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1.
Langmuir ; 40(36): 18917-18924, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39186619

RESUMEN

Silicone-in-water emulsions have found widespread use as lubricants, water repellants, softeners, binders, antiblocking agents, antislip agents, and defoamers across a diverse range of markets including textiles, coatings, pharmaceuticals, and home and personal care. Stable incorporation of silicone emulsions into formulated products for these applications can be a challenge. This study seeks to enable formulation by investigating the impact of the degree of ethoxylation of sodium lauryl ether sulfate (SLES) surfactants on their ability to displace surfactant stabilizer at the silicone-water interfaces of polydimethylsiloxane (PDMS)-in-water emulsion droplets. Building this understanding will greatly enable the manufacture of home and personal care products prepared by introducing silicone emulsions into SLES-rich formulations. Nuclear magnetic resonance (NMR) measurements reveal that SLES can displace the triethanolamine dodecylbenzenesulfonate stabilizer at the droplet surfaces. Both capillary electrophoresis (CE) measurements and molecular dynamics simulations of the interfacial tension (IFT) between silicone and water measurements suggest that SLES mixtures with a higher average degree of ethoxylation are more surface active at the silicone─water interface. The molecular dynamics simulations predict a systematic decrease in PDMS-water IFT with increase in degree of ethoxylation (simulations predict a decrease of 1.3 mN/m per mole of ethylene oxide). Optical microscopy reveals that the presence of SLES at the droplet surfaces promotes the formation of loose flocs of droplets that break up upon dilution. Overall, these fundamental insights will aid in formulating silicone emulsions into products to achieve optimal performance.

2.
Biomed Eng Online ; 23(1): 82, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152411

RESUMEN

BACKGROUND: Iron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press-strain loop (LV-PSL). METHODS: Sixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL < Hb < 9 g/dL. Thirty-three healthy individuals were used as the control (Group A). The global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global waste work (GWW), global work efficiency (GWE) were derived using LV-PSL analysis. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal left ventricular systolic function in IDA patients. RESULTS: Compared to group A, GWI and GCW were reduced in group B (both P < 0.01). Compared with groups B and A, GLS, GWI, GCW and GWE, and E/A were all diminished, and GWW, LVEDV, LVESV, and E/mean e' were all increased in group C (all P < 0.01). GLS was positively correlated with GWI, GCW, and GWE (r = 0.679, 0.681, and 0.447, all P < 0.01), and negatively associated with GWW (r = - 0.411, all P < 0.01). For GWI, area under the ROC curve (AUROC) was 0.783. The optimal GWI threshold for detecting abnormal LV systolic function in IDA was1763 mmHg%, with sensitivity of 0.71 and specificity of 0.78. CONCLUSIONS: LV-PSL allows noninvasive quantitative assessment of early impaired LV systolic function in IDA patients with preserved LV ejection fraction, and GWI has high sensitivity and specificity compared with other parameters.


Asunto(s)
Anemia Ferropénica , Sístole , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Anemia Ferropénica/fisiopatología , Persona de Mediana Edad , Adulto , Curva ROC , Estrés Mecánico , Ecocardiografía , Disfunción Ventricular Izquierda/fisiopatología
3.
Biomacromolecules ; 25(6): 3823-3830, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38773865

RESUMEN

Sustainability and circularity are key issues facing the global polymer industry. The search for biodegradable and environmentally-friendly polymers that can replace conventional materials is a difficult challenge that has been met with limited success. Alternatives must be cost-effective, scalable, and provide equivalent performance. We report that latexes made by the conventional emulsion polymerization of vinyl acetate and functional vinyl ester monomers are efficient thickeners for consumer products and biodegrade in wastewater. This approach uses readily-available starting materials and polymerization is carried out in water at room temperature, in one pot, and generates negligible waste. Moreover, the knowledge that poly(vinyl ester)s are biodegradable will lead to the design of new green polymer materials.


