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1.
BMC Endocr Disord ; 24(1): 139, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095726

RESUMEN

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes worldwide. The aim of this study was to assess the prevalence of DR in hospitalized patients with type 2 diabetes (T2DM) in Tibet and to identify risk factors that may influence the occurrence of DR. METHODS: This was a cross-sectional study conducted in a third-class hospital in the Tibet Autonomous Region. The prevalence of DR in hospitalized patients with T2DM was measured. Univariate and multivariate logistic regression, restricted cubic spline (RCS) analysis and receiver-operating characteristic curve analysis were used to investigate the risk factors for DR. RESULTS: The prevalence of DR was 29.3%. The duration of diabetes; concentrations of 25-OH-VitD3, hemoglobin, fasting insulin, alanine aminotransferase, total bilirubin, and creatinine; and HOMA-IR were significantly different between DR patients and non-DR patients (all P < 0.05). Univariate and multivariate logistic regression revealed that a longer duration of diabetes and lower 25-OH-VitD3 levels were associated with increased DR risk. RCS analysis suggested overall positive associations of the duration of diabetes and 25-OH-VitD3 concentrations with DR risk (P nonlinearity < 0.05). The turning points for the duration of diabetes and 25-OH-VitD3 concentrations were 5.1 years and 10.6 ng/mL, respectively. The sensitivity, specificity, and area under the receiver-operating characteristic curve for the combination of the duration of diabetes and 25-OH-VitD3 levels were 79.4%, 69.4% and 0.764, respectively. CONCLUSIONS: Given the high prevalence of DR in hospitalized patients with T2DM in Tibet, vitamin D supplementation seems to be important in the prevention of DR to some degree.


Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Deficiencia de Vitamina D , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Femenino , Masculino , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Retinopatía Diabética/sangre , Persona de Mediana Edad , Tibet/epidemiología , Factores de Riesgo , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/sangre , Prevalencia , Anciano , Adulto
2.
J Phys Chem Lett ; : 8636-8641, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150705

RESUMEN

This study presents an investigation of the 2-butynyl alcohol···CO2 adduct, combining pulsed jet Fourier transform microwave spectroscopy with quantum chemical calculations. Two distinct isomers have been observed in the pulsed jet with a relative population ratio of 3/2. It marks the first instance of microwave spectroscopic evidence, to the best of our knowledge, suggesting the existence of a CCO2···π-C≡C- tetrel bond (π-C≡C-···π*CO2 interaction) in both observed isomers. This study highlights the importance of noncovalent interactions involving CO2 in reactant complexes, paving the way for more efficient applications of CO2 by understanding the physical basis of these noncovalent bonds.

3.
J Bone Miner Res ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167757

RESUMEN

Osteoporosis, characterized by low bone mineral density (BMD), is a highly heritable metabolic bone disorder. While single nucleotide variations (SNVs) have been extensively studied, they explain only a fraction of BMD heritability. While genomic structural variations (SVs) are large-scale genomic alterations that contribute to genetic diversity in shaping phenotypic variations, the role of SVs in osteoporosis susceptibility remains poorly understood. This study aims to identify and prioritize genes that harbor BMD-related SVs. We performed whole genome sequencing on 4982 subjects from the Louisiana Osteoporosis Study. To obtain high-confidence SVs, the detection of SVs was performed using an ensemble approach. The SVs were tested for association with BMD variation at the hip (HIP), femoral neck (FNK), and lumbar spine (SPN), respectively. Additionally, we conducted co-occurrence analysis using multi-omics approaches to prioritize the identified genes based on their functional importance. Stratification was employed to explore the sex- and ethnicity-specific effects. We identified significant SV-BMD associations: 125 for FNK-BMD, 99 for SPN-BMD, and 83 for HIP-BMD. We observed SVs that were commonly associated with both FNK and HIP BMDs in our combined and stratified analyses. These SVs explain 13.3% to 19.1% of BMD variation. Novel bone-related genes emerged, including LINC02370, ZNF family genes, and ZDHHC family genes. Additionally, FMN2, carrying BMD-related deletions, showed associations with FNK or HIP BMDs, with sex-specific effects. The co-occurrence analysis prioritized an RNA gene LINC00494 and ZNF family genes positively associated with BMDs at different skeletal sites. Two potential causal genes, IBSP and SPP1, for osteoporosis were also identified. Our study uncovers new insights into genetic factors influencing BMD through SV analysis. We highlight BMD-related SVs, revealing a mix of shared and specific genetic influences across skeletal sites and gender or ethnicity. These findings suggest potential roles in osteoporosis pathophysiology, opening avenues for further research and therapeutic targets.

