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1.
RSC Adv ; 14(36): 25975-25985, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39161444

RESUMO

A two-step method for preparing composite coatings with different composition on Ti alloys using softened spark microarc oxidation technology was proposed. The nucleation and growth processes of a softened spark layer, as well as the influence of softened sparks on the deposition of anions in electrolytes, were studied. The results show that the process voltage of the softened spark discharge on the selective laser-melted Ti6Al4V alloy was lower than the breakdown voltage of its anodic oxide film. The softened sparks prioritized nucleation at the coating/substrate interface in the initial spark discharge area rather than in the microarc discharge area. On one hand, the softened spark layer grew towards the Ti6Al4V substrate, and on the other hand, the molten oxide generated by the softened sparking was transferred into the external porous layer. The softened sparks generated inside the coating promoted the rutile phase formation and linear growth in the thickness of the softened spark layer. Ca and P are mainly distributed in the external porous layer or at the interface between the softened-spark and external porous layers. Nevertheless, softened sparking had little effect on the initial micro/nanoporous structures of the coatings.

2.
J Biochem Mol Toxicol ; 38(9): e23794, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39163615

RESUMO

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate-induced injury model of mouse hippocampal neurons HT-22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate-induced HT-22 cells. The results showed that ISO inhibited glutamate-induced ferroptosis of neuronal cells through nuclear factor E2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT-22 cells with ISO significantly reduced glutamate-induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long-chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT-22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT-22 cells was increased, and the expression of downstream heme oxygenase-1 protein was upregulated. In summary, ISO protects HT-22 cells from glutamate-induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway.


Assuntos
Ferroptose , Ácido Glutâmico , Fator 2 Relacionado a NF-E2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Transdução de Sinais , Animais , Ferroptose/efeitos dos fármacos , Camundongos , Ácido Glutâmico/toxicidade , Ácido Glutâmico/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Isoquinolinas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
3.
Heliyon ; 10(14): e34295, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39130409

RESUMO

Metabolic syndrome(MS) is a separate risk factor for the advancement of atherosclerosis(AS) plaque but mechanism behind this remains unclear. There may be a significant role for the immune system in this process. This study aims to identify potential diagnostic genes in MS patients at a higher risk of developing and progressing to AS. Datasets were retrevied from gene expression omnibus(GEO) database and differentially expressed genes were identified. Hub genes, immune cell dysregulation and AS subtypes were identified using a conbination of muliple bioinformatic analysis, machine learning and consensus clustering. Diagnostic value of hub genes was estimated using a nomogram and ROC analysis. Finally, enrichment analysis, competing endogenous RNA(ceRNA) network, single-cell RNA(scRNA) sequencing analysis and drug-protein interaction prediction was constructed to identify the functional roles, potential regulators and distribution for hub genes. Four hub genes and two macrophage-related subtypes were identified. Their strong diagnostic value was validated and functional process were identified. ScRNA analysis identified the macrophage differentiation regulation function of F13A1. CeRNA network and drug-protein binding modes revealed the potential therapeutic method. Four immune-correlated hub genes(F13A1, MMRN1, SLCO2A1 and ZNF521) were identified with their diagnostic value being assesed, which F13A1 was found strong correlated with macrophage differentiation and could be potential diagnostic and therapeutic marker for AS progression in MS patients.

4.
Exp Brain Res ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136723

RESUMO

This study aimed to utilize the nonnegative matrix factorization (NNMF) algorithm for muscle synergy analysis, extracting synergy structures and muscle weightings and mining biomarkers reflecting changes in muscle fatigue from these synergy structures. A leg press exercise to induce fatigue was performed by 11 participants. Surface electromyography (sEMG) data from seven muscles, electrocardiography (ECG) data, Borg CR-10 scale scores, and the z-axis acceleration of the weight block were simultaneously collected. Three indices were derived from the synergy structures: activation phase difference, coactivation area, and coactivation time. The indicators were further validated for single-leg landing. Differences in heart rate (HR) and heart rate variability (HRV) were observed across different fatigue levels, with varying degrees of disparity. The median frequency (MDF) exhibited a consistent decline in the primary working muscle groups. Significant differences were noted in activation phase difference, coactivation area, and coactivation time before and after fatigue onset. Moreover, a significant correlation was found between the activation phase difference and the coactivation area with fatigue intensity. The further application of single-leg landing demonstrated the effectiveness of the coactivation area. These indices can serve as biomarkers reflecting simultaneous alterations in the central nervous system and muscle activity post-exertion.

