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1.
Front Mol Biosci ; 11: 1452290, 2024.
Article in English | MEDLINE | ID: mdl-39211744

ABSTRACT

Inositol 1,4,5-Trisphosphate Receptor-Interacting Protein-Like 1 (ITPRIPL1), a single-pass type I membrane protein located in the membrane, functions as an inhibitory ligand of CD3ε. Recent studies have shown that its expression suppresses T cells activation and promote tumor immune evasion. Despite increasing evidence suggesting that ITPRIPL1 plays a significant role in tumor growth, no systematic pan-cancer analysis of ITPRIPL1 has been conducted to date. This study utilized datasets curated from The Cancer Genome Atlas, Genotype Tissue-Expression, and Human Protein Atlas to investigate the relationship between ITPRIPL1 expression and clinical outcomes, immune infiltration, and drug sensitivity across 33 cancer types. We employed multiple methods to assess its prognostic value in pan-cancer, such as univariate Cox regression, survival analysis, and ROC curve analysis and explored the relationship between ITPRIPL1 and tumor mutation burden (TMB), tumor microsatellite instability (MSI), CNV, DNA methylation, immune-related genes, immune cell infiltration, and drug sensitivity to reveal its immunological role. The mRNA expression levels of the ITPRIPL1 gene vary significantly across multiple types of cancer and significantly reduced in breast cancer. Conversely, high ITPRIPL1 expression was associated with a better prognosis in BRCA. Furthermore, the expression of ITPRIPL1 highly correlates with the presence of tumor-infiltrating immune cells and immune checkpoint genes across various types of cancers. Additionally, ITPRIPL1 expression was associated with TMB in 6 cancer types and with MSI in 13 cancer types. High expression of ITPRIPL1 serves as a protective factor in certain cancer types, correlating with longer overall survival in BRCA. Our study further confirms that ITPRIPL1 participates in regulating immune infiltration and affecting the prognosis of patients in pan-cancer. These findings underscore the promising potential of ITPRIPL1 as a therapeutic target for human cancer.

3.
Pediatrics ; 154(2)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38978512

ABSTRACT

BACKGROUND: Nine-valent human papillomavirus (9vHPV) vaccines can be administered in 2 doses 6 to 12 months apart in adolescents. The impact of extended dose intervals is unknown. We report immunogenicity and safety data in adolescents of a second 9vHPV vaccine dose administered ≥1 year after the first. METHODS: This open-label safety and immunogenicity study (NCT04708041) assessed extended-interval 2-dose regimens of 9vHPV vaccine among adolescents (10 to 15 years) who received 2 9vHPV vaccine doses: the first ≥1 year before enrollment, and second, at enrollment (day 1). We measured serologic responses to vaccine-targeted human papillomavirus (HPV) types at enrollment day 1 (pre-dose 2) and 1 month post-dose 2 (month 1) using a competitive LuminexV® immunoassay. We estimated effects of dose interval on geometric mean titers (GMTs) using regression modeling. Participants reported adverse events (AEs) through 15 days after vaccination. RESULTS: We enrolled 146 adolescents (mean age 13.3 years) with median 25 months since first 9vHPV vaccine dose (range: 12-53 months). Across vaccine-targeted HPV types, GMTs increased from day 1 to month 1; seropositivity at month 1 was 100%. Anti-HPV GMTs at month 1 were not affected by differences in dose interval of 12 to 53 months, based on regression modeling. The most common AEs were mild-to-moderate injection site reactions; no serious AEs were reported. CONCLUSIONS: Extending the interval between first and second 9vHPV vaccine doses to 12 to 53 months did not affect antibody responses, with favorable safety profile. These results support feasibility of extended interval regimens for 9vHPV vaccine.


