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1.
Front Pharmacol ; 15: 1359939, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933676

RESUMEN

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

2.
Methods Cell Biol ; 188: 131-152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38880521

RESUMEN

Renal injury often occurs as a complication in autoimmune diseases such as systemic lupus erythematosus (SLE). It is estimated that a minimum of 20% SLE patients develop lupus nephritis, a condition that can be fatal when the pathology progresses to end-stage renal disease. Studies in animal models showed that incidence of immune cell infiltrates in the kidney was linked to pathological injury and correlated with severe lupus nephritis. Thus, preventing immune cell infiltration into the kidney is a potential approach to impede the progression to an end-stage disease. A requirement to investigate the role of kidney-infiltrating leukocytes is the development of reproducible and efficient protocols for purification and characterization of immune cells in kidney samples. This chapter describes a detailed methodology that discriminates tissue-resident leukocytes from blood-circulating cells that are found in kidney. Our protocol was designed to maximize cell viability and to reduce variability among samples, with a combination of intravascular staining and magnetic bead separation for leukocyte enrichment. Experiments included as example were performed with FcγRIIb[KO] mice, a well-characterized murine model of SLE. We identified T cells and macrophages as the primary leukocyte subsets infiltrating into the kidney during severe nephritis, and we extensively characterized them phenotypically by flow cytometry.


Asunto(s)
Modelos Animales de Enfermedad , Riñón , Leucocitos , Nefritis Lúpica , Animales , Nefritis Lúpica/patología , Nefritis Lúpica/inmunología , Ratones , Riñón/patología , Leucocitos/inmunología , Leucocitos/patología , Separación Celular/métodos , Ratones Noqueados , Macrófagos/inmunología , Macrófagos/patología , Citometría de Flujo/métodos , Linfocitos T/inmunología , Receptores de IgG/metabolismo
3.
Acta Chim Slov ; 71(2): 295-303, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38919097

RESUMEN

A new phenanthroline derivative bearing imidazole group, (2-(3,5-di(pyridin-4-yl)phenyl)-1-p-tolyl-1H-imidazo[4,5-f][1,10]phenanthroline) (1), has been devised. 1 can be used as a multifunctional probe exhibiting a highly sensitive colorimetric response to Fe2+ and a selectively ratiometric fluorescent response to Zn2+ in a buffer-ethanol solution. The absorption enhancement accompanied by a visual color change from colorless to red upon addition of Fe2+, makes 1 a suitable naked-eye sensor for Fe2+. Moreover, 1 displayed a Zn2+-induced red-shift of emission (44 nm) showing a color change from blue to light cyan under a 365-nm UV lamp. Its practical imaging applicability for intracellular Zn2+ was confirmed in HeLa cells using a confocal microscope. The improved emission properties and cell imaging capability would provide a new approach for fluorescence sensation for Zn2+.

4.
Opt Express ; 32(9): 16478-16490, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859273

RESUMEN

In this work, we quantitatively investigate the SBS threshold in high-power narrow-linewidth fiber amplifiers seeded with phase-modulated single-frequency lasers in presence of weak end feedback. The impacts of the end feedback and spectral linewidths on the SBS threshold are demonstrated in detail through comparative experiments and numerical simulations, respectively. In the experiment, we have pointed out a practical method to estimate the end reflectivity in high-power fiber amplifiers. Based on this estimation, the SBS threshold characters of the high-power narrow-linewidth fiber amplifiers with different end reflectivity and seed linewidths are investigated. By reducing the end reflectivity, a 2.85 times SBS threshold enhancement has been achieved at the most susceptible linewidth (16.8 GHz). Furthermore, we propose a spectral evolution model to investigate the SBS threshold in high-power narrow-linewidth fiber amplifiers, which is even capable for calculating SBS thresholds of the systems with tens of GHz linewidth while weak end reflection is considered. The simulation results demonstrate that end reflection will obviously affect the SBS threshold when the linewidth of the seed laser is broadened beyond 5 GHz, especially for the spectral linewidth of seed lasers nearing the Brillouin frequency shift. Besides, when the end reflectivity is set to be stronger than -65 dB, the SBS threshold performs a tendency to decline and then rise with the growth of seed linewidth. The experiment and simulation results provide a new optimization sight for the SBS effect suppression in high-power narrow-linewidth fiber amplifiers.

