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The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal and cross-sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917; PFDR <0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048; PFDR = 0.010), AST to ALT ratio (HR, 1.195; PFDR <0.001), gamma-glutamyl transpeptidase (GGT; HR, 1.066; PFDR <0.001), alcoholic liver disease (ALD; HR, 2.872; PFDR <0.001), and fibrosis and cirrhosis of liver (HR, 2.285; PFDR = 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U-shaped association between Alb and AST and incident ACD (Pnonlinear <0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (PFDR <0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcortical regions, including hippocampus, amygdala, thalamus, pallidum, and fusiform (PFDR <0.05). In sensitivity analysis, metabolic dysfunction-associated steatotic liver disease (MASLD) was associated with the risk of ACD and brain subcortical changes. Our findings provide substantial evidence that liver dysfunction may be an important factor for incident dementia. Early intervention in the unhealthy liver may help prevent cognitive impairment and dementia incidence.
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Demência , Hepatopatias , Adulto , Humanos , Estudos Prospectivos , Estudos Transversais , Hepatopatias/epidemiologia , Fígado , Cognição , Bilirrubina , Encéfalo , Cirrose Hepática , Demência/epidemiologia , Aspartato AminotransferasesRESUMO
Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (ß = -0.115, pFDR < 0.001), GLO (ß = -0.184, pFDR < 0.001), and A/G (ß = 0.182, pFDR < 0.001) and CSF ß-amyloid1-42 (Aß1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach.
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Doença de Alzheimer , Disfunção Cognitiva , Globulinas , Humanos , Doença de Alzheimer/patologia , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Albuminas , Fígado , Fragmentos de Peptídeos/líquido cefalorraquidianoRESUMO
Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aß42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aß42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aß42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aß pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aß pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aß pathology. Fibrinogen was associated with both cognition and Aß pathology. Aß pathology may be a critical mediator for impacts of fibrinogen on cognition.
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As electrocatalysts, molecular catalysts with large aromatic systems (such as terpyridine, porphyrin, or phthalocyanine) have been widely applied in the CO2 reduction reaction (CO2RR). However, these monomeric catalysts tend to aggregate due to strong π-π interactions, resulting in limited accessibility of the active site. In light of these challenges, we present a novel strategy of active site isolation for enhancing the CO2RR. Six Ru(Tpy)2 were integrated into the skeleton of a metallo-organic supramolecule by stepwise self-assembly in order to form a rhombus-fused six-pointed star R1 with active site isolation. The turnover frequency (TOF) of R1 was as high as 10.73 s-1 at -0.6 V versus reversible hydrogen electrode (vs RHE), which is the best reported value so far at the same potential to our knowledge. Furthermore, by increasing the connector density on R1's skeleton, a more stable triangle-fused six-pointed star T1 was successfully synthesized. T1 exhibits exceptional stability up to 126 h at -0.4 V vs RHE and excellent TOF values of CO. The strategy of active site isolation and connector density increment significantly enhanced the catalytic activity by increasing the exposure of the active site. This work provides a starting point for the design of molecular catalysts and facilitates the development of a new generation of catalysts with a high catalytic performance.
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BACKGROUND: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic 'second-hit' variants. METHODS: To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to aggregate structural variants present in <1% of 100kGP participants. Small variants were assessed using population allele frequency data and SpliceAI. Literature searches and publicly available online tools were used for further annotation of pathogenicity. RESULTS: Using these strategies, 8/31 cases were solved, increasing the overall diagnostic yield of this cohort from 10/41 (24.4%) to 18/41 (43.9%). Exemplar cases include a patient with cystic fibrosis harbouring a novel exonic LINE1 insertion in CFTR and a patient with generalised arterial calcification of infancy with complex interlinked duplications involving exons 2-6 of ENPP1. Although ambiguous by short-read WGS, the ENPP1 variant structure was resolved using optical genome mapping and RNA analysis. CONCLUSION: Systematic examination of cryptic variants across a multi-disease cohort successfully identifies additional pathogenic variants. WGS data analysis in autosomal recessive rare disease should consider complex structural and small intronic variants as potentially pathogenic second hits.