5.
Chemistry ; : e202402458, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39126402

RESUMO

The difunctionalization of alkenes represents a powerful tool to incorporate two functional groups into the alkene bones for increasing molecular complexity and has been widely utilizations in chemical synthesis. Upon the catalysis of the green, sustainable, mild photo-/electrochemistry technologies, much attentions have been attracted to the development of new tactics for the transformations of the important alkene and alkane feedstocks driven by C-H radical functionalization. Herein, we summarize recent advances in the photo-/electrocatalytic difunctionalization of alkenes enabled by C-H radical functionalization. We detailedly discuss the substrate scope and the mechanisms of the photo-/electrocatalytic alkene difunctionalization reactions by selecting impressive synthetic examples, which are divided into four sections based on the final terminated step, including oxidative radical-polar crossover coupling, reductive radical-polar crossover coupling, radical-radical coupling, and transition-metal-catalyzed coupling.

6.
Biomed Pharmacother ; 178: 117260, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39116788

RESUMO

The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20 %, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives. Based on this conformation, we designed and synthesized four series of derivatives. By evaluating their affinity and anti-HCC effects, we confirmed that these compounds exert anti-HCC activity by inhibiting ULK1. The structure-activity relationship was summarized, with derivative A4 showing 10 times higher activity than XST-14 and superior efficacy to sorafenib against HCC. A4 has excellent effect on reducing tumor growth and enhancing sorafenib activity in HepG2 and HCCLM3 cells. Moreover, we verified the therapeutic effect of A4 in sorafenib-resistant HCC cells both in vivo and in vitro. These results suggest that inhibiting ULK1 to regulate autophagy may become a new treatment method for HCC and that A4 will be used as a lead drug for HCC in further research. Overall, A4 shows good drug safety and efficacy, offering hope for prolonging the survival of HCC patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39133214

RESUMO

Two novel rod-shaped, strictly aerobic, non-motile and Gram-stain-negative bacterial strains, designated SDUM040013T and SDUM040014T, were isolated from kelp seedlings in Weihai, PR China. Cells of strain SDUM040013T were 0.3-0.4 µm wide and 0.8-1.8 µm long, catalase-positive and oxidase-positive. Growth of SDUM040013T was observed at 0-37 °C (optimum, 28-30 °C) and pH 5.5-9 (optimum, pH 8.0) and in the presence of 1-8 % (w/v) NaCl (optimum, 2 %). The DNA G+C content of strain SDUM040013T was 50.5 %. Strain SDUM040013T showed the highest 16S rRNA gene sequence similarity (97.1 %) to Gilvimarinus chinensis. Cells of strain SDUM040014T were 0.4-0.5 µm wide and 1.0-1.4 µm long, catalase-positive and oxidase-positive. Growth of SDUM040014T was observed at 4-40 °C (optimum, 28-30 °C) and pH 5.5-9 (optimum, pH 8.5) and in the presence of 0-8 % (w/v) NaCl (optimum, 2 %). The DNA G+C content of strain SDUM040014T was 56.5 %. Strain SDUM040014T showed the highest 16S rRNA gene sequence similarity (96.2%) to Gilvimarinus polysaccharolyticus. The isoprenoid quinone of both strains was Q-8 and the predominant fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c) and C16 : 0. Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were the major polar lipids. Given these phenotypic and chemotaxonomic properties, as well as phylogenetic data, strains SDUM040013T and SDUM040014T were considered to represent two novel species of the genus Gilvimarinus, for which the names Gilvimarinus gilvus sp. nov. and Gilvimarinus algae sp. nov. are proposed. The type strains are SDUM040013T (=KCTC 8123T=MCCC 1H01413T) and SDUM040014T (=KCTC 8124T=MCCC 1H01414T), respectively.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Kelp , Filogenia , RNA Ribossômico 16S , Plântula , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Ácidos Graxos/química , China , DNA Bacteriano/genética , Kelp/microbiologia , Plântula/microbiologia , Ubiquinona/análogos & derivados
8.
Heliyon ; 10(11): e32407, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38947441

