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1.
Front Bioeng Biotechnol ; 12: 1346404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737539

RESUMO

Objective: Titanium implants are widely used in surgeries for their biocompatibility and mechanical properties. However, excessive titanium particle release can cause implant failure. This study explores Atomic Layer Deposition (ALD) to coat commercially pure titanium (Cp-Ti) with TiO2, aiming to improve its frictional and corrosion resistance while reducing particle release. By comparing TiO2 films with varying ALD cycle numbers, we assess surface properties, particle release, friction, and corrosion performance, providing insights into mitigating particle release from implants. Methods: Cp-Ti surfaces were prepared and coated with TiO2 films of 100, 300, and 500 ALD cycles. Surface characterization involved SEM, EDX, and XRD. Friction was tested using SEM, nanoindentation, and ICP-MS. Corrosion resistance was evaluated through immersion tests and electrochemical analysis. Cytotoxicity was assessed using BMSCs. Results: Surface characterization revealed smoother surfaces with increased ALD cycles, confirming successful TiO2 deposition. Friction testing showed reduced friction coefficients with higher ALD cycles, supported by nanoindentation results. Corrosion resistance improved with increasing ALD cycles, as evidenced by electrochemical tests and reduced titanium release. Cytotoxicity studies showed no significant cytotoxic effects. Conclusion: ALD-coated TiO2 films significantly enhance frictional and corrosion resistance of titanium implants while reducing particle release. The study underscores the importance of ALD cycle numbers in optimizing film performance, offering insights for designing implants with improved properties.

2.
Plant Commun ; : 100975, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38751121

RESUMO

Yield prediction is the primary goal of genomic selection (GS)-assisted crop breeding. As yield is a complex quantitative trait, making predictions from genotypic data is challenging. Transfer learning can produce an effective model for a target task by leveraging knowledge from a different, but related, source domain, considered as a great potential method for improving yield prediction by integrating multi-trait data. However, it has not been applied to genotype-to-phenotype prediction before due to the lack of an efficient implementation framework. We therefore developed TrG2P, a transfer learning-based framework. TrG2P first employs convolutional neural networks (CNN) to train models using non-yield trait phenotypic and genotypic data, thus obtaining the pre-trained models. Subsequently, the convolutional layer parameters from these pre-trained models are transferred to the yield prediction task, and the fully connected layers are retrained, thus obtaining the fine-tuned models. Finally, the convolutional layer and the first fully connected layer of the fine-tuned models are fused, and the last fully connected layer is trained to enhance prediction performance. We applied TrG2P to five sets of genotypic and phenotypic data from maize (Zea mays), rice (Oryza sativa), and wheat (Triticum aestivum), and compared model precision to that of seven other popular GS tools: rrBLUP, Random Forest, Support Vector Regression, LightGBM, CNN, DeepGS, and DNNGP. TrG2P improved the accuracy of yield prediction by 39.9%, 6.8%, and 1.8% in rice, maize, and wheat, respectively, compared to predictions generated by the best performing comparison model. Our work therefore demonstrated that transfer learning is an effective strategy for improving yield prediction by integrating information from non-yield trait data. We attribute the enhanced prediction accuracy to the valuable information available from traits associated with yield and to training dataset augmentation. The Python implementation of TrG2P is available at https://github.com/lijinlong1991/TrG2P. The web-based tool is available at http://trg2p.ebreed.cn:81.

3.
Cell ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38781969

RESUMO

Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.

4.
J Control Release ; 370: 811-820, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38754632

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and life-threatening lung disease for which treatment options are limited. Glycyrrhetinic acid (GA) is a triterpenoid with multiple biological effects, such as anti-inflammatory and anti-fibrotic properties. Herein, inhalable milk-derived extracellular vesicles (mEVs) encapsulating GA (mEVs@GA) were screened and evaluated for IPF treatment. The results indicated that the loading efficiency of GA in mEVs@GA was 8.65%. Therapeutic effects of inhalable mEVs@GA were investigated in vitro and in vivo. The mEVs@GA demonstrated superior anti-inflammatory effects on LPS-stimulated MHS cells. Furthermore, repeated noninvasive inhalation delivery of mEVs@GA in bleomycin-induced IPF mice could decrease the levels of transforming growth factors ß1 (TGF-ß1), Smad3 and inflammatory cytokines IL-6, IL-1ß and TNF-α. The mEVs@GA effectively diminished the development of fibrosis and improved pulmonary function in the IPF mice model at a quarter of the dose compared with the pirfenidone oral administration group. Additionally, compared to pirfenidone-loaded mEVs, mEVs@GA demonstrated superior efficacy at the same drug concentration in the pharmacodynamic study. Overall, inhaled mEVs@GA have the potential to serve as an effective therapeutic option in the treatment of IPF.

