Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 621
Filtrar
1.
Nature ; 629(8010): 74-79, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38693415

RESUMEN

Within the family of two-dimensional dielectrics, rhombohedral boron nitride (rBN) is considerably promising owing to having not only the superior properties of hexagonal boron nitride1-4-including low permittivity and dissipation, strong electrical insulation, good chemical stability, high thermal conductivity and atomic flatness without dangling bonds-but also useful optical nonlinearity and interfacial ferroelectricity originating from the broken in-plane and out-of-plane centrosymmetry5-23. However, the preparation of large-sized single-crystal rBN layers remains a challenge24-26, owing to the requisite unprecedented growth controls to coordinate the lattice orientation of each layer and the sliding vector of every interface. Here we report a facile methodology using bevel-edge epitaxy to prepare centimetre-sized single-crystal rBN layers with exact interlayer ABC stacking on a vicinal nickel surface. We realized successful accurate fabrication over a single-crystal nickel substrate with bunched step edges of the terrace facet (100) at the bevel facet (110), which simultaneously guided the consistent boron-nitrogen bond orientation in each BN layer and the rhombohedral stacking of BN layers via nucleation near each bevel facet. The pure rhombohedral phase of the as-grown BN layers was verified, and consequently showed robust, homogeneous and switchable ferroelectricity with a high Curie temperature. Our work provides an effective route for accurate stacking-controlled growth of single-crystal two-dimensional layers and presents a foundation for applicable multifunctional devices based on stacked two-dimensional materials.

2.
Am J Chin Med ; : 1-19, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38699996

RESUMEN

Panax notoginseng saponins (PNS), the primary medicinal ingredient of Panax notoginseng, mitigates cerebral ischemia-reperfusion injury (CIRI) by inhibiting inflammation, regulating oxidative stress, promoting angiogenesis, and improving microcirculation. Moreover, PNS activates nuclear factor erythroid 2-related factor 2 (Nrf2), which is known to inhibit ferroptosis and reduce inflammation in the rat brain. However, the molecular regulatory roles of PNS in CIRI-induced ferroptosis remain unclear. In this study, we aimed to investigate the effects of PNS on ferroptosis and inflammation in CIRI. We induced ferroptosis in SH-SY5Y cells via erastin stimulation and oxygen glucose deprivation/re-oxygenation (OGD/R) in vitro. Furthermore, we determined the effect of PNS treatment in a rat model of middle cerebral artery occlusion/reperfusion and assessed the underlying mechanism. We also analyzed the changes in the expression of ferroptosis-related proteins and inflammatory factors in the established rat model. OGD/R led to an increase in the levels of ferroptosis markers in SH-SY5Y cells, which were reduced by PNS treatment. In the rat model, combined treatment with an Nrf2 agonist, Nrf2 inhibitor, and PNS-Nrf2 inhibitor confirmed that PNS promotes Nrf2 nuclear localization and reduces ferroptosis and inflammatory responses, thereby mitigating brain injury. Mechanistically, PNS treatment facilitated Nrf2 activation, thereby regulating the expression of iron overload and lipid peroxidation-related proteins and the activities of anti-oxidant enzymes. This cascade inhibited ferroptosis and mitigated CIRI. Altogether, these results suggest that the ferroptosis-mediated activation of Nrf2 by PNS reduces inflammation and is a promising therapeutic approach for CIRI.

3.
Clin Pharmacol Ther ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38751031

RESUMEN

Bispecific T-cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. BsTCEs enable physical connections between T cells and tumor cells to enhance T-cell activity against cancer. Despite several marketing approvals, the development of bsTCEs remains challenging, especially at early clinical translational stages. The intricate design of bsTCEs makes their pharmacologic effects and safety profiles highly dependent on patient's immunological and tumor conditions. Such context-dependent pharmacology introduces considerable uncertainty into translational efforts. In this study, we developed a Quantitative Systems Pharmacology (QSP) model, through context unification, that can facilitate the translation of bsTCEs preclinical data into clinical activity. Through characterizing the formation dynamics of immunological synapse (IS) induced by bsTCEs, this model unifies a broad range of contexts related to target affinity, tumor characteristics, and immunological conditions. After rigorous calibration using both experimental and clinical data, the model enables consistent translation of drug potency observed under diverse experimental conditions into predictable exposure-response relationships in patients. Moreover, the model can help identify optimal target-binding affinities and minimum efficacious concentrations across different clinical contexts. This QSP approach holds significant promise for the future development of bsTCEs.

