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1.
Ren Fail ; 46(2): 2390566, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39230050

ABSTRACT

OBJECTIVE: To investigate the association between atherogenic index of plasma (AIP) and kidney stones (KS) occurrence and recurrence. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Non-pregnant adults who provided complete information on AIP and KS were included in the analyses. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). KS was ascertained with questionnaires. Weighted multivariable logistic regression model and restricted cubic spline (RCS) were applied to examine the associations between AIP and KS occurrence and recurrence. RESULTS: A total of 6488 subjects (weighted mean age 43.19 years and 49.26% male) with a weighted mean AIP of 0.66 were included in this study. The multivariable-adjusted OR for nephrolithiasis occurrence across consecutive tertiles was 1.00 (reference), 1.21 (95% CI: 0.90-1.62), and 1.85 (95% CI: 1.39-2.48), respectively. Moreover, each SD increment of AIP was associated with a 50% (OR:1.50, 95% CI: 1.25-1.81) higher risk of nephrolithiasis recurrence. RCSs showed significant and linear dose-response relationships between AIP and nephrolithiasis occurrence (p-overall = 0.006, p-nonlinear = 0.689) and recurrence (p-overall = 0.001, p-nonlinear = 0.848). The positive associations between AIP and nephrolithiasis occurrence and recurrence persisted in sensitivity analyses, suggesting the robustness of the results. CONCLUSION: In the current US nationally representative cross-sectional study, AIP was positively associated with KS occurrence and recurrence.


Subject(s)
Atherosclerosis , Kidney Calculi , Nutrition Surveys , Humans , Male , Female , Cross-Sectional Studies , Adult , Kidney Calculi/epidemiology , Kidney Calculi/blood , Middle Aged , Prevalence , Atherosclerosis/epidemiology , Atherosclerosis/blood , Atherosclerosis/etiology , Triglycerides/blood , Risk Factors , Recurrence , Cholesterol, HDL/blood , United States/epidemiology , Logistic Models
2.
Sci Adv ; 10(37): eadp3487, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39270026

ABSTRACT

Polaritons are light-matter quasiparticles that govern the optical response of quantum materials at the nanoscale, enabling on-chip communication and local sensing. Here, we report Landau-phonon polaritons (LPPs) in magnetized charge-neutral graphene encapsulated in hexagonal boron nitride (hBN). These quasiparticles emerge from the interaction of Dirac magnetoexciton modes in graphene with the hyperbolic phonon polariton modes in hBN. Using infrared magneto-nanoscopy, we reveal the ability to completely halt the LPP propagation in real space at quantized magnetic fields, defying the conventional optical selection rules. The LPP-based nanoscopy also tells apart two fundamental many-body phenomena: the Fermi velocity renormalization and field-dependent magnetoexciton binding energies. Our results highlight the potential of magnetically tuned Dirac heterostructures for precise nanoscale control and sensing of light-matter interaction.

3.
Exp Brain Res ; 242(10): 2391-2404, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39136723

ABSTRACT

This study aimed to utilize the nonnegative matrix factorization (NNMF) algorithm for muscle synergy analysis, extracting synergy structures and muscle weightings and mining biomarkers reflecting changes in muscle fatigue from these synergy structures. A leg press exercise to induce fatigue was performed by 11 participants. Surface electromyography (sEMG) data from seven muscles, electrocardiography (ECG) data, Borg CR-10 scale scores, and the z-axis acceleration of the weight block were simultaneously collected. Three indices were derived from the synergy structures: activation phase difference, coactivation area, and coactivation time. The indicators were further validated for single-leg landing. Differences in heart rate (HR) and heart rate variability (HRV) were observed across different fatigue levels, with varying degrees of disparity. The median frequency (MDF) exhibited a consistent decline in the primary working muscle groups. Significant differences were noted in activation phase difference, coactivation area, and coactivation time before and after fatigue onset. Moreover, a significant correlation was found between the activation phase difference and the coactivation area with fatigue intensity. The further application of single-leg landing demonstrated the effectiveness of the coactivation area. These indices can serve as biomarkers reflecting simultaneous alterations in the central nervous system and muscle activity post-exertion.


