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1.
Cell Signal ; : 111279, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944255

ABSTRACT

BACKGROUND: The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key role in the regulation of embryonic stem cell proteasome activity. However, the role of PSMD11 in hepatocellular carcinoma has not been studied. In this study, it was found that the expression of PSMD11 in HCC tissues was significantly higher than that in para-cancerous tissues, and was associated with poor prognosis. The results of in vitro experiments showed that PSMD11 knockdown could effectively inhibit the proliferation and apoptosis of hepatoma cell lines, and flow cytometry showed that the G0/G1 phase was significantly prolonged. Through protein spectrometry, immunoprecipitation and in vitro experiments, it was found that PSMD11 can promote the proliferation of hepatocellular carcinoma through regulating the ubiquitination of CDK4 and enhancing its protein stability. This study explores the mechanism of action of PSMD11 in hepatocellular carcinoma and provides new insights for the treatment of hepatocellular carcinoma.

2.
Biochem Pharmacol ; 226: 116374, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38906226

ABSTRACT

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, and its main clinical manifestation is retinal vascular dysfunction. DR causes blindness and is a problem with significant global health implications. However, treating DR is still challenging. In this study, we aimed to explore the role of polo-like kinase-3 (PLK-3) and the potential regulatory mechanism in DR. Sprague-Dawley rats were injected intraperitoneally with streptozotocin (STZ, 60 mg/kg) to induce a rat model of DR, and rat retinal microvascular endothelial cells (RRMECs) were treated with high glucose (HG, 25 mmol/L glucose) to develop a cell model of DR. We found that PLK-3 was significantly downregulated in the retinal tissues of STZ-induced diabetic rats and HG-induced RRMECs. Lentivirus-mediated PLK-3 overexpression alleviated the histological damages in DR rats. After HG stimulation, cell proliferation, migration, and angiogenesis in RRMECs were inhibited after PLK-3 upregulation. By using label-free proteomics, we identified 82 differentially expressed proteins downstream of PLK-3, including BRCA1-associated protein 1 (BAP1), which was significantly upregulated in PLK-3-overexpressed RRMECs compared to control cells under the HG condition. In vivo and in vitro assays indicated that the forced expression of PLK-3 increased the phosphorylation of BAP1 at serine 592 and caspase-8 expression. Detailed evidence showed that BAP1-shRNA-mediated knockdown restored the cell function in HG-treated RRMECs when PLK-3 was overexpressed. Collectively, this study shows that PLK-3 alleviates retinal vascular dysfunction in DR by inhibiting the phosphorylation of BAP1. Thus, PLK-3 may develop as a promising target for the therapy of DR.

3.
J Inflamm Res ; 17: 3879-3891, 2024.
Article in English | MEDLINE | ID: mdl-38911986

ABSTRACT

Background: Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients. Methods: A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission. Results: Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002-1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935-0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000-1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154-2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 -0.981). Conclusion: sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.

4.
RSC Adv ; 14(25): 17547-17556, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38828273

ABSTRACT

Dredged sediment poses significant challenges for transportation and subsequent treatment due to its high water content and large volume. Coagulation, a common method of dewatering, can significantly enhance the dewatering performance of dredged sediment. This study synthesized a cationic starch-based flocculant [starch-3-chloro-2-hydroxypropyl trimethylammonium chloride (St-CTA)] through etherification for the flocculation dewatering of dredged sediment. The effectiveness and mechanism of St-CTA as a dewatering flocculant for dredged sediment were investigated. The results demonstrated that when the dosage of St-CTA was 12 mg g-1 TSS (total suspended solids), the dehydration property of dredged sediment substantially improved, with the specific resistance to filtration (SRF) decreasing by 93.3%, the capillary suction time (CST) by 93.5%, and the water content of the filter cake (WC) by 9.7%. The removal rate of turbidity of the supernatant from the conditioned dredged sediment reached 99.6%, accelerating the settling speed and effectively capturing and separating fine particles from the sediment. St-CTA significantly increased the median particle size (D50), altered the microstructure and extracellular polymeric substances (EPS) of the flocs, and increased the fractal dimension of the flocs, making them more compact and conducive to the formation of drainage channels. These findings confirm the feasibility of using potentially environmentally friendly St-CTA as a rapid dewatering conditioning agent for sediment.

