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1.
Artículo en Inglés | MEDLINE | ID: mdl-39093673

RESUMEN

Teaching Visual Question Answering (VQA) models to refrain from answering unanswerable questions is necessary for building a trustworthy AI system. Existing studies, though have explored various aspects of VQA but somewhat ignored this particular attribute. This paper aims to bridge the research gap by contributing a comprehensive dataset, called UNK-VQA. The dataset is specifically designed to address the challenge of questions that models do not know. To this end, we first augment the existing data via deliberate perturbations on either the image or question. In specific, we carefully ensure that the question-image semantics remain close to the original unperturbed distribution. By this means, the identification of unanswerable questions becomes challenging, setting our dataset apart from others that involve mere image replacement. We then extensively evaluate the zero- and few-shot performance of several emerging multi-modal large models and discover their significant limitations when applied to our dataset. Additionally, we also propose a straightforward method to tackle these unanswerable questions. This dataset, we believe, will serve as a valuable benchmark for enhancing the abstention capability of VQA models, thereby leading to increased trustworthiness of AI systems. We have made the dataset available to facilitate further exploration in this area.

2.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167447, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39089636

RESUMEN

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which serves the critical pillar for the treatment of non-small cell lung cancer (NSCLC). However, the acquired resistance remains a challenge for its clinical application, for which, practical strategies to reverse gefitinib resistance in NSCLC are necessary. Ferroptosis, a programmed cell death driven by ferritin-dependent lipid peroxidation, involves in NSCLC progression and related chemoresistance. In our previous work, the self-synthesised EGFR inhibitor Yfq07 (N4, N6-disubstituted pyrimidine-4,6-diamine derivatives) displayed a considerable inhibitory effect on NSCLC both in vitro and in vivo. Herein, we observed that Yfq07 suppressed the proliferation of PC-9GR and HCC827GR cells, two gefitinib resistance NSCLC cell lines. Mechanically, Yfq07 inhibited the phosphorylation of the Discoidin Domain Receptor 1 (DDR1), a receptor tyrosine kinase (RTK) highly expressed in multiple cancers, accompanied by downregulated miR-3648 and upregulated SOCS2. Inhibition or knockdown of DDR1 suppressed the proliferation, migration, and invasion of gefitinib-resistant NSCLC cells, and on the other hand, also downregulated miR-3648 and promoted SOCS2 expression. More specifically, miR-3648 targeted the 3'UTR segment of SOCS2 mRNA and thus affecting the P-ERK signalling pathway to regulate the malignant behaviors of gefitinib-resistant NSCLC cells. Furthermore, Yfq07 also indirectly induced the ferroptosis of gefitinib-resistant NSCLC cells via SOCS2 triggered inhibition of xCT-GPX4 pathway. In conclusion, our study indicates that DDR1 inhibitor Yfq07 promotes ferroptosis and reverses gefitinib-resistance of NSCLC through DDR1-miR-3648-SOCS2 signalling pathway, which provides insights for targeted therapy of gefitinib-resistant NSCLC and drug developments targeting ferroptosis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptor con Dominio Discoidina 1 , Resistencia a Antineoplásicos , Ferroptosis , Gefitinib , Neoplasias Pulmonares , Ferroptosis/efectos de los fármacos , Humanos , Gefitinib/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Línea Celular Tumoral , Receptor con Dominio Discoidina 1/metabolismo , Receptor con Dominio Discoidina 1/genética , Proliferación Celular/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Ratones , Proteínas Supresoras de la Señalización de Citocinas
3.
Angew Chem Int Ed Engl ; : e202411361, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39073279

RESUMEN

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

4.
Gut ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38955401

RESUMEN

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.

5.
Aging (Albany NY) ; 16(11): 10142-10164, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38870259

RESUMEN

HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.