Subject(s)
Electromyography , Heart Rate , Muscle Fatigue , Muscle, Skeletal , Humans , Male , Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Young Adult , Adult , Heart Rate/physiology , Electrocardiography , Female , Algorithms
4.
Int Immunopharmacol ; 140: 112910, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39121604

ABSTRACT

This research investigated the intricate relationship between ferroptosis and sepsis by utilizing advanced genomic and pharmacological methodologies. Specifically, we obtained expression quantitative trait loci (eQTLs) for 435 genes associated with ferroptosis from the eQTLGen Consortium and detected notable cis-eQTLs for 281 of these genes. Next, we conducted a detailed analysis to assess the impact of these eQTLs on susceptibility to sepsis using Mendelian randomization (MR) with data from a cohort of 10,154 sepsis patients and 452,764 controls sourced from the UK Biobank. MR analysis revealed 16 ferroptosis-related genes that exhibited significant associations with sepsis outcomes. To bolster the robustness of these findings, sensitivity analyses were performed to assess pleiotropy and heterogeneity, thus confirming the reliability of the causal inferences. Furthermore, single-cell RNA sequencing data from sepsis patients offered a detailed examination of gene expression profiles, demonstrating varying levels of ferroptosis marker expression across different cell types. Pathway enrichment analysis utilizing gene set enrichment analysis (GSEA) further revealed the key biological pathways involved in the progression of sepsis. Additionally, the use of computational molecular docking facilitated the prediction of interactions between identified genes and potential therapeutic compounds, highlighting novel drug targets. In conclusion, our integrated approach combining genomics and pharmacology offers valuable insights into the involvement of ferroptosis in sepsis, laying the groundwork for potential therapeutic strategies targeting this cell death pathway to enhance sepsis management.


Subject(s)
Ferroptosis , Mendelian Randomization Analysis , Quantitative Trait Loci , Sepsis , Single-Cell Analysis , Ferroptosis/genetics , Humans , Sepsis/genetics , Sepsis/drug therapy , Genomics/methods , Molecular Docking Simulation , Genetic Predisposition to Disease
5.
Small ; : e2406165, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39126365

ABSTRACT

The calcium looping technology employing CaO-based sorbents is pivotal for capturing CO2 from flue gas. However, the intrinsic low thermodynamic stability of CaO-based sorbents and the requisite molding step induce severe sintering issues, diminishing their cyclic stability. Herein, a high-entropy fluorite oxide (HEFO) inert stabilizer premised on entropy stabilization and synergistic effect strategies is introduced. HEFO-modified, CaO-based sorbent pellets are synthesized via a rapid cigarette butt-assisted combustion process (15 min) combined with the graphite molding method. Post-multiple cycles, their CO2 capture capacity reaches 0.373 g g-1, which is 2.6-fold superior to that of pure CaO, demonstrating markedly enhanced anti-sintering properties. First, the subtle morphological and crystallographic modifications suggest that the inherent entropy stability of HEFO imparts robust thermal resistance. Concurrently, the disordered structure of single-phase HEFO exhibits a high affinity for CaO, resulting in an interface binding energy of -1.83 eV, in sharp contrast to the -0.112 eV of pure CaO, thereby restricting CaO migration. Additionally, the multi-element synergistic effect of HEFO reduces the energy barrier by 0.15 eV, leading to a 40% and 140% increase in carbonation and calcination rates, respectively. This work presents highly efficient and rapidly synthesized CaO-based sorbent pellets, showcasing promising potential for industrial application.

6.
Adv Sci (Weinh) ; : e2403305, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39159052

ABSTRACT

Ferroptosis is known to mediate the pathogenesis of chemotherapeutic drug-induced acute kidney injury (AKI); however, leveraging the benefits of ferroptosis-based treatments for nephroprotection remains challenging. Here, ultrasmall nanodots, denoted as FerroD, comprising the amphiphilic conjugate (tetraphenylethylene-L-serine-deferoxamine, TPE-lys-Ser-DFO (TSD)) and entrapped ferrostatin-1 are designed. After being internalized through kidney injury molecule-1-mediated endocytosis, FerroD can simultaneously remove the overloaded iron ions and eliminate the overproduction of lipid peroxides by the coordination-disassembly mechanisms, which collectively confer prominent inhibition efficiency of ferroptosis. In cisplatin (CDDP)-induced AKI mice, FerroD equipped with dual anti-ferroptotic ability can provide long-term nephroprotective effects. This study may shed new light on the design and clinical translation of therapeutics targeting ferroptosis for various ferroptosis-related kidney diseases.

