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1.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38796691

RESUMEN

Limited gene capture efficiency and spot size of spatial transcriptome (ST) data pose significant challenges in cell-type characterization. The heterogeneity and complexity of cell composition in the mammalian brain make it more challenging to accurately annotate ST data from brain. Many algorithms attempt to characterize subtypes of neuron by integrating ST data with single-nucleus RNA sequencing (snRNA-seq) or single-cell RNA sequencing. However, assessing the accuracy of these algorithms on Stereo-seq ST data remains unresolved. Here, we benchmarked 9 mapping algorithms using 10 ST datasets from four mouse brain regions in two different resolutions and 24 pseudo-ST datasets from snRNA-seq. Both actual ST data and pseudo-ST data were mapped using snRNA-seq datasets from the corresponding brain regions as reference data. After comparing the performance across different areas and resolutions of the mouse brain, we have reached the conclusion that both robust cell-type decomposition and SpatialDWLS demonstrated superior robustness and accuracy in cell-type annotation. Testing with publicly available snRNA-seq data from another sequencing platform in the cortex region further validated our conclusions. Altogether, we developed a workflow for assessing suitability of mapping algorithm that fits for ST datasets, which can improve the efficiency and accuracy of spatial data annotation.


Asunto(s)
Algoritmos , Benchmarking , Encéfalo , Análisis de la Célula Individual , Animales , Ratones , Encéfalo/metabolismo , Análisis de la Célula Individual/métodos , RNA-Seq/métodos , Transcriptoma , Análisis de Secuencia de ARN/métodos , Neuronas/metabolismo , Perfilación de la Expresión Génica/métodos
2.
N Engl J Med ; 387(1): 9-20, 2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35665782

RESUMEN

BACKGROUND: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers. METHODS: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients. RESULTS: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events. CONCLUSIONS: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).


Asunto(s)
Antineoplásicos Inmunológicos , Neoplasias de la Mama , Receptor ErbB-2 , Trastuzumab , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/secundario , Camptotecina/análogos & derivados , Progresión de la Enfermedad , Femenino , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/uso terapéutico , Inmunohistoquímica , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico
3.
BMC Biol ; 22(1): 29, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317233

RESUMEN

BACKGROUND: Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the "opposite" voltage-sensing properties of hERG and HCN remains unknown. RESULTS: We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We identified that a long-QT syndrome type 2-related mutation within the VSD, K525N, mediated an inwardly rectifying non-deactivating current, perturbing the channel closure, but sparing the open state and inactivated state. K525N rescued the current of a non-functional mutation in the pore helix region (F627Y) of hERG. K525N&F627Y switched hERG into a hyperpolarization-activated channel. The reactivated inward current induced by hyperpolarization mediated by K525N&F627Y can be inhibited by E-4031 and dofetilide quite well. Moreover, we report an extracellular interaction between the S1 helix and the S5-P region is crucial for modulating the gating polarity. The alanine substitution of several residues in this region (F431A, C566A, I607A, and Y611A) impaired the inward current of K525N&F627Y. CONCLUSIONS: Our data provide evidence that a potential cooperation mechanism in the extracellular vestibule of the VSD and the PD would determine the gating polarity in hERG.


Asunto(s)
Canal de Potasio ERG1 , Activación del Canal Iónico , Humanos , Secuencia de Aminoácidos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Activación del Canal Iónico/genética , Mutación , Nucleótidos Cíclicos , Canal de Potasio ERG1/genética
4.
Cancer ; 130(6): 851-862, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-37933913

