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The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.
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COVID-19/metabolismo , Regulación de la Expresión Génica , Proteoma/biosíntesis , Proteómica , SARS-CoV-2/metabolismo , Autopsia , COVID-19/patología , COVID-19/terapia , Femenino , Humanos , Masculino , Especificidad de ÓrganosRESUMEN
Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.
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Infecciones por Coronavirus/sangre , Metabolómica , Neumonía Viral/sangre , Proteómica , Adulto , Aminoácidos/metabolismo , Biomarcadores/sangre , COVID-19 , Análisis por Conglomerados , Infecciones por Coronavirus/fisiopatología , Femenino , Humanos , Metabolismo de los Lípidos , Aprendizaje Automático , Macrófagos/patología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
RNA polymerase II (RNA Pol II) subunits are thought to be involved in various transcription-associated processes, but it is unclear whether they play different regulatory roles in modulating gene expression. Here, we performed nascent and mature transcript sequencing after the acute degradation of 12 mammalian RNA Pol II subunits and profiled their genomic binding sites and protein interactomes to dissect their molecular functions. We found that RNA Pol II subunits contribute differently to RNA Pol II cellular localization and transcription processes and preferentially regulate RNA processing (such as RNA splicing and 3' end maturation). Genes sensitive to the depletion of different RNA Pol II subunits tend to be involved in diverse biological functions and show different RNA half-lives. Sequences, associated protein factors, and RNA structures are correlated with RNA Pol II subunit-mediated differential gene expression. These findings collectively suggest that the heterogeneity of RNA Pol II and different genes appear to depend on some of the subunits.
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ARN Polimerasa II , Empalme del ARN , Animales , ARN Polimerasa II/metabolismo , Proteolisis , Procesamiento Postranscripcional del ARN , ARN/metabolismo , Transcripción Genética , Mamíferos/metabolismoRESUMEN
Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer's and Parkinson's diseases1. FTLD typically presents in 45 to 64 year olds with behavioural changes or progressive decline of language skills2. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions with TAR DNA-binding protein (TDP-43) immunoreactivity3. Here we extracted amyloid fibrils from brains of four patients representing four of the five FTLD-TDP subclasses, and determined their structures by cryo-electron microscopy. Unexpectedly, all amyloid fibrils examined were composed of a 135-residue carboxy-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP4. In addition to TMEM106B fibrils, we detected abundant non-fibrillar aggregated TDP-43 by immunogold labelling. Our observations confirm that FTLD-TDP is associated with amyloid fibrils, and that the fibrils are formed by TMEM106B rather than TDP-43.
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Amiloide , Proteínas de Unión al ADN , Degeneración Lobar Frontotemporal , Proteínas de la Membrana , Proteínas del Tejido Nervioso , Amiloide/ultraestructura , Microscopía por Crioelectrón , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/ultraestructura , Degeneración Lobar Frontotemporal/metabolismo , Degeneración Lobar Frontotemporal/patología , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/ultraestructura , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/ultraestructuraRESUMEN
Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Anciano , Humanos , Masculino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Envejecimiento/genética , Mutación , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , PronósticoRESUMEN
Recent advances in synthetic biology and materials science have given rise to a new form of materials, namely engineered living materials (ELMs), which are composed of living matter or cell communities embedded in self-regenerating matrices of their own or artificial scaffolds. Like natural materials such as bone, wood, and skin, ELMs, which possess the functional capabilities of living organisms, can grow, self-organize, and self-repair when needed. They also spontaneously perform programmed biological functions upon sensing external cues. Currently, ELMs show promise for green energy production, bioremediation, disease treatment, and fabricating advanced smart materials. This review first introduces the dynamic features of natural living systems and their potential for developing novel materials. We then summarize the recent research progress on living materials and emerging design strategies from both synthetic biology and materials science perspectives. Finally, we discuss the positive impacts of living materials on promoting sustainability and key future research directions.