4.
Front Plant Sci ; 15: 1368814, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119492

RESUMEN

Forest fires play a pivotal role in influencing ecosystem evolution, exerting a profound impact on plant diversity and community stability. Understanding post-fire recovery strategies holds significant scientific importance for the ecological succession and restoration of forest ecosystems. This study utilized Partial Least Squares Path Modeling (PLS-PM) to investigate dynamic relationships among plant species diversity, phylogenetic diversity, soil properties, and community stability during various recovery stages (5-year, 15-year, and 23-year) following wildfires on the northeastern margin of the Qinghai-Tibet Plateau. The findings revealed: (1) Over time, species richness significantly decreased (p< 0.05 or p< 0.01), while species diversity and dominance increased, resulting in uniform species distribution. Community stability progressively improved, with increased species compositional similarity. (2) Throughout succession, phylogenetic diversity (PD) significantly decreased (p< 0.01), accompanied by rising Mean Pairwise Distance (MPD) and Mean Nearest Taxon Distance (MNTD). Net Relatedness Index (NRI) shifted from positive to negative, indicating an increasing aggregation and dominance of plants with similar evolutionary traits in burned areas. Early succession witnessed simultaneous environmental filtering and competitive exclusion, shifting predominantly to competitive exclusion in later stages. (3) PLS-PM revealed that in the early recovery stage, soil properties mainly affected community stability, while species diversity metamorphosed into the primary factor in the mid-to-late stages. In summary, this study showed that plant diversity and phylogenetic variation were successful in revealing changes in community structure during the succession process. Soil characteristics functioned as selective barriers for plant communities during succession, and community stability underwent a multi-faceted and dynamic process. The soil-plant dynamic feedback continuously enhanced soil conditions and community vegetation structure thereby augmenting stability. Post-fire vegetation gradually transitioned towards the original native state, demonstrating inherent ecological self-recovery capabilities in the absence of secondary disturbances.

5.
Sci Transl Med ; 16(756): eadi0178, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018369

RESUMEN

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)-dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer.


Asunto(s)
Fibroblastos Asociados al Cáncer , Modelos Animales de Enfermedad , Vesículas Extracelulares , Neoplasias Pancreáticas , Animales , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Ratones , Masculino , Línea Celular Tumoral , Invasividad Neoplásica , Femenino , Proteína 1 de Unión a la Caja Y
6.
J Enzyme Inhib Med Chem ; 39(1): 2367129, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39051546

RESUMEN

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.


Asunto(s)
Arginina , Glutamina , Neoplasias , Prolina , Humanos , Glutamina/metabolismo , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Prolina/metabolismo , Prolina/química , Arginina/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Estructura Molecular , Animales
7.
Life Sci Space Res (Amst) ; 42: 91-98, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39067997