Asunto(s)
Emulsiones , Emulsiones/química , Polimerizacion , Polímeros/química , Álcalis/química , Biodegradación Ambiental , Látex/química , Compuestos de Vinilo/química , Aguas Residuales/química
4.
Med ; 5(8): 909-925.e7, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-38670112

RESUMEN

BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry. FINDINGS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic ß-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. FUNDINGS: This study was supported by MOST and NSFC of China.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Control Glucémico , Micobioma , Humanos , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/sangre , Persona de Mediana Edad , Masculino , Femenino , Microbioma Gastrointestinal/fisiología , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina , Fusarium/genética , Hongos/genética , Adulto , Glucemia/metabolismo , Anciano , Ascomicetos/genética , Metabolómica
5.
Ren Fail ; 46(1): 2332491, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38584145

RESUMEN

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. RESULTS: The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. CONCLUSION: LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Enfermedades Renales , Humanos , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina , Enfermedades Renales/patología , Mutación , Apolipoproteínas E/genética
6.
Front Immunol ; 15: 1285813, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38426091

RESUMEN

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.


Asunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Biomarcadores , Angiografía Coronaria , Osteopontina/genética , Placa Aterosclerótica/patología
7.
J Am Chem Soc ; 146(9): 6336-6344, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38381858

RESUMEN

Actuating materials convert different forms of energy into mechanical responses. To satisfy various application scenarios, they are desired to have rich categories, novel functionalities, clear structure-property relationships, fast responses, and, in particular, giant and reversible shape changes. Herein, we report a phase transition-driven ferroelectric crystal, (rac-3-HOPD)PbI3 (3-HOPD = 3-hydroxypiperidine cation), showing intriguingly large and anisotropic room-temperature actuating behaviors. The crystal consists of rigid one-dimensional [PbI3] anionic chains running along the a-axis and discrete disk-like cations loosely wrapping around the chains, leaving room for anisotropic shape changes in both the b- and c-axes. The shape change is switched by a ferroelectric phase transition occurring at around room temperature (294 K), driven by the exceptionally synergistic order-disorder and displacive phase transition. The rotation of the cations exerts internal pressure on the stacking structure to trigger an exceptionally large displacement of the inorganic chains, corresponding to a crystal lattice transformation with length changes of +24.6% and -17.5% along the b- and c-axis, respectively. Single crystal-based prototype devices of circuit switches and elevators have been fabricated by exploiting the unconventional negative temperature-dependent actuating behaviors. This work provides a new model for the development of multifunctional mechanically responsive materials.

8.
Int J Mol Med ; 53(3)2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38299238

RESUMEN

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the EdU staining assay data shown in Figs. 4C and 5C and the western blotting data shown in Fig. 4E were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time. Owing to the fact that contentious data in the above article had already been submitted for publication elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 169, 2021; DOI: 10.3892/ijmm.2021.5002].

9.
Respiration ; 103(2): 95-99, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38272003

RESUMEN

INTRODUCTION: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. CASE PRESENTATION: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. CONCLUSION: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.


Asunto(s)
Hipertensión Pulmonar , Mediastinitis , Hipertensión Arterial Pulmonar , Esclerosis , Masculino , Humanos , Persona de Mediana Edad , Mediastino , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/complicaciones , Mediastinitis/complicaciones , Mediastinitis/diagnóstico , Hipertensión Arterial Pulmonar/patología
10.
BMC Cardiovasc Disord ; 24(1): 33, 2024 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184555

RESUMEN

OBJECTIVE: To investigate the association between circulating secretoneurin (SN) and angiographic coronary collateralization in stable angina patients with chronic coronary total occlusion (CTO). METHODS: SN concentrations in serum were measured in 641 stable angina patients with CTO by radioimmunoassay. The status of coronary collaterals from the contra-lateral vessel was visually estimated using the Rentrop grading system, and was categorized into poor (grade 0 or 1) or good (grade 2 or 3) collateralization. RESULTS: Serum SN levels were significantly higher in patients with good coronary collaterals compared to those with poor collaterals (175.23 ± 52.09 pmol/L vs. 143.29 ± 42.01 pmol/L, P < 0.001). Serum SN increased stepwise across Rentrop score 0 to 3 (P < 0.001), and increasing SN tertiles were associated with higher proportion of good coronary collateralization (OR, 1.907; 95% CI, 1.558 ~ 2.335, P < 0.001). After adjustment for confounding variables, serum SN (per tertile) remained an independent factor for predicting good coronary collaterals (OR, 1.870; 95% CI, 1.515 ~ 2.309; P < 0.001). Moreover, the diagnostic value of serum SN (per tertile) was consistent after stratifying patients based on gender, age, body mass index, hypertension, diabetes, history of smoking, severity of coronary artery disease and kidney function (OR: 1.511 ~ 2.680, P interaction ≥ 0.327). CONCLUSION: Elevated circulating SN reflects good angiographic coronary collaterals in stable angina patients with CTO. The findings may provide insight into decision-making for these patients.


