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1.
Pain Ther ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38748200

INTRODUCTION: Tension-type headache (TTH) is common but challenging to manage due to limited effectiveness of conventional treatments. This study examines six complementary and alternative medicine (CAM) interventions through network meta-analysis to identify effective TTH management strategies. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, OVID, CNKI, Wanfang, VIP, and CBM databases for randomized controlled trials on CAM for TTH treatment. Headache frequency and intensity were the primary outcomes. Methodological quality was evaluated on the basis of the Cochrane risk of bias tool. We used R software to conduct this Bayesian network meta-analysis. We used mean difference (MD) with 95% credible intervals (CI) to calculate the continuous outcomes and analyzed the percentages of the surface under the cumulative ranking (SUCRA) curve. RESULTS: In total, 32 randomized controlled trials (RCTs) with 2405 participants were analyzed. For reducing headache intensity, the network meta-analysis shows that acupuncture therapy combined with traditional Chinese medicine (AT_TCM), manual therapy (MT), psychological treatment (PT), and traditional Chinese medicine combined with acupuncture and manual therapy (TCM_AT_MT) are superior to Western medicine (WM). In the SUCRA curve, TCM_AT_MT is the best for reducing headache frequency (HF). CONCLUSIONS: This review, assessed as low-quality evidence by GRADE, cautiously suggests potential benefits of PT over other CAM interventions for TTH and indicates TCM_AT_MT might better reduce HF. It