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1.
J Environ Sci (China) ; 149: 386-393, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181651

RESUMO

To understand the smoke level and NOx emission characteristics of in-use construction machinery in Beijing, we selected 905 construction machines in Beijing from August 2022 to April 2023 to monitor the emission level of smoke and NOx. The exhaust smoke level and excessive emission situation of different machinery types were identified, and their NOx emission levels were monitored according to the free acceleration method. We investigated the correlation of NOx and smoke emission, and proposed suggestions for controlling pollution discharge from construction machinery in the future. The results show that the exhaust smoke level was 0-2.62 m-1, followed a log-normal distribution (µ = -1.73, δ = 1.09, R2 = 0.99), with a 5.64% exceedance rate. Differences were observed among machinery types, with low-power engine forklifts showing higher smoke levels. The NOx emission range was 71-1516 ppm, followed a normal distribution (µ = 565.54, δ = 309.51, R2 = 0.83). Differences among machinery types were relatively small. Engine rated net power had the most significant impact on NOx emissions. Thus, NOx emissions from construction machinery need further attention. Furthermore, we found a weak negative correlation (p < 0.05) between the emission level of smoke and NOx, that is the synergic emission reduction effect is poor, emphasizing the need for NOx emission limits. In the future, the oversight in Beijing should prioritize phasing out China Ⅰ and China Ⅱ machinery, and monitor emissions from high-power engine China Ⅲ machinery.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Fumaça , Pequim , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Fumaça/análise , Emissões de Veículos/análise , Óxidos de Nitrogênio/análise , Indústria da Construção
2.
Artigo em Inglês | MEDLINE | ID: mdl-39423077

RESUMO

In this article, an optimal surrounding control algorithm is proposed for multiple unmanned surface vessels (USVs), in which actor-critic reinforcement learning (RL) is utilized to optimize the merging process. Specifically, the multiple-USV optimal surrounding control problem is first transformed into the Hamilton-Jacobi-Bellman (HJB) equation, which is difficult to solve due to its nonlinearity. An adaptive actor-critic RL control paradigm is then proposed to obtain the optimal surround strategy, wherein the Bellman residual error is utilized to construct the network update laws. Particularly, a virtual controller representing intermediate transitions and an actual controller operating on a dynamics model are employed as surrounding control solutions for second-order USVs; thus, optimal surrounding control of the USVs is guaranteed. In addition, the stability of the proposed controller is analyzed by means of Lyapunov theory functions. Finally, numerical simulation results demonstrate that the proposed actor-critic RL-based surrounding controller can achieve the surrounding objective while optimizing the evolution process and obtains 9.76% and 20.85% reduction in trajectory length and energy consumption compared with the existing controller.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39412669

RESUMO

PURPOSE: As the major active ingredient of Polygonatum sibriricum Red., polysaccharide of Polygonati Rhizome (PSP) has been reported to possess various pharmacological activities, especially for the treatment of chronic disorders in the elderly. This study evaluated the effect of PSP on the activities of major cytochrome P450 enzymes (CYP450) isoforms, aiming to provide theoretical reference for its co-prescription with other drugs and prevent the risk of adverse drug-drug interaction. METHODS: The activities of CYP450 isoforms were assessed in human liver microsomes with specific probe substances. Through Lineweaver-Burk fitting models, the effect of PSP on the activity of inhibited CYP450 isoforms was characterized by competitive and non-competitive models. Dose-dependent and time-dependent experiments were also performed to completely understand the inhibition. RESULTS: Among experimental isoforms, PSP significantly inhibited the activities of CYP2C9, 2D6, and 3A4 in a concentration-dependent manner with IC50 values of 14.01, 17.63, and 5.33 µM. The inhibition of CYP2C9 and 2D6 was best fitted with the competitive model with the Ki values of 7.15 and 8.92 µM, respectively, while the inhibition of CYP3A4 was non-competitive with the Ki value of 2.63 µM. Additionally, the inhibition of CYP3A4 by PSP also showed time-dependent characteristics with the inhibition parameters, KI of 1.273 µM-1 and Kinact of 0.036 min-1. CONCLUSION: PSP exerted moderate inhibition on CYP2C9 and 2D6 and strong inhibition of CYP3A4. The dosage of CYP2C9-, 2D6-, and 3A4-metabolized drugs should be adjusted when co-administrated with PSP and its sourced herbs.

