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1.
Insects ; 15(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38667367

RESUMO

Fushi-tarazu factor 1 (FTZ-F1) is a class of transcription factors belonging to the nuclear receptor superfamily and an important molting regulator in insects; however, its detailed function in the molting process of Locusta migratoria is still unclear. This study identified two FTZ-F1 transcripts (LmFTZ-F1-X1 and LmFTZ-F1-X2) in L. migratoria. The classical domains of FTZ-F1 were present in their protein sequences and distinguished based on their variable N-terminal domains. Reverse-transcription quantitative polymerase chain reaction analysis revealed that LmFTZ-F1-X1 and LmFTZ-F1-X2 were highly expressed in the integument. RNA interference (RNAi) was used to explore the function of LmFTZ-F1s in the molting of the third-instar nymph. Separate LmFTZ-F1-X1 or LmFTZ-F1-X2 silencing did not affect the normal development of third-instar nymphs; however, the simultaneous RNAi of LmFTZ-F1-X1 and LmFTZ-F1-X2 caused the nymphs to be trapped in the third instar stage and finally die. Furthermore, the hematoxylin-eosin and chitin staining of the cuticle showed that the new cuticles were thickened after silencing the LmFTZ-F1s compared to the controls. RNA-seq analysis showed that genes encoding four cuticle proteins, two chitin synthesis enzymes, and cytochrome P450 303a1 were differentially expressed between dsGFP- and dsLmFTZ-F1s-injected groups. Taken together, LmFTZ-F1-X1 and LmFTZ-F1-X2 are involved in the ecdysis of locusts, possibly by regulating the expression of genes involved in cuticle formation, chitin synthesis, and other key molting processes.

2.
Comput Biol Med ; 174: 108489, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38640633

RESUMO

Deep neural networks (DNNs) involve advanced image processing but depend on large quantities of high-quality labeled data. The presence of noisy data significantly degrades the DNN model performance. In the medical field, where model accuracy is crucial and labels for pathological images are scarce and expensive to obtain, the need to handle noisy data is even more urgent. Deep networks exhibit a memorization effect, they tend to prioritize remembering clean labels initially. Therefore, early stopping is highly effective in managing learning with noisy labels. Previous research has often concentrated on developing robust loss functions or implementing training constraints to mitigate the impact of noisy labels; however, such approaches have frequently resulted in underfitting. We propose using knowledge distillation to slow the learning process of the target network rather than preventing late-stage training from being affected by noisy labels. In this paper, we introduce a data sample self-selection strategy based on early stopping to filter out most of the noisy data. Additionally, we employ the distillation training method with dual teacher networks to ensure the steady learning of the student network. The experimental results show that our method outperforms current state-of-the-art methods for handling noisy labels on both synthetic and real-world noisy datasets. In particular, on the real-world pathological image dataset Chaoyang, the highest classification accuracy increased by 2.39 %. Our method leverages the model's predictions based on training history to select cleaner datasets and retrains them using these cleaner datasets, significantly mitigating the impact of noisy labels on model performance.


Assuntos
Redes Neurais de Computação , Humanos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
3.
Angew Chem Int Ed Engl ; : e202404329, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683742

RESUMO

A hitherto unknown class of C4-symmetric Caryl-Cß (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.

4.
Molecules ; 29(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474531

RESUMO

A enantioselective tandem transformation, concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs), in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, providing highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

5.
Bioresour Technol ; 399: 130563, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38461871

RESUMO

An ultralight 3D carbon fiber aerogel with good flexibility is developed via soaking cotton in water and then calcinating at a high temperature. This cotton-derived carbon material is constituted by amorphous carbon and retains slight oxygen-containing groups. Besides, a lot of hollow carbon nanocapsules are yielded on the inside surface, resulting in abundant micropores and mesopores. Systemic investigations explore the molecular transformation from cotton to carbon fiber, and the formation of carbon nanocapsules. In the adsorption process for methyl orange (MO), this carbon fiber aerogel exhibits both a rapid adsorption rate and the ultrahigh adsorbability of 862.9 mg/g, outclassing most of carbon materials reported. Therefore, a dynamic sewage treatment system is built and consecutively removes hydrosoluble pollution for a long-term running time. For the cotton-derived carbon fiber aerogel, the good mechanical flexibility, excellent adsorption property, and high stability jointly provide a vast application prospect in future industrial wastewater remediation.