RESUMEN

BACKGROUND: With the largest sample size to date, the authors' objective was to investigate the incidence of primary-to-metastatic human epidermal growth factor 2 (HER2) conversion and the predictors for such conversion. Moreover, no previous studies have evaluated the prognosis of patients who have negative HER2 expression (HER2-0) versus low HER2 expression (HER2-low) when HER2 status was assessed based on all recurrent/metastatic lesions. METHODS: The authors included 1299 patients who had available HER2 status of primary breast tumors and paired recurrent/metastatic lesions at Fudan University Shanghai Cancer Center and West China Hospital. RESULTS: In total, 370 patients (28.5%) experienced primary-to-metastatic HER2 conversion. Intrapatient intermetastasis spatial heterogeneity and temporal heterogeneity of HER2 were detected. When assessing HER2 based on recurrent/metastatic tumors, patients who had HER2-0 tumors had significantly shorter overall survival than those who had HER2-low tumors in the overall population and in the estrogen receptor (ER)-negative subgroup. However, when assessing HER2 based on primary tumors, there was no difference in overall survival between patients who had HER2-0 versus HER2-low tumors. Moreover, patients who had tumors that converted from HER2-0 to HER2-low had longer overall survival than those who had consistent HER2-0 status in the ER-negative subgroup. By combining four predictors (ER status, Ki67 index, biopsy site, and disease-free interval), the authors established the first prediction tool to estimate the probability of HER2-0 tumors converting to HER2-low/positive tumors. CONCLUSIONS: Intrapatient primary-to-metastatic and intermetastatic HER2 heterogeneity were observed in this large-scale cohort study. When evaluating HER2 based on recurrent/metastatic tumors, an overall survival difference was observed between patients who had HER2-0 versus HER2-low, recurrent/metastatic breast tumors. The developed prediction tool might help clinicians screen out patients with primary HER2-0 tumors that have a high probability of HER2 status conversion and recommend them for re-biopsy, thus helping to screen out candidate patients for trastuzumab deruxtecan treatment.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Estudios de Cohortes , China , Pronóstico , Receptores de Progesterona/metabolismo
5.
BMC Med ; 22(1): 285, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38972971

RESUMEN

BACKGROUND: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. METHODS: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. RESULTS: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50-26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15-28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25-35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. CONCLUSIONS: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.


Asunto(s)
Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/epidemiología , Humanos , Incidencia , Salud Global , Femenino , Masculino
6.
Small ; 20(6): e2304743, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37803930

RESUMEN

Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h-1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination.

7.
J Med Virol ; 96(5): e29521, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38727013

RESUMEN

Methylation panels, tools for investigating epigenetic changes associated with diseases like cancer, can identify DNA methylation patterns indicative of disease, providing diagnostic or prognostic insights. However, the application of methylation panels focusing on the sex-determining region Y-box 1 (SOX1) and paired box gene 1 (PAX1) genes for diagnosing cervical lesions is under-researched. This study aims to examine the diagnostic performance of PAX1/SOX1 gene methylation as a marker for cervical precancerous lesions and its potential application in triage diagnosis. From September 2022 to April 2023, 181 patients with abnormal HPV-DNA tests or cytological exam results requiring colposcopy were studied at Hubei Maternal and Child Health Hospital, China. Data were collected from colposcopy, cytology, HPV-DNA tests, and PAX1/SOX1 methylation detection. Patients were categorized as control, cervical intraepithelial neoplasia Grade 1 (CIN1), Grade 2 (CIN2), Grade 3 (CIN3), and cervical cancer (CC) groups based on histopathology. We performed HPV testing, liquid-based cytology, and PAX1/SOX1 gene methylation testing. We evaluated the diagnostic value of methylation detection in cervical cancer using DNA methylation positivity rate, sensitivity, specificity, and area under the curve (AUC), and explored its potential for triage diagnosis. PAX1/SOX1 methylation positivity rates were: control 17.1%, CIN1 22.5%, CIN2 100.0%, CIN3 90.0%, and CC 100.0%. The AUC values for PAX1 gene methylation detection in diagnosing CIN1+, CIN2+, and CIN3+ were 0.52 (95% confidence interval [CI]: 0.43-0.62), 0.88 (95% CI: 0.80-0.97), and 0.88 (95% CI: 0.75-1.00), respectively. Corresponding AUC values for SOX1 gene methylation detection were 0.47 (95% CI: 0.40-0.58), 0.80 (95% CI: 0.68-0.93), and 0.92 (95% CI: 0.811-1.00), respectively. In HPV16/18-negative patients, methylation detection showed sensitivity of 32.4% and specificity of 83.7% for CIN1+. For CIN2+ and CIN3+, sensitivity was all 100%, with specificities of 83.0% and 81.1%. Among the patients who underwent colposcopy examination, 166 cases had cytological examination results ≤ASCUS, of which 37 cases were positive for methylation, and the colposcopy referral rate was 22.29%. PAX1/SOX1 gene methylation detection exhibits strong diagnostic efficacy for cervical precancerous lesions and holds significant value in triage diagnosis.


