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1.
IEEE Trans Cybern ; PP2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381633

RESUMO

Predicting the trajectory of pedestrians in crowd scenarios is indispensable in self-driving or autonomous mobile robot field because estimating the future locations of pedestrians around is beneficial for policy decision to avoid collision. It is a challenging issue because humans have different walking motions, and the interactions between humans and objects in the current environment, especially between humans themselves, are complex. Previous researchers focused on how to model human-human interactions but neglected the relative importance of interactions. To address this issue, a novel mechanism based on correntropy is introduced. The proposed mechanism not only can measure the relative importance of human-human interactions but also can build personal space for each pedestrian. An interaction module, including this data-driven mechanism, is further proposed. In the proposed module, the data-driven mechanism can effectively extract the feature representations of dynamic human-human interactions in the scene and calculate the corresponding weights to represent the importance of different interactions. To share such social messages among pedestrians, an interaction-aware architecture based on long short-term memory network for trajectory prediction is designed. Experiments are conducted on two public datasets. Experimental results demonstrate that our model can achieve better performance than several latest methods with good performance.

2.
Cell Death Dis ; 15(2): 158, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383528

RESUMO

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance. Schematic depicting that HMGA1 maintains intracellular redox homeostasis against ferroptosis by assisting ATF4 to activate SLC7A11 transcription, resulting in ESCC resistance to chemotherapy.

3.
J Med Chem ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385264

RESUMO

PAR4 is a promising antithrombotic target with potential for separation of efficacy from bleeding risk relative to current antiplatelet therapies. In an effort to discover a novel PAR4 antagonist chemotype, a quinoxaline-based HTS hit 3 with low µM potency was identified. Optimization of the HTS hit through the use of positional SAR scanning and the design of conformationally constrained cores led to the discovery of a quinoxaline-benzothiazole series as potent and selective PAR4 antagonists. The lead compound 48, possessing a 2 nM IC50 against PAR4 activation by γ-thrombin in platelet-rich plasma (PRP) and greater than 2500-fold selectivity versus PAR1, demonstrated robust antithrombotic efficacy and minimal bleeding in the cynomolgus monkey models.

4.
PLoS Genet ; 20(2): e1011163, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377137

RESUMO

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

5.
ACS Omega ; 9(6): 6578-6587, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371800

RESUMO

Polymer blending offers an effective and economical approach to overcome the performance limitations of poly(lactic acid) (PLA). In this study, a series of copolymers poly(ethylene succinate-co-lactic acid) (PESL) were synthesized, featuring lactic acid (LA) contents that ranged from 20 to 86 wt %. This synthesis involved a one-pot industrial melt polycondensation process using succinic acid (SA), ethylene glycol (EG), and LA, catalyzed by titanium tetraisopropoxide (TTP). The goal was to produce a fully biobased copolymer expected to exhibit partial miscibility with pure poly(lactic acid) (PLA). To assess the capability of PESL copolymers in toughening PLA, we conducted tensile testing on PLA/PESL blends containing 15 wt % PESL. As a result, an elongation at break for the blends with 15 wt % loading of the copolymer PESL72 was directly enhanced to 250% with an ultimate strength of 35 MPa, compared to brittle PLA with less 10% tensile length. The morphological features of interfacial adhesion before and after tensile failure were measured by scanning electron microscopy (SEM). A significant enhancement in the chain mobility of the PLA/PESL blends was further evidenced by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). These findings hold promise for the development of functional packaging materials based on PLA. The proposed copolymer design, which boasts strong industrial feasibility, can serve as a valuable guide for enhancing the toughness of PLA.