RESUMEN

A Closed Aquatic Ecosystem (CAES) housed an aquatic plant Ceratophyllum demersum, zebrafish (Danio rerio), and microbes that were simultaneously obtained with the zebrafish, and it was used to study the operation of the ecosystem. The results indicated that the CAES can operate steadily for about 4 weeks. The dissolved oxygen (DO), pH, and conductivity values of the ecosystem regularly oscillated, while the total nitrogen of the water decreased and the total phosphate slightly increased. Additionally, the chemical oxygen demand (COD, a measure of organic compounds) of the water after the experiment increased to 39 times more than that of the water before the experiment. The meta-genomic data showed that the number of genera decreased by 38 % and the top 10 most abundant genera were almost completely different before and after the experiment, which demonstrated a great shift in the microbes during the operation process. These results suggested that although the CAES operated steadily during the 28-day experiment, there were more organic materials and less nitrogen in the water by the end of the experiment, which may have influenced the structure and operation of the ecosystem. Thus, it is necessary to remove superfluous plant biomass from the CAES and supply nitrogen to keep the ecosystem stable.


Asunto(s)
Sistemas Ecológicos Cerrados , Nitrógeno , Pez Cebra , Animales , Nitrógeno/análisis , Nitrógeno/metabolismo , Ecosistema , Nutrientes/análisis , Concentración de Iones de Hidrógeno , Oxígeno/metabolismo , Oxígeno/análisis
8.
J Environ Manage ; 365: 121685, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38963964

RESUMEN

Ternary alkali-activated binder was prepared by blast furnace slag (GGBS), recycled powder (RP) and waste glass powder (WGP) using simplex centroid design method. By measuring the fluidity, setting time, drying shrinkage and mechanical property of specimen, the complementary effect of GGBS, RP and WGP was discussed. The reaction mechanism and microstructure were explored by X-ray diffraction and scanning electron microscopy. The results reveal that the addition of RP could significantly reduce the fluidity and setting time of paste, while WGP can obviously improve the rheological property and play a retarding role. The workability of paste can be effectively regulated by mixing RP and WGP together. Whether added alone or in combination, RP and WGP can effectively improve the shrinkage performance. In the ternary system, GGBS can be rapidly activated and form a skeleton structure. The fine RP particles can play a good role in filling the structure, and the pozzolanic reaction of WGP gradually occurs, which makes the microstructure more compact. The incorporation of GGBS, RP and WGP can promote the growth of hydration products, improve the density of microstructure, and form a certain complementary effect.


Asunto(s)
Álcalis , Vidrio , Polvos , Reciclaje , Vidrio/química , Álcalis/química , Difracción de Rayos X , Microscopía Electrónica de Rastreo
9.
Neurosci Lett ; 837: 137913, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39032803

RESUMEN

OBJECTIVE: Parkinson's disease (PD) has been identified as a genetically influenced disease linked to various genetic loci. Previous studies have suggested that neurodegenerative illnesses, including PD, Alzheimer's disease, and Amyotrophic lateral sclerosis (ALS), may share certain genetic loci. Recently, the NEK1 gene was identified as overlapping between PD and ALS. We therefore wanted to explore the potential association between the NEK1 gene single nucleotide polymorphisms (SNPs) and the clinical features and pathophysiology of sporadic PD in a northern Chinese population. METHODS: A total of 510 sporadic PD patients and 510 age- and sex-matched healthy controls (HCs) were included in this study. Two SNPs (rs4563461 and rs66509122) of the NEK1 gene were genotyped using polymerase chain reaction (PCR). And we analyzed the association between NEK1 gene polymorphisms and clinical manifestations. RESULTS: Allele T (C vs. T, P = 0.018) and genotype TT (CC vs. TT: P = 0.021) of rs66509122 among PD group and HCs were significantly different. In addition, we discovered that the rs66509122 genotype TT was associated with depression in early-onset PD (EOPD) (P = 0.031) and diabetes in female PD (P = 0.032). Unfortunately, no distinct correlation of rs4563461 polymorphisms with sporadic PD susceptibility was found in either the overall group (C vs. T, P = 0.086) or other subgroups. However, the T allele of rs4563461 was significantly correlated with sleep disorders in the PD group, especially in the late-onset PD (LOPD) group and male PD group. CONCLUSION: This study found that the NEK1 rs66509122 polymorphism was associated with a lower risk of sporadic PD, while T allele of rs66509122 may be a protective factor for PD. The NEK1 rs4563461 and rs66509122 polymorphisms both showed correlations with some non-motor symptoms in sporadic PD patients. Further research with a larger sample and varied ethnic groups is needed to investigate the role of NEK1 gene polymorphisms in the pathophysiology of PD.