5.
Sci Rep ; 14(1): 13000, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844819

RESUMEN

The Marine Predator Algorithm (MPA) has unique advantages as an important branch of population-based algorithms. However, it emerges more disadvantages gradually, such as traps to local optima, insufficient diversity, and premature convergence, when dealing with complex problems in practical industrial engineering design applications. In response to these limitations, this paper proposes a novel Improved Marine Predator Algorithm (IMPA). By introducing an adaptive weight adjustment strategy and a dynamic social learning mechanism, this study significantly improves the encounter frequency and efficiency between predators and preys in marine ecosystems. The performance of the IMPA was evaluated through benchmark functions, CEC2021 suite problems, and engineering design problems, including welded beam design, tension/compression spring design, pressure vessel design, and three-bar design. The results indicate that the IMPA has achieved significant success in the optimization process over other methods, exhibiting excellent performance in both solving optimal parameter solutions and optimizing objective function values. The IMPA performs well in terms of accuracy and robustness, which also proves its efficiency in successfully solving complex industrial engineering design problems.

6.
ESC Heart Fail ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773746

RESUMEN

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

7.
Diagn Microbiol Infect Dis ; 109(3): 116278, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38723451

RESUMEN

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Sensibilidad y Especificidad , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Masculino , Femenino , Metagenómica/métodos , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Adulto Joven , Enfermedades de la Columna Vertebral/microbiología , Enfermedades de la Columna Vertebral/diagnóstico
8.
Neuroreport ; 35(9): 568-576, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38652513

RESUMEN

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.


Asunto(s)
Oftalmopatía de Graves , Imagen por Resonancia Magnética , Corteza Visual Primaria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Oftalmopatía de Graves/fisiopatología , Oftalmopatía de Graves/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Corteza Visual Primaria/fisiopatología , Corteza Visual Primaria/diagnóstico por imagen , Corteza Visual Primaria/fisiología , Máquina de Vectores de Soporte , Mapeo Encefálico/métodos , Adulto , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Corteza Visual/fisiopatología , Corteza Visual/diagnóstico por imagen
9.
Environ Microbiol Rep ; 16(2): e13248, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38581137

RESUMEN

Sulphate-reducing bacteria (SRB) are the main culprits of microbiologically influenced corrosion in water-flooding petroleum reservoirs, but some sulphur-oxidising bacteria (SOB) are stimulated when nitrate and oxygen are injected, which control the growth of SRB. This study aimed to determine the distributions of SRB and SOB communities in injection-production systems and to analyse the responses of these bacteria to different treatments involving nitrate and oxygen. Desulfovibrio, Desulfobacca, Desulfobulbus, Sulfuricurvum and Dechloromonas were commonly detected via 16S rRNA gene sequencing. Still, no significant differences were observed for either the SRB or SOB communities between injection and production wells. Three groups of water samples collected from different sampling sites were incubated. Statistical analysis of functional gene (dsrB and soxB) clone libraries and quantitative polymerase chain reaction showed that the SOB community structures were more strongly affected by the nitrate and oxygen levels than SRB clustered according to the sampling site; moreover, both the SRB and SOB community abundances significantly changed. Additionally, the highest SRB inhibitory effect and the lowest dsrB/soxB ratio were obtained under high concentrations of nitrate and oxygen in the three groups, suggesting that the synergistic effect of nitrate and oxygen level was strong on the inhibition of SRB by potential SOB.


Asunto(s)
Desulfovibrio , Petróleo , Nitratos , Sulfatos , Agua , ARN Ribosómico 16S/genética , Bacterias , Desulfovibrio/genética , Compuestos Orgánicos , Azufre , Oxidación-Reducción
10.
Eur J Surg Oncol ; 50(6): 108280, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38537365

RESUMEN

BACKGROUND: The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. METHODS: Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. RESULTS: Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively. CONCLUSIONS: TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.


Asunto(s)
Gastrectomía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Quimioterapia Adyuvante , Tasa de Supervivencia , Terapia Neoadyuvante , Estudios Retrospectivos , Supervivencia sin Enfermedad , Estadificación de Neoplasias , Factores de Riesgo , Adulto , Resultado del Tratamiento
11.
J Phys Chem Lett ; 15(13): 3619-3626, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38530255

RESUMEN

The light-harvesting (LH) and reaction center (RC) core complex of purple bacterium Roseiflexus castenholzii, B880-B800-RC, are different from those of the typical photosynthetic unit, (B850-B800)x-B880-RC. To investigate the excitation flowing dynamics in this unique complex, two-dimensional electronic spectroscopy is employed. The obtained time constants for the exciton relaxation in B880, exciton relaxation in B800, B800 → B880 energy transfer (EET), and B880 → closed RC EET are 43 fs, 177 fs, 1.9 ps, and 205 ps, respectively. These time constants result in an overall EET efficiency similar to that of the typical photosynthetic unit. Analysis of the oscillatory signals reveals that while several vibronic coherences are involved in the exciton relaxation process, only one prominent vibronic coherence, with a frequency of 27 cm-1 and coupled to the B880 electronic transition, may contribute to the B800 → B880 EET process.

