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1.
J Gene Med ; 26(10): e3741, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39357835

RESUMEN

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.


Asunto(s)
Aspartatoamoníaco Ligasa , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteína Forkhead Box M1 , Regulación Neoplásica de la Expresión Génica , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Aspartatoamoníaco Ligasa/genética , Aspartatoamoníaco Ligasa/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Movimiento Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Pronóstico , Animales , Ratones , Masculino , Resistencia a Antineoplásicos/genética , Femenino , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N
2.
Int J Surg ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39361874

RESUMEN

Few studies have illustrated the role of the joint line convergence angle (JLCA) in the correlation between the arithmetic hip-knee-ankle angle (aHKA) and mechanical hip-knee-ankle angle (mHKA). We aimed to determine this role and to evaluate the effect of the JLCA in predicting constitutional alignment using the aHKA. A total of 107 normal participants (214 knees) and 246 patients (477 knees) with osteoarthritis(OA) were retrospectively examined using long-leg radiographs. The formula was calculated geometrically on plain radiographs of the knee based on the relationships among the mHKA, aHKA, and JLCA, and the distribution of the JLCA between the groups was determined. The effect of the JLCA on the prediction of constitutional alignment using the aHKA were evaluated. The geometric formula was determined to be 'mHKA=180°+aHKA - JLCA', and was verified. The median (quartile 1, quartile 3) JLCA was 2.0° (1.0°, 3.5°) and 2.5° (1.0°, 4.5°) in the normal and OA groups, respectively. The JLCA affected the prediction of constitutional alignment based on the aHKA. It should be considered when constitutional alignment is predicted based on the aHKA in patients with high JLCA values.

3.
Nano Lett ; 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39392787

RESUMEN

Uric acid is typically measured through blood tests, which can be inconvenient and uncomfortable for patients. Herein, we propose a wearable surface-enhanced Raman scattering (SERS) chip, incorporating a hydrogel membrane with integrated plasmonic trimers, for noninvasive monitoring of uric acid in sweat. The plasmonic trimers feature sub 5 nm nanogaps, generating strong electromagnetic fields to boost the Raman signal of surrounding molecules. Simultaneously, the hydrogel membrane pumps sweat through these gaps, efficiently capturing sweat biomarkers for SERS detection. The chip can achieve saturation adsorption of sweat within 5 min, eliminating variations in individual sweat production rates. Dynamic SERS tracking of uric acid and lactic acid levels during anaerobic exercise reveals a temporary suppression of uric acid metabolism, likely due to metabolic competition with lactic acid. Furthermore, long-term monitoring correlates well with blood test results, confirming that regular exercise helps reduce serum uric acid levels and supporting its potential in managing hyperuricemia.

4.
J Nutr Health Aging ; 28(12): 100394, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39418751

RESUMEN

BACKGROUND: Homeostatic dysregulation (HD), the measure of aging-related physiological dysregulation, serves as an essential intervenable indicator of aging. OBJECTIVE: To explore the associations of three healthy dietary patterns with HD, investigate the most recommended dietary patterns, and identify the significant beneficial and harmful food groups METHODS: This prospective cohort study included 8,288 participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC), with a female majority (61.6%). Dietary information was obtained through the baseline food frequency questionnaire (FFQ). Three dietary patterns were constructed: Dietary Approaches to Stop Hypertension (DASH), alternative Mediterranean diets (aMED), and Healthy Diet Score (HDS). HD was constructed based on clinical biomarkers and anthropometric measurements. Follow-up analyses adjusted for baseline data were employed to assess the longitudinal associations of three dietary patterns at baseline with HD at follow-up. Additionally, quantile G-computation was utilized to evaluate the relative contribution of each food group to the association with HD. RESULTS: Over a follow-up period of 2.0 years, all healthy dietary patterns exhibited negative associations with HD, with ßQ5/Q1 = -0.112, 95%CI (-0.172, -0.051) for HDS, with ßQ5/Q1 = -0.073, 95%CI (-0.134, -0.012) for aMED, with ßQ5/Q1 = -0.047, 95%CI (-0.107,0.014) for DASH. The results of the component analyses revealed that soybean products were the most significant beneficial food group (relative contribution of 24.0%), while alcohol was identified as the major harmful food group (relative contribution of 76.9%). CONCLUSION: Healthy dietary patterns, especially HDS, are negatively associated with HD. Additionally, soybean products and alcohol are the most significant beneficial and detrimental food groups respectively. Developing appropriate nutritional strategies may help reduce the burden of disease and promote healthy aging.