5.
ACS Appl Mater Interfaces ; 16(19): 24235-24247, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38688002

RESUMO

The spread of upper respiratory tract (URT) infections harms people's health and causes social burdens. Developing targeted treatment strategies for URT infections that exhibit good biocompatibility, stability, and strong antimicrobial effects remains challenging. The dual antimicrobial and antiviral effects of iodine (I2) in combination with the cooling sensation of l-menthol in the respiratory tract can simultaneously alleviate URT inflammation symptoms. However, as both I2 and l-menthol are volatile, addressing stability issues is crucial. In this study, a potassium iodide ß-cyclodextrin metal-organic framework [ß-CD-POF(I)] with appropriate particle size was used to coload and deliver I2 and l-menthol. Primarily, ß-CD-POF(I) was employed as the most efficient carrier to significantly enhance the stability of I2, surpassing any other known protection strategies in the pharmaceutical field (CD complexations, PVP conjugations, and cadexomer iodine). The mechanism underlying the improvement in stability of I2 by ß-CD-POF(I) was investigated through scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and molecular docking. The results revealed that the key processes involved in improving stability were the inclusion of I2 by ß-CD cavities in ß-CD-POF(I) and the formation of polyiodide anion between iodine ions and I2. Furthermore, the potential of ß-CD-POF(I) to load and deliver drugs was validated, and coloading of l-menthol and I2 demonstrated reliable stability. ß-CD-POF(I) achieved a rate of URT deposition ≥95% in vitro, and the combined antibacterial effects of coloaded I2 and l-menthol was better than I2 or PVP-I alone, with no irritation noted following URT administration in rabbits. Therefore, the stable coloading of drugs by ß-CD-POF(I), leading to enhanced antimicrobial effects, provides a new strategy for treating URT infections.


Assuntos
Antibacterianos , Iodo , Estruturas Metalorgânicas , beta-Ciclodextrinas , Iodo/química , Iodo/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , beta-Ciclodextrinas/química , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Testes de Sensibilidade Microbiana , Coelhos , Portadores de Fármacos/química , Staphylococcus aureus/efeitos dos fármacos , Simulação de Acoplamento Molecular
6.
Chin Med J (Engl) ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38595093

RESUMO

ABSTRACT: B7-H3 (CD276), an immune checkpoint protein of the B7 family, exhibits significant upregulation in solid tumors and hematologic malignancies, exerting a crucial role in their pathophysiology. The distinct differential expression of B7-H3 between tumors and normal tissues and its multifaceted involvement in tumor pathogenesis position it as a promising therapeutic target for tumors. In the context of acute myeloid leukemia (AML), B7-H3 is prominently overexpressed and closely associated with unfavorable prognoses, yet it has remained understudied. Despite various ongoing clinical trials demonstrating the potential efficacy of immunotherapies targeting B7-H3, the precise underlying mechanisms responsible for B7-H3-mediated proliferation and immune evasion in AML remain enigmatic. In view of this, we comprehensively outline the current research progress concerning B7-H3 in AML, encompassing in-depth discussions on its structural attributes, receptor interactions, expression profiles, and biological significance in normal tissues and AML. Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

8.
Nanomaterials (Basel) ; 14(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38607121

RESUMO

The magnetization mechanism of Co-doped BaTiO3 ultrathin films is a subject of debate, which results in difficulties with the design of new multiferroics based on BaTiO3 matrixes. With the aid of a first-principles approach, it was observed that when the interstitial site and Ti vacancy were filled with Co, the configuration behaved in a nonmagnetic manner, indicating the significance of the Co content. Moreover, in the case of Co substituting two neighboring Ti atoms, when a direct current field was applied in the [100] direction, the magnetic domains excluding those in the [100], [010], and [001] directions were directed away. Further, the magnetoelectric constant was evaluated at ~449.3 mV/cmOe, showing strong magnetoelectric coupling at room temperature. Clearly, our study indicates that strict control of Ba, Ti, O, and Co stoichiometry can induce an electric and magnetic field conversion in two-dimensional BaTiO3 and may provide a new candidate for single-phase multiferroics for application in next-generation multifunctional devices.

