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1.
Chem Sci ; 15(18): 6916-6923, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38725518

RESUMO

Two-dimensional (2D) nonmagnetic semiconductors with large Rashba-Dresselhaus (R-D) spin splitting at valence or conduction bands are attractive for magnetic-field-free spintronic applications. However, so far, the number of 2D R-D inorganic semiconductors has been quite limited, and the factors that determine R-D spin splitting as well as rational design of giant spin splitting, remain unclear. For this purpose, by exploiting 2D chiral metal-organic frameworks (CMOFs) as a platform, we theoretically develop a three-step screening method to obtain a series of candidate 2D R-D semiconductors with valence band spin splitting up to 97.2 meV and corresponding R-D coupling constants up to 1.37 eV Å. Interestingly, the valence band spin texture is reversible by flipping the chirality of CMOFs. Furthermore, five keys for obtaining giant R-D spin splitting in 2D CMOFs are successfully identified: (i) chirality, (ii) large spin-orbit coupling, (iii) narrow band gap, (iv) valence and conduction bands having the same symmetry at the Γ point, and (v) strong ligand field.

2.
Transl Oncol ; 45: 101974, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38710133

RESUMO

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

3.
Signal Transduct Target Ther ; 9(1): 131, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740785

RESUMO

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Epitopos , Imunoglobulina M , SARS-CoV-2 , Anticorpos de Domínio Único , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/química , Humanos , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/farmacologia , Epitopos/imunologia , Epitopos/genética , Epitopos/química , Animais , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/genética , Imunoglobulina M/imunologia , Imunoglobulina M/genética , Camundongos , Domínios Proteicos , Microscopia Crioeletrônica
4.
Indian J Hematol Blood Transfus ; 40(2): 368-369, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38708168

RESUMO

The typical rod-shaped HbC crystals in the peripheral blood smear often provide the diagnostic clue to the HbC disease. This case highlights that a careful review of blood film morphology may be helpful to detect HbC disease, although this case's routine blood test is normal and do not meet the rules of re-examinations.

5.
Int J Nanomedicine ; 19: 3943-3956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708179

RESUMO

Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.


Assuntos
Doenças Autoimunes , Exossomos , Exossomos/imunologia , Humanos , Doenças Autoimunes/terapia , Doenças Autoimunes/imunologia , Animais , Nanopartículas/química
6.
Chem Commun (Camb) ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712400

RESUMO

Toll-like receptor 7/8 (TLR-7/8) agonists serve as a promising class of pattern recognition receptors that effectively evoke the innate immune response, making them promising immunomodulatory agents for tumor immunotherapy. However, the uncontrollable administration of TLR-7/8 agonists frequently leads to the occurrence of severe immune-related adverse events (irAEs). Thus, it is imperative to strategically design tumor-microenvironment-associated biomarkers or exogenous stimuli responsive TLR-7/8 agonists in order to accurately evaluate and activate innate immune responses. No comprehensive elucidation has been documented thus far regarding TLR-7/8 immune agonists that are specifically engineered to enhance immune activation. In this feature article, we provide an overview of the advancements in TLR-7/8 agonists, aiming to enhance the comprehension of their mechanisms and promote the clinical progression through nanomedicine strategies. The current challenges and future directions of cancer immunotherapy are also discussed, with the hope that this work will inspire researchers to explore innovative applications for triggering immune responses through TLR-7/8 agonists.

7.
PhytoKeys ; 241: 191-200, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721013

RESUMO

A new spleenwort species, Aspleniumguodanum, was found and described from Danxia landform region in Guangdong, China. The new species has close resemblance to A.subcrenatum Ching ex S.H.Wu in morphology, but can be distinguished by having plants small, stipes and rachises not covered with fibrous scales, relatively fewer pairs of pinnae, pinnae short, pinna margin weakly biserrate, pinna apex acute and lower pinnae obviously reduced. Phylogenetic analyses, based on six plastid markers (atpB, rbcL, rps4 & rps4-trnS and trnL & trnL-F) of the new species and its relatives, support a close relationship between A.guodanum and A.subcrenatum. Only one population with no more than 50 individuals were found and, therefore, it is recommended to be classified as Critically Endangered (CR) following IUCN Red List Criteria.