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Ciencia de los Materiales , Biología SintéticaRESUMEN
Liver cancer is among the top leading causes of cancer mortality worldwide. Particularly, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) have been extensively investigated from the aspect of tumor biology. However, a comprehensive and systematic understanding of the molecular characteristics of HCC and CCA remains absent. Here, we characterized the proteome landscapes of HCC and CCA using the data-independent acquisition (DIA) mass spectrometry (MS) method. By comparing the quantitative proteomes of HCC and CCA, we found several differences between the two cancer types. In particular, we found an abnormal lipid metabolism in HCC and activated extracellular matrix-related pathways in CCA. We next developed a three-protein classifier to distinguish CCA from HCC, achieving an area under the curve (AUC) of 0.92, and an accuracy of 90% in an independent validation cohort of 51 patients. The distinct molecular characteristics of HCC and CCA presented in this study provide new insights into the tumor biology of these two major important primary liver cancers. Our findings may help develop more efficient diagnostic approaches and new targeted drug treatments.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteoma , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Estudios RetrospectivosRESUMEN
Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.
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COVID-19 , Humanos , Proteómica , Anticuerpos Antivirales , Inmunoglobulina M , Inmunoglobulina GRESUMEN
As p-type phase-change degenerate semiconductors, crystalline and amorphous germanium telluride (GeTe) exhibit metallic and semiconducting properties, respectively. However, the massive structural defects and strong interface scattering in amorphous GeTe films significantly reduce their performance. In this work, two-dimensional (2D) p-type GeTe nanosheets are synthesized via a specially designed space-confined chemical vapor deposition (CVD) method, with the thickness of the GeTe nanosheets reduced to 1.9 nm. The space-confined CVD method improves the crystallinity of ultrathin GeTe by lowering the partial pressure of the reactant gas, resulting in GeTe nanosheets with excellent p-type semiconductor properties, such as a satisfactory on/off ratio of 105. Temperature-dependent electrical measurements demonstrate that variable-range hopping and optical-phonon-assisted hopping mechanisms dominate transport behavior at low and high temperatures, respectively. GeTe devices exhibit significantly high responsivity (6589 and 2.2 A W-1 at 633 and 980 nm, respectively) and detectivity (1.67 × 1011 and 1.3 × 108 Jones at 633 and 980 nm, respectively), making them feasible for broadband photodetectors in the visible to near-infrared range. Furthermore, the fabricated GeTe/WS2 diode exhibits a rectification ratio of 103 at zero gate voltage. These satisfactory p-type semiconductor properties demonstrate that ultrathin GeTe exhibits enormous potential for applications in optoelectronic interconnection circuits.
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Carbon-based hole transport layer-free perovskite solar cells (PSCs) based on methylammonium lead triiodide (MAPbI3 ) have become one of the research focus due to low cost, easy preparation, and good optoelectronic properties. However, instability of perovskite under vacancy defects and stress-strain makes it difficult to achieve high-efficiency and stable power output. Here, a soft-structured long-chain 2D pentanamine iodide (abbreviated as "PI") is used to improve perovskite quality and interfacial mechanical compatibility. PI containing CH3 (CH2 )4 NH3 + and I- ions not only passivate defects at grain boundaries, but also effectively alleviate residual stress during high temperature annealing via decreasing Young's modulus of perovskite film. Most importantly, PI effectively increases matching degree of Young's modulus between MAPbI3 (47.1 GPa) and carbon (6.7 GPa), and strengthens adhesive fracture energy (Gc ) between perovskite and carbon, which is helpful for outward release of nascent interfacial stress generated under service conditions. Consequently, photoelectric conversion efficiency (PCE) of optimal device is enhanced from 10.85% to 13.76% and operational stability is also significantly improved. 83.1% output is maintained after aging for 720 h at room temperature and 25-60% relative humidity (RH). This strategy of regulation from chemistry and physics provides a strategy for efficient and stable carbon-based PSCs.