12.
Prep Biochem Biotechnol ; : 1-5, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477625

RESUMEN

α-L-rhamnosidase (Rha) is ubiquitous in nature and has high feasibility in the food and biotechnology industries. A green and environmentally friendly method was used to improve the activity of Rha. Here, we show that the effects of ultrasound treatment on the Rha. Ultrasonic treatment at 80 W for 10 min yielded the highest enzyme activity. Treatment increased enzyme activity by 26.3% and half-life by 124 min. Further, treatment increased the catalytic efficiency of Rha and increased the substrate conversion rate by 33.88%. These results demonstrate that ultrasound increases the catalytic activity and stability of Rha. Thus, ultrasonic treatment of Rha is cost-effective on the industrial scale.

13.
Int J Surg ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38537085

RESUMEN

BACKGROUND: Robotic gastrectomy is a safe and feasible approach for gastric cancer (GC); however, its long-term oncological efficacy remains unclear. We evaluated the long-term survival outcomes and recurrence patterns of patients with locally advanced proximal GC who underwent robotic total gastrectomy (RTG). METHODS: This prospective study (FUGES-014 study) enrolled 48 patients with locally advanced proximal GC who underwent RTG between March 2018 and February 2020 at a tertiary referral teaching hospital. Patients who underwent laparoscopic total gastrectomy (LTG) in the FUGES-002 study were enrolled in a 2:1 ratio to compare the survival outcomes between RTG and LTG. The primary endpoint of the FUGES-014 study was postoperative 30-day morbidity and has been previously reported. Here we reported the results of 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence patterns. RESULTS: After propensity score matching, 48 patients in the RTG and 96 patients in the LTG groups were included. The 3-year DFS rates were 77.1% (95% confidence interval [CI] 66.1-89.9%) for the RTG and 68.8% (95% CI 60.1-78.7%) for the LTG groups ( P =0.261). The 3-year OS rates were not significantly different between the groups (85.4% vs. 74.0%, P =0.122). Recurrence occurred in nine patients (18.8%) in the RTG and 27 (28.1%) patients in the LTG groups ( P =0.234). Recurrence patterns and causes of death were similar between the groups ( P >0.05). CONCLUSIONS: The oncological outcome of RTG was non-inferior to that of LTG. Thus, RTG might be an alternative surgical treatment for locally advanced proximal GC.

14.
Pancreas ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38530976

RESUMEN

OBJECTIVES: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on caerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood. METHODS: A caerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of caerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules. RESULTS: We found that exosomes derived from caerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in caerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells. CONCLUSIONS: Exosomes derived from caerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

15.
J Phys Chem Lett ; 15(12): 3470-3477, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38512331

RESUMEN

The photosystem of filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii comprises a light-harvesting (LH) complex encircling a reaction center (RC), which intensely absorbs blue-green light by carotenoid (Car) and near-infrared light by bacteriochlorophyll (BChl). To explore the influence of light quality (color) on the photosynthetic activity, we compared the pigment compositions and triplet excitation dynamics of the LH-RCs from Rfl. castenholzii was adapted to blue-green light (bg-LH-RC) and to near-infrared light (nir-LH-RC). Both LH-RCs bind γ-carotene derivatives; however, compared to that of nir-LH-RC (12%), bg-LH-RC contains substantially higher keto-γ-carotene content (43%) and shows considerably faster BChl-to-Car triplet excitation transfer (10.9 ns vs 15.0 ns). For bg-LH-RC, but not nir-LH-RC, selective photoexcitation of Car and the 800 nm-absorbing BChl led to Car-to-Car triplet transfer and BChl-Car singlet fission reactions, respectively. The unique excitation dynamics of bg-LH-RC enhances its photoprotection, which is crucial for the survival of aquatic anoxygenic phototrophs from photooxidative stress.


