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1.
Molecules ; 29(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39125025

RESUMEN

Synthetic radicals have intrinsic power for cascading and multifunctional reactions to construct diverse molecular scaffolds. In the previous review series, we covered 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-difunctionalizations, addition followed by cyclization reactions, and cycloaddition-initiated difunctionalizations. Presented in this paper are radical addition-initiated trifunctionalization reactions of alkenes, alkynes, and their derivatives. After the initial radical addition, there are different pathways, such as group or hydrogen atom transfer, cyclization, and radical coupling, to complete the second and third functionalizations.

2.
Front Neurol ; 15: 1346522, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144709

RESUMEN

Introduction: This study aims to examine brain activity during different swallowing actions in patients with dysphagia caused by medullary infarction (MI) before and after treatment using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Methods: Fifteen patients were enrolled in this study. Brain activation during saliva swallowing and effortful saliva swallowing was observed using BOLD imaging in the acute phase of stroke and after 4 weeks of rehabilitation training. Differences in the activation of brain regions during saliva swallowing before and after treatment, during effortful saliva swallowing before and after treatment, and between the two swallowing actions before and after treatment were compared. Results: In the acute phase of stroke, only the bilateral precentral and left lingual gyrus were partially activated during saliva swallowing, and there was no obvious activation in the insula. Effortful saliva swallowing activated more brain regions than saliva swallowing before treatment, including the bilateral supplementary motor area (SMA), postcentral gyrus, and right insular cortex. The number of brain regions activated during saliva swallowing increased after treatment, including the bilateral precentral gyrus, postcentral gyrus, insula, thalamus, and SMA. Discussion: Cortical activation increases after recovery from dysphagia, and the increased activation of the postcentral gyrus might play a functional compensatory role. Effortful saliva swallowing is a more effective rehabilitation training method for patients with dysphagia caused by MI.

3.
Front Plant Sci ; 15: 1297499, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139721

RESUMEN

Boehmeria is a taxonomically challenging group within the nettle family (Urticaceae). The polyphyly of the genus has been proposed by previous studies with respect to five genera (Debregeasia, Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus). Extensive homoplasy of morphological characters has made generic delimitation problematic. Previous studies in other plant groups suggest that plastome structural variations have the potential to provide characters useful in reconstructing evolutionary relationships. We aimed to test this across Boehmeria and its allied genera by mapping plastome structural variations onto a resolved strongly supported phylogeny. In doing so, we expanded the sampling of the plastome to include Cypholophus, Sarcochlamys, Archiboehmeria, and Astrothalamus for the first time. The results of our phylogenomic analyses provide strong support for Sarcochlamys as being more closely related to Leucosyke puya than to Boehmeria and for the clustering of Boehmeria s.l. into four subclades. The sizes of the plastomes in Boehmeria s.l. ranged from 142,627 bp to 170,958 bp. The plastomes recovered a typical quadripartite structure comprising 127~146 genes. We observe several obvious structural variations across the taxa such as gene loss and multiple gene duplication, inverted repeat (IR) contraction and wide expansions, and inversions. Moreover, we recover a trend for these variations that the early clades were relatively conserved in evolution, whereas the later diverging clades were variable. We propose that the structural variations documented may be linked to the adaptation of Boehmeria s.l. to a wide range of habitats, from moist broadleaf forests in Asia to xeric shrublands and deserts in Africa. This study confirms that variation in plastome gene loss/duplication, IR contraction/expansion, and inversions can provide evidence useful for the reconstruction of evolutionary relationships.

4.
Sci Prog ; 107(3): 368504241275402, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39150380

RESUMEN

Double-row planetary gear set (PGS) is a common form of the PGS, which is relatively more complex than the regular PGSs. It consists of one sun gear, several long planets, several short planets, two ring gears, and one carrier. Due to the significantly wider tooth width of the long planet compared to the sun gear, the axial meshing position between the sun gear and the long planet can be adjusted. The vibrations of PGS should vary with different axial meshing positions. If the axial position of the sun gear is optimized, the vibrations of PGS can be reduced. This work establishes a dynamic model of a double-row PGS. The dynamic model considers the mesh forces of the gear pairs and the supporting forces of the bearing. The effect of the sun gear axial position on the sun gear and ring gear #2 vibrations are investigated. Finally, the recommended axial position for the sun gear is provided.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39155161