Asunto(s)
Predisposición Genética a la Enfermedad , Quinasa 1 Relacionada con NIMA , Enfermedad de Parkinson , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , China/epidemiología , Pueblos del Este de Asia/genética , Estudios de Asociación Genética , Genotipo , Quinasa 1 Relacionada con NIMA/genética , Enfermedad de Parkinson/genética
10.
Int J Biol Macromol ; 277(Pt 2): 134292, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39084439

RESUMEN

Congenital cataracts, a prevalent cause of blindness in children, are associated with protein aggregation. γD-crystallin, essential for sustaining lens transparency, exists as a monomer and exhibits excellent structural stability. In our cohort, we identified a nonsense mutation (c.451_452insGACT, p.Y151X) in the CRYGD gene. To explore the effect of truncation mutations on the structure of γD-crystallin, we examined the Y151X and T160RfsX8 mutations, both located in the Greek key motif 4 at the cellular and protein level in this study. Both truncation mutations induced protein misfolding and resulted in the formation of insoluble aggregates when overexpressed in HLE B3 and HEK 293T cells. Moreover, heat, UV irradiation, and oxidative stress increased the proportion of aggregates of mutants in the cells. We next purified γD-crystallin to estimate its structural changes. Truncation mutations led to conformational disruption and a concomitant decrease in protein solubility. Molecular dynamics simulations further demonstrated that partial deletion of the conserved domain within the Greek key motif 4 markedly compromised the overall stability of the protein structure. Finally, co-expression of α-crystallins facilitated the proper folding of truncated mutants and mitigated protein aggregation. In summary, the structural integrity of the Greek key motif 4 in γD-crystallin is crucial for overall structural stability.


Asunto(s)
Catarata , Agregado de Proteínas , Estabilidad Proteica , gamma-Cristalinas , Humanos , gamma-Cristalinas/genética , gamma-Cristalinas/química , gamma-Cristalinas/metabolismo , Catarata/genética , Catarata/metabolismo , Células HEK293 , Mutación , Simulación de Dinámica Molecular , Pliegue de Proteína , Conformación Proteica , Solubilidad , Agregación Patológica de Proteínas/genética
11.
Phytomedicine ; 132: 155847, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996505

RESUMEN

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.


Asunto(s)
Akkermansia , Antidepresivos , Depresión , Microbioma Gastrointestinal , Hypericum , Interleucina-1beta , FN-kappa B , Triptófano , Animales , Hypericum/química , Microbioma Gastrointestinal/efectos de los fármacos , Depresión/tratamiento farmacológico , Triptófano/metabolismo , Triptófano/farmacología , Masculino , FN-kappa B/metabolismo , Interleucina-1beta/metabolismo , Ratones , Antidepresivos/farmacología , Ratones Endogámicos C57BL , Caspasa 1/metabolismo , Trasplante de Microbiota Fecal , Verrucomicrobia , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Disbiosis/tratamiento farmacológico , Disbiosis/microbiología , Modelos Animales de Enfermedad
12.
Fundam Res ; 4(2): 394-400, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38933503

