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1.
Nat Commun ; 15(1): 3485, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664427

RESUMEN

Spider silk exhibits an excellent combination of high strength and toughness, which originates from the hierarchical self-assembled structure of spidroin during fiber spinning. In this work, superfine nanofibrils are established in polyelectrolyte artificial spider silk by optimizing the flexibility of polymer chains, which exhibits combination of breaking strength and toughness ranging from 1.83 GPa and 238 MJ m-3 to 0.53 GPa and 700 MJ m-3, respectively. This is achieved by introducing ions to control the dissociation of polymer chains and evaporation-induced self-assembly under external stress. In addition, the artificial spider silk possesses thermally-driven supercontraction ability. This work provides inspiration for the design of high-performance fiber materials.


Asunto(s)
Nanofibras , Polielectrolitos , Seda , Arañas , Animales , Nanofibras/química , Arañas/química , Seda/química , Polielectrolitos/química , Resistencia a la Tracción , Músculos , Materiales Biomiméticos/química
2.
Angew Chem Int Ed Engl ; : e202405314, 2024 Apr 11.
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 10-5M, 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 10-5M) 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.

3.
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.

4.
Chem Sci ; 15(13): 4757-4762, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38550678

RESUMEN

α-Keto-, ß-acetoxy- and ß-amidoalkylsilyl peroxides are prepared from various precursors and utilized for Fe-catalyzed and visible-light-promoted radical functionalization with coupling partners under mild conditions with a broad substrate scope.

5.
Histol Histopathol ; : 18707, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38293776

RESUMEN

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

6.
Adv Mater ; 36(9): e2309315, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37944553

RESUMEN

Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy)2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics.


Asunto(s)
Neoplasias , Semicarbazonas , Humanos , Neoplasias/tratamiento farmacológico , Semicarbacidas , Péptidos , Microambiente Tumoral
7.
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
8.
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
9.
Biomimetics (Basel) ; 8(8)2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38132543

RESUMEN

Research on the efficiency and quality issues faced in aircraft assembly was conducted in this article. A new method of human-machine collaborative riveting was proposed, which combined the flexibility of manual collaboration with the precise control of automatic riveting. The research works include: (1) a theoretical model of pneumatic hammer riveting was established to clarify the principle and parameters of riveting process. (2) A smart bucking bar was designed to support the data collection and extraction of manual collaborative riveting process. (3) An automatic riveting experimental platform was designed to test the automatic riveting process incorporating the extracted manual riveting process parameters, and further an optimization strategy was proposed for the automatic riveting process. (4) A human-machine collaborative riveting experimental platform was developed to conduct the verification work. Through the theoretical analysis, experimental research, system scheme design, and process parameters optimization, the application and verification of human-machine collaborative assembly technology have been achieved. This technology is expected to be comprehensively promoted in the field of aircraft manufacturing, and for breaking through the current difficulties of low production efficiency and poor assembly quality control.

10.
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
11.
Nat Commun ; 14(1): 7510, 2023 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-37980361

RESUMEN

The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.


Asunto(s)
Antiinfecciosos , Óxido Nítrico , Animales , Ratones , Óxido Nítrico/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ciprofloxacina/farmacología , Biopelículas , Antiinfecciosos/farmacología , Pseudomonas aeruginosa/fisiología , Pruebas de Sensibilidad Microbiana
12.
Molecules ; 28(22)2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-38005221

RESUMEN

Due to their structural and property tunability, semiconductive conjugated polymers (CPs) have emerged as promising candidates for photocatalytic water splitting. Compared with inorganic materials, the photocatalytic performance of mono-component polymers was limited by the fast recombination of photoexcited charge carriers, and they always needed to catch up to expectations. To this end, researchers established molecular donor-acceptor heterostructures, which could notably promote oxygen production efficiency due to their more effective charge carrier separation. In this work, easy Schiff base reactions between side-chain -CHO groups and terminal -NH2 groups were used to introduce benzene and perylene diimide (PDI) into the molecular heterostructure to serve as electron donors (D) and electron acceptors (A). In particular, for the first time, we employed the molecular heterostructures of CPs to promote photocatalytic O2 production. One prepared molecular heterostructure was demonstrated to improve oxygen generation rate (up to 0.53 mmol g-1 h-1) through visible light-driven water splitting. Interestingly, based on the photoelectric properties, a stepwise two-electron/two-electron pathway constituted the photocatalytic mechanism for oxygen production with the molecular heterostructure. These results provide insights into designing and fabricating high-performance molecular heterostructures for photocatalytic oxygen production.