Asunto(s)
Angina Estable , Hipertensión , Neuropéptidos , Humanos , Angina Estable/diagnóstico por imagen , Corazón
11.
Biochem Biophys Res Commun ; 681: 218-224, 2023 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-37783120

RESUMEN

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) is clinically and genetically heterogeneous, with concurrent RB1/TP53 mutations, indicating an increased risk of transformation into small cell lung cancer (SCLC). When tumor cells convert into a different histological subtype, they lose their dependence on the original oncogenic driver, resulting in therapeutic resistance. However, the molecular details associated with this transformation remain unclear. It has been difficult to define molecular mechanisms of neuroendocrine (NE) transformation in lung cancer due to a lack of pre- and post-transformation clinical samples. In this study, we established a NSCLC cell line with concurrent RB1/TP53 mutations and built corresponding patient-derived xenograft (PDX) models to investigate the mechanisms underlying transformation to SCLC. Studying these PDX models, we demonstrate that EGFR loss facilitates lineage plasticity of lung adenocarcinoma initiated by biallelic mutations of TP53 and RB1. Gene expression analysis of these EGFR knockout tumors revealed altered expression of neuroendocrine synapse-associated lineage genes. There is an increased expression of epigenetic reprogramming factors like Sox2 and gene associated with neural development like NTRK in these EGFR knockout tumors. These findings uncovered the role of EGFR in the acquisition of plasticity, which is the ability of a cell to substantially modify its identity and take on a new phenotype, and defined a novel landscape of potential drivers of NE transformation in lung cancer.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Adenocarcinoma del Pulmón/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/patología , Animales
12.
ACS Omega ; 8(37): 33658-33674, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37744850

RESUMEN

Bromodomain and extra-terminal domain (BET) proteins play an important role in epigenetic regulation and are linked to several diseases; therefore, they are interesting targets. BET has two bromodomains: bromodomain 1 (BD1) and BD2. Selective targeting of BD1 or BD2 may produce different activities and greater effects than pan-BD inhibitors. However, the selective mechanism of the specific core must be studied at the atomic level. This study determined the effectiveness of pyrrolopyridone analogues to selectively inhibit BD2 using a pan-BD inhibitor (ABBV-075) and a selective-BD2 inhibitor (ABBV-744). Molecular dynamics simulations and calculations of binding free energies were used to systematically study the selectivity of BD2 inhibition by the pyrrolopyridone analogues. Overall, the pyrrolopyridone analogue inhibitors targeting BD2 interacted mainly with the following amino acid pairs between bromodomain-containing protein 4 (BRD4)-BD1 and BRD4-BD2 complexes: I146/V439, N140/N433, D144/H437, P82/P375, V87/V380, D88/D381, and Y139/Y432. The pyrrolopyridone analogues targeting BRD4-BD2 were divided into five regions based on selectivity mechanism. These results suggest that the R3 and R5 regions of pyrrolopyridone analogues can be modified to improve the selectivity between BRD4-BD1 and BRD4-BD2. The selectivity of BD2 inhibition by pyrrolopyridone analogues can be used to design novel BD2 inhibitors based on a pyrrolopyridone core.

13.
Mitochondrial DNA B Resour ; 8(8): 836-840, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37554696

RESUMEN

Duck breed Longshengcui (Anas platyrhynchos Linnaeus, 1758 breed Longshengcui, LSC) is one of the famous native breed of the Guangxi Zhuang Nationality Autonomous Region in China. In this study, we report the complete mitochondrial genome of LSC. The mitogenome (GenBank accession no. MZ895120) has 16,602 bp in length and consisted of the well-known 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and the control region. The phylogenetic analysis showed that LSC and Zhijiang duck have highly similar genetic relationship. These results are helpful for the conservation of genetic resources and phylogeny of this species.