RESUMEN

Protein misfolding and aggregation are crucial pathogenic factors for cataracts, which are the leading cause of visual impairment worldwide. α-crystallin, as a small molecular chaperone, is involved in preventing protein misfolding and maintaining lens transparency. The chaperone activity of α-crystallin depends on its oligomeric state. Our previous work identified a natural compound, celastrol, which could regulate the oligomeric state of αB-crystallin. In this work, based on the UNcle and SEC analysis, we found that celastrol induced αB-crystallin to form large oligomers. Large oligomer formation enhanced the chaperone activity of αB-crystallin and prevented aggregation of the cataract-causing mutant ßA3-G91del. The interactions between αB-crystallin and celastrol were detected by the FRET (Fluorescence Resonance Energy Transfer) technique, and verified by molecular docking. At least 9 binding patterns were recognized, and some binding sites covered the groove structure of αB-crystallin. Interestingly, αB-R120G, a cataract-causing mutation located at the groove structure, and celastrol can decrease the aggregates of αB-R120G. Overall, our results suggested celastrol not only promoted the formation of large αB-crystallin oligomers, which enhanced its chaperone activity, but also bound to the groove structure of its α-crystallin domain to maintain its structural stability. Celastrol might serve as a chemical and pharmacological chaperone for cataract treatment.

13.
Front Artif Intell ; 7: 1355287, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919268

RESUMEN

Introduction: Osteoporosis, characterized by low bone mineral density (BMD), is an increasingly serious public health issue. So far, several traditional regression models and machine learning (ML) algorithms have been proposed for predicting osteoporosis risk. However, these models have shown relatively low accuracy in clinical implementation. Recently proposed deep learning (DL) approaches, such as deep neural network (DNN), which can discover knowledge from complex hidden interactions, offer a new opportunity to improve predictive performance. In this study, we aimed to assess whether DNN can achieve a better performance in osteoporosis risk prediction. Methods: By utilizing hip BMD and extensive demographic and routine clinical data of 8,134 subjects with age more than 40 from the Louisiana Osteoporosis Study (LOS), we developed and constructed a novel DNN framework for predicting osteoporosis risk and compared its performance in osteoporosis risk prediction with four conventional ML models, namely random forest (RF), artificial neural network (ANN), k-nearest neighbor (KNN), and support vector machine (SVM), as well as a traditional regression model termed osteoporosis self-assessment tool (OST). Model performance was assessed by area under 'receiver operating curve' (AUC) and accuracy. Results: By using 16 discriminative variables, we observed that the DNN approach achieved the best predictive performance (AUC = 0.848) in classifying osteoporosis (hip BMD T-score ≤ -1.0) and non-osteoporosis risk (hip BMD T-score > -1.0) subjects, compared to the other approaches. Feature importance analysis showed that the top 10 most important variables identified by the DNN model were weight, age, gender, grip strength, height, beer drinking, diastolic pressure, alcohol drinking, smoke years, and economic level. Furthermore, we performed subsampling analysis to assess the effects of varying number of sample size and variables on the predictive performance of these tested models. Notably, we observed that the DNN model performed equally well (AUC = 0.846) even by utilizing only the top 10 most important variables for osteoporosis risk prediction. Meanwhile, the DNN model can still achieve a high predictive performance (AUC = 0.826) when sample size was reduced to 50% of the original dataset. Conclusion: In conclusion, we developed a novel DNN model which was considered to be an effective algorithm for early diagnosis and intervention of osteoporosis in the aging population.

14.
ArXiv ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38855554

RESUMEN

Hip fractures present a significant healthcare challenge, especially within aging populations, where they are often caused by falls. These fractures lead to substantial morbidity and mortality, emphasizing the need for timely surgical intervention. Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. We propose a novel staged model that combines advanced imaging and clinical data to improve predictive performance. By using convolutional neural networks (CNNs) to extract features from hip DXA images, along with clinical variables, shape measurements, and texture features, our method provides a comprehensive framework for assessing fracture risk. The study cohort included 547 patients, with 94 experiencing hip fracture. A staged machine learning-based model was developed using two ensemble models: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and DXA imaging features). This staged approach used uncertainty quantification from Ensemble 1 to decide if DXA features are necessary for further prediction. Ensemble 2 exhibited the highest performance, achieving an Area Under the Curve (AUC) of 0.9541, an accuracy of 0.9195, a sensitivity of 0.8078, and a specificity of 0.9427. The staged model also performed well, with an AUC of 0.8486, an accuracy of 0.8611, a sensitivity of 0.5578, and a specificity of 0.9249, outperforming Ensemble 1, which had an AUC of 0.5549, an accuracy of 0.7239, a sensitivity of 0.1956, and a specificity of 0.8343. Furthermore, the staged model suggested that 54.49% of patients did not require DXA scanning. It effectively balanced accuracy and specificity, offering a robust solution when DXA data acquisition is not always feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of the advanced modeling strategies. Our staged approach offers a cost-effective holistic view of patients' health. It could identify individuals at risk with a high accuracy but reduce the unnecessary DXA scanning. Our approach has great promise to guide interventions to prevent hip fractures with reduced cost and radiation.

