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1.
Support Care Cancer ; 32(5): 287, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619660

RESUMO

PURPOSE: Advanced lung cancer and its treatment serve as a sudden stressful event that profoundly impacts the psychological experience of both the patients and their primary caregiver. This study used dyadic analyses to explore the dyadic effects of social support on benefit finding and whether hope level mediates the patient-caregiver dyads in advanced lung cancer. METHODS: Two hundred ninety-five pairs of patients with advanced lung cancer and primary caregivers completed the Social Support Rating Scale (SSRS), the Herth Hope Index (HHI), and the Benefit Finding Scale (BFS). Dyadic analyses were conducted using structural equation modelling based on the actor-partner interdependence mediation model. RESULTS: The results indicated that for both patients (B = 0.259, 95% CI = 0.135-0.423, P < 0.001) and their primary caregivers (B = 0.596, 95% CI = 0.403-0.838, P < 0.001), hope level mediated the actor effect of social support on benefit finding; social support was positively associated with hope level and further enhanced benefit finding. Regarding partner effects (B = 0.242, 95% CI = 0.119-0.404, P < 0.001), primary caregivers' social support significantly indirectly affected patients' benefit finding through patients' hope level. CONCLUSION: There is an interaction between social support, hope level, and benefit finding in patients with advanced lung cancer and their primary caregivers. Healthcare professionals ought to be vigilant in recognizing patients and caregivers who are vulnerable, have limited social support, and possess diminished hope levels. At the same time, nurses should provide timely psychological support and counseling to patients and their caregivers, encourage them to actively participate in social activities, and inspire their confidence and hope in life, thus improving their benefit findings.


Assuntos
Cuidadores , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Pessoal de Saúde , Apoio Social , Análise de Classes Latentes
2.
Br J Haematol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622924

RESUMO

Juvenile myelomonocytic leukaemia (JMML) is a rare myeloproliferative neoplasm requiring haematopoietic stem cell transplantation (HSCT) for potential cure. Relapse poses a significant obstacle to JMML HSCT treatment, as the lack of effective minimal residual disease (MRD)-monitoring methods leads to delayed interventions. This retrospective study utilized the droplet digital PCR (ddPCR) technique, a highly sensitive nucleic acid detection and quantification technique, to monitor MRD in 32 JMML patients. The results demonstrated that ddPCR detected relapse manifestations earlier than traditional methods and uncovered molecular insights into JMML MRD dynamics. The findings emphasized a critical 1- to 3-month window post-HSCT for detecting molecular relapse, with 66.7% (8/12) of relapses occurring within this period. Slow MRD clearance post-HSCT was observed, as 65% (13/20) of non-relapse patients took over 6 months to achieve ddPCR-MRD negativity. Furthermore, bone marrow ddPCR-MRD levels at 1-month post-HSCT proved to be prognostically significant. Relapsed patients exhibited significantly elevated ddPCR-MRD levels at this time point (p = 0.026), with a cut-off of 0.465% effectively stratifying overall survival (p = 0.007), event-free survival (p = 0.035) and cumulative incidence of relapse (p = 0.035). In conclusion, this study underscored ddPCR's superiority in JMML MRD monitoring post-HSCT. It provided valuable insights into JMML MRD dynamics, offering guidance for the effective management of JMML.

3.
Lancet Infect Dis ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38614117

RESUMO

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

4.
J Nucl Med ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604764

RESUMO

68Ga-labeled nanobody (68Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of 68Ga-NC-BCH for PET to determine its in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying claudin-18 isoform 2 (CLDN18.2) expression in gastrointestinal cancer patients. Methods: Initially, we synthesized the probe 68Ga-NC-BCH and performed preclinical evaluations on human gastric adenocarcinoma cell lines and xenograft mouse models. Next, we performed a translational study with a pilot cohort of patients with advanced gastrointestinal cancer on a total-body PET/CT scanner. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship between tumor uptake and CLDN18.2 expression were evaluated. Results: 68Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,68Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. 68Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with 18F-FDG, 68Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. Conclusion: A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that 68Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.

