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1.
Proc Natl Acad Sci U S A ; 120(29): e2213824120, 2023 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-37428923

RESUMEN

Cohn et al. (2019) conducted a wallet drop experiment in 40 countries to measure "civic honesty around the globe," which has received worldwide attention but also sparked controversies over using the email response rate as the sole metric of civic honesty. Relying on the lone measurement may overlook cultural differences in behaviors that demonstrate civic honesty. To investigate this issue, we conducted an extended replication study in China, utilizing email response and wallet recovery to assess civic honesty. We found a significantly higher level of civic honesty in China, as measured by the wallet recovery rate, than reported in the original study, while email response rates remained similar. To resolve the divergent results, we introduce a cultural dimension, individualism versus collectivism, to study civic honesty across diverse cultures. We hypothesize that cultural differences in individualism and collectivism could influence how individuals prioritize actions when handling a lost wallet, such as contacting the wallet owner or safeguarding the wallet. In reanalyzing Cohn et al.'s data, we found that email response rates were inversely related to collectivism indices at the country level. However, our replication study in China demonstrated that the likelihood of wallet recovery was positively correlated with collectivism indicators at the provincial level. Consequently, relying solely on email response rates to gauge civic honesty in cross-country comparisons may neglect the vital individualism versus collectivism dimension. Our study not only helps reconcile the controversy surrounding Cohn et al.'s influential field experiment but also furnishes a fresh cultural perspective to evaluate civic honesty.


Asunto(s)
Individualidad , Humanos , China
2.
Am J Hum Genet ; 109(4): 571-586, 2022 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-35240055

RESUMEN

TIAM Rac1-associated GEF 1 (TIAM1) regulates RAC1 signaling pathways that affect the control of neuronal morphogenesis and neurite outgrowth by modulating the actin cytoskeletal network. To date, TIAM1 has not been associated with a Mendelian disorder. Here, we describe five individuals with bi-allelic TIAM1 missense variants who have developmental delay, intellectual disability, speech delay, and seizures. Bioinformatic analyses demonstrate that these variants are rare and likely pathogenic. We found that the Drosophila ortholog of TIAM1, still life (sif), is expressed in larval and adult central nervous system (CNS) and is mainly expressed in a subset of neurons, but not in glia. Loss of sif reduces the survival rate, and the surviving adults exhibit climbing defects, are prone to severe seizures, and have a short lifespan. The TIAM1 reference (Ref) cDNA partially rescues the sif loss-of-function (LoF) phenotypes. We also assessed the function associated with three TIAM1 variants carried by two of the probands and compared them to the TIAM1 Ref cDNA function in vivo. TIAM1 p.Arg23Cys has reduced rescue ability when compared to TIAM1 Ref, suggesting that it is a partial LoF variant. In ectopic expression studies, both wild-type sif and TIAM1 Ref are toxic, whereas the three variants (p.Leu862Phe, p.Arg23Cys, and p.Gly328Val) show reduced toxicity, suggesting that they are partial LoF variants. In summary, we provide evidence that sif is important for appropriate neural function and that TIAM1 variants observed in the probands are disruptive, thus implicating loss of TIAM1 in neurological phenotypes in humans.


Asunto(s)
Discapacidad Intelectual , Alelos , Animales , Niño , ADN Complementario , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Drosophila/genética , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Fenotipo , Convulsiones/genética , Proteína 1 de Invasión e Inducción de Metástasis del Linfoma-T/genética
3.
Chemistry ; : e202401911, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079912

RESUMEN

In the realm of biological macromolecules, entities such as nucleic acids and proteins are distinguished by their homochirality, consistently defined chain lengths, and integral sequence-dependent functionalities. Historically, these refined attributes have eluded traditional synthetic polymers, which often exhibit wide variabilities in chain lengths, limited batch-to-batch reproducibility, and stochastic monomer arrangements. Bridging this divide represents a pivotal challenge within the domain of polymer science-a challenge that the burgeoning discipline of precision polymer chemistry is poised to address. Recent advancements have yielded precision polymers that boast prescribed monomer sequences and narrow molecular weight distributions, heralding a new era for developing model systems to decipher structure-property correlations within functional polymers, analogous to those within biological matrices. This review discusses the innovative liquid-phase and solid-phase synthesis techniques for creating precision polymers and the advanced characterization tools essential for dissecting their structure and properties. We highlight potential applications in self-assembly, catalysis, data storage, imaging, and therapy, and provide insights into the future challenges and directions of precision polymers.