4.
Front Mol Biosci ; 11: 1367331, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38596618

RESUMEN

Osteosarcoma, the most prevalent primary bone tumor in children and young adults, can often be successfully treated with standard chemotherapy and surgery when diagnosed at an early stage. However, patients presenting with metastases face significant challenges in achieving a cure. Despite advancements in classical therapies over the past few decades, clinical outcomes for osteosarcoma have not substantially improved. Recently, there has been increased understanding of the biology of osteosarcoma, leading to the identification of new therapeutic targets. One such target is MET, a tyrosine kinase receptor for Hepatocyte Growth Factor (HGF) encoded by the MET gene. In vitro and in vivo studies have demonstrated that the HGF/MET pathway plays a crucial role in cancer growth, invasion, metastasis, and drug resistance across various cancers. Clinical trials targeting this pathway are already underway for lung cancer and hepatocellular carcinoma. Moreover, MET has also been implicated in promoting osteosarcoma progression. This review summarizes 3 decades' worth of research on MET's involvement in osteosarcoma and further explores its potential as a therapeutic target for patients with this disease.

5.
ISA Trans ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38616475

RESUMEN

The accurate positioning and swing suppression of tower cranes remain open problems, especially when considering unknown payload masses, frictions and wind disturbances, making the controller design more challenging. Therefore, considering the factors, without linearization to 5-DOF tower crane dynamics, an improved non-singular fast terminal sliding mode control (INFTSMC) scheme is proposed, which can drive the trolley, jib and cable to the desired positions accurately within finite time while suppressing payload swings effectively under the unknown payload masses, frictions and wind disturbances. Specifically, an improved sliding mode surface is designed to suppress payload swings; a chattering problem is attenuated by constructing an enhanced convergence law; a payload mass estimation strategy is designed to eliminate the vertical positioning error; adaptive schemes are proposed to counteract the effects of unknown frictions and wind disturbances. The stability of the closed-loop system is proven rigorously by using the Lyapunov principle and LaSalle's invariance theorem. Comparative simulations are implemented to validate the superior control performances and robustness of the proposed method.

6.
Science ; 384(6692): eadk6200, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38574174

RESUMEN

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.


Asunto(s)
Andrógenos , Células Dendríticas , Inmunidad Innata , Linfocitos , Caracteres Sexuales , Piel , Femenino , Masculino , Andrógenos/metabolismo , Células Dendríticas/inmunología , Hormonas Esteroides Gonadales/metabolismo , Linfocitos/inmunología , Piel/inmunología , Animales , Ratones , Ratones Endogámicos C57BL , Microbiota
7.
Opt Express ; 32(6): 9562-9572, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571187

RESUMEN

We demonstrated a high-performance partially corrugated waveguide distributed feedback (PCW-DFB) laser with high output power, low relative intensity noise (RIN) and narrow linewidth. By introducing offset quantum-well structure that provides enough threshold gain difference for single transverse mode operation, the laser can achieve single mode behavior with an 8-µm-wide ridge waveguide. The laser has been designed by the simulation model based on the coupled wave equations, and the fabricated PCW-DFB laser with the cavity length of 1.3 mm exhibited an output power higher than 190 mW. Stable single mode characteristics have been achieved with a side-mode suppression-ratio (SMSR) over 55 dB. The RIN was less than -160.5 dB/Hz at an injection current of 470 mA, and the linewidth reached 45 kHz.

