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1.
Int J Neurosci ; : 1-7, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38717343

RESUMEN

OBJECTIVE: To explore the effect of nursing intervention and quality feedback guided by stress system theory on neurological function recovery and post-traumatic growth in patients with cerebral hemorrhage. METHODS: 120 patients with cerebral hemorrhage admitted to our hospital from October 2022 to November 2023 were selected, 47 patients in the control group received routine medical care, and 73 patients in the observation group were added nursing intervention measures under the guidance of stress system theory on this basis. The effects of the intervention were evaluated by Posttraumatic Growth Inventory (PTGI), self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS), Barthel index (BI) and Chinese scale of clinical neurological impairment in stroke patients (CSS). RESULTS: After intervention, the PTGI score in the observation group was significantly higher than that in the control group (p < 0.05). The SAS and SDS scores were significantly lower than those of the control group (p < 0.001), indicating that the nursing intervention effectively alleviated the anxiety and depression of patients. At the same time, the BI index of the observation group was significantly increased, and the CSS score was significantly decreased (p < 0.001), indicating that the patients' self-care ability of daily life and the recovery level of neurological function were significantly improved. CONCLUSION: Nursing intervention and quality feedback strategy under the guidance of stress system theory can effectively improve the neurological recovery ability and post-traumatic growth level of patients with cerebral hemorrhage, and has a significant effect on improving the psychological state and quality of life of patients.

2.
J Environ Manage ; 360: 121188, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38759556

RESUMEN

Afforestation is an acknowledged method for rehabilitating deteriorated riparian ecosystems, presenting multiple functions to alleviate the repercussions of river damming and climate change. However, how ecosystem multifunctionality (EMF) responds to inundation in riparian afforestation ecosystems remains relatively unexplored. Thus, this article aimed to disclose how EMF alters with varying inundation intensities and to elucidate the key drivers of this variation based on riparian reforestation experiments in the Three Gorges Reservoir Region in China. Our EMF analysis encompassed wood production, carbon storage, nutrient cycling, decomposition, and water regulation under different inundation intensities. We examined their correlation with soil properties and microbial diversity. The results indicated a substantial reduction in EMF with heightened inundation intensity, which was primarily due to the decline in most individual functions. Notably, soil bacterial diversity (23.02%), soil properties such as oxidation-reduction potential (ORP, 11.75%), and temperature (5.85%) emerged as pivotal variables elucidating EMF changes under varying inundation intensities. Soil bacterial diversity and ORP declined as inundation intensified but were positively associated with EMF. In contrast, soil temperature rose with increased inundation intensity and exhibited a negative correlation with EMF. Further insights gleaned from structural equation modeling revealed that inundation reduced EMF directly and indirectly by reducing soil ORP and bacterial diversity and increasing soil temperature. This work underscores the adverse effects of dam inundation on riparian EMF and the crucial role soil characteristics and microbial diversity play in mediating EMF in response to inundation. These insights are pivotal for the conservation of biodiversity and functioning following afforestation in dam-induced riparian habitats.

3.
Diagn Microbiol Infect Dis ; 109(4): 116350, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38761614

RESUMEN

BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern. CASE PRESENTATION: We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient's history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18. CONCLUSIONS: This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease's characteristics, pathogenesis, detection methods, and available treatments.

4.
Environ Sci Technol ; 58(17): 7469-7479, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38557082

RESUMEN

Trivalent arsenicals such as arsenite (AsIII) and methylarsenite (MAsIII) are thought to be ubiquitous in flooded paddy soils and have higher toxicity than pentavalent forms. Fungi are widely prevalent in the rice rhizosphere, and the latter is considered a hotspot for As uptake. However, few studies have focused on alleviating As toxicity in paddy soils using fungi. In this study, we investigated the mechanism by which the protein TaGlo1, derived from the As-resistant fungal strain Trichoderma asperellum SM-12F1, mitigates AsIII and MAsIII toxicity in paddy soils. Taglo1 gene expression in Escherichia coli BL21 conferred strong resistance to AsIII and MAsIII, while purified TaGlo1 showed a high affinity for AsIII and MAsIII. Three cysteine residues (Cys13, Cys18, and Cys71) play crucial roles in binding with AsIII, while only two (Cys13 and Cys18) play crucial roles for MAsIII binding. TaGlo1 had a stronger binding strength for MAsIII than AsIII. Importantly, up to 90.2% of the homologous TaGlo1 proteins originate from fungi by GenBank searching. In the rhizospheres of 14 Chinese paddy soils, Taglo1 was widely distributed and its gene abundance increased with porewater As. This study highlights the potential of fungi to mitigate As toxicity and availability in the soil-rice continuum and suggests future microbial strategies for bioremediation.