Assuntos
Nanocápsulas , Poluentes Químicos da Água , Fibra de Carbono , Carbono , Esgotos , Adsorção , Gossypium
6.
Org Lett ; 26(9): 1970-1974, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38421216

RESUMO

A well-defined tridentate chiral sulfoxide-N-olefin ligand has been designed and applied in rhodium-catalyzed asymmetric allylic substitutions of racemic allylic carbonates, providing the branched allylic products in good yields with good to high enantioselectivities and excellent regioselectivities. This reaction mechanism, which involves the possible hemilability of olefin coordination on sulfoxide-N-olefin hybrid ligands with rhodium, is elaborated as well.

7.
Am J Chin Med ; 52(1): 231-252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328828

RESUMO

Berberine has been demonstrated to alleviate cerebral ischemia/reperfusion injury, but its neuroprotective mechanism has yet to be understood. Studies have indicated that ischemic neuronal damage was frequently driven by autophagic/lysosomal dysfunction, which could be restored by boosting transcription factor EB (TFEB) nuclear translocation. Therefore, this study investigated the pharmacological effects of berberine on TFEB-regulated autophagic/lysosomal signaling in neurons after cerebral stroke. A rat model of ischemic stroke and a neuronal ischemia model in HT22 cells were prepared using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively. Berberine was pre-administered at a dose of 100[Formula: see text]mg/kg/d for three days in rats and 90[Formula: see text][Formula: see text]M in HT22 neurons for 12[Formula: see text]h. 24[Formula: see text]h after MCAO and 2[Formula: see text]h after OGD, the penumbral tissues and OGD neurons were obtained to detect nuclear and cytoplasmic TFEB, and the key proteins in the autophagic/lysosomal pathway were examined using western blot and immunofluorescence, respectively. Meanwhile, neuron survival, infarct volume, and neurological deficits were assessed to evaluate the therapeutic efficacy. The results showed that berberine prominently facilitated TFEB nuclear translocation, as indicated by increased nuclear expression in penumbral neurons as well as in OGD HT22 cells. Consequently, both autophagic activity and lysosomal capacity were simultaneously augmented to alleviate the ischemic injury. However, berberine-conferred neuroprotection could be greatly counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Meanwhile, autophagy inhibitor 3-Methyladenine (3-MA) also slightly neutralized the pharmacological effect of berberine on ameliorating autophagic/lysosomal dysfunction. Our study suggests that berberine-induced neuroprotection against ischemic stroke is elicited by enhancing autophagic flux via facilitation of TFEB nuclear translocation in neurons.


Assuntos
Berberina , Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Ratos , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Autofagia , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/farmacologia
9.
Insect Sci ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214184

RESUMO

The foregut, located at the front of the digestive tract, serves a vital role in insects by storing and grinding food into small particles. The innermost layer of the foregut known as the chitinous intima, comes into direct contact with the food and acts as a protective barrier against abrasive particles. Knickkopf (Knk) is required for chitin organization in the chitinous exoskeleton, tracheae and wings. Despite its significance, little is known about the biological function of Knk in the foregut. In this study, we found that LmKnk was stably expressed in the foregut, and highly expressed before molting in Locusta migratoria. To ascertain the biological function of LmKnk in the foregut, we synthesized specific double-stranded LmKnk (dsLmKnk) and injected it into locusts. Our findings showed a significant decrease in the foregut size, along with reduced food intake and accumulation of residues in the foregut after dsLmKnk injection. Morphological observations revealed that newly formed intima became thinner and lacked chitin lamella. Furthermore, fluorescence immunohistochemistry revealed that LmKnk was located in the apical region of new intima and epithelial cells. Taken together, this study provides insights into the biological function of LmKnk in the foregut, and identifies the potential target gene for exploring biological pest management strategies.

10.
Nat Commun ; 15(1): 513, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218871

RESUMO

Among today's nonvolatile memories, ferroelectric-based capacitors, tunnel junctions and field-effect transistors (FET) are already industrially integrated and/or intensively investigated to improve their performances. Concurrently, because of the tremendous development of artificial intelligence and big-data issues, there is an urgent need to realize high-density crossbar arrays, a prerequisite for the future of memories and emerging computing algorithms. Here, a two-terminal ferroelectric fin diode (FFD) in which a ferroelectric capacitor and a fin-like semiconductor channel are combined to share both top and bottom electrodes is designed. Such a device not only shows both digital and analog memory functionalities but is also robust and universal as it works using two very different ferroelectric materials. When compared to all current nonvolatile memories, it cumulatively demonstrates an endurance up to 1010 cycles, an ON/OFF ratio of ~102, a feature size of 30 nm, an operating energy of ~20 fJ and an operation speed of 100 ns. Beyond these superior performances, the simple two-terminal structure and their self-rectifying ratio of ~ 104 permit to consider them as new electronic building blocks for designing passive crossbar arrays which are crucial for the future in-memory computing.