5.
Comput Biol Med ; 178: 108703, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38850961

ABSTRACT

Most cancer types have both diffuse and non-diffuse subtypes, which have rather distinct morphologies, namely scattered tiny tumors vs. one solid tumor, and different levels of aggressiveness. However, the causes for forming such distinct subtypes remain largely unknown. Using the diffuse and non-diffuse gastric cancers (GCs) as the illustrative example, we present a computational study based on the transcriptomic data from the TCGA and GEO databases, to address the following questions: (i) What are the key molecular determinants that give rise to the distinct morphologies between diffuse and non-diffuse cancers? (ii) What are the main reasons for diffuse cancers to be generally more aggressive than non-diffuse ones of the same cancer type? (iii) What are the reasons for their distinct immunoactivities? And (iv) why do diffuse cancers on average tend to take place in younger patients? The study is conducted using the framework we have previously developed for elucidation of general drivers cancer formation and development. Our main discoveries are: (a) the level of (poly-) sialic acids deployed on the surface of cancer cells is a significant factor contributing to questions (i) and (ii); (b) poly-sialic acids synthesized by ST8SIA4 are the key to question (iii); and (c) the circulating growth factors specifically needed by the diffuse subtype dictate the answer to question (iv). All these predictions are substantiated by published experimental studies. Our further analyses on breast, prostate, lung, liver, and thyroid cancers reveal that these discoveries generally apply to the diffuse subtypes of these cancer types, hence indicating the generality of our discoveries.

6.
Cancer Lett ; 597: 217059, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876383

ABSTRACT

5-Methylcytosine (m5C) methylation is a significant post-transcriptional modification that play a crucial role in the development and progression of numerous cancers. Whereas the functions and molecular mechanisms underlying m5C methylation in gliomas remain unclear. This study dedicated to explore changes of m5C levels and the clinical significance of the m5C writer NSUN4 in gliomas. We found that high m5C levels were negatively related to prognosis of patients with glioma. Moreover, gain- and loss-of-function experiments revealed the role of NSUN4 in enhancing m5C modification of mRNA to promote the malignant progression of glioma. Mechanistically speaking, NSUN4-mediated m5C alterations regulated ALYREF binding to CDC42 mRNA, thereby impacting the mRNA stability of CDC42. We also demonstrated that CDC42 promoted glioma proliferation, migration, and invasion by activating the PI3K-AKT pathway. Additionally, rescue experiments proved that CDC42 overexpression weaken the inhibitory effect of NSUN4 knockdown on the malignant progression of gliomas in vitro and in vivo. Our findings elucidated that NSUN4-mediated high m5C levels promote ALYREF binding to CDC42 mRNA and regulate its stability, thereby driving the malignant progression of glioma. This provides theoretical support for targeted the treatment of gliomas.

7.
J Environ Manage ; 364: 121451, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38878576

ABSTRACT

A double-decision optimization model based on the road grade optimization strategy and considered comprehensive traffic environment benefit is proposed to control the traffic noise. The upper-level model maximizes the comprehensive traffic environment benefit, including network noise emission and traffic efficiency. Adjusting the emphasis on noise optimization benefits and traffic efficiency in road network planning through setting weights. The lower-level resolves the question of network traffic flow assignment using a stochastic user-equilibrium model. The increase of traffic environment demand, network noise emissions decrease and travel time rises. In the case, with a low environmental requirement (weighting with 1.1), the sound pressure emission of the network decreases by 9.23% with only a 4.01% increase in travel time. Under the high environmental requirement (weighting with 0.2), the sound pressure decreases by 26.8%, but the travel time rises by as high as 30.9%. The network is optimized towards road grade degradation and is the first to optimize the arterial roads. In addition, it is found that the influence of speed on traffic noise is greater than that of traffic volume through case validation. This method proposing traffic noise optimization strategies at the road network planning level provides technical support for the proactive governance of traffic noise pollution and the improvement of traffic sound environment quality.