8.
Clin Transl Oncol ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602642

RESUMEN

PURPOSE: This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs). RESULTS: A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1-7.3), and the median OS was 15.3 months (95% CI: 12.9-17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients. CONCLUSION: The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.

9.
Commun Biol ; 7(1): 396, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561411

RESUMEN

Myocardial ischemia-reperfusion injury (MIRI) is involved in the pathogenesis of multiple cardiovascular diseases. This study elucidated the biological function of lysine acetyltransferase 5 (KAT5) in cardiomyocyte pyroptosis during MIRI. Oxygen-glucose deprivation/reoxygenation and left anterior descending coronary artery ligation were used to establish MIRI models. Here we show, KAT5 and STIP1 homology and U-box-containing protein 1 (STUB1) were downregulated, while large tumor suppressor kinase 2 (LATS2) was upregulated in MIRI models. KAT5/STUB1 overexpression or LATS2 silencing repressed cardiomyocyte pyroptosis. Mechanistically, KAT5 promoted STUB1 transcription via acetylation modulation, and subsequently caused ubiquitination and degradation of LATS2, which activated YAP/ß-catenin pathway. Notably, the inhibitory effect of STUB1 overexpression on cardiomyocyte pyroptosis was abolished by LATS2 overexpression or KAT5 depletion. Our findings suggest that KAT5 overexpression inhibits NLRP3-mediated cardiomyocyte pyroptosis to relieve MIRI through modulation of STUB1/LATS2/YAP/ß-catenin axis, providing a potential therapeutic target for MIRI.


Asunto(s)
Daño por Reperfusión Miocárdica , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Piroptosis , Ubiquitinación , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Lisina Acetiltransferasa 5/metabolismo
10.
Int J Med Microbiol ; 315: 151619, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38564936

RESUMEN

BACKGROUND: To analysis of quasispecies (QS) changes and high-frequency mutations in the BCP/PreC/C region of patients at different phases of hepatitis B virus (HBV) infection and provides novel biomarkers for the diagnosis of chronic hepatitis B (CHB) patients. METHODS: With the application of next-generation sequencing technology, we were able to sequence the HBV BCP/PreC/C regions in 40 patients, each at different phases of the HBV infection. The heterogeneity of QS and the frequency of mutations were calculated using MEGA 7 software. RESULTS: Our results show that the complexity and diversity of the BCP/PreC/C QS in HBeAg-positive CHB patients are significantly higher than those in HBeAg-positive chronic infection patients, while HBeAg-negative chronic infection patients had significantly higher QS complexity and diversity than HBeAg-negative CHB patients. In addition, HBeAg-negative patients showed reduced complexity but increased diversity compared with HBeAg-positive patients. Receiver operating characteristic curves showed that G1764A, C2102T, dN and complexity of QS could be used as potential biomarkers for diagnosing HBeAg-positive CHB, while the A2189C, dS and complexity of QS could be used as potential biomarkers for diagnosing HBeAg-negative chronic hepatitis. Finally, our study also found that G1896A and A2159G may be hotspot mutations affecting HBeAg seroconversion. CONCLUSION: Our research elucidates the evolution of HBV by analyzing QS heterogeneity and mutation patterns, offering novel serum biomarkers for enhancing clinical diagnosis and disease prognosis. This comprehensive approach sheds light on the intricate dynamics of HBV progression and paves the way for more precise medical interventions.

11.
Heliyon ; 10(8): e29419, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681648

RESUMEN

Introduction: Wernicke encephalopathy (WE) is a potentially fatal condition caused by thiamine (vitamin B1) deficiency. Chronic alcoholism is the most common cause of WE; however, other conditions responsible for thiamine deficiency should also be considered. Case Report: We report the case of a 64-year-old woman with a history of diabetes who presented with confusion and apathy. Magnetic resonance imaging of the brain showed T2 hyperintensities involving dorsolateral medulla oblongata, tegmentum of the pons, vermis of the cerebellum, periaqueductal region, and the bilateral mammillary bodies. She had a history of intravenous glucose administration before her mental symptoms developed. On suspicion of WE, she was treated with a high dose of thiamine empirically. Her clinical condition improved rapidly in 2 weeks. Conclusion: Endogenous thiamine stores can be rapidly depleted in the case of enhanced glucose oxidation. Patients who receive glucose should also be prescribed thiamine to avoid inducing or exacerbating WE.