14.
RSC Adv ; 13(23): 15901-15909, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37260566

RESUMEN

Thermal diffusion of particles in dilute aqueous suspensions is driven by the interactions between the dispersing medium and the particle, which are largely influenced by the properties of the medium. Using a commercial instrument to generate thermophoresis, we developed a method to quantify the migration of colloids in a temperature gradient and further studied how it varies based on the composition and pH of the dispersing medium and with an anionic surfactant, at different salt concentrations. Thermophoretic migration of aqueous suspensions of carboxylate-modified polystyrene particles with different compositions is measured as MicroScale Thermophoresis (MST) traces and a mathematical model is developed to extract the Soret coefficient (ST). Soret coefficient measurements obtained using the developed method are in-line with previous theories and scientific findings from other literature, indicating a dependence of the ST on the Debye length and surface charge density of the suspended particles, both of which are controlled by the composition of the dispersing medium. The thermophobic/thermophilic behavior of particles is also found to be strongly influenced by the thermoelectric effect of the buffer ions. In this paper, a new analytical model is introduced and applied to complex systems to understand their thermophoretic behavior as a function of solvent properties.

15.
Anal Chem ; 95(7): 3840-3847, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36762381

RESUMEN

Submicrometer colloidal particles are widely applied in a variety of industrial products. While precise size and surface charge control is crucial to the stability and functionality of these materials, a tool to determine these properties with sufficient resolution, detection sensitivity, and robustness is still not available. The recently reported offline coupling of asymmetrical flow field-flow fractionation and capillary electrophoresis (AF4 × CE) shows success in improving the separation resolution for nanoparticles; however, challenges remain for sensitive multiple-component submicrometer particle analysis because of wide size and mobility distributions. We here report offline coupling of an AF4 method and a CE method, which utilized the online reversed electrode polarity stacking mode, to successfully characterize a five-component, submicrometer particle mixture. The mixture was successfully separated and detected with an improved inter- and intracomponent resolution. Therefore, our developed platform holds great potential for industrial applications involving multiple-component particle mixtures.

16.
Anal Chem ; 95(5): 3019-3027, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36706440

RESUMEN

Breast cancer is the most commonly diagnosed cancer type worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) is an important subtype of breast cancer and results in an increased risk of recurrence and metastasis in patients. At present, immunohistochemistry (IHC) is used to detect the expression of HER2 in breast cancer tissues as the golden standard. However, IHC has some shortcomings, such as large subjective impact, long time consumption, expensive reagents, etc. In this paper, a combined morphological and spectroscopic diagnostic method based on label-free surface-enhanced Raman scattering (SERS) for HER2 expression in breast cancer is proposed. It can not only quantitively detect HER2 expression in breast cancer tissues by spectroscopic measurements but also give morphological images reflecting the distribution of HER2 in tissues. The results show that the consistency between this method and IHC is 95% and achieves the annotation of tumor regions on tissue sections. This method is time-consuming, quantifiable, intuitive, scalable, and easy to understand. Combined with deep learning approaches, it is expected to promote the development of clinical detection and diagnosis technology for breast cancer and other cancers.


Asunto(s)
Neoplasias de la Mama , Espectrometría Raman , Humanos , Femenino , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Inmunohistoquímica , Biomarcadores de Tumor
17.
Signal Transduct Target Ther ; 7(1): 380, 2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36402752

RESUMEN

Pleural and peritoneal metastasis accompanied by malignant pleural effusion (MPE) or malignant ascites (MA) is frequent in patients with advanced solid tumors that originate from the lung, breast, gastrointestinal tract and ovary. Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities. However, malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction. Here, we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA, which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment. Interestingly, we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells. Based on this feature, a novel PD-L1-targeting chimeric switch receptor (PD-L1.BB CSR) was designed, which can bind to PD-L1, switching the inhibitory signal into an additional 4-1BB signal. When co-expressed with a 2nd-generation CAR, PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment, causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models. Further investigations revealed elevated expressions of T-cell activation, proliferation, and cytotoxicity-related genes, and we confirmed that PD-L1 scFv and 4-1BB intracellular domain, the two important components of PD-L1.BB CSR, were both necessary for the functional improvements of CAR-T cells. Overall, our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells. Based on this study, a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis (NCT04684459).