Asunto(s)
Metilación de ADN , Factores de Transcripción Paired Box , Infecciones por Papillomavirus , Factores de Transcripción SOXB1 , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Biomarcadores de Tumor/genética , China , Colposcopía , Detección Precoz del Cáncer/métodos , Factores de Transcripción Paired Box/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Sensibilidad y Especificidad , Factores de Transcripción SOXB1/genética , Triaje/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética
8.
FASEB J ; 37(5): e22898, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37022664

RESUMEN

Nonalcoholic fatty liver disease (NAFLD), which leads to insulin resistance, steatosis, and even hepatocellular carcinoma, is the most common chronic liver disease worldwide, however, effective treatment is still lacking. This study determined the role of liver FGF21 and the mechanisms underlying the protective effects of time-restricted feeding (TRF) in NAFLD. FGF21 liver knockout (FGF21 LKO) mice and C57BL/6 wild-type (WT) mice were fed either a normal or a high-fat diet (HFD) for 16 weeks. Mice with diet-induced obesity (DIO) were also used. The mice were fed either ad libitum or in a time-restricted manner. Serum FGF21 levels were significantly increased after 16 weeks of TRF. TRF prevented body weight gain, improved glucose homeostasis, and protected against high-fat diet-induced hepatosteatosis and liver damage. The expression of genes related to liver lipogenesis and inflammation was reduced in TRF mice, but the expression of genes involved in fatty acid ß-oxidation was increased. However, those beneficial effects of TRF were blunted in the FGF21 LKO mice. Moreover, TRF promoted improvements in insulin sensitivity and liver damage in DIO mice. Our data show that liver FGF21 signaling was involved in the effect of TRF on high-fat diet-induced fatty liver.


Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Dieta Alta en Grasa , Hígado/metabolismo , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo
9.
Ann Hematol ; 103(8): 2699-2709, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38736014

RESUMEN

There has been no severity evaluation model for pediatric patients with hemophagocytic lymphohistiocytosis (HLH) that uses readily available parameters. This study aimed to develop a novel model for predicting the early mortality risk in pediatric patients with HLH using easily obtained parameters whatever etiologic subtype. Patients from one center were divided into training and validation sets for model derivation. The developed model was validated using an independent validation cohort from the second center. The prediction model with nomogram was developed based on logistic regression. The model performance underwent internal and external evaluation and validation using the area under the receiver operating characteristic curve (AUC), calibration curve with 1000 bootstrap resampling, and decision curve analysis (DCA). Model performance was compared with the most prevalent severity evaluation scores, including the PELOD-2, P-MODS, and pSOFA scores. The prediction model included nine variables: glutamic-pyruvic transaminase, albumin, globulin, myohemoglobin, creatine kinase, serum potassium, procalcitonin, serum ferritin, and interval between onset and diagnosis. The AUC of the model for predicting the 28-day mortality was 0.933 and 0.932 in the training and validation sets, respectively. The AUC values of the HScore, PELOD-2, P-MODS and pSOFA were 0.815, 0.745, 0.659 and 0.788, respectively. The DCA of the 28-day mortality prediction exhibited a greater net benefit than the HScore, PELOD-2, P-MODS and pSOFA. Subgroup analyses demonstrated good model performance across HLH subtypes. The novel mortality prediction model in this study can contribute to the rapid assessment of early mortality risk after diagnosis with readily available parameters.


Asunto(s)
Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/sangre , Femenino , Masculino , Preescolar , Niño , Lactante , Medición de Riesgo , Índice de Severidad de la Enfermedad , Adolescente , Nomogramas , Estudios Retrospectivos , Curva ROC , Factores de Riesgo
10.
Reprod Biomed Online ; 49(2): 103912, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810314