Subject(s)
Noise, Transportation , Noise, Transportation/prevention & control , Noise , Models, Theoretical , Cities
8.
Methods ; 228: 38-47, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38772499

ABSTRACT

Human leukocyte antigen (HLA) molecules play critically significant role within the realm of immunotherapy due to their capacities to recognize and bind exogenous antigens such as peptides, subsequently delivering them to immune cells. Predicting the binding between peptides and HLA molecules (pHLA) can expedite the screening of immunogenic peptides and facilitate vaccine design. However, traditional experimental methods are time-consuming and inefficient. In this study, an efficient method based on deep learning was developed for predicting peptide-HLA binding, which treated peptide sequences as linguistic entities. It combined the architectures of textCNN and BiLSTM to create a deep neural network model called APEX-pHLA. This model operated without limitations related to HLA class I allele variants and peptide segment lengths, enabling efficient encoding of sequence features for both HLA and peptide segments. On the independent test set, the model achieved Accuracy, ROC_AUC, F1, and MCC is 0.9449, 0.9850, 0.9453, and 0.8899, respectively. Similarly, on an external test set, the results were 0.9803, 0.9574, 0.8835, and 0.7863, respectively. These findings outperformed fifteen methods previously reported in the literature. The accurate prediction capability of the APEX-pHLA model in peptide-HLA binding might provide valuable insights for future HLA vaccine design.


Subject(s)
Histocompatibility Antigens Class I , Peptides , Protein Binding , Humans , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class I/metabolism , Peptides/chemistry , Peptides/immunology , Deep Learning , HLA Antigens/immunology , HLA Antigens/genetics , Neural Networks, Computer , Computational Biology/methods
9.
Reprod Biol ; 24(2): 100889, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38733657

ABSTRACT

Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process of follicle development and is associated with various ovarian diseases. This review aims to provide a comprehensive overview of mitophagy regulation, emphasizing its role at different stages of follicular development. Additionally, the study illuminates the relationship between mitophagy and ovarian diseases, including ovary aging (OA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS). A detailed understanding of mitophagy could reveal valuable insights and novel strategies for managing female ovarian reproductive health.


Subject(s)
Mitophagy , Ovarian Follicle , Mitophagy/physiology , Female , Ovarian Follicle/physiology , Humans , Animals , Mitochondria/physiology , Mitochondria/metabolism , Primary Ovarian Insufficiency
10.
Cancer Manag Res ; 16: 403-420, 2024.
Article in English | MEDLINE | ID: mdl-38736589

ABSTRACT

Background: Chemokines and chemokine receptors (CCRs) are involved in a variety of anti-tumour and pro-tumour immune processes in vivo, such as angiogenesis, metastasis, proliferation and invasiveness, and influence patient prognosis and response to therapy. Methods: CCRs differentially expressed in HCC and associated with prognosis were extracted from TCGA and GEO databases, and the obtained CCRs were then used to construct signature genes, and the signature gene were selected for expression validation as well as functional experiments to explore the role of CCRs in the treatment and prognosis of HCC. Results: We constructed a prognostic model including five CCRs (CCL20, CCL23, CCR3, CCR10, and CXCR3) and validated the expression of signature genes. The model's risk score is an independent prognostic factor for HCC. We have also developed prognostic model nomograms for clinical use. In addition, we validated that CCR3 expression is associated with poor prognosis in HCC, and the proliferation and migration ability of HCC cells was significantly inhibited after interfering with the expression of CCR3 in MHCC-LM3. We also looked at differences in pathway enrichment, immune infiltration and immune checkpoints. Finally, we found that risk scores were also correlated with drug sensitivity, the high-risk group had a better sensitivity to sorafenib. Conclusion: The CCRs-related gene signature may better assess HCC prognosis and response to immunotherapy and tyrosine kinase inhibitors such as sorafenib in HCC, providing prospective solutions for diagnosis and treatment.

