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1.
Artículo en Inglés | MEDLINE | ID: mdl-39352424

RESUMEN

PURPOSE: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [18F]Florzolotau PET in PSP. METHODS: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like. RESULTS: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses. CONCLUSION: Through the application of the suggested visual reading algorithm, [18F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP.

2.
Int J Biol Macromol ; : 136809, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39447799

RESUMEN

The rising demand for premium quality fruits and vegetables has resulted in an increased necessity for the advancement in active food packaging. This study aimed to develop eugenol-loaded Ag@MOF/poly(lactic acid) (Ag@MOF-EU/PLA) composite films to assess their efficacy in preserving zucchini. The results revealed that Ag@MOF-EU can be uniformly distributed within the PLA matrix, which significantly enhanced the tensile strength, hydrophobicity, and UV-blocking capacity of PLA films, and at the same time had no significant effect on the thermal properties and WVP of the PLA films. Moreover, the resulting Ag@MOF-EU/PLA films exhibited no cytotoxicity. In a food simulant (50 % ethanol), the release behavior of the EU demonstrated a sustained release over 20 days. Furthermore, Ag@MOF-EU/PLA had an enhanced antimicrobial activity and DPPH scavenging activity, compared to PLA films. The preservation experiment involving zucchini elucidated that the Ag@MOF-EU/PLA composite film could extend the shelf life of zucchini by maintaining color, reducing weight loss, delaying the decline in firmness, and inhibiting the growth of total viable colonies. These findings indicated that the Ag@MOF-EU/PLA films developed within the scope of this research possess the potential to serve as effective food-active packaging materials.

3.
Sci Total Environ ; : 177032, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39447913

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are harmful and widespread pollutants in the environment, posing an ecological threat. However, exploring the influence of PAHs on environmental bacterial communities in different habitats (soil, water, and sediment) remains a major challenge. We collected and reanalyzed 1924 16S rRNA sequencing samples to determine the effects of PAHs on bacterial communities in different habitats and used machine learning to predict potential degrading bacteria. It was found that PAHs had substantial effects on the bacterial community, and that the bacterial community structure changed differently in different habitats. PAH contamination decreased the relative abundance of Proteobacteria in the soil (16.3 %) and sediment (10.1 %), whereas the abundance of Proteobacteria in water increased by 20.2 %. Among the tested models, the random forest model best identified the effects of PAHs on bacterial groups, with an accuracy of 99.51 % for soil, 97.72 % for sediment, and 100 % for water at the genus level. Using the random forest model, we identified 70 biomarkers that respond to PAHs, including potentially degrading microorganisms such as A4b, Bacillus, Flavobacterium and Polynucleobacter. Furthermore, PAH contamination did not significantly alter the functions of bacterial communities in the environment. This study provides a candidate strain set for future screening of PAH-degrading bacteria and contributes to the study of the adaptability of engineered PAH-degrading bacteria to the environment.

5.
Int J Biol Macromol ; 279(Pt 3): 135319, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39236951

RESUMEN

Developing phosphorus removal adsorbents with high adsorption performance and excellent structural stability remains a challenge. Herein, a chitosan (CS) - amidated lignin (AL) gel-bead adsorbent with high efficiency in immobilizing lanthanum hydroxide (La(OH)3) was fabricated via an in situ precipitation and freeze-drying strategy (abbreviated as La@ALCSx). The abundant hydroxyl and amino groups in CS promoted excellent loading of La(OH)3 on the surface and inside of the adsorbent. The introduction of lignin enhanced the structural stability of the beads along with the mass transfer efficiency. Owing to the porous structure and high La utilization, the adsorption capacity of La@ALCS2 reached 130.52 mg P g-1. Intra-sphere complexation of La(OH)3 with phosphate resulted in high adsorption selectivity of La@ALCS2. Moreover, the millimeter-sized of La@ALCS2 has favourable recoverability and maintains high adsorption performance after five adsorption-desorption cycles. Characterization analysis indicated that electrostatic attraction and ligand exchange were the main adsorption mechanisms. The excellent phosphorus removal efficiency, separation efficiency and recyclability of La@ALCSx provide a viable solution for the remediation of phosphate contaminated waters.