4.
Biomacromolecules ; 25(9): 5402-5416, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39105715

RESUMEN

Peptides and polypeptides feature a variety of active functional groups on their side chains (including carboxylic acid, hydroxyl, amino, and thiol groups), enabling diverse chemical modifications. This versatility makes them highly valuable in stimuli-responsive systems. Notably, pH-responsive peptides and polypeptides, due to their ability to respond to pH changes, hold significant promise for applications in cellular pathology and tumor targeting. Extensive researches have highlighted the potentials of low pH insertion peptides (pHLIPs), peptide-drug conjugates (PDCs), and antibody-drug conjugates (ADCs) in biomedicine. Peptide self-assemblies, with their structural stability, ease of regulation, excellent biocompatibility, and biodegradability, offer immense potentials in the development of novel materials and biomedical applications. We also explore specific examples of their applications in drug delivery, tumor targeting, and tissue engineering, while discussing future challenges and potential advancements in the field of pH-responsive self-assembling peptide-based biomaterials.


Asunto(s)
Sistemas de Liberación de Medicamentos , Péptidos , Concentración de Iones de Hidrógeno , Péptidos/química , Humanos , Sistemas de Liberación de Medicamentos/métodos , Materiales Biocompatibles/química , Ingeniería de Tejidos/métodos , Animales , Neoplasias/tratamiento farmacológico , Inmunoconjugados/química
5.
Biomacromolecules ; 25(9): 5454-5467, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39196319

RESUMEN

The fundamental building block of living organisms is the cell, which is the universal biological base of all living entities. This micrometric mass of cytoplasm and the membrane border have fascinated scientists due to the highly complex and multicompartmentalized structure. This specific organization enables numerous metabolic reactions to occur simultaneously and in segregated spaces, without disturbing each other, but with a promotion of inter- and intracellular communication of biomolecules. At present, artificial nano- and microcompartments, whether as single components or self-organized in multicompartment architectures, hold significant value in the study of life development and advanced functional materials and in the fabrication of molecular devices for medical applications. These artificial compartments also possess the properties to encapsulate, protect, and control the release of bio(macro)molecules through selective transport processes, and they are capable of embedding or being connected with other types of compartments. The self-assembly mechanism of specific synthetic compartments and thus the fabrication of a simulated organelle membrane are some of the major aspects to gain insight. Considerable efforts have now been devoted to design various nano- and microcompartments and understand their functionality for precise control over properties. Of particular interest is the use of polymeric vesicles for communication in synthetic cells and colloidal systems to reinitiate chemical and biological communication and thus close the gap toward biological functions. Multicompartment systems can now be effectively created with a high level of hierarchical control. In this way, these structures can not only be explored to deepen our understanding of the functional organization of living cells, but also pave the way for many more exciting developments in the biomedical field.


Asunto(s)
Células Artificiales , Polímeros , Células Artificiales/química , Células Artificiales/metabolismo , Polímeros/química , Humanos
6.
Macromol Rapid Commun ; 45(4): e2300566, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37931779

