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1.
Animals (Basel) ; 14(17)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39272310

ABSTRACT

Dietary energy is crucial for ruminants' performance and health. To determine optimal dietary energy levels for growing sheep, we evaluated their growth performance, nutrient digestibility, rumen fermentation, barrier function, and microbiota under varying metabolic energy (ME) diets. Forty-five growing Yunnan semi-fine wool sheep, aged 10 months and weighing 30.8 ± 1.9 kg, were randomly allocated to five treatments, each receiving diets with ME levels of 8.0, 8.6, 9.2, 9.8 or 10.4 MJ/kg. The results showed that with increasing dietary energy, the average daily gain (ADG) as well as the digestibility of dry matter (DM) and organic matter (OM) increased (p < 0.05), while the feed conversion ratio (FCR) decreased linearly (p = 0.01). The concentration of total VFA (p = 0.03) and propionate (p = 0.01) in the rumen increased linearly, while rumen pH (p < 0.01) and the acetate-propionate ratio (p = 0.01) decreased linearly. Meanwhile, the protein contents of Claudin-4, Claudin-7, Occludin and ZO-1 as well as the relative mRNA expression of Claudin-4 and Occludin also increased (p < 0.05). In addition, rumen bacterial diversity decreased with the increase of dietary energy, and the relative abundance of some bacteria (like Saccharofermentans, Prevotella and Succiniclasticum) changed. In conclusion, increasing dietary energy levels enhanced growth performance, nutrient digestibility, rumen fermentation, and barrier function, and altered the rumen bacterial community distribution. The optimal dietary ME for these parameters in sheep at this growth stage was between 9.8 and 10.4 MJ/kg.

2.
Biomater Transl ; 5(1): 21-32, 2024.
Article in English | MEDLINE | ID: mdl-39220668

ABSTRACT

In recent years, advances in microfabrication technology and tissue engineering have propelled the development of a novel drug screening and disease modelling platform known as organoid-on-a-chip. This platform integrates organoids and organ-on-a-chip technologies, emerging as a promising approach for in vitro modelling of human organ physiology. Organoid-on-a-chip devices leverage microfluidic systems to simulate the physiological microenvironment of specific organs, offering a more dynamic and flexible setting that can mimic a more comprehensive human biological context. However, the lack of functional vasculature has remained a significant challenge in this technology. Vascularisation is crucial for the long-term culture and in vitro modelling of organoids, holding important implications for drug development and personalised medical approaches. This review provides an overview of research progress in developing vascularised organoid-on-a-chip models, addressing methods for in vitro vascularisation and advancements in vascularised organoids. The aim is to serve as a reference for future endeavors in constructing fully functional vascularised organoid-on-a-chip platforms.

3.
Front Pharmacol ; 15: 1453595, 2024.
Article in English | MEDLINE | ID: mdl-39221143

ABSTRACT

This study investigated the potential of immune checkpoint inhibitors (ICIs) combined with chemotherapy as a promising treatment approach for malignancies. This report focuses on a patient with drug-induced liver injury (DILI) following the administration of chemotherapy and ICIs. A 63-year-old patient with non-small cell lung adenocarcinoma (NSCLC) initially underwent γ-knife treatment and subsequently received a combination of chemotherapy comprising bevacizumab and camrelizumab. Due to liver abnormalities, both chemotherapy and ICIs were stopped on day 21. The patient's liver function improved within a month after methylprednisolone treatment. Subsequently, the patient received carboplatin, pemetrexed, and bevacizumab without complications. This finding supported the notion that DILI was likely triggered by the ICI. This case series details a complex instance of DILI resulting from the use of ICIs and pemetrexed/carboplatin. The alignment of the pathological findings and clinical presentation strongly suggested ICI-induced DILI, which was further supported by the definitive response to steroid treatment. This information is important for clinicians, as it emphasizes the importance of closely monitoring liver function and being aware of potential adverse effects associated with ICIs. Such insights contribute to more effective patient care.