RESUMEN

RESEARCH QUESTION: What are the metabolic characteristics of follicular fluid in patients with ovarian endometriosis undergoing IVF? DESIGN: This was an exploratory cohort study on endometriosis. In total, 19 infertile patients with ovarian endometriosis diagnosed by laparoscopy, and 23 controls matched in terms of age and body mass index (women with infertility due to male or tubal factors) were enrolled in this study. All patients underwent IVF treatment with a gonadotrophin-releasing hormone antagonist protocol, and follicular fluid was collected at oocyte retrieval. The metabolomics of follicular fluid samples was analysed using an ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). The best combination of biomarkers was selected by performing stepwise logistic regression analysis with backward elimination. RESULTS: Fifteen metabolites were identified as biomarkers associated with endometriosis. A final model containing 8-hydroxy-2-deoxyguanosine, biotin, n-acetyl-L-methionine and n-methylnicotinamide was constructed. Receiver operating characteristic analysis confirmed the value of these parameters in diagnosing endometriosis, with sensitivity of 94.7% and specificity of 95.7%. Enrichment analysis via the Kyoto Encyclopedia of Genes and Genome showed that 15 metabolites were enriched in eight metabolic pathways. CONCLUSION: Metabolomics based on UHPLC-OE-MS effectively characterized the metabolomics analysis of follicular fluid in patients with ovarian endometriosis. These findings may provide a new basis for better understanding of how diseases progress, and for the discovery of new biomarkers.


Asunto(s)
Endometriosis , Fertilización In Vitro , Líquido Folicular , Metaboloma , Humanos , Femenino , Líquido Folicular/metabolismo , Líquido Folicular/química , Endometriosis/metabolismo , Proyectos Piloto , Adulto , Metabolómica , Biomarcadores/metabolismo , Biomarcadores/análisis , Infertilidad Femenina/metabolismo , Cromatografía Líquida de Alta Presión , Enfermedades del Ovario/metabolismo , Estudios de Casos y Controles
11.
Phys Chem Chem Phys ; 26(12): 9155-9169, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38165855

RESUMEN

Src homology 2-domain-containing tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase that is widely expressed in a variety of cells and regulates the immune response of T cells through the PD-1 pathway. However, the activation mechanism and allosteric effects of SHP2 remain unclear, hindering the development of small molecule inhibitors. For the first time, in this study, the complex structure formed by the intact PD-1 tail and SHP2 was modeled. The molecular recognition and conformational changes of inactive/active SHP2 versus ITIM/ITSM were compared based on prolonged MD simulations. The relative flexibility of the two SH2 domains during MD simulations contributes to the recruitment of ITIM/ITSM and supports the subsequent conformational change of SHP2. The binding free energy calculation shows that inactive SHP2 has a higher affinity for ITIM/ITSM than active SHP2, mainly because the former's N-SH2 refers to the α-state. In addition, a significant decrease in the contribution to the binding energy of certain residues (e.g., R32, S34, K35, T42, and K55) of conformationally transformed SHP2 contributes to the above result. These detailed changes during conformational transition will provide theoretical guidance for the molecular design of subsequent novel anticancer drugs.


Asunto(s)
Receptor de Muerte Celular Programada 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Proteína Tirosina Fosfatasa no Receptora Tipo 11/química , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Dominios Homologos src
12.
J Appl Microbiol ; 135(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38449343

RESUMEN

AIMS: This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. METHODS AND RESULTS: The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l-1. CONCLUSIONS: I. terricola could successfully adjust its membrane structure and function below 60 g l-1 of citric acid. However, for citric acid concentrations above 80 g l-1, its structure and function were dramatically changed, which might result in reduced functionality.


Asunto(s)
Estructuras de la Membrana Celular , Ácido Cítrico , Pichia , Ácido Cítrico/farmacología , Ácidos Grasos/farmacología , Membrana Celular , Fluidez de la Membrana
13.
J Chem Phys ; 160(2)2024 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-38205850

RESUMEN

Doubly resonant sum frequency generation (DR-SFG) serves as a potent characteristic technique for probing the electronic spectra and vibronic coupling of molecules on surfaces. In this study, we successfully developed a novel infrared (IR)-white light (WL) DR-SFG spectroscopy based on narrowband IR and tunable broadband WL. This novel method was employed to explore the excitation spectrum and vibronic couplings of sub-monolayer Rhodamine 6G molecules. Our findings elucidate that the xanthene skeleton vibrational modes exhibit strong coupling with the S0-S1 electronic transition. Notably, we observed not only the 0-0 transition of the S0-S1 electronic continuum but also the 0-1 transition, a first time observation in the realm of DR-SFG spectroscopy. This advanced DR-SFG spectroscopy methodology facilitates a more sensitive examination of electronic spectra and the coupling between electronic transitions and vibrational modes, heralding a significant advancement in the understanding of molecular interactions on surfaces.

