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1.
Front Cardiovasc Med ; 11: 1399787, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39077115

RESUMEN

Objective: This study aimed to evaluate the integration of the Hospital-Community-Home (HCH) model with the Self-Mutual-Group (SMG) health management model for high-risk populations with cardiovascular disease in the Yuhua community of Shijiazhuang city. The study focused on implementing care interventions (HCH, SMG) with a specific emphasis on SMG to promote beneficial views/behaviors, enhance self-efficacy/agency, and address detrimental determinants of health, ultimately leading to durable changes and healthier lifestyles. Comparing the HCH model with the combined SMG model helps to comprehensively assess the strengths and weaknesses of different health management approaches. This comparison contributes to theoretical innovation and practical development in the field of health management, as well as improving patients' health outcomes and quality of life. Methods: This study employed a quasi-experimental design. Using stratified sampling, individuals who underwent health examinations in Community A and Community B from Shijiazhuang city between May 2023 and August 2023 were randomly selected. After informing the participants about the study and obtaining informed consent via telephone, high-risk patients with cardiovascular disease were screened based on their medical examination reports. Data on lifestyle behaviors, self-efficacy, medical responses, quality of life, and readmission rates were collected and compared before and after the intervention. Results: A total of 526 eligible participants were included, with 241 in the control group and 285 in the study group. After the intervention, there was no significant change in the proportions of smokers, alcohol consumers, and individuals engaging in leisure exercises in the control group. However, in the study group, the proportions of smokers and alcohol consumers significantly decreased, while the proportion of individuals engaging in leisure exercises significantly increased. After the intervention, both the study group and the control group showed significant increases in scores on the General Self-Efficacy Scale-Schwarzer (GSES) and the Seattle Angina Questionnaire (SAQ), with the study group scoring significantly higher than the control group. Avoidance and surrender scores significantly increased after the intervention, with the study group scoring significantly lower than the control group. Confrontation scores significantly increased after the intervention, with the study group scoring significantly higher than the control group. During the follow-up period, the study group had a significantly lower readmission rate than the control group. Conclusion: The integration of HCH with SMG health management model can significantly improve lifestyle behaviors, optimize medical responses, enhance self-efficacy and quality of life, and significantly reduce readmission rates among high-risk populations with cardiovascular disease.

2.
Forensic Sci Int ; 361: 112113, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38936202

RESUMEN

Human Y chromosome reflects the evolutionary process of males. Male lineage tracing by Y chromosome is of great use in evolutionary, forensic, and anthropological studies. Identifying the male lineage based on the specific distribution of Y haplogroups narrows down the investigation scope, which has been used in forensic scenarios. However, existing software aids in familial searching using Y-STRs (Y-chromosome short tandem repeats) to predict Y-SNP (Y-chromosome single nucleotide polymorphism) haplogroups, they often lack resolution. In this study, we developed YHP (Y Haplogroup Predictor), a novel software offering high-resolution haplogroup inference without requiring extensive Y-SNP sequencing. Leveraging existing datasets (219 haplogroups, 4064 samples in total), YHP predicts haplogroups with 0.923 accuracy under the highest haplogroup resolution, employing a random forest algorithm. YHP, available on Github (https://github.com/cissy123/YHP-Y-Haplogroup-Predictor-), facilitates high-resolution haplogroup prediction, haplotype mismatch analysis, and haplotype similarity comparison. Notably, it demonstrates efficacy in East Asian populations, benefiting from training data from eight distinct East Asian ethnic populations. Moreover, it enables seamless integration of additional training sets, extending its utility to diverse populations.

3.
Int Immunopharmacol ; 136: 112288, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823181

RESUMEN

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.