7.
J Med Chem ; 67(15): 12887-12911, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39033411

ABSTRACT

Soluble epoxide hydrolase (sEH) and HDAC6 mediate the NF-κB pathway in inflammatory responses, and their inhibitors exhibit powerful anti-inflammatory and analgesic activities in treating both inflammation and pain. Therefore, a series of dual-targeting inhibitors containing urea or squaramide and hydroxamic acid moieties were designed and synthesized, and their role as a new sEH/HDAC6 dual-targeting inhibitor in inflammatory pain was evaluated in a formalin-induced mice model and a xylene-induced mouse ear swelling model. Among them, compounds 28g and 28j showed the best inhibitory and selectivity of sEH and HDAC6. Compound 28g had satisfactory pharmacokinetic characteristics in rats. Following administration at 30 mg/kg, compound 28g exhibited more effective analgesic activity than either an sEH inhibitor (GL-B437) or an HDAC6 inhibitor (Rocilinostat) alone and coadministration of both inhibitors. Thus, these novel sEH/HDAC6 dual-targeting inhibitors exhibited powerful analgesic activity in nociceptive behavior and are worthy of further development.


Subject(s)
Analgesics , Drug Design , Epoxide Hydrolases , Histone Deacetylase 6 , Histone Deacetylase Inhibitors , Inflammation , Pain , Animals , Histone Deacetylase 6/antagonists & inhibitors , Histone Deacetylase 6/metabolism , Pain/drug therapy , Mice , Inflammation/drug therapy , Analgesics/chemical synthesis , Analgesics/pharmacology , Analgesics/therapeutic use , Analgesics/pharmacokinetics , Analgesics/chemistry , Male , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylase Inhibitors/pharmacokinetics , Epoxide Hydrolases/antagonists & inhibitors , Epoxide Hydrolases/metabolism , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Humans
8.
Angew Chem Int Ed Engl ; : e202411508, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014940

ABSTRACT

The conversion of CO2 to C2 through photocatalysis poses significant challenges, and one of the biggest hurdles stems from the sluggishness of the multi-electron transfer process. Herein, taking metal-organic framework (PFC-98) as a model photocatalyst, we report a new strategy to facilitate charge separation. This strategy involves matching the energy levels of the lowest unoccupied node and linker orbitals of the MOF, thereby creating the lowest unoccupied crystal orbital (LUCO) delocalized over both the node and linker. This feature enables the direct excitation of electrons from photosensitive linker to the catalytic centers, achieving a direct charge transfer (DCT) pathway. For comparison, an isoreticular MOF (PFC-6) based on analogue components but with far apart frontier energy level was synthesized. The delocalized LUCO caused the presence of an internal charge-separated state (ICS), prolonging the excited state lifetime and further inhibiting the electron-hole recombination. The presence of an internal charge-separated state (ICS) prolongs the excited state lifetime and further inhibits the electron-hole recombination. Moreover, it also induced abundant electrons accumulating at the catalytic sites, enabling the multi-electron transfer process. As a result, the material featuring delocalized LUCO exhibits superior overall CO2 photocatalytic performance with high C2 production yield and selectivity.

9.
Plant Physiol Biochem ; 213: 108792, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38851149

ABSTRACT

Tuber flesh pigmentation, conferred by the presence of secondary metabolite anthocyanins, is one of many key agronomic traits for potato tubers. Although several genes of potato anthocyanin biosynthesis have been reported, transcription factors (TFs) contributing to tuber flesh pigmentation are still not fully understood. In this study, transcriptomic profiling of diploid potato accessions with or without tuber flesh pigmentation was conducted and genes of the anthocyanin biosynthesis pathway were found significantly enriched within the 1435 differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and connectivity analysis pinpointed a subset of 173 genes closely related to the key biosynthetic gene StDFR. Of the eight transcription factors in the subset, group III WRKY StWRKY70, was chosen for showing high connectivity to StDFR and ten other anthocyanin biosynthetic genes and homology to known WRKYs of anthocyanin pathway. The transient activation assay showed StWRKY70 predominantly stimulated the expression of StDFR and StANS as well as the accumulation of anthocyanins by enhancing the function of the MYB transcription factor StAN1. Furthermore, the interaction between StWRKY70 and StAN1 was verified by Y2H and BiFC. Our analysis discovered a new transcriptional activator StWRKY70 which potentially involved in tuber flesh pigmentation, thus may lay the foundation for deciphering how the WRKY-MYB-bHLH-WD40 (WRKY-MBW) complex regulate the accumulation of anthocyanins and provide new strategies to breed for more nutritious potato varieties with enhanced tuber flesh anthocyanins.