14.
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
15.
Int J Biol Macromol ; 253(Pt 4): 127092, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37758109

RESUMEN

In this study, the effects of the direct addition of curdlan on the physicochemical, structural, and functional properties of heat-induced soy protein isolate (SPI) gels were evaluated. Results demonstrated that the direct incorporation of curdlan enhanced the gel-forming performance, water-holding capacity, and gel strength of heat-induced SPI gels. The presence of curdlan reduced the free water molecules and α-helix content in the SPI structure and contributed to the construction of stable SPI gels with uniform and compact network structures, as visually proven by microstructure observations. Moreover, compared with the SPI gel alone, the curdlan-SPI composite gels presented a more pronounced viscoelastic property and thermal stability mainly due to the intermolecular hydrogen bonding interaction between curdlan and the SPI molecules. Our findings suggest that the direct incorporation of curdlan can effectively ameliorate the gelling characteristics of heat-induced SPI gels, indicating its potential application as a promising gel improver in the food industry.


Asunto(s)
Proteínas de Soja , Agua , Proteínas de Soja/química , Enlace de Hidrógeno , Geles/química , Agua/química
16.
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
17.
ACS Appl Mater Interfaces ; 15(33): 39827-39836, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37578118

RESUMEN

Recently, spiropyran-based composites have gained more attention on account of their stimuli-responsive essence, especially of the fascinating and green photo stimulus. However, the great dipole moment change between the ring-opened merocyanine and ring-closed spiropyran requires a large free volume available for isomerization, which significantly restrains the photoisomerization of spiropyran-based nanocomposites. Herein, a fascinating pathway by regulating the states both of spiropyran and the immobilized nanoparticle supports was put forward to facilitate the photoisomerization. The results demonstrated that the spiropyran grafting percentage of 5.18% and immobilized supports with less aggregation, high specific surface area, large pore size, and noncrystalline structure were suitable to fabricate spiropyran-based nanocomposites, which showed a significant improvement for Pb2+ and Cr3+ removal from aqueous solution on account of free photoisomerization of spiropyran on the support's surface. This work will pave the pathway to extend the exploitation of spiropyran-based nanocomposites in various fields such as biotechnology, physiology, and electronics to photonics and environmental-friendly fields.

18.
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
19.
Front Pharmacol ; 14: 1033859, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37435496

RESUMEN

Introduction: Temporal lobe epilepsy (TLE) is the most common subtype of epilepsy in adults and is characterized by neuronal loss, gliosis, and sprouting mossy fibers in the hippocampus. But the mechanism underlying neuronal loss has not been fully elucidated. A new programmed cell death, cuproptosis, has recently been discovered; however, its role in TLE is not clear. Methods: We first investigated the copper ion concentration in the hippocampus tissue. Then, using the Sample dataset and E-MTAB-3123 dataset, we analyzed the features of 12 cuproptosis-related genes in TLEs and controls using the bioinformatics tools. Then, the expression of the key cuproptosis genes were confirmed using real-time PCR and immunohistochemical staining (IHC). Finally, the Enrichr database was used to screen the small molecules and drugs targeting key cuproptosis genes in TLE. Results: The Sample dataset displayed four differentially expressed cuproptosis-related genes (DECRGs; LIPT1, GLS, PDHA1, and CDKN2A) while the E-MTAB-3123 dataset revealed seven DECRGs (LIPT1, DLD, FDX1, GLS, PDHB, PDHA1, and DLAT). Remarkably, only LIPT1 was uniformly upregulated in both datasets. Additionally, these DECRGs are implicated in the TCA cycle and pyruvate metabolism-both crucial for cell cuproptosis-as well as various immune cell infiltrations, especially macrophages and T cells, in the TLE hippocampus. Interestingly, DECRGs were linked to most infiltrating immune cells during TLE's acute phase, but this association considerably weakened in the latent phase. In the chronic phase, DECRGs were connected with several T-cell subclasses. Moreover, LIPT1, FDX1, DLD, and PDHB were related to TLE identification. PCR and IHC further confirmed LIPT1 and FDX1's upregulation in TLE compared to controls. Finally, using the Enrichr database, we found that chlorzoxazone and piperlongumine inhibited cell cuproptosis by targeting LIPT1, FDX1, DLD, and PDHB. Conclusion: Our findings suggest that cuproptosis is directly related to TLE. The signature of cuproptosis-related genes presents new clues for exploring the roles of neuronal death in TLE. Furthermore, LIPT1 and FDX1 appear as potential targets of neuronal cuproptosis for controlling TLE's seizures and progression.

20.
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
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