6.
J Mater Chem B ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376394

RESUMO

Methotrexate (MTX) is one of the first-line drugs used for the treatment of moderate to severe psoriasis. However, low bioavailability and systemic side effects of traditional oral and injectable MTX greatly limit its clinical application. Delivering MTX using dissolving microneedles (MNs) into psoriasis-like skin lesion could improve the in situ therapeutic effects with higher bioavailability and less side effects. Here, we propose a novel therapeutic approach for psoriasis involving MN-assisted percutaneous delivery of chitosan-coated hollow mesoporous silica nanoparticles containing MTX (MTX@HMSN/CS). The MTX@HMSN/CS-loaded MNs were strong enough to successfully penetrate the psoriasiform thickened epidermis, allowing MTX@HMSN/CS to be accurately delivered to the site of skin lesion following the rapid dissolution of MNs. MTX was then released continuously from HMSN/CS for at least one week to maintain effective therapeutic drug concentration for skin lesion with long-term anti-proliferative and anti-inflammatory effects. Incubation with MTX@HMSN/CS not only inhibited the proliferation of human immortalized keratinocytes (HaCaT cells), but also significantly reduced the expression of proinflammatory cytokines and chemokines. In addition, MTX@HMSN/CS-loaded MNs showed better efficacy in alleviating psoriasis-like skin inflammation than MTX-loaded MNs at the same dose. Compared to psoriasiform mice treated with 15.8 µg MTX-loaded MNs every day, 47.4 µg MTX@HMSN/CS-loaded MNs reduce the frequency of treatment to once every 3 days and achieve comparable amelioration. Therefore, MTX@HMSN/CS loaded MNs are a promising treatment strategy for psoriasis due to their durability, efficacy, convenience, and safety in relieving psoriasis-like skin inflammation.

7.
Sci Rep ; 14(1): 4041, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369540

RESUMO

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ7Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 µm. A negative correlation of δ7Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ7Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites.

8.
Chem Biodivers ; : e202400188, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372184

RESUMO

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3 ± 0.12 and 22.1 ± 0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

9.
Sci Total Environ ; 920: 170894, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38367736

RESUMO

Polypropylene microplastics (PP-MPs) are emerging environmental contaminants that have the potential to cause adverse effects on aquatic organisms. Reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) is a valuable tool for assessing the gene expression profiles under PP-MPs stress. To obtain an accurate gene expression profile of tissue inflammation and apoptosis that reflects the molecular mechanisms underlying the impact of PP-MPs on Chinese sturgeon, identifying reliable reference genes is crucial for RT-qPCR analysis. In this study, we constructed an experiment model of Chinese sturgeon exposed to PP-MPs, assessed the pathological injury, metabolic profile responses and oxidative stress in liver, evaluated the reliability of 8 reliable reference genes by 4 commonly used algorithms including GeNorm, NormFinder, BeatKeeper, Delta Ct, and then analyzed the performance of inflammatory response genes in liver, spleen and kidney with the best reference gene. HE staining revealed that the cytoplasm full small vacuoles and nucleus diameter increased were occurred in the liver cell of PP-MPs in treatment groups. Additionally, oxidative and biochemical parameters were significantly changes in the liver of treatment groups. For the reference genes in PP-MPs exposure experiments, this study screening the optimal reference genes including: EF1α and GAPDH for liver and spleen, and GAPDH and RPS18 for kidney. Besides, 2 inflammatory response genes (NLRP3, TNF-α) were chosen to assess the optimal reference genes using the least stable reference gene (TUB) as a control, verified the practicality of the select reference genes in different tissues. We also found that the low concentration of PP-MPs could induce the liver tissue damage and inflammatory response in Chinese sturgeon. Our study initially evaluated the impact of short-time exposure with PP-MPs in Chinese sturgeon and provided 3 sets of validated optimal reference genes in Chinese sturgeon exposure to PP-MPs.