Asunto(s)
Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Ubiquitinación , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Ubiquitinación/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Pronóstico , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Masculino , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Transcriptoma
6.
Artículo en Inglés | MEDLINE | ID: mdl-38879151

RESUMEN

The thermogenic capacity of brown adipose tissue (BAT) in rodents decreases with prolonged heat exposure. However, the underlying mechanisms are not well understood. In this study, Kunming mice were acclimated at 23 ± 1 °C and 33 ± 1 °C for four weeks each to examine the body heat balance and BAT alterations. Results showed that heat-acclimated Kunming mice exhibited reduced body mass and elevated body temperature. Additionally, they displayed lower resting metabolic rates, diminished non-shivering thermogenesis, and reduced BAT thermogenic function. Metabolically, there was a significant reduction in several key metabolites involved in energy metabolism in BAT, including thiamine pyrophosphate, citric acid, cis-Aconitate, isocitric acid, oxoglutaric acid, succinate, fumarate, L-Malic acid, oxaloacetate, flavin mononucleotide, nicotinamide adenine dinucleotide, and adenosine 5'-triphosphate. These findings suggest that BAT adapts to heat acclimation by regulating pathways related to pyruvate oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, which may help maintain thermal homeostasis in Kunming mice.


Asunto(s)
Tejido Adiposo Pardo , Metabolismo Energético , Termogénesis , Animales , Tejido Adiposo Pardo/metabolismo , Ratones , Masculino , Aclimatación/fisiología , Calor
7.
Plants (Basel) ; 13(12)2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38931091

RESUMEN

Glutamine synthetase (GS) is a key enzyme involved in nitrogen metabolism. GS can be divided into cytosolic and plastidic subtypes and has been reported to respond to various biotic and abiotic stresses. However, little research has been reported on the function of GS in mulberry. In this study, the full length of MaGS2 was cloned, resulting in 1302 bp encoding 433 amino acid residues. MaGS2 carried the typical GS2 motifs and clustered with plastidic-subtype GSs in the phylogenetic analysis. MaGS2 localized in chloroplasts, demonstrating that MaGS2 is a plastidic GS. The expression profile showed that MaGS2 is highly expressed in sclerotiniose pathogen-infected fruit and sclerotiniose-resistant fruit, demonstrating that MaGS2 is associated with the response to sclerotiniose in mulberry. Furthermore, the overexpression of MaGS2 in tobacco decreased the resistance against Ciboria shiraiana, and the knockdown of MaGS2 in mulberry by VIGS increased the resistance against C. shiraiana, demonstrating the role of MaGS2 as a negative regulator of mulberry resistance to C. shiraiana infection.

8.
Nanomicro Lett ; 16(1): 228, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935160

RESUMEN

Ammonia (NH3) is a carbon-free, hydrogen-rich chemical related to global food safety, clean energy, and environmental protection. As an essential technology for meeting the requirements raised by such issues, NH3 capture has been intensively explored by researchers in both fundamental and applied fields. The four typical methods used are (1) solvent absorption by ionic liquids and their derivatives, (2) adsorption by porous solids, (3) ab-adsorption by porous liquids, and (4) membrane separation. Rooted in the development of advanced materials for NH3 capture, we conducted a coherent review of the design of different materials, mainly in the past 5 years, their interactions with NH3 molecules and construction of transport pathways, as well as the structure-property relationship, with specific examples discussed. Finally, the challenges in current research and future worthwhile directions for NH3 capture materials are proposed.

9.
Int J Mol Sci ; 25(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38791191

RESUMEN

Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.


Asunto(s)
Hidrogeles , Neoplasias , Hidrogeles/química , Humanos , Porosidad , Animales , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia/métodos , Inmunomodulación/efectos de los fármacos , Ingeniería de Tejidos/métodos , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/uso terapéutico , Microambiente Tumoral/inmunología
10.
Heliyon ; 10(10): e30827, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38765048