11.
ACS Med Chem Lett ; 15(5): 595-601, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38746892

ABSTRACT

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

12.
Sci Rep ; 14(1): 9196, 2024 04 22.
Article in English | MEDLINE | ID: mdl-38649699

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Uncontrolled cell proliferation, invasion and migration of pancreatic cancer cells are the fundamental causes of death in PDAC patients. Our previous studies showed that KLF9 inhibits the proliferation, invasion and migration of pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In this study, we found that platelet-activating factor acetylhydrolase IB3 (PAFAH1B3) is highly expressed in pancreatic cancer tissues and cells. In vitro and in vivo studies showed that overexpression of PAFAH1B3 promoted the proliferation and invasion of pancreatic cancer cells, while downregulation of PAFAH1B3 inhibited these processes. We found that KLF9 expression is negatively correlated with PAFAH1B3 expression in pancreatic cancer tissues and cells. Western blotting revealed that KLF9 negatively regulates the expression of PAFAH1B3 in pancreatic cancer tissues and cells. Rescue experiments showed that overexpression of PAFAH1B3 could partially attenuate the suppression of pancreatic cancer cell proliferation, invasion and migration induced by KLF9 overexpression. Finally, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried out, and the results showed that KLF9 directly binds to the promoter of PAFAH1B3 and inhibits its transcriptional activity. In conclusion, our study indicated that KLF9 can inhibit the proliferation, invasion, migration and metastasis of pancreatic cancer cells by inhibiting PAFAH1B3.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors , Pancreatic Neoplasms , Animals , Female , Humans , Male , Mice , 1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism
13.
Virol J ; 21(1): 96, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671532

ABSTRACT

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.


Subject(s)
Biomarkers , COVID-19 , Adult , Aged , Female , Humans , Male , Middle Aged , Biomarkers/blood , COVID-19/mortality , COVID-19/blood , COVID-19/diagnosis , Inflammation/blood , Lipopolysaccharide Receptors/blood , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , ROC Curve , SARS-CoV-2/physiology , Severity of Illness Index
14.
Sci Total Environ ; 927: 172160, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38575030

ABSTRACT

Recovering gold from wastewater has both economic and environmental benefits. However, how to effectively recover it is challenging. In this work, a novel Fe-based metal-organic framework (MOF) was synthesized and decorated with 2,5-thiophenedicarboxylic acid to have a well-developed porous architecture to effectively recover Au(III) from water. The maximum Au(III) sorption capacity by the finally-synthesized porous material MIL-101(Fe)-TDCA reached 2350 mg/g at pH = 6.00 ± 0.15, which is one of the highest among all literature-reported relevant materials including MOFs, and high sorption strength can be maintained within a wide pH range from 2.0 to 10.0. Besides, Au(III) sorption efficiency at low concentrations (i.e., 3.5 × 104 mg/mL) reached over 99%. Mechanically, outstanding Au(III) sorption by MIL-101(Fe)-TDCA resulted from the O/N/S-containing moieties on its surface, large surface area and porosity. The N- and S-containing functionalities (CS, CONH) served as electron donors to chelate Au(III). The O-containing (FeOFe, COFe, COOH, and coordinated H2O) and N-containing (CONH) moieties on MIL-101(Fe)-TDCA interacted with OH groups on the hydrolyzed species of Au(III) (AuCl3(OH)-, AuCl2(OH)2-, and AuCl(OH)3-) by hydrogen bond, which further increased Au(III) sorption. Furthermore, about 45.71% of Au(III) was reduced to gold nanoparticles by CS groups on the decorated 2,5-dithiophene dicarboxylic acid during sorption on MIL-101(Fe)-TDCA. Over 98.35% of Au(III) was selectively sorbed on MIL-101(Fe)-TDCA at pH 4.0, much higher than that of the coexisting heavy metal ions including Cu(II), Zn(II), Pb(II), and Ni(II) (< 5%), despite their same concentration at 0.01 mg/mL. Although sorption selectivity of a noble metal Pt(IV) by MIL-101(Fe)-TDCA is relatively poor (68.23%), it could be acceptable. Moreover, reusability of MIL-101(Fe)-TDCA is also excellent, since above 90.5% Au(III) still can be sorbed after two sorption-desorption cycles. Overall, excellent sorption performance and the roughly-calculated gold recycling benefits (26.30%) highlight that MIL-101(Fe)-TDCA is a promising porous material for gold recovery from the aqueous phase.