10.
BMC Med ; 22(1): 75, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373990

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed tumor treatment. However, the risk of pulmonary adverse events (PAEs) associated with ICI combination therapy is still unclear. We aimed to provide a PAE overview and risk ordering of ICIs used in tumor treatment. METHODS: We searched the databases of PubMed, PsycINFO, Embase, Cochrane Library, CINAHL, Web of Science, Scopus, and clinical trial websites during January 2011-April 2023 to identify phase II and III randomized clinical trials (RCTs) and single-arm clinical trials wherein at least one treatment arm received ICIs (e.g., ICI monotherapy, a combination of two ICIs, or ICIs in combination with conventional cancer therapy). We reported the results of PAEs. Additionally, we compared risks of PAEs between different drug classes using a Bayesian network meta-analysis. RESULTS: Among 143 RCTs and 24 single-arm trials, the incidence of all-grade and grade 3-4 PAEs were highest with programmed death L1 (PD-L1) plus cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and plus chemotherapy and anti-PD1 plus anti-CTLA4, the lowest with targeted therapy drug plus chemotherapy and anti-PD1 plus anti-PDL1. Anti-PD1 plus anti-CTLA4 and plus chemotherapy was the intervention with the highest risk for all-grade and 3-4 grade PAEs, and the intervention with the lowest risk was chemotherapy and anti-PD1 plus anti-PDL1. In terms of all-grade PAEs, chemotherapy was safer than ICI monotherapy. Except for the anti-PD1 plus anti-PDL1 regimen, no significant difference in the risk of grade 3-4 PAEs was detected between dual-ICIs and single-ICIs. Furthermore, the risk of PAEs associated with nivolumab, pembrolizumab, and atezolizumab may be dose dependent. CONCLUSIONS: In the single-drug regimen, anti-PD1 caused the greatest incidence of PAEs. The risk of PAEs was higher with all single-ICIs than with chemotherapy. However, no significant difference in the risk of PAEs was detected between single-ICIs. In the combined regimen, anti-PD1 plus anti-CTLA4 and plus chemotherapy showed the greatest risk of PAEs, but there were no significant differences in risk between dual-ICIs and single-ICIs.


Assuntos
Antineoplásicos Imunológicos , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Metanálise em Rede , Neoplasias/epidemiologia , Incidência
11.
Nat Commun ; 15(1): 1484, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374147

RESUMO

Flatbands play an important role in correlated quantum matter and have promising applications in photonic lattices. Synthetic magnetic fields and destructive interference in lattices are traditionally used to obtain flatbands. However, such methods can only obtain a few flatbands with most bands remaining dispersive. Here we realize all-band-flat photonic lattices of an arbitrary size by precisely controlling the coupling strengths between lattice sites to mimic those in Fock-state lattices. This allows us to go beyond the perturbative regime of strain engineering and group all eigenmodes in flatbands, which simultaneously achieves high band flatness and large usable bandwidth. We map out the distribution of each flatband in the lattices and selectively excite the eigenmodes with different chiralities. Our method paves a way in controlling band structure and topology of photonic lattices.

12.
Fitoterapia ; 174: 105868, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38378133

RESUMO

In this study, the extract from Artabotrys hexapetalus showed strong antifungal activity against phytopathogenic fungi in vitro. Four unreported aporphine alkaloids, hexapetalusine A-D (1-4), were isolated from stems and roots of Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids (5-10). Their chemical structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1-3 were determined using single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1-3) were special amidic isomers. Additionally, all isolated compounds were evaluated for their antifungal activity against four phytopathogenic fungi in vitro. Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia lunata. Liriodenine (5) displayed significant antifungal activity against Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is obviously better than positive control nystatin, suggesting that it had great potential to be developed into an effective and eco-friendly fungicide.

13.
Integr Med Res ; 13(1): 101021, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379605

RESUMO

Background: The integration of acupuncture with intramuscular injection of diclofenac sodium can expedite the onset of analgesia in treating acute renal colic caused by urolithiasis. However, it remains unclear whether acupuncture can accelerate pain relief constantly until complete remission. This study aimed to explore the extent to which acupuncture can expedite the onset time of response or complete pain relief in treating acute renal colic, and the predictive value of patient characteristics for treatment efficacy. Methods: This secondary analysis utilized data from a prior randomized controlled trial. Eighty patients with acute renal colic were randomly assigned 1:1 to the acupuncture group or the sham acupuncture group. After intramuscular injection of diclofenac sodium, acupuncture or sham acupuncture was delivered to patients. The outcomes included time to response (at least a 50 % reduction in pain) and complete pain relief. Between-group comparison under the 2 events was estimated by Kaplan-Meier methodology. Subgroup analysis was performed utilizing the Cox proportional hazards model. Results: The median response time and complete pain relief time in the acupuncture group were lower than those in the sham acupuncture group (5 vs 30 min, Log Rank P < 0.001; 20 min vs not observed, Log Rank P < 0.001, respectively). Hazard Ratios (HRs) for response across all subgroups favored the acupuncture group. All HRs for complete pain relief favored acupuncture, expect large stone and moderate pain at baseline. No interaction was found in either event. Conclusion: Acupuncture can accelerate the response time and complete pain relief time for patients with acute renal colic, with the efficacy universally. Trial registration: This study has been registered at Chinese Clinical Trial Registry: ChiCTR1900025202.