RESUMEN

Neutrophil extracellular traps (NETs) and other factors play a significant role in impacting the prognosis of patients with Hepatocellular carcinoma (HCC). Nevertheless, further research is warranted to fully elucidate the prognostic implications of NETs in patients with HCC. We employed a hierarchical clustering technique to examine the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data and identified subtypes associated with NETs. Subsequently, we utilized LASSO regression analysis to identify a distinct gene expression pattern within these subtypes. The strength of this signature was further validated through analysis of TCGA-LIHC and International Cancer Genome Consortium-Liver Cancer (ICGC-LIRI-JP) data. Our findings resulted in the construction of a six-gene signature related to NETs, which can predict survival outcomes in HCC patients. To enhance the predictive accuracy of our tool, we developed a nomogram that integrates the NETs signature with clinicopathological characteristics. We validated the significance of NETs in HCC patients using qRT-PCR and immunohistochemistry assays, along with in vitro experiments targeting high-risk genes. Furthermore, our exploration of the immune microenvironment uncovered augmented immune-specific metrics within the low-risk cohort, implying potential disparities in immune-related attributes between the high-risk and low-risk contingents. In summary, the NETs signature we discovered serves as a valuable biomarker and provides guidance for personalized therapy in HCC patients.

11.
Mar Pollut Bull ; 203: 116424, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692004

RESUMEN

Bloom-induced macroalgal enrichment on the seafloor can substantially facilitate dissolved sulfide (DS) production through sulfate reduction. The reaction of DS with sedimentary reactive iron (Fe) is the main mechanism of DS consumption, which however usually could not effectively prevent DS accumulation caused by pulsed macroalgal enrichment. Here we used incubations to investigate the performance of Fe-rich red soil for buffering of DS produced from macroalgae (Ulva prolifera)-enriched sediment. Based on our results, a combination of red soil additions (6.8 kg/m2) before and immediately after pulsed macroalgal deposition (455 g/m2) can effectively cap DS within the red soil layer. The effective DS buffering is mainly due to ample Fe-oxide surface sites available for reaction with DS. Only a small loss (4 %) of buffering capacity after 18-d incubation suggests that the red soil is capable of prolonged DS buffering in macroalgae-enriched sediments.


Asunto(s)
Sedimentos Geológicos , Hierro , Suelo , Sulfuros , Ulva , Sulfuros/análisis , Sedimentos Geológicos/química , Suelo/química , Algas Marinas , Algas Comestibles
12.
Front Chem ; 12: 1384301, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562527

RESUMEN

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks. Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers. Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 µM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties. Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study's mechanistic exploration, highlighting B7's simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.

13.
Curr Med Chem ; 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38310387

RESUMEN

BACKGROUND: The High Mobility Group Nucleosomal Binding Domain 1 Gene (HMGN1) is crucial for epigenetic regulation. However, the specific function of HMGN1 in cancer development is unclear. METHODS: Raw data on HMGN1 expression were procured from Genotype-Tissue Expression (GTEx), the University of Alabama- Birmingham CANcer data analysis Portal (UALCAN), and The Cancer Genome Atlas (TCGA). Thereafter, the pan-cancer analysis was implemented to understand the HMGN1 expression patterns, prognostic value, and immunological features. Furthermore, the Gene Set Enrichment Analysis (GSEA) was executed via R language. In addition, the relationship between HMGN1 and the sensitivity of antitumor drugs was also determined. Finally, real-time PCR (RT-PCR) experiments were carried out. RESULTS: Pan-cancer analysis revealed that HMGN1 was upregulated in several solid tumors and was associated with pathological staging and poor prognosis. In addition, HMGN1 was found to be involved in regulating the tumor microenvironment. The GSEA enrichment analysis indicated that HMGN1 assisted in the regulation of oncogenic processes, especially metabolic and immune pathways. Furthermore, HMGN1 expression was linked to microsatellite instability (MSI) and tumor mutational burden (TMB) across diverse tumor types. RT-PCR assays indicated that HMGN1 was overexpressed in the gastric and breast cancer cell lines and tissues. CONCLUSION: This study highlighted the potential of HMGN1 as a biomarker for pan- - cancer analysis.