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Doenças Raras , Humanos , Mutação/genética , Sequência de Bases , Éxons , Mapeamento CromossômicoRESUMO
BACKGROUND: Anti-synthetase syndrome (AS) is a rare autoimmune idiopathic inflammatory myopathy (IIM) with diverse manifestations, including arthritis, interstitial lung disease (ILD), Raynaud's phenomenon, unexplained persistent fever, and mechanic's hands. CASE PRESENTATION: We present the case of a 72-year-old woman, previously healthy, who was admitted to our hospital for treatment of cough and rapid breathing. The patient had elevated white blood cells and C-reactive protein, and tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). She was initially diagnosed with community-acquired pneumonia and received tamoxifen for anti-infection treatment, but her dystonia worsened. She eventually required non-invasive ventilator support, tested positive for SARS-Cov-2 again, and started antiviral therapy, corticosteroids to reduce alveolar effusion, anticoagulation, and other treatments. However, her condition continued to deteriorate, with the lowest oxygenation index reaching only 80mmHg. Ultimately, she underwent tracheal intubation and mechanical ventilation. Chest CT revealed rapid progressive interstitial changes in her lungs, and her hands showed noticeable fraternization changes. At this point, we suspected that the novel coronavirus infection might be associated with autoimmune diseases. The patient's autoimmune antibody spectrum showed positive results for anti-recombinant RO-52 antibody and myositis-specific antibody anti-alanyl tRNA synthetase (anti-PL-12). The patient was treated with dexamethasone sodium phosphate for anti-inflammatory and anti-fibrotic effects. After successful extubation, the patient was discharged with only oral prednisone tablets at a dose of 30 mg. CONCLUSIONS: This case presents an early diagnosis and successful treatment of anti-synthetase syndrome combined with SARS-Cov-2 infection, emphasizing the importance of comprehensive physical examination. Additionally, it highlights the rapid progression of interstitial lung disease under SARS-Cov-2 infection, which is often difficult to distinguish on imaging. In cases where treatment for SARS-Cov-2 infection is ineffective, early screening for autoimmune diseases is recommended. As there is currently no standardized method for treating AS-ILD, the successful treatment of this case provides a reference for clinical research on anti-synthetase syndrome in the later stage.
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Doenças Autoimunes , COVID-19 , Doenças Pulmonares Intersticiais , Miosite , Humanos , Feminino , Idoso , COVID-19/complicações , SARS-CoV-2 , Miosite/complicações , Miosite/diagnóstico , Miosite/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Autoimunes/complicações , AutoanticorposRESUMO
Lysine-specific peptide and protein modification strategies are widely used to study charge-related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge-related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge-related protein properties, such as liquid-liquid phase separation behaviour of α-synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine-containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins.
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Hidroxilamina , Lisina , Lisina/química , Hidroxilamina/química , Proteínas/química , Amidinas/química , alfa-Sinucleína/química , Peptídeos/químicaRESUMO
Deep red/near-infrared (NIR, >650â nm) emissive organic luminophores with aggregation-induced emission (AIE) behaviours have emerged as promising candidates for applications in optoelectronic devices and biological fields. However, the molecular design philosophy for AIE luminogens (AIEgens) with narrow band gaps are rarely explored. Herein, we rationally designed two red organic luminophores, FITPA and FIMPA, by considering the enlargement of transition dipole moment in the charge-transfer state and the transformation from aggregation-caused quenching (ACQ) to AIE. The transition dipole moments were effectively enhanced with a "V-shaped" molecular configuration. Meanwhile, the ACQ-to-AIE transformation from FITPA to FIMPA was induced by a methoxy-substitution strategy. The experimental and theoretical results demonstrated that the ACQ-to-AIE transformation originated from a crystallization-induced emission (CIE) effect because of additional weak interactions in the aggregate state introduced by methoxy groups. Owing to the enhanced transition dipole moment and AIE behaviour, FIMPA presented intense luminescence covering the red-to-NIR region, with a photoluminescence quantum yield (PLQY) of up to 38 % in solid state. The promising cell-imaging performance further verified the great potential of FIMPA in biological applications. These results provide a guideline for the development of red and NIR AIEgens through comprehensive consideration of both the effect of molecular structure and molecular interactions in aggregate states.
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Considering the fact that site-selective late-stage diversification of peptides and proteins remains a challenge for biochemistry, strategies targeting low-abundance natural amino acids need to be further developed. As an extremely oxidation-sensitive and low-abundance amino acid, methionine emerges as a promising target for chemo- and site-selective modification. Herein we report an efficient and highly selective modification on methionine residues by one-pot O- and N-transfer reaction, generating sulfoximine-modified peptides with near-perfect conversion within 10 min. Moreover, the great tolerance to other natural amino acids has been demonstrated in reactions with various peptide substrates. To demonstrate the generality of this protocol, we have modified natural peptides and obtained sulfoximination products with high conversion rates. This methodology provides a novel strategy as the expansion of the methionine-based peptide functionalization toolbox.