14.
Sci Total Environ ; 918: 170744, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38325483

RESUMO

Microorganisms capable of simultaneously remediating heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) pollution hold significant importance in bioremediation efforts. In this study, we investigated the ability of Pseudomonas aeruginosa AO-4 to simultaneously degrade phenanthrene (PHE) and reduce Cr (VI). Specifically, it has the ability to reduce 100 % of Cr (VI) (30 mg/L) while degrading 43.8 % of PHE (50 mg/L). In batch experiments, it was observed that the presence of Cr (VI) can enhance the degradation of PHE by strain AO-4. The solubility of PHE in soluble extracellular polymeric substances (S-EPS) was found to be related to the initial concentration of Cr (VI), which could explain why Cr (VI) promotes the degradation of PHE. Additionally, XPS analysis confirmed that Cr (VI) was reduced to Cr (III) with S-EPS produced by Pseudomonas aeruginosa AO-4. GC-MS analysis was conducted to analyze the degradation metabolites of phenanthrene, di(2-ethylhexyl) phthalate and 2TMS derivatives of salicylic acid were detected, indicating that Pseudomonas aeruginosa AO-4 is capable of degrading phenanthrene through two distinct pathways. These findings demonstrate the potential of Pseudomonas aeruginosa AO-4 in the treatment of co-contamination scenarios involving PAHs and HMs.


Assuntos
Metais Pesados , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Pseudomonas aeruginosa/metabolismo , Biodegradação Ambiental , Fenantrenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Metais Pesados/metabolismo
15.
Mol Metab ; 81: 101892, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38331318

RESUMO

BACKGROUND: Myoprotein degradation accelerates in obese individuals, resulting in a decline in muscular mass. Atg7 plays a crucial role in regulating protein stability and function through both autophagy-dependent and independent pathways. As obesity progresses, the expression of Atg7 gradually rises in muscle tissue. Nonetheless, the precise impact and mechanism of Atg7 in promoting muscle mass decline in obesity remain uncertain. The study aimed to elucidate the role and underly mechanism of Atg7 action in the context of obesity-induced muscle mass decline. METHODS: In this study, we established a murine model of high-fat diet-induced obesity (DIO) and introduced adeno-associated virus delivery of short hairpin RNA to knock down Atg7 (shAtg7) into the gastrocnemius muscle. We then examined the expressions of Atg7 and myoprotein degradation markers in the gastrocnemius tissues of obese patients and mice using immunofluorescence and western blotting techniques. To further investigate the effects of Atg7, we assessed skeletal muscle cell diameter and the myoprotein degradation pathway in C2C12 and HSkMC cells in the presence or absence of Atg7. Immunofluorescence staining for MyHC and western blotting were utilized for this purpose. To understand the transcriptional regulation of Atg7 in response to myoprotein degradation, we conducted luciferase reporter assays and chromatin immunoprecipitation experiments to examine whether FoxO3a enhances the transcription of Atg7. Moreover, we explored the role of Akt in Atg7-mediated regulation and its relevance to obesity-induced muscle mass decline. This was accomplished by Akt knockdown, treatment with MK2206, and GST pulldown assays to assess the interaction between Atg7 and Akt. RESULTS: After 20 weeks of being on a high-fat diet, obesity was induced, leading to a significant decrease in the gastrocnemius muscle area and a decline in muscle performance. This was accompanied by a notable increase in Atg7 protein expression (p < 0.01). Similarly, in gastrocnemius tissues of obese patients when compared to nonobese individuals, there was a significant increase in both Atg7 (p < 0.01) and TRIM63 (p < 0.01) levels. When palmitic acid was administered to C2C12 cells, it resulted in increased Atg7 (p < 0.01), LC3Ⅱ/Ⅰ (p < 0.01), and p62 levels (p < 0.01). Additionally, it promoted FoxO3a-mediated transcription of Atg7. The knockdown of Atg7 in the gastrocnemius partially reversed DIO-induced muscle mass decline. Furthermore, when Atg7 was knocked down in C2C12 and HSkMC cells, it mitigated palmitic acid-induced insulin resistance, increased the p-Akt/Akt ratio (p < 0.01), and reduced TRIM63 (p < 0.01). Muscular atrophy mediated by Atg7 was reversed by genetic knockdown of Akt and treatment with the p-Akt inhibitor MK2206. Palmitic acid administration increased the binding between Atg7 and Akt (p < 0.01) while weakening the binding of PDK1 (p < 0.01) and PDK2 (p < 0.01) to Akt. GST pulldown assays demonstrated that Atg7 directly interacted with the C-terminal domain of Akt. CONCLUSION: The consumption of a high-fat diet, along with lipid-induced effects, led to the inhibition of Akt signaling, which, in turn, promoted FoxO3a-mediated transcription, increasing Atg7 levels in muscle cells. The excess Atg7 inhibited the phosphorylation of Akt, leading to a cyclic activation of FoxO3a and exacerbating the decline in muscle mass regulated by obesity. Consequently, Atg7 serves as a regulatory point in determining the decline in muscle mass induced by obesity.

