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1.
Food Chem ; 460(Pt 2): 140612, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39089034

ABSTRACT

Sorghum seeds can discolor during storage. Treatment of seeds with citric acid improves sensory quality and antioxidant activity. This study compared the differences in phenotypic and antioxidant activity between citric acid-treated and water-treated sorghum seeds. The study used transcriptomics and metabolomics approaches to investigate the regulatory mechanisms. The ∆a, ∆b and ∆l values of citric acid-treated sorghum seeds significantly increased after 6 months of storage. The SOD, POD and CAT enzyme activities of the citric acid-treated group were 1.94, 1.91 and 2.45 times higher than those of the control, respectively. The joint transcriptome and metabolome analysis showed that the citric acid-induced changes were mainly focused on the flavonoid biosynthetic pathway. Citric acid treatment up-regulated CHS, ANR, MYB and bHLH genes and promoted flavonoid accumulation. In conclusion, citric acid treatment promotes flavonoid accumulation, delays sorghum seed discoloration, and enhances antioxidant activity and storage life.

2.
Adv Mater ; : e2406343, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39096067

ABSTRACT

To improve the performance of Lithium-Sulfur (Li-S) batteries, the reaction catalysts of lithium polysulfides (LiPSs) reactions should have the characteristics of large surface area, efficient atomic utilization, high conductivity, small size, good stability, and strong adjustability. Herein, Anderson-type polyoxometalate ([TMMo6O24]n-, TM = Co, Ni, Fe, represented by TMMo6 POMs) are used as the modified materials for Li-S battery separator. By customizing the central metal atoms, this work gains insights into the layer-by-layer electron transfer mechanism between TMMo6 units and LiPSs, similar to the collision effect of a bowling ball. Theoretical analysis and in situ experimental characterization show that the changes of CoMo6 units with moderate binding energy and lowest Gibbs free energy result in the formation of robust polar bonds and prolonged S─S bonds after adsorption. Hence, the representative Li-S battery with CoMo6 and graphene composite modified separator has a high initial capacity of 1588.6 mA h g-1 at 0.2 C, excellent cycle performance of more than 3000 cycles at 5 C, and uniform Li+ transport over 1900 h. More importantly, this work has revealed the inherent contradiction between the kinetics and thermodynamics, achieving a stable cycle in the temperature range of -20 to 60 °C.

3.
J Clin Oncol ; : JCO2400500, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39102629

ABSTRACT

PURPOSE: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear. METHODS: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes. RESULTS: Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within CRLF2-, DUX4-, and KMT2A-rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases. CONCLUSION: Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.

4.
Biomater Res ; 28: 0047, 2024.
Article in English | MEDLINE | ID: mdl-38952714

ABSTRACT

Intervertebral discs (IVDs) have a limited self-regenerative capacity and current strategies for IVD regeneration are unsatisfactory. Recent studies showed that small extracellular vesicles derived from M2 macrophage cells (M2-sEVs) inhibited inflammation by delivery of various bioactive molecules to recipient cells, which indicated that M2-sEVs may offer a therapeutic strategy for the repair of IVDs. Herein, we investigated the roles and mechanisms of M2-sEVs on IVD regeneration. The in vitro results demonstrated that M2-sEVs inhibited pyroptosis, preserved cellular viability, and promoted migration of nucleus pulposus cells (NPCs). Bioinformatics analysis and verification experiments of microRNA (miR) expression showed that miR-221-3p was highly expressed in M2-sEVs. The mechanism of action was explored and indicated that M2-sEVs inhibited pyroptosis of NPCs through transfer of miR-221-3p, which suppressed the expression levels of phosphatase and tensin homolog and NOD-, LRR-, and pyrin domain-containing protein 3. Moreover, we fabricated decellularized ECM-hydrogel (dECM) for sustained release of M2-sEVs, which exhibited biocompatibility and controlled release properties. The in vivo results revealed that dECM-hydrogel containing M2-sEVs (dECM/M2-sEVs) delayed the degeneration of intervertebral disc degeneration (IDD) models. In addition to demonstrating a promising therapeutic for IDD, this study provided valuable data for furthering the understanding of the roles and mechanisms of M2-sEVs in IVD regeneration.