RESUMEN

Donor-acceptor (D-A) conjugated polymer (CP) featuring high charge mobility and widely tunable energy bands have shown promising prospects in photocatalysis. In this work, a library of ternary D-A CPs (22 polymers) based on benzothiadiazole, bithiophene, and fluorene derivatives (i.e., fluorene [Fl], 9,9-dihexylfluorene [HF], and 9,9'-spirobifluorene [SF]) with and without alkyl side chains, and with 3D geometry are designed and synthesized via atom-economical direct C-H arylation polymerization to explore the synergetic effects of stereochemistry, D/A ratio, and alkyl chains on the properties and photocatalytic performances, which reveal that 1) the cross-shaped 3D spirobifluorene (SF) building block shows the highest hydrogen evolution rates (HER) owing to the sufficient photocatalytic active sites exposed, 2) the alkyl-free linear polymer (FlBtBT0.05 ) exhibit the highest photocatalytic pollutant degradation performance owing to its superior charge separation, and 3) the alkyl side chains are redundances that will exert detrimental effects on the aqueous photocatalysis owing to their insulating and hydrophobic property. The structure-property-performance correlation results obtained will provide a desirable guideline for the rational design of CP-based photocatalysts.


Asunto(s)
Contaminantes Ambientales , Fluorenos , Hidrógeno , Polimerizacion , Polímeros
7.
Molecules ; 29(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38474617

RESUMEN

Conjugated polymers (CPs) have attracted much attention in recent years due to their structural abundance and tunable energy bands. Compared with CP-based materials, the inorganic semiconductor TiO2 has the advantages of low cost, non-toxicity and high photocatalytic hydrogen production (PHP) performance. However, studies on polymeric-inorganic heterojunctions, composed of D-A type CPs and TiO2, for boosting the PHP efficiency are still rare. Herein, an elucidation that the photocatalytic hydrogen evolution activity can actually be improved by forming polymeric-inorganic heterojunctions TFl@TiO2, TS@TiO2 and TSO2@TiO2, facilely synthesized through efficient in situ direct C-H arylation polymerization, is given. The compatible energy levels between virgin TiO2 and polymeric semiconductors enable the resulting functionalized CP@TiO2 heterojunctions to exhibit a considerable photocatalytic hydrogen evolution rate (HER). Especially, the HER of TSO2@TiO2 heterojunction reaches up to 11,220 µmol g-1 h-1, approximately 5.47 and 1260 times higher than that of pristine TSO2 and TiO2 photocatalysts. The intrinsic merits of a donor-acceptor conjugated polymer and the interfacial interaction between CP and TiO2 account for the excellent PHP activity, facilitating the separation of photo-generated excitons. Considering the outstanding PHP behavior, our work discloses that the coupling of inorganic semiconductors and suitable D-A conjugated CPs would play significant roles in the photocatalysis community.

8.
Molecules ; 29(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39275079

RESUMEN

Three small donor molecule materials (S1, S2, S3) based on dithiophene [2,3-d:2',3'-d']dithiophene [1,2-b:4,5-b']dithiophene (DTBDT) utilized in this study were synthesized using the Vilsmeier-Haack reaction, traditional Stille coupling, and Knoevenagel condensation. Then, a variety of characterization methods were applied to study the differences in optical properties and photovoltaic devices among the three. By synthesizing S2 using a thiophene π-bridge based on S1, the blue shift in ultraviolet absorption can be enhanced, the band gap and energy level can be reduced, the open circuit voltage (VOC) can be increased to 0.75 V using the S2:Y6 device, and a power conversion efficiency (PCE) of 3% can be achieved. Also, after developing the device using Y6, S3 introduced the alkyl chain of thiophene π-bridge to S2, which improved the solubility of tiny donor molecules, achieved the maximum short-circuit current (JSC = 10.59 mA/cm2), filling factor (FF = 49.72%), and PCE (4.25%). Thus, a viable option for future design and synthesis of small donor molecule materials is to incorporate thiophene π-bridges into these materials, along with alkyl chains, in order to enhance the device's morphology and charge transfer behavior.