14.
J Biomol Struct Dyn ; : 1-13, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38381715

RESUMEN

Renal fibrosis plays a crucial role in the progression of renal diseases, yet the lack of effective diagnostic markers poses challenges in scientific and clinical practices. In this study, we employed machine learning techniques to identify potential biomarkers for renal fibrosis. Utilizing two datasets from the GEO database, we applied LASSO, SVM-RFE and RF algorithms to screen for differentially expressed genes related to inflammatory responses between the renal fibrosis group and the control group. As a result, we identified four genes (CCL5, IFITM1, RIPK2, and TNFAIP6) as promising diagnostic indicators for renal fibrosis. These genes were further validated through in vivo experiments and immunohistochemistry, demonstrating their utility as reliable markers for assessing renal fibrosis. Additionally, we conducted a comprehensive analysis to explore the relationship between these candidate biomarkers, immunity, and drug sensitivity. Integrating these findings, we developed a nomogram with a high discriminative ability, achieving a concordance index of 0.933, enabling the prediction of disease risk in patients with renal fibrosis. Overall, our study presents a predictive model for renal fibrosis and highlights the significance of four potential biomarkers, facilitating clinical diagnosis and personalized treatment. This finding presents valuable insights for advancing precision medicine approaches in the management of renal fibrosis.Communicated by Ramaswamy H. Sarma.

15.
World J Emerg Med ; 15(1): 28-34, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38188557

RESUMEN

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that causes bacterial pneumonia. However, with increasing bacterial resistance, there is an urgent need to develop new drugs to treat S. pneumoniae infections. Nanodefensin with a 14-carbon saturated fatty acid (ND-C14) is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of human α-defensin 5 (HD5) via an amide bond. However, it is unclear whether ND-C14 is effective against lung infections caused by S. pneumoniae. METHODS: In vitro, three groups were established, including the control group, and the HD5 and ND-C14 treatment groups. A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S. pneumoniae. The morphological changes of S. pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy. In vivo, mice were divided into sham, vehicle, and ND-C14 treatment groups. Mice in the sham group were treated with 25 µL of phosphate-buffered saline (PBS). Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25 µL of bacterial suspension with 2×108 CFU/mL (total bacterial count: 5×106 CFU), and then the mice were given 25 µL PBS or intratracheally injected with 25 µL of ND-C14 (including 20 µg or 50 µg), respectively. Survival rates were evaluated in the vehicle and ND-C14 treatment groups. Bacterial burden in the blood and bronchoalveolar lavage fluid were counted. The lung histology of the mice was assessed. A propidium iodide uptake assay was used to clarify the destructive effect of ND-C14 against S. pneumoniae. RESULTS: Compared with HD5, ND-C14 had a better bactericidal effect against S. pneumoniae because of its stronger ability to destroy the membrane structure of S. pneumoniae in vitro. In vivo, ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S. pneumoniae. ND-C14 reduced bacterial burden and lung tissue injury. Moreover, ND-C14 had a membrane permeation effect on S. pneumoniae, and its destructive ability increased with increasing ND-C14 concentration. CONCLUSION: The ND-C14 may improve bactericidal effects on S. pneumoniae both in vitro and in vivo.

16.
Materials (Basel) ; 17(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38276467

RESUMEN

The as-cast [Co40Cr25(FeNi)35-yMoy]100-xCx (x = 0, 0.5, y = 3, 4, 5 at.%) HEAs (high-entropy alloys) were prepared by a vacuum arc melting furnace and were then hot rolled. The effect of C and Mo elements on the microstructure evolution and mechanical properties of HEAs was systematically analyzed. The results showed that when no C atoms were added, the HEAs consisted of FCC + HCP dual-phase structure. In addition, as the Mo content increased, the grain size of the alloy increased from 17 µm to 47 µm. However, only the FCC phase appeared after adding 0.5 at.% carbon in Mo microalloyed HEAs, and the grain size of the Mo4C0.5 HEA decreased significantly. Due to the Mo atom content exceeding the solid solution limit, the carbides of Mo combined with the C element appeared in the Mo5C0.5 HEA. The strength of C and Mo microalloyed HEAs significantly increased compared to HEAs with no C added. However, the Mo4C0.5 HEA exhibited excellent comprehensive mechanical properties, which was superior to a majority of reported HEAs and conventional metal alloys. Its yield strength, tensile strength, and elongation were 757 MPa, 1186 MPa, and 69%, respectively. The strengthening mechanism was a combination of fine grain strengthening, TWIP effect, and solid solution strengthening.