Subject(s)
Anthocyanins , Gene Expression Profiling , Gene Expression Regulation, Plant , Plant Proteins , Plant Tubers , Solanum tuberosum , Transcription Factors , Anthocyanins/metabolism , Anthocyanins/biosynthesis , Anthocyanins/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Tubers/genetics , Plant Tubers/metabolism , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptome/genetics
10.
Heliyon ; 10(9): e30726, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765164

ABSTRACT

Objectives: Glioma, the most common and aggressive form of brain cancer, possesses a complex biology, which makes elucidating its underlying mechanisms and developing effective treatment strategies challenging. Lactylation is a recently discovered post-translational modification and has emerged as a novel research target to understand its role in various biological processes and diseases. Herein, we explored the role of lactylation in gliomas. Methods: Single-cell RNA-sequencing (scRNA-seq) data were downloaded from the Tumour Immune Single-Cell Hub database. The R package 'Seurat' was used for processing the scRNA-seq data. Lactylation-related genes were identified from published literature and the Molecular Signatures Database. An unsupervised clustering method was used to identify glioma subtypes based on identified lactylation-related genes. Differences among the various clusters were examined, including clinical features, differentially expressed genes (DEGs), enriched pathways and immune cell infiltrates. A lactylation score was generated to predict the overall survival (OS) of patients with glioma using DEGs between the two clusters. Results: The lactylation-related genes were obtained from the scRNA-seq data, identifying two molecular subtypes, and a prognostic signature was established to stratify patients with glioma into high- and low-score groups. Analysis of the tumour immune microenvironment revealed that patients in the high-score group exhibited increased immune cell infiltration, chemokine expression and immune checkpoint expression but exhibited worse OS and better response to immunotherapy. Conclusions: Altogether, we established a novel signature based on lactylation-related clusters for robust survival prediction and immunotherapeutic response in gliomas.

11.
Nanoscale ; 16(18): 9136, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38661520

ABSTRACT

Expression of concern for 'Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery' by Xiaoyong Wang et al., Nanoscale, 2013, 5, 8098-8104, https://doi.org/10.1039/C3NR02797J.


Subject(s)
Gadolinium , Magnetic Resonance Imaging , RNA, Small Interfering , RNA, Small Interfering/chemistry , RNA, Small Interfering/metabolism , Gadolinium/chemistry , Humans , Ferric Compounds/chemistry , Contrast Media/chemistry , Magnetic Iron Oxide Nanoparticles/chemistry , Animals
12.
Nano Lett ; 24(18): 5444-5452, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38639448

ABSTRACT

We report, for the first time, a new synthetic strategy for the preparation of crystalline two-dimensional olefin-linked covalent organic frameworks (COFs) based on aldol condensation between benzodifurandione and aromatic aldehydes. Olefin-linked COFs can be facilely crystallized through either a pyridine-promoted solvothermal process or a benzoic anhydride-mediated organic flux synthesis. The resultant COF leaf with high in-plane π-conjugation exhibits efficient visible-light-driven photoreduction of carbon dioxide (CO2) with water (H2O) in the absence of any photosensitizer, sacrificial agents, or cocatalysts. The production rate of carbon monoxide (CO) reaches as high as 158.1 µmol g-1 h-1 with near 100% CO selectivity, which is accompanied by the oxidation of H2O to oxygen. Both theoretical and experimental results confirm that the key lies in achieving exceptional photoinduced charge separation and low exciton binding. We anticipate that our findings will facilitate new possibilities for the development of semiconducting COFs with structural diversity and functional variability.

13.
Adv Healthc Mater ; : e2400908, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598819

ABSTRACT

The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, is developed to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and veliparib (the poly ADP-ribose polymerase (PARP) inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicit potent pro-apoptotic effects. In vivo studies suggest that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibit tumor growth in the A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner.