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Phthalate esters (PAEs), accompanied by phthalate monoesters as hydrolysis metabolites in humans, have been widely used as plasticizers and exhibited disruptive effects on the endocrine and metabolic systems. The present study aims to investigate the inhibition behavior of PAEs and phthalate monoesters on the activity of the important hydrolytic enzymes, carboxylesterases (CESs), to elucidate the toxicity mechanism from a new perspective. The results showed significant inhibition on CES1 and CES2 by most PAEs, but not by phthalate monoesters, above which the activity of CES1 was strongly inhibited by DCHP, DEHP, DiOP, DiPP, DNP, DPP and BBZP, with inhibition ratios exceeding 80%. Kinetic analyses and in vitro-in vivo extrapolation were conducted, revealing that PAEs have the potential to disrupt the metabolism of endogenous substances catalyzed by CES1 in vivo. Molecular docking results revealed that hydrogen bonds and hydrophobic contacts formed by ester bonds contributed to the interaction of PAEs towards CES1. These findings will be beneficial for understanding the adverse effect of PAEs and phthalate monoesters.
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Dietilhexil Ftalato , Ácidos Ftálicos , Humanos , Hidrolasas de Éster Carboxílico , Simulación del Acoplamiento Molecular , Ácidos Ftálicos/toxicidad , Plastificantes/toxicidad , Ésteres/química , Dibutil Ftalato , Dietilhexil Ftalato/toxicidad , Dietilhexil Ftalato/química , ChinaRESUMEN
ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent.
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Apéndice Atrial , Fibrilación Atrial , Ecocardiografía Tridimensional , Inhibidores del Factor Xa , Rivaroxabán , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/diagnóstico , Femenino , Masculino , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Apéndice Atrial/efectos de los fármacos , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Trombosis/fisiopatología , Valor Predictivo de las Pruebas , Función del Atrio Izquierdo/efectos de los fármacos , Terapia Trombolítica , Función Ventricular Izquierda/efectos de los fármacos , Factores de TiempoRESUMEN
The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.
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Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.
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Proteínas de Insectos , Larva , Mariposas Nocturnas , Animales , Mariposas Nocturnas/inmunología , Mariposas Nocturnas/genética , Mariposas Nocturnas/microbiología , Mariposas Nocturnas/crecimiento & desarrollo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Larva/crecimiento & desarrollo , Larva/microbiología , Bacillus thuringiensis , Beauveria/fisiología , Péptidos Antimicrobianos/genética , Pupa/crecimiento & desarrollo , Interferencia de ARNRESUMEN
Exploiting noble-metal-free systems for high-performance photocatalytic CO2 reduction still presents a key challenge, partially due to the long-standing difficulties in developing potent and durable earth-abundant photosensitizers. Therefore, based on the very cheap aluminum metal, we have deployed a systematic series of homoleptic Al(III) photosensitizers featuring 2-pyridylpyrrolide ligands for CO2 photoreduction. The combined studies of steady-state and time-resolved spectroscopy as well as quantum chemical calculations demonstrate that in anerobic CH3CN solutions at room temperature, visible-light excitation of the Al(III) photosensitizers leads to an efficient population of singlet excited states with nanosecond-scale lifetimes and notable emission quantum yields (10-40%). The results of transient absorption spectroscopy further identified the presence of emissive singlet and unexpectedly nonemissive triplet excited states. More importantly, the introduction of methyl groups at the pyrrolide rings can greatly improve the visible-light absorption, reducing power, and durability of the Al(III) photosensitizers. With triethanolamine, BIH (1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole), and an Fe(II)-quaterpyridine catalyst, the most methylated Al(III) photosensitizer achieves an apparent quantum efficiency of 2.8% at 450 nm for selective (>99%) CO2-to-CO conversion, which is nearly 28 times that of the unmethylated one (0.1%) under identical conditions. The optimal system realizes a maximum turnover number of 10250 and higher robustness than the systems with Ru(II) and Cu(I) benchmark photosensitizers. Quenching experiments using fluorescence spectroscopy elucidate that the photoinduced electron transfer in the Al(III)-sensitized system follows a reductive quenching pathway. The remarkable tunability and cost efficiency of these Al(III) photosensitizers should allow them as promising components in noble-metal-free systems for solar fuel conversion.