12.
Nanoscale Adv ; 6(8): 1997-2001, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38633051

RESUMEN

Herein, F-doped CDs with bright red SSF were synthesized by a solvothermal method using trifluoroethanol as the solvent and m-hydroxybenzaldehyde as the carbon source. Strong F-F interactions are vital for inducing crystallization, and solid luminescence is achieved by blocking the nonradiative energy dissipation pathways of crystalline organizations.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38687669

RESUMEN

Deep neural networks (DNNs) have made great breakthroughs and seen applications in many domains. However, the incomparable accuracy of DNNs is achieved with the cost of considerable memory consumption and high computational complexity, which restricts their deployment on conventional desktops and portable devices. To address this issue, low-rank factorization, which decomposes the neural network parameters into smaller sized matrices or tensors, has emerged as a promising technique for network compression. In this article, we propose leveraging the emerging tensor ring (TR) factorization to compress the neural network. We investigate the impact of both parameter tensor reshaping and TR decomposition (TRD) on the total number of compressed parameters. To achieve the maximal parameter compression, we propose an algorithm based on prime factorization that simultaneously identifies the optimal tensor reshaping and TRD. In addition, we discover that different execution orders of the core tensors result in varying computational complexities. To identify the optimal execution order, we construct a novel tree structure. Based on this structure, we propose a top-to-bottom splitting algorithm to schedule the execution of core tensors, thereby minimizing computational complexity. We have performed extensive experiments using three kinds of neural networks with three different datasets. The experimental results demonstrate that, compared with the three state-of-the-art algorithms for low-rank factorization, our algorithm can achieve better performance with much lower memory consumption and lower computational complexity.

14.
Ecotoxicol Environ Saf ; 277: 116326, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38640800

RESUMEN

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities' composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the "microbiota-intestine-brain axis" and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies.


Asunto(s)
Antimonio , Microbioma Gastrointestinal , Contaminantes Químicos del Agua , Pez Cebra , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Antimonio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Metaboloma/efectos de los fármacos , Metabolómica
15.
ACS Omega ; 9(14): 15845-15853, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38617662

RESUMEN

Developing an environmentally friendly soy protein-based film that offers excellent performance has garnered considerable interest while also posing a significant challenge. Herein, we propose the strategy of covalent and noncovalent cross-linking to improve the mechanical properties of the films. First, chemical denaturation was carried out under the combined action of sodium sulfite, sodium dodecyl sulfate, sodium hydroxide, and urea to reshape the structure of the protein to improve the solubility of protein and release active groups. Then, microcrystalline cellulose (MCC) derived from low-cost agro-industrial byproducts (corn husk) was employed to balance the covalent cross-linking reaction between proteins and the noncovalent reaction between MCC and protein. The results indicate that the structure and properties of the soy protein-based films were modified and improved through chemical treatment in conjunction with biomass enhancement. It is concluded that the addition of 1% MCC improves the tensile strength, elastic modulus, water solubility, and water vapor permeability of "MCC-1%" by 64.7, 75.9, 22.7, and 12.9%, respectively. Additionally, the resulting film of "MCC-1%" exhibits better resistance to thermal degradation and improved thermo-stability. However, the elongation at break decreased by increasing the addition of MCC. Thus, this work may provide a simple and affordable approach to preparing a high-performing soy protein-based film.