15.
Nat Commun ; 15(1): 3489, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664426

ABSTRACT

The polar oceans play a vital role in regulating atmospheric CO2 concentrations (pCO2) during the Pleistocene glacial cycles. However, despite being the largest modern reservoir of respired carbon, the impact of the subarctic Pacific remains poorly understood due to limited records. Here, we present high-resolution, 230Th-normalized export productivity records from the subarctic northwestern Pacific covering the last five glacial cycles. Our records display pronounced, glacial-interglacial cyclicity superimposed with precessional-driven variability, with warm interglacial climate and high boreal summer insolation providing favorable conditions to sustain upwelling of nutrient-rich subsurface waters and hence increased export productivity. Our transient model simulations consistently show that ice sheets and to a lesser degree, precession are the main drivers that control the strength and latitudinal position of the westerlies. Enhanced upwelling of nutrient/carbon-rich water caused by the intensification and poleward migration of the northern westerlies during warmer climate intervals would have led to the release of previously sequestered CO2 from the subarctic Pacific to the atmosphere. Our results also highlight the significant role of the subarctic Pacific in modulating pCO2 changes during the Pleistocene climate cycles, especially on precession timescale ( ~ 20 kyr).

16.
Cell Commun Signal ; 22(1): 168, 2024 03 07.
Article in English | MEDLINE | ID: mdl-38454413

ABSTRACT

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.


Subject(s)
Colorectal Neoplasms , Animals , Humans , Mice , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes , Colorectal Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating , Nuclear Proteins , Repressor Proteins , Tumor Escape
17.
Chemosphere ; 357: 141854, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38556181

ABSTRACT

This study investigates the nitrogen removal efficacy and microbial community dynamics in seawater aquaculture effluent treatment using three different substrate combinations of microscale laboratory aerated filters (MFs) - MF1 (LECA), MF2 (LECA/Fe-C), and MF3 (LECA/Pyrite). The findings indicated that the COD removal exceeded 95% across all MFs, with higher removal efficiencies in MF2 and MF3. In terms of nitrogen removal performance, MF2 exhibited the highest average nitrogen removal of 93.17%, achieving a 12.35% and 3.56% increase compared to MF1 (80.82%) and MF3 (89.61%), respectively. High-throughput sequencing analysis revealed that the Fe-C substrate significantly enhanced the diversity of the microbial community. Notably, in MF2, the salinophilic denitrifying bacterium Halomonas was significantly enriched, accounting for 42.6% of the total microbial community, which was beneficial for nitrogen removal. Moreover, an in-depth analysis of nitrogen metabolic pathways and microbial enzymes indicated that MF2 and MF3 possessed a high abundance of nitrification and denitrification enzymes, related to the high removal rates of NH4+-N and NO3--N. Therefore, the combination of LECA with iron-based materials significantly enhances the nitrogen removal efficiency from mariculture wastewater.


Subject(s)
Aquaculture , Denitrification , Iron , Microbiota , Nitrogen , Waste Disposal, Fluid , Wastewater , Wastewater/chemistry , Wastewater/microbiology , Nitrogen/metabolism , Nitrogen/analysis , Iron/metabolism , Waste Disposal, Fluid/methods , Seawater/microbiology , Filtration/methods , Nitrification , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/metabolism , Water Purification/methods
18.
Se Pu ; 42(3): 282-290, 2024 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-38503705