9.
Angew Chem Int Ed Engl ; 63(6): e202313370, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37875462

RESUMEN

Precise sequence-defined polymers (SDPs) with uniform chain-to-chain structure including chain length, unit sequence, and end functionalities represent the pinnacle of sophistication in the realm of polymer science. For example, the absolute control over the unit sequence of SDPs allows for the bottom-up design of polymers with hierarchical microstructures and functions. Accompanied with the development of synthetic techniques towards precision SDPs, the decoding of SDP sequences and construction of advanced functions irreplaceable by other synthetic materials is of central importance. In this Minireview, we focus on recent advances in SDP sequencing techniques including tandem mass spectrometry (MS), chemically assisted primary MS, as well as other non-destructive sequencing methods such as nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and nanopore sequencing. Additionally, we delve into the promising prospects of SDP functions in the area of cutting-edge biological research. Topics of exploration include gene delivery systems, the development of hybrid materials combining SDPs and nucleic acids, protein recognition and regulation, as well as the interplay between chirality and biological functions. A brief outlook towards the future directions of SDPs is also presented.


Asunto(s)
Polímeros , Proteínas , Polímeros/química , Proteínas/química , Espectrometría de Masas en Tándem
10.
Angew Chem Int Ed Engl ; : e202409981, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037730

RESUMEN

Mediated electron transfer (MET) is fundamental to many biological functions, including cellular respiration, photosynthesis, and enzymatic catalysis. However, leveraging the MET process to enable the release of therapeutic gases has been largely unexplored. Herein, we report the bio-inspired activation of a series of UV-absorbing N-nitrosamide derivatives (NOA) under red light exposure, enabling the quantitative release of nitric oxide (NO) gasotransmitter via an MET process. The cornerstone of our design is the covalent linkage of a 2,4-dinitroaniline moiety, which acts as an electron mediator to the N-nitrosamide groups. This facilitates efficient electron transfer from the excited palladium(II) meso-tetraphenyltetrabenzoporphyrin (PdTPTBP) photocatalyst and the selective activation of NOA. Our approach has been validated with distinct photocatalysts and various N-nitrosamides, including those derived from carbamates, amides, and ureas. Notably, the modulation of the linker length between the electron mediator and N-nitrosamide groups serves as a regulatory mechanism for controlling NO release kinetics. Moreover, this biomimetic NO release platform demonstrates effective operation under both normoxic and hypoxic conditions, and it enables localized delivery of NO under physiological conditions, exhibiting significant anticancer efficacy within the phototherapeutic window and enhanced selectivity towards tumor cells.

11.
Angew Chem Int Ed Engl ; : e202415588, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305234

RESUMEN

Electron beam (EB) and extreme ultraviolet (EUV) lithography are advanced techniques capable of achieving sub-10 nm resolutions, critical for fabricating next-generation nanostructures and semiconductor devices. However, developing EUV photoresists that meet all demands for resolution, line edge roughness (LER), and sensitivity (RLS) remains a significant challenge. Herein, we introduce high-performance photoresists based on single-component self-immolative polymers (SIPs) with inherent signal amplification via cascade degradation. These SIPs function as dual-tone photoresists under both EB and EUV lithography, with performance primarily determined by the exposure dose. Lithographic evaluations show that discrete SIPs provide significant improvements over disperse counterparts, achieving higher resolution and reduced LER. Specifically, a discrete SIP with a DP of 12 produces a line-space pattern with a resolution of approximately 18 nm and an LER of 1.8 nm, compared to 21 nm resolution and 2.5 nm LER for disperse SIPs. Additionally, these SIP-based photoresists, enriched with aromatic structures, exhibit excellent etch resistance. The single-component nature and potential to address the RLS trade-off underscore the promise of discrete SIPs for EUV lithography.

12.
Angew Chem Int Ed Engl ; 63(24): e202405314, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38602843

RESUMEN

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5 M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5 M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