Asunto(s)
Síndrome de Liberación de Citoquinas , Nomogramas , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Síndrome de Trombocitopenia Febril Grave/inmunología , Anciano , Estudios de Cohortes , Pronóstico , Adulto , Estudios Retrospectivos
4.
Animals (Basel) ; 14(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38891739

RESUMEN

Agonistic behavior has been identified as a limiting factor in the development of intensive L. vannamei aquaculture. However, the characteristics and molecular mechanisms underlying agonistic behavior in L. vannamei remain unclear. In this study, we quantified agonistic behavior through a behavioral observation system and generated a comprehensive database of eyestalk and brain ganglion tissues obtained from both aggressive and nonaggressive L. vannamei employing transcriptome analysis. The results showed that there were nine behavior patterns in L. vannamei which were correlated, and the fighting followed a specific process. Transcriptome analysis revealed 5083 differentially expressed genes (DEGs) in eyestalk and 1239 DEGs in brain ganglion between aggressive and nonaggressive L. vannamei. Moreover, these DEGs were primarily enriched in the pathways related to the energy metabolism process and signal transduction. Specifically, the phototransduction (dme04745) signaling pathway emerges as a potential key pathway for the adjustment of the L. vannamei agonistic behavior. The G protein-coupled receptor kinase 1-like (LOC113809193) was screened out as a significant candidate gene within the phototransduction pathway. Therefore, these findings contribute to an enhanced comprehension of crustacean agonistic behavior and provide a theoretical basis for the selection and breeding of L. vannamei varieties suitable for high-density aquaculture environments.

5.
Nano Lett ; 24(26): 8098-8106, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38913786

RESUMEN

The development of multifunctional MXene-based fabrics for smart textiles and portable devices has garnered significant attention. However, very limited studies have focused on their structure design and associated mechanical properties. Here, the supertough MXene fiber felts composed of MXene/sodium alginate (SA) fibers were fabricated. The fracture strength and bending stiffness of felts can be up to 97.8 MPa and 1.04 N mm2, respectively. Besides, the fracture toughness of felts was evaluated using the classic Griffith theory, yielding to a critical stress intensity factor of 1.79 MPam. In addition, this kind of felt presents outstanding electrothermal conversion performance (up to 119 °C at a voltage of 2.5 V), high cryogenic and high-temperature tolerance of photothermal conversion performance (-196 to 160 °C), and excellent electromagnetic interference (EMI) shielding effectiveness (54.4 dB in the X-band). This work provides new structural design concepts for high-performance MXene-based textiles, broadening their future applications.

6.
J Virol ; 98(7): e0078624, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38916398

RESUMEN

Severe fever with thrombocytopenia syndrome (SFTS) virus and hantavirus are categorized under the Bunyavirales order. The severe disease progression in both SFTS and hemorrhagic fever with renal syndrome (HFRS) is associated with cytokine storms. This study aimed to explore the differences in cytokine profiles and immune responses between the two diseases. A cross-sectional, single-center study involved 100 participants, comprising 46 SFTS patients, 48 HFRS patients, and 6 healthy controls. The study employed the Luminex cytokine detection platform to measure 48 cytokines. The differences in cytokine profiles and immune characteristics between the two diseases were further analyzed using multiple linear regression, principal component analysis, and random forest method. Among the 48 cytokines tested, 30 showed elevated levels in SFTS and/or HFRS compared to the healthy control group. Furthermore, there were 19 cytokines that exhibited significant differences between SFTS and HFRS. Random forest analysis suggested that TRAIL and CTACK were predictive of SFTS, while IL2Ralpha, MIG, IL-8, IFNalpha2, HGF, SCF, MCP-3, and PDGFBB were more common with HFRS. It was further verified by the receiver operating characteristic with area under the curve >0.8 and P-values <0.05, except for TRAIL. Significant differences were observed in the cytokine profiles of SFTS and HFRS, with TRAIL, IL2Ralpha, MIG, and IL-8 being the top 4 cytokines that most clearly distinguished the two diseases. IMPORTANCE: SFTS and HFRS differ in terms of cytokine immune characteristics. TRAIL, IL-2Ralpha, MIG, and IL-8 were the top 4 that differed markedly between SFTS and HFRS.