Asunto(s)
Quitosano , Lantano , Lignina , Fosfatos , Contaminantes Químicos del Agua , Purificación del Agua , Lantano/química , Quitosano/química , Lignina/química , Adsorción , Fosfatos/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos , Geles/química , Hidróxidos/química , Agua/química , Microesferas , Concentración de Iones de Hidrógeno
6.
Small ; : e2401977, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189525

RESUMEN

Photocatalytic biorefinery has been gaining increasing attention as a promising method for utilizing biomass and solar energy, yet it still faces the key challenge of designing stable, efficient, and cost-effective photocatalysts. In this study, cobalt sulfide/ C. I. Pigment Yellow 53 composite photocatalysts (CoS/PY53-CSx) with a core-shell structure, which has abundant sulfur (S) vacancies, are developed using a simple hydrothermal method. The CoS nanocage with S vacancies not only offers numerous active sites but also enhances the light-trapping performance of PY53. Moreover, the internal electric field within the core-shell CoS/PY53-CSx further enhances charge separation/transfer efficiency while reducing electron transfer resistance, thereby boosting photocatalytic activity. Remarkably, 75.2% of xylonic acid and 22.8 µmol of CO from xylose are obtained using CoS/PY53-CS0.1 in an air atmosphere. Recycling experiments demonstrate that CoS/PY53-CS0.1 exhibits excellent recyclability due to the strong bonding force between the core and shell. In addition, electron spin resonance characterization combined with poisoning experiments suggests that h+ and ·O2 - serve as the main oxidation active species during this system. This work presents a simple and cost-effective method for efficient photocatalytic biorefinery.

7.
Cancer Cell ; 42(8): 1370-1385.e9, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39137726

RESUMEN

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors. Using single-cell-RNA-sequencing and spatial-enhanced-resolution-omics-sequencing (Stereo-seq), we reveal that TLS+ tumors are enriched with IgG+ plasma cells (PCs), while TLS- tumors are characterized with IgA+ PCs. By generating TLS-associated PC-derived monoclonal antibodies in vitro, we show that TLS-PCs secrete tumor-targeting antibodies. As the proof-of-concept, we demonstrate the anti-tumor activities of TLS-PC-mAb6 antibody in humanized mouse model of colorectal cancer. We identify a fibroblast lineage secreting CCL19 that facilitates lymphocyte trafficking to TLSs. CCL19 treatment promotes TLS neogenesis and prevents tumor growth in mice. Our data uncover the central role of CCL19+ fibroblasts in TLS formation, which in turn generates therapeutic antibodies to restrict CRLM.


Asunto(s)
Quimiocina CCL19 , Neoplasias Colorrectales , Inmunoglobulina G , Neoplasias Hepáticas , Estructuras Linfoides Terciarias , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Animales , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Ratones , Inmunoglobulina G/inmunología , Quimiocina CCL19/metabolismo , Quimiocina CCL19/genética , Fibroblastos/metabolismo , Fibroblastos/inmunología , Anticuerpos Monoclonales/farmacología , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Femenino , Línea Celular Tumoral
8.
Mol Neurobiol ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052185

RESUMEN

Alzheimer's disease (AD) is a leading neurodegenerative disorder with substantial impacts on cognition and behavior. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has been used to treat various neuropsychiatric disorders, but its efficacy in AD has not been thoroughly investigated. This study examines the neuroprotective effects of rTMS in the 5xFAD mouse model of AD, with a particular focus on its modulation of GABAergic neuronal activity via the GABRG2 and SNAP25 proteins. Transcriptomic sequencing of rTMS-treated 5xFAD mice revealed 32 genes influenced by the treatment, among which GABRG2 was identified as a critical modulatory target. Electrophysiological assessments, including whole-cell patch clamp recordings from frontal cortex neurons, demonstrated significant alterations in inhibitory synaptic currents following rTMS. Subsequent experiments involved sh-GABRG2 transduction combined with rTMS treatment (20Hz, 14 days), examining behavioral responses, GABAergic neuron functionality, cortical GABA expression, cerebrospinal fluid GABA concentrations, ß-amyloid accumulation, and pro-inflammatory cytokine levels. The results indicated notable improvements in behavioral performance, enhanced functionality of GABAergic neurons, and reductions in ß-amyloid deposition and neuroinflammation after rTMS treatment. Further analysis revealed that SNAP25 overexpression could counteract the negative effects of GABRG2 silencing, highlighting the crucial role of SNAP25 downstream of GABRG2 in mediating rTMS's therapeutic effects in AD. This research highlights rTMS's potential to modulate synaptic and vesicular transport mechanisms, offering a promising avenue for ameliorating symptoms of AD through neuroprotective pathways.