11.
Eur J Pediatr ; 183(3): 1209-1221, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38085281

RESUMO

Although the risk of autism spectrum disorder (ASD) has been reported to be associated with interpregnancy intervals (IPIs), their association remains debatable due to inconsistent findings in existing studies. Therefore, the present study aimed to explore their association. PubMed, Embase, Web of Science, and the Cochrane Library were systematically retrieved up to May 25, 2022. An updated search was performed on May 25, 2023, to encompass recent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Our primary outcome measures were expressed as adjusted odds ratios (ORs). Given various control measures for IPI and diverse IPI thresholds in the included studies, a Bayesian network meta-analysis was performed. Eight studies were included, involving 24,865 children with ASD and 2,890,289 children without ASD. Compared to an IPI of 24 to 35 months, various IPIs were significantly associated with a higher risk of ASD (IPIs < 6 months: OR = 1.63, 95% CI 1.53-1.74, n = 5; IPIs of 6-11 months: OR = 1.50, 95% CI 1.42-1.59, n = 4; IPIs of 12-23 months: OR = 1.19, 95% CI 1.12-1.23, n = 10; IPIs of 36-59 months: OR = 0.96, 95% CI 0.94-0.99, n = 2; IPIs of 60-119 months: OR = 1.15, 95% CI 1.10-1.20, n = 4; IPIs > 120 months: OR = 1.57, 95% CI 1.43-1.72, n = 4). After adjusting confounding variables, our analysis delineated a U-shaped restricted cubic spline curve, underscoring that both substantially short (< 24 months) and excessively long IPIs (> 72 months) are significantly correlated with an increased risk of ASD.  Conclusion: Our analysis indicates that both shorter and longer IPIs might predispose children to a higher risk of ASD. Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months. What is Known: • An association between autism spectrum disorder (ASD) and interpregnancy intervals (IPIs) has been speculated in some reports. • This association remains debatable due to inconsistent findings in available studies. What is New: • Our study delineated a U-shaped restricted cubic spline curve, suggesting that both shorter and longer IPIs predispose children to a higher risk of ASD. • Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months.


Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Fatores de Risco , Intervalo entre Nascimentos , Teorema de Bayes , Metanálise em Rede
12.
Adv Sci (Weinh) ; 11(3): e2303555, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38009796

RESUMO

A20-binding inhibitor of NF-κB activation (ABIN1) is a polyubiquitin-binding protein that regulates cell death and immune responses. Although Abin1 is located on chromosome 5q in the region commonly deleted in patients with 5q minus syndrome, the most distinct of the myelodysplastic syndromes (MDSs), the precise role of ABIN1 in MDSs remains unknown. In this study, mice with a mutation disrupting the polyubiquitin-binding site (Abin1Q478H/Q478H ) is generated. These mice develop MDS-like diseases characterized by anemia, thrombocytopenia, and megakaryocyte dysplasia. Extramedullary hematopoiesis and bone marrow failure are also observed in Abin1Q478H/Q478H mice. Although Abin1Q478H/Q478H cells are sensitive to RIPK1 kinase-RIPK3-MLKL-dependent necroptosis, only anemia and splenomegaly are alleviated by RIPK3 deficiency but not by MLKL deficiency or the RIPK1 kinase-dead mutation. This indicates that the necroptosis-independent function of RIPK3 is critical for anemia development in Abin1Q478H/Q478H mice. Notably, Abin1Q478H/Q478H mice exhibit higher levels of type I interferon (IFN-I) expression in bone marrow cells compared towild-type mice. Consistently, blocking type I IFN signaling through the co-deletion of Ifnar1 greatly ameliorated anemia, thrombocytopenia, and splenomegaly in Abin1Q478H/Q478H mice. Together, these results demonstrates that ABIN1(Q478) prevents the development of hematopoietic deficiencies by regulating type I IFN expression.