RESUMEN

BACKGROUND: Within the tumor microenvironment, survival pressures are prevalent with potent drivers of tumor progression, angiogenesis, and therapeutic resistance. N6-methyladenosine (m6A) methylation has been recognized as a critical post-transcriptional mechanism regulating various aspects of mRNA metabolism. Understanding the intricate interplay between survival pressures and m6A modification provides new insights into the molecular mechanisms underlying hepatocellular carcinoma (HCC) progression and highlights the potential for targeting the survival pressures-m6A axis in HCC diagnosis and treatment. DATA SOURCES: A literature search was conducted in PubMed, MEDLINE, and Web of Science for relevant articles published up to April 2024. The keywords used for the search included hepatocellular carcinoma, cellular survival, survival pressure, N6-methyladenosine, tumor microenvironment, stress response, and hypoxia. RESULTS: This review delves into the multifaceted roles of survival pressures and m6A RNA methylation in HCC, highlighting how survival pressures modulate the m6A landscape, the impact of m6A modification on survival pressure-responsive gene expression, and the consequent effects on HCC cell survival, proliferation, metastasis, and resistance to treatment. Furthermore, we explored the therapeutic potential of targeting this crosstalk, proposing strategies that leverage the understanding of survival pressures and m6A RNA methylation mechanisms to develop novel, and more effective treatments for HCC. CONCLUSIONS: The interplay between survival pressures and m6A RNA methylation emerges as a complex regulatory network that influences HCC pathogenesis and progression.

6.
ACS Nano ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153194

RESUMEN

Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.

7.
Int J Biol Sci ; 20(10): 3986-4006, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39113711

RESUMEN

Lymph node (LN) metastasis is the dominant cause of death in bladder cancer (BCa) patients, but the underlying mechanism remains largely unknown. In recent years, accumulating studies have confirmed that bidirectional mitochondria-nucleus communication is essential for sustaining multiple function of mitochondria. However, little has been studied regarding whether and how the translocation of mitochondrial proteins is involved in LN metastasis. In this study, we first identified that the SUMO E3 ligase MUL1 was significantly downregulated in LN-metastatic BCa tissues and correlated with a good prognosis. Mechanistically, MUL1 SUMOylated HSPA9 at the K612 residue, leading to HSPA9 export from mitochondria and interaction with SUZ12 and in the nucleus. Consequently, MUL1 induced the ubiquitination-mediated degradation of SUZ12 and EZH2 and induced downstream STAT3 pathway inhibition in a HSPA9-dependent manner. Importantly, mutation of HSPA9 SUMO-conjugation motifs limited the translocation of mitochondrial HSPA9 and blocked the HSPA9-SUZ12 and HSPA9-EZH2 interactions. With mutation of the HSPA9 K612 site, the suppressive role of MUL1 overexpression was lost in BCa cells. Further in vitro and in vivo assays revealed that MUL1 inhibits the metastasis and proliferation of BCa cells. Overall, our study reveals a novel function and molecular mechanism of SUMO E3 ligases in LN metastasis.


Asunto(s)
Proteínas HSP70 de Choque Térmico , Metástasis Linfática , Ubiquitina-Proteína Ligasas , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/genética , Línea Celular Tumoral , Mitocondrias/metabolismo , Animales , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Masculino , Sumoilación , Femenino , Proteínas Mitocondriales
8.
Front Med (Lausanne) ; 11: 1399247, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114831

RESUMEN

Objective: In several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures. Methods: From each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models. Results: We reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, -0.02 to 0.08; p = 0.24), operative time (MD, -4.53; 95% CI, -12.08 to 3.01; p = 0.24), and blood loss (MD, -25.69; 95% CI, -62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation. Conclusion: There was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss. Systematic Review Registration: PROSPERO [CRD42023470025].