16.
Environ Sci Ecotechnol ; 21: 100394, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38357480

RESUMO

Crop residue burning (CRB) is a major contributor to air pollution in China. Current fire detection methods, however, are limited by either temporal resolution or accuracy, hindering the analysis of CRB's diurnal characteristics. Here we explore the diurnal spatiotemporal patterns and environmental impacts of CRB in China from 2019 to 2021 using the recently released NSMC-Himawari-8 hourly fire product. Our analysis identifies a decreasing directionality in CRB distribution in the Northeast and a notable southward shift of the CRB center, especially in winter, averaging an annual southward movement of 7.5°. Additionally, we observe a pronounced skewed distribution in daily CRB, predominantly between 17:00 and 20:00. Notably, nighttime CRB in China for the years 2019, 2020, and 2021 accounted for 51.9%, 48.5%, and 38.0% respectively, underscoring its significant environmental impact. The study further quantifies the hourly emissions from CRB in China over this period, with total emissions of CO, PM10, and PM2.5 amounting to 12,236, 2,530, and 2,258 Gg, respectively. Our findings also reveal variable lag effects of CRB on regional air quality and pollutants across different seasons, with the strongest impacts in spring and more immediate effects in late autumn. This research provides valuable insights for the regulation and control of diurnal CRB before and after large-scale agricultural activities in China, as well as the associated haze and other pollution weather conditions it causes.