Asunto(s)
Chloroflexi , Chloroflexi/química , Chloroflexi/metabolismo , Carotenoides , Complejos de Proteína Captadores de Luz/química , Fotosíntesis , Bacterioclorofilas/metabolismo , Proteínas Bacterianas/química
16.
J Affect Disord ; 351: 895-903, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38342317

RESUMEN

OBJECTIVE: Impulse control behaviors (ICBs) and apathy are believed to represent opposite motivational expressions of the same behavioral spectrum involving hypo- and hyperdopaminergic status, but this has been recently debated. Our study aims to estimate the co-occurrence of ICBs and apathy in early Parkinson's disease (PD) and to determine whether this complex neuropsychiatric condition is an important marker of PD prognoses. METHODS: Neuropsychiatric symptoms, clinical data, neuroimaging results, and demographic data from de novo PD patients were obtained from the Parkinson's Progression Markers Initiative, a prospective, multicenter, observational cohort. The clinical characteristics of ICBs co-occurring with apathy and their prevalence were analyzed. We compared the prognoses of the different groups during the 8-year follow-up. Multivariate Cox regression analysis was conducted to predict the development of levodopa-induced dyskinesia (LID) using baseline neuropsychiatric symptoms. RESULTS: A total of 422 PD patients and 195 healthy controls (HCs) were included. In brief, 87 (20.6 %) de novo PD patients and 37 (19.0 %) HCs had ICBs at baseline. Among them, 23 (26.4 %) de novo PD patients and 3 (8.1 %) HCs had clinical symptoms of both ICBs and apathy. The ICBs and apathy group had more severe non-motor symptoms than the isolated ICBs group. Cox regression analysis demonstrated that the co-occurrence of ICBs and apathy was a risk factor for LID development (HR 2.229, 95 % CI 1.209 to 4.110, p = 0.010). CONCLUSIONS: Co-occurrence of ICBs and apathy is common in patients with early PD and may help to identify the risk of LID development.


Asunto(s)
Apatía , Trastornos Disruptivos, del Control de Impulso y de la Conducta , Discinesias , Enfermedad de Parkinson , Humanos , Trastornos Disruptivos, del Control de Impulso y de la Conducta/inducido químicamente , Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Discinesias/complicaciones , Incidencia , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/complicaciones , Estudios Prospectivos
17.
Thorac Cancer ; 15(10): 755-763, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38390683

RESUMEN

BACKGROUND: The surgical Apgar score (SAS) quantifying three intraoperative indexes has been confirmed to be significantly associated with postoperative morbidity and prognosis in many surgical specialties. However, there are great limitations in its application for esophageal cancer (EC). This study aimed to assess the predictive capability of esophagectomy SAS (eSAS) in determining postoperative morbidity and overall survival (OS) in EC patients who had undergone neoadjuvant therapy. METHODS: A retrospective evaluation was conducted on a cohort of 221 patients in which surgery- and tumor-related data were extracted and analyzed. Major morbidity was defined as complications meeting the criteria of Clavien-Dindo classification III or higher during hospitalization. Univariate and multivariate analyses were performed to identify potential risk factors for major morbidity. Kaplan-Meier analysis was utilized to calculate the OS and relapse-free survival (RFS). RESULTS: The results exhibited that eSAS demonstrated potential predictive value for postoperative morbidity with an optimal cutoff value of 6. The eSAS and diabetes mellitus were two independent risk factors for the major morbidity; however, no correlation between the eSAS and the OS or RFS was detected. CONCLUSION: The eSAS could be used as a predictor of major morbidity, while it was not correlated with OS and RFS.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Humanos , Recién Nacido , Esofagectomía/efectos adversos , Esofagectomía/métodos , Estudios Retrospectivos , Puntaje de Apgar , Terapia Neoadyuvante/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Recurrencia Local de Neoplasia/cirugía , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/complicaciones
18.
J Integr Plant Biol ; 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38411333

RESUMEN

Halorhodospira (Hlr.) halochloris is a triply extremophilic phototrophic purple sulfur bacterium, as it is thermophilic, alkaliphilic, and extremely halophilic. The light-harvesting-reaction center (LH1-RC) core complex of this bacterium displays an LH1-Qy transition at 1,016 nm, which is the lowest-energy wavelength absorption among all known phototrophs. Here we report the cryo-EM structure of the LH1-RC at 2.42 Å resolution. The LH1 complex forms a tricyclic ring structure composed of 16 αßγ-polypeptides and one αß-heterodimer around the RC. From the cryo-EM density map, two previously unrecognized integral membrane proteins, referred to as protein G and protein Q, were identified. Both of these proteins are single transmembrane-spanning helices located between the LH1 ring and the RC L-subunit and are absent from the LH1-RC complexes of all other purple bacteria of which the structures have been determined so far. Besides bacteriochlorophyll b molecules (B1020) located on the periplasmic side of the Hlr. halochloris membrane, there are also two arrays of bacteriochlorophyll b molecules (B800 and B820) located on the cytoplasmic side. Only a single copy of a carotenoid (lycopene) was resolved in the Hlr. halochloris LH1-α3ß3 and this was positioned within the complex. The potential quinone channel should be the space between the LH1-α3ß3 that accommodates the single lycopene but does not contain a γ-polypeptide, B800 and B820. Our results provide a structural explanation for the unusual Qy red shift and carotenoid absorption in the Hlr. halochloris spectrum and reveal new insights into photosynthetic mechanisms employed by a species that thrives under the harshest conditions of any phototrophic microorganism known.