15.
NAR Genom Bioinform ; 6(2): lqae071, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38881578

RESUMEN

Mass spectrometry is a powerful and widely used tool for generating proteomics, lipidomics and metabolomics profiles, which is pivotal for elucidating biological processes and identifying biomarkers. However, missing values in mass spectrometry-based omics data may pose a critical challenge for the comprehensive identification of biomarkers and elucidation of the biological processes underlying human complex disorders. To alleviate this issue, various imputation methods for mass spectrometry-based omics data have been developed. However, a comprehensive comparison of these imputation methods is still lacking, and researchers are frequently confronted with a multitude of options without a clear rationale for method selection. To address this pressing need, we developed omicsMIC (mass spectrometry-based omics with Missing values Imputation methods Comparison platform), an interactive platform that provides researchers with a versatile framework to evaluate the performance of 28 diverse imputation methods. omicsMIC offers a nuanced perspective, acknowledging the inherent heterogeneity in biological data and the unique attributes of each dataset. Our platform empowers researchers to make data-driven decisions in imputation method selection based on real-time visualizations of the outcomes associated with different imputation strategies. The comprehensive benchmarking and versatility of omicsMIC make it a valuable tool for the scientific community engaged in mass spectrometry-based omics research. omicsMIC is freely available at https://github.com/WQLin8/omicsMIC.

16.
Am J Cardiovasc Drugs ; 24(4): 557-568, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38782884

RESUMEN

PURPOSE: The objective of this investigation is to examine the benefits and potential risks of these drugs in individuals by varying baseline low-density lipoprotein cholesterol (LDL-C) values, utilizing the concept of the number needed to treat (NNT). METHODS: We extensively searched electronic databases, such as PubMed, EMBASE, Cochrane, and Web of Science, up to 6 August 2023. Baseline LDL-C values were stratified into four categories: < 100, 100-129, 130-159, and ≥ 160 mg/dL. Risk ratios (RRs) and NNT values were computed. RESULTS: This analysis incorporated data from 46 randomized controlled trials (RCTs), encompassing a total of 237,870 participants. The meta-regression analysis demonstrated an incremental diminishing risk of major adverse cardiovascular events (MACE) with increasing baseline LDL-C values. Statins exhibited a significant reduction in MACE [number needed to treat to benefit (NNTB) 31, 95% confidence interval (CI) 25-37], but this effect was observed only in individuals with baseline LDL-C values of 100 mg/dL or higher. Ezetimibe and PCSK9 inhibitors also were effective in reducing MACE (NNTB 18, 95% CI 11-41, and NNTB 18, 95% CI 16-24). Notably, the safety outcomes of statins and ezetimibe did not reach statistical significance, while the incidence of injection-site reactions with PCSK9 inhibitors was statistically significant [number needed to treat to harm (NNTH) 41, 95% CI 80-26]. CONCLUSION: Statins, ezetimibe, and PCSK9 inhibitors demonstrated a substantial capacity to reduce MACE, particularly among individuals whose baseline LDL-C values were relatively higher. The NNT visually demonstrates the gradient between baseline LDL-C and cardiovascular disease (CVD) risk. SYSTEMATIC REVIEW REGISTRATION: Registration: PROSPERO identifier number: CRD42023458630.