17.
J Diabetes Investig ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363189

RESUMO

AIMS/INTRODUCTION: Serum asprosin is expected to become a screening indicator in early-stage diabetic heart disease. The relationship between serum asprosin and left ventricular diastolic dysfunction (LVDD) was studied in elderly patients with type 2 diabetes mellitus in the community. MATERIALS AND METHODS: A total of 252 elderly patients with type 2 diabetes mellitus were recruited from Zhuoma Community Care Station and Chengbei West Street Community Care Service Center in Changzhi City of Shanxi Province from November 2019 to July 2021. Patients were divided into the LVDD group (n = 195) and the non-LVDD group (n = 57). The t-test, Mann-Whitney U test, and χ2 test were used to compare indicators between the LVDD group and the non-LVDD group. Pearson or Spearman correlation analysis was adopted to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was applied to analyze the influencing factors on LVDD. RESULTS: Compared with patients without LVDD, patients with LVDD had a higher level of low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), and asprosin, but a lower level of early diastolic movement speed (A) to diastolic movement velocity (E) (E/A). Asprosin was positively associated with waist circumference (WC), body mass index (BMI), creatinine, triglycerides (P < 0.05), and negatively associated with E/A and high density lipoprotein cholesterol HDL-C (P < 0.05). The risk of LVDD increased with elevated asprosin levels after adjustment for age, systolic blood pressure (SBP), BMI, FPG, and LDL-C. Compared with patients in the lowest tertile of serum asprosin (<275.25 pg/mL), a serum level of asprosin between 275.25-355.08 pg/mL [OR (95% CI) is 2.368 (1.169-4.796), P < 0.05] and asprosin >355.08 pg/mL [OR (95% CI) is 2.549 (1.275-5.095), P < 0.05] patients have a higher risk of left ventricular diastolic dysfunction. CONCLUSIONS: Serum asprosin was positively associated with left ventricular diastolic dysfunction, and the risk of LVDD increased significantly with increased serum levels of asprosin.

18.
Commun Biol ; 7(1): 181, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38351296

RESUMO

Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.


Assuntos
Asma , Metaloproteinase 9 da Matriz , Animais , Camundongos , Humanos , Metaloproteinase 9 da Matriz/genética , Lipopolissacarídeos , Asma/tratamento farmacológico , Asma/genética , Brônquios , Perfilação da Expressão Gênica
19.
Mol Ther ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38311850

RESUMO

Cardiac fibrosis, a crucial pathological characteristic of various cardiac diseases, presents a significant treatment challenge. It involves the deposition of the extracellular matrix (ECM) and is influenced by genetic and epigenetic factors. Prior investigations have predominantly centered on delineating the substantial influence of epigenetic and epitranscriptomic mechanisms in driving the progression of fibrosis. Recent studies have illuminated additional avenues for modulating the progression of fibrosis, offering potential solutions to the challenging issues surrounding fibrosis treatment. In the context of cardiac fibrosis, an intricate interplay exists between m6A epitranscriptomic and epigenetics. This interplay governs various pathophysiological processes: mitochondrial dysfunction, mitochondrial fission, oxidative stress, autophagy, apoptosis, pyroptosis, ferroptosis, cell fate switching, and cell differentiation, all of which affect the advancement of cardiac fibrosis. In this comprehensive review, we meticulously analyze pertinent studies, emphasizing the interplay between m6A epitranscriptomics and partial epigenetics (including histone modifications and noncoding RNA), aiming to provide novel insights for cardiac fibrosis treatment.

20.
Clin Cosmet Investig Dermatol ; 17: 365-382, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352064

RESUMO

Background: Psoriasis is a frequent form of chronic inflammation in dermatology that is unmistakably linked to the metabolic syndrome (MetS) and its elements. This study was to explore the current status and new developments in the global research, and the holistic landscape of this field more intuitively through bibliometric analysis of scientific output and activity. Methods: Publications regarding psoriasis and MetS were searched and chosen from the database of the Web of Science Core Collection. Excel 2019, VOSviewer, and CiteSpace software were utilized to conduct bibliometric analysis. Results: There were 1096 publications included. The scientific outputs in this field had increased from 2004 to 2022, and the expansion could continue in the following years. The United States contributed the most publications (241, 21.99%) and had the most citation frequency (13,489 times). The University of California System was the most productive affiliation. Girolomoni G., Armstrong A.W., Gisondi P. and Gelfand J.M. were key and influential researchers. Journal of the European Academy of Dermatology and Venereology published the greatest number of articles (65 articles). By analyzing keyword frequency and clustering, we have identified the following areas of research interest and frontiers: prevalence, risk, association, gene expression, waist circumference, adipose tissue inflammation, vascular inflammation, cardiovascular disease, psoriatic arthritis, and fibrosis. Conclusion: This bibliometric analysis elucidates research domain of psoriasis and MetS, portraying present hotspots and future emerging trends. This field has generated significant interest and displays potential for further growth. The United States has made distinguished contributions, and currently dominates this field.

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