5.
Small ; : e2403234, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963174

ABSTRACT

Manganese halides are one of the most potential candidates for large-area flat-panel detection owing to their biological safety and all-solution preparation. However, reducing photon scattering and enhancing the efficient luminescence of scintillator screens remains a challenge due to their uncontrollable crystallization and serious nonradiative recombination. Herein, an organic cation modulation is reported to control the crystallization process and enhance the luminescence properties of manganese halides. Given the industrial requirements of the X-ray flat-panel detector, the large-area A2MnBr4 screen (900 cm2) with excellent uniformity is blade-coated at 60 °C. Theoretical calculations and in situ measurements reveal that organic cations with larger steric hindrance can slow down the crystallization of the screen, thus neatening the crystal arrangement and reducing the photon scattering. Moreover, larger steric hindrance can also endow the material with higher exciton binding energy, which is beneficial for restraining nonradiative recombination. Therefore, the BPP2MnBr4 (BPP = C25H22P+) screen with larger steric hindrance exhibits a superior spatial resolution (>20 lp mm-1) and ultra-low detection limit (< 250 nGyair s-1). This is the first time steric hindrance modulation is used in blade-coated scintillator screens, and it believes this study will provide some guidance for the development of high-performance manganese halide scintillators.

6.
Angew Chem Int Ed Engl ; : e202409419, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975974

ABSTRACT

The local acidity at the anode surface during electrolysis is apparently stronger than that in bulk electrolyte due to the deprotonation from the reactant, which leads to the deteriorated electrocatalytic performances and product distributions. Here, an anode-electrolyte interfacial acidity regulation strategy has been proposed to inhibit local acidification at the surface of anode and enhance the electrocatalytic activity and selectivity of anodic reactions. As a proof of the concept, CeO2-x Lewis acid component has been employed as a supporter to load Au nanoparticles to accelerate the diffusion and enrichment of OH- toward the anode surface, so as to accelerate the electrocatalytic alcohol oxidation reaction. As the result, Au/CeO2-x exhibits much enhanced lactic acid selectivity of 81% and electrochemical activity of 693 mA·cm-2 current density in glycerol oxidation reaction compared to pure Au. Mechanism investigation reveals that the introduced Lewis acid promotes the mass transport and concentration of OH- on the anode surface, thus promoting the generation of lactic acid through the simultaneous enhancements of Faradaic and non-Faradaic processes. Attractively, the proposed strategy can be used for the electro-oxidation performance enhancements of a variety of alcohols, which thereby provides a new perspective for efficient alcohol electro-oxidations and the corresponding electrocatalyst design.

7.
Cancer Sci ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970292

ABSTRACT

The specificity and clinical relevance of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa), as well as the effect of androgen deprivation therapy (ADT) on CAFs, remain to be fully elucidated. Using cell lineage diversity and weighted gene co-expression network analysis (WGCNA), we pinpointed a unique CAF signature exclusive to PCa. The specificity of this CAF signature was validated through single-cell RNA sequencing (scRNA-seq), cell line RNA sequencing, and immunohistochemistry. This signature associates CAFs with tumor progression, elevated Gleason scores, and the emergence of castration resistant prostate cancer (CRPC). Using scRNA-seq on collected samples, we demonstrated that the CAF-specific signature is not altered by ADT, maintaining its peak signal output. Identifying a PCa-specific CAF signature and observing signaling changes in CAFs after ADT lay essential groundwork for further PCa studies.