14.
BMC Public Health ; 24(1): 1212, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693488

RESUMEN

BACKGROUND: Combining smoking with poor eating habits significantly elevates the risk of chronic illnesses and early death. Understanding of how dietary quality shifts post-smoking cessation remains limited. The objective of this study is to examine dietary quality - using Healthy Eating Index (HEI - 2020) and its 13 components, among current, former, and never smokers, and particularly the impact of quitting and the duration of cessation on dietary habits. METHODS: A cross-sectional analysis of 31,569 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 was conducted. Dietary quality was assessed using HEI-2020 scores, which were determined by NIH developed - simple HEI scoring algorithm per person. Smoking status was categorized into current, former, and never smokers, with further subdivisions for current (heavy/light smokers) and former smokers (duration post-cessation). Descriptive analysis and multiple regression models weighted to represent the US population were performed. RESULTS: The current smoking rate was 19.4%, with a higher prevalence in males (22.5%) than females (17.5%). Current smokers reported statistically significantly lower HEI total score than both former and never smokers. Former smokers exhibited HEI scores similar to those of never smokers. The adjusted HEI total scores for current, former, and never smokers were 49.2, 54.0, and 53.3, respectively, with a statistically significant difference (p < 0.001). Moreover, light smokers had better total HEI score than heavy smokers (46.8 vs. 50.8, p < 0.001, respectively), but former and never smokers scored even higher. Quitting smoking immediately improved dietary quality, with former smokers reaching the dietary levels of never smokers within 5-10 years (53.8 vs. 53.3, p > 0.05, respectively). Compared to current smokers, former smokers tended to consume more beneficial foods (e.g., fruits, vegetables, greens and beans, whole grains, proteins, and fatty acids), while also consuming more sodium and less added sugar. CONCLUSIONS: Current smokers, particularly heavy smokers, exhibit poorer dietary habits than former and never smokers. The dietary quality of former smokers aligns with never smokers over time, highlighting the positive impact of smoking cessation on diet. This has implications for reducing chronic disease risks associated with poor diet and smoking.


Asunto(s)
Dieta Saludable , Encuestas Nutricionales , Fumar , Humanos , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Dieta Saludable/estadística & datos numéricos , Estados Unidos/epidemiología , Fumar/epidemiología , Adulto Joven , Cese del Hábito de Fumar/estadística & datos numéricos , Anciano , Conducta Alimentaria
15.
Echocardiography ; 41(1): e15747, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38284682

RESUMEN

OBJECTIVES: Congenital ventricular outpouching (CVO) is a rare cardiac malformation that can manifest as congenital ventricular aneurysm (CVA) and/or congenital ventricular diverticula (CVD). In this study, we describe the prenatal features and postnatal follow-up of 27 cases of CVO. METHODS: The clinical data of 27 patients with CVO who attended Sir Run Run Shaw Hospital Affiliated to the Medical College of Zhejiang University (Zhejiang Province, China) and Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Zhejiang Province, China) from April 2013 to October 2022 were retrospectively analyzed. The patients were also followed up by telephone. The prenatal characteristics and postnatal outcomes of the patients with CVO were evaluated. RESULTS: CVO was detected in 26 cases prenatally, 14 (51.85%) were diagnosed with CVA, nine (33.33%) were diagnosed with CVD, three (11.11%) were equivocal for CVA/CVD, and one (3.70%) was detected with CVA postnatally. Six patients underwent follow-up fetal echocardiography approximately 4 weeks after the initial echocardiography examination, and a significant difference in CVO size was observed between the two examinations (P = .02). Eight patients (29.63%) demonstrated cardiovascular dysfunction, and the median CVO size in fetuses with and without cardiovascular dysfunction was 205 (range: 169-396) mm2 and 124 (range: 92-154.5) mm2 , respectively (P = .01). Correlation was found between CVO size and fetal cardiac dysfunction (p = .000, r = .778). Eight patients (29.63%) had cardiac/extracardiac defects. Thirteen patients were live born, 12 were terminated pregnancies, and two were lost to follow-up. The postpartum size of the CVOs remained stable in six patients, decreased in two patients, dissolved in three patients, and were surgically removed in two patients. With the exception of one patient with CVA complicated with complex congenital cardiac malformation who underwent surgical treatment after birth and who had postoperative left ventricular dysfunction (Case 1), the prognosis of all of the patients was good. CONCLUSION: CVO is often associated with cardiac malformations. The size of prenatal CVOs can increase with gestational development, and cardiovascular dysfunction is significantly related to CVO size. The postpartum prognosis of patients with CVO is good. Echocardiography plays a key role in the diagnosis of congenital ventricular outpouching. Prenatal counseling should be cautious regarding the diagnosis and the prognosis although our cases had a favorable prognosis.