Asunto(s)
Citocinas , Fiebre Hemorrágica con Síndrome Renal , Síndrome de Trombocitopenia Febril Grave , Humanos , Fiebre Hemorrágica con Síndrome Renal/inmunología , Fiebre Hemorrágica con Síndrome Renal/virología , Fiebre Hemorrágica con Síndrome Renal/sangre , Citocinas/sangre , Masculino , Síndrome de Trombocitopenia Febril Grave/inmunología , Síndrome de Trombocitopenia Febril Grave/virología , Persona de Mediana Edad , Femenino , Estudios Transversales , Adulto , Anciano , Phlebovirus/inmunología
7.
Colloids Surf B Biointerfaces ; 241: 114056, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38924851

RESUMEN

Although nucleic acids have been widely used as templates for the synthesis of nanomaterials, the synthesis of RNA-templated gold nanoclusters (AuNCs) has not been explored. In this work, we developed a simple strategy for synthesis of RNA-templated fluorescent AuNCs. We first evaluated the adsorption of different nucleoside monophosphates (NMP) on gold atoms. Our density function theory simulation and isothermal titration calorimetry measurements demonstrated that adenosine monophosphate (AMP) is a superior gold binder than other NMPs or deoxyadenosine monophosphate. Afterwards, NMP-templated synthesis of AuNCs was conducted in various pH environments, and our results indicated that bright green light-emitting AMP-templated AuNCs can be obtained at pH ∼6.0. In order to study the synthesis mechanism of AuNCs, we investigated the effects of reducing agent type and addition time, and the negative charge carried by template nucleotides on the fluorescence of AuNCs. Finally, we extended the template AMP into RNA hairpin structure, the fluorescence intensity was the highest when the cyclic bases were poly 16 A. This study opens new routes to synthesize fluorescent AuNCs using RNA templates.


Asunto(s)
Oro , Nanopartículas del Metal , ARN , ARN/química , Oro/química , Nanopartículas del Metal/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Concentración de Iones de Hidrógeno , Fluorescencia , Adenosina Monofosfato/química , Teoría Funcional de la Densidad
8.
Chem Asian J ; 19(13): e202400375, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693700

RESUMEN

Methane and its oxidation product (i. e., CO2) are both greenhouse gases. In the product chain of CO hydrogenation to hydrocarbon reaction, methane is also an unwanted product due to its poor added value. Herein we investigated the effect of structure-directing agent urotropine on cobalt-based catalyst supported on Al-O-Zn type carrier and achieved an initial and pioneering exploration of methane-free CO hydrogenation to hydrocarbon reaction at mild CO conversion range. The catalyst modified by urotropine has a nanoflower micromorphology and can significantly change the reaction performance, almost completely eliminating the ability of the catalyst to inhibit C-C coupling within a mild CO conversion range, that is, it can produce no or less C1-C4 gaseous hydrocarbons, while rich in condensed hydrocarbons (i. e., C5+ hydrocarbon selectivity can reach as high as 92.8 %-100.0 %).

9.
Biosens Bioelectron ; 258: 116336, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38692222

RESUMEN

As pure antipodes may differ in biological interactions, pharmacology, and toxicity, discrimination of enantiomers is important in the pharmaceutical and agrochemical industries. Two major challenges in enantiomer determination are transducing and amplifying the distinct chiral-recognition signals. In this study, a light-sensitive organic photoelectrochemical transistor (OPECT) with homochiral character is developed for enantiomer discrimination. Demonstrated with the discrimination of glucose enantiomers, the photoelectrochemically active gate electrode is prepared by integrating Au nanoparticles (AuNPs) and a chiral Cu(II)-metal-organic framework (c-CuMOF) onto TiO2 nanotube arrays (TNT). The captured glucose enantiomers are oxidized to hydrogen peroxide (H2O2) by the oxidase-mimicking AuNPs-loaded c-CuMOF. Based on the confinement effect of the mesopocket structure of the c-CuMOF and the remarkable charge transfer ability of the 1D nanotubular architecture, variations in H2O2 yield are translated into significant changes in OPECT drain currents (ID) by inducing a catalytic precipitation reaction. Variations in ID confer a sensitive discrimination of glucose enantiomers with a limit of detection (LOD) of 0.07 µM for L-Glu and 0.05 µM for D-Glu. This enantiomer-driven gate electrode response strategy not only provides a new route for enantiomer identification, but also helps to understand the origin of the high stereoselectivity in living systems.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Glucosa , Oro , Peróxido de Hidrógeno , Límite de Detección , Nanopartículas del Metal , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Técnicas Biosensibles/instrumentación , Oro/química , Técnicas Electroquímicas/instrumentación , Estereoisomerismo , Nanopartículas del Metal/química , Glucosa/análisis , Glucosa/química , Glucosa/aislamiento & purificación , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Titanio/química , Transistores Electrónicos , Cobre/química , Luz , Monosacáridos/análisis , Monosacáridos/química , Nanotubos/química
10.
J Am Chem Soc ; 146(20): 14318-14327, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38718345