9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(5): 617-621, 2024 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-38684312

RESUMO

OBJECTIVE: To explore the characteristics of a fetus with chromosome 1p36 deletion syndrome and 3p26.3p25.2 duplication. METHODS: A pregnant woman who had attended the Genetic Counseling Clinic of Linyi People's Hospital on February 22, 2022 and her fetus were selected as the study subjects. Clinical data were collected. Chromosomal karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were carried out for the prenatal diagnosis. RESULTS: Ultrasonography at 24th gestational week revealed that the fetus had ventricular septal defect, single umbilical artery, and slight widening of left lateral ventricle (12 mm). The woman was found to have a karyotype of 46,XX,t(1;3)(p36.22;p25.2), and the result of FISH was t(1;3)(3pter+,1qter+;1pter+,3qter+). The fetus was found to have a karyotype of 46,X?,add(1)(p36), and CMA confirmed that it has a 9.0 Mb deletion at 1p36.33p36.22 and a 12.6 Mb duplication at 3p26.3p25.2. Combining the maternal karyotype, the molecular karyotype of the fetus was determined as 46,X?,der(1)t(1;3)(p36.22;p25.2)mat.arr[hg19]1p36.33p36.22(849467_9882666)×1, 3p26.3p25.2(61892_12699607)×3, with the former known to be associated with 1p36 deletion syndrome. CONCLUSION: The fetus was diagnosed with 1p36 deletion syndrome, and its 1p36.33p36.22 deletion and 3p26.3p25.2 duplication had both derived from the balanced translocation carried by its mother.


Assuntos
Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 3 , Cariotipagem , Diagnóstico Pré-Natal , Humanos , Feminino , Cromossomos Humanos Par 1/genética , Gravidez , Cromossomos Humanos Par 3/genética , Adulto , Trissomia/genética , Trissomia/diagnóstico , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/embriologia , Transtornos Cromossômicos/diagnóstico , Hibridização in Situ Fluorescente , Feto/anormalidades
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(5): 626-631, 2024 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-38684314

RESUMO

OBJECTIVE: To explore the genetic basis for a patient with Disorders of sex development (DSD). METHODS: A female patient who had presented at the Linyi People's Hospital due to primary amenorrhea on April 6, 2022 was selected as the study subject. Conventional chromosomal karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), fluorescence quantitative PCR and Sanger sequencing were carried out for the patient. RESULTS: The patient, a 14-year-old female, had featured short statue, multiple nevi, and primary amenorrhea. She was found to have a karyotype of 46,X,idic(Y)(p11.3)[59]/45,X[39]/47,X,idic(Y)(p11.3)×2[2]. The result of FISH assay was 46,X,der(Y).ish idic(Y)(p11.3)(SRY+)[59]/45,X[39]/47,X,der(Y)×2.ish idic(Y)(p11.3)(SRY+)[2]. That of CMA was arr[GRCh37](X)×1,(Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1. The patient had no deletion in the AZF region of Y chromosome, and was negative for variant of SRY gene. Combining the above results, her molecular karyotype was determined as mos 46,X,idic(Y)(p11.32)[59]/45,X[39]/47,X,idic(Y)(p11.32)×2[2].ish 46,X,idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[59]/45,X(DXZ1+,DYZ1-,DYZ3-,SRY-)[39]/47,X,der(Y)×2.ish idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[2].arr[GRCh37](X)×1, (Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1. The patient was diagnosed with mosaicism DSD with idic(Y)(p11.32). CONCLUSION: The abnormal mosaicism karyotype probably underlay the DSD in this patient.


Assuntos
Cromossomos Humanos Y , Transtornos do Desenvolvimento Sexual , Cariotipagem , Humanos , Feminino , Adolescente , Cromossomos Humanos Y/genética , Transtornos do Desenvolvimento Sexual/genética , Hibridização in Situ Fluorescente , Aberrações dos Cromossomos Sexuais , Testes Genéticos
11.
Stress Health ; : e3412, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651677