8.
Angew Chem Int Ed Engl ; : e202411502, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39072890

ABSTRACT

Plastic pollution, an increasingly serious global problem, can be addressed through the full lifecycle management of plastics, including plastics recycling as one of the most promising approaches. System design, catalyst development, and product separation are the keys in improving the economics of electrocatalytic plastics recycling. Here, a membrane-free co-production system was devised to produce succinic acid (SA) at both anode and cathode respectively by the co-electrolysis of polybutylene succinate (PBS) waste plastics and biomass-derived maleic acid (MA) for the first time. To this end, Cr3+-Ni(OH)2 electrocatalyst featuring much enhanced 1,4-butanediol (BDO) oxidation reaction (BOR) activity has been synthesized and the role of doped Cr has been revealed as an "electron puller" to accelerate the rate-determining step (RDS) in the Ni2+/Ni3+ cycling. Impressively, an extra-high SA production rate of 3.02 g h-1 and ultra-high apparent Faraday efficiency towards SA (FEapparent=181.5%) have been obtained. A carbon dioxide-assisted sequential precipitation approach has been developed to produce high-purity SA and byproduct NaHCO3 solids. Preliminary techno-economic analysis demonstrates that the reported system is economically profitable and promising for future industrial applications.

9.
Oncol Lett ; 28(3): 405, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38983127

ABSTRACT

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

10.
Ecotoxicol Environ Saf ; 281: 116674, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38964056

ABSTRACT

The persistence of the novel brominated flame retardant, bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), in the environment and its potential for bioaccumulation in living organisms, including humans, further exacerbate its health risks. Therefore, ongoing research is crucial for fully understanding the extent of TBPH's neurotoxicity and for developing effective mitigation strategies. This study aims to investigate the potential neurotoxicity of TBPH on mouse neurobehavior and to evaluate the protective effects of the natural antioxidant astaxanthin (AST) against TBPH-induced neurotoxicity. The results indicate that exposure to TBPH can lead to a decline in learning and memory abilities and abnormal behaviors in mice, which may be associated with oxidative stress responses and apoptosis in the hippocampus. TBPH may disrupt the normal function of hippocampal neurons by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Mice exposed to TBPH treated with AST showed improved learning and memory abilities in the Morris water maze (MWM) and Step-down test (SDT). AST, through its antioxidant action, was able to significantly reduce the increase in reactive oxygen species (ROS) levels induced by TBPH, the increased expression of apoptosis markers, and the activation of the ERK1/2-FOS signaling pathway, alleviating TBPH-induced apoptosis in hippocampal neurons and improving neurobehavioral outcomes. These findings suggest that AST may alleviate the neurotoxicity of TBPH by modulating molecular events related to apoptosis and the ERK1/2-FOS signaling pathway. Thus, this study provides evidence for AST as a potential interventional strategy for the prevention or treatment of cognitive decline associated with environmental neurotoxicant exposure.


Subject(s)
Hippocampus , MAP Kinase Signaling System , Reactive Oxygen Species , Xanthophylls , Animals , Xanthophylls/pharmacology , Mice , Reactive Oxygen Species/metabolism , Hippocampus/drug effects , MAP Kinase Signaling System/drug effects , Male , Behavior, Animal/drug effects , Oxidative Stress/drug effects , Flame Retardants/toxicity , Antioxidants/pharmacology , Phthalic Acids/toxicity , Apoptosis/drug effects , Neurons/drug effects , Maze Learning/drug effects
11.
Opt Lett ; 49(13): 3810-3813, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950273

ABSTRACT

Exceptional points (EPs) of non-Hermitian systems are sensitive to perturbations and facilitate the development of highly sensitive gyroscopes. We propose a compact multi-mode optical gyroscope protocol that incorporates two coupled rings and exhibits a fourth-order EP, achieving higher sensitivity compared to gyroscopes based on second-order EPs. We show that the gyroscope sensitivity can be further improved by deviating from the fourth-order EP due to the gain dependence on the cavity intensity. Furthermore, our protocol exhibits resilience against backscattering from counter-propagating modes, which leads to a reduced angular random walk (ARW) factor and increased sensitivity. These features make our protocol highly promising for advancing high-performance optical gyroscopes and enhancing angular velocity sensing technologies.