5.
Front Plant Sci ; 15: 1418585, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220008

RESUMEN

Introduction: Dandelion is widely used in clinical practice due to its beneficial effects. Polyphenolic compounds are considered the main anti-inflammatory active ingredient of dandelion, but the gene expression patterns of polyphenolic compounds in different dandelion tissues are still unclear. Methods: In this study, we combined a nontargeted metabolome, PacBio Iso-seq transcriptome, and Illumina RNA-seq transcriptome to investigate the relationship between polyphenols and gene expression in roots, flowers, and leaves of flowering dandelion plants. Results: Eighty-eight flavonoids and twenty-five phenolic acids were identified, and 64 candidate genes involved in flavonoid biosynthesis and 63 candidate genes involved in chicoric acid biosynthesis were identified. Most flavonoid and chicoric acid-related genes demonstrated the highest content in flowers. RNA-seq analysis revealed that genes involved in polyphenol biosynthesis pathways, such as CHS, CHI, F3H, F3'H, FLS, HQT, and CAS, which are crucial for the accumulation of flavonoids and chicoric acid, were upregulated in flowers. Discussion: The combination of transcriptomic and metabolomic data can help us better understand the biosynthetic pathways of polyphenols in dandelion. These results provide abundant genetic resources for further studying the regulatory mechanism of dandelion polyphenol biosynthesis.

7.
Cell Biochem Funct ; 42(7): e4115, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39264203

RESUMEN

In this study, the protective effects of Panax notoginseng saponins (PNS) against gamma radiation-induced DNA damage and associated physiological alterations in Swiss albino mice were investigated. Exposure to gamma radiation led to a dose-dependent increase in cytokinesis-blocked micronuclei (CBMN) double-strand DNA breaks (DSBs), dicentric aberrations (DC), formation in peripheral blood mononuclear cells. However, pretreatment with PNS at concentrations of 1, 5, and 10 µg/mL significantly attenuated the frequencies of DC and CBMN in a concentration-dependent manner. PNS administration before radiation exposure also reduced radiation-induced DSBs in BL, indicating protection against reactive oxygen species generation and DNA damage. Notably, pretreatment with PNS at 10 µg/mL prevented the overexpression of γ-H2AX, proteins associated with DNA damage response, in irradiated mice. In addition, in vivo studies showed intraperitoneal administration of PNS (25 mg/kg body weight) for 1 h before radiation exposure mitigated lipid peroxidation levels and restored antioxidant status, countering oxidative damage induced by gamma radiation. Furthermore, PNS pretreatment reversed the decrease in hemoglobin (Hb) content, white blood cell count, and red blood cell count in irradiated mice, indicating preservation of hematological parameters. Overall, PNS demonstrated an anticlastogenic effect by modulating radiation-induced DSBs and preventing oxidative damage, thus highlighting its potential as a protective agent against radiation-induced DNA damage and associated physiological alterations. Clinically, PNS will be beneficial for cancer patients undergoing radiotherapy, but their pharmacological properties and toxicity profiles need to be studied.


Asunto(s)
Rayos gamma , Panax notoginseng , Saponinas , Animales , Rayos gamma/efectos adversos , Saponinas/farmacología , Ratones , Panax notoginseng/química , Humanos , Masculino , Daño del ADN/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de la radiación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Protectores contra Radiación/farmacología , Roturas del ADN de Doble Cadena/efectos de los fármacos , Roturas del ADN de Doble Cadena/efectos de la radiación , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Monocitos/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología
8.
Clin Transl Oncol ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276288