RESUMO

Infertility can be stressful for infertile couples. This study aims to examine the intra-dyadic associations between stigma, communication patterns, and infertility-related stress in couples undergoing artificial insemination by donor semen (AID). This cross-sectional study was conducted from January to April 2021. Two hundred and three couples undergoing AID were recruited from a reproductive centre in China. All of the couples completed a two-item stigma questionnaire, Communication Pattern Questionnaire, and Fertility Problem Inventory. The actor-partner interdependence mediation analysis was performed using AMOS 23.0. The analysis demonstrated significant actor-actor effects for couples undergoing AID. More specifically, higher levels of stigma among wives and husbands were associated with more negative communication patterns, thereby increasing their own infertility-related stress. Simultaneously, there was a significant partner-actor effect among infertile wives, demonstrating that the husband's stigma can affect his wife's infertility-related stress by influencing her communication patterns. Couples undergoing AID experience increased infertility-related stress when they have high levels of stigma and negative communication patterns, and husbands' stigma is correlated to wives' communication patterns. Therefore, dyadic interventions aiming to improving stigma and enhancing positive communication may be conducive to reducing infertility-related stress.

12.
Med Image Anal ; 94: 103158, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569379

RESUMO

Magnetic resonance (MR) images collected in 2D clinical protocols typically have large inter-slice spacing, resulting in high in-plane resolution and reduced through-plane resolution. Super-resolution technique can enhance the through-plane resolution of MR images to facilitate downstream visualization and computer-aided diagnosis. However, most existing works train the super-resolution network at a fixed scaling factor, which is not friendly to clinical scenes of varying inter-slice spacing in MR scanning. Inspired by the recent progress in implicit neural representation, we propose a Spatial Attention-based Implicit Neural Representation (SA-INR) network for arbitrary reduction of MR inter-slice spacing. The SA-INR aims to represent an MR image as a continuous implicit function of 3D coordinates. In this way, the SA-INR can reconstruct the MR image with arbitrary inter-slice spacing by continuously sampling the coordinates in 3D space. In particular, a local-aware spatial attention operation is introduced to model nearby voxels and their affinity more accurately in a larger receptive field. Meanwhile, to improve the computational efficiency, a gradient-guided gating mask is proposed for applying the local-aware spatial attention to selected areas only. We evaluate our method on the public HCP-1200 dataset and the clinical knee MR dataset to demonstrate its superiority over other existing methods.


Assuntos
Diagnóstico por Computador , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Redes Neurais de Computação , Articulação do Joelho , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodos
13.
Adv Sci (Weinh) ; 11(19): e2309648, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38483885

RESUMO

Multi-foci lenses are essential components for optical communications, virtual reality display and microscopy, yet the bulkiness of conventional counterparts has significantly hindered their widespread applications. Benefiting from the unprecedented capability of metasurfaces in light modulation, metalenses are able to provide multi-foci functionality with a more compact footprint. However, achieving imaging quality comparable to that of corresponding single-foci metalenses at each focal point poses a challenge for existing multi-foci metalenses. Here, a polarization-independent all-dielectric multi-foci metalens is proposed and experimentally demonstrated by spatially integrating single-foci optical sparse-aperture sub-metalenses. Such design enables the metalens to generate multiple focal points, while maintaining the ability to capture target information comparable to that of a single-foci metalens. The proposed multi-foci metalens is composed of square-nanohole units array fabricated by two-photon polymerization. The focusing characteristic and imaging capability are demonstrated upon the illumination of an unpolarized light beam. This work finds a novel route toward multi-foci metalenses and may open a new avenue for dealing with the trade-off between multi-foci functionality and high-quality imaging performance.

14.
Nature ; 627(8005): 789-796, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38538940

RESUMO

The Antarctic Circumpolar Current (ACC) represents the world's largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1-3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial-interglacial cycles5-8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11-13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

15.
PLoS One ; 19(3): e0298262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547234

RESUMO

MCF7 cells have been used as an experimental model for breast cancer for decades. Typically, a culture medium is designed to supply cells with the nutrients essential for their continuous proliferation. Each medium has a specific nutritional composition. Therefore, cells cultured in different media may exhibit differences in their metabolism. However, only a few studies have investigated the effects of media on cells. In this study, we compared the effects of Dulbecco's modified Eagle medium (DMEM) and minimum essential medium alpha modification (αMEM) on MCF7 cells. The two media differentially affected the morphology, cell cycle, and proliferation of MCF7 cells, but had no effect on cell death. Replacement of DMEM with αMEM led to a decrease in ATP production and an increase in reactive oxygen species production, but did not affect the cell viability. RNA-sequencing and bioinformatic analyses revealed 721 significantly upregulated and 1247 downregulated genes in cells cultured in αMEM for 48 h compared with that in cells cultured in DMEM. The enriched gene ontology terms were related to mitosis and cell proliferation. Kyoto encyclopedia of genes and genomes analysis revealed cell cycle and DNA replication as the top two significant pathways. MCF7 cells were hypoxic when cultured in αMEM. These results show that the culture medium considerably affects cultured cells. Thus, the stability of the culture system in a study is very important to obtain reliable results.