5.
Cell Signal ; 119: 111168, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599441

RESUMO

Cell division cycle-associated (CDCA) gene family members are essential cell proliferation regulators and play critical roles in various cancers. However, the function of the CDCA family genes in gliomas remains unclear. This study aims to elucidate the role of CDCA family members in gliomas using in vitro and in vivo experiments and bioinformatic analyses. We included eight glioma cohorts in this study. An unsupervised clustering algorithm was used to identify novel CDCA gene family clusters. Then, we utilized multi-omics data to elucidate the prognostic disparities, biological functionalities, genomic alterations, and immune microenvironment among glioma patients. Subsequently, the scRNA-seq analysis and spatial transcriptomic sequencing analysis were carried out to explore the expression distribution of CDCA2 in glioma samples. In vivo and in vitro experiments were used to investigate the effects of CDCA2 on the viability, migration, and invasion of glioma cells. Finally, based on ten machine-learning algorithms, we constructed an artificial intelligence-driven CDCA gene family signature called the machine learning-based CDCA gene family score (MLCS). Our results suggested that patients with the higher expression levels of CDCA family genes had a worse prognosis, more activated RAS signaling pathways, and more activated immunosuppressive microenvironments. CDCA2 knockdown inhibited the proliferation, migration, and invasion of glioma cells. In addition, the MLCS had robust and favorable prognostic predictive ability and could predict the response to immunotherapy and chemotherapy drug sensitivity.

6.
CNS Neurosci Ther ; 30(4): e14707, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584329

RESUMO

AIMS: Mitochondria-associated endoplasmic reticulum membranes (MAMs) serve as a crucial bridge connecting the endoplasmic reticulum (ER) and mitochondria within cells. Vesicle-associated membrane protein-associated protein B (VAPB) and protein tyrosine phosphatase interacting protein 51 (PTPIP51) are responsible for the formation and stability of MAMs, which have been implicated in the pathogenesis of various diseases. However, the role of MAMs in ischemic stroke (IS) remains unclear. We aimed to investigate the role of MAMs tethering protein VAPB-PTPIP51 in experimental cerebral ischemia. METHODS: We simulated cerebral ischemia-reperfusion injury (CIRI) by using a mouse middle cerebral artery occlusion (MCAO) model. RESULTS: We observed a decrease in VAPB-PTPIP51 expression in the brain tissue. Our findings suggested compromised MAMs after MCAO, as a decreased mitochondria-ER contact (MERC) coverage and an increased distance were observed through the transmission electron microscope (TEM). Upon VAPB or PTPIP51 knockdown, the damage to MAMs was exacerbated, accompanied by excessive autophagy activation and increased reactive oxygen species (ROS) production, resulting in an enlarged infarct area and exacerbated neurological deficits. Notably, we observed that this damage was concomitant with the inhibition of the PI3K/AKT/mTOR pathway and was successfully mitigated by the treatment with the PI3K activator. CONCLUSIONS: Our findings suggest that the downregulation of VAPB-PTPIP51 expression after IS mediates structural damage to MAMs. This may exacerbate CIRI by inhibiting the PI3K pathway and activating autophagy, thus providing new therapeutic targets for IS.


Assuntos
AVC Isquêmico , Traumatismo por Reperfusão , Humanos , AVC Isquêmico/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Mitocondriais , Retículo Endoplasmático/metabolismo , Mitocôndrias/metabolismo , Traumatismo por Reperfusão/metabolismo , Autofagia , Proteínas de Transporte Vesicular/metabolismo
7.
World J Gastrointest Surg ; 16(3): 966-973, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577088

RESUMO

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

8.
Food Funct ; 15(8): 4079-4094, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38563230

RESUMO

Gastritis is a common disease characterized by gastric ulcers and severe bleeding. Excessive daily alcohol consumption can cause acute gastritis, impacting individuals' quality of life. This study aims to explore the protective effects of different ethanol-fractional polysaccharides of Dendrobium officinale (EPDO) on acute alcohol-induced gastric injury in vivo. Results showed that EPDO-80, identified as a ß-glucan, exhibited significant anti-inflammatory properties in pathology. It could reduce the area of gastric mucosal injury and cell infiltration. EPDO-80 had a dose-effect relationship in reducing the levels of malondialdehyde and cyclooxygenase-2 and decreasing the levels of inflammation mediators such as tumor necrosis factor α. More extensively, EPDO-80 could inhibit the activation of the TNFR/IκB/NF-κB signaling pathway, reducing the production of TNF-α mRNA and cell apoptosis in organs. Conversely, EPDO-80 could promote changes in the gut microbiota structure. These findings suggest that EPDO-80 could have great potential in limiting oxidative stress and inflammation mediated by inhibiting the NF-κB signaling pathway, which is highly related to its ß-glucan structure and functions in gut microbiota.