RESUMEN

PURPOSE: The epidemiologic data of metabolic associated fatty liver disease (MAFLD) in breast cancer (BC) patients remains limited. We aimed to investigate the prevalence and clinicopathological characteristics of hepatic steatosis (HS) and MAFLD in Chinese BC women at initial diagnosis. METHODS: 3217 non-metastatic primary BC women with MAFLD evaluation indexes at initial diagnosis and 32,170 age-matched (in a 1:10 ratio) contemporaneous health check-up women were enrolled. RESULTS: The prevalence of HS (21.5% vs. 19.7%, p = 0.013) and MAFLD (20.8% vs. 18.6%, p = 0.002) were significantly higher in BC women than in health check-ups, respectively. Meanwhile, the prevalence of HS/MAFLD among elderly BC women (≥ 60 years) was significantly higher than the health check-ups (38.7%/37.6% vs 31.9%/30.8%), respectively. In BC women with HS/MAFLD, the prevalence of overweight/obesity was up to 85.7%/88.6%, dyslipidemia and elevated blood pressure were 63.2%/63.7% and 59.7%/61.7%, respectively. No statistical significance of the expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER-2) and Ki67 were found between BC women with HS/MAFLD and BC women without HS/MAFLD. After adjustment, BC women with HS showed significantly higher risk of lymph node metastasis than BC women without HS. Subjects with HS/MAFLD had higher risks of overweight/obesity, dyslipidemia, elevated blood pressure, hyperuricemia, and elevated enzymes than those without HS/MAFLD. CONCLUSIONS: Compared with health check-ups, BC patients have higher prevalence of HS/MAFLD. HS/MAFLD coexist with high prevalence of metabolic complications, and the risk of lymph node metastasis was significantly higher in BC women with HS than in BC women without HS.

9.
BMC Med ; 22(1): 370, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256817

RESUMEN

BACKGROUND: Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions. METHODS: A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD. RESULTS: Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62-1.89), hypertensive diseases (1.49, 1.38-1.62), cardiac arrests (1.52, 1.30-1.77), arrhythmia (1.76, 1.44-2.15), cerebrovascular diseases (1.86, 1.65-2.10), stroke (1.77, 1.54-2.03), ischemic stroke (1.85, 1.61-2.12), atherosclerosis (1.77, 1.57-1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15-1.51), pneumonia (1.37, 1.16-1.61), inflammatory bowel diseases (1.34, 1.16-1.55), liver diseases (1.59, 1.43-1.77), type 2 diabetes (1.48, 1.26-1.73), lipoprotein metabolism disorders (2.20, 1.96-2.47), purine metabolism disorders (1.61, 1.38-1.88), anemia (1.29, 1.15-1.45), sleep disorders (1.54, 1.33-1.78), renal failure (1.44, 1.21-1.72), kidney stone (1.27, 1.13-1.43), osteoarthritis (2.18, 2.00-2.39), osteoporosis (1.36, 1.14-1.61). OM had max weights for joint effects of AP on many conditions. CONCLUSIONS: Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Enfermedades Cardiovasculares , Material Particulado , Humanos , China/epidemiología , Contaminación del Aire/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Enfermedades Cardiovasculares/epidemiología , Adulto , Ozono/efectos adversos , Ozono/análisis , Anciano , Exposición a Riesgos Ambientales/efectos adversos , Factores de Riesgo , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis
10.
Plant Cell Environ ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39238330

RESUMEN

Respiratory Burst Oxidase Homologues (RBOHs) are involved in plant growth, development, and stress adaptation. How OsRBOHs affect root hair formation and consequently nutrient acquisition and drought resistance in rice is not well understood. We knocked out six OsRBOH genes in rice that were expressed in roots and identified OsRBOHE as the only one affecting root hair formation. OsRBOHE was strongly expressed in the root epidermis, root hairs and tiller buds. OsRBOHE is localised at the plasma membrane. Knockout of OsRBOHE decreased reactive oxygen species generation in the root hairs and tiller buds, downregulated genes involved in cell wall biogenesis, and decreased root hair length and tillering by 90% and 30%, respectively. Knockout of OsRBOHE decreased phosphorus acquisition only in low available P soil under aerobic conditions, but not in high P soil or under flooded conditions when P was likely not limited by diffusion. Knockout of OsRBOHE markedly decreased drought resistance of rice plants through the effect on root hair formation and the associated rhizosheath. Taken together, OsRBOHE is crucial for root hair formation and tillering and consequently on drought resistance in rice. The contribution of root hairs to P acquisition in rice is limited to aerobic soil.