Subject(s)
Immunization Schedule , Immunogenicity, Vaccine , Papillomavirus Infections , Papillomavirus Vaccines , Humans , Adolescent , Female , Male , Child , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/immunology , Papillomavirus Infections/prevention & control , Antibodies, Viral/blood
4.
BMC Plant Biol ; 24(1): 646, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977970

ABSTRACT

Long-term application of green manure (GM) and nitrogen (N) fertilizers markedly improved soil fertility and boosted rice yield in ecologically fragile karst paddy fields. However, the precise response mechanisms of the soil bacterial community to varying amounts of green manure alone and in combination with N fertilizer in such environments remain poorly elucidated. In this study, we investigated the soil bacterial communities, keystone taxa, and their relationship with soil environmental variables across eight fertilization treatments. These treatments included group without N addition (N0M0, no N fertilizer and no GM; N0M22.5, 22.5 t/ha GM; N0M45, 45 t/ha GM, N0M67.5, 67.5 t/ha GM) and group with N addition (NM0, N fertilizer and no GM; NM22.5, N fertilizer and 22.5 t/ha GM; NM45, N fertilizer and 45 t/ha GM; NM67.5, N fertilizer and 67.5 t/ha GM). The results revealed that increasing green manure input significantly boosted rice yield by 15.51-22.08% and 21.84-35% in both the group without and with N addition, respectively, compared to N0M0 treatment. Moreover, with escalating green manure input, soil TN, AN, AK, and AP showed an increasing trend in the group without N addition. However, following the addition of N fertilizer, TN and AN content initially rose, followed by a decline due to the enhanced nutrient availability for rice. Furthermore, the application of a large amount of N fertilizer decreased the C: N ratio in the soil, resulting in significant changes in both the soil microbial community and its function. Particularly noteworthy was the transition of keystone taxa from their original roles as N-fixing and carbon-degrading groups (oligotrophs) to roles in carbon degradation (copiotrophs), nitrification, and denitrification. This shift in soil community and function might serve as a primary factor contributing to enhanced nutrient utilization efficiency in rice, thus significantly promoting rice yield.


Subject(s)
Bacteria , Fertilizers , Manure , Nitrogen , Oryza , Soil Microbiology , Oryza/growth & development , Fertilizers/analysis , Nitrogen/metabolism , Bacteria/metabolism , Soil/chemistry , Agriculture/methods , Microbiota
5.
Int J Biol Macromol ; 273(Pt 2): 132944, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38851616

ABSTRACT

Lignin-based microcapsules are extremely attractive for their biodegradability and photolysis resistance. However, the water-soluble all-lignin shells were unsatisfactory in terms of rainfall and foliar retention, and lacked the test of agricultural production practices. Herein, a novel microcapsule based on a flexible skeleton formed by interfacial polymerization and absorbed with lignin particles (LPMCs) was prepared in this study. Further analysis demonstrated that the shell was formed by cross-linking the two materials in layers and showed excellent flexibility and photolysis resistance. The pesticide loaded LPMCs showed about 98.68 % and 73.00 % improvement in scour resistance and photolysis resistance, respectively, as compared to the bare active ingredient. The foliar retention performance of LPMCs was tested in peanut plantations during the rainy season. LPMCs loaded with pyraclostrobin (Pyr) and tebuconazole (Teb) exhibited the best foliar disease control and optimum plant architecture, resulting in an increase in yield of about 5.36 %. LPMCs have a promising application prospect in the efficient pesticide utilization, by controlling its deformation, adhesion and release, an effective strategy for controlling diseases and managing plant growth was developed.


Subject(s)
Capsules , Lignin , Plant Leaves , Lignin/chemistry , Plant Leaves/chemistry , Strobilurins/chemistry , Ultraviolet Rays , Triazoles/chemistry , Photolysis , Arachis/chemistry , Pesticides/chemistry
6.
Int J Surg ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38920322

ABSTRACT

OBJECTIVE: The purpose of this study is to investigate potential associations between body fat composition and postoperative outcomes in patients with hepatectomy or liver transplantation. METHODS: Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between body fat composition and outcomes of patients with liver surgery from the start of each database to October 29, 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies. RESULTS: This analysis included a total of 29 articles with a combined patient cohort of 6,435 individuals. The results demonstrated that patients with high intramuscular fat content (IMFC) had significantly inferior OS (HR: 2.07, 95% CI: 1.69-2.53, P < 0.001) and RFS (HR: 1.61, 95% CI: 1.20-2.16, P = 0.002) and a higher risk of major complications (HR: 2.20, 95% CI: 1.59-3.05, P < 0.001). We also found that the presence of high visceral-to-subcutaneous fat tissue ratio (VSR) in patients with liver surgery was significantly related to poorer OS (HR: 1.70, 95% CI: 1.44-2.00, P < 0.001) and PFS (HR: 1.29, 95% CI: 1.11-1.50, P = 0.001) and a higher major complication rate (HR: 2.31, 95% CI: 1.17-4.56, P = 0.016). Besides, the synthesized findings indicated there is no significant correlation between visceral fat tissue and survival outcomes or postoperative complications. CONCLUSION: In summary, preoperative IMFC and VSR have the potential to forecast poorer OS and RFS and a higher risk of complications for patients undergoing hepatectomy or liver transplantation.