Asunto(s)
Enfermedades Cardiovasculares , LDL-Colesterol , Humanos , LDL-Colesterol/sangre , Enfermedades Cardiovasculares/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipolipemiantes/uso terapéutico , Hipolipemiantes/efectos adversos , Números Necesarios a Tratar , Ezetimiba/uso terapéutico , Ezetimiba/efectos adversos , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/efectos adversos , Inhibidores de PCSK9 , Medición de Riesgo , Adulto
17.
PLoS Negl Trop Dis ; 18(5): e0012212, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38787872

RESUMEN

BACKGROUND: Cryptosporidium spp. cause watery diarrhea in humans and animals, especially in infants and neonates. They parasitize the apical surface of the epithelial cells in the intestinal lumen. However, the pathogenesis of Cryptosporidium-induced diarrhea is not fully understood yet. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we infected C57BL/6j neonatal mice with C. parvum IIa and IId subtypes, and examined oocyst burden, pathological changes, and intestinal epithelial permeability during the infection. In addition, transcriptomic analyses were used to study the mechanism of diarrhea induced by the C. parvum IId subtype. The neonatal mice were sensitive to both C. parvum IIa and IId infection, but the IId subtype caused a wide oocyst shedding window and maintained the high oocyst burden in the mice compared with the IIa subtype. In addition, the mice infected with C. parvum IId resulted in severe intestinal damage at the peak of infection, leading to increased permeability of the epithelial barrier. The KEGG, GO and GSEA analyses revealed that the downregulation of adherens junction and cell junction molecules at 11 dpi. Meanwhile, E-cadherin, which is associated with adherens junction, was reduced at the protein level in mouse ileum at peak and late infection. CONCLUSIONS/SIGNIFICANCE: C. parvum IId infection causes more severe pathological damage than C. parvum IIa infection in neonatal mice. Furthermore, the impairment of the epithelial barrier during C. parvum IId infection results from the downregulation of intestinal junction proteins.


Asunto(s)
Animales Recién Nacidos , Criptosporidiosis , Cryptosporidium parvum , Regulación hacia Abajo , Mucosa Intestinal , Ratones Endogámicos C57BL , Animales , Cryptosporidium parvum/genética , Criptosporidiosis/parasitología , Criptosporidiosis/patología , Ratones , Mucosa Intestinal/parasitología , Mucosa Intestinal/patología , Cadherinas/metabolismo , Cadherinas/genética , Diarrea/parasitología , Células Epiteliales/parasitología , Femenino , Oocistos , Íleon/parasitología , Íleon/patología , Modelos Animales de Enfermedad
18.
Sci Rep ; 14(1): 10706, 2024 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729979

RESUMEN

Wildfires, as an environmental filter, are pivotal ecological disturbances that reshape plant communities and soil dynamics, playing a crucial role in regulating biogeographic patterns and ecosystem services. In this study, we aim to explore the effects of wildfires on forest ecosystems, specifically focusing on the plant-soil feedback mechanisms within the northeastern margin of the Qinghai-Tibet Plateau (QTP). Utilizing Partial Least Squares Path Modeling (PLS-PM), we investigated the interrelationships among soil physicochemical properties, enzyme activities, species diversity, and community stability at varying post-fire recovery stages (5, 15, and 23 years). Results indicated that in the early recovery stages, rapid changes in soil properties such as decreased pH (p < 0.001) and increased nutrient availability facilitate the emergence of early successional species with high resource utilization traits. As the ecosystem evolved toward a climax community, the soil and vegetation exhibit increased stability. Furthermore, soil enzyme activities displayed dynamic patterns that corresponded with changes in soil nutrient content, directly influencing the regeneration and diversity of plant communities. Importantly, our study documented a transition in the influence of soil properties on community stability from direct positive effects in initial recovery phases to negative impacts in later stages, while indirect benefits accrue through increased species diversity and enzyme activity. Vegetation composition and structure changed dynamically with recovery time during community succession. Plant nutrient absorption and accumulation affected nutrient dynamics in the soil, influencing plant regeneration, distribution, and diversity. Our results underscore the complex interactions between soil and vegetation that drive the recovery dynamics post-wildfire, highlighting the resilience of forest ecosystems to fire disturbances. This study contributes to the understanding of post-fire recovery processes and offers valuable insights for the management and restoration of fire-affected forest ecosystems.