8.
Nano Lett ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723608

RESUMO

Gamma-prefoldin (γPFD), a unique chaperone found in the extremely thermophilic methanogen Methanocaldococcus jannaschii, self-assembles into filaments in vitro, which so far have been observed using transmission electron microscopy and cryo-electron microscopy. Utilizing three-dimensional stochastic optical reconstruction microscopy (3D-STORM), here we achieve ∼20 nm resolution by precisely locating individual fluorescent molecules, hence resolving γPFD ultrastructure both in vitro and in vivo. Through CF647 NHS ester labeling, we first demonstrate the accurate visualization of filaments and bundles with purified γPFD. Next, by implementing immunofluorescence labeling after creating a 3xFLAG-tagged γPFD strain, we successfully visualize γPFD in M. jannaschii cells. Through 3D-STORM and two-color STORM imaging with DNA, we show the widespread distribution of filamentous γPFD structures within the cell. These findings provide valuable insights into the structure and localization of γPFD, opening up possibilities for studying intriguing nanoscale components not only in archaea but also in other microorganisms.

9.
Invest Ophthalmol Vis Sci ; 65(5): 3, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691090

RESUMO

Purpose: Forty-hertz light flicker stimulation has been proven to reduce neurodegeneration, but its effect on optic nerve regeneration is unclear. This study explores the effect of 40-Hz light flicker in promoting optic nerve regeneration in zebrafish and investigates the underlying mechanisms. Methods: Wild-type and mpeg1:EGFP zebrafish were used to establish a model of optic nerve crush. Biocytin tracing and hematoxylin and eosin staining were employed to observe whether 40-Hz light flicker promotes regeneration of retinal ganglion cell axons and dendrites. Optomotor and optokinetic responses were evaluated to assess recovery of visual function. Immunofluorescence staining of mpeg1:EGFP zebrafish was performed to observe changes in microglia. Differentially expressed genes that promote optic nerve regeneration following 40-Hz light flicker stimulation were identified and validated through RNA-sequencing analysis and quantitative real-time PCR (qRT-PCR). Results: Zebrafish exhibited spontaneous optic nerve regeneration after optic nerve injury and restored visual function. We observed that 40-Hz light flicker significantly activated microglia following optic nerve injury and promoted regeneration of retinal ganglion cell axons and dendrites, as well as recovery of visual function. Transcriptomics and qRT-PCR analyses revealed that 40-Hz light flicker increased the expression of genes associated with neuronal plasticity, including bdnf, npas4a, fosab, fosb, egr4, and ier2a. Conclusions: To our knowledge, this study is the first to demonstrate that 40-Hz light flicker stimulation promotes regeneration of retinal ganglion cell axons and dendrites and recovery of visual function in zebrafish, which is associated with microglial activation and enhancement of neural plasticity.


Assuntos
Microglia , Regeneração Nervosa , Plasticidade Neuronal , Traumatismos do Nervo Óptico , Células Ganglionares da Retina , Peixe-Zebra , Animais , Microglia/fisiologia , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Óptico/fisiopatologia , Plasticidade Neuronal/fisiologia , Células Ganglionares da Retina/fisiologia , Estimulação Luminosa , Modelos Animais de Doenças , Nervo Óptico/fisiologia , Axônios/fisiologia , Reação em Cadeia da Polimerase em Tempo Real
11.
Adv Mater ; : e2401327, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692704