13.
Proteins ; 91(9): 1245-1253, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37186412

RESUMEN

Understanding the process of protein-RNA interaction is essential for structural biology. The thermodynamic process is an important part to uncover the protein-RNA interaction mechanism. The regulatory networks between protein and RNA in organisms are dominated by the binding or dissociation in the cells. Therefore, determining the binding affinity for protein-RNA complexes can help us to understand the regulation mechanism of protein-RNA interaction. Since it is time-consuming and labor-intensive to determine the binding affinity for protein-RNA complexes by experimental methods, it is necessary and urgent to develop computational methods to predict that. To develop a binding affinity prediction model, first we update the dataset of protein-RNA binding affinity benchmark (PRBAB), which includes 145 complexes now. Second, we extract the structural features based on complex structure, and then we analyze and select the representative structural features to train the regression model. Third, we random select the subset from the PRBAB2.0 to fit the protein-RNA binding affinity determined by experiment. In the end, we tested our model on the nonredundant PDBbind dataset, and the results showed that Pearson correlation coefficient r = .57 and RMSE = 2.51 kcal/mol. The Pearson correlation coefficient achieves 0.7 while removing 5 complex structures with modified residues/nucleotides and metal ions. While testing on ProNAB, the results showed that 71.60% of the prediction achieves Pearson correlation coefficient r = .61 and RMSE = 1.56 kcal/mol with experiment values.


Asunto(s)
Benchmarking , Nucleótidos , ARN , Proyectos de Investigación , Termodinámica
14.
J Am Chem Soc ; 145(32): 17755-17766, 2023 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-37527404

RESUMEN

Precise activation of polymer nanoparticles at lesion sites is crucial to achieve favorable therapeutic efficacy. However, conventional endogenous stimuli-responsive polymer nanoparticles probably suffer from few triggers to stimulate the polymer degradation and subsequent functions. Here, we describe oxidation-responsive poly(ferrocene) amphiphiles containing phenylboronic acid ester and ferrocene as the repeating backbone units. Upon triggering by hydrogen peroxide inside the tumor cells, the phenylboronic acid ester bonds are broken and poly(ferrocene) units are degraded to afford free ferrocene and noticeable hydroxide ions. The released hydroxide ions can immediately improve the pH value within the poly(ferrocene) aggregates, and the degradation rate of the phenylboronic acid ester backbone is further promoted by the upregulated pH; thereupon, the accelerated degradation can release much more additional hydroxide ions to improve the pH, thus achieving a positive self-amplified cascade degradation of poly(ferrocene) aggregates accompanied by oxidative stress boosting and efficient cargo release. Specifically, the poly(ferrocene) aggregates can be degraded up to ∼90% within 12 h when triggered by H2O2, while ferrocene-free control nanoparticles are degraded by only 30% within 12 days. In addition, the maleimide moieties tethered in the hydrophilic corona can capture blood albumin to form an albumin-rich protein corona and significantly improve favorable tumor accumulation. The current oxidation-responsive poly(ferrocene) amphiphiles can efficiently inhibit tumors in vitro and in vivo. This work provides a proof-of-concept paradigm for self-amplified polymer degradation and concurrent oxidative stress, which is promising in actively regulated precision medicine.


Asunto(s)
Peróxido de Hidrógeno , Nanopartículas , Peróxido de Hidrógeno/química , Polímeros/farmacología , Polímeros/química , Estrés Oxidativo , Concentración de Iones de Hidrógeno , Albúminas , Ésteres , Nanopartículas/química
15.
J Am Chem Soc ; 145(42): 23176-23187, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37822292

RESUMEN

Polymeric nanoparticles (NPs) have been extensively designed for theranostic agent delivery. Previous methods for tracking their biological behavior and assessing theranostic efficacy heavily rely on fluorescence or isotope labeling. However, these labeling techniques may alter the physicochemical properties of the labeled NPs, leading to inaccurate biodistribution information. Therefore, it is highly desirable to develop label-free techniques for accurately assessing the biological fate of polymeric NPs. Here, we create discrete oligourethane amphiphiles (DOAs) with methoxy (OMe), hydroxyl (OH), and maleimide (MI) moieties at the dendritic oligo(ethylene glycol) (dOEG) ends. We obtained four types of digital nanorods (NRs) with distinct surface functional groups through self-assembly of a single DOA (OMe and OH NRs) or coassembly of two DOAs (OMe-MI and OH-MI NRs). These unique NRs can be directly quantified in a label-free manner by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Specifically, OMe-MI NRs exhibited the best blood circulation, and OH-MI showed the highest area under the curve (AUC) value after intravenous injection. Biodistribution studies demonstrated that MI-containing NRs generally had lower accumulation in the liver and spleen compared to that of MI-free NRs, except for the comparison between OMe and OMe-MI NRs in the liver. Proteomics studies unveiled the formation of distinct protein coronas that may greatly affect the biological behavior of NRs. This study not only provides a label-free technique for quantifying the pharmacokinetics and biodistribution of polymeric NRs but also highlights the significant impact of surface functional groups on the biological fate of polymeric NPs.