RESUMO

Background: Colchicine is a common therapeutic agent for inflammatory conditions such as gout, yet its narrow therapeutic range frequently results in cases of overdose and subsequent poisoning. Acute colchicine poisoning can be difficult to identify due to its nonspecific clinical manifestations, posing a diagnostic challenge for emergency physicians without a clear history of colchicine ingestion. Case presentation: This report describes a tragic case of acute colchicine poisoning that resulted in three familial homicides. The patients presented with fever, abdominal pain, and diarrhea, which rapidly escalated to shock during their emergency department visits. Laboratory tests revealed a marked leukocytosis, mild elevation in procalcitonin (PCT), significantly elevated creatine kinase (CK) and CK-MB levels, and liver function abnormalities. Despite treatment with carbapenem antibiotics and aggressive fluid resuscitation, the patients' condition deteriorated, marked by a progressive decline in leukocytes and neutrophils. Initially misdiagnosed as septic shock, the ineffectiveness of the standard treatment protocols led to a fatal outcome for all three individuals. Conclusion: Emergency physicians should consider acute colchicine poisoning as a differential diagnosis in patients presenting with shock and the following clinical indicators: (1) pronounced increase in peripheral leukocytes with a disproportionate rise in neutrophils; (2) discordance between the level of serum procalcitonin and the severity of presumed septic shock; (3) early increase in serum creatine kinase (CK) and CK-MB; (4) poor response to antibiotics and resuscitative efforts, accompanied by a continuous decrease in white blood cells and neutrophils. This case underscores the critical need for awareness of colchicine toxicity in the emergency setting, particularly when the clinical presentation mimics septic shock but fails to respond to standard treatments.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38976006

RESUMO

Bio-cement is a green and energy-saving building material that has attracted much attention in the field of ecological environment and geotechnical engineering in recent years. The aim of this study is to investigate the use of bio-cement (enzyme-induced calcium carbonate precipitation-EICP) in combination with admixtures for the improvement of desert sands, which can effectively improve the mechanical properties of desert sands and is particularly suitable for sand-rich countries. In addition, the suitability of tap water in bio-cement was elucidated and the optimum ratio of each influencing factor when tap water is used as a solvent was derived. The results showed that peak values of unconfined compressive strength (maximum increase of about 130 times), shear strength (increase of 27.09%), calcium carbonate precipitation value (increase of about 4.39 times), and permeability (decrease of about 93.72 times) were obtained in the specimens modified by EICP combined with admixture as compared to the specimens modified by EICP only. The incorporation of skimmed milk powder, though significantly increasing the strength, is not conducive to cost control. The microscopic tests show that the incorporation of admixtures can provide nucleation sites for EICP, thus improving the properties of desert sand. This work can provide new research ideas for cross-fertilization between the disciplines of bio-engineering, ecology, and civil engineering.

10.
Angew Chem Int Ed Engl ; : e202411508, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014940

RESUMO

The conversion of CO2 to C2 through photocatalysis poses significant challenges, and one of the biggest hurdles stems from the sluggishness of the multi-electron transfer process. Herein, taking metal-organic framework (PFC-98) as a model photocatalyst, we report a new strategy to facilitate charge separation. This strategy involves matching the energy levels of the lowest unoccupied node and linker orbitals of the MOF, thereby creating the lowest unoccupied crystal orbital (LUCO) delocalized over both the node and linker. This feature enables the direct excitation of electrons from photosensitive linker to the catalytic centers, achieving a direct charge transfer (DCT) pathway. For comparison, an isoreticular MOF (PFC-6) based on analogue components but with far apart frontier energy level was synthesized. The delocalized LUCO caused the presence of an internal charge-separated state (ICS), prolonging the excited state lifetime and further inhibiting the electron-hole recombination. The presence of an internal charge-separated state (ICS) prolongs the excited state lifetime and further inhibits the electron-hole recombination. Moreover, it also induced abundant electrons accumulating at the catalytic sites, enabling the multi-electron transfer process. As a result, the material featuring delocalized LUCO exhibits superior overall CO2 photocatalytic performance with high C2 production yield and selectivity.