RESUMO

The interface between electrodes and neural tissues plays a pivotal role in determining the efficacy and fidelity of neural activity recording and modulation. While considerable efforts have been made to improve the electrode-tissue interface, the majority of studies have primarily concentrated on the development of biocompatible neural electrodes through abiotic materials and structural engineering. In this study, an approach is presented that seamlessly integrates abiotic and biotic engineering principles into the electrode-tissue interface. Specifically, ultraflexible neural electrodes with short hairpin RNAs (shRNAs) designed to silence the expression of endogenous genes within neural tissues are combined. The system facilitates shRNA-mediated knockdown of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and polypyrimidine tract-binding protein 1 (PTBP1), two essential genes associated in neural survival/growth and neurogenesis, within specific cell populations located at the electrode-tissue interface. Additionally, it is demonstrated that the downregulation of PTEN in neurons can result in an enlargement of neuronal cell bodies at the electrode-tissue interface. Furthermore, the system enables long-term monitoring of neuronal activities following PTEN knockdown in a mouse model of Parkinson's disease and traumatic brain injury. The system provides a versatile approach for genetically engineering the electrode-tissue interface with unparalleled precision, paving the way for the development of regenerative electronics and next-generation brain-machine interfaces.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38693866

RESUMO

AIMS: Evaluation of left and right ventricular longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and right ventricular longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30-days and 1-year after aortic valve replacement (AVR). METHODS AND RESULTS: LV longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV-PA coupling were evaluated in patients from the PARTNER-2A surgical AVR (SAVR) arm (n=985) and from the PARTNER-2 SAPIEN-3 registry (n=719). TAPSE and RV-PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV-PA coupling at baseline were associated with increased risk of the composite of death, hospitalization, and stroke at 5-years (Adjusted-HRs for LV LS<15%: 1.24 95%CI 1.05-1.45, p=0.001; TAPSE<14mm: 1.44 95%CI 1.21-1.73, p<0.001; RV/PA coupling<0.55mm/mmHg: 1.32 95% CI 1.07-1.63, p=0.011). Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5-years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95%CI 1.08-1.68, p=0.009) but not with TAVR (HR: 1.12, 95%CI 0.88-1.42). Lower RV-PA coupling at 30-days showed the strongest association with cardiac mortality. CONCLUSION: SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV-PA coupling. Lower TAPSE and RV-PA coupling at 30-days were associated with inferior clinical outcomes at 5-years. In patients with LVEF<50%, TAVR was associated with superior 5-year outcomes.

13.
Bioact Mater ; 37: 378-392, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38689658

RESUMO

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvß3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.

14.
Transl Psychiatry ; 14(1): 202, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734669

RESUMO

The pathogenesis of major depressive disorder (MDD) involves lipid metabolism. Our earlier research also revealed that MDD patients had much lower total cholesterol (TC) concentrations than healthy controls (HCs). However, it is still unclear why TC decreased in MDD. Here, based on the Ingenuity Knowledge Base's ingenuity pathway analysis, we found that sodium voltage-gated channel alpha subunit 11A (SCN11A) might serve as a link between low lipid levels and MDD. We analyzed the TC levels and used ELISA kits to measure the levels of SCN11A in the serum from 139 MDD patients, and 65 HCs to confirm this theory and explore the potential involvement of SCN11A in MDD. The findings revealed that TC levels were considerably lower and SCN11A levels were remarkably increased in MDD patients than those in HCs, while they were significantly reversed in drug-treatment MDD patients than in drug-naïve MDD patients. There was no significant difference in SCN11A levels among MDD patients who used single or multiple antidepressants, and selective serotonin reuptake inhibitors or other antidepressants. Pearson correlation analysis showed that the levels of TC and SCN11A were linked with the Hamilton Depression Rating Scales score. A substantial association was also found between TC and SCN11A. Moreover, a discriminative model made up of SCN11A was discovered, which produced an area under a curve of 0.9571 in the training set and 0.9357 in the testing set. Taken together, our findings indicated that SCN11A may serve as a link between low lipid levels and MDD, and showed promise as a candidate biomarker for MDD.