ABSTRACT

Saussurea costus, a perennial herb belonging to the Asteraceae family, is a vital ingredient in traditional Chinese medicine. Increased demands for the herb have led to its widespread cultivation in China, but the corresponding increase in pesticide use has raised concerns about pesticide residues. Such residues would affect the safety and global market potential of Saussurea costus. Thus, a simple method is crucial to detect pesticide residues. The QuEChERS technique, in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS), is commonly used for residue detection. However, traditional adsorbents may be unable to purify complex herbal mixtures well, affecting accuracy and instrument performance. Choosing suitable purification materials for Saussurea costus samples with complex matrices is of significant importance. This study focused on the detection of 35 prohibited pesticides in Saussurea costus. A rapid detection method was established by combining the QuEChERS technique with GC-MS/MS and utilizing a combination of multiwalled carbon nanotubes (MWCNTs), octadecylsilane-bonded silica gel (C18), and anhydrous magnesium sulfate (MgSO4) as the purification adsorbent. The samples were extracted with acetonitrile, purified by an improved QuEChERS process, subjected to GC-MS/MS analysis in multiple reaction monitoring (MRM) mode, and quantified using the internal standard method. The purification effects of four materials (C18, MWCNTs, N-propyl ethylenediamine (PSA), and graphitized carbon black (GCB)) and their optimal dosages were investigated by considering the matrix characteristics of the samples. An orthogonal experimental design was employed to optimize the ratio of adsorbent combinations, and the optimal adsorbent combination was determined to be 450 mg of MgSO4, 400 mg of C18, and 50 mg of MWCNTs. Matrix effect (ME) evaluation of the S. costus matrix showed that 31 target compounds strongly exhibited matrix-enhancement effects. Thus, matrix-matched calibration was employed in this study. Methodological investigation revealed that the standard curves for the 35 pesticides exhibited good linearity, with correlation coefficients (r2) greater than 0.9970. The average recoveries at three spiked levels ranged from 69.6% to 126.9%, and the relative standard deviations (RSDs) for parallel groups were all less than 10%. The limits of detection (LODs) and quantification (LOQs) ranged from 0.2 to 5.4 µg/kg and from 0.6 to 18.1 µg/kg, respectively. The developed method was used to screen and detect 35 pesticide residues in 20 batches of S. costus samples, and the target compounds were detected in six batches. The proposed method is simple, sensitive, and accurate. Thus, it is suitable for the rapid screening and detection of the 35 pesticide residues in S. costus and provides technical support for the cultivation, production, and quality control of the herb.


Subject(s)
Nanotubes, Carbon , Pesticide Residues , Saussurea , Tandem Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry/methods , Nanotubes, Carbon/analysis , Nanotubes, Carbon/chemistry , Pesticide Residues/analysis
19.
Sensors (Basel) ; 24(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38544076

ABSTRACT

Radio frequency identification (RFID) is well known as an identification, track, and trace approach and is considered to be the key physical layer technology for the industrial internet of things (IIoT). However, IIoT systems have to introduce additional complex sensor networks for pervasive monitoring, and there are still challenges related to item-level sensing and data recording. To overcome the shortage, this work proposes an artificial intelligence (AI)-assisted RFID-based multi-sensing technology. Both passive and semi-passive RFID tag-integrated multi-sensors are developed. The main contributions and the novelty of this investigation are as follows. A UHF RFID tag-integrated multi-sensor with a boosted charge pump is proposed; it enables high RF signal sensitivity and a long operational range. The whole hardware design, including the antenna and energy harvester, are studied. Moreover, a demonstration with real-world ham product sensing data is conducted. This work also proposes and successfully demonstrates the integration of machine learning algorithms, specifically the NARX neural network, with RFID sensing data for food product quality assessment and sensing (QAS). This application of machine learning to RFID-generated data for quality assessment is also a novel aspect of the research. The deployment of an autoregressive model with an exogenous input (NARX) neural network model, tailored for nonlinear processes, emerges as the most effective, achieving a root mean square error (RMSE) of 0.007 and an R-squared value of 0.99 for ham product QAS. By deploying the technology, low-cost, timely, and flexible product QAS can be achieved in manufacturing industries, which helps product quality improvement and the optimization of the manufacturing line and supply chain.

20.
Materials (Basel) ; 17(5)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38473571

ABSTRACT

This study investigates the influence of varying austenitizing temperatures on the microstructure and mechanical properties of 35Si2MnCr2Ni3MoV steel, utilizing Charpy impact testing and microscopic analysis techniques such as scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The findings reveal that optimal combination of strength and toughness is achieved at an austenitizing temperature of 980 °C, resulting in an impact toughness of 67.2 J and a tensile strength of 2032 MPa. The prior austenite grain size initially decreases slightly with increasing temperature, then enlarges significantly beyond 1100 °C. The martensite blocks' and packets' structures exhibit a similar trend. The proportion of high-angle grain boundaries, determined by the density of the packets, peaks at 980 °C, providing maximal resistance to crack propagation. The amount of retained austenite increases noticeably after 980 °C; beyond 1200 °C, the coarsening of packets and a decrease in density reduce the likelihood of trapping retained austenite. Across different austenitizing temperatures, the steel demonstrates superior crack initiation resistance compared to crack propagation resistance, with the fracture mode transitioning from ductile dimple fracture to quasi-cleavage fracture as the austenitizing temperature increases.

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