9.
J Pediatr (Rio J) ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38642591

RESUMO

OBJECTIVE: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. METHODS: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. RESULTS: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). CONCLUSION: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups.

10.
Int J Biol Macromol ; 267(Pt 2): 131534, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636158

RESUMO

We reported here an interesting source of Alpinia zerumbet Polysaccharides (named AZPs) from the residues after extracting essential oil by steam distillation from Alpinia zerumbet fructus. After a series of purifications, a homogeneous polysaccharide (AZP-2) of molecular weight 1.25 × 105 Da was obtained. Structure, anti-inflammatory activity, and anti-inflammatory mechanism were investigated. AZP-2 was mainly composed of galactose, arabinose, xylopyranose, glucose, and galacturonic acid. The main linkage structure of AZP-2 was determined after integrating the nuclear magnetic resonance (NMR) and methylation analysis, and the structure was comparatively complex. The results indicated that AZP-2 significantly decreased the production of NO and ROS in the inflammatory model established by lipopolysaccharide (LPS) stimulated RAW264.7, particularly at the concentration of 200 µg/mL. Furthermore, AZP-2 significantly modulated the secretion of both pro-inflammatory and anti-inflammatory cytokines. Notably, the mechanism of AZP-2 exhibiting inhibitory effects was related to regulating the NF-κB signaling pathway. Overall, AZP-2 could be used as a potential anti-inflammatory agent for further in-depth studies.

11.
J Phys Chem A ; 128(14): 2743-2751, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38557005

RESUMO

We constructed a new ab initio potential energy surface (PES) for CO-N2O which includes the intramolecular Q3 normal coordinate for the N2O ν3 antisymmetric stretching vibration. The intermolecular potential was evaluated employing the supermolecular method at the [CCSD(T)]-F12a level, with the aug-cc-pVTZ basis set plus bond functions. By integral over the intramolecular Q3 coordinate, we obtained the vibrationally averaged PESs for the CO-N2O system in the ground and ν3 excited states of N2O. Each PES features one nearly T-shaped global minimum and one skewed T-shaped local minimum. Based on these obtained PESs of CO-N2O, the radial discrete variable representation/angle finite base representation method and the Lanczos algorithm were applied for the calculations of bound states and rovibrational energy levels. The calculated ν3 vibrational band origin shift of the N2O monomer in CO-N2O is 2.7570 cm-1, matching well with the observed value of 2.9048 cm-1. The computed microwave and infrared transition frequencies, as well as the rotational parameters, are consistent with the experimental observations.

12.
Int J Infect Dis ; : 107043, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583826

RESUMO

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαß+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.

13.
ACS Sens ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499997

RESUMO

Electromagnetic sensors with flexible antennas as sensing elements have attracted increasing attention in noninvasive continuous glucose monitoring for diabetic patients. The significant radiation performance loss of flexible antennas during mechanical deformation impairs the reliability of glucose monitoring. Here, we present flexible ultrawideband monopole antennas composed of Ti3C2 MXene and cellulose nanofibril (CNF) composite films for continuous glucose monitoring. The flexible MXene/CNF antenna with 20% CNF content can obtain a gain of up to 3.33 dBi and a radiation efficiency of up to 65.40% at a frequency range from 2.3 to 6.0 GHz. Compared with the pure MXene antenna, this antenna offers a comparable radiation performance and a lower performance loss in mechanical bending deformation. Moreover, the MXene/CNF antenna shows a stable response to fetal bovine serum/glucose, with a correlation of >0.9 at the reference glucose levels, and responds sensitively to the variations in blood glucose levels during human trials. The proposed strategy enhancing the mechanical robustness of MXene-based flexible antennas makes metallic two-dimensional nanomaterials more promising in wearable electromagnetic sensors.