Assuntos
Colesterol , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Colesterol/sangue , Estudos de Casos e Controles , Antidepressivos/uso terapêutico
15.
Front Aging Neurosci ; 16: 1363115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737585

RESUMO

Objective: The non-motor symptoms of Parkinson's disease (PD) are an important part of PD. In recent years, more and more non-drug interventions have been applied to alleviate the non-motor symptoms of PD, but the relevant evidence is limited. This systematic review and meta-analysis was designed to evaluate the efficacy of non-drug interventions in patients with non-motor symptoms in patients with PD. Methods: Seven databases, including Pubmed, Embease, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database (WANFANG), VIP database (VIP), and China Biomedical Literature Service System (CBM) were searched from the establishment of the database to December 2023. Non-drug interventions such as acupuncture, cognitive behavioral therapy (CBT), exercise, repetitive transcranial magnetic stimulation (rTMS), and non-motor symptoms of Parkinson's disease were selected as search words, and two independent evaluators evaluated the included literature's bias risk and data extraction. The therapeutic efficacy was evaluated by the Parkinson's Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination (MMSE), and Parkinson's Disease Questionnaire-39 (PDQ-39). RevMan 5.4.1 (Reviewer Manager Software 5.4.1). Cochrane Collaboration, Oxford, United Kingdom analyzed the data and estimated the average effect and the 95% confidence interval (CI). A heterogeneity test is used to assess differences in the efficacy of different non-drug treatments. Results: We selected 36 from 4,027 articles to participate in this meta-analysis, involving 2,158 participants. Our combined results show that: PDSS: [mean difference (MD) = -19.35, 95% CI (-30.4 to -8.28), p < 0.0006]; HAMD: [MD = -2.98, 95% CI (-4.29 to -1.67), p < 0.00001]; BDI: [MD = -2.69, 95% CI (-4.24 to 4.80), p = 0.006]; HAMA: [MD = -2.00, 95% CI (-2.83 to -1.17), p < 0.00001]; MMSE: [MD = 1.20, 95% CI (0.71 to 1.68), p < 0.00001]; CoMA: [MD = 2.10, 95% CI (-0.97 to 3.23), p = 0.0003]; PDQ-39: [MD = -4.03, 95% CI (-5.96 to -1.57), p < 0.00001]. Conclusion: The four non-drug measures used in our review showed significant improvements in sleep, depression, anxiety, cognition, constipation, and quality of life compared with the control group, and no serious adverse events were reported in the included research evidence, and we found that there were some differences among the subgroups of different intervention methods, but due to the less literature included in the subgroup, and the comparison was more indirect. So, we should interpret these results carefully. Systematic review registration: www.crd.york.ac.uk/PROSPERO, identifier CRD42023486897.

16.
Nutrients ; 16(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732579

RESUMO

BACKGROUND: Cognitive impairment (CI) is a common mental health disorder among older adults, and dietary patterns have an impact on cognitive function. However, no systematic researches have constructed anti-inflammatory diet (AID) and protein-enriched diet (PED) to explore their association with CI among older adults in China. METHODS: The data used in this study were obtained from the 2018 waves of the China Longitudinal Health and Longevity Survey (CLHLS). We construct AID, PED, and calculate scores for CI. We use binary logistic regression to explore the relationship between them, and use restrictive cubic splines to determine whether the relationships are non-linear. Subgroup analysis and sensitivity analysis were used to demonstrate the robustness of the results. RESULTS: A total of 8692 participants (mean age is 83.53 years) were included in the analysis. We found that participants with a higher AID (OR = 0.789, 95% confidence interval: 0.740-0.842, p < 0.001) and PED (OR = 0.910, 95% confidence interval: 0.866-0.956, p < 0.001) score showed lower odds of suffering from CI. Besides, the relationship between the two dietary patterns and CI is linear, and the results of subgroup analysis and sensitivity analysis are also significant. CONCLUSION: Higher intakes of AID and PED are associated with a lower risk of CI among older adults, which has important implications for future prevention and control of CI from a dietary and nutritional perspective.