Asunto(s)
Contaminantes del Suelo , Suelo , Suelo/química , Arsenitos , Microbiología del Suelo , Oryza
5.
BMC Cancer ; 24(1): 531, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671390

RESUMEN

OBJECTIVE: In the pathogenesis of myeloproliferative neoplasms (MPN), inflammation plays an important role. However, it is unclear whether there is a causal link between inflammation and MPNs. We used a bidirectional, two-sample Mendelian randomization (MR) approach to investigate the causal relationship between systemic inflammatory cytokines and myeloproliferative neoplasms. METHODS: A genome-wide association study (GWAS) of 8293 European participants identified genetic instrumental variables for circulating cytokines and growth factors. Summary statistics of MPN were obtained from a GWAS including 1086 cases and 407,155 controls of European ancestry. The inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS: Our results showed that higher Interleukin-2 receptor, alpha subunit (IL-2rα) levels, and higher Interferon gamma-induced protein 10 (IP-10) levels were associated with an increased risk of MPN (OR = 1.36,95%CI = 1.03-1.81, P = 0.032; OR = 1.55,95%CI = 1.09-2.22, P = 0.015; respectively).In addition, Genetically predicted MPN promotes expression of the inflammatory cytokines interleukin-10 (IL-10) (BETA = 0.033, 95% CI = 0.003 ~ 0.064, P = 0.032) and monokine induced by interferon-gamma (MIG) (BETA = 0.052, 95% CI = 0.002-0.102, P = 0.043) and, on activation, normal T cells express and secrete RANTES (BETA = 0.055, 95% CI = 0.0090.1, P = 0.018). CONCLUSION: Our findings suggest that cytokines are essential to the pathophysiology of MPN. More research is required if these biomarkers can be used to prevent and treat MPN.


Asunto(s)
Citocinas , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mieloproliferativos , Humanos , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/sangre , Citocinas/sangre , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Masculino , Predisposición Genética a la Enfermedad , Femenino , Estudios de Casos y Controles , Inflamación/genética , Inflamación/sangre
6.
Heliyon ; 10(8): e29857, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681571

RESUMEN

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

7.
Angew Chem Int Ed Engl ; 63(21): e202400926, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38529812

RESUMEN

Hydrogen-bonded organic frameworks (HOFs) are porous nanomaterials that offer exceptional biocompatibility and versatility for integrating proteins for biomedical applications. This minireview concisely discusses recent advancements in the chemistry and functionality of protein-HOF interfaces. It particularly focuses on strategic methodologies, such as the careful selection of building blocks and the genetic engineering of proteins, to facilitate protein-HOF interactions. We examine the role of enzyme encapsulation within HOFs, highlighting its capability to preserve enzyme function, a crucial aspect for applications in biosensing and disease diagnosis. Moreover, we discuss the emerging utility of nanoscale HOFs for intracellular protein delivery, illustrating their applicability as nanoreactors for intracellular catalysis and neuroprotective biorthogonal catalysis within cellular compartments. We highlight the significant advancement of designing biodegradable HOFs tailored for cytosolic protein delivery, underscoring their promising application in targeted cancer therapies. Finally, we provide a perspective viewpoint on the design of biocompatible protein-HOF assemblies, underlining their promising prospects in drug delivery, disease diagnosis, and broader biomedical applications.