11.
Adv Sci (Weinh) ; : e2404534, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39033540

RESUMO

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

12.
Angew Chem Int Ed Engl ; : e202409948, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949953

RESUMO

As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe2Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe2Co] crystals to alternating irradiation with 785 nm and 532 nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532 nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785 nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories.

13.
Toxicology ; 507: 153886, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39002880

RESUMO

Benzo[a]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10 µM BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25 µM) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe2+, malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe2+, MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens.


Assuntos
Benzo(a)pireno , Movimento Celular , Ferroptose , Ferroptose/efeitos dos fármacos , Humanos , Benzo(a)pireno/toxicidade , Movimento Celular/efeitos dos fármacos , Linhagem Celular , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Espécies Reativas de Oxigênio/metabolismo , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Peroxidação de Lipídeos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Ferritinas , Oxirredutases , Antígenos CD
14.
J Pharm Pharmacol ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39045884

RESUMO

OBJECTIVES: Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD. METHODS: The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments. KEY FINDINGS: Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway. CONCLUSIONS: Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells.

15.
Nat Commun ; 15(1): 4702, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830878

RESUMO

Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]- anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10-4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α31 component (~89 mV Oe-1 cm-1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

16.
Nat Commun ; 15(1): 5183, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890370

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in early trials for relapsed/refractory diffuse large B cell lymphoma (DLBCL). However, its efficacy in treating primary refractory DLBCL has not been comprehensively investigated, and the underlying resistance mechanisms remain unclear. Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints. Among the 12 enrolled patients, 8 experienced grade 4 hematologic toxicity of treatment-emergent adverse event. No grade ≥3 cytokine release syndrome or neurotoxicity occurred. Single-cell RNA sequencing revealed an increase proportion of C1QB-expressing macrophages in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from M2 macrophages was found to inhibit CAR-T cells cytotoxicity by inducing an immunosuppressive state in CD8+ T cells, leading to their exhaustion. Possible interactions between macrophages and CD8+ T cells, mediating lipid metabolism (AFR1-FAS), immune checkpoint activation, and T cell exhaustion (LGALS9-HAVCR2, CD86-CTLA4, and NECTIN2-TIGIT) were enhanced during disease progression. These findings suggest that cholesterol efflux from macrophages may trigger CD8+ T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.


Assuntos
Colesterol , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Macrófagos , Receptores de Antígenos Quiméricos , Humanos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/genética , Macrófagos/metabolismo , Macrófagos/imunologia , Imunoterapia Adotiva/métodos , Pessoa de Meia-Idade , Feminino , Masculino , Colesterol/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Idoso , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Adulto , Resistencia a Medicamentos Antineoplásicos
17.
ACS Nano ; 18(26): 16715-16725, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38876985

RESUMO

Nonlead low-dimensional halide perovskites attract considerable attention as X-ray scintillators. However, most scintillation screens exhibit pronounced light scattering, which detrimentally reduces the quality of X-ray imaging. Herein, we employed a simple and straightforward solvent-free melt-quenching method to fabricate a large-area zero-dimension (0D) antimony-based perovskite transparent medium, namely (C20H20P)2SbCl5 (C20H20P+ = ethyltriphenylphosphine). The transparency is due to the large steric hindrance of C20H20P+, which hinders the formation of crystals during the quenching process, thus forming a glass with low refractive index and uniform structure. This medium exhibits a high transmittance exceeding 80% in the range of 450-800 nm and shows a large Stokes shift of 245 nm, thereby minimizing light scattering, mitigating self-absorption, and enhancing the clarity of X-ray imaging. Moreover, it exhibits a high radioluminescence light yield of ∼12,535 photons MeV-1 and displays a high X-ray spatial resolution of 30 lp mm-1 owing to its high transparency. This study presents an alternative candidate for achieving high-quality X-ray detection and extends the applicability of transparent perovskite scintillators.