11.
J Autoimmun ; 149: 103304, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39232430

RESUMEN

The main pathogenic features of immunoglobulin A vasculitis (IgAV) are overactive B cells and elevated production of IgA, which requires help from T follicular helper 17 (Tfh17) cells. To evaluate the pathological role of Tfh17 cells in IgAV, we investigated the mechanism responsible for Tfh17 differentiation and explored how to ameliorate IgAV by modulating Tfh17 generation. Peripheral blood mononuclear cells from IgAV patients were analyzed by flow cytometry. In vitro culture was performed to assess the modulation of cytokine-induced phenotypes. IgAV rats were used to explore the therapeutic effects of IL-6 blockade and the regulatory functions of IL-6 in Tfh17 cells. Serum cytokine and IgA levels were measured by ELISA while histopathological changes were evaluated by H&E,PAS or immunofluorescence staining. Frequency of CD4+CXCR5+CCR6+ Tfh17 cells were increased in IgAV patients and associated with disease severity. There was also a significant infiltration of Tfh17 cells in the kidney of human IgAV nephritis patients. IL-6 promoted the dendritic cell production of TGF-ß and Tfh17 differentiation. In IgAV rats, the in vivo blockade of IL-6 signaling inhibited Tfh17 differentiation, resulting in reduction of the germinal center and IgA production. Suppression of Tfh17 cells using IL-6 blockade greatly ameliorated clinical symptoms such as hemorrhagic rash and bloody stool and decreased IgA deposition and mesangial proliferation in the kidney in IgAV rats. Our findings suggest that suppression of Tfh17 differentiation can alleviate IgA-mediated vasculitis and may permit the development of tailored medicines for treating IgAV.

12.
Psychiatry Res ; 342: 116183, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39303554

RESUMEN

OBJECTIVE: This study aimed to compare the neuropsychological function in early adolescence between children born small for gestational age (SGA) or large for gestational age (LGA) and those born appropriate for gestational age (AGA). METHODS: This retrospective cohort study utilized data from the Adolescent Brain Cognitive Development study in 2016-18. Children born of singleton pregnancy with complete information of birth weight and delivery week were enrolled. Their neuropsychological functioning were assessed by the brain structural magnetic resonance imaging (MRI), combined with cognitive and behavioral measurements. Linear mixed-effects models and subgroup analyses were performed. RESULTS: Among 5,922 children aged 9-11, children born SGA and LGA demonstrated similar cognitive and behavioral performances as children born AGA (P > 0.05). In the MRI measurement, brain area and volume were lower among SGA children compared to AGA children (t=-5.626, Cohen's d = 0.448, P < 0.001; t=-6.071, Cohen's d = 0.427, P < 0.001); brain area and volume were higher among LGA children compared to AGA children (t = 8.562, Cohen's d = 0.470, P < 0.001; t = 8.562, Cohen's d = 0.470, P < 0.001). Cortical thickness was of no statistical difference (P > 0.05). These associations were confirmed by sensitivity analyses and propensity score matching. CONCLUSION: Children born of SGA and LGA status were associated with altered brain area and volume structure in early adolescence.

13.
Huan Jing Ke Xue ; 45(9): 5395-5405, 2024 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-39323157

RESUMEN

With the drying and warming of the climate and irrational grazing, various types of grasslands in Inner Mongolia have been degraded to different degrees, and different management modes will inevitably affect the plant diversity and vegetation carbon stock of soil grasslands. To clarify the changes and influencing factors of plant diversity and carbon stock in different types of grasslands under different management modes, plant species composition, aboveground biomass, and vegetation carbon were analyzed based on 18 sentinel monitoring stations across three different types of grasslands in Inner Mongolia. The results showed that grazing increased the dominance of typical grassland and desert grassland, whereas meadow grassland decreased, and the evenness index and Shannon Wiener diversity index increased less in meadow grassland and desert grassland. Grazing decreased graminaceous biomass in meadow grassland and typical grassland, whereas it increased in desert grassland. Above-ground vegetation and below-ground root carbon stocks were much higher than those in grazing areas, 1.5 and 1.2 higher, respectively, but vegetation carbon stocks in long-term grazing sites were significantly lower than those in short-term grazing. Further, the structural equations showed that the effects of geographic location, climatic factors, and soil factors on the biomass and vegetation carbon stocks of the three grassland types differed significantly. The results can provide a reference for the ecologically sustainable development of grassland and the optimization of management mode.


Asunto(s)
Biodiversidad , Carbono , Pradera , Poaceae , Carbono/análisis , China , Poaceae/crecimiento & desarrollo , Herbivoria , Animales , Biomasa , Conservación de los Recursos Naturales , Suelo/química
14.
J Nanobiotechnology ; 22(1): 586, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39342329

RESUMEN

Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate ß-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.