Asunto(s)
Enlace de Hidrógeno , Proteínas , Humanos , Proteínas/química , Proteínas/metabolismo , Materiales Biocompatibles/química , Estructuras Metalorgánicas/química , Sistemas de Liberación de Medicamentos
8.
Front Public Health ; 12: 1301724, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38425467

RESUMEN

Background: Tetanus is a rare surgical infectious disease with a high reported relevant mortality. It still remains a serious problem in public health, particularly in low-income and middle-income countries. The purpose of this study was to investigate the management and prognosis of adult generalized tetanus in our hospital. Methods: A total of 20 adult generalized tetanus patients were recruited in this retrospective observational study. Patients were retrieved from the hospital data base via discharge diagnosis. Patients were divided into two groups (Severe or Non-severe tetanus group) based on the severity of tetanus by using the Ablett classification. The differences between the two groups were compared. Results: The study included 11 males (55%) and 9 females (45%). All tetanus patients recovered. The median age was 53.5 years [IQR: 19-78]. There were 1 mild (Grade 1) case (5%),5 moderate (Grade 2) cases (25%), 2 severe (Grade 3) cases (10%), and 12 very severe (Grade 4) cases (60%). Nineteen patients (95%) did not have tetanus immunization before. The majority of patients were farmers (60%), and came from rural areas (60%). Thirteen (65%) patients had a history of puncture injury. The rate of wound debridement after admission was 60% overall. Thirteen (65%) patients required mechanical ventilation for a median of 21 [IQR:12-41] days. Autonomic instability occurred in 13 (65%) patients. Pulmonary infections occurred in 12 (60%) patients. Median duration of hospital stay was 29.5 [IQR:12-68] days. More patients in the Severe group needed ICU admission, wound debridement, mechanical ventilation and heavy sedation combined with muscle relaxants (p < 0.05). The hospital stay was significantly longer in patients in the Severe group (p < 0.05). Conclusion: After effective treatment, all adult patients with generalized tetanus in this study were cured and discharged. Severe tetanus requires early ICU treatment, wound debridement and effective treatment of autonomic instability.


Asunto(s)
Tétanos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , China/epidemiología , Pronóstico , Estudios Retrospectivos , Centros de Atención Terciaria , Tétanos/terapia , Tétanos/diagnóstico , Adulto Joven , Anciano
9.
Front Plant Sci ; 15: 1325141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38434434

RESUMEN

Understanding the response of soil microbial communities to pathogenic Ralstonia solanacearum is crucial for preventing bacterial wilt outbreaks. In this study, we investigated the soil physicochemical and microbial community to assess their impact on the pathogenic R.solanacearum through metagenomics. Our results revealed that certain archaeal taxa were the main contributors influencing the health of plants. Additionally, the presence of the pathogen showed a strong negative correlation with soil phosphorus levels, while soil phosphorus was significantly correlated with bacterial and archaeal communities. We found that the network of microbial interactions in healthy plant rhizosphere soils was more complex compared to diseased soils. The diseased soil network had more linkages, particularly related to the pathogen occurrence. Within the network, the family Comamonadaceae, specifically Ramlibacter_tataouinensis, was enriched in healthy samples and showed a significantly negative correlation with the pathogen. In terms of archaea, Halorubrum, Halorussus_halophilus (family: Halobacteriaceae), and Natronomonas_pharaonis (family: Haloarculaceae) were enriched in healthy plant rhizosphere soils and showed negative correlations with R.solanacearum. These findings suggested that the presence of these archaea may potentially reduce the occurrence of bacterial wilt disease. On the other hand, Halostagnicola_larseniia and Haloterrigena_sp._BND6 (family: Natrialbaceae) had higher relative abundance in diseased plants and exhibited significantly positive correlations with R.solanacearum, indicating their potential contribution to the pathogen's occurrence. Moreover, we explored the possibility of functional gene sharing among the correlating bacterial pairs within the Molecular Ecological Network. Our analysis revealed 468 entries of horizontal gene transfer (HGT) events, emphasizing the significance of HGT in shaping the adaptive traits of plant-associated bacteria, particularly in relation to host colonization and pathogenicity. Overall, this work revealed key factors, patterns and response mechanisms underlying the rhizosphere soil microbial populations. The findings offer valuable guidance for effectively controlling soil-borne bacterial diseases and developing sustainable agriculture practices.

10.
Appl Opt ; 63(5): 1377-1384, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38437318

RESUMEN

Optical delay lines have wide applications in terahertz time-domain spectroscopy and optical coherence tomography. In this study, a fast-rotating optical delay line (FRODL) with 24 turntable reflection surfaces was designed. By analyzing the working principle of the FRODL, a mathematical model was established for the nonlinear parameter error of the FRODL delay time. By constructing the polarization Michelson interference system and testing the FRODL structure, the error of actual assembly parameters of the FRODL was approximately 0.015 mm, the actual delay time of the FRODL was greater than 43.5 ps, and the linearity was 99.785%.