Assuntos
Transcriptoma , Humanos , Células MCF-7 , Células Cultivadas , Proliferação de Células , Sobrevivência Celular , Meios de Cultura/farmacologia
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 331-334, 2024 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-38448024

RESUMO

OBJECTIVE: To explore the genetic etiology of two patients with Gitelman syndrome (GS). METHODS: Two patients who had presented at the Linyi People's Hospital in January and June 2022 respectively were selected as the study subjects. Peripheral blood samples of them were collected and subjected to whole exome sequencing (WES). Electrolyte levels in their serum and urine were detected. Candidate variants were verified by Sanger sequencing. PyMOL software was used to predict the impact of the variants on the protein structure. RESULTS: Patient 1 was a 27-year-old female with decreased serum levels of sodium, potassium, chloride and magnesium, along with decreased urine chloride and calcium. WES revealed that she has harbored compound heterozygous variants of the SLC12A3 gene, namely c.1456G>A (p.D486N) and c.179C>T (p.T60M). The former was inherited from her mother and known to be pathogenic. Patient 2 was a 4-year-old male with lower serum sodium, chloride and magnesium levels, and his serum potassium level was found to be critically low. He was found to harbor compound heterozygous variants of c.602-16G>A and c.805_806insTTGGCGTGGTCTCGGTCA (p.V268_T269insIGVVSV) of the SLC12A3 gene, which were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2_Supporting+PP3; PVS1+PM2_Supporting+PM4). CONCLUSION: The above heterozygous variants of the SLC12A3 gene probably underlay the GS in these patients.


Assuntos
Síndrome de Gitelman , Humanos , Feminino , Masculino , Adulto , Pré-Escolar , Síndrome de Gitelman/genética , Cloretos , Magnésio , Potássio , Sódio , Membro 3 da Família 12 de Carreador de Soluto/genética
17.
J Transl Med ; 22(1): 244, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448996

RESUMO

AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematological malignancies. However, viral infections, particularly EBV infection, frequently occur following allo-HSCT and can result in multi-tissue and organ damage. Due to the lack of effective antiviral drugs, these infections can even progress to post-transplant lymphoproliferative disorders (PTLD), thereby impacting the prognosis. In light of this, our objective is to develop a prediction model for EBV infection following allo-HSCT. METHODS: A total of 466 patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between September 2019 and December 2020 were included in this study. The patients were divided into a development cohort and a validation cohort based on the timing of their transplantation. Our aim was to develop and validate a grading scale using these cohorts to predict the risk of EBV infection within the first year after haplo-HSCT. Additionally, single-cell RNA sequencing (sc-RNAseq) data from the bone marrow of healthy donors were utilized to assess the impact of age on immune cells and viral infection. RESULTS: In the multivariate logistic regression model, four predictors were retained: donor age, female-to-male transplant, graft MNC (mononuclear cell) dose, and CD8 dose. Based on these predictors, an EBV reactivation predicting score system was constructed. The scoring system demonstrated good calibration in both the derivation and validation cohorts, as confirmed by the Hosmer-Lemeshow test (p > 0.05). The scoring system also exhibited favorable discriminative ability, as indicated by the C statistics of 0.72 in the derivation cohort and 0.60 in the validation cohort. Furthermore, the clinical efficacy of the scoring system was evaluated using Kaplan-Meier curves based on risk ratings. The results showed significant differences in EBV reactivation rates between different risk groups, with p-values less than 0.001 in both the derivation and validation cohorts, indicating robust clinical utility. The analysis of sc-RNAseq data from the bone marrow of healthy donors revealed that older age had a profound impact on the quantity and quality of immune subsets. Functional enrichment analysis highlighted that older age was associated with a higher risk of infection. Specifically, CD8 + T cells from older individuals showed enrichment in the pathway of "viral carcinogenesis", while older CD14 + monocytes exhibited enrichment in the pathway of "regulation of viral entry into host cell." These findings suggest that older age may contribute to an increased susceptibility to viral infections, as evidenced by the altered immune profiles observed in the sc-RNAseq data. CONCLUSION: Overall, these results demonstrate the development and validation of an effective scoring system for predicting EBV reactivation after haplo-HSCT, and provide insights into the impact of age on immune subsets and viral infection susceptibility based on sc-RNAseq analysis of healthy donors' bone marrow.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Humanos , Feminino , Masculino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais , Linfócitos T CD8-Positivos , Calibragem
18.
Food Chem ; 446: 138791, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38422638