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PURPOSE: To determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant non-small-cell lung cancer (NSCLC). METHOD: Randomized controlled trials (RCTs) that compared the survival outcomes between adjuvant EGFR-TKIs and adjuvant chemotherapy or a placebo, or between different EGFR-TKI treatment durations for resected NSCLC, were eligible for inclusion. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effective measures using random-effect or fixed-effect models. Subgroup analysis was also performed. RESULTS: Eleven RCTs involving 2102 EGFR-mutant NSCLC patients with or without EGFR-TKI adjuvant therapy were included. For all stage IB-IIIA NSCLC patients, EGFR-TKIs adjuvant therapy could not only significantly improve DFS (HR 0.43, 95% CI 0.30-0.63, P < 0.001) and 2- and 3-year DFS rates, but also improve OS (HR 0.72, 95% CI, 0.54-0.96, P = 0.024), compared with chemotherapy or the placebo. Further subgroup analyses indicated prolonged OS from first-generation EGFR-TKI adjuvant therapy in stage III patients, compared with chemotherapy or the placebo (HR for OS, 0.34; 95% CI, 0.18-0.63; P = 0.001). Of note, osimertinib adjuvant therapy led to the OS benefit expanding from stage III to stage II-III patients, with significantly improved DFS and a lower risk of brain recurrence, compared with the placebo. A 2-year treatment duration with EGFR-TKI adjuvant therapy showed a significantly lower recurrence risk than a ≤ 1-year duration. CONCLUSION: The DFS advantage from first-generation EGFR-TKI adjuvant therapy can translate into an OS benefit in stage III NSCLC patients. Osimertinib might be more suitable for adjuvant therapy than first-generation EGFR-TKIs, because of the lower recurrence rate and the potential OS benefit even in early-stage patients. The optimal treatment duration for EGFR-TKIs at different stages of disease needs to be validated.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Inhibidores de Proteínas Quinasas/efectos adversos , Receptores ErbB , Ensayos Clínicos Controlados Aleatorios como Asunto , MutaciónRESUMEN
Objectives Oral health problem is prevalent in the elderly population which is also at high risk of Parkinson's disease (PD). However, the association between self-reported oral health and PD is still unclear. We aimed to explore the association between baseline self-reported oral health (mouth ulcers, painful gums, bleeding gums, loosen teeth, toothache, dentures) and future incidence of PD. Methods Participants were enrolled in the UK biobank from 2006 to 2010 and those without PD at baseline were included in the current study. We used Cox regression analysis to explore the question and adjusted for age, sex, body mass index, smoking, drinking, ethnicity, education, socioeconomic status, and average total household income before tax. Results We included 421180 participants with a mean age of 56.26 years old and 46.5% of them were male. And 2339 participants were diagnosed with PD in the follow-up. Mouth ulcers, loosen teeth, dentures, toothache, and bleeding gums were not related to the risk of PD. Painful gums were related to a higher risk of PD (HR: 1.39, 95%CI: 1.12-1.72, P = 0.003), and similar results were reached after adjusting for gene risk (HR: 1.39, 95%CI: 1.12-1.73, P = 0.003), or source of diagnosis (HR: 1.39, 95%CI: 1.12-1.72, P = 0.002), and time of diagnosis (HR: 1.29, 95%CI: 1.03-1.63, P = 0.02). Conclusions Our study has demonstrated a substantial correlation between painful gums and elevated susceptibility to PD, underscoring the potential advantages of implementing oral health interventions for decreasing the risk of PD.