11.
Cancer Cell Int ; 24(1): 97, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443961

RESUMEN

Gastrointestinal cancer, one of the most common cancers, continues to be a major cause of mortality and morbidity globally. Accumulating evidence has shown that alterations in mitochondrial energy metabolism are involved in developing various clinical diseases. NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4), encoded by the NDUFA4 gene located on human chromosome 7p21.3, is a component of mitochondrial respiratory chain complex IV and integral to mitochondrial energy metabolism. Recent researchers have disclosed that NDUFA4 is implicated in the pathogenesis of various diseases, including gastrointestinal cancer. Aberrant expression of NDUFA4 leads to the alteration in mitochondrial energy metabolism, thereby regulating the growth and metastasis of cancer cells, indicating that it might be a new promising target for cancer intervention. This article comprehensively reviews the structure, regulatory mechanism, and biological function of NDUFA4. Of note, the expression and roles of NDUFA4 in gastrointestinal cancer including colorectal cancer, liver cancer, gastric cancer, and so on were discussed. Finally, the existing problems of NDUFA4-based intervention on gastrointestinal cancer are discussed to provide help to strengthen the understanding of the carcinogenesis of gastrointestinal cancer, as well as the development of new strategies for clinical intervention.

12.
Immunology ; 172(2): 235-251, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38425094

RESUMEN

Myocarditis has emerged as a rare but lethal immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism and the specific therapeutic targets remain underexplored. In this study, we aim to characterise the transcriptomic profiles based on single-cell RNA sequencing from ICI-related myocarditis. Peripheral blood mononuclear cell (PBMC) samples were collected from four groups for single-cell RNA sequencing: (1) patients with newly diagnosed lung squamous cell carcinoma before treatment (Control Group); (2) patients with lung squamous cell carcinoma with PD-1 inhibitor therapy who did not develop myocarditis (PD-1 Group); (3) patients during fulminant ICI-related myocarditis onset (Myocarditis Group); and (4) Patients with fulminant ICI-related myocarditis during disease remission (Recovery Group). Subcluster determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were performed after scRNA-seq. Bulk-RNA sequencing was performed for further validation. Our results revealed the diversity of cellular populations in ICI-related myocarditis, marked by their distinct transcriptional profiles and biological functions. Monocytes, NKs as well as B cells contribute to the regulation of innate immunity and inflammation in ICI-related myocarditis. With integrated analysis of scRNA-seq and bulk sequencing, we identified S100A protein family as a potential serum marker for ICI-related myocarditis. Our study has created a cell atlas of PBMC during ICI-related myocarditis, which would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI-related myocarditis in continuous exploration.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Inmunidad Innata , Neoplasias Pulmonares , Miocarditis , Análisis de la Célula Individual , Humanos , Miocarditis/inmunología , Miocarditis/inducido químicamente , Miocarditis/genética , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Transcriptoma , Análisis de Secuencia de ARN , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Anciano , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Perfilación de la Expresión Génica
13.
Sci Total Environ ; 926: 171820, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38513857

RESUMEN

Atmospheric brown carbon (BrC) aerosols were investigated at two urban sites in southern (Hefei) and northern (Shijiazhuang) China during summer and winter of 2019-2020 to explore regional variability in their compositional and optical properties. Organic matter in ambient PM2.5 samples were characterized at molecular level using ultrahigh performance liquid chromatography coupled with a diode array detector and an Orbitrap mass spectrometer. Although the molecular composition of organic aerosols varied substantially over different ambient environments, they were mainly composed by CHO and CHON species in positive ionization mode while CHO and CHOS species in negative mode. The mass absorption coefficients of BrC aerosols at wavelength range 250-450 nm were relatively higher for winter samples in both cities and for Shijiazhuang samples in both seasons, partly attributed to the higher concentration levels of anthropogenic air pollutants in these environments. The absorption Ångström exponents further revealed that BrC aerosols in winter seasons and in Shijiazhuang had a greater capacity of absorption at shorter wavelengths. A total of 26 BrC species with strong absorption were unambiguously identified from different environments, which mainly consisted of CHO, CHON, and CHN species and had higher degrees of unsaturation and lower degrees of oxidation. The presence and abundance of these BrC species varied dynamically across the seasons and cities, with a greater number of species presented in the winter of Shijiazhuang. The BrC species together contributed 12-26 % in the total absorbance of light-absorbing organic components at 250-450 nm. This study highlights the regional differences in BrC properties influenced by the sources and atmospheric processes, which should be taken into account to assess their climate impacts.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38494367