7.
Front Oncol ; 14: 1367477, 2024.
Article in English | MEDLINE | ID: mdl-38939332

ABSTRACT

Inadequate tissue volume at the lower pole of the breast following tumor excision can compromise aesthetic outcomes when employing the conventional inverted-T reconstruction technique. With the aim of reducing postoperative deformities, we have refined this technique. A total of 104 patients underwent the T technique, while 32 underwent the modified T technique and 72 underwent the traditional T technique. In this study, we present the surgical outcomes of the modified T technique group and compare both surgical and oncological outcomes with those of the traditional T technique group. In the modified T technique group, the average tumor size was 23.34 mm, and the mean operation duration was 107.75 min, which was significantly shorter than that of the traditional T technique (p = 0.039). Additionally, the average blood loss was 95.93 mL, which was significantly lower than that of the traditional T technique (p = 0.011). Although complication rates did not differ significantly between the two groups (p = 0.839), the modified T technique yielded superior aesthetic outcomes compared to the traditional T technique (p = 0.019). Survival analysis indicated no significant difference in 5-year recurrence-free survival between the two groups, both before and after propensity score matching (p = 0.381 vs. p = 0.277). As part of our series of oncoplastic techniques for the lower breast quadrant, the modified inverted-T technique utilizes a cost-effective flap to address lower pole defects, mitigating deformities and restoring the breast's natural shape.

8.
Plant Cell Rep ; 43(6): 160, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825616

ABSTRACT

KEY MESSAGE: LeBAHD56 is preferentially expressed in tissues where shikonin and its derivatives are biosynthesized, and it confers shikonin acylation in vivo. Two WRKY transcriptional factors might regulate LeBAHD56's expression. Shikonin and its derivatives, found in the roots of Lithospermum erythrorhizon, have extensive application in the field of medicine, cosmetics, and other industries. Prior research has demonstrated that LeBAHD1(LeSAT1) is responsible for the biochemical process of shikonin acylation both in vitro and in vivo. However, with the exception of its documented in vitro biochemical function, there is no in vivo genetic evidence supporting the acylation function of the highly homologous gene of LeSAT1, LeBAHD56(LeSAT2), apart from its reported role. Here, we validated the critical acylation function of LeBAHD56 for shikonin using overexpression (OE) and CRISPR/Cas9-based knockout (KO) strategies. The results showed that the OE lines had a significantly higher ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than the control. In contrast, the KO lines had a significantly lower ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than controls. As for its detailed expression patterns, we found that LeBAHD56 is preferentially expressed in roots and callus cells, which are the biosynthesis sites for shikonin and its derivatives. In addition, we anticipated that a wide range of putative transcription factors might control its transcription and verified the direct binding of two crucial WRKY members to the LeBAHD56 promoter's W-box. Our results not only confirmed the in vivo function of LeBAHD56 in shikonin acylation, but also shed light on its transcriptional regulation.


Subject(s)
Gene Expression Regulation, Plant , Lithospermum , Naphthoquinones , Plant Proteins , Plants, Genetically Modified , Naphthoquinones/metabolism , Lithospermum/genetics , Lithospermum/metabolism , Acylation , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Roots/genetics , Plant Roots/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , CRISPR-Cas Systems , Anthraquinones
9.
Chem Commun (Camb) ; 60(47): 6063-6066, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38780308

ABSTRACT

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.

10.
Chemistry ; 30(35): e202401150, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38639722

ABSTRACT

In this study, a series of H-bonded arylamide foldamers bearing benzoselenadiazole ends with solvent-responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV-vis spectroscopy experiments show that the absorption wavelength of H-bonded arylamide foldamers are significantly red-shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state.