4.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39248620

ABSTRACT

In this study, a high-precision counterweight self-calibrating surface thermometer is designed to reduce human and environmental influences on a thermocouple surface thermometer during measuring. A self-weighted spring structure based on a copper substrate is designed to ensure perfect contact between the surface thermometer and the temperature source. In conjunction, a wind guard is coupled with insulating materials to optimize the thermal exchange of the surface thermometer. Subsequently, the maximum error is reduced to ±1.5 °C by system hardware optimization. However, hardware calibration alone is insufficient. Furthermore, a back propagation neural network is employed to calibrate the surface thermometer. Temperature sensor data are collected under various surface source temperatures and airflow velocities to train the neural network. Hence, the effectiveness of the proposed Gaussian function in enhancing the measurement accuracy of the surface temperature sensor is demonstrated. The results show higher stability and repeatability in temperature measurement than thermocouple-based surface thermometers. The proposed thermometer exhibits robustness against environmental and operational variability with a maximum indication error of -0.2 °C. In contrast, the maximum error of the surface thermometer is between -2.8 and -6.8 °C. Regarding repeatability, the standard deviation with the proposed device is 0.2%, highlighting its accuracy and consistency of performance. These results can mostly be attributed to the synergistic effect of clever mechanical design and software optimization, resulting in a surface thermometer with outstanding accuracy and repeatability.

5.
Taiwan J Obstet Gynecol ; 63(5): 764-767, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39266162

ABSTRACT

OBJECTIVE: To help determine the pathogenicity of 4p16.1 microduplications, we reported two asymptomatic families carrying this variation. CASE REPORT: We present the prenatal diagnosis and genetic analysis of two normal families with 4p16.1 microduplications. CONCLUSION: This paper highlights two families with clinically asymptomatic 4p16.1 microduplications that assisted in determining the pathogenicity of this fragment. The findings can be used as a reference for genetic counseling in cases of similar abnormalities encountered during future prenatal diagnosis.


Subject(s)
Chromosomes, Human, Pair 4 , Phenotype , Humans , Female , Pregnancy , Adult , Chromosomes, Human, Pair 4/genetics , Chromosome Duplication/genetics , Genetic Testing/methods , Genetic Counseling , Pedigree , Prenatal Diagnosis/methods , Ultrasonography, Prenatal
6.
NPJ Vaccines ; 9(1): 171, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39289377

ABSTRACT

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.

7.
aBIOTECH ; 5(3): 408-412, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39279853

ABSTRACT

Root-associated microbiota profoundly affect crop health and productivity. Plants can selectively recruit beneficial microbes from the soil and actively balance microbe-triggered plant-growth promotion and stress tolerance enhancement. The cost associated with this is the root-mediated support of a certain number of specific microbes under nutrient limitation. Thus, it is important to consider the dynamic changes in microbial quantity when it comes to nutrient condition-induced root microbiome reassembly. Quantitative microbiome profiling (QMP) has recently emerged as a means to estimate the specific microbial load variation of a root microbiome (instead of the traditional approach quantifying relative microbial abundances) and data from the QMP approach can be more closely correlated with plant development and/or function. However, due to a lack of detailed-QMP data, how soil nutrient conditions affect quantitative changes in microbial assembly of the root-associated microbiome remains poorly understood. A recent study quantified the dynamics of the soybean root microbiome, under unbalanced fertilization, using QMP and provided data on the use of specific synthetic communities (SynComs) for sustaining crop productivity. In this editorial, we explore potential opportunities for utilizing QMP to decode the microbiome for sustainable agriculture.

8.
BMC Med ; 22(1): 352, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39218882

ABSTRACT

BACKGROUND: The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment. METHODS: We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA). RESULTS: The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes. CONCLUSIONS: Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features.


Subject(s)
Brain Neoplasms , DNA Methylation , Glioma , Magnetic Resonance Imaging , Humans , Glioma/genetics , Glioma/immunology , DNA Methylation/genetics , Female , Male , Brain Neoplasms/genetics , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Middle Aged , Adult , Machine Learning , Phenotype , Aged , Biomarkers, Tumor/genetics
9.
Cancer Lett ; 601: 217177, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39179096

ABSTRACT

Abnormal metabolism has emerged as a prominent hallmark of cancer and plays a pivotal role in carcinogenesis and progression of lung adenocarcinoma (LUAD). In this study, single-cell sequencing revealed that the metabolic enzyme 6-phosphogluconate dehydrogenase (PGD), which is a critical regulator of the pentose phosphate pathway (PPP), is significantly upregulated in the malignant epithelial cell subpopulation during malignant progression. However, the precise functional significance of PGD in LUAD and its underlying mechanisms remain elusive. Through the integration of TCGA database analysis and LUAD tissue microarray data, it was found that PGD expression was significantly upregulated in LUAD and closely correlated with a poor prognosis in LUAD patients. Moreover, in vitro and in vivo analyses demonstrated that PGD knockout and inhibition of its activity mitigated the proliferation, migration, and invasion of LUAD cells. Mechanistically, immunoprecipitation-mass spectrometry (IP-MS) revealed for the first time that IQGAP1 is a robust novel interacting protein of PGD. PGD decreased p-AMPK levels by competitively interacting with the IQ domain of the known AMPKα binding partner IQGAP1, which promoted glycolysis and fatty acid synthesis in LUAD cells. Furthermore, we demonstrated that the combination of Physcion (a PGD-specific inhibitor) and metformin (an AMPK agonist) could inhibit tumor growth more effectively both in vivo and in vitro. Collectively, these findings suggest that PGD is a potential prognostic biomarker and therapeutic target for LUAD.