12.
Perioper Med (Lond) ; 13(1): 69, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982526

ABSTRACT

The purpose of this study is to systematically analyze the development trend, research hotspots, and future development direction on the treatment of neuropathic pain (NP) with spinal cord stimulation through bibliometric method. We extracted the literature related to the treatment of NP with spinal cord stimulation from January 2004 to December 2023 from the Web of Science database. As a result, a total of 264 articles were retrieved. By analyzing the annual published articles, authors, countries, institutions, journals, co-cited literature, and keywords, we found that the count of publication in this field has been experiencing an overall growth, and the publications within the past 5 years accounted for 42% of the total output. Experts from the United States and the UK have made significant contributions in this field and established a stable collaborative team, initially establishing an international cooperation network. Pain is the frequently cited journal in this field. The study on spinal cord stimulation therapy for NP especially the study on spinal cord stimulation therapy for back surgery failure syndrome (FBSS) and its potential mechanisms are the research hotspots in this field, while the study on novel paradigms such as high-frequency spinal cord stimulation and spinal cord burst stimulation represents the future development directions. In short, spinal cord stimulation has been an effective treatment method for NP. The novel paradigms of spinal cord stimulation are the key point of future research in this field.

13.
Int J Biol Macromol ; 276(Pt 1): 133871, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39009257

ABSTRACT

Camptothecin (CPT) is a monoterpenoid indole alkaloid with a wide spectrum of anticancer activity. However, its application is hindered by poor solubility, lack of targeting specificity, and severe side effects. Structural derivatization of CPT and the development of suitable drug delivery systems are potential strategies for addressing these issues. In this study, we discovered that the protein Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) from Homo sapiens catalyzes CPT to yield 9-hydroxycamptothecin (9-HCPT), which exhibits increased water solubility and cytotoxicity. We then created a RNA-protein complex based drug delivery system with enzyme and pH responsiveness and improved the targeting and stability of the nanomedicine through protein module assembly. The subcellular localization of nanoparticles can be visualized using fluorescent RNA probes. Our results not only identified the protein CYP1A1 responsible for the structural derivatization of CPT to synthesize 9-HCPT but also offered potential strategies for enhancing the utilization of silk-based drug delivery systems in tumor therapy.

14.
Syst Rev ; 13(1): 187, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026375

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) has become a public health issue. Several systematic reviews (SRs) and meta-analyses (MAs) indicate that traditional Chinese exercise (TCE) may be an effective treatment for reducing pain and stiffness and improving physical function in people with knee osteoarthritis (KOA). OBJECTIVES: To evaluate the literature quality and evidence for the systematic reviews of TCE for KOA and provide evidence to support the clinical application of TCE for KOA. METHODS: Eight databases were searched from their inception to January 3, 2023, to retrieve relevant literature, including China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Scientific Journal Database (VIP), China Biology Medical literature database (CBM), PubMed, Embase, Web of Science and Cochrane Library, without restrictions on publication date or language. AMSTAR-2 and PRISMA 2020 assessed the methodological and reporting quality of included SRs/MAs. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was utilized to evaluate the quality of evidence. RESULTS: A total of 18 SRs/MAs were included. The methodological quality was "very low" based on AMSTAR-2. The overall reporting quality was deficient based on PRISMA 2020. The quality of Chinese and English literature differed, with English literature being superior in methodological and reporting quality. Among 93 pieces of evidence obtained, 46 (49.46%) were of very low quality, 34 (36.56%) were of low quality, 13 (13.98%) were of moderate quality, and none were of high quality. TCE was supported by 76 pieces of evidence (81.72%). CONCLUSION: TCE appears beneficial and safe for managing KOA. However, due to the relatively low methodological and evidentiary quality of included SRs/MAs, clinicians should interpret these findings cautiously.