19.
Acta Biochim Biophys Sin (Shanghai) ; 56(2): 210-222, 2024 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273783

RESUMEN

Lung adenocarcinoma (LUAD) is one of the most aggressive types of lung cancer. The prognosis of LUAD patients remains poor, and the overall efficacy of gemcitabine-based chemotherapy is still unsatisfactory. Long noncoding RNAs (lncRNAs) play important roles in several cancer types by interacting with multiple proteins, RNA, and DNA. However, the relationship between lncRNA dysregulation and gemcitabine resistance in LUAD has not been fully elucidated. In this study, lncRNA CYTOR expression and its association with the prognosis of LUAD patients are assessed by quantitative RT-PCR and Kaplan-Meier survival analysis. In vitro and in vivo functional studies are conducted to evaluate the biological functions of CYTOR in LUAD. The underlying mechanism regarding the tumor-promoting effects of CYTOR is explored using RNA immunoprecipitation, biotin-labelled RNA pulldown, luciferase reporter assays, and western blot analysis. We identify that CYTOR is an oncogenic lncRNA and is apparently upregulated in LUAD by analysing TCGA-LUAD data. High CYTOR expression is a poor prognostic factor for LUAD. Functional studies reveal that CYTOR confers LUAD cells with stronger resistance to gemcitabine treatment and upregulates the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. Mechanically, CYTOR acts as a competitive endogenous RNA (ceRNA) to absorb miR-125a-5p, weakens the antitumor function of miR-125a-5p, and ultimately upregulates ANLN and RRM2 expressions. Taken together, this study explains the mechanism of lncRNA in the gemcitabine resistance of LUAD and formulates a theoretical framework for the in depth study of LUAD.


Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Gemcitabina , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proliferación Celular/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Adenocarcinoma/genética , Transición Epitelial-Mesenquimal/genética , Pulmón/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
20.
Environ Sci Pollut Res Int ; 31(7): 11307-11320, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38217811

RESUMEN

High-fluoride groundwater is commonly found in coastal areas worldwide, while its formation mechanism remains elusive. Herein, a comprehensive study was performed to identify the major controlling factor of high-fluoride groundwater occurrence along the eastern coast of China. Hydrogeochemical methods were employed to examine the distribution patterns of seawater intrusion and fluoride concentration and the impact of seawater intrusion on the fluoride concentration. The results indicate that seawater intrusion significantly influences the groundwater evolution process in the study areas. The groundwater in Laizhou Bay was affected by brine, and the groundwater in Tianjin and Jiangsu was affected by seawater with a mixing ratio lower than 40% and 20%, respectively. And the fluoride concentration in groundwater from Tianjin, Laizhou Bay, and Jiangsu generally exceeded 1 mg/L, with the average of 2.3 mg/L, 24.9 mg/L, and 34.6 mg/L, respectively. Both the degree of seawater intrusion and the fluoride concentration exhibit a consistent pattern: Laizhou Bay > Tianjin > Jiangsu. Cl- concentration in groundwater varies positively with the F- concentration (y = 0.66x - 1.31). Moreover, the spatial distribution of areas with high-fluoride groundwater mirrors that of seawater intrusion. The high-fluoride groundwater varies spatially and is related to the degree, stage, and type of seawater intrusion. In other words, when seawater intrusion intensifies more or groundwater in the freshwater renewal phase with higher Na+/Ca2+ or the presence of paleo-seawater intrusion with higher fluoride concentration of brine, the concentration of fluoride in groundwater is higher. As seawater intrusion intensifies, the high-fluoride groundwater in the study areas generally poses a higher health risk to human. These findings enhance our comprehension of the mechanisms underpinning high-fluoride groundwater in coastal regions and the environmental ramifications of seawater intrusion.


Asunto(s)
Fluoruros , Agua Subterránea , Sales (Química) , Humanos , Fluoruros/análisis , Monitoreo del Ambiente/métodos , Agua de Mar , China
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