Subject(s)
AMP-Activated Protein Kinases , Adenocarcinoma of Lung , Fatty Acids , Glycolysis , Lung Neoplasms , Phosphogluconate Dehydrogenase , Humans , Phosphogluconate Dehydrogenase/genetics , Phosphogluconate Dehydrogenase/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , Animals , Mice , Fatty Acids/metabolism , Fatty Acids/biosynthesis , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Cell Line, Tumor , Cell Proliferation , Female , Signal Transduction , Male , Mice, Nude , Prognosis , Xenograft Model Antitumor Assays , Gene Expression Regulation, Neoplastic , Cell Movement
10.
ACS Nano ; 18(36): 25193-25204, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39193830

ABSTRACT

Opto-electrophysiology neural probes targeting single-cell levels offer an important avenue for elucidating the intrinsic mechanisms of the nervous system using different physical quantities, representing a significant future direction for brain-computer interface (BCI) devices. However, the highly integrated structure poses significant challenges to fabrication processes and the presence of photoelectric artifacts complicates the extraction and analysis of target signals. Here, we propose a highly miniaturized and integrated opto-electrophysiology neural probe for electrical recording and optical stimulation at the single-cell/subcellular level. The design of a total internal reflection layer addresses the photoelectric artifacts that are more pronounced in single-cell devices compared to conventional implantable BCI devices. Finite element simulations and electrical signal tests demonstrate that the opto-electrophysiology neural probe eliminates the photoelectric artifacts in the time domain, which represents a significant breakthrough for optoelectrical integrated BCI devices. Our proposed opto-electrophysiology neural probe holds substantial potential for promoting the development of in vivo BCI devices and developing advanced therapeutic strategies for neurological disorders.


Subject(s)
Artifacts , Neurons , Neurons/physiology , Brain-Computer Interfaces , Animals , Single-Cell Analysis/instrumentation , Humans
11.
Front Vet Sci ; 11: 1394631, 2024.
Article in English | MEDLINE | ID: mdl-39193367

ABSTRACT

Canine distemper (CD) is a virulent disease caused by the canine distemper virus (CDV) in canines and mustelidaes with high mortality. The incidence of CDV is worldwide distribution and it has caused huge economic losses to multiple industries around the world. There are many studies investigating the prevalence of CD infection, but no comprehensive analysis of CDV infection in minks, foxes and raccoon dogs worldwide has therefore been carried out. The aim of this meta is to provide a comprehensive assessment of the prevalence of CDV infection in minks, foxes and raccoon dogs dogs through a meta-analysis of articles published from around the world. Data from 8,582 small carnivores in 12 countries were used to calculate the combined prevalence of CD. A total of 22.6% (1,937/8,582) of minks, foxes and raccoon dogs tested positive for CD. The prevalence was higher in Asia (13.8, 95% CI: 22.2-45.6), especially in South Korea (65.8, 95% CI: 83.3-95.8). Our study found that the incidence of CD was also associated with geographic climate, population size, health status, and breeding patterns. CD is more commonly transmitted in minks, foxes and raccoon dogs. However, the concentrated breeding as an economic animal has led to an increase in the prevalence rate. The difference analysis study recommended that countries develop appropriate preventive and control measures based on the prevalence in the minks, foxes, and raccoon dogs industries, and that reducing stocking density is important to reduce the incidence of CDV. In addition, CDV is more common in winter, so vaccination in winter should be strengthened and expanded to reduce the incidence of CD in minks, foxes and raccoon dogs.