14.
Int J Biol Macromol ; 265(Pt 2): 130988, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518942

RESUMO

Codonopsis pilosula is a famous edible and medicinal plants, in which polysaccharides are recognized as one of the important active ingredients. A neutral polysaccharide (CPP-1) was purified from C. pilosula. The structure was characterized by HPSEC-MALLS-RID, UV, FT-IR, GC-MS, methylation analysis, and NMR. The results showed that CPP-1 was a homogeneous pure polysaccharide, mainly containing fructose and glucose, and a small amount of arabinose. Methylation analysis showed that CPP-1 composed of →1)-Fruf-(2→, Fruf-(1→ and Glcp-(1→ residues. Combined the NMR results the structure of CPP-1 was confirmed as α-D-Glcp-(1 â†’ [2)-ß-D-Fruf-(1 â†’ 2)-ß-D-Fruf-(1]26 â†’ 2)-ß-D-Fruf with the molecular weight of 4.890 × 103 Da. The model of AML12 hepatocyte fat damage was established in vitro. The results showed that CPP-1 could increase the activity of SOD and CAT antioxidant enzymes and reduce the content of MDA, thus protecting cells from oxidative damage. Subsequently, the liver protective effect of CPP-1 was studied in the mouse model of nonalcoholic fatty liver disease (NAFLD) induced by the high-fat diet. The results showed that CPP-1 significantly reduced the body weight, liver index, and body fat index of NAFLD mice, and significantly improved liver function. Therefore, CPP-1 should be a potential candidate for the treatment of NAFLD.


Assuntos
Codonopsis , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Codonopsis/química , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Antioxidantes/farmacologia
15.
J Hazard Mater ; 470: 134142, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38555669

RESUMO

Low testosterone (T) levels are associated with many common diseases, such as obesity, male infertility, depression, and cardiovascular disease. It is well known that environmental cadmium (Cd) exposure can induce T decline, but the exact mechanism remains unclear. We established a murine model in which Cd exposure induced testicular T decline. Based on the model, we found Cd caused mitochondrial fusion disorder and Parkin mitochondrial translocation in mouse testes. MFN1 overexpression confirmed that MFN1-dependent mitochondrial fusion disorder mediated the Cd-induced T synthesis suppression in Leydig cells. Further data confirmed Cd induced the decrease of MFN1 protein by increasing ubiquitin degradation. Testicular specific Parkin knockdown confirmed Cd induced the ubiquitin-dependent degradation of MFN1 protein through promoting Parkin mitochondrial translocation in mouse testes. Expectedly, testicular specific Parkin knockdown also mitigated testicular T decline. Mito-TEMPO, a targeted inhibitor for mitochondrial reactive oxygen species (mtROS), alleviated Cd-caused Parkin mitochondrial translocation and mitochondrial fusion disorder. As above, Parkin mitochondrial translocation induced mitochondrial fusion disorder and the following T synthesis repression in Cd-exposed Leydig cells. Collectively, our study elucidates a novel mechanism through which Cd induces T decline and provides a new treatment strategy for patients with androgen disorders.

16.
Transplant Direct ; 10(4): e1588, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38529355

RESUMO

Background: Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. Methods: A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results: Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P < 0.001). On unadjusted analysis, the survival difference among the 5 groups was insignificant (P = 0.07). Following adjustment, the periods of 11 am to 5 pm (HR: 1.09, 95% CI, 1.02-1.17; P = 0.012), 5 pm to 10 pm (HR: 1.11; 95% CI, 1.04-1.19; P = 0.002), and 10 pm to 4 am (HR: 1.07; 95% CI, 1.01-1.15; P = 0.034), were all independently associated with increased long-term mortality. Notably, the time of 8 am to 11 am was not associated with a change in survival (HR: 1.04; 95% CI, 0.96-1.14; P = 0.3). Conclusions: Given the independent association of donor timing and survival after adjustment in a large national cohort, further investigation into the role of donor circadian rhythm and donor procurement time is warranted in preclinical and clinical studies. Understanding the underlying mechanisms of this observation could potentially lead to the development of effective treatments and donor procurement processes that prepare the organs for transplantation in a better condition.