Asunto(s)
Cardiopatías Congénitas , Ultrasonografía Prenatal , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Estudios de Seguimiento , Cardiopatías Congénitas/diagnóstico por imagen , Feto
16.
Euro Surveill ; 29(24)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873796

RESUMEN

In 2003-2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19PAS, 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23, bla OXA-72, and/or bla NDM-5. Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Proteínas Bacterianas , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , beta-Lactamasas/genética , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Humanos , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Proteínas Bacterianas/genética , Ucrania/epidemiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Filogenia , Farmacorresistencia Bacteriana Múltiple/genética , Georgia (República)/epidemiología , Tipificación de Secuencias Multilocus
17.
J Environ Manage ; 360: 121020, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38763116

RESUMEN

Reducing soil erosion (SE) is crucial for achieving harmony between human society and the ecological environment. The cultivated land fragmentation (CLF), directly or indirectly, alters soil structure, diminishes its water-holding capacity, and escalates the risk of SE. Scientific assessment of the effect of CLF on SE can provide new insights into controlling of SE across watersheds in China. However, few studies have quantified the effect of CLF on SE. Therefore, we utilized land use change data in the Yangtze River basin from 2000 to 2020, measuring the levels of CLF and SE using Fragstats and InVEST models. The bivariate spatial autocorrelation model was employed to reveal the spatial relationship between CLF and SE. Additionally, we constructed a spatial Durbin model and introduced the geographically and temporally weighted regression model to analyze the role of CLF on SE. The south bank of the upper and middle reaches of the Yangtze River basin exhibited high CLF and SE. The bivariate spatial autocorrelation results showed a significant positive spatial correlation between CLF and SE. The spatial Durbin model results showed that CLF had a spatial spillover effect and time lag on SE, and the effect of CLF on SE had an inverted "N" curve. The study also confirmed that last SE and neighboring SE areas influenced local SE. Currently, CLF had a negative effect on SE in the Sichuan Basin, Yunnan-Guizhou Plateau, and the middle and lower Yangtze River Plain, and positively in Qinghai, Hunan, and Jiangxi provinces. These findings suggest that the government should enhance cross-regional and cross-sectoral cooperation and monitoring of cultivated land changes to prevent and control SE effectively.


Asunto(s)
Ríos , Erosión del Suelo , Suelo , China , Suelo/química , Conservación de los Recursos Naturales , Agricultura , Monitoreo del Ambiente
18.
J Environ Manage ; 364: 121371, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38879965

RESUMEN

Rapid urbanization and high-intensity socio-economic activities in China have caused severe ecological problems. Implementing ecological restoration in China has become an inevitable way to restore the ecosystem. Ecosystem health is crucial for evaluating ecological conditions and trends, but comprehensive national studies that use quantitative ecosystem health assessments to guide specific ecological restoration are lacking. This study constructs the Vigor-Organization-Resilience-Services (VORS) model to evaluate the ecosystem health level of China during 2000-2020. Then, through the natural breakpoint and intelligent clustering correction, we carried out the ecological restoration zoning and proposed corresponding measures. The results show that China's overall ecosystem health declined from 2000 to 2020, and ecological restoration is imminent. The spatial pattern of ecosystem health is generally favorable in the south and usually poor in the north. China protects poor ecosystems' health well but needs more for better ones. To combat this degradation, we propose a zoning strategy that classifies the landscape into five categories: Ecosystem Conservation Areas (3.47%), focusing on biodiversity preservation; Ecosystem Enhancement Areas (10.53%), aiming at increasing ecological resilience; Ecosystem Buffer Zones (23.04%), intending to mitigate human impacts; Ecosystem Correction Zones (33.79%), targeting at restoring degraded ecosystems; and Ecosystem Reshaping Zones (29.17%), designing to revitalize ecological functions. The ecological restoration zoning in China proposed in this study, combined with appropriate and practical restoration tools, will help mitigate ecological problems and improve stability and ecosystem health.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , China , Biodiversidad , Urbanización , Ecología , Humanos
19.
J Sci Food Agric ; 104(11): 6405-6416, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38497362