9.
Front Plant Sci ; 15: 1357193, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104844

RESUMEN

Introduction: Rapid and accurate estimation of leaf area index (LAI) is of great significance for the precision agriculture because LAI is an important parameter to evaluate crop canopy structure and growth status. Methods: In this study, 20 vegetation indices were constructed by using cotton canopy spectra. Then, cotton LAI estimation models were constructed based on multiple machine learning (ML) methods extreme learning machine (ELM), random forest (RF), back propagation (BP), multivariable linear regression (MLR), support vector machine (SVM)], and the optimal modeling strategy (RF) was selected. Finally, the vegetation indices with a high correlation with LAI were fused to construct the VI-fusion RF model, to explore the potential of multi-vegetation index fusion in the estimation of cotton LAI. Results: The RF model had the highest estimation accuracy among the LAI estimation models, and the estimation accuracy of models constructed by fusing multiple VIs was higher than that of models constructed based on single VIs. Among the multi-VI fusion models, the RF model constructed based on the fusion of seven vegetation indices (MNDSI, SRI, GRVI, REP, CIred-edge, MSR, and NVI) had the highest estimation accuracy, with coefficient of determination (R2), rootmean square error (RMSE), normalized rootmean square error (NRMSE), and mean absolute error (MAE) of 0.90, 0.50, 0.14, and 0.26, respectively. Discussion: Appropriate fusion of vegetation indices can include more spectral features in modeling and significantly improve the cotton LAI estimation accuracy. This study will provide a technical reference for improving the cotton LAI estimation accuracy, and the proposed method has great potential for crop growth monitoring applications.

10.
Angew Chem Int Ed Engl ; : e202410846, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106196

RESUMEN

Polyamide plays a pivotal role in engineering thermoplastics. Constrained by the harsh conditions and arduous procedures for its industrial synthesis, developing facile synthesis of polyamides is still challengeable and holds profound significance. Herein, we successfully utilized water as one of the monomers to synthesize functional polyamides under ambient conditions. A powerful multicomponent polymerization of water, isocyanides, and chlorooximes was established in phosphate-buffered saline. Soluble and thermally stable polyamides with high weight-average molecular weights (up to 53900) were obtained in excellent yields (up to 95%). The polymerization exhibits unique polymerization-induced emission characteristics, successfully converting non-emissive monomers into unconventional emissive polymers. Notably, the resultant polyamides could undergo effective post-modification via the hydroxyl-yne click reaction. By incorporating various functional groups into the polyamide, its emission color could be fine-tuned from blue to green and to red. Remarkably, the refractive index (n) of the polyamide at 589 nm could be increased from 1.6173 to 1.7227 and the Δn could be unprecedentedly as high as 0.1054 for non-heavy atom-containing polymers after post-modification, and its micron-thick films exhibited excellent transparency in the visible region. Thus, this work not only establishes a powerful polymerization toward novel polyamides but also opens up an avenue for their versatile functionalization.

11.
Neuro Oncol ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110121

RESUMEN

BACKGROUND: Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. METHODS: We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. RESULTS: Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. DISSCUSSION: Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.

12.
Turk J Gastroenterol ; 35(4): 335-342, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39128078

RESUMEN

BACKGROUND/AIMS:  The relationship between neutrophil-to-lymphocyte ratio (NLR) and liver fibrosis in nonalcoholic fatty liver disease remains controversial. The aim of this study was to examine the association between NLR and liver fibrosis. MATERIALS AND METHODS:  We conducted a cross-sectional analysis using the National Health and Nutrition Examination Survey. Vibration-controlled transient elastography was used to assess liver fibrosis and its severity. Neutrophil-to-lymphocyte ratio was calculated as the ratio of neutrophil count to lymphocyte count. RESULTS:  This study included 1620 US adults with a mean age of 52.9 years, of which 53.3% were male. The obese population accounted for 62.5%, 68.5% had hypertension, 31.1% had diabetes, and 16% had significant liver fibrosis. After adjusting for all covariates, a positive correlation was observed between NLR and the severity of liver fibrosis (ß = 0.57, 95% CI = 0.22-0.92, P = .001), which remained stable across different subgroups. CONCLUSION:  This study suggests that elevated NLR levels are positively correlated with the severity of liver fibrosis in patients with nonalcoholic fatty liver disease, and these results can be well generalized to the US adult population.


Asunto(s)
Cirrosis Hepática , Linfocitos , Neutrófilos , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Índice de Severidad de la Enfermedad , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Femenino , Persona de Mediana Edad , Estudios Transversales , Cirrosis Hepática/sangre , Estados Unidos/epidemiología , Adulto , Recuento de Linfocitos , Recuento de Leucocitos , Diagnóstico por Imagen de Elasticidad , Anciano
13.
Int J Pharm ; 663: 124570, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39134291