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A series of novel Cp*Ir complexes with nitrogen-rich NÌN bidentate ligands were developed for the catalytic dehydrogenation of formic acid in water under base-free conditions. These complexes were synthesized by using pyridyl 1,2,4-triazole, methylated species, or pyridyl 1,2,3-triazole as a N-site regulation ligand and were fully characterized. Complex 1-H2O bearing 1,2,4-triazole achieved a high turnover frequency of 14192 h-1 at 90 °C in 4 M FA aqueous solution. The terminal and bridged Ir-H intermediates of 1-H2O were successfully detected by 1H NMR and mass spectrometry measurements. Kinetic isotope effect experiments and density functional theory (DFT) calculations were performed; then a plausible mechanism was proposed involving the ß-hydride elimination and formation of H2. Water-assisted H2 release was proven to be the rate-determining step of the reaction. The distribution of Mulliken charges on N atoms of triazole ligand internally revealed that the ortho site N2 of 1-H2O with a higher electron density was conducive to efficient proton transfer. Additionally, the advantage of water-assisted short-range bridge of 1,2,4-triazole moieties led to a higher catalytic activity of 1-H2O. This study demonstrated the effectiveness of nitrogen-rich ligands on FA dehydrogenation and revealed a good strategy for N site regulation in the development of new homogeneous catalysts.
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This study used the tert-butylcalix[6]arene (TBC[6]) as the ligand and successfully synthesized six TBC[6]-stabilized titanium-oxo clusters (TOCs) by the one-step solvothermal reaction. These six compounds were [Ti4O2(TBC[6])2] (Ti4), {Ti2(TBC[6])(EtO)2(SaH2)2} (Ti2-SA, H2Sa = squaric acid), {Ti2(TBC[6])2(EtO)2(Oa)} (Ti2-OA, H2Oa = oxalic acid), [H2Ti4(TBC[6])(BA)2(EtO)10] (Ti4-BA, HBA = benzoic acid), [Ti6O2(TBC[6])(BA)4(OiPr)10] (Ti6-BA), and [Ti8(TBC[6])2(Sal)4(EtO)16] (Ti8-Sal, H2Sal = salicylic acid). These clusters contain one or two TBC[6] ligands, with the biconical or monoconical configuration, greatly increasing the variety of TOCs it could support. The introduction of auxiliary carboxylic ligands can further stimulate the growth of structures, with the cluster core gradually increased from {Ti-TBC[6]-Ti} to {Ti2-TBC[6]-Ti2}, to {Ti3-TBC[6]-Ti3}, and finally to {Ti3-TBC[6]-Ti2-TBC[6]-Ti3} with 3.1 nm length. Structural regulation may affect their solution stability, absorption spectra, and photocurrent response. The study of catalytic activities shows that these clusters can be used as recyclable heterogeneous photocatalysts for the oxidation of sulfide to sulfoxide. The catalytic efficiency of the TBC[6]-Tix system is closely related to the cluster structure, and the exposure of the Ti site on the catalyst surface can significantly enhance the catalytic activity of the clusters.
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Nanocluster catalysts face a significant challenge in striking the right balance between stability and catalytic activity. Here, we present a thiacalix[4]arene-protected 6-electron [Ag30(TC4A)4(iPrS)8] nanocluster that demonstrates both high stability and catalytic activity. The Ag30 nanocluster features a metallic core, Ag104+, consisting of two Ag3 triangles and one Ag4 square, shielded by four {Ag5@(TC4A)4} staple motifs. Based on DFT calculations, the Ag104+ metallic kernel can be viewed as a trimer comprising 2-electron superatomic units, exhibiting a valence electron structure similar to that of the Be3 molecule. Notably, this is the first crystallographic evidence of the trimerization of 2-electron superatomic units. Ag30 can reduce CO2 into CO with a Faraday efficiency of 93.4% at -0.9 V versus RHE along with excellent long-term stability. Its catalytic activity is far superior to that of the chain-like AgI polymer ∞1{[H2Ag5(TC4A)(iPrS)3]} (∞1Agn), with the composition similar to Ag30. DFT calculations elucidated the catalytic mechanism to clarify the contrasting catalytic performances of the Ag30 and ∞1Agn polymers and disclosed that the intrinsically higher activity of Ag30 may be due to the greater stability of the dual adsorption mode of the *COOH intermediate on the metallic core.