Assuntos
Disfunção Cognitiva , Humanos , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/epidemiologia , Masculino , Feminino , China/epidemiologia , Estudos Transversais , Idoso de 80 Anos ou mais , Idoso , Proteínas Alimentares/administração & dosagem , Dieta , Fatores de Risco , Estudos Longitudinais , Cognição
17.
Inorg Chem ; 63(19): 8846-8852, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38695272

RESUMO

Double perovskites (DPs) have attracted attention in the field of luminescence due to their inherent broadband emission of self-trapping excitons. In this work, we choose [(CH3)3NCH2CHCH2]+ and [CH3CHOHCH2NH2]+ as organic cations to synthesize two new organic-inorganic hybrid DPs, [(CH3)3NCH2CHCH2]2KInCl6 (1) and [CH3CHOHCH2NH2]2KInCl6 (2). The [KCl6]3- and [InCl6]3- octahedra are interchangeably connected by sharing two opposite faces, forming a one-dimensional coordination chain. Each K atom coordinates with six chlorine atoms in 1, while it coordinates with two oxygen atoms in addition to the six chlorine atoms in 2. The coordination between ions K and O in compound 2 may have significantly reduced its luminescence. As a result, compound 1 shows bright-yellow light with a quantum yield of more than 90%, while 2 shows weak blue light with a quantum yield of only 0.98%. In addition, different from no phase transition found in 2, 1 undergoes a reversible phase transition at 324/307 K in the heating-cooling cycle. Through structural and spectral analysis and density functional theory calculation, we conclude that the larger degree of [InCl6]3- octahedral distortion and the larger anion distance (In···In) also cause the PLQY of compound 1 to be higher than that of compound 2.

18.
Mol Biol Rep ; 51(1): 536, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642155

RESUMO

OBJECTIVES: This study aimed to identify the causative variants in a patient with Waardenburg syndrome (WS) type 2 using whole exome sequencing (WES). METHODS: The clinical features of the patient were collected. WES was performed on the patient and his parents to screen causative genetic variants and Sanger sequencing was performed to validate the candidate mutation. The AlphaFold2 software was used to predict the changes in the 3D structure of the mutant protein. Western blotting and immunocytochemistry were used to determine the SOX10 mutant in vitro. RESULTS: A de novo variant of SOX10 gene, NM_006941.4: c.707_714del (p. H236Pfs*42), was identified, and it was predicted to disrupt the wild-type DIM/HMG conformation in SOX10. In-vitro analysis showed an increased level of expression of the mutant compared to the wild-type. CONCLUSIONS: Our findings helped to understand the genotype-phenotype association in WS2 cases with SOX10 mutations.


Assuntos
Fatores de Transcrição SOXE , Síndrome de Waardenburg , Criança , Humanos , China , Mutação/genética , Linhagem , Fatores de Transcrição SOXE/genética , Síndrome de Waardenburg/genética , População do Leste Asiático/genética
19.
Sci Adv ; 10(16): eadj4079, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38630827

RESUMO

Ceramic materials with high strength and chemical inertness are widely used as engineering materials. However, the brittle nature limits their applications as fracture occurs before the onset of plastic yielding. There has been limited success despite extensive efforts to enhance the deformability of ceramics. Here we report a method for enhancing the room temperature plastic deformability of ceramics by artificially introducing abundant defects into the materials via preloading at elevated temperatures. After the preloading treatment, single crystal (SC) TiO2 exhibited a substantial increase in deformability, achieving 10% strain at room temperature. SC α-Al2O3 also showed plastic deformability, 6 to 7.5% strain, by using the preloading strategy. These preinjected defects enabled the plastic deformation process of the ceramics at room temperature. These findings suggest a great potential for defect engineering in achieving plasticity in ceramics at room temperature.

20.
BMC Plant Biol ; 24(1): 272, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605293

RESUMO

BACKGROUND: Glycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of 'Gan Cao' in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed. RESULTS: This research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata. CONCLUSION: Compared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.


Assuntos
Glycyrrhiza uralensis , Glycyrrhiza , Glycyrrhiza/metabolismo , Tolerância ao Sal/genética , Transcriptoma , Lignina/metabolismo , Flavonoides/metabolismo , Antioxidantes/metabolismo , Carotenoides/metabolismo , Transporte de Íons , Carbono/metabolismo , Solo , Fatores de Transcrição/genética
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