Subject(s)
Exercise Therapy , Osteoarthritis, Knee , Systematic Reviews as Topic , Humans , Exercise Therapy/methods , Medicine, Chinese Traditional/methods , Osteoarthritis, Knee/therapy
15.
Nat Commun ; 15(1): 6098, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030230

ABSTRACT

The electrochemical oxygen reduction reaction (ORR) to produce hydrogen peroxide (H2O2) is appealing due to its sustainability. However, its efficiency is compromised by the competing 4e- ORR pathway. In this work, we report a hierarchical carbon nanosheet array electrode with a single-atom Ni catalyst synthesized using organic molecule-intercalated layered double hydroxides as precursors. The electrode exhibits excellent 2e- ORR performance under alkaline conditions and achieves H2O2 yield rates of 0.73 mol gcat-1 h-1 in the H-cell and 5.48 mol gcat-1 h-1 in the flow cell, outperforming most reported catalysts. The experimental results show that the Ni atoms selectively adsorb O2, while carbon nanosheets generate reactive hydrogen species, synergistically enhancing H2O2 production. Furthermore, a coupling reaction system integrating the 2e- ORR with ethylene glycol oxidation significantly enhances H2O2 yield rate to 7.30 mol gcat-1 h-1 while producing valuable glycolic acid. Moreover, we convert alkaline electrolyte containing H2O2 directly into the downstream product sodium perborate to reduce the separation cost further. Techno-economic analysis validates the economic viability of this system.

16.
Entropy (Basel) ; 26(7)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39056963

ABSTRACT

In this paper, we investigate the impact of classical optical communications in quantum key distribution (QKD) over hollow-core fiber (HCF), multi-core fiber (MCF) and single-core fiber (SCF) and propose wavelength allocation schemes to enhance QKD performance. Firstly, we theoretically analyze noise interference in QKD over HCF, MCF and SCF, such as spontaneous Raman scattering (SpRS) and four-wave mixing (FWM). To mitigate these noise types and optimize QKD performance, we propose a joint noise suppression wavelength allocation (JSWA) scheme. FWM noise suppression wavelength allocation and Raman noise suppression wavelength allocation are also proposed for comparison. The JSWA scheme indicates a significant enhancement in extending the simultaneous transmission distance of classical signals and QKD, reaching approximately 100 km in HCF and 165 km in MCF under a classical power per channel of 10 dBm. Therefore, MCF offers a longer secure transmission distance compared with HCF when classical signals and QKD coexist in the C-band. However, when classical signals are in the C-band and QKD operates in the O-band, the performance of QKD in HCF surpasses that in MCF. This research establishes technical foundations for the design and deployment of QKD optical networks.

17.
Plant Commun ; : 101041, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39030906

ABSTRACT

Diatoms, a group of prevalent marine algae, significantly contribute to global primary productivity. Their substantial biomass is linked to enhanced absorption of blue-green light underwater, facilitated by fucoxanthin chlorophyll a/c-binding proteins (FCPs), exhibiting oligomeric diversity across diatom species. Utilizing mild CN-PAGE analysis on solubilized thylakoid membranes, we displayed monomeric, dimeric, trimeric, tetrameric and pentameric FCPs in diatoms. Mass spectrometry analysis revealed each oligomeric FCP has specific protein compositions, constituting a large Lhcf family of FCP antennas. In addition, we resolved the structures of Thalassiosira pseudonana FCP (Tp-FCP) homotrimer and Chaetoceros gracilis FCP (Cg-FCP) pentamer by cryo-electron microscopy at 2.73 Å and 2.65 Å resolutions, respectively. The distinct pigment composition and organization in various oligomeric FCPs change their blue-green light-harvesting, excitation energy transfer pathways. In comparison to dimeric and trimeric FCPs, Cg-FCP tetramer and Cg-FCP pentamer exhibit stronger absorption by Chls c, red-shifted and broader Chl a fluorescence emission, as well as more robust circular dichroism signals originating from Chl a-carotenoid dimers. These spectroscopic characteristics indicate that Chl a molecules in Cg-FCP tetramer and Cg-FCP pentamer are more heterogeneous than in both dimers and Tp-FCP trimer. The structural and spectroscopic insights provided by this study contribute to a better understanding of the mechanisms that empower diatoms to adapt to fluctuating light environments.