Asunto(s)
Nanopartículas , Nanotubos , Distribución Tisular , Nanotubos/química , Nanopartículas/química , Espectrometría de Masas
16.
BMC Med ; 21(1): 500, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110931

RESUMEN

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.


Asunto(s)
Epilepsia , Esclerosis Tuberosa , Humanos , Fluorodesoxiglucosa F18 , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/metabolismo , Reproducibilidad de los Resultados , Glucólisis , Estudios Retrospectivos
17.
Annu Rev Public Health ; 44: 55-74, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36626834

RESUMEN

Public health surveillance is defined as the ongoing, systematic collection, analysis, and interpretation of health data and is closely integrated with the timely dissemination of information that the public needs to know and upon which the public should act. Public health surveillance is central to modern public health practice by contributing data and information usually through a national notifiable disease reporting system (NNDRS). Although early identification and prediction of future disease trends may be technically feasible, more work is needed to improve accuracy so that policy makers can use these predictions to guide prevention and control efforts. In this article, we review the advantages and limitations of the current NNDRS in most countries, discuss some lessons learned about prevention and control from the first wave of COVID-19, and describe some technological innovations in public health surveillance, including geographic information systems (GIS), spatial modeling, artificial intelligence, information technology, data science, and the digital twin method. We conclude that the technology-driven innovative public health surveillance systems are expected to further improve the timeliness, completeness, and accuracy of case reporting during outbreaks and also enhance feedback and transparency, whereby all stakeholders should receive actionable information on control and be able to limit disease risk earlier than ever before.


Asunto(s)
COVID-19 , Vigilancia en Salud Pública , Humanos , Vigilancia en Salud Pública/métodos , Inteligencia Artificial , COVID-19/epidemiología , COVID-19/prevención & control , Sistemas de Información Geográfica , Medición de Riesgo , Vigilancia de la Población/métodos , Salud Pública
18.
Acc Chem Res ; 55(23): 3404-3416, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36351034

RESUMEN

In nature, cells are highly compartmentalized into many organelles that are well separated from the rest of the cellular space by unique membrane structures, which are of crucial importance to allow cells to perform various physiological functions in such a small and crowded space. Learning from the ubiquitous membrane structures of cells and organelles has continuously inspired the development of artificial self-assembled nanostructures, with lipid vesicles (liposomes) and polymer vesicles (polymersomes) being the most representative examples. Similar to the membrane-bound structures of cells and organelles, both liposomes and polymersomes contain an aqueous interior enclosed by a bilayer membrane. Therefore, liposomes and polymersomes have been extensively investigated to mimic the fundamental structures and functions of living cells. For example, liposomes and polymersomes have been successfully engineered as nanocarriers, smart nanoreactors, artificial organelles, and so on. Notably, living cells can exchange both energy and materials with surrounding environments, benefiting from the selective permeability of lipid membranes. The permselectivity of cell membranes is thus an essential attribute of living organisms. Compared to liposomes, polymersomes have increased structural stability but low membrane permeability. Indeed, polymersomes are almost impermeable to small molecules, ions, and even water molecules. To improve the permeability of polymersomes, much effort has been devoted to the incorporation of channel proteins, the coassembly of oppositely charged block copolymers (BCPs), the development of stimuli-responsive BCPs, and so on. Despite great achievements, these approaches generally lead to decreased stability of polymersomes and, sometimes, polymersome disintegration. In this Account, we discuss our recent efforts to reconcile the stability and permeability of polymersomes via a traceless cross-linking approach. Although cross-linking reactions within bilayer membranes generally lead to decreased permeability, the traceless cross-linking approach can concurrently improve the stability and permeability of polymersomes. Specifically, stimuli-responsive polymersomes undergo either covalent cross-linking or noncovalent cross-linking reactions under specific stimuli to increase bilayer stability, while the cross-linking processes can concurrently permeabilize polymersome bilayers through cross-linking-driven hydrophobic-to-hydrophilic transitions. Notably, unlike conventional cross-linking processes requiring additional cross-linkers, the traceless cross-linking process does not involve extra cross-linking agents but takes full advantage of the in situ generated active moieties. By taking advantage of the simultaneous modulation of the stability and permeability of polymersomes via traceless cross-linking, these polymersomes can be further engineered as smart nanocarriers and nanoreactors. The robustness and generality of this approach have been validated by both extracellular and intracellular stimuli such as light irradiation, glutathione, and hydrogen peroxide. Moreover, many functional groups such as fluorescent dyes and contrast agents can be integrated into this versatile platform as well, enabling the construction of theranostic nanovectors capable of responding to pathological microenvironments. This Account provides a new approach to regulating the permeability of polymersomes while maintaining their structural stability.