RESUMEN

BACKGROUND AND AIM: To explore the association of triglyceride glucose index-body mass index (TyG-BMI) and its dynamic changes with the risk of hypertension among middle-aged and older Chinese adults based on a large-sample prospective cohort study. METHODS AND RESULTS: Participants over 45 years old and without a history of hypertension were included from the China Health and Retirement Longitudinal Study registry. Data were collected in 2011 and followed up in 2015. TyG index and TyG-BMI were calculated as ln (triglyceride∗glucose/2) and TyG index∗BMI, respectively. We performed multivariate logistic regression analysis to identify the relationship between the TyG index, TyG-BMI and their dynamic change and the risk of hypertension. In the analyses, 3885 participants were included. After 4 years of follow-up, 1705 (43.89 %) patients developed hypertension. Logistic regression analysis revealed that after adjustments for all potential confounding factors, the highest tertile of baseline TyG index, baseline TyG-BMI, and the dynamic change in TyG-BMI were each associated with higher hypertension incidence than the lowest tertile: OR,1.38, 95 % CI, 1.17-1.63, OR,1.28, 95 % CI, 1.06-1.56, and OR, 1.26, 95 % CI, 1.07-1.48, respectively, whereas TyG index change was not. Moreover, the risk of hypertension increased with increasing levels of baseline TyG index (P for trend < 0.001), baseline TyG-BMI (P for trend = 0.013), and the dynamic change in TyG-BMI (P for trend = 0.006). CONCLUSIONS: The baseline TyG index, baseline TyG-BMI, and the dynamic changes in TyG-BMI were significantly and positively associated with the risk of hypertension in Chinese adults older than 45 years.

15.
Adv Sci (Weinh) ; 11(15): e2304203, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38342610

RESUMEN

Tumors often overexpress glucose-regulated proteins, and agents that interfere with the production or activity of these proteins may represent novel cancer treatments. The chlorpromazine derivative JX57 exhibits promising effects against endometrial cancer with minimal extrapyramidal side effects; however, its mechanisms of action are currently unknown. Here, glucose-regulated protein 75 kD (GRP75) is identified as a direct target of JX57 using activity-based protein profiling and loss-of-function experiments. The findings show that GRP75 is necessary for the biological activity of JX57, as JX57 exhibits moderate anticancer properties in GRP75-deficient cancer cells, both in vitro and in vivo. High GRP75 expression is correlated with poor differentiation and poor survival in patients with endometrial cancer, whereas the knockdown of GRP75 can significantly suppress tumor growth. Mechanistically, the direct binding of JX57 to GRP75 impairs the structure of the mitochondria-associated endoplasmic reticulum membrane and disrupts the endoplasmic reticulum-mitochondrial calcium homeostasis, resulting in a mitochondrial energy crisis and AMP-activated protein kinase activation. Taken together, these findings highlight GRP75 as a potential prognostic biomarker and direct therapeutic target in endometrial cancer and suggest that the chlorpromazine derivative JX57 can potentially be a new therapeutic option for endometrial cancer.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Neoplasias Endometriales , Proteínas HSP70 de Choque Térmico , Proteínas de la Membrana , Femenino , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Clorpromazina/farmacología , Clorpromazina/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/metabolismo , Mitocondrias/metabolismo
16.
Ann Hematol ; 103(6): 1877-1885, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38308019