RESUMEN

A multi-component paclitaxel (PTX) -loaded ß-elemene nanoemulsion by transferrin modification (Tf-PE-MEs) was developed to enhance non-small-cell lung cancer (NSCLC) treatment. After transferrin modification, the particle size of Tf-PE-MEs was (14.87 ± 1.84) nm, and the zeta potential was (-10.19 ± 0.870) mV, respectively. In vitro experiments showed that Tf-PE-MEs induced massive apoptosis in A549 cells, indicating that it had significant cytotoxicity to A549 cells. Through transferrin modification, Tf-PE-MEs accumulated at the tumor site efficiently with overexpressed transferrin receptor (TfR) on the surface of A549 cells. This will allow increasing PTX and ß-elemene concentration in the target cells, enhancing the therapeutic effect. Compared to PTX alone, Tf-PE-MEs displayed good anti-tumor efficacy and diminished systemic toxicity in vivo studies. With favourable therapeutic potential, this study provides a new strategy for the combined anticancer treatment of non-small cell lung cancer.

14.
Strabismus ; : 1-7, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136452

RESUMEN

Introduction: Physical activity in adolescence plays an important role in reducing the lifetime risk of chronic disease. Recent studies have shown that individuals with amblyopia may have difficulties with coordinating balance and may be at greater risk of developing fine motor impairments. The purpose of this study was to determine if there is an association between the presence of amblyopia and physical activity (PA) in adolescents. Methods: Adolescent patients aged 12-18 years with a history of childhood amblyopia were age- and gender-matched to control patients with no other ocular pathology aside from refractive error. Each participant's best corrected visual acuity and refractive error were recorded in addition to their height and weight to calculate body mass index (BMI). A 32-question electronic survey was used to calculate self-reported physical activity level (PAL) score and type of PA over the previous seven days. The Ainsworth Compendium of Physical Activities was taken as a reference to calculate Metabolic Equivalent of Task (MET) minutes for the most frequently performed activity. Results: A total of 26 adolescents with amblyopia (10 strabismic, 16 anisometropic) and 26 healthy controls were recruited. The MET-minute values were 2404.3 ± 2313.9 in the control group and 905.6 ± 1196.0 in the amblyopia group (p = .008). The PAL scores were similar between amblyopia and control groups (1.15 ± 0.70 versus 1.24 ± 0.60, p = .63); however, BMI was significantly higher in amblyopia participants (25.2 ± 6.3 versus 21.1 ± 5.4, p = .003). When compared with controls, amblyopes perceived physical activity to be of significantly lower importance in their lives compared to controls (p = .009). Discussion: Amblyopic adolescents may represent a population with increased vulnerability to significantly lower energy expenditure and higher BMI. Future studies with a larger number of participants and further investigation into the impact of refractive error on physical activity are warranted.

15.
J Biol Chem ; : 107619, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39098530

RESUMEN

Alzheimer's disease (AD) poses an immense challenge in healthcare, lacking effective therapies. This study investigates the potential of AAD23, a selective M2 receptor antagonist, in proactively preventing cognitive impairments and cholinergic neuronal degeneration in GRK5-deficient Swedish APP (GAP) mice. GAP mice manifest cognitive deficits by 7 months and develop senile plaques (SPs) by 9 months. A six-month AAD23 treatment was initiated at 5 months and stopped at 11 months before behavioral assessments without the treatment. AAD23-treated mice exhibited preserved cognitive abilities and improved cholinergic axonal health in the nucleus basalis of Meynert (NBM) akin to wild-type mice. Conversely, vehicle-treated GAP mice displayed memory deficits and pronounced cholinergic axonal swellings in the NBM. Notably, AAD23 treatment did not alter SPs and microgliosis. These findings highlight AAD23's efficacy in forestalling AD-related cognitive decline in GRK5-deficient subjects, attributing its success to restoring cholinergic neuronal integrity and resilience, enhancing resistance against diverse degenerative insults.

16.
Part Fibre Toxicol ; 21(1): 30, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39118174

RESUMEN

Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.