RESUMEN

BACKGROUND: Due to the high level of organic acids - primarily citric acid - black, red, and white currants have an excessively sour taste, making taste adjustment during processing challenging. This study investigated and evaluated the effects of an inoculation dose of the acid-reducing yeast Issatchenkia terricola WJL-G4 on several aspect such as physicochemical properties, chromaticity, active substances, and antioxidant capacity. A sensory evaluation was also conducted. RESULTS: The results indicated that, when the inoculation dose increased from 2% to 12%, the total phenol, total flavonoid, and total anthocyanin content, and antioxidant capacity in currant juice decreased. A low inoculation dose (2-4%) was beneficial for preserving the total phenol and total flavonoid content. Although the levels of most phenolic compounds decreased, the concentrations of caffeic acid, p-coumaric acid, ferulic acid, rutin, and epicatechin were significantly higher than the control after fermentation. Overall acceptability and taste scores of fermented currants improved compared with those of the control group. CONCLUSION: This experiment provided an effective solution, with a theoretical basis, to the problems of the sour taste and harsh flavor of currant juice. © 2024 Society of Chemical Industry.


Asunto(s)
Antocianinas , Antioxidantes , Fermentación , Jugos de Frutas y Vegetales , Fenoles , Ribes , Gusto , Ribes/química , Antioxidantes/análisis , Antioxidantes/química , Jugos de Frutas y Vegetales/análisis , Humanos , Fenoles/análisis , Fenoles/química , Antocianinas/análisis , Antocianinas/química , Flavonoides/análisis , Frutas/química , Saccharomycetales/metabolismo , Color
20.
J Environ Sci (China) ; 138: 301-311, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38135397

RESUMEN

Environmental effects of nano remediation engineering of arsenic (As) pollution need to be considered. In this study, the roles of Fe2O3 and TiO2 nanoparticles (NPs) on the microbial mediated As mobilization from As contaminated soil were investigated. The addition of Fe2O3 and TiO2 NPs restrained As(V) release, and stimulated As(III) release. As(V) concentration decreased by 94% and 93% after Fe2O3 addition, and decreased by 89% and 45% after TiO2 addition compared to the Biotic and Biotic+Acetate (amended with sodium acetate) controls, respectively. The maximum values of As(III) were 20.5 and 27.1 µg/L at 48 d after Fe2O3 and TiO2 NPs addition, respectively, and were higher than that in Biotic+Acetate control (12.9 µg/L). The released As co-precipitated with Fe in soils in the presence of Fe2O3 NPs, but adsorbed on TiO2 NPs in the presence of TiO2 NPs. Moreover, the addition of NPs amended with sodium acetate as the electron donor clearly promoted As(V) reduction induced by microbes. The NPs addition changed the relative abundance of soil bacterial community, while Proteobacteria (42.8%-70.4%), Planctomycetes (2.6%-14.3%), and Firmicutes (3.5%-25.4%) were the dominant microorganisms in soils. Several potential As/Fe reducing bacteria were related to Pseudomonas, Geobacter, Desulfuromonas, and Thiobacillus. The addition of Fe2O3 and TiO2 NPs induced to the decrease of arrA gene. The results indicated that the addition of NPs had a negative impact on soil microbial population in a long term. The findings offer a relatively comprehensive assessment of Fe2O3 and TiO2 NPs effects on As mobilization and soil bacterial communities.


Asunto(s)
Arsénico , Microbiota , Nanopartículas , Arsénico/metabolismo , Suelo , Acetato de Sodio/metabolismo , Acetato de Sodio/farmacología , Bacterias/metabolismo
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