RESUMEN

Multiband convergence has attracted significant interest due to its positive effects on further improving thermoelectric performance. However, the current research mainly focuses on two- or three-band convergence in lead chalcogenides through doping and alloying. Therefore, exploring a new strategy to facilitate more-band convergence has instructive significance and practical value in thermoelectric research. Herein, we first propose a high-entropy strategy to achieve four-band convergence for optimizing thermoelectric performance. Taking high-entropy AgSbPbSnGeTe5 as an example, we found that the emergence of more-band convergence occurs as the configuration entropy increases; in particular, the four-band convergence occurs in high-entropy AgSbPbSnGeTe5. The overlap of multiatom orbitals in the high-entropy sample contributes to the convergence of four valence bands, promoting the improvement of electrical performance. Meanwhile, due to large lattice distortion and disordered atoms, the phonon mean free path is effectively compressed, resulting in low lattice thermal conductivity of high-entropy AgSbPbSnGeTe5. Consequently, AgSbPbSnGeTe5 achieved an intrinsically high ZT value of 1.22 at 673 K, providing a cornerstone for further optimizing thermoelectric performance. For example, by generally optimizing the carrier concentration, a peak ZT value of ∼1.75 at 723 K is achieved. These insights offer a comprehensive understanding of the band structure affected by unique structures of high-entropy materials and also shed useful light on innovation mechanisms and functionalities for future improvement of thermoelectric performance.

11.
Front Immunol ; 15: 1379114, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812521

RESUMEN

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients. Methods: The prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis. Results: The levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P <0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load (P<0.01). Discussion: For the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects.


Asunto(s)
Biomarcadores , Citocinas , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Síndrome de Trombocitopenia Febril Grave/sangre , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Síndrome de Trombocitopenia Febril Grave/mortalidad , Síndrome de Trombocitopenia Febril Grave/inmunología , Femenino , Biomarcadores/sangre , Pronóstico , Persona de Mediana Edad , Citocinas/sangre , Anciano , Estudios Prospectivos , Estudios Longitudinales , Curva ROC
12.
Nat Commun ; 15(1): 4643, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821959

RESUMEN

Silk nanofibrils (SNFs), the fundamental building blocks of silk fibers, endow them with exceptional properties. However, the intricate mechanism governing SNF assembly, a process involving both protein conformational transitions and protein molecule conjunctions, remains elusive. This lack of understanding has hindered the development of artificial silk spinning techniques. In this study, we address this challenge by employing a graphene plasmonic infrared sensor in conjunction with multi-scale molecular dynamics (MD). This unique approach allows us to probe the secondary structure of nanoscale assembly intermediates (0.8-6.2 nm) and their morphological evolution. It also provides insights into the dynamics of silk fibroin (SF) over extended molecular timeframes. Our novel findings reveal that amorphous SFs undergo a conformational transition towards ß-sheet-rich oligomers on graphene. These oligomers then connect to evolve into SNFs. These insights provide a comprehensive picture of SNF assembly, paving the way for advancements in biomimetic silk spinning.