17.
Sci Total Environ ; 916: 170071, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38242465

RESUMEN

The Belt and Road Initiative (BRI) is an open platform for international cooperation proposed by China to promote common global development and prosperity. The BRI can promote the optimal allocation of resources and promote in-depth cooperation in international trade. Meanwhile, it can establish a green supply chain cooperation network to help BRI countries achieve green transformation. BRI has made a notable contribution to the rapid growth of cross-border trade. However, it has also brought environmental impacts. Given that little attention has been paid to the trade-embodied particulate matter 2.5 related human health impacts (PM2.5-HHI) throughout the BRI, this study accounts for and traces the embodied PM2.5-HHI flows between the BRI countries and non-Belt and Road Initiative (non-BRI) countries. Moreover, this study also uncovers the critical socioeconomic drivers of PM2.5-HHI changes in BRI countries during 1990-2015, based on the multi-regional input-output based structural decomposition analysis (MRIO-SDA). Results show that, firstly, BRI countries had significantly increased their economic added value by exporting products to the non-BRI countries. They also have brought PM2.5-HHI to themselves. Secondly, the final demand of BRI countries was the largest potential driving force of PM2.5-HHI of BRI countries. Thirdly, the emission intensity change of BRI is the key socioeconomic factor for reducing PM2.5-HHI. While per capita final demand level change of BRI and production structure change of non-BRI are the key socioeconomic factors for increasing PM2.5-HHI. The study's findings on the one hand can help reduce the PM2.5-HHI and impacts of environmental pollution of BRI countries from a global perspective by providing scientific support. On the other hand, they can help provide relevant policy recommendations for the green transformation of BRI and the construction of green BRI.


Asunto(s)
Comercio , Internacionalidad , Humanos , China , Ambiente , Material Particulado/análisis , Desarrollo Económico , Dióxido de Carbono/análisis
18.
Plant Physiol Biochem ; 206: 108289, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38154294

RESUMEN

Mulberry is a traditional economic tree with various values in sericulture, ecology, food industry and medicine. Expansins (EXPs) are known as cell wall expansion related proteins and have been characterized to involve in plant development and responses to diverse stresses. In present study, twenty EXP and expansin-like (EXL) genes were identified in mulberry. RNA-seq results indicated that three EXP and EXL genes showed up-regulated expression level under sclerotiniose pathogen infection in three independent RNA-seq datasets. The most significant upregulated EXPA11 was selected as key EXP involving in response to sclerotiniose pathogen infection in mulberry. Furthermore, a comprehensive functional analysis was performed to reveal subcellular location, tissue expression profile of MaEXPA11 in mulberry. Down-regulation of MaEXPA11 using virus induced gene silence (VIGS) was performed to explore the function of MaEXPA11 in Morus alba. Results showed that MaEXPA11 can positively regulate mulberry resistance to Ciboria shiraiana infection and negatively regulate mulberry resistance to cold or drought stress.


Asunto(s)
Morus , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Morus/genética , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas
19.
Anal Methods ; 15(48): 6643-6647, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38044886

RESUMEN

Combining powerful adsorption capacity, simple preparation, rapid separation as well as superior stability and recyclability, a polyurea-magnetic hierarchical porous composite has been prepared. It demonstrates efficient physisorption for anionic metabolites in less than one minute and is promising for application to the analysis of a broad range of anionic metabolites in complex matrices.

20.
Front Plant Sci ; 14: 1301445, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38107010

RESUMEN

As we face increasing challenges of world food security and malnutrition, coarse cereals are coming into favor as an important supplement to human staple foods due to their high nutritional value. In addition, their functional components, such as flavonoids and polyphenols, make them an important food source for healthy diets. However, we lack a systematic understanding of the importance of coarse cereals for world food security and nutritional goals. This review summarizes the worldwide cultivation and distribution of coarse cereals, indicating that the global area for coarse cereal cultivation is steadily increasing. This paper also focuses on the special adaptive mechanisms of coarse cereals to drought and discusses the strategies to improve coarse cereal crop yields from the perspective of agricultural production systems. The future possibilities, challenges, and opportunities for coarse cereal production are summarized in the face of food security challenges, and new ideas for world coarse cereal production are suggested.

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