14.
Sci Rep ; 14(1): 8389, 2024 04 10.
Article in English | MEDLINE | ID: mdl-38600093

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Gemcitabine , Cell Proliferation , Cell Line, Tumor , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Cell Cycle , Mitogen-Activated Protein Kinase Kinases , Cyclin-Dependent Kinase 4
15.
Environ Sci Technol ; 58(18): 7691-7709, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38664958

ABSTRACT

More and more attention has been paid to condensable particulate matter (CPM) since its emissions have surpassed that of filterable particulate matter (FPM) with the large-scale application of ultralow-emission reform. CPM is a gaseous material in the flue stack but instantly turns into particles after leaving the stack. It is composed of inorganic and organic components. Organic components are an important part of CPM, and they are an irritant, teratogenic, and carcinogenic, which triggers photochemical smog, urban haze, and acid deposition. CPM organic components can aggravate air pollution and climate change; therefore, consideration should be given to them. Based on existing methods for removing atmospheric organic pollutants and combined with the characteristics of CPM organic components, we provide a critical overview from the aspects of (i) fundamental cognition of CPM, (ii) common methods to control CPM organic components, and (iii) catalytic oxidation of CPM organic components. As one of the most encouraging methods, catalytic oxidation is discussed in detail, especially in combination with selective catalytic reduction (SCR) technology, to meet the growing demands for multipollutant control (MPC). We believe that this review is inspiring for a fuller understanding and deeper exploration of promising approaches to control CPM organic components.


Subject(s)
Air Pollutants , Particulate Matter , Air Pollution/prevention & control
16.
Chemosphere ; 353: 141638, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38442775

ABSTRACT

Condensable particulate matter (CPM) from coal combustion is the focus of current pollutant emission studies, and CPM can be divided into inorganic and organic fractions according to the component characteristics. At present, the effects of different factors in the combustion process on the organic and inorganic components of CPM have not been discussed systematically. Here, we conducted combustion experiments collected the generated CPM on a well-controlled drip tube furnace, and investigated the effects of different factors on the generation of organic and inorganic components of CPM by varying the furnace wall insulation temperature, the ratio of gas supply components and the water vapor content in the flue gas. The results showed that the increase in combustion temperature (1300-1500 °C) and oxygen concentration (15-25%) reduced the total CPM generation by 9.8% and 19.98%, respectively, and the intervention of water vapor increased the ability of the whole CPM sampling device to capture ultrafine condensable particles. The generation of CPM organic components decreased with the enhancement of combustion temperature and oxygen content on combustion characteristics, and alkanes shifted to low carbon content. The amount of CPM inorganic components increased with the increase of water vapor content in the flue gas, and this change was dominated by SO42-. The above results provide a feasible idea for the next step of the precise reduction of CPM components.


Subject(s)
Air Pollutants , Particulate Matter , Particulate Matter/analysis , Air Pollutants/analysis , Coal , Steam , Power Plants , Oxygen
17.
ACS Nano ; 18(11): 8337-8349, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38437640

ABSTRACT

The combination of anti-rheumatoid arthritis (RA) drugs methotrexate (MTX) and baricitinib (BTN) has been reported to improve RA treatment efficacy. However, study on the strategy of combination is elusive when considering the benefit of the synergy between MTX and BTN. In this study, we found that the N-heterocyclic rings in the MTX and BTN offer hydrogen bonds and π-π stacking interactions, driving the formation of exquisite vesicular morphology of nanovesicles, denoted as MB NVs. The MB NVs with the MTX/BTN weight ratio of 2:1, MB NVs (2:1), showed an improved anti-RA effect through the synergy between the anti-inflammatory and antiproliferative responses. This work presents that the intermolecular interactions between drug molecules could mediate the coassembly behavior into nanomedicine as well as the therapy synergy both in vitro and in vivo, which may provide further understanding on the rational design of combination nanomedicine for therapeutic purposes.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Azetidines , Purines , Pyrazoles , Sulfonamides , Humans , Methotrexate/pharmacology , Methotrexate/therapeutic use , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Nanomedicine , Arthritis, Rheumatoid/drug therapy , Treatment Outcome , Drug Therapy, Combination
18.
Langenbecks Arch Surg ; 409(1): 81, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38430305