4.
J Colloid Interface Sci ; 679(Pt B): 307-323, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39454262

RESUMO

The integration of photothermal and near-infrared (NIR) imaging capabilities of indocyanine green (ICG) small molecules has attracted considerable attention in tumor diagnosis and treatment. However, the abnormal upregulation of cellular heat shock proteins (HSPs) induced by photothermal therapy (PTT) enhances cellular heat resistance, thereby severely affecting the efficacy of PTT. In this study, to address the impact of HSPs on the efficacy of PTT while obtaining high-quality NIR fluorescence imaging in the NIR region, we designed a targeted peptide@ICG nanofluorescent probe encapsulated in liposomes. The introduced cRGD targeting peptide not only possesses tumor-targeting capabilities but also features LA as the last amino acid in the targeting peptide, which can generate nitric oxide (NO) under reactive oxygen species (ROS) triggering. It can happen under 808 nm single-light source NIR light, and the guanidine group in the peptide decomposes and combines with singlet oxygen molecules to generate NO gas molecules, thereby exerting an elevated photothermal effect by inhibiting the expression of HSP70. In addition, the nanoprobes enable deep imaging and treatment of glioma in situ and can be combined with a laser speckle contrast imaging (LSCI) system for multimodal imaging. This composite probe demonstrates synergistic tumor therapeutic effects of photodynamic therapy (PDT), PTT, and gas therapy, offering a promising strategy for cancer treatment.

5.
Adv Healthc Mater ; : e2401358, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39402781

RESUMO

Precise theranostics of tumors is intricately linked to the early detection and monitoring of lymph nodes (LN) and metastases, making the targeted localization of LNs essential for tumor identification. However, designing LN-targeting probes remains a significant challenge due to issues such as lymphatic uptake, biocompatibility, and fluorescence stability. To address these challenges, near-infrared II (NIR-II) fluorescence probes are developed through meticulous analysis of LN physiological structure and passive targeting strategy for LN detection and tumor therapy. An LPP-QDs-IR-820 nanocomposite (NCs) is engineered, comprising the IR-820 molecules and ultrabright PbS@CdS quantum dots (QDs), which are encapsulated within a liposome-SH-mPEG2000 polymer matrix. These NCs demonstrates remarkable lymphatic enrichment, facilitating real-time tracking of LN via electrostatic repulsion and extracellular matrix effects. Importantly, the NCs exhibit negligible in vivo toxicity and high biocompatibility. The intense NIR-II fluorescence emissions of IR-820 and PbS@CdS QDs confer upon the NCs a high NIR-II fluorescence quantum yield (6%). The cervical tumors and their deep microvessels are clearly observed via NIR-II fluorescence imaging. Moreover, the photothermal properties of IR-820 enable the NCs to achieve a photothermal conversion efficiency of 36.56%, leading to effective photothermal therapy in cervical tumor mice.

7.
Metabolites ; 14(9)2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39330502

RESUMO

Drylands cover more than 40% of global land surface and will continue to expand by 10% at the end of this century. Understanding the resistance mechanisms of native species is of particular importance for vegetation restoration and management in drylands. In the present study, metabolome of a dominant shrub Campylotropis polyantha in a dry-hot valley were investigated. Compared to plants grown at the wetter site, C. polyantha tended to slow down carbon (C) assimilation to prevent water loss concurrent with low foliar reactive oxygen species and sugar concentrations at the drier and hotter site. Nitrogen (N) assimilation and turn over were stimulated under stressful conditions and higher leaf N content was kept at the expense of root N pools. At the drier site, roots contained more water but less N compounds derived from the citric acid cycle. The site had little effect on metabolites partitioning between leaves and roots. Generally, roots contained more C but less N. Aromatic compounds were differently impacted by site conditions. The present study, for the first time, uncovers the apparent metabolic adaptations of C. polyantha to hostile dryland conditions. However, due to the limited number of samples, we are cautious about drawing general conclusions regarding the resistance mechanisms. Further studies with a broader spatial range and larger time scale are therefore recommended to provide more robust information for vegetation restoration and management in dryland areas under a changing climate.

8.
Front Genet ; 15: 1432105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233740

RESUMO

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity's impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction.Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources.