Assuntos
Anemia , Interferon Tipo I , Trombocitopenia , Animais , Humanos , Camundongos , Poliubiquitina , Esplenomegalia
13.
ACS Omega ; 8(48): 46113-46126, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38075780

RESUMO

With the discovery and exploration of tight sandstone gas reservoirs in the Sichuan Basin, the Middle Jurassic Shaximiao Formation has gradually become the focus of exploration. However, the gas source of the Shaximiao Formation in the Western Sichuan Basin is still controversial, and research on the hydrocarbon generation and expulsion histories of the primary source rocks lags behind, which restricts the study of tight sandstone gas reservoir dynamics within the Shaximiao Formation in the Western Sichuan Basin and further affects the oil and gas exploration process. This paper, utilizing geochemical parameters, including 82 natural gas components and 68 carbon isotopes, conducted an investigation into the origin identification of natural gas and gas-source comparisons within the Shaximiao Formation in the Western Sichuan Basin. By utilizing basin modeling technology, we reconstructed the histories of hydrocarbon generation and expulsion of the primary source rocks and identified the potential exploration areas. The findings indicate that the natural gas within the Shaximiao Formation in the Western Sichuan Basin is characterized by a typical high-maturity wet gas-dry gas reservoir. It is a thermogenic coal-type gas produced by kerogen cracking, and the gas source is primarily type-III kerogen. The main source of natural gas is the coal-measure source rock of the Upper Triassic Xujiahe 5 Formation, which has mainly experienced two stages of increasing maturity, characterized by "two stages of gas generation and one stage of gas expulsion". The hydrocarbon generation and expulsion histories for the source rocks within the Xujiahe 5 Formation is shown as follows: the source rocks of the Xujiahe 5 Formation reached the hydrocarbon generation threshold by the end of the Early Jurassic and peaked in hydrocarbon generation by the end of the Late Jurassic, and then the natural gas migrated to the paleostructural highs of the Shaximiao Formation to form the paleo-gas reservoir. From the end of the Early Cretaceous, the paleo-gas reservoir underwent adjustments and transformations to evolve into the present-day gas reservoir. The source rocks exhibit substantial potential for the forming of large-medium and extralarge gas fields, with favorable exploration zones concentrated in the southern and central portions of the study area. The research findings can provide a scientific foundation for the next exploration and deployment of natural gas resources within the Shaximiao Formation in the Western Sichuan Basin.

14.
Heliyon ; 9(11): e21867, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027562

RESUMO

Millions of people worldwide suffer from intervertebral disc degeneration (IVDD), which imposes a significant socioeconomic burden on society. There is an urgent clinical demand for more effective treatments for IVDD because conventional treatments can only alleviate the symptoms rather than preventing the progression of IVDD. Hydrogels, a class of elastic biomaterials with good biocompatibility, are promising candidates for intervertebral disc repair and regeneration. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. This review summarizes the latest findings and developments in using bioactive factors-released bioactive injectable hydrogels for the repair and regeneration of intervertebral discs. It focuses on the analysis and summary of the use of multifunctional injectable hydrogels to delivery bioactive factors (cells, exosomes, growth factors, genes, drugs) for disc regeneration, providing guidance for future study. Finally, we discussed and analyzed the optimal timing for the application of controlled-release hydrogels in the treatment of IVDD to meet the high standards required for intervertebral disc regeneration and precision medicine.

15.
EMBO Rep ; 24(12): e57925, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37965894

RESUMO

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.


Assuntos
Senilidade Prematura , Linfócitos T , Animais , Camundongos , Envelhecimento/genética , Senilidade Prematura/genética , Apoptose , Inflamação , Mamíferos
16.
Medicine (Baltimore) ; 102(42): e35691, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37861530

RESUMO

BACKGROUND: In order to overcome the shortcomings of common surgical fixation methods for Distal Tibiofibular Syndesmosis (DTS) injuries, which include the inability to exercise early, significant surgical trauma, and the risk of loosening and breakage of implants, we have designed and implemented a new technique using steel cable fixation to treat DTS injuries. METHODS: Twenty-six patients treated with steel cable fixation for DTS injury between March 2013 and March 2019 in the Second Hospital of Tangshan City trauma department were followed up to monitor the efficacy of treatment. There were 16 males and 10 females between the ages of 19 and 64, with a mean age of 41.81 ± 9.54 years. All patients were examined by X-ray and CT for 3 days before and after surgery. The patients were then reexamined by X-ray 6 and 9 weeks postoperatively, and by CT 1 year later. The treatment results were evaluated by comparing the distal tibiofibular anterior, middle, and posterior gap changes and the Baird-Jackson score. RESULTS: The 26 patients attained good postoperative repositioning, with a fracture healing time of 2.5 to 3 months. and the Baird-Jackson score was 96 ± 2.78. After surgery, the DTS gaps observed in the CT scans taken 3 days and 1 year postoperatively in all patients were significantly reduced compared to the preoperative measurements, with statistical significance (P < .05). However, when comparing the CT scans taken 1 year postoperatively to those at 3 days postoperatively, there was no significant change in the anterior gap. The middle and posterior gaps of DTS showed a slight increase with statistical significance (P < .05), but all measurements remained within the normal range. CONCLUSION: Steel cable fixation for DTS injury has the advantages of reliable fixation, early functional exercise, and reduction in the number of operations, and no adverse effects or complications were found.