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Metionina , Proteínas , Metionina/química , Metionina/metabolismo , Proteínas/química , Peptídeos/química , Racemetionina/metabolismo , Estresse OxidativoRESUMO
BACKGROUND Circulating calcium mainly carries out its physiologic function in its ionized form (iCa). Clinically, iCa is usually estimated by multiplying the total calcium (TCa) level by 0.5 in the general population, but this method is not accurate when applied to patients on long-term hemodialysis (CHD). Accordingly, this study aimed to develop a predictive function for iCa in patients on CHD by incorporating TCa and other additional variables. MATERIAL AND METHODS This was a retrospective cross-sectional study consisting of 2 cross-sectional datasets: a derivation set including 469 CHD patients in June 2019, and a validation set including 446 CHD patients in September 2019. The derivation set's data were analyzed using the stepwise model selection of machine learning with 10-fold cross-validation to develop a predictive function for iCa. This predictive function was then applied to the validation set's data, and the predictive function's estimated iCa was compared with the actual laboratory iCa by using the paired-samples t test and intraclass correlation coefficient. RESULTS After analyzing the routine laboratory data parameters of patients in the derivation set, the following 5 variables were included in the predictive function of iCa: blood urea nitrogen, creatinine, phosphate, TCa, and albumin. This predictive function was applied to the validation set to yield an estimated iCa level that was not significantly different from the laboratory-measured iCa level of the validation dataset (P=0.676) with an excellent ICC of 0.905. CONCLUSIONS We developed a new predictive function that accurately measures the iCa in patients on CHD by using routine laboratory data.
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Cálcio , Hipercalcemia , Diálise Renal , Insuficiência Renal Crônica , Humanos , Cálcio/sangue , Estudos Transversais , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapiaRESUMO
BACKGROUND Hyperparathyroidism poses significant risks for patients prior to kidney transplantation. However, the outcomes of patients who undergo parathyroidectomy before renal transplantation compared to those without such a procedure remain uncertain. This real-world data study aimed to examine the clinical outcomes of both patient groups. MATERIAL AND METHODS Using the Taiwan National Health Insurance Research Database, we conducted a retrospective cohort study on patients who underwent renal transplantation between January 2005 and December 2015. The patients were divided into two groups: a case group (n=294) with parathyroidectomy and a control group (n=588) without the need for parathyroidectomy before kidney transplantation. The groups were matched based on age, sex, dialysis vintage, and baseline characteristics at a 1:2 ratio. Hazard ratios (HR) were estimated using the Cox regression model. The main outcomes assessed were graft failure, mortality, and major adverse cardiovascular events (MACE) recorded until December 2019. RESULTS During a mean follow-up period of 6 years, a significant difference was observed in graft failure (HR 1.40; 95% confidence interval 1.10-1.79, p=0.007) between the two groups. After further adjustment, graft failure remained significant (HR 1.52; 95% CI 1.07-2.15, p=0.019). Additionally, machine learning-based feature selection identified the importance of parathyroidectomy (ranked 9 out of 11) before kidney transplantation in predicting subsequent graft failure. CONCLUSIONS Our study demonstrates that severe hyperparathyroidism requiring parathyroidectomy before kidney transplantation may contribute to poor post-transplant graft outcomes compared to patients who do not require parathyroidectomy.