11.
Phys Rev Lett ; 132(13): 138401, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38613297

ABSTRACT

Chirality is an essential nature of biological systems. However, it remains obscure how the handedness at the microscale is translated into chiral morphogenesis at the tissue level. Here, we investigate three-dimensional (3D) tissue morphogenesis using an active fluid theory invoking chirality. We show that the coordination of achiral and chiral stresses, arising from microscopic interactions and energy input of individual cells, can engender the self-organization of 3D papillary and helical structures. The achiral active stress drives the nucleation of asterlike topological defects, which initiate 3D out-of-plane budding, followed by rodlike elongation. The chiral active stress excites vortexlike topological defects, which favor the tip spheroidization and twisting of the elongated rod. These results unravel the chiral morphogenesis observed in our experiments of 3D organoids generated by human embryonic stem cells.


Subject(s)
Cell Division , Humans , Morphogenesis
12.
NeuroRehabilitation ; 54(3): 421-434, 2024.
Article in English | MEDLINE | ID: mdl-38640179

ABSTRACT

BACKGROUND: The therapeutic effect and mechanism of robot-assisted upper limb training (RT) combined with intermittent theta burst stimulation (iTBS) for stroke patients are unclear. OBJECTIVE: The purpose of this study was to evaluate changes in brain activation after combination therapy and RT alone using functional near-infrared spectroscopy (fNIRS). METHODS: Patients were randomly assigned to two groups (iTBS + RT Group, n = 18, and RT Group, n = 18). Training was conducted five times a week for four weeks. fNIRS was used to measure changes in oxyhemoglobin in both the primary motor cortex (M1) and pre-motor and supplementary motor area (pSMA) during affected limb movement. Fugl-Meyer Assessment-Upper Extremity (FMA-UE) was employed for evaluating the function of upper limbs. RESULTS: Thirty-two patients with subacute stroke completed the study. The cortex of both hemispheres was extensively activated prior to treatment in the RT group. After training, overactivation decreased. The brain activation of the combined treatment group transferred to the affected side after the treatment. There was a notable enhancement in the FMA-UE scores for both groups, with the combined group's progress significantly surpassing that of the RT group. CONCLUSION: RT combined with iTBS can improve the motor function of stroke patients and promote the balance between cerebral hemispheres.


Subject(s)
Motor Cortex , Robotics , Spectroscopy, Near-Infrared , Stroke Rehabilitation , Stroke , Transcranial Magnetic Stimulation , Upper Extremity , Humans , Male , Female , Spectroscopy, Near-Infrared/methods , Middle Aged , Stroke Rehabilitation/methods , Upper Extremity/physiopathology , Transcranial Magnetic Stimulation/methods , Stroke/physiopathology , Stroke/therapy , Aged , Motor Cortex/physiopathology , Adult , Combined Modality Therapy , Treatment Outcome
13.
Hum Vaccin Immunother ; 20(1): 2321035, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38497448

ABSTRACT

There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 µg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.


Despite the use of pneumococcal vaccines, the burden of pneumococcal disease in children persists. V114, a 15-valent pneumococcal conjugate vaccine, was immunogenic and well-tolerated in healthy South Korean infants and toddlers.


Subject(s)
Antibodies, Bacterial , Pneumococcal Vaccines , Humans , Infant , Immunoglobulin G , Republic of Korea , Vaccines, Conjugate
14.
Sci Total Environ ; 919: 170823, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38342464

ABSTRACT

The tertiary industry, led by service sectors, usually have "clean" production processes and thus is ignored by current PM2.5 pollution mitigation strategies in China. Actually, the tertiary industry heavily relies on the supplies from its upstream industries, resulting in pollutant emissions and economic benefits transferring among different regions. With the application of the multiregional input-output (MRIO) model, our study explores the emission contribution from the tertiary industry's consumption activities in China and analyses the accompanying emission-economy relationship. We find that the production process of tertiary industry (with the sector Transportation excluded) contributes only ∼1 % of China's PM2.5-related emissions in 2017. However, its consumption-based emission contributions could increase to 11 %-17 %, among which >95 % are indirectly contributed. More than 40 % of tertiary industry consumption-based emissions, accompanied by 25 % of the consumption-based value added, are transferred via interprovincial trade. The proportion of transferred emissions even exceeds 50 % for the top 10 importers. The spatial pattern of value-added flows is nearly opposite to that of emission flows. Our results also reveal that among the 30 provinces and 870 interprovincial trading pairs, 6 provinces are experiencing environmental-economic win, 7 provinces are experiencing environmental-economic loss, and in detail 326 trading pairs are experiencing environmental-economic win or loss. To reduce the unexpected emissions and inequalities embodied in seemingly "clean" industries, consumption activities should be considered and strengthened in China's new-stage environmental policies.