9.
Nat Commun ; 15(1): 5879, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-38997253

RESUMEN

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.


Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Xantenos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Xantenos/síntesis química , Xantenos/farmacología , Xantenos/química , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Descubrimiento de Drogas , Estructura Molecular
10.
Neuropharmacology ; 255: 110006, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38763325

RESUMEN

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aß deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction.


Asunto(s)
Disfunción Cognitiva , Edaravona , Glicoproteínas de Membrana , Receptores Inmunológicos , Receptor Toll-Like 4 , Regulación hacia Arriba , Animales , Receptor Toll-Like 4/metabolismo , Ratones , Masculino , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Glicoproteínas de Membrana/metabolismo , Edaravona/farmacología , Edaravona/uso terapéutico , Regulación hacia Arriba/efectos de los fármacos , Ratones Transgénicos , Fármacos Neuroprotectores/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Ratones Endogámicos C57BL , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Modelos Animales de Enfermedad , Presenilina-1/genética
11.
Inorg Chem ; 63(23): 10471-10480, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38787770

RESUMEN

Two quaternary manganese selenites, A2(Mn2O)(SeO3)3 (A = K, Rb), have been synthesized by hydrothermal reactions. They both crystallize in a complex triclinic (P-1) structure built of Jahn-Teller (JT) distorted Mn3+O4+2 octahedra, connected into nearly isosceles [Mn3O14] triangles, themselves arranged into so-called "sawtooth (ST) chains". The K and Rb compounds show subtle variations in the orientations of the MnO4 planes inside the elementary triangles. The ST chains are structurally and magnetically isolated by SeO3 groups and alkali cations. In the ST chains, predominant ferromagnetic interactions were calculated and verified experimentally, which finally order antiferromagnetically between the chains around TN ≈ 22 K. The spin exchanges calculated by DFT + U and fitted by Monte Carlo simulations allow for the quantification of an effective "overall" model. The specific role of the µ3-O bridge on the ferromagnetic (FM) exchanges is discussed, together with spin reorientations observed in the ordered state. Magnetocrystalline anisotropy along the [110] direction stabilized by ∼50 meV per Mn by spin-orbit coupling (SOC) was found by DFT + U + SOC.

12.
Int Immunopharmacol ; 134: 112233, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38735256

RESUMEN

Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field.


Asunto(s)
Inmunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/diagnóstico por imagen , Inmunoterapia/métodos , Animales , Ultrasonografía/métodos , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Microburbujas , Inmunoterapia Adoptiva/métodos , Terapia Combinada , Terapia por Ultrasonido/métodos
13.
J Phys Condens Matter ; 36(33)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38729186

RESUMEN

Spin reorientation transition is an ubiquitous phenomenon observed in magnetic rare earth orthferrites RFeO3, which has garnered significant attention in recent years due to its potential applications in spintronics or magnetoelectric devices. Although a plenty of experimental works suggest that the magnetic interaction between R3+and Fe3+spins is at the heart of the spin reorientation, but a direct and conclusive theoretical support has been lacking thus far, primarily due to the challenging nature of handling R 4felectrons. In this paper, we explored DyFeO3as an example by means of comprehensive first principles calculations, and compared two different approaches, where the Dy 4felectrons were treated separately as core or valence states, aiming to elucidate the role of Dy 4felectrons, particularly in the context of the spin reorientation transition. The comparison provides a solid piece of evidence for the experimental argument that the Dy3+-Fe3+magnetic interactions play a vital role in triggering spin reorientation of Fe3+moments at low temperatures. The findings revealed here not only extend our understanding on the underlying mechanism for spin reorientation transition in RFeO3, but also highlight the importance of explicit description of R 4felectrons in rationally reproducing their structural, electronic and magnetic properties.