13.
Dev Cell ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38821057

RESUMEN

The interactions of environmental compartments with epithelial cells are essential for mammary gland development and homeostasis. Currently, the direct crosstalk between the endothelial niche and mammary epithelial cells remains poorly understood. Here, we show that faciogenital dysplasia 5 (FGD5) is enriched in mammary basal cells (BCs) and mediates critical interactions between basal and endothelial cells (ECs) in the mammary gland. Conditional deletion of Fgd5 reduced, whereas conditional knockin of Fgd5 increased, the engraftment and expansion of BCs, regulating ductal morphogenesis in the mammary gland. Mechanistically, murine mammary BC-expressed FGD5 inhibited the transcriptional activity of activating transcription factor 3 (ATF3), leading to subsequent transcriptional activation and secretion of CXCL14. Furthermore, activation of CXCL14/CXCR4/ERK signaling in primary murine mammary stromal ECs enhanced the expression of HIF-1α-regulated hedgehog ligands, which initiated a positive feedback loop to promote the function of BCs. Collectively, these findings identify functionally important interactions between BCs and the endothelial niche that occur through the FGD5/CXCL14/hedgehog axis.

14.
Nature ; 629(8014): 1091-1099, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38750363

RESUMEN

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.


Asunto(s)
Adansonia , Filogenia , Adansonia/clasificación , Adansonia/genética , Biodiversidad , Conservación de los Recursos Naturales , Ecología , Especies en Peligro de Extinción , Evolución Molecular , Genoma de Planta/genética , Madagascar , Dinámica Poblacional , Elevación del Nivel del Mar
15.
Inflammopharmacology ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767761

RESUMEN

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease with a relapsing-remitting course. Although its etiology remains unknown, excessive oxidative stress in colon is a major intermediate factor that can promote the progression of UC. In the present study, we investigated the effect and the underlying mechanisms of 4-Octyl itaconate (OI) on dextran sulfate sodium (DSS)-induced UC in mice. Our work identified that OI alleviated the colitis by reducing the oxidative stress and the apoptosis in colon tissue, then increasing the tight junction proteins expression and in turn enhancing the intestinal barrier function, thereby creating less severe inflammatory responses. Moreover, our results demonstrated that OI reduced the Kelch-like ECH-associated protein 1 (KEAP1) expression and subsequent upregulated nuclear factor E2-related factor (NRF2) expression and its nuclear translocation which in turn induced the expression of glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). In addition, ML385, a NRF2 antagonist, can inhibit the protective effects of OI on UC, indicating that the role of OI in this colitis model could be dependent on the activation of KEAP1-NRF2 pathway. Notably, OI co-administration significantly enhanced the therapeutic effects of mesalazine or 1400W on UC. Collectively, itaconate may have a great potential for use in the treatment of IBD.

16.
Cancer Res ; 84(15): 2450-2467, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38718305

RESUMEN

Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Herein, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing N-methyl-N-nitrosourea-induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK-cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL. Significance: Targeting HDAC3 suppresses progression of T-cell lymphoma by activating ATF3 to induce secretion of CXCL12 and promote infiltration of NK cells, providing an immunostimulatory approach for treating T-cell lymphoma patients.


Asunto(s)
Factor de Transcripción Activador 3 , Quimiocina CXCL12 , Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Células Asesinas Naturales , Linfoma de Células T Periférico , Animales , Inhibidores de Histona Desacetilasas/farmacología , Ratones , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/inmunología , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/genética , Humanos , Quimiocina CXCL12/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Factor de Transcripción Activador 3/metabolismo , Factor de Transcripción Activador 3/genética , Línea Celular Tumoral , Femenino , Masculino , Ratones Endogámicos C57BL , Pronóstico
17.
Bioact Mater ; 38: 438-454, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38770428