12.
Int J Biol Macromol ; 279(Pt 3): 134991, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39197602

ABSTRACT

In this study, bacterial cellulose (BC) and BC/locust bean gum (LBG) composite produced from banana hydrolysate were both used as the adsorbent for various organic dyes adsorption especially for malachite green (MG) adsorption for the first time. The BC/LBG(2%) composite exhibited significantly enhanced swelling rate and textural characteristics while maintained the basic structure of BC as depicted by XRD, FT-IR, and NMR, providing a foundation for its application as an excellent adsorbent. The composite exhibited a high adsorption rate and adsorption capacity for MG (exceeding 95 % and 2000 mg/g), and had a good selectivity for MG adsorption in the solution containing crystal violet (CV), rhodamine B (RB), and methyl orange (MO). The MG adsorption process conformed to multiple models including Langmuir and pseudo-first-order models. And the adsorption mechanism mainly comprised chemical adsorption (hydrogen bonding and electrostatic interactions) and physical adsorption. The reusability of BC/LBG(2%) composite was attractive for industrial application that the MG adsorption rate reduced merely a little (still higher than 88 %) after the 5th regeneration process. Overall, considering its adsorption capacity, selectivity, and reusability, BC/LBG(2%) composite prepared by in-situ fermentation with LBG addition was a competent adsorbent for MG adsorption and MG containing wastewater treatment.

13.
RNA Biol ; 21(1): 1-15, 2024 Jan.
Article in English | MEDLINE | ID: mdl-39180763

ABSTRACT

Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.


Subject(s)
RNA, Circular , RNA, Messenger , RNA, Circular/genetics , Humans , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA/genetics , RNA/metabolism , Binding Sites , Exons , Gene Expression Regulation , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/genetics , RNA Splicing
14.
Rev Cardiovasc Med ; 25(7): 241, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39139412

ABSTRACT

Background: The improvement rate and predictors of secondary mitral regurgitation in patients with aortic regurgitation undergoing transcatheter aortic valve replacement (TAVR) remain unclear. This study aimed to identify predictors of persistent moderate to severe secondary mitral regurgitation after TAVR in patients with aortic regurgitation by assessing mitral valve geometry with computed tomography (CT). Methods: This retrospective cohort study reviewed 242 consecutive patients with aortic regurgitation who underwent TAVR between May 2014 and December 2022. Patients with primary or less than moderate mitral regurgitation were excluded. Mitral annular dimensions (area, perimeter, anteroposterior, intercommissural, and trigone-to-trigone diameter), mitral valve tenting geometry (mitral valve tenting area [MVTA] and mitral valve tenting height [MVTH]), and papillary muscle displacement were systematically measured at CT. Mitral regurgitation improvement was assessed at 3 months after TAVR by echocardiography. Logistic regression was performed to explore the association of mitral valve geometry with mitral regurgitation improvement after TAVR. Results: A total of 75 patients (mean age, 74 ± 7 years; 32.0% female) with moderate to severe secondary mitral regurgitation were included in the final analysis. Mitral regurgitation improved in 49 patients and remained unchanged in 26 patients. Mitral annular dimensions, including area, perimeter, anteroposterior, and intercommissural diameter, were associated with mitral regurgitation improvement. MVTA and MVTH were risk factors for sustained mitral regurgitation. In addition, QRS duration > 120 ms and atrial fibrillation had an impact on the mitral regurgitation improvement. Mitral annular area (odds ratio [OR], 1.41; 95% confidence interval [CI]: 1.05, 1.90; p = 0.02) and MVTA (OR, 7.24; 95% CI: 1.72, 30.44; p = 0.007) were independent predictors of persistent secondary mitral regurgitation after TAVR. Conclusions: Mitral annular area and MVTA were independent predictors of persistent secondary mitral regurgitation after TAVR.

15.
J Asthma ; : 1-7, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39087928

ABSTRACT

BACKGROUND: Immune cells may have a significant role in the pathophysiology of asthma, according to increasing evidence, although it is yet unclear how immune cells cause asthma. Therefore, we aimed to use Mendelian randomization (MR) methods to investigate this causal relationship. METHODS: This study explored the causal effects between immune cells and asthma using a two-sample MR technique. Using publicly available genetic data, the causal connection between asthma risk and 731 immune cell phenotypes was investigated. Sensitivity analysis guaranteed the results' stability. To further evaluate the existence of reverse causality, we employed reverse MR analysis. RESULTS: According to the inverse-variance weighted (IVW) method, five immune cell phenotypes were found to be statistically significantly associated with asthma risk (p < 0.001). Among them, TCRgd %T cell (OR = 0.968, 95%CI = 0.951 - 0.986), TCRgd %lymphocyte (OR = 0.978, 95%CI = 0.965 - 0.991), HLA DR + NK AC (OR = 0.966, 95% CI = 0.947 - 0.986) and CD3 on CD4 Treg (OR = 0.956, 95%CI= 0.931 - 0.981), four phenotypes that resulted in a decreased risk of asthma. CD25 on transitional (OR = 1.033, 95%CI = 1.014 - 1.052) resulted in an increased risk of asthma. Reverse MR analysis revealed that asthma increases HLA DR + NK AC levels (p < 0.05). CONCLUSION: The results of MR analysis showed a causal relationship between immune cell phenotype and asthma risk, which provides a direction for future asthma treatment.