14.
Regen Biomater ; 11: rbae039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38746707

RESUMEN

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

15.
Front Aging Neurosci ; 16: 1390915, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38752208

RESUMEN

Background: Recent studies show testosterone (T) deficiency worsens cognitive impairment in Alzheimer's disease (AD) patients. Mitochondrial dysfunction, as an early event of AD, is becoming critical hallmark of AD pathogenesis. However, currently, whether T deficiency exacerbates mitochondrial dysfunction of men with AD remains unclear. Objective: The purpose of this study is to explore the effects of T deficiency on mitochondrial dysfunction of male AD mouse models and its potential mechanisms. Methods: Alzheimer's disease animal model with T deficiency was performed by castration to 3-month-old male APP/PS1 mice. Hippocampal mitochondrial function of mice was analyzed by spectrophotometry and flow cytometry. The gene expression levels related to mitochondrial biogenesis and mitochondrial dynamics were determined through quantitative real-time PCR (qPCR) and western blot analysis. SH-SY5Y cells treated with flutamide, T and/or H2O2 were processed for analyzing the potential mechanisms of T on mitochondrial dysfunction. Results: Testosterone deficiency significantly aggravated the cognitive deficits and hippocampal pathologic damage of male APP/PS1 mice. These effects were consistent with exacerbated mitochondrial dysfunction by gonadectomy to male APP/PS1 mice, reflected by further increase in oxidative damage and decrease in mitochondrial membrane potential, complex IV activity and ATP levels. More importantly, T deficiency induced the exacerbation of compromised mitochondrial homeostasis in male APP/PS1 mice by exerting detrimental effects on mitochondrial biogenesis and mitochondrial dynamics at mRNA and protein level, leading to more defective mitochondria accumulated in the hippocampus. In vitro studies using SH-SY5Y cells validated T's protective effects on the H2O2-induced mitochondrial dysfunction, mitochondrial biogenesis impairment, and mitochondrial dynamics imbalance. Administering androgen receptor (AR) antagonist flutamide weakened the beneficial effects of T pretreatment on H2O2-treated SH-SY5Y cells, demonstrating a critical role of classical AR pathway in maintaining mitochondrial function. Conclusion: Testosterone deficiency exacerbates hippocampal mitochondrial dysfunction of male APP/PS1 mice by accumulating more defective mitochondria. Thus, appropriate T levels in the early stage of AD might be beneficial in delaying AD pathology by improving mitochondrial biogenesis and mitochondrial dynamics.

17.
Cell Transplant ; 33: 9636897241247951, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38651796

RESUMEN

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown. Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3-4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8-18 weeks after CAR T cell infusion. These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3-4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load. The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3-4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3-4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3-4 persistent cytopenia than in those without cytopenia. Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.


Asunto(s)
Antígenos CD19 , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Femenino , Persona de Mediana Edad , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Adulto , Antígenos CD19/metabolismo , Anciano , Receptores Quiméricos de Antígenos/uso terapéutico , Adulto Joven , Citopenia
18.
Artículo en Inglés | MEDLINE | ID: mdl-38573002

RESUMEN

Aims: Erythropoiesis is controlled by several factors, including oxygen level under different circumstances. However, the role of hypoxia in erythroid differentiation and the underlying mechanisms are poorly understood. We studied the effect and mechanism of hypoxia on erythroid differentiation of K562 cells and observed the effect of hypoxia on early erythropoiesis of zebrafish. Results: Compared with normal oxygen culture, both hemin-induced erythroid differentiation of K562 cells and the early erythropoiesis of zebrafish were inhibited under hypoxic treatment conditions. Hypoxia-inducible factor 1 alpha (HIF1α) plays a major role in the response to hypoxia. Here, we obtained a stable HIF1α knockout K562 cell line using the CRISPR-Cas9 technology and further demonstrated that HIF1α knockout promoted hemin-induced erythroid differentiation of K562 cells under hypoxia. We demonstrated an HIF1-mediated induction of the nuclear factor interleukin-3 (NFIL3) regulated in K562 cells under hypoxia. Interestingly, a gradual decrease in NFIL3 expression was detected during erythroid differentiation of erythropoietin-induced CD34+ hematopoietic stem/progenitor cells (HSPCs) and hemin-induced K562 cells. Notably, erythroid differentiation was inhibited by enforced expression of NFIL3 under normoxia and was promoted by the knockdown of NFIL3 under hypoxia in hemin-treated K562 cells. In addition, a target of NFIL3, pim-1 proto-oncogene, serine/threonine kinase (PIM1), was obtained by RNA microarray after NFIL3 knockdown. PIM1 can rescue the inhibitory effect of NFIL3 on hemin-induced erythroid differentiation of K562 cells. Innovation and Conclusion: Our findings demonstrate that the HIF1α-NFIL3-PIM1 signaling axis plays an important role in erythroid differentiation under hypoxia. These results will provide useful clues for preventing the damage of acute hypoxia to erythropoiesis.