Asunto(s)
Liposomas , Nanoestructuras , Permeabilidad , Polímeros/química , Nanoestructuras/química , Agua , Lípidos
19.
Macromol Rapid Commun ; 44(23): e2300318, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37572085

RESUMEN

It is an urgent need to develop efficient solid state cooling technologies and materials with high cycle life. Poly-p-phenylene benzodioxole (PBO) is a high performance fiber with excellent mechanical properties. In this work, for the first time, elasto- and twistocaloric cooling of PBO fibers by stretching and twisting of the PBO fiber bundles is reported. The cooling temperature reaches -0.4 and -1.3 K, for fiber stretching and twisting, respectively. A self-coiled PBO fiber achieves maximum cooling of -3.7 K upon stretching by 35% strain, with an exceptionally high cycle life of 200 000 times. During the twisting of the PBO fibers, reversible changes in the intensity of the diffraction peaks in X-ray diffraction patterns are observed. A strain-sensitive color change application is realized by coating a self-coiled PBO fiber with liquid crystallite dyes. This work provides new perspectives for PBO fibers as a high cycle-life solid-state refrigeration material.


Asunto(s)
Cicloparafinas , Compuestos Heterocíclicos , Frío , Temperatura , Benzodioxoles
20.
Cereb Cortex ; 32(23): 5259-5272, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-35195262

RESUMEN

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults, with pathological mechanisms remaining to be fully elucidated. Fibroblast Growth Factor 13 (FGF13) encodes an intracellular protein involved in microtubule stabilization and regulation of voltage-gated sodium channels (VGSCs) function. FGF13 mutation has been identified in patients with inherent seizure, suggesting a potential association between FGF13 and the etiology of TLE. Here, we set to explore the pathological role of FGF13 in the etiology of TLE. RESULTS: We found that the expression of FGF13 was increased in the cortical lesions and CA1 region of sclerotic hippocampus and correlated with the seizure frequency in TLE patients. Also, Fgf13 expression was increased in the hippocampus of chronic TLE mice generated by kainic acid (KA) injection. Furthermore, Fgf13 knockdown or overexpression was respectively found to attenuate or potentiate the effects of KA on axonal length, somatic area and the VGSCs-mediated current in the hippocampal neurons. CONCLUSIONS: Taken together, these findings suggest that FGF13 is involved in the pathogenesis of TLE by modulating microtubule activity and neuronal excitability.


Asunto(s)
Epilepsia del Lóbulo Temporal , Factores de Crecimiento de Fibroblastos , Animales , Ratones , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/patología , Factores de Crecimiento de Fibroblastos/genética , Hipocampo/metabolismo , Ácido Kaínico , Convulsiones
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