16.
Sci Total Environ ; 926: 171809, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38513845

RESUMEN

Soil cadmium (Cd) can affect crop growth and food safety, and through the enrichment in the food chain, it ultimately poses a risk to human health. Reducing the re-mobilization of Cd caused by the release of protons and acids by crops and microorganisms after stabilization is one of the significant technical challenges in agricultural activities. This study aimed to investigate the re-mobilization of stabilized Cd within the clay mineral-bound fraction of soil and its subsequent accumulation in crops utilizing nitrogen ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N), at 60 and 120 mg kg-1. Furthermore, the study harvested root exudates at various growth stages to assess their direct influence on the re-mobilization of stabilized Cd and to evaluate the indirect effects mediated by soil microorganisms. The results revealed that, in contrast to the NO3--N treatment, the NH4+-N treatment significantly enhanced the conversion of clay mineral-bound Cd in the soil to NH4NO3-extractable Cd. It also amplified the accumulation of Cd in edible amaranth, with concentrations in roots and shoots rising from 1.7-6.0 mg kg-1 to 4.3-9.8 mg kg-1. The introduction of NH4+-N caused a decrease in the pH value of the rhizosphere soil and stimulated the production and secretion organic and amino acids, such as oxalic acid, lactic acid, stearic acid, succinic acid, and l-serine, from the crop roots. Furthermore, compared to NO3--N, the combined interaction of root exudates with NH4+-N has a more pronounced impact on the abundance of microbial genes associated with glycolysis pathway and tricarboxylic acid cycle, such as pkfA, pfkB, sucB, sucC, and sucD. The effects of NH4+-N on crops and microorganisms ultimately result in a significant increase in the re-mobilization of stabilized Cd. However, the simulated experiments showed that microorganisms only contribute to 3.8-6.6 % of the re-mobilization of clay mineral-bound Cd in soil. Therefore, the fundamental strategy to inhibit the re-mobilization of stabilized Cd in vegetable cultivation involves the regulation of proton and organic acid secretion by crops.


Asunto(s)
Contaminantes del Suelo , Suelo , Humanos , Suelo/química , Cadmio/análisis , Arcilla , Nitrógeno/metabolismo , Compuestos Orgánicos/metabolismo , Productos Agrícolas/metabolismo , Minerales/metabolismo , Fertilización , Contaminantes del Suelo/análisis
17.
Int J Biol Macromol ; 264(Pt 2): 130470, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38453124

RESUMEN

LKB1 (liver kinase B1) is a key upstream kinase of AMPK and plays an important role in various cellular activities. While the function and mechanism of LKB1 have been widely reported in the study of tumor, there are few reports on its role in bacterial infectious diseases, especially in shrimp. In the present study, molecular characterization revealed that LvLKB1 has an open reading frame (ORF) of 1266 bp encoding 421 amino acids with a molecular weight of about 48 KDa, including the kinase region, N-terminal regulatory domain and C-terminal regulatory domain. LvLKB1 in hepatopancreas and hemocytes was significantly upregulated after infection with Vibrio alginolyticus (V. alginolyticus). After silencing LvLKB1 gene in Litopenaeus vannamei (L. vannamei) and artificially infecting V. alginolyticus, the survival rate of L. vannamei was significantly decreased. Subsequently, it was found that the expression of inflammatory factors in hepatopancreas and hemocytes of shrimp was up-regulated, and the expression of lipid oxidation factors was decreased after silencing LKB1, leading to the phenomenon of lipid accumulation in hepatopancreas. In order to explore the mechanism, autophagy levels of shrimp were detected after silencing LKB1, which showed that autophagy levels in hepatopancreas and hemocytes were significantly reduced. Further studies conclusively showed that silencing LvLKB1 inhibited AMPK phosphorylation induced by V. alginolyticus infection, thereby activating TOR pathway and inhibiting autophagy in shrimp. These results indicate that LvLKB1 regulates autophagy through AMPK/TOR signaling pathway to alleviate the damage caused by V. alginolyticus infection.


Asunto(s)
Penaeidae , Vibriosis , Animales , Vibrio alginolyticus/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Transducción de Señal , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Autofagia , Lípidos , Penaeidae/microbiología , Inmunidad Innata/genética , Hemocitos/metabolismo , Proteínas de Artrópodos/química
18.
Genome Res ; 34(2): 310-325, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38479837

RESUMEN

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter-enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.