Asunto(s)
Vesículas Extracelulares , Metástasis Linfática , Neoplasias de la Boca , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Microfluídica/métodos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Biomarcadores de Tumor/metabolismo , Femenino , Dispositivos Laboratorio en un Chip , Masculino , Periodo Posoperatorio , Persona de Mediana Edad , Drenaje/métodos
15.
Adv Sci (Weinh) ; : e2404854, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258786

RESUMEN

Cancer is a systemic heterogeneous disease involving complex molecular networks. Tumor formation involves an epithelial-mesenchymal transition (EMT), which promotes both metastasis and plasticity of cancer cells. Recent experiments have proposed that cancer cells can be transformed into adipocytes via a combination of drugs. However, the underlying mechanisms for how these drugs work, from a molecular network perspective, remain elusive. To reveal the mechanism of cancer-adipose conversion (CAC), this study adopts a systems biology approach by combing mathematical modeling and molecular experiments, based on underlying molecular regulatory networks. Four types of attractors are identified, corresponding to epithelial (E), mesenchymal (M), adipose (A) and partial/intermediate EMT (P) cell states on the CAC landscape. Landscape and transition path results illustrate that intermediate states play critical roles in the cancer to adipose transition. Through a landscape control approach, two new therapeutic strategies for drug combinations are identified, that promote CAC. These predictions are verified by molecular experiments in different cell lines. The combined computational and experimental approach provides a powerful tool to explore molecular mechanisms for cell fate transitions in cancer networks. The results reveal underlying mechanisms of intermediate cell states that govern the CAC, and identified new potential drug combinations to induce cancer adipogenesis.

16.
Asian J Pharm Sci ; 19(4): 100929, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39258001

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that leads to interstitial inflammation, lung damage, and eventually life-threatening complications. Among various pathologic factors, Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF. It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes. Thus, the inhibition of Smad4 expression in pulmonary fibroblasts by small interfering RNAs (siRNAs) might be a promising therapeutic strategy for IPF. Herein, we engineered exosome membranes (EM) by cationic lipid (i.e., DOTAP) to load siRNAs against Smad4 (DOTAP/siSmad4@EM), and investigated their specific delivery to pulmonary fibroblasts for treating IPF in a mouse model via pulmonary administration. As reference nanoscaffolds, undecorated DOTAP/siSmad4 complexes (lipoplexes, consisting of cationic lipid DOTAP and siRNAs) and siSmad4-loaded lipid nanoparticles (DOTAP/siSmad4@lipo, consisting of lipoplexes fused with DPPC-Chol liposomes) were also prepared. The results showed that DOTAP/siSmad4@EM exhibited a higher cellular uptake and gene silencing efficacies in mouse pulmonary fibroblasts (viz., MLg2908) as compared to the two reference nanoscaffolds. Furthermore, the outcomes of the in vivo experiments illustrated that DOTAP/siSmad4@EM could significantly down-regulate the Smad4 expression with augmented anti-fibrosis efficiency. Additionally, the DOTAP/siSmad4@EM conferred excellent biocompatibility with low cytokine levels in bronchoalveolar lavage fluid and proinflammatory responses in the pulmonary area. Taken together, the outcomes of our investigation imply that specific inhibition of Smad4 expression in pulmonary fibroblasts by pulmonary administrated DOTAP/siSmad4@EM is a promising therapeutic strategy for IPF, which could safely and effectively deliver siRNA drugs to the targeted site of action.

17.
J Am Chem Soc ; 146(40): 27802-27808, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39320037

RESUMEN

The practical application of Li-CO2 batteries is significantly hindered by high charge potential and short lifespan, mainly due to sluggish reaction kinetics and inadequate reaction reversibility. Homogeneous catalysts added to the electrolyte provide a promising strategy to address these issues. In this work, the third-generation Grubbs catalyst (G-III), which is efficient for olefin metathesis reactions, has been adopted as a homogeneous catalyst for Li-CO2 batteries. Batteries with G-III exhibited a low overpotential of 0.86 V and a lifespan of 1300 h at a current density of 300 mA g-1. Even at a high current density of 2000 mA g-1, the batteries remained stable for over 300 cycles, with an initial overpotential of 1.11 V. A two-step discharge/charge reaction involving Li2C2O4 as an intermediate was well illustrated, attributed to both low overpotentials and high specific capacity. These findings provide insights into catalyst selection and mechanism analysis for Li-CO2 batteries, offering practical strategies for Li-CO2 battery performance enhancement and practical applications.