15.
Front Immunol ; 15: 1347683, 2024.
Article in English | MEDLINE | ID: mdl-38343537

ABSTRACT

Background: Pancreatic cancer remains an extremely malignant digestive tract tumor, posing a significant global public health burden. Patients with pancreatic cancer, once metastasis occurs, lose all hope of cure, and prognosis is extremely poor. It is important to investigate liver metastasis of Pancreatic cancer in depth, not just because it is the most common form of metastasis in pancreatic cancer, but also because it is crucial for treatment planning and prognosis assessment. This study aims to delve into the mechanisms of pancreatic cancer liver metastasis, with the goal of providing crucial scientific groundwork for the development of future treatment methods and drugs. Methods: We explored the mechanisms of pancreatic cancer liver metastasis using single-cell sequencing data (GSE155698 and GSE154778) and bulk data (GSE71729, GSE19279, TCGA-PAAD). Initially, Seurat package was employed for single-cell data processing to obtain expression matrices for primary pancreatic cancer lesions and liver metastatic lesions. Subsequently, high-dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify genes associated with liver metastasis. Machine learning algorithms and COX regression models were employed to further screen genes related to patient prognosis. Informed by both biological understanding and the outcomes of algorithms, we meticulously identified the ultimate set of liver metastasis-related gene (LRG). In the study of LRG genes, various databases were utilized to validate their association with pancreatic cancer liver metastasis. In order to analyze the effects of these agents on tumor microenvironment, we conducted an in-depth analysis, including changes in signaling pathways (GSVA), cell differentiation (pseudo-temporal analysis), cell communication networks (cell communication analysis), and downstream transcription factors (transcription factor activity prediction). Additionally, drug sensitivity analysis and metabolic analysis were performed to reveal the effects of LRG on gemcitabine resistance and metabolic pathways. Finally, functional experiments were conducted by silencing the expression of LRG in PANC-1 and Bx-PC-3 cells to validate its influence to proliferation and invasiveness on PANC-1 and Bx-PC-3 cells. Results: Through a series of algorithmic filters, we identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis elucidated the activation of the TGF-beta signaling pathway by PAK2 to promote the occurrence of liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis revealed that overexpression of PAK2 promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. CCK8 experiments showed that silencing PAK2 led to a decrease in the proliferative capacity of pancreatic cancer cells and scratch experiments demonstrated that low expression of PAK2 decreased invasion capability in pancreatic cancer cells. Flow cytometry reveals that PAK2 significantly inhibited apoptosis in pancreatic cancer cell lines. Molecules related to the TGF-beta pathway decreased with the inhibition of PAK2, and there were corresponding significant changes in molecules associated with EMT. Conclusion: PAK2 facilitated the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-beta signaling pathway. Simultaneously, it decreased the differentiation level of cancer cells, consequently enhancing their malignancy. Additionally, PAK2 fostered communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. In summary, PAK2 emerged as a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis.


Subject(s)
Liver Neoplasms , Pancreatic Neoplasms , Humans , Gemcitabine , Cell Proliferation , Pancreatic Neoplasms/pathology , Transcription Factors , Transforming Growth Factor beta/pharmacology , Liver Neoplasms/genetics , Tumor Microenvironment , p21-Activated Kinases/genetics
17.
Comput Biol Chem ; 109: 108010, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38232515

ABSTRACT

1,4-dihydropyridine derivatives (1,4-DHPs) are a class of drugs used to treat cardiovascular diseases, but these drugs can cause liver injury. To reveal the toxicity characteristics of these compounds, we used a series of assays, including cell viability, enzyme activity detection, and western blotting, to investigate the toxicity of seven kinds of 1,4-DHPs (0-100 µM) on HepG2 cells and establish 3D-QSAR model based on relevant toxicity data. After HepG2 cells were treated with 1,4-DHPs for 24 h, high-dose (100 µM) 1,4-DHPs decreased cell viability to varying degrees, while ROS and MDA contents were significantly increased, and ATP content was reduced. Moreover, with the concentration of 100 µM 1,4-DHPs (Nimodipine, Nitrendipine, Cilnidipine, and Manidipine) were markedly inhibited the phosphorylation levels of mTOR protein. The results of the 3D-QSAR model showed that the non-cross validation coefficient (R2) and cross validation coefficient (Q2) of the model were 0.982 and 0.652, respectively. Combined with external validation and the Williams diagram, the model showed good predictability and application domain. Based on the CoMSIA 3D contour map, the introduction of large volume and hydrogen bond receptor groups on the carbonyl oxygen side chains of the 1,4-DHPs ring 3- and 5- was beneficial for reducing the toxicity of 1,4-DHPs. The results of this study could supplement information on the cytotoxicity of 1,4-DHPs, and could provide theoretical support for predicting the toxicity of 1,4-DHPs.