Asunto(s)
Cromatina , Cromosomas , Animales , Porcinos/genética , Cromatina/genética , Haplotipos , Cromosomas/genética , Genoma , Mamíferos/genética
19.
Sci Rep ; 14(1): 6403, 2024 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493251

RESUMEN

Chinese patent medicine (CPM) is a typical type of traditional Chinese medicine (TCM) preparation that uses Chinese herbs as raw materials and is an important means of treating diseases in TCM. Chinese patent medicine instructions (CPMI) serve as a guide for patients to use drugs safely and effectively. In this study, we apply a pre-trained language model to the domain of CPM. We have meticulously assembled, processed, and released the first CPMI dataset and fine-tuned the ChatGLM-6B base model, resulting in the development of CPMI-ChatGLM. We employed consumer-grade graphics cards for parameter-efficient fine-tuning and investigated the impact of LoRA and P-Tuning v2, as well as different data scales and instruction data settings on model performance. We evaluated CPMI-ChatGLM using BLEU, ROUGE, and BARTScore metrics. Our model achieved scores of 0.7641, 0.8188, 0.7738, 0.8107, and - 2.4786 on the BLEU-4, ROUGE-1, ROUGE-2, ROUGE-L and BARTScore metrics, respectively. In comparison experiments and human evaluation with four large language models of similar parameter scales, CPMI-ChatGLM demonstrated state-of-the-art performance. CPMI-ChatGLM demonstrates commendable proficiency in CPM recommendations, making it a promising tool for auxiliary diagnosis and treatment. Furthermore, the various attributes in the CPMI dataset can be used for data mining and analysis, providing practical application value and research significance.


Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos sin Prescripción , Humanos , Medicina Tradicional China/métodos , Minería de Datos , Medicamentos Herbarios Chinos/uso terapéutico
20.
Nat Sci Sleep ; 16: 279-289, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495839

RESUMEN

Objective: To examine the relationship between pregnancy-related anxiety, family functions, and sleep quality, and to determine whether family functions mediate the relationship between pregnancy-related anxiety and sleep quality. Methods: A cross-sectional survey was conducted on pregnant women between April to August in 2022 in the obstetrics outpatient clinic of a tertiary care hospital in the Ningxia Hui Autonomous Region of China. A total of 1014 pregnant women aged 18 years and older were surveyed. They completed questionnaires, including: general demographic characteristics, the Pregnancy-related anxiety scale (PAQ), the Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR), and the Pittsburgh Sleep Quality Index Questionnaire (PSQI). Model 4 in PROCESS was used to analyze the relationships among pregnancy-related anxiety, family functions, and sleep quality, with family functions as a mediator. Results: Among the 1014 pregnant women, the pregnancy-related anxiety scale score was (21.84 ± 5.64). The total score of the family functions scale was (8.10±2.26), and the overall sleep quality scale score was (7.89±2.99). When participants were grouped according to different socio-demographic characteristics, the study showed that all variables differed from anxiety, family functions or sleep quality, except for age, pre-pregnancy BMI and whether or not they had a first birth, which was not associated with anxiety, family functions, or sleep quality (P<0.05). The pregnancy-related anxiety was positively associated with sleep quality (P<0.01), while family functions were negatively associated with sleep quality (P<0.01). In addition, family functions mediate the relationship between pregnancy-related anxiety and sleep quality during pregnancy, on the first and second trimesters, intermediation rate is 9.31% (P<0.05), and on the third trimesters, intermediation rate is 21.38% (P<0.05). Conclusion: Pregnancy- related anxiety is a risk factor for sleep quality, however, family functions are protective factors for sleep quality. Family functions play an intermediary role in sleep quality caused by pregnancy-related anxiety, especially on the third trimesters. This finding may provide a scientific basis for developing intervention strategies to improve the sleep quality of pregnant women.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...