9.
PeerJ ; 12: e17980, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308831

RESUMO

Objective: By assessing the genetic diversity and associated selective traits of Kirghiz sheep (KIR), we aim to uncover the mechanisms that contribute to sheep's adaptability to the Pamir Plateau environment. Methods: This study utilized Illumina Ovine SNP50 BeadChip data from KIR residing in the Pamir Plateau, Qira Black sheep (QBS) inhabiting the Taklamakan Desert, and commonly introduced breeds including Dorper sheep (DOR), Suffolk sheep (SUF), and Hu sheep (HU). The data was analyzed using principal component analysis, phylogenetic analysis, population admixture analysis, kinship matrix analysis, linkage disequilibrium analysis, and selective signature analysis. We employed four methods for selective signature analysis: fixation index (Fst), cross-population extended homozygosity (XP-EHH), integrated haplotype score (iHS), and nucleotide diversity (Pi). These methods aim to uncover the genetic mechanisms underlying the germplasm resources of Kirghiz sheep, enhance their production traits, and explore their adaptation to challenging environmental conditions. Results: The test results unveiled potential selective signals associated with adaptive traits and growth characteristics in sheep under harsh environmental conditions, and annotated the corresponding genes accordingly. These genes encompass various functionalities such as adaptations associated with plateau, cold, and arid environment (ETAA1, UBE3D, TLE4, NXPH1, MAT2B, PPARGC1A, VEGFA, TBX15 and PLXNA4), wool traits (LMO3, TRPS1, EPHA5), body size traits (PLXNA2, EFNA5), reproductive traits (PPP3CA, PDHA2, NTRK2), and immunity (GATA3). Conclusion: Our study identified candidate genes associated with the production traits and adaptation to the harsh environment of the Pamir Plateau in Kirghiz sheep. These findings provide valuable resources for local sheep breeding programs. The objective of this study is to offer valuable insights for the sustainable development of the Kirghiz sheep industry.


Assuntos
Polimorfismo de Nucleotídeo Único , Animais , Ovinos/genética , Polimorfismo de Nucleotídeo Único/genética , Desequilíbrio de Ligação/genética , Carneiro Doméstico/genética , Filogenia , Variação Genética/genética
10.
Sci Rep ; 14(1): 22056, 2024 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333775

RESUMO

The extra domain B splice variant of fibronectin (EDB-FN), which is overexpressed in several cancers, is an approved diagnostic and therapeutic target of cancers. The aim of this study was to evaluate the EDB-FN-targeting peptide EDBp as a noninvasive imaging modality for molecular imaging of breast cancer in mice. Western blot, flow cytometry and immunofluorescence were used to assess the expression level of EDB-FN and its binding to EDRp in MCF7, SKBR3, 4T1, EMT6, MDA-MB-231 and MDA-MB-453 cells. Establishment MDA-MB-231-luc cells-based subcutaneous tumor model mice or pulmonary metastasis model mice. The EDRp molecular probes to perform fluorescent probes for near-infrared fluorescence (NIRF)·and PET imaging of model mice. Our results demonstrate that EDBp-Cy5 had a strong binding ability to the MDA-MB-231 cells and exhibited specific tumor accumulation in MDA-MB-231 subcutaneous and pulmonary metastasis model mice. Importantly, the EDBp peptide-based radiotracer [18F]-AlF-NOTA-EDBp provided excellent diagnostic value for positron emission tomography (PET) imaging of breast cancer, especially in subcutaneous model mice. The uptake of [18F]-AlF-NOTA-EDBp in subcutaneous tumors (6.53 ± 0.89%, ID/g) was unexpectedly higher than that in the kidney (4.96 ± 0.20, %ID/g). The high tumor uptake of these probes in mice suggests their potential for application in imaging of EDB-FN-positive breast cancer for disease staging of regional and distant metastases.


Assuntos
Neoplasias da Mama , Fibronectinas , Corantes Fluorescentes , Tomografia por Emissão de Pósitrons , Animais , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Fibronectinas/metabolismo , Imagem Óptica/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos BALB C
11.
Hematology ; 29(1): 2399362, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39279268