Asunto(s)
Barrera Hematotesticular , Desoxiadenosinas , Nanopartículas , Poliestirenos , Espermatogénesis , Testículo , Animales , Masculino , Desoxiadenosinas/farmacología , Barrera Hematotesticular/efectos de los fármacos , Poliestirenos/toxicidad , Nanopartículas/toxicidad , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Simulación del Acoplamiento Molecular , Microplásticos/toxicidad , Receptor Toll-Like 4/metabolismo , Apoptosis/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Sustancias Protectoras/farmacología
17.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39101499

RESUMEN

Genome-scale metabolic models (GEMs) are powerful tools for predicting cellular metabolic and physiological states. However, there are still missing reactions in GEMs due to incomplete knowledge. Recent gaps filling methods suggest directly predicting missing responses without relying on phenotypic data. However, they do not differentiate between substrates and products when constructing the prediction models, which affects the predictive performance of the models. In this paper, we propose a hyperedge prediction model that distinguishes substrates and products based on dual-scale fused hypergraph convolution, DSHCNet, for inferring the missing reactions to effectively fill gaps in the GEM. First, we model each hyperedge as a heterogeneous complete graph and then decompose it into three subgraphs at both homogeneous and heterogeneous scales. Then we design two graph convolution-based models to, respectively, extract features of the vertices in two scales, which are then fused via the attention mechanism. Finally, the features of all vertices are further pooled to generate the representative feature of the hyperedge. The strategy of graph decomposition in DSHCNet enables the vertices to engage in message passing independently at both scales, thereby enhancing the capability of information propagation and making the obtained product and substrate features more distinguishable. The experimental results show that the average recovery rate of missing reactions obtained by DSHCNet is at least 11.7% higher than that of the state-of-the-art methods, and that the gap-filled GEMs based on our DSHCNet model achieve the best prediction performance, demonstrating the superiority of our method.


Asunto(s)
Redes y Vías Metabólicas , Algoritmos , Modelos Biológicos , Genoma , Biología Computacional/métodos
18.
PNAS Nexus ; 3(8): pgae291, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108300

RESUMEN

Atmospheric sulfate aerosols contribute significantly to air pollution and climate change. Sulfate formation mechanisms during winter haze events in northern China have recently received considerable attention, with more than 10 studies published in high-impact journals. However, the conclusions from in-field measurements, laboratory studies, and numerical simulations are inconsistent and even contradictory. Here, we propose a physically based yet simple method to clarify the debate on the dominant sulfate formation pathway. Based on the hazes evolving in the synoptic scale, first, a characteristic sulfate formation rate is derived using the Eulerian mass conservation equation constrained by in situ observations. Then, this characteristic value is treated as a guideline to determine the dominant sulfate formation pathway with a 0D chemical box model. Our observation-derived results establish a linkage between studies from laboratory experiments and chemical transport model simulations. A convergent understanding could therefore be reached on sulfate formation mechanisms in China's wintertime haze. This method is universal and can be applied to various haze conditions and different secondary products.

19.
Acta Crystallogr E Crystallogr Commun ; 80(Pt 8): 873-877, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39108777

RESUMEN

In the title mol-ecule, C11H11BrO3, the di-hydro-indene moiety is essentially planar but with a slight twist in the saturated portion of the five-membered ring. The meth-oxy groups lie close to the above plane. In the crystal, π-stacking inter-actions between six-membered rings form stacks of mol-ecules extending along the a-axis direction, which are linked by weak C-H⋯O and C-H⋯Br hydrogen bonds. A Hirshfeld surface analysis was performed showing H⋯H, O⋯H/H⋯O and Br⋯H/H⋯Br contacts make the largest contributions to inter-molecular inter-actions in the crystal.

20.
Infect Drug Resist ; 17: 3537-3545, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161468

RESUMEN

Background: Brucellosis is a zoonotic disease that can affect various organs, including the spine. Cervical spondylitis caused by Brucella is rare but can lead to significant morbidity if not diagnosed and treated promptly. Case Presentation: We report a case of a 46-year-old female who presented with intermittent high fever and intractable neck, shoulder, and back pain for two months. She was diagnosed with Brucella cervical spondylitis based on clinical manifestations, Rose-Bengal Plate Agglutination Test (RBPT, positive), and cervical MRI findings. She was treated with a combination of antibiotics for at least two weeks, followed by surgical intervention including abscess clearance, partial vertebral resection, and titanium mesh bone fusion. Real-time Polymerase Chain Reaction (RT-PCR) confirmed the presence of sheep Brucella DNA. The patient recovered well postoperatively with significant pain reduction and restoration of full mobility in the right upper limb. Conclusion: This case highlights the diagnostic value of RT-PCR and tissue biopsy in cervical brucellosis spondylitis. Our study found that anterior cervical subtotal corpectomy can restore cervical stability, clear abscess, and relieve spinal cord compression on the basis of drug treatment, with good clinical results.

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