RESUMEN

Pure red cell aplasia (PRCA) is a rare bone marrow disorder characterized by a severe reduction or absence of erythroid precursor cells, without affecting granulocytes and megakaryocytes. Immunosuppressive therapies, particularly cyclosporine, have demonstrated efficacy as a primary treatment. This study aims to develop a predictive model for assessing the efficacy of cyclosporine in acquired PRCA (aPRCA). This retrospective study encompasses newly treated aPRCA patients at the General Hospital of Tianjin Medical University. Diagnosis criteria include severe anemia, and absolute reticulocyte count below 10 × 109/L, with normal white blood cell and platelet counts, and a severe reduction in bone marrow erythroblasts. Cyclosporine therapy was administered, with dose adjustments based on blood concentration. Response to cyclosporine was evaluated according to established criteria. Statistical analysis involved logistic multi-factor regression, generating a predictive model. The study included 112 aPRCA patients with a median age of 63.5 years. Patients presented with severe anemia (median Hb, 56 g/L) and reduced reticulocyte levels. Eighty-six patients had no bone marrow nucleated erythroblasts. Primary PRCA accounted for 62 cases (55.4%), and secondary PRCA accounted for 50 cases (44.6%). Univariate analysis revealed that ferritin, platelet to lymphocyte ratio (PLR), and CD4/CD8 ratio influenced treatment response. Multivariate analysis further supported the predictive value of these factors. A prediction model was constructed using ferritin, PLR, and CD4/CD8 ratio, demonstrating high sensitivity and specificity. The ferritin, PLR, and CD4/CD8-based nomogram showed good predictive ability for aPRCA response to cyclosporine. This model has potential clinical value for individualized diagnosis and treatment of aPRCA patients.


Asunto(s)
Ciclosporina , Nomogramas , Aplasia Pura de Células Rojas , Humanos , Ciclosporina/uso terapéutico , Aplasia Pura de Células Rojas/tratamiento farmacológico , Aplasia Pura de Células Rojas/sangre , Persona de Mediana Edad , Femenino , Masculino , Estudios Retrospectivos , Anciano , Adulto , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Anciano de 80 o más Años
18.
Mol Biotechnol ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38407689

RESUMEN

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p.

19.
Materials (Basel) ; 17(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38399090

RESUMEN

Multi-layer lightweight composite structures are widely used in the field of aviation and aerospace during the processes of manufacturing and use, and, as such, they inevitably produce defects, damage, and other quality problems, creating the need for timely non-destructive testing procedures and the convenient repair or replacement of quality problems related to the material. When using terahertz non-destructive testing technology to detect defects in multi-layer lightweight composite materials, due to the complexity of their structure and defect types, there are many signal characteristics of terahertz waves propagating in the structures, and there is no obvious rule behind them, resulting in a large gap between the recognition results and the actual ones. In this study, we introduced a U-Net-BiLSTM network that combines the strengths of the U-Net and BiLSTM networks. The U-Net network extracts the spatial features of THz signals, while the BiLSTM network captures their temporal features. By optimizing the network structure and various parameters, we obtained a model tailored to THz spectroscopy data. This model was subsequently employed for the identification and quantitative analysis of defects in multi-layer lightweight composite structures using THz non-destructive testing. The proposed U-Net-BiLSTM network achieved an accuracy of 99.45% in typical defect identification, with a comprehensive F1 score of 99.43%, outperforming the CNN, ResNet, U-Net, and BiLSTM networks. By leveraging defect classification and thickness recognition, this study successfully reconstructed three-dimensional THz defect images, thereby realizing quantitative defect detection.

20.
Front Cell Dev Biol ; 12: 1359084, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410372

RESUMEN

Multiple myeloma (MM), a stage-developed plasma cell malignancy, evolves from monoclonal gammopathy of undetermined significance (MGUS) or smoldering MM (SMM). Emerging therapies including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, chimeric antigen-T/natural killer (NK) cells, bispecific T-cell engagers, selective inhibitors of nuclear export, and small-molecule targeted therapy have considerably improved patient survival. However, MM remains incurable owing to inevitable drug resistance and post-relapse rapid progression. NK cells with germline-encoded receptors are involved in the natural evolution of MGUS/SMM to active MM. NK cells actively recognize aberrant plasma cells undergoing malignant transformation but are yet to proliferate during the elimination phase, a process that has not been revealed in the immune editing theory. They are potential effector cells that have been neglected in the therapeutic process. Herein, we characterized changes in NK cells regarding disease evolution and elucidated its role in the early clinical monitoring of MM. Additionally, we systematically explored dynamic changes in NK cells from treated patients who are in remission or relapse to explore future combination therapy strategies to overcome drug resistance.

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