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1.
Angew Chem Int Ed Engl ; : e202408016, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38828671

RESUMEN

Expanding the diversity of multi-macrocyclic nanocarbons, particularly those with all-benzene scaffolds, represents intriguing yet challenging synthetic tasks. Complementary to the existing synthetic approaches, here we report an efficient and modular post-functionalization strategy employing iridium-catalyzed C-H borylation of the highly strained meta-cycloparaphenylenes (mCPPs) and an mCPP-derived catenane. Based on the functionalized macrocyclic synthons, a number of novel all-benzene topological structures including linear and cyclic chains, polycatenane, and pretzelane have been successfully prepared and characterized, thereby showcasing the synthetic utility and potential of the post-functionalization strategy.

2.
bioRxiv ; 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38826421

RESUMEN

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, neurobehavioral phenotypes including autism and attention deficit hyperactivity disorder (ADHD), and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function that will pave the way for future molecular studies into DESSH. These studies begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac , with advantages in each model.

3.
Discov Med ; 36(184): 936-945, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38798253

RESUMEN

BACKGROUND: Inflammation is a key pathological process in bacterial meningitis, and the transforming growth factor-beta-activated kinase 1 (TAK1)/nuclear factor-kappa B (NF-κB) pathway is implicated in the activation of microglia and the production of inflammatory factors. Interleukin (IL)-10 is an anti-inflammatory cytokine acting in an autocrine fashion in macrophages to limit inflammatory responses by decreasing the production of pro-inflammatory cytokines. This paper investigates how IL-10 can inhibit microglia activation and reduce the inflammatory response of nervous system diseases. METHODS: This study used a pneumococcal-induced in Pneumococcal meningitis (PM) C57BL/6 mice and BV-2 cells model of microglial activation, assessing the effects of IL-10 on the TAK1/NF-κB pathway. The impact of IL-10 on microglial autophagy was investigated through western blot and immunofluorescence. The effects of IL-10 were evaluated by examining cellular activation markers and the activity of molecular signaling pathways (such as phosphorylation levels of TAK1 and NF-κB). RESULTS: Pneumococcus induced the activation of microglia and reduced IL-10. IL-10 inhibited the TAK1/NF-κB pathway, reducing the pneumococcal-induced inflammatory response in microglia. IL-10 ameliorated pneumococcal infection-induced microglial injury by inhibiting autophagy. Animal experiment results also showed that IL-10 inhibited inflammation and autophagy during Pneumococcal meningitis in mice. CONCLUSION: Our study demonstrates that IL-10 reduces the inflammatory response of microglia by inhibiting the TAK1/NF-κB pathway. Additionally, IL-10 ameliorates pneumococcal infection-induced microglial injury by inhibiting the process of autophagy. These results provide a new theoretical basis and offer new insights for developing strategies to treat bacterial meningitis.


Asunto(s)
Interleucina-10 , Quinasas Quinasa Quinasa PAM , Meningitis Neumocócica , Ratones Endogámicos C57BL , Microglía , FN-kappa B , Animales , Interleucina-10/metabolismo , Microglía/metabolismo , Microglía/efectos de los fármacos , Microglía/patología , Ratones , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/inmunología , Meningitis Neumocócica/patología , FN-kappa B/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Inflamación/patología , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad , Línea Celular , Streptococcus pneumoniae
4.
J Photochem Photobiol B ; 255: 112927, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701631

RESUMEN

Since the mechanism underlying real-time acquisition of mechanical strength during laser-induced skin wound fusion remains unclear, and collagen is the primary constituent of skin tissue, this study investigates the structural and mechanical alterations in collagen at temperatures ranging from 40 °C to 60 °C using various spectroscopic techniques and molecular dynamics calculations. The COMSOL Multiphysics coupling is employed to simulate the three-dimensional temperature field, stress-strain relationship, and light intensity distribution in the laser thermal affected zone of skin wounds during dual-beam laser welding process. Raman spectroscopy, synchronous fluorescence spectroscopy and circular dichroism measurement results confirm that laser energy activates biological activity in residues, leading to a transformation in the originally fractured structure of collagen protein for enhanced mechanical strength. Molecular dynamics simulations reveal that stable hydrogen bonds form at amino acid residues within the central region of collagen protein when the overall temperature peak around the wound reaches 60 °C, thereby providing stability to previously fractured skin incisions and imparting instantaneous strength. However, under a 55 °C system, Type I collagen ensures macrostructural stability while activating biological properties at amino acid bases to promote wound healing function; this finding aligns with experimental analysis results. The COMSOL simulation outcomes also correspond well with macroscopic morphology after laser welding samples, confirming that by maintaining temperatures between 55 °C-60 °C during laser welding of skin incisions not only can certain instantaneous mechanical strength be achieved but irreversible thermal damage can also be effectively controlled. It is anticipated that these findings will provide valuable insights into understanding the healing mechanism for laser-welded skin wounds.