18.
Nat Commun ; 15(1): 7563, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39214983

RESUMEN

Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we construct a global microbial smORFs catalog (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes. GMSC contains 965 million non-redundant smORFs with comprehensive annotations. We find that archaea harbor more smORFs proportionally than bacteria. We moreover provide a tool called GMSC-mapper to identify and annotate small proteins from microbial (meta)genomes. Overall, this publicly-available resource demonstrates the immense and underexplored diversity of small proteins.


Asunto(s)
Archaea , Bacterias , Metagenoma , Microbiota , Sistemas de Lectura Abierta , Microbiota/genética , Sistemas de Lectura Abierta/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Metagenoma/genética , Archaea/genética , Archaea/metabolismo , Archaea/clasificación , Anotación de Secuencia Molecular , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
19.
Animals (Basel) ; 14(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39199878

RESUMEN

Currently, nearly 70% of giant panda populations are facing survival challenges. The introduction of wild individuals can bring vitality to them. To explore this possibility, we hypothetically introduced giant pandas from Tangjiahe and Wanglang into Liziping and Daxiangling Nature Reserves. We collected feces from these areas and analyzed the genetic diversity and population viability before and after introduction using nine microsatellite loci. The results showed the genetic level and viability of the large populations were better than the small populations. We investigated the effects of time intervals (2a, 5a, and 10a; year: a) and gender combinations (female: F; male: M) on the rejuvenation of small populations. Finally, five introduction plans (1F/2a, 2F/5a, 1F1M/5a, 3F/10a, and 2F1M/10a) were obtained to make Liziping meet the long-term survival standard after 100 years, and six plans (1F/2a, 2F/5a, 1F1M/5a, 4F/10a, 3F1M/10a, and 2F2M/10a) were obtained in Daxiangling. The more females were introduced, the greater the impact on the large populations. After introducing individuals, the number of alleles and expected heterozygosity of the Liziping population are at least 6.667 and 0.688, and for the Daxiangling population, they are 7.111 and 0.734, respectively. Our study provides theoretical support for the translocation of giant pandas, a reference for the restoration of other endangered species worldwide.

20.
Rheumatol Int ; 44(10): 2167-2177, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39192023

RESUMEN

The study aimed to investigate the pattern and trend of Musculoskeletal (MSK) disorders in people aged 5-19 years from 1990 to 2021. The data was sourced from the Global Burden of Disease study 2021. The Age-standardized DALYs rates (ASDR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized incidence rate (ASIR) and their corresponding average annual percent change (AAPC) for MSK disorders were evaluated by sex, region, and sociodemographic index (SDI) quintiles. Globally, the ASPR of MSK disorders among children and adolescents increased per 100,000 population from 3048.66 (95% confidence interval [CI]: 2336.68-3887.02) in 1990 to 3105.46 (95% CI: 2421.09-3904.95) in 2021 (AAPC 0.06 [95% CI: 0.05-0.07]). In 2021, individuals aged 15-19 experienced the highest burden compared to those aged 5-9 and 10-14. In 2021, high SDI countries had the highest ASIR, ASPR, ASDR of MSK disorders. The AAPC of ASPR in high SDI countries showed a stark contrast to that in low SDI countries for the same period (AAPC 0.48 vs. AAPC -0.03). From 1990 to 2021, in low SDI and low-middle SDI countries, the increase in DALYs was primarily due to population growth. However, in middle SDI, high-middle, and high SDI countries, the increases were mainly due to epidemiological changes. Globally, patients aged 10-14 experienced better care compared to those in the 5-9 and 15-19 age groups. Specific preventive health measures are needed for females and adolescents aged 15-19 in high SDI countries.


Asunto(s)
Carga Global de Enfermedades , Enfermedades Musculoesqueléticas , Humanos , Adolescente , Niño , Enfermedades Musculoesqueléticas/epidemiología , Masculino , Femenino , Carga Global de Enfermedades/tendencias , Preescolar , Adulto Joven , Prevalencia , Incidencia , Salud Global , Distribución por Edad
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