19.
Ying Yong Sheng Tai Xue Bao ; 35(4): 897-908, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38884224

RESUMO

Understanding water absorption mechanisms of sand-fixing plants is important for the rational establishment of plant community structures, thereby providing a scientific basis for desertification control and the efficient utilization of water resources in sandy areas. Based on the hydrogen and oxygen isotopic compositions of precipi-tation, soil water, xylem water, and groundwater, coupled with soil water-heat dynamics, annual water consumption characteristics of vegetation, using the multi-source linear mixing model (IsoSource), we analyzed the differences in water sources between Salix psammophila and Artemisia ordosica, during winter and the growing season. We further examined the effects of groundwater depth (2 m and 10 m), soil freezing-thawing, and drought on their water utilization to elucidate water absorption mechanisms of those species. The results showed that: 1) During soil freezing-thawing period (January to March), S. psammophila mainly utilized soil water in 60-120 cm depths below the frozen layer (69.1%). In the green-up season (April and May), soil water from the 0-60 cm layers could satisfy the water demand of S. psammophila (30.9%-87.6%). During the dry period of the growing season (June), it predominantly utilized soil water at the depth of 120-160 cm (27.4%-40.8%). Over the rainy season (July and September), soil water in 0-60 cm depths provided 59.8%-67.9% of the total water required. A. ordosica, with shallow roots, could not utilize soil water after complete freezing of root zone but could overwinter by storing water in rhizomes during autumn. During the growing season, it primarily relied on 0-40 cm soil layer (23.4%-86.8%). During the dry period, it mainly utilized soil water from 40-80 cm and 80-160 cm soil layers, with utilization rates of 14.6%-74.4% and 21.8%-78.2%, respectively. 2) With decreasing groundwater depth, vegetation shifted its water absorption depth upward, with water source of S. psammophila transitioning from 120-160 cm to 60-160 cm layers, while A. ordosica shifted water absorption depth from 80-160 cm to 0-40 cm. S. psammophila's utilization of soil water is influenced by transpiration, adopting an "on-demand" approach to achieve a balance between water supply and energy conservation, whereas A. ordosica tends to utilize shallow soil water, exhibiting a higher depen-dence on water sources from a single soil layer.


Assuntos
Artemisia , Salix , Areia , Solo , Água , Água/análise , Água/metabolismo , Artemisia/crescimento & desenvolvimento , Artemisia/metabolismo , China , Solo/química , Salix/crescimento & desenvolvimento , Salix/metabolismo , Clima Desértico , Água Subterrânea/química , Água Subterrânea/análise , Ecossistema
20.
Angew Chem Int Ed Engl ; 63(33): e202408247, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-38837719

RESUMO

The construction of mechanically responsive materials with reversible shape-shifting, shape-locking, and stretchability holds promise for a wide range of applications in fields such as soft robotics and flexible electronics. Here, we report novel thermoelastic one-dimensional organic-inorganic hybrids (R/S-Hmpy)PbI3 (Hmpy=2-hydroxymethyl-pyrrolidinium) to show mechanical responses. The single crystals undergo two phase transitions at 310 K and 380 K. When heated to 380 K, they show shape-shifting and expansion along the b-axis by about 13.4 %, corresponding to a larger deformation than that of thermally activated shape memory alloys (8.5 %), and exhibit a strong actuation force. During the cooling process, the stretched crystal shape maintains and a shape-locking phenomenon occurs, which is lifted when the temperature decreases to 305 K. Meanwhile, due to the introduction of chiral ions, the thermal switching shows a 10-fold second-order nonlinear switching contrast (common values typically below 3-fold). This study presents a thermoelastic actuator based on shape-shifting and -locking of organic-inorganic hybrids for the first time. The dielectric and nonlinear optical switching properties of organic-inorganic hybrids broaden the range of applications of mechanically responsive crystals.

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