ABSTRACT

PURPOSE: This study aims to compare the efficiency and clinical outcomes between the suctioning ureteral access sheath (UAS) group and the traditional UAS group during retrograde intrarenal surgery (RIRS) for kidney stones and explore the impact of suctioning UAS on postoperative infectious complications. METHODS: We retrospectively reviewed the clinical data of 162 patients with kidney stones who underwent RIRS with a traditional UAS (n = 74) or a suctioning UAS (n = 71) between March 2021 and May 2023. RESULTS: The mean operative time in suctioning UAS group (39.03 ± 18.01 s) was significantly shorter than that (49.73 ± 20.77 s) in the traditional UAS group (P = 0.037). The mean postoperative hospital stay was significantly shorter in the suctioning UAS group (1.57 ± 0.82d) compared with the traditional UAS group (2.30 ± 1.6 2 d) (P = 0.032). The instant SFRs were significantly higher in the suctioning UAS group (88.73%) than in the traditional UAS group (75.68%) (P = 0.040). The overall SFR in suctioning UAS group (92.96%) was slightly higher than the traditional UAS group (85.14%). The incidence of overall complications was significantly higher in the traditional UAS group (35.14%) than in the suctioning UAS group (16.90%) (P = 0.013). In multivariate analysis, female patients (OR 0.053, P = 0.018), positive urine WBC (OR 10.382, P = 0.034), operative time > 60 min (OR 20.231, P = 0.032), and the application of traditional UAS (OR 0.042, P = 0.017) were independent risk factors associated with infectious complications. CONCLUSION: We demonstrated that suctioning UAS provided a higher instant SFR and fewer postoperative infectious complications during RIRS, and patients with predictable risk factors for infectious complications could potentially benefit from the use of the suctioning UAS.


Subject(s)
Kidney Calculi , Ureter , Humans , Female , Retrospective Studies , Kidney Calculi/surgery , Length of Stay , Multivariate Analysis , Postoperative Complications/epidemiology
19.
MAGMA ; 37(3): 397-409, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38386151

ABSTRACT

Subject motion is a long-standing problem of magnetic resonance imaging (MRI), which can seriously deteriorate the image quality. Various prospective and retrospective methods have been proposed for MRI motion correction, among which deep learning approaches have achieved state-of-the-art motion correction performance. This survey paper aims to provide a comprehensive review of deep learning-based MRI motion correction methods. Neural networks used for motion artifacts reduction and motion estimation in the image domain or frequency domain are detailed. Furthermore, besides motion-corrected MRI reconstruction, how estimated motion is applied in other downstream tasks is briefly introduced, aiming to strengthen the interaction between different research areas. Finally, we identify current limitations and point out future directions of deep learning-based MRI motion correction.


Subject(s)
Algorithms , Artifacts , Artificial Intelligence , Deep Learning , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Motion , Neural Networks, Computer , Humans , Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Brain/diagnostic imaging , Movement
20.
Int Urol Nephrol ; 56(7): 2165-2177, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38372840

ABSTRACT

PURPOSE: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis. METHODS: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC). CCK-8 assay was used to detect the effect of CASR on the proliferation of HK-2 cells. RNA-Sequencing was applied to explore potential pathways regulated by CASR in HK-2 cells. RESULTS: PCR and western blot results showed that CASR expression was significantly increased in CASR cells and was decreased in shCASR cells when compared to their corresponding negative control, respectively. CCK-8 assay revealed that CASR inhibited the proliferation of HK-2 cells. RNA-Sequencing results suggested that the shCASR HK-2 cells exhibited a significant up-regulation of 345 genes and a down-regulation of 366 genes. These differentially expressed genes (DEGs) were related to cell apoptosis and cell development. In CASR HK-2 cells, 1103 DEGs primarily functioned in mitochondrial energy metabolism, and amino acid metabolism. With the Venn diagram, 4 DEGs (Clorf116, ENPP3, IL20RB, and CLDN2) were selected as the hub genes regulated by CASR. Enrichment analysis revealed that these hub genes were involved in cell-cell junction, and epithelial cell development. CONCLUSIONS: In summary, our investigation has the potential to offer novel perspectives on CASR regulating cell-cell junction in HK-2 cells.


Subject(s)
Epithelial Cells , Kidney Tubules , Receptors, Calcium-Sensing , Receptors, Calcium-Sensing/genetics , Receptors, Calcium-Sensing/metabolism , Humans , Epithelial Cells/metabolism , Kidney Tubules/cytology , Kidney Tubules/metabolism , Intercellular Junctions/metabolism , Cells, Cultured , Cell Proliferation , Nephrolithiasis/genetics , Nephrolithiasis/metabolism , Gene Expression Regulation , Cell Line
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