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Hiperparatireoidismo , Transplante de Rim , Humanos , Transplante de Rim/métodos , Estudos Retrospectivos , Paratireoidectomia/efeitos adversos , Hiperparatireoidismo/cirurgia , Hiperparatireoidismo/etiologia , Diálise Renal , Sobrevivência de EnxertoRESUMO
INTRODUCTION: To examine the extent to which positron emission tomography (PET)-, cerebrospinal fluid (CSF)-, and plasma-related amyloid-ß/tau/neurodegeneration (A/T/N) biomarkers are associated with Alzheimer's disease (AD) neuropathology at autopsy. METHODS: A total of 100 participants who respectively underwent antemortem biomarker measurements and postmortem neuropathology were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined the associations of PET-, CSF-, and plasma-related A/T/N biomarkers in combinations or alone with AD neuropathological changes (ADNC). RESULTS: PET- and CSF-related A/T/N biomarkers in combination showed high concordance with the ADNC stage and alone showed high accuracy in discriminating autopsy-confirmed AD. However, the plasma-related A/T/N biomarkers alone showed better discriminative performance only when combined with apolipoprotein E (APO)E ε4 genotype. DISCUSSION: This study supports that PET- and CSF-related A/T/N profiles can be used to predict accurately the stages of AD neuropathology. For diagnostic settings, PET-, CSF-, and plasma-related A/T/N biomarkers are all useful diagnostic tools to detect the presence of AD neuropathology. HIGHLIGHTS: PET- and CSF-related A/T/N biomarkers in combination can accurately predict the specific stages of AD neuropathology. PET- and CSF-related A/T/N biomarkers alone may serve as a precise diagnostic tool for detecting AD neuropathology at autopsy. Plasma-related A/T/N biomarkers may need combined risk factors when used as a diagnostic tool. Aß PET and CSF p-tau181/Aß42 were most consistent with Aß pathology, while tau PET and CSF p-tau181/Aß42 were most consistent with tau pathology.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Autopsia , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Biomarcadores/líquido cefalorraquidianoRESUMO
INTRODUCTION: This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late clinical stages. METHODS: We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non-dementia and dementia, as early or late clinical stages. RESULTS: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aß)42/phosphorylated tau (p-tau)181 showed excellent performance in differentiating autopsy-confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aß42 performed better in the early clinical stage, while CSF p-tau181, CSF t-tau, and plasma p-tau181 performed better in the late clinical stage. DISCUSSION: Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD. HIGHLIGHTS: Amyloid PET and CSF Aß42/p-tau181 were the most promising candidate biomarkers for predicting AD pathology. CSF Aß42 can serve as a candidate predictive biomarker in the early clinical stage of AD. CSF p-tau181, CSF t-tau, and plasma p-tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD. Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD-related biomarkers for AD pathology.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Autopsia , Proteínas tau/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidianoRESUMO
Defects in perovskite are key factors in limiting the photovoltaic performance and stability of perovskite solar cells (PSCs). Generally, choline halide (ChX) can effectively passivate defects by binding with charged point defects of perovskite. However, we verified that ChI can react with CsPbI3 to form a novel crystal phase of one-dimensional (1D) ChPbI3 , which constructs 1D/3D heterostructure with 3D CsPbI3 , passivating the defects of CsPbI3 more effectively and then resulting in significantly improved photoluminescence lifetime from 20.2â ns to 49.4â ns. Moreover, the outstanding chemical inertness of 1D ChPbI3 and the repair of undesired δ-CsPbI3 deficiency during its formation process can significantly enhance the stability of CsPbI3 film. Benefiting from 1D/3D heterostructure, CsPbI3 carbon-based PSCs (C-PSCs) delivered a champion efficiency of 18.05 % and a new certified record of 17.8 % in hole transport material (HTM)-free inorganic C-PSCs.
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Compostos de Cálcio , Carbono , Colina , ÓxidosRESUMO
To better exploit all-liquid 3D architectures, it is essential to understand dynamic processes that occur during printing one liquid in a second immiscible liquid. Here, the interfacial assembly and transition of 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (H6 TPPS) over time provides an opportunity to monitor the interfacial behavior of nanoparticle surfactants (NPSs) during all-liquid printing. The formation of J-aggregates of H4 TPPS2- at the interface and the interfacial conversion of the J-aggregates of H4 TPPS2- to H-aggregates of H2 TPPS4- is demonstrated by interfacial rheology and in situ atomic force microscopy. Equally important are the chromogenic changes that are characteristic of the state of aggregation, where J-aggregates are green in color and H-aggregates are red in color. In all-liquid 3D printed structures, the conversion in the aggregate state with time is reflected in a spatially varying change in the color, providing a simple, direct means of assessing the aggregation state of the molecules and the mechanical properties of the assemblies, linking a macroscopic observable (color) to mechanical properties.
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Porfirinas , Porfirinas/química , Reologia , Tensoativos/químicaRESUMO
In response to rapidly changing societal conditions stemming from the COVID-19 pandemic, we summarize data sources with potential to produce timely and spatially granular measures of physical, economic, and social conditions relevant to public health surveillance, and we briefly describe emerging analytic methods to improve small-area estimation. To inform this article, we reviewed published systematic review articles set in the United States from 2015 to 2020 and conducted unstructured interviews with senior content experts in public heath practice, academia, and industry. We identified a modest number of data sources with high potential for generating timely and spatially granular measures of physical, economic, and social determinants of health. We also summarized modeling and machine-learning techniques useful to support development of time-sensitive surveillance measures that may be critical for responding to future major events such as the COVID-19 pandemic. (Am J Public Health. 2022;112(10):1436-1445. https://doi.org/10.2105/AJPH.2022.306917).