Asunto(s)
Colágeno , Rayos Láser , Simulación de Dinámica Molecular , Piel , Espectrometría Raman , Piel/química , Piel/efectos de la radiación , Colágeno/química , Colágeno/metabolismo , Cicatrización de Heridas , Enlace de Hidrógeno , Análisis de Elementos Finitos , Animales , Dicroismo Circular , Temperatura , Espectrometría de Fluorescencia
5.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38732079

RESUMEN

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats' SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.


Asunto(s)
Factores de Transcripción ARNTL , Ritmo Circadiano , Mitofagia , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares , Animales , Ratas , Ritmo Circadiano/fisiología , Masculino , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Simulación de Ingravidez , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiología , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Temperatura Corporal , Frecuencia Cardíaca , Ratas Sprague-Dawley , Proteolisis
6.
J Am Chem Soc ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738985

RESUMEN

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

7.
Sci Rep ; 14(1): 11022, 2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745042

RESUMEN

The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Aprendizaje Automático , Humanos , Femenino , Masculino , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico , Adulto , Persona de Mediana Edad , Máquina de Vectores de Soporte , Curva ROC , Hemorragia Cerebral/diagnóstico
8.
Zhongguo Zhen Jiu ; 44(5): 495-502, 2024 May 12.
Artículo en Chino | MEDLINE | ID: mdl-38764098

RESUMEN

OBJECTIVE: To establish and validate a clinical prediction model of acupuncture and moxibustion for Bell's palsy so as to provide a tool for predicting the effect of acupuncture and moxibustion on Bell's palsy. METHODS: A total of 269 patients with Bell's palsy were collected from department of acupuncture, moxibustion and tuina, Shengli Oilfield Central Hospital, neurology department, Shenxian County Central Hospital and department of rehabilitation medicine, Dongying Municipal Hospital of TCM from June 2018 to June 2023. All of these cases were treated with acupuncture and moxibustion. Of them, 182 cases, from department of acupuncture, moxibustion and tuina, Shengli Oilfield Central Hospital and neurology department, Shenxian County Central Hospital, were randomized into a training group (128 cases) and an internal validation group (54 cases); 87 cases from department of rehabilitation medicine, Dongying Municipal Hospital of TCM were assigned to an external validation group. The clinical data of all of the cases were extracted from the electronic medical record information platform. Using SPSS25.0 and R4.2.3, through univariate and multivariate Logistic regression analysis, the independent factors influencing the effects of acupuncture and moxibustion on Bell's palsy were identified. By means of internal and external validations, the receiver operating characteristic curve (ROC), the goodness-of-fit curve (GFC) and the decision curve analysis (DCA) were plotted. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the model were calculated; and its comprehensive performance was evaluated. RESULTS: The results of the multivariate Logistic regression analysis showed that the independent factors for the unsatisfactory effect on Bell's palsy were advanced age, severe symptoms before treatment, no use of steroids within 72 h of onset, and lack of acupuncture-moxibustion therapy during the acute phase or single acupuncture-moxibustion protocol (P<0.05, P<0.01). Based on these factors, nomogram model and online columnar plot prediction tool (https://bmuchen.shinyapps.io/dynnomapp/) were established. The area under the ROC curve of the model was 0.921 (95% CI: 0.877, 0.966), 0.876 (95% CI: 0.787, 0.966), and 0.846 (95% CI: 0.766, 0.926) in the training group, the internal validation group, and the external validation group, respectively, indicating good predictive value. The model showed a satisfactory calibration curve alignment. The decision threshold in the range of 0 to 0.8 provided clinical benefits for participants. The model exhibited the sensitivity from 65.9% to 88.0%, the specificity ranging from 77.3% to 90.7%, the accuracy from 77.8% to 85.9%, the positive predictive value from 83.3% to 90.1%, and the negative predictive value from 70.8% to 78.7%. The comprehensive evaluation indicated a satisfactory clinical application value of the model. CONCLUSION: The clinical prediction model of acupuncture and moxibustion for Bell's palsy is valuable in its practice and promotion to a certain extent. The predicted results are conductive to clinicians' judgement of the effect of acupuncture and moxibustion for this disease and making effective and high-quality clinical decisions, as well as formulating the optimal therapeutic regimen.