Subject(s)
Calcium Channel Blockers , Dihydropyridines , Quantitative Structure-Activity Relationship , Calcium Channel Blockers/pharmacology , Liver , TOR Serine-Threonine Kinases
18.
Sci Bull (Beijing) ; 69(4): 544-553, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38158290

ABSTRACT

Household consumption in China is associated with substantial PM2.5 pollution, through activities directly (i.e., fuel use) and/or indirectly (i.e., consumption of goods and services) causing pollutant emissions. Urban and rural households exhibit different consumption preferences and living areas, thus their contributions to and suffering from air pollution could differ. Assessing this contrast is crucial for comprehending the environmental impacts of the nation's ongoing urbanization process. Here we quantify Chinese urban and rural households' contributions to ambient PM2.5 pollution and the health risks they suffer from, by integrating economic, atmospheric, and health models and/or datasets. The national premature deaths related to long-term exposure to PM2.5 pollution contributed by total household consumption are estimated to be 1.1 million cases in 2015, among which 56% are urban households and 44% are rural households. For pollution contributed indirectly, urban households, especially in developed provinces, tend to bear lower mortality risks compared with the portions of deaths or pollution they contribute. The opposite results are true for direct pollution. With China's rapid urbanization process, without adequate reduction in emission intensity, the increased indirect pollution-associated premature deaths could largely offset that avoided by reduced direct pollution, and the indirect pollution-associated urban-rural inequalities might become severer. Developing pollution mitigation strategies from both production and consumption sides could help with reducing pollution-related mortality and associated urban-rural inequality.


Subject(s)
Air Pollution , Environmental Pollutants , Humans , Particulate Matter/adverse effects , Air Pollution/adverse effects , Urbanization , China/epidemiology
19.
Dalton Trans ; 52(46): 17273-17278, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37937453

ABSTRACT

The exploitation of highly active and stable catalysts for reduction of CO2 and water oxidation is one of the approaches to facilitate scalable and sustainable CO2 reduction potentially at the industrial scale. Herein, a feasible strategy to rationally build an overall CO2 + H2O electrocatalytic reaction device is the preparation and matchup of a high-performance CO2 reduction catalyst and low-cost and highly active oxygen anode catalyst. A heterostructured nanosheet, γ-NiOOH/NiCO3/Ni(HCOO)2, exhibited superior catalytic activity in the oxygen evolution reaction, and was integrated with CoPc/Fe-N-C to build an overall CO2 + H2O cell with a current density of 10 mA cm-2 at a very low cell voltage of 1.97 V, and the faradaic deficiency of CO2 to CO was maintained at greater than 90% at 1.9 V.

20.
Angew Chem Int Ed Engl ; 62(52): e202314052, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-37945536

ABSTRACT

Azide compounds are widely used and especially, polymers bearing pendant azide groups are highly desired in numerous fields. However, harsh reaction conditions are always mandatory to achieve full azidation, causing severe side reactions and degradation of the polymers. Herein, we report the design and preparation of two azide ionic liquids (AILs) with azide anion and triethylene glycol (E3 )-containing cation, [P444E3 ][N3 ] and [MIME3 ][N3 ]. Compared with the traditional sodium azide (NaN3 ) approach, both AILs showed much higher reaction rates and functional-group tolerance. More importantly, they could act as both reagents and solvents for the quantitative azidation of various polymeric precursors under mild conditions. Theoretical simulations suggested that the outstanding performance of AILs originated from the existence of ion pairs during the reaction, and the E3 moieties played a crucial role. Lastly, after the reaction, the AILs could be easily regenerated, presenting a safer, greener, and highly efficient synthesis route for azide polymers.

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