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COVID-19 , COVID-19/epidemiologia , Previsões , Humanos , Pandemias , Saúde Pública , Vigilância em Saúde Pública , Condições Sociais , Revisões Sistemáticas como Assunto , Estados Unidos/epidemiologiaRESUMO
Titanium metal-organic frameworks (Ti-MOFs), as an appealing type of artificial photocatalyst, have shown great potential in the field of solar energy conversion due to their well-studied photoredox activity (similar to TiO2 ) and good optical responsiveness of linkers, which serve as the antenna to absorb visible-light. Although much effort has been dedicated to developing Ti-MOFs with high photocatalytic activity, their solar energy conversion performances are still poor. Herein, we have implemented a covalent-integration strategy to construct a series of multivariate Ti-MOF/COF hybrid materials PdTCPPâPCN-415(NH2 )/TpPa (composites 1, 2, and 3), featuring excellent visible-light utilization, a suitable band gap, and high surface area for photocatalytic H2 production. Notably, the resulting composites demonstrated remarkably enhanced visible-light-driven photocatalytic H2 evolution performance, especially for the composite 2 with a maximum H2 evolution rate of 13.98â mmol g-1 h-1 (turnover frequency (TOF)=227â h-1 ), which is much higher than that of PdTCPPâPCN-415(NH2 ) (0.21â mmol g-1 h-1 ) and TpPa (6.51â mmol g-1 h-1 ). Our work thereby suggests a new approach to highly efficient photocatalysts for H2 evolution and beyond.
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PURPOSE: Genome sequencing (GS) for diagnosis of rare genetic disease is being introduced into the clinic, but the complexity of the data poses challenges for developing pipelines with high diagnostic sensitivity. We evaluated the performance of the Genomics England 100,000 Genomes Project (100kGP) panel-based pipelines, using craniosynostosis as a test disease. METHODS: GS data from 114 probands with craniosynostosis and their relatives (314 samples), negative on routine genetic testing, were scrutinized by a specialized research team, and diagnoses compared with those made by 100kGP. RESULTS: Sixteen likely pathogenic/pathogenic variants were identified by 100kGP. Eighteen additional likely pathogenic/pathogenic variants were identified by the research team, indicating that for craniosynostosis, 100kGP panels had a diagnostic sensitivity of only 47%. Measures that could have augmented diagnoses were improved calling of existing panel genes (+18% sensitivity), review of updated panels (+12%), comprehensive analysis of de novo small variants (+29%), and copy-number/structural variants (+9%). Recent NHS England recommendations that partially incorporate these measures should achieve 85% overall sensitivity (+38%). CONCLUSION: GS identified likely pathogenic/pathogenic variants in 29.8% of previously undiagnosed patients with craniosynostosis. This demonstrates the value of research analysis and the importance of continually improving algorithms to maximize the potential of clinical GS.
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Craniossinostoses , Testes Genéticos , Sequência de Bases , Mapeamento Cromossômico , Craniossinostoses/diagnóstico , Craniossinostoses/genética , Humanos , Doenças Raras/genéticaRESUMO
Aggregation-induced emission (AIE) provides a new opportunity to overcome the drawbacks of traditional aggregation-induced quenching of chromophores. The applications of AIE-active fluorophores have spread across various fields. In particular, the employment of AIEgens in drug delivery systems (DDSs) can achieve imaging-guided therapy and pharmacodynamic monitoring. As a result, polymeric AIE-active DDSs are attracting increasing attention due to their obvious advantages, including easy fabrication and tunable optical properties by molecular design. Additionally, the design of polymeric AIE-active DDSs is a promising method for cancer therapy, antibacterial treatment, and pharmacodynamic monitoring, which indeed helps improve the effectiveness of related disease treatments and confirms its potential social importance. Here, we summarize the current available polymeric AIE-active DDSs from design to applications. In the design section, we introduce synthetic strategies and structures of AIE-active polymers, as well as responsive strategies for specific drug delivery. In the application section, typical polymeric AIE-active DDSs used for cancer therapy, bacterial treatment, and drug delivery monitoring are summarized with selected examples to elaborate on their wide applications.
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Antibacterianos/administração & dosagem , Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Infecções Bacterianas/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Fluorescência , Humanos , Neoplasias/tratamento farmacológicoRESUMO
Chemical protein modifications facilitate the investigation of natural posttranslational protein modifications and allow the design of proteins with new functions. Proteins can be modified at a late stage on amino acid side chains by chemical methods. The indole moiety of tryptophan residues is an emerging target of such chemical modification strategies because of its unique reactivity and low abundance. This review provides an overview of the recently developed methods of tryptophan modification at the peptide and protein levels.