17.
Mol Pharm ; 21(4): 2034-2042, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38456403

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis and nonspecific symptoms and progresses rapidly, is the most common pancreatic cancer type. Inhibitors targeting KRAS G12D and G12C mutations have been pivotal in PDAC treatment. Cancer cells with different KRAS mutations exhibit various degrees of glutamine dependency; in particular, cells with KRAS G12D mutations exhibit increased glutamine uptake. (2S,4R)-4-[18F]FGln has recently been developed for clinical cancer diagnosis and tumor cell metabolism analysis. Thus, we verified the heterogeneity of glutamine dependency in PDAC models with different KRAS mutations by a visual and noninvasive method with (2S,4R)-4-[18F]FGln. Two tumor-bearing mouse models (bearing the KRAS G12D or G12C mutation) were injected with (2S,4R)-4-[18F]FGln, and positron emission tomography (PET) imaging features and biodistribution were observed and analyzed. The SUVmax in the regions of interest (ROI) was significantly higher in PANC-1 (G12D) tumors than in MIA PaCa-2 (G12C) tumors. Biodistribution analysis revealed higher tumor accumulation of (2S,4R)-4-[18F]FGln and other metrics, such as T/M and T/B, in the PANC-1 mouse models compared to those in the MIAPaCa-2 mouse models. In conclusion, PDAC cells with the KRAS G12D and G12C mutations exhibit various degrees of (2S,4R)-4-[18F]FGln uptake, indicating that (2S,4R)-4-[18F]FGln might be applied to detect KRAS G12C and G12D mutations and provide treatment guidance.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/genética , Glutamina/metabolismo , Glutamina/farmacologia , Mutação , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Distribuição Tecidual , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacologia
18.
ACS Nano ; 18(11): 8248-8258, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38428021

RESUMO

Imposing quantum confinement has the potential to significantly modulate both the structural and optical parameters of interest in many material systems. In this work, we investigate strongly confined ultrathin perovskite nanoplatelets APbBr3. We compare the all-inorganic and hybrid compositions with the A-sites cesium and formamidinium, respectively. Compared to each other and their bulk counterparts, the materials show significant differences in variable-temperature structural and optical evolution. We quantify and correlate structural asymmetry with the excitonic transition energy, spectral purity, and emission rate. Negative thermal expansion, structural and photoluminescence asymmetry, photoluminescence full width at half-maximum, and splitting between bright and dark excitonic levels are found to be reduced in the hybrid composition. This work provides composition- and structure-based mechanisms for engineering of the excitons in these materials.

19.
Molecules ; 29(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474488

RESUMO

Supercapacitors (SCs) are a novel type of energy storage device that exhibit features such as a short charging time, a long service life, excellent temperature characteristics, energy saving, and environmental protection. The capacitance of SCs depends on the electrode materials. Currently, carbon-based materials, transition metal oxides/hydroxides, and conductive polymers are widely used as electrode materials. However, the low specific capacitance of carbon-based materials, high cost of transition metal oxides/hydroxides, and poor cycling performance of conductive polymers as electrodes limit their applications. Copper-sulfur compounds used as electrode materials exhibit excellent electrical conductivity, a wide voltage range, high specific capacitance, diverse structures, and abundant copper reserves, and have been widely studied in catalysis, sensors, supercapacitors, solar cells, and other fields. This review summarizes the application of copper-sulfur compounds in SCs, details the research directions and development strategies of copper-sulfur compounds in SCs, and analyses and summarizes the research hotspots and outlook, so as to provide a reference and guidance for the use of copper-sulfur compounds.

20.
Phys Chem Chem Phys ; 26(11): 8842-8849, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426259

RESUMO

The metal-semiconductor (M-S) contact is usually an Ohmic contact or a Schottky contact, which greatly affects the electronic properties of devices, and it remains a huge challenge to realize a low-resistance Ohmic contact in a metal-semiconductor junction (MSJ). Herein, we systematically studied the band structures, electrostatic potential, charge transfer, Schottky barrier height of carriers, effective carrier masses, and tunneling probability of carriers of a germanene (Ge)/GaAs MSJ. The transition from the Schottky to the Ohmic contact can be caused by applying certain biaxial strains or electric fields, which weakens the Fermi level pinning (FLP) effect and reduces contact resistance. Meanwhile, the electron injection efficiency of Ge/(GaAs)As MSJ (PTB > 27%) is far superior to that of other two-dimensional (2D) vdW MSJs. This work indicates that Ge/GaAs heterostructures are the most compatible for applying high-effective 2D electronic nanodevices under controllable conditions.

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