Asunto(s)
Terapia por Acupuntura , Parálisis de Bell , Moxibustión , Humanos , Masculino , Femenino , Parálisis de Bell/terapia , Persona de Mediana Edad , Adulto , Adulto Joven , Anciano , Adolescente , Resultado del Tratamiento , Curva ROC
9.
Sci Rep ; 14(1): 11776, 2024 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782999

RESUMEN

This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case-control study was conducted, and high-throughput sequencing of the V4-V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.


Asunto(s)
Microbioma Gastrointestinal , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , ARN Ribosómico 16S , Humanos , Accidente Cerebrovascular Isquémico/microbiología , Masculino , Accidente Cerebrovascular Hemorrágico/microbiología , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Anciano , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento
10.
J Mater Chem B ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38742807

RESUMEN

Bacterial infections in wounds significantly impair the healing process. The use of natural antibacterial products over synthetic antibiotics has emerged as a new trend to address antimicrobial resistance. An ideal tissue engineering scaffold to treat infected wounds should possess antibacterial properties, while simultaneously promoting tissue regrowth. Synthesis of hydrogel scaffolds with antibacterial properties using hemp shive (HT1/HT2) lignin, sugarcane bagasse (SCB) lignin and cellulose was carried out. All lignin samples had low molecular weights and were constituted of G-type ß-5 dimers, linked by ß-O-4 bonds, as determined by MALDI-TOF-MS. Hemp lignin was more cytotoxic to mouse fibroblasts (L929) compared to SCB lignin. All lignin samples demonstrated antibacterial properties against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, with greater efficiency against Gram-negative strains. 3D hydrogels were engineered by crosslinking SCB lignin with SCB cellulose in varying weight ratios in the presence of epichlorohydrin. The stiffness of the hydrogels could be tailored by varying the lignin concentration. All hydrogels were biocompatible; however, better fibroblast adhesion was observed on the blended hydrogels compared to the 100% cellulose hydrogel, with the cellulose : lignin 70 : 30 hydrogel showing the highest L929 proliferation and best antibacterial properties with a 24-hour bacterial growth reduction ranging from 30.8 to 57.3%.

11.
Sci Rep ; 14(1): 10148, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698130

RESUMEN

We demonstrate enhanced acoustic sensing arising from the synergy between resonator-based acoustic sensor and deep learning. We numerically verify that both vibration amplitude and phase are enhanced and preserved at and off the resonance in our compact acoustic sensor housing three cavities. In addition, we experimentally measure the response of our sensor to single-frequency and siren signals, based on which we train convolutional neural networks (CNNs). We observe that the CNN trained by using both amplitude and phase features achieve the best accuracy on predicting the incident direction of both types of signals. This is even though the signals are broadband and affected by noise thought to be difficult for resonators. We attribute the improvement to a complementary effect between the two features enabled by the combination of resonant effect and deep learning. This observation is further supported by comparing to the CNNs trained by the features extracted from signals measured on reference sensor without resonators, whose performances fall far behind. Our results suggest the advantage of this synergetic approach to enhance the sensing performance of compact acoustic sensors on both narrow- and broad-band signals, which paves the way for the development of advanced sensing technology that has potential applications in autonomous driving systems to detect emergency vehicles.