16.
Sci Adv ; 10(33): eado0112, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39151000

ABSTRACT

Although reactive nitrogen (Nr) emissions from food and energy production contribute to multi-dimensional environmental damages, integrated management of Nr is still lacking owing to unclear future mitigation potentials and benefits. Here, we find that by 2050, high-ambition compared to low-ambition N interventions reduce global ammonia and nitrogen oxide emissions by 21 and 22 TgN/a, respectively, equivalent to 40 and 52% of their 2015 levels. This would mitigate population-weighted PM2.5 by 6 g/m3 and avoid premature deaths by 817 k (16%), mitigate ozone by 4 ppbv, avoid premature deaths by 252k (34%) and crop yield losses by 122 million tons (4.3%), and decrease terrestrial ecosystem areas exceeding critical load by 420 Mha (69%). Without nitrogen interventions, most environmental damages examined will deteriorate between 2015 and 2050; Africa and Asia are the most vulnerable but also benefit the most from interventions. Nitrogen interventions support sustainable development goals related to air, health, and ecosystems.


Subject(s)
Air Pollution , Ecosystem , Nitrogen , Air Pollution/prevention & control , Air Pollutants/analysis , Ammonia , Ozone
17.
Cell Mol Biol Lett ; 29(1): 110, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39153986

ABSTRACT

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. METHODS: To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT-qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1's regulation of autophagy in GC. RESULTS: Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. CONCLUSION: PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC.


Subject(s)
Autophagy , Carrier Proteins , Heterogeneous-Nuclear Ribonucleoproteins , Oxidative Stress , Polypyrimidine Tract-Binding Protein , Stomach Neoplasms , Polypyrimidine Tract-Binding Protein/metabolism , Polypyrimidine Tract-Binding Protein/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Autophagy/genetics , Humans , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Animals , Carrier Proteins/metabolism , Carrier Proteins/genetics , Oxidative Stress/genetics , Cell Line, Tumor , Mice , Disease Progression , Mice, Nude , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , Gene Knockdown Techniques , Mice, Inbred BALB C , Male
18.
J Phys Chem Lett ; 15(34): 8715-8720, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39159485

ABSTRACT

The photoresist formulation is closely related to the material properties, and its composition content determines the lithography imaging quality. To satisfy the process requirements, imaging verification of extensive formulations is required through lithography experiments. Identifying photoresist formulations with a high imaging performance has become a challenge. Herein, we develop a formulation discriminator of a metal oxide nanoparticle photoresist for a contact layer applied to electron beam lithography. This discriminator consists of convolutional neural network photoresist imaging and formulation classification models. A photoresist imaging model is adopted to predict the contact width of variable formulations, while a formulation classification model is used to classify formulations according to relative local critical dimension uniformity (RLCDU). The verification results indicate that the discriminator can accurately recognize photoresist formulations that simultaneously meet the conditions of contact width and RLCDU, and its feasibility has been demonstrated, providing a valuable reference for the preparation of photoresist materials.

19.
Chemistry ; : e202402875, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39148303

ABSTRACT

Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.

20.
Clin Nutr ; 43(9): 2057-2068, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39088962

ABSTRACT

BACKGROUND: The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. METHODS: A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). RESULTS: A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. CONCLUSION: A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone.


Subject(s)
Gastrointestinal Neoplasms , Hand Strength , Nutritional Status , Humans , Male , Female , Aged , Hand Strength/physiology , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/physiopathology , Prognosis , Middle Aged , China/epidemiology , Cohort Studies , Nutrition Assessment , Risk Factors , Proportional Hazards Models , Colorectal Neoplasms/mortality , Colorectal Neoplasms/physiopathology , Kaplan-Meier Estimate , Stomach Neoplasms/mortality , Stomach Neoplasms/physiopathology
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