19.
Phys Chem Chem Phys ; 26(16): 12806-12819, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38619877

RESUMEN

Combining the phosphonic acid group with the sulfonic acid group in PEMs has been shown to be an effective strategy for improving the fuel cell performance. However, the interplay of two different ionic groups and the resulting effect on the membrane properties have not been fully elucidated. Here, we used classical molecular dynamics simulation to investigate the morphologies, transport properties and effects of ionic groups in a novel perfluorinated PEM containing two ionic groups (PFSA-PFPA) in comparison to the corresponding homopolymers. Phase separations between hydrophilic and hydrophobic domains are confirmed in these PEMs and result from the evolution of water clusters formed around the ionic groups. The combination of both ionic groups brings a complicated morphological feature in PFSA-PFPA, with near-cylindrical aqueous domains of large length scales interconnected by tortuous domains of small sizes. And we found that the self-diffusion coefficients of water molecules are strongly related to morphologies, with the water transport in PFSA-PFPA lying between two analogous homopolymers. At the molecular level, we found that the sulfonic and phosphonic acid groups have distinct effects on the coordination behaviors and the dynamics of water molecules and hydronium ions. Strong electrostatic interactions lead to compact coordination structures and sluggish dynamics of hydronium ions around phosphonic acid groups, which determine the morphological evolution and transport properties in PFSA-PFPA. Our study affords insights into the relationship between molecular characteristics and transport properties bridged by phase-separated morphologies in a novel PEM containing both sulfonic acid and phosphonic acid groups, which deepens the understanding of the interplay between two ionic groups and may inspire the rational design of high-performance PEMs.

20.
Med Sci Monit ; 30: e942888, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38576138

RESUMEN

BACKGROUND This retrospective study aimed to compare patient outcomes from standard total knee arthroplasty (TKA) vs navigation-guided arthroplasty using the Brainlab software-guided surgical system at Cangzhou Hospital of Integrated TCM-WM, Hebei, Hebei Province, China from January 2021 to July 2023. MATERIAL AND METHODS A total of 239 patients who underwent total knee arthroplasty in Cangzhou Hospital of Integrated TCM-WM, Hebei from January 2021 to July 2023 were retrospectively analyzed. According to the inclusion criteria, 212 eligible patients were selected for analysis and divided into a Navigation Group (NG) (n=105) and a Traditional Group (TG) (n=107) according to surgical method used. Outcomes measured included duration of disease, operative time, intraoperative blood loss volume, postoperative length of hospital stay, and pain measured by the hospital for special surgery knee score (HSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and forgotten joint score (FJS). RESULTS The comparison of perioperative results between the 2 groups showed that the incision length in the NG was significantly longer than that in the TG (P<0.001, 95% Cl 2.59-3.35). At 3 months after surgery, the HSS score of the NG was statistically higher than that of the TG (P=0.002, 95% Cl 3.42-4.46); the WOMAC score of the NG was lower than that of the TG (P<0.001, 95% Cl -4.41-2.87); and the FJS score of the NG was significantly higher than that of the TG (P=0.003, 95% Cl 2.39-3.67). CONCLUSIONS Compared with conventional TKA, use of the Brainlab navigation system is associated with a longer incision, more accurate implantation position of the prosthesis, faster recovery of knee joint function, and helps patients to "forget" about their knee prosthesis in the short term.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Herida Quirúrgica , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Resultado del Tratamiento
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