RESUMO

INTRODUCTION: Acute promyelocytic leukemia (APL) is mainly due to the chromosome translocation t(15; 17) (q22; q12), leading to the formation of PML-RARα fusion protein. However, some patients carried rare translocation involving RARα gene, and they were referred to as variant APL caused by the RAR family (RARα, RARB, and RARG) and partner genes. PLZF-RARα was a rare type of molecular genetic abnormality with unfavorable prognosis that has been reported in few cases in variant APL. Knowledge of PLZF-RARα (+) APL treatment remains limited understood. CASE REPORT: We presented a case of variant APL in a 47-year-old female, who was PLZF-RARα positive detected by reverse transcription polymerase chain reaction (RT-PCR). The patient did not respond to all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide (As2O3) combined induction chemotherapy. Then, the patient was treated with Venetoclax combining with decitabine as the salvage therapy and achieved morphological remission and PLZF/RARα gene negative. CONCLUSION: Venetoclax combining with decitabine can be used as an effective therapy in the PLZF-RARα positive APL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes , Decitabina , Leucemia Promielocítica Aguda , Proteínas de Fusão Oncogênica , Sulfonamidas , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Feminino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Decitabina/uso terapêutico , Decitabina/administração & dosagem , Sulfonamidas/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/uso terapêutico
12.
J Orthop Surg Res ; 19(1): 604, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342253

RESUMO

OBJECTIVES: The incidence of hemidiaphragmatic paresis (HDP) in superior trunk block (STB) usually depends on the dose of local anesthetic. This study aimed to further evaluate the impact of a lower volume (10 mL) of the same low concentration (0.25%) ropivacaine compared to a conventional volume (15 mL), on diaphragmatic function and analgesic efficacy under a multimodal analgesia regimen for shoulder arthroscopy. METHODS: Patients scheduled to undergo shoulder arthroscopy were randomized allocated to receive either 10 mL or 15 mL of 0.25% ropivacaine in the STB under ultrasound guidance prior to general anesthesia. The primary outcome was the percentage reduction in diaphragm excursion (ΔDE) between baseline and 30 min after block. Secondary outcomes included DE and diaphragm thickening fraction (DTF) before and after block, incidence of HDP, onset of sensory/motor block, duration of analgesia/motor block, dermatomal coverage area of the block, postoperative pain severity, pre- and post-block respiratory function and intraoperative hemodynamic parameters, the use of other anesthetic and analgesic drugs, post-block complications, and adverse events post-surgery. RESULTS: Compared with 15 mL volume, 10 mL ropivacaine significantly reduced the incidence of post-block HDP (as measured by ΔDE: 39.47% vs. 64.10%; and by post-block DTF: 13.16% vs. 33.33%). There was no significant difference in onset of sensory block, duration of analgesia/motor block, dermatomal coverage area of the block, postoperative pain severity between the two groups, except that the onset of motor block was significantly slower in the 10 mL group than in the 15 mL group. Pre- and post-block respiratory function and intraoperative hemodynamic parameters, the use of other anesthetic and analgesic drugs, post-block complications, or postoperative adverse events were not significantly different between the two groups. CONCLUSION: In shoulder arthroscopy, STB with 10 mL of ropivacaine can reduce the incidence of HDP with no significant difference in analgesic effects under a multimodal analgesia regimen compared with 15 mL. TRIAL REGISTRATION: We registered the study at chictr.org ( ChiCTR2200057543 , 14/03/2022. https://www.chictr.ogr.cn.


Assuntos
Anestésicos Locais , Artroscopia , Diafragma , Bloqueio Nervoso , Ropivacaina , Articulação do Ombro , Ultrassonografia de Intervenção , Humanos , Ropivacaina/administração & dosagem , Artroscopia/métodos , Masculino , Feminino , Anestésicos Locais/administração & dosagem , Pessoa de Meia-Idade , Adulto , Ultrassonografia de Intervenção/métodos , Diafragma/diagnóstico por imagem , Diafragma/efeitos dos fármacos , Diafragma/inervação , Articulação do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Paralisia Respiratória/prevenção & controle , Paralisia Respiratória/etiologia
13.
Micromachines (Basel) ; 15(9)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39337802

RESUMO

A novel polishing method is proposed to increase material removal rates through the acceleration of abrasive movements using micro-jets formed by spontaneous collapses of bubbles due to the cavitation in a special-shaped Venturi tube. The Venturi structure is optimized by numerical simulations. Process-related parameters for the optimal cavitation ratio are investigated for achieving maximum adaptation to polishing flat workpieces. Furthermore, this novel approach enhances processing efficiency by approximately 60% compared to traditional abrasive flow polishing. The processing method that employs cavitation bubbles within a special-shaped Venturi tube to augment the flow of abrasive particles holds significant potential for material polishing applications.