Asunto(s)
Neoplasias Peritoneales , Derrame Pleural Maligno , Femenino , Humanos , Antígeno B7-H1/genética , Activación de Linfocitos , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/terapia , Derrame Pleural Maligno/metabolismo , Linfocitos T , Ensayos Clínicos Fase I como Asunto
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 606-613, 2022 Aug.
Artículo en Chino | MEDLINE | ID: mdl-36065693

RESUMEN

Objective To evaluate and compare the value of quantitative parameters of preoperative dual-energy CT and MRI on KRAS mutation in rectal cancer,and to explore the correlations between postoperative pathological indicators and KRAS mutation. Methods This study retrospectively analyzed 50 patients with rectal cancer confirmed by surgery and pathology and receiving KRAS genetic testing in Lanzhou University Second Hospital from August 2017 to April 2021.According to the results of genetic testing,the patients were assigned into a wild-type group (29 patients) and a mutant type group (21 patients).The preoperative baseline data included sex,age,and serum tumor markers,and the postoperative pathological data included pathological stage,lymphovascular invasion,perineural invasion,and lymph node metastasis.The quantitative parameters of three-phase energy spectral CT included iodine (water) concentration,water (iodine) concentration,effective atomic number,and normalized iodine concentration.The quantitative parameters of apparent diffusion coefficient (ADC) included minimum ADC,average ADC,and relative ADC.In addition,the width of the superior rectal vein was obtained from the CT images of the venous phase,and the tumor segmentation,the maximum axial length of tumor,and the maximum longitudinal length of tumor were obtained from the MRI images.The qualitative and quantitative data were compared by χ2 test,t-test,and Mann-Whitney U test.The diagnostic efficacy of the two detection methods for KRAS mutations in rectal cancer was compared,and the receiver operating characteristic curve was employed to evaluate the diagnostic efficacy. Results The KRAS mutation rate was higher in the carbohydrate antigen 199 abnormal group than the normal group (P=0.036) and higher in the positive group of lymphovascular invasion (P=0.034).The KRAS mutant type group had higher normalized iodine concentration in the venous phase (P=0.016) and lower average ADC and relative ADC (P=0.008, P=0.002,respectively) than the wild-type group.Among them,relative ADC had the highest diagnostic efficiency (AUC=0.755). Conclusion The quantitative parameters of dual-energy CT and ADC have similar diagnostic efficiency for KRAS mutation in rectal cancer,and relative ADC is superior to other parameters.


Asunto(s)
Yodo , Neoplasias del Recto , Humanos , Imagen por Resonancia Magnética , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/genética , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Agua
19.
J Nurs Manag ; 30(7): 3322-3329, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36017688

RESUMEN

AIM: This study aimed to explore the mediating effects of adversity quotient and the moderating effect of self-efficacy on the relationship between the organizational climate and the work engagement of intensive care unit nurses. BACKGROUND: A good organizational climate can contribute to a high level of work engagement. Adversity quotient and self-efficacy are the key factors affecting nurses' work engagement, while the mechanism of these factors in the organizational climate and work engagement remains unclear. This study was conducted to contribute to the relevant field research. METHODS: The study used a cross-sectional research design and surveyed 323 intensive care unit nurses working in a public hospital in China. The data were analysed using descriptive statistical methods: Pearson correlation analysis and PROCESS macro Model 7 in the regression analysis. RESULTS: Organizational climate was positively correlated with work engagement and adversity quotient. The indirect effect of organizational climate on work engagement through adversity quotient was positive. Furthermore, self-efficacy moderated the relationship between the two factors. CONCLUSION: Cultivating organizational climate and adversity quotients is an important strategy to improve the work engagement of intensive care unit nurses, particularly for nurses with high self-efficacy. IMPLICATIONS FOR NURSING MANAGEMENT: Administrators should make efforts to create a good organizational climate and cultivate nurses' adversity quotients and self-efficacy to decrease their intent to leave.


Asunto(s)
Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Humanos , Compromiso Laboral , Autoeficacia , Estudios Transversales , Encuestas y Cuestionarios , Unidades de Cuidados Intensivos , Cultura Organizacional , Satisfacción en el Trabajo
20.
Mol Psychiatry ; 27(8): 3214-3222, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35668158

RESUMEN

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Trastornos del Inicio y del Mantenimiento del Sueño , Embarazo , Femenino , Humanos , Anciano , COVID-19/epidemiología , Pandemias , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Prevalencia , Depresión/epidemiología , Depresión/etiología , SARS-CoV-2 , Ansiedad/epidemiología , Ansiedad/etiología , Factores de Riesgo , Enfermedades Transmisibles/epidemiología
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