Asunto(s)
Ecosistema , Suelo , Incendios Forestales , Suelo/química , Tibet , Bosques , Biodiversidad , Plantas/metabolismo
19.
Photodiagnosis Photodyn Ther ; 47: 104104, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38679154

RESUMEN

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study aims to investigate the mechanisms of PDT in the treatment of CCA and try to improve the therapeutic effect of PDT by intervening associated signaling pathways. METHODS: The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of CCA cell lines following PDT. Apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. A transmission electron microscope was used to study the changes in cell mitochondria after PDT. The levels of glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), lactate dehydrogenase (LDH), and lipid peroxide (LPO) were determined. Changes in the expression of apoptosis and ferroptosis-related proteins were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Xenograft tumor models were developed to investigate the effects of PDT on tumor proliferation, apoptosis, and ferroptosis in vivo. RESULTS: PDT inhibited tumor proliferation and induced apoptosis both in vivo and in vitro. This treatment led to swelling and damage of the mitochondria in affected cells. Furthermore, ROS levels rose, accompanied by an increase in the proportion of apoptotic-positive cells. The expressions of Bax and Caspase-3 were upregulated, while the Bcl-2 was downregulated. Meanwhile, PDT triggered ferroptosis, marked by decreased expressions of GPX4 and SLC7A11, and reduced GSH levels. This was accompanied by upregulation of P53 expression and heightened levels of Fe2+, LPO, MDA, and LDH. After inducing the ferroptosis pathway, the therapeutic effect of PDT was enhanced, the tumor tissue was further reduced, and the degree of malignancy was reduced. CONCLUSION: PDT promotes apoptosis and ferroptosis of cholangiocarcinoma cells by activating the P53/SLC7A11/GPX4 signaling pathway and inhibits the growth of cholangiocarcinoma. Inducing ferroptosis can enhance the effectiveness of photodynamic therapy.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Apoptosis , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Fotoquimioterapia , Fármacos Fotosensibilizantes , Transducción de Señal , Proteína p53 Supresora de Tumor , Colangiocarcinoma/tratamiento farmacológico , Fotoquimioterapia/métodos , Ferroptosis/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Línea Celular Tumoral , Animales , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Sistema de Transporte de Aminoácidos y+/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Porfirinas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Photodiagnosis Photodyn Ther ; 46: 104098, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38642727

RESUMEN

Intraductal papillary mucinous neoplasm of the bile tract is a rare biliary tumor characterized by mucin growth within the bile duct. In the early stages, it often presents without significant obstruction, this often leads to its discovery in the advanced stages. We report a case of a 63-year-old female with an intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). The patient had a history of intrahepatic bile duct stones and biliary ascariasis. She gradually developed symptoms such as jaundice and intermittent fever before admission, and a bile duct biopsy confirmed the diagnosis of IPMN-B. Currently, endoscopic photodynamic therapy (PDT) is considered an effective treatment for bile duct cancer. In this case, we performed two sessions of PDT guided by SpyGlass. The patient experienced complete remission postoperatively, and there has been no evidence of tumor recurrence or metastasis in the three years following the procedure.


Asunto(s)
Neoplasias de los Conductos Biliares , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Femenino , Persona de Mediana Edad , Fotoquimioterapia/métodos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Adenocarcinoma Mucinoso/tratamiento farmacológico , Ácido Aminolevulínico/uso terapéutico
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