14.
Proc Natl Acad Sci U S A ; 121(35): e2405877121, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39163338

RESUMO

The advent of drones has revolutionized various aspects of our lives, and in the realm of biological systems, molecular drones hold immense promise as "magic bullets" for major diseases. Herein, we introduce a unique class of fluorinated macromolecular amphiphiles, designed in the shape of jellyfish, serving as exemplary molecular drones for fluorine-19 MRI (19F MRI) and fluorescence imaging (FLI)-guided drug delivery, status reporting, and targeted cancer therapy. Functioning akin to their mechanical counterparts, these biocompatible molecular drones autonomously assemble with hydrophobic drugs to form uniform nanoparticles, facilitating efficient drug delivery into cells. The status of drug delivery can be tracked through aggregation-induced emission (AIE) of FLI and 19F MRI. Furthermore, when loaded with a heptamethine cyanine fluorescent dye IR-780, these molecular drones enable near-infrared (NIR) FL detection of tumors and precise delivery of the photosensitizer. Similarly, when loaded with doxorubicin (DOX), they enable targeted chemotherapy with fluorescence resonance energy transfer (FRET) FL for real-time status updates, resulting in enhanced therapeutic efficacy. Compared to conventional drug delivery systems, molecular drones stand out for their simplicity, precise structure, versatility, and ability to provide instantaneous status updates. This study presents prototype molecular drones capable of executing fundamental drone functions, laying the groundwork for the development of more sophisticated molecular machines with significant biomedical implications.


Assuntos
Doxorrubicina , Sistemas de Liberação de Medicamentos , Humanos , Animais , Sistemas de Liberação de Medicamentos/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Halogenação , Camundongos , Nanopartículas/química , Corantes Fluorescentes/química , Substâncias Macromoleculares/química , Imagem Óptica/métodos , Imagem por Ressonância Magnética de Flúor-19/métodos , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
15.
Adv Mater ; 36(40): e2406552, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39169735

RESUMO

Spin currents of perpendicularly polarized spins (z spins) have received blooming interest for the potential in energy-efficient spin-orbit torque switching of perpendicular magnetization in the absence of a magnetic field. However, generation of z spins is limited mainly to magnetically or crystallographically low-symmetry single crystals that are hardly compatible with the integration to semiconductor circuits. This work reports efficient generation of z spins in sputter-deposited polycrystalline heavy metal devices via a new mechanism of broken electric symmetries in both the transverse and perpendicular directions. Both the damping-like and field-like spin-orbit torques of z spins can be tuned significantly by varying the degree of the electric asymmetries via the length, width, and thickness of devices as well as by varying the type of the heavy metals. The presence of z spins also enables deterministic, nearly-full, external-magnetic-field-free switching of a uniform perpendicularly magnetized FeCoB layer, the core structure of magnetic tunnel junctions, with high coercivity at a low current density. These results establish the first universal, energy-efficient, integration-friendly approach to generate z-spin current by electric asymmetry design for dense and low-power spin-torque memory and computing technologies and will stimulate investigation of z-spin currents in various polycrystalline materials.

16.
Curr Drug Metab ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39108114

RESUMO

BACKGROUND: Yunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear. OBJECTIVE: The objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC. METHODS: The efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice. RESULTS: The presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco- 2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice. CONCLUSION: YAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.

17.
BMC Psychiatry ; 24(1): 583, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192231

RESUMO

BACKGROUND: This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . METHODS: A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. RESULTS: During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = - 0.346, P < 0.01) and positively correlated with sleep quality (beta = 0.846, P < 0.001), indicating that students experiencing depressive symptoms were more likely to have a later chronotype and poor sleep quality. A later chronotype (beta = - 0.019, P < 0.05) and poor sleep quality (beta = 0.066, P < 0.01) predicted suicidal ideation. Depression emerged as a direct and significant risk factor for suicidal ideation (effect value = 0.535, 95% confidence interval: 0.449 ~ 0.622). Chronotype and sleep quality were found to have potential mediating effects on the relationship between depression and suicidal ideation; however, the chain-mediating effect of chronotype and sleep quality was not statistically significant. CONCLUSIONS: Our findings suggest that during the COVID-19 pandemic, depression can precipitate suicidal ideation through its influence on sleep chronotype and quality. These compelling findings highlight the urgency of early intervention strategies intended to mitigate suicidal thoughts, particularly among students exhibiting depressive symptoms, who experience disrupted sleep patterns and poor sleep quality.