RESUMEN

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

18.
J Am Med Inform Assoc ; 31(6): 1268-1279, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38598532

RESUMEN

OBJECTIVES: Herbal prescription recommendation (HPR) is a hot topic and challenging issue in field of clinical decision support of traditional Chinese medicine (TCM). However, almost all previous HPR methods have not adhered to the clinical principles of syndrome differentiation and treatment planning of TCM, which has resulted in suboptimal performance and difficulties in application to real-world clinical scenarios. MATERIALS AND METHODS: We emphasize the synergy among diagnosis and treatment procedure in real-world TCM clinical settings to propose the PresRecST model, which effectively combines the key components of symptom collection, syndrome differentiation, treatment method determination, and herb recommendation. This model integrates a self-curated TCM knowledge graph to learn the high-quality representations of TCM biomedical entities and performs 3 stages of clinical predictions to meet the principle of systematic sequential procedure of TCM decision making. RESULTS: To address the limitations of previous datasets, we constructed the TCM-Lung dataset, which is suitable for the simultaneous training of the syndrome differentiation, treatment method determination, and herb recommendation. Overall experimental results on 2 datasets demonstrate that the proposed PresRecST outperforms the state-of-the-art algorithm by significant improvements (eg, improvements of P@5 by 4.70%, P@10 by 5.37%, P@20 by 3.08% compared with the best baseline). DISCUSSION: The workflow of PresRecST effectively integrates the embedding vectors of the knowledge graph for progressive recommendation tasks, and it closely aligns with the actual diagnostic and treatment procedures followed by TCM doctors. A series of ablation experiments and case study show the availability and interpretability of PresRecST, indicating the proposed PresRecST can be beneficial for assisting the diagnosis and treatment in real-world TCM clinical settings. CONCLUSION: Our technology can be applied in a progressive recommendation scenario, providing recommendations for related items in a progressive manner, which can assist in providing more reliable diagnoses and herbal therapies for TCM clinical task.


Asunto(s)
Algoritmos , Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Sistemas de Apoyo a Decisiones Clínicas , Diagnóstico Diferencial , Síndrome , Conjuntos de Datos como Asunto , Prescripciones de Medicamentos
19.
Front Genet ; 15: 1381832, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38666292

RESUMEN

Asia arowana (Scleropages formosus) is an ornamental fish with high economic value, while its sex determination mechanism is still poorly understood. By far, no morphological evidence or molecular marker has been developed for effective distinguishment of genders, which poses a critical challenge to our captive breeding efforts. In this study, we sequenced gonadal transcriptomes of adult Asian arowanas and revealed differential expression profiling of sex-related genes. Based on the comparative transcriptomics analysis of testes (n = 3) and ovaries (n = 3), we identified a total of 8,872 differentially expressed genes (DEGs) and 18,490 differentially expressed transposable elements (TEs) between male and female individuals. Interestingly, the expression of TEs usually has been more significantly testis-biased than related coding genes. As expected, several genes related to females (such as foxl2 and cyp19a1a) are significantly transcribed in the ovary, and some genes related to male gonad development (such as dmrt1, gsdf and amh) are highly expressed in the testis. This sexual dimorphism is valuable for ascertaining the differential expression patterns of sex-related genes and enriching the genetic resources of this economically important species. These valuable genetic materials thereby provide instructive references for gender identification and one-to-one breeding practices so as to expand fish numbers for a rapid elevation of economic value.

20.
Nano Lett ; 24(14): 4248-4255, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38557042

RESUMEN

Grain boundaries (GBs) in two-dimensional (2D) covalent organic frameworks (COFs) unavoidably form during the fabrication process, playing pivotal roles in the physical characteristics of COFs. Herein, molecular dynamics simulations were employed to elucidate the fracture failure and thermal transport mechanisms of polycrystalline COFs (p-COFs). The results revealed that the tilt angle of GBs significantly influences out-of-plane wrinkles and residual stress in monolayer p-COFs. The tensile strength of p-COFs can be enhanced and weakened with the tilt angle, which exhibits an inverse relationship with the defect density. The crack always originates from weaker heptagon rings during uniaxial tension. Notably, the thermal transport in p-COFs is insensitive to the GBs due to the variation of minor polymer chain length at defects, which is abnormal for other 2D crystalline materials. This study contributes insights into the impact of GBs in p-COFs and offers theoretical guidance for structural design and practical applications of advanced COFs.

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