18.
Discov Oncol ; 15(1): 300, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39044005

ABSTRACT

Cuproptosis is a novel type to regulate cell death with copper-dependent manner, and has been reported to involve in the occurrence and development of various malignant tumors. However, the association between cuproptosis and the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remained unclear. To address this question, we integrated the single cell RNA sequencing (scRNA-seq) datasets of ccRCC across different stages, systematically examined the distinctive expression patterns of cuproptosis-related genes (CRGs) within the TME of ccRCC, and explored the crucial signatures using the spatial transcriptome sequencing (ST-seq) dataset. The cuproptosis activities reduced in cancer tissues along with the ccRCC development, and recovered after therapy. We identified HILPDA+ ccRCC1 subtype, characterized with hypoxia, as cuproptosis susceptible cells associated with a better prognosis. The main co-expression modules of HILPDA+ ccRCC1 subtype highlighted the role in anion transport, response to oxygen species and PD-L1-PD-1 pathway. Furthermore, the immunosuppressive cells might interact with HILPDA+ ccRCC1 subtype via HAVCR2-LGALS9, C3-C3AR1, HLA-A-CD8B and HLA-C-CD8A axises to shape the cuproptosis-related TME landscape. In summary, we anticipate that this study will offer valuable insights and potential strategies of cuproptosis for therapy of ccRCC.

19.
Health Place ; 89: 103283, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38850725

ABSTRACT

As a global public health problem, sedentary behavior has attracted more and more attention. Although numerous studies have demonstrated many benefits of green spaces to health, causal evidence on how green spaces affect people's sedentary behavior is scarce. This study used a natural experiment to evaluate the impact of greenway intervention on sedentary behavior. Two waves of data were collected in 2016 and 2019 (before and after the intervention) at East Lake Greenway (102-km-long) in Wuhan, China, with 1020 participants in 52 neighborhoods. We adopted three major methods to evaluate the impact of greenway intervention on sedentary behavior, including Propensity Score Matching and difference-in-difference (PSM-DID) method (with both individual and neighborhood variables to match samples), continuous treatment DID method (with distance to the greenway as the continuous treatment), and mediation analysis (with moderate to vigorous physical activity or MVPA, and walking time as the mediator). The results revealed that the greenway intervention significantly reduced participants' sedentary time and the intervention has a distance decay effect. The closer to the greenway, the greater decrease in sedentary time after the greenway opening. Furthermore, we found that MVPA and walking time mediate the impact of the greenway intervention on the change in sedentary behavior. The effect of greenway intervention was more beneficial for those under the age of 60, those who were employed, or those who were married. Our findings provided robust evidence that exposure to urban greenways affects sedentary behavior and such green infrastructures help protect public health in high-density urban areas.

20.
J Mater Chem B ; 12(25): 6128-6136, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38836578

ABSTRACT

Boron neutron capture therapy (BNCT) is an emerging approach for treating malignant tumors with binary targeting. However, its clinical application has been hampered by insufficient 10B accumulation in tumors and low 10B concentration ratios of tumor-to-blood (T/B) and tumor-to-normal tissue (T/N). Herein, we developed fluorinated BPA derivatives with different fluorine groups as boron delivery agents for enabling sufficient 10B accumulation in tumors and enhancing T/B and T/N ratios. Our findings demonstrated that fluorinated BPA derivatives had good biological safety. Furthermore, fluorinated BPA derivatives showed improved 10B accumulation in tumors and enhanced T/B and T/N ratios compared to the clinical boron drug fructose-BPA (f-BPA). In particular, in B16-F10 tumor-bearing mice, fluorinated BPA derivatives met the requirements for clinical BNCT even at half of the clinical dose. Thus, fluorinated BPA derivatives are potentially effective boron delivery agents for clinical BNCT in melanoma.


Subject(s)
Benzhydryl Compounds , Boron Neutron Capture Therapy , Halogenation , Animals , Mice , Boron Neutron Capture Therapy/methods , Benzhydryl Compounds/chemistry , Benzhydryl Compounds/pharmacology , Phenols/chemistry , Phenols/pharmacology , Humans , Mice, Inbred C57BL , Boron Compounds/chemistry , Boron Compounds/pharmacology , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Molecular Structure
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