Assuntos
COVID-19 , Depressão , Qualidade do Sono , Estudantes , Ideação Suicida , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Estudantes/psicologia , Feminino , Masculino , China/epidemiologia , Depressão/psicologia , Depressão/epidemiologia , Adulto Jovem , Universidades , Adulto , Adolescente , Ritmo Circadiano/fisiologia , Inquéritos e Questionários , Prevalência , Cronotipo
18.
Anal Chim Acta ; 1319: 342983, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39122281

RESUMO

BACKGROUND: Deciphering the molecular dynamics (MD) of rotaxanes is crucial for designing and refining their applications in molecular devices. This study employed fluorine-19 nuclear magnetic resonance (19F NMR) and magnetic resonance imaging (MRI) to unveil the interplay between mechanical bonds and steric hindrance in a series of fluorinated rotaxanes. RESULTS: 1H/19F NMR revealed stable "Z"-shaped wheel conformations minimizing steric clashes and favoring π-π interactions with the axle. Utilizing fluorines and axle protons as reporters, 1H/19F relaxation rates and solid-state 19F NMR studies demonstrated that mechanical bond primarily governs wheel motion, while steric hindrance dictates axle movement. Intriguingly, mechanical bond mainly affects local axle groups, leaving distant ones minimally impacted. MD simulations corroborated these findings. Temperature-dependent 19F NMR indicated that energy input enhances rotational motion and wheel conformational transitions. Furthermore, the drastic increase in 19F relaxation rates upon mechanical bond formation and steric hindrance enables sensitive and selective 19F MRI visualization of MD changes. SIGNIFICANCE: This study, by elucidating the roles of internal and external factors on rotaxane molecular dynamics using 19F NMR/MRI, offers valuable insights that can advance the field of rotaxane-based molecular devices.

19.
Metabolites ; 14(8)2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39195549

RESUMO

In recent years, afforestation has been conducted in China's hot and dry valleys. However, there is still a paucity of knowledge regarding the performance of tree species in these semi-arid regions, particularly with regard to interspecies differences. The present study compares the growth and metabolome characteristics of two widely used cypress species, namely Cupressus chengiana and Platycladus orientalis, grown at two sites with distinct climate conditions in the hot and dry Minjiang Valley in southwestern China. The findings indicate that C. chengiana trees exhibit superior growth rates compared to P. orientalis trees at both study sites. In comparison to P. orientalis trees, C. chengiana trees demonstrated a greater tendency to close their stomata in order to prevent water loss at the hotter and drier site, Llianghekou (LHK). Additionally, C. chengiana trees exhibited significantly lower hydrogen peroxide levels than P. orientalis trees, either due to lower production and/or higher scavenging of reactive oxygen species. C. chengiana trees accumulated soluble sugars as well as sugar derivatives, particularly those involved in sucrose and galactose metabolisms under stressful conditions. The species-specific differences were also reflected in metabolites involved in the tricarboxylic acid cycle, nitrogen, and secondary metabolisms. The metabolome profiles of the two species appeared to be influenced by the prevailing climatic conditions. It appeared that the trees at the drier and hotter site, LHK, were capable of efficient nitrogen uptake from the soil despite the low soil nitrogen concentration. This study is the first to compare the growth performance and metabolic profiles of two widely used tree species with high resistance to adverse conditions. In addition to the species-specific differences and adaptations to different sites, the present study also provides insights into potential management strategies to alleviate abiotic stress, particularly with regard to nitrogen nutrients, in the context of climate change.

20.
Adv Sci (Weinh) ; 11(36): e2401014, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39083299

RESUMO

Precise identification of glioblastoma (GBM) microinfiltration, which is essential for achieving complete resection, remains an enormous challenge in clinical practice. Here, the study demonstrates that Raman spectroscopy effectively identifies GBM microinfiltration with cellular resolution in clinical specimens. The spectral differences between infiltrative lesions and normal brain tissues are attributed to phospholipids, nucleic acids, amino acids, and unsaturated fatty acids. These biochemical metabolites identified by Raman spectroscopy are further confirmed by spatial metabolomics. Based on differential spectra, Raman imaging resolves important morphological information relevant to GBM lesions in a label-free manner. The area under the receiver operating characteristic curve (AUC) for Raman spectroscopy combined with machine learning in detecting infiltrative lesions exceeds 95%. Most importantly, the cancer cell threshold identified by Raman spectroscopy is as low as 3 human GBM cells per 0.01 mm2. Raman spectroscopy enables the detection of previously undetectable diffusely infiltrative cancer cells, which holds potential value in guiding complete tumor resection in GBM patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Análise Espectral Raman , Análise Espectral Raman/métodos , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo
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