Assuntos
Fraturas do Tornozelo , Traumatismos do Tornozelo , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Tornozelo/cirurgia , Resultado do Tratamento , Traumatismos do Tornozelo/diagnóstico por imagem , Traumatismos do Tornozelo/cirurgia
18.
Nat Mater ; 22(12): 1499-1506, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37770677

RESUMO

Recently, the increasing demand for data-centric applications is driving the elimination of image sensing, memory and computing unit interface, thus promising for latency- and energy-strict applications. Although dedicated electronic hardware has inspired the development of in-memory computing and in-sensor computing, folding the entire signal chain into one device remains challenging. Here an in-memory sensing and computing architecture is demonstrated using ferroelectric-defined reconfigurable two-dimensional photodiode arrays. High-level cognitive computing is realized based on the multiplications of light power and photoresponsivity through the photocurrent generation process and Kirchhoff's law. The weight is stored and programmed locally by the ferroelectric domains, enabling 51 (>5 bit) distinguishable weight states with linear, symmetric and reversible manipulation characteristics. Image recognition can be performed without any external memory and computing units. The three-in-one paradigm, integrating high-level computing, weight memorization and high-performance sensing, paves the way for a computing architecture with low energy consumption, low latency and reduced hardware overhead.

19.
Cell Death Dis ; 14(8): 555, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620300

RESUMO

Necroptosis, a programmed cell death with necrotic-like morphology, has been recognized as an important driver in various inflammatory diseases. Inhibition of necroptosis has shown potential promise in the therapy of multiple human diseases. However, very few necroptosis inhibitors are available for clinical use as yet. Here, we identified an FDA-approved anti-cancer drug, Vemurafenib, as a potent inhibitor of necroptosis. Through direct binding, Vemurafenib blocked the kinase activity of receptor-interacting protein kinases 1 (RIPK1), impeded the downstream signaling and necrosome complex assembly, and inhibited necroptosis. Compared with Necrostain-1, Vemurafenib stabilized RIPK1 in an inactive DLG-out conformation by occupying a distinct allosteric hydrophobic pocket. Furthermore, pretreatment with Vemurafenib provided strong protection against necroptosis-associated diseases in vivo. Altogether, our results demonstrate that Vemurafenib is an effective RIPK1 antagonist and provide rationale and preclinical evidence for the potential application of approved drug in necroptosis-related diseases.


Assuntos
Necroptose , Proteína Serina-Treonina Quinases de Interação com Receptores , Vemurafenib , Humanos , Necrose , Fosforilação , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Vemurafenib/farmacologia
20.
Polymers (Basel) ; 15(14)2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37514444

RESUMO

The infrared camouflage textile materials with soft and wear-resistant properties can effectively reduce the possibility of soldiers and military equipment being exposed to infrared detectors. In this paper, the infrared camouflage textile composites with intelligent temperature adjustment ability were prepared by different methods, using phase change microcapsule as the main raw material and high polymer polyurethane as the matrix, combining the two factors of temperature control and emissivity reduction. It was tested by differential scanning calorimeter, temperature change tester, infrared emissivity tester, and infrared imager. The results show that the temperature regulation effect of textile materials finished by coating method is better than dip rolling method, the temperature regulation ability and presentation effect are the best when the microcapsule content is 27%. When the bottom layer of infrared camouflage textile composite is 27% phase change microcapsule and the surface layer is 20% copper powder, its infrared emissivity in the band of 2-22 µm is 0.656, and the rate of heating and cooling is obviously slowed down. It has excellent heat storage and temperature regulation function, which can reduce the skin surface temperature by more than 6 °C and effectively reduce the infrared radiation. This study can provide reference for laboratory preparation and industrial production of infrared camouflage composite material. The infrared camouflage textile composite prepared are expected to be used in the field of military textiles.

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