13.
iScience ; 27(6): 109917, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38812544

RESUMEN

During space travel, microgravity leads to disturbances in cognitive function, while the underlying mechanism is still unclear. Simulated microgravity mice showed neuronal age-like changes in the hippocampus of our study. In the context of microgravity, we discovered m6A modification reshapes in the hippocampal region. When paired with RNA-seq and MeRIP-seq, Shox2 was found to be a powerful regulator in hippocampal neuron that respondes to microgravity. Decreased expression of senescence-associated secretory phenotype factors and improved genes related to synapses led to the restoration of memory function in the hippocampus upon increased expression of Shox2. Moreover, we discovered that IGF2BP2 was required for the m6A modification of the Shox2, and overexpressed IGF2BP2 in the hippocampus protected against both neuronal senescence and learning and memory decline caused by loss of gravity. Accordingly, our research identified the hippocampal IGF2BP2-Shox2 axis as a possible therapeutic approach to maintaining cognitive function during space travel.

14.
Natl Sci Rev ; 11(5): nwae081, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38577675

RESUMEN

Hierarchical self-assembly with long-range order above centimeters widely exists in nature. Mimicking similar structures to promote reaction kinetics of electrochemical energy devices is of immense interest, yet remains challenging. Here, we report a bottom-up self-assembly approach to constructing ordered mesoporous nanofibers with a structure resembling vascular bundles via electrospinning. The synthesis involves self-assembling polystyrene (PS) homopolymer, amphiphilic diblock copolymer, and precursors into supramolecular micelles. Elongational dynamics of viscoelastic micelle solution together with fast solvent evaporation during electrospinning cause simultaneous close packing and uniaxial stretching of micelles, consequently producing polymer nanofibers consisting of oriented micelles. The method is versatile for the fabrication of large-scale ordered mesoporous nanofibers with adjustable pore diameter and various compositions such as carbon, SiO2, TiO2 and WO3. The aligned longitudinal mesopores connected side-by-side by tiny pores offer highly exposed active sites and expedite electron/ion transport. The assembled electrodes deliver outstanding performance for lithium metal batteries.

15.
Materials (Basel) ; 17(3)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38591581

RESUMEN

Fused silica was polished to a high quality by a CO2 laser beam with a rapid scanning rate. The rapid scanning rate produced a line laser heat source, resulting in a "polishing line" during the polishing process. The Taguchi method was used to evaluate the comprehensive influence of polishing process parameters on the polishing qualities. Four factors, namely the length of laser reciprocating scanning (A), laser beam scanning speed (B), feed speed (C), and defocusing amount (D), were investigated in this study. The optimal process parameter combination (A1B1C1D1) was obtained. The surface roughness of fused silica was reduced from Ra = 0.157 µm to 0.005 µm. Through analysis of variance (ANOVA), it was found that laser beam scanning speed (B) had a significant influence on the polishing quality. The interaction of the two factors plays a decisive role in the determination of the best process parameters, and the influence of other multi-factor interaction can be ignored; the interaction between A × B is the largest, with a contribution of 42.69%.

16.
J Am Chem Soc ; 146(15): 10908-10916, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38579155

RESUMEN

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

17.
Int J Nanomedicine ; 19: 3315-3332, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617797

RESUMEN

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases. Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats. Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro. Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases.


Asunto(s)
Infarto del Miocardio , Isquemia Miocárdica , Animales , Ratas , Peróxido de Hidrógeno , Infarto del Miocardio/tratamiento farmacológico , Miocardio , Carbono
18.
Insects ; 15(4)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38667373

RESUMEN

Angaracris rhodopa (Fischer et Walheim), Calliptamus abbreviatus (Ikonnikov), Myrmeleotettix palpalis (Zubowsky), and Oedaleus decorus asiaticus (Bey-Bienko) are the main grasshoppers that harm the natural grassland in the Hexi Corridor in Gansu, northwest China. In this study, the MaxEnt model was employed to identify the key environmental factors affecting the distribution of the four grasshoppers' habitats and to assess their distribution under current and future climate conditions. The aim was to provide a basis for grasshopper monitoring, prediction, and precise control. In this study, distribution of suitable habitats for A. rhodopa, C. abbreviates, M. palpalis, O. decorus asiaticus were predicted under current and future climatic scenarios using the Maxent model. The average AUC (area under the ROC curve) and TSS (true skill statistic) values of the four grasshoppers were greater than 0.9, and the simulation results were excellent and highly reliable. The mean annual precipitation was the main factor limiting the current range of suitable areas for these four species. Under the current climate, A. rhodopa, C. abbreviatus, and O. decorus asiaticus were mainly distributed in the central and eastern parts of the Hexi Corridor, and M. palpalis was distributed throughout the Hexi Corridor, with a suitable area of 1.29 × 104, 1.43 × 104, 1.44 × 104, and 2.12 × 104 km2, accounting for 13.7%, 15.2%, 15.3%, and 22.5% of the total area of the grasslands in the Hexi Corridor, respectively. The highly suitable areas of A. rhodopa, C. abbreviatus, and O. decorus asiaticus were mainly distributed in the eastern-central part of Zhangye City, the western part of Wuwei City, and the western and southern parts of Jinchang City, with areas of 0.20 × 104, 0.29 × 104, and 0.35 × 104 km2, accounting for 2.2%, 3%, and 3.7% of the grassland area, respectively. The high habitat of M. palpalis was mainly distributed in the southeast of Jiuquan City, the west, middle, and east of Zhangye City, the west of Wuwei City, and the west and south of Jinchang City, with an area of 0.32 × 104 km2, accounting for 3.4% of the grassland area. In the 2030s, the range of A. rhodopa, C. abbreviatus, and O. decorus asiaticus was predicted to increase; the range of M. palpalis will decrease. The results of this study could provide a theoretical basis for the precise monitoring and control of key areas of grasshoppers in the Hexi Corridor.

19.
Biomaterials ; 308: 122558, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38581764

RESUMEN

Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating. This exosome-encapsulated hyaluronic acid macroporous hydrogel HD-DP7/Exo can achieve long-term storage and transport by lyophilization and can be rapidly redissolved for treatment. After comprehensively comparing the therapeutic effects of HucMSC-Exos and HucMSC-loaded hydrogels, we found that HucMSC-Exos could also effectively regulate fibroblasts, vascular endothelial cells, and macrophages and inhibit myofibroblast-mediated fibrosis, thus promoting tissue regeneration and inhibiting scar formation in a mouse model of deep second-degree burn infection healing. These properties of lyophilized storage and whole-process-repair make HD-DP7/Exo have potential application value and application prospects.


Asunto(s)
Péptidos Antimicrobianos , Exosomas , Hidrogeles , MicroARNs , Cicatrización de Heridas , Animales , Exosomas/metabolismo , Hidrogeles/química , Cicatrización de Heridas/efectos de los fármacos , Ratones , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Vendajes , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Quemaduras/terapia , Ácido Hialurónico/química , Masculino , Cicatriz , Ratones Endogámicos C57BL
20.
Food Res Int ; 184: 114205, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38609253

RESUMEN

With the advent of industrialization, there has been a substantial increase in the production and consumption of ultra-processed foods (UPFs). These processed foods often contain artificially synthesized additives, such as emulsifiers. Emulsifiers constitute approximately half of the total amount of food additives, with Tween 80 being a commonly used emulsifier in the food industry. Concurrently, China is undergoing significant demographic changes, transitioning into an aging society. Despite this demographic shift, there is insufficient research on the health implications of food emulsifiers, particularly on the elderly population. In this study, we present novel findings indicating that even at low concentrations, Tween 80 suppressed the viability of multiple cell types. Prolonged in vivo exposure to 1 % Tween 80 in drinking water induced liver lipid accumulation and insulin resistance in young adult mice under a regular chow diet. Intriguingly, in mice with high-fat diet (HFD) induced metabolic dysfunction-associated steatotic liver disease (MASLD), this inductive effect was masked. In aged mice, liver lipid accumulation was replicated under prolonged Tween 80 exposure. We further revealed that Tween 80 induced inflammation in both adult and aged mice, with a more pronounced inflammation in aged mice. In conclusion, our study provides compelling evidence that Tween 80 could contribute to a low-grade inflammation and liver lipid accumulation. These findings underscore the need for increasing attention regarding the consumption of UPFs with Tween 80 as the emulsifier, particularly in the elderly consumers.


Asunto(s)
Hígado Graso , Polisorbatos , Humanos , Anciano , Adulto Joven , Animales , Ratones , Polisorbatos/efectos adversos , Dieta Alta en Grasa , Emulsionantes/efectos adversos , Inflamación , Lípidos
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