angle random walk is decreased from 0.531076°/h/âHz to 6.65894 × 10-3°/h/âHz and its bias stability is decreased from 32.7364°/h to 0.259247°/h.
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Submerged macrophytes are effective in ecological restoration of water bodies polluted by nitrogen and phosphorus, and its restoration capacity depends on underwater illumination condition. This study explored the influencing mechanism of illumination on Vallisneria spinulosa Yan (V. spinulosa Yan) for water restoration. Addition of underwater light source increased the total nitrogen, ammonia nitrogen, total phosphorus, and phosphate removal loads of the V. spinulosa Yan growth system by 61.5, 39.2, 8.5, and 5.0 mg m-2 d-1, respectively. Meanwhile, the growth of V. spinulosa Yan was obviously promoted, even with high water turbidity. Although the biological nitrogen removal processes were inhibited by adding underwater light source, the growth of V. spinulosa Yan can be significantly improved, thus enhancing the efficiency of water purification via the absorption of nitrogen and phosphorus by V. spinulosa Yan. This study provides a theoretical foundation and technical support for application of submerged macrophytes in ecological water restoration.
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Luz , Nitrógeno , Fósforo , Rizosfera , Purificación del Agua , Purificación del Agua/métodos , Hydrocharitaceae/metabolismo , Hydrocharitaceae/crecimiento & desarrollo , Biodegradación Ambiental , Agua , EcosistemaRESUMEN
The misfolding and aggregation of α-synuclein monomers usually cause the occurrence and development of Parkinson's disease (PD). It is important to develop effective methods for detection of α-synuclein aggregates. Carbon dots (CDs) could be the potential fluorescence probe for this purpose owing to their appreciated optical properties. However, undefined structure of CDs and complicated three-dimensional structure of protein severely hindered the design of fluorescence probe towards protein aggregates. Herein, a red emissive fluorescent amphiphilic CD, named as CL-9, was designed with a high sensitivity to α-synuclein fibrils by a one-step heating process, using the ternary carbon source, including Congo red, l-tryptophan and urea. The CL-9 exhibited turn-on red emissive fluorescence towards α-synuclein fibril, but remained no change towards its monomer. Compared with the original Congo red dye, CL-9 exhibited stronger turn-on red fluorescence towards α-synuclein fibrils with better anti-photobleaching resistance, biocompatibility and signal-to-noise ratio. The CL-9 was successful as a fluorescent probe to image α-synuclein fibrils in NL-5901 C. elegans. The present study provided a feasible approach using the multiple carbon sources to construct the CDs based fluorescence probe targeting amyloid proteins.
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Carbono , Colorantes Fluorescentes , alfa-Sinucleína , alfa-Sinucleína/química , alfa-Sinucleína/análisis , Carbono/química , Colorantes Fluorescentes/química , Animales , Puntos Cuánticos/química , Humanos , Caenorhabditis elegans/metabolismo , Rojo Congo/química , Amiloide/química , Tamaño de la Partícula , Imagen ÓpticaRESUMEN
Prostate cancer(PCa), a leading global health concern, profoundly impacts millions of men worldwide. Progressing through two stages, it initially develops within the prostate and subsequently extends to vital organs such as lymph nodes, bones, lungs, and the liver. In the early phases, castration therapy is often employed to mitigate androgen effects. However, when prostate cancer becomes resistant to this treatment, alternative strategies become imperative. As diagnostic and treatment methodologies for prostate cancer continually advance, radioligand therapy (RLT) has emerged as a promising avenue, yielding noteworthy outcomes. The fundamental principle of RLT involves delivering radionuclide drugs to cancerous lesions through specific carriers or technologies. Subsequently, these radionuclide drugs release radioactive energy, facilitating the destruction of cancer cell tissues. At present, the positron emission tomography (PET) targeting PSMA has been widely developed for the use of diagnosis and staging of PCa. Notably, FDA-approved prostate-specific membrane antigen (PSMA) targeting agents, such as 68Ga-PSMA-11 and 177Lu-PSMA-617, represent significant milestones in enhancing diagnostic precision and therapeutic efficacy. This review emphasizes the current research status and outcomes of various radionuclide-labeled PSMA ligands. The objective is to provide valuable insights for the continued advancement of diagnostic and therapeutic approaches in the realm of prostate cancer.