RESUMO

Acid-sensitive CdTe quantum dots-loaded alginate hydrogel (CdTe QDs-AH) beads were designed for the visual detection of SO2 residues. As proof of concept, two types of CdTe QDs were selected as model probes and embedded in AH beads. The entire test was performed within 25 min in a modified double-layer test tube with one bead fixed above the sample solution. Adding citric acid and heating at 70 ℃ for 20 min transformed the sulfites in the solution into SO2 gas, which then quenched the fluorescence of the CdTe QDs-AH beads. Using this assay, qualitative, naked-eye detection of SO2 residues was achieved in the concentration range of 25-300 ppm, as well as precise quantification was possible based on the difference in the average fluorescence brightness of the beads before and after the reaction. Five food types were successfully analysed using this method, which is simpler and more economical than existing methods, and does not require complex pretreatment.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Pontos Quânticos/química , Dióxido de Enxofre , Compostos de Cádmio/química , Hidrogéis , Telúrio/química , Espectrometria de Fluorescência/métodos
19.
Bone Marrow Transplant ; 59(4): 496-504, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267585

RESUMO

Adult T-cell acute lymphoblastic leukemia (T-ALL) is highly aggressive with poor prognoses, while hematopoietic stem cell transplantation (HSCT) is a curable option. However, no transplant-specific prognostic model for adult T-ALL is available. We identified 301 adult T-ALL patients who received HSCT at our hospital between 2010 and 2022. These patients were randomly assigned at a 7:3 ratio to a derivation group of 210 patients and a validation group of 91 patients. Next, we developed a prognostic risk score system for adult T-ALL with HSCT, which we named COMM, including 4 predictors (central nervous system involvement, Non-CR1 (CR2+ or NR) at HSCT, minimal residual disease (MRD) ≥ 0.01% after first induction therapy, and MRD ≥ 0.01% before HSCT). Patients were categorized into three risk groups, low-risk (0), intermediate-risk (1-4), and high-risk (5-12), and their 3-year overall survival (OS) were 87.5% (95%CI, 78-93%), 65.7% (95%CI, 53-76%) and 20% (95%CI, 10-20%; P < 0.001), respectively. The area under the subject operating characteristic curve for 2-, 3- or 5-year OS in the derivation cohort and in the validation cohort were all greater than 0.75. Based on internal validation, COMM score system proved to be a reliable prognostic model that could discriminate and calibrate well. We expect that the first prognostic model in adults T-ALL after HSCT can provide a reference of prognostic consultation for patients and families, and also contribute to future research to develop risk adapted interventions for high-risk populations.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Linfócitos T
20.
Plant J ; 118(2): 457-468, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38198228

RESUMO

Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea mays L.), one of the most highly produced cereal crops worldwide, would have a global impact on human health. PLASTID TERMINAL OXIDASE (PTOX) genes play an important role in carotenoid metabolism; however, the possible function of PTOX in carotenoid biosynthesis in maize has not yet been explored. In this study, we characterized the maize PTOX locus by forward- and reverse-genetic analyses. While most higher plant species possess a single copy of the PTOX gene, maize carries two tandemly duplicated copies. Characterization of mutants revealed that disruption of either copy resulted in a carotenoid-deficient phenotype. We identified mutations in the PTOX genes as being causal of the classic maize mutant, albescent1. Remarkably, overexpression of ZmPTOX1 significantly improved the content of carotenoids, especially ß-carotene (provitamin A), which was increased by ~threefold, in maize kernels. Overall, our study shows that maize PTOX locus plays an important role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.


Assuntos
Oxirredutases , Zea mays , Humanos , Oxirredutases/genética , Oxirredutases/metabolismo , Zea mays/genética , Zea mays/metabolismo , Carotenoides/metabolismo , beta Caroteno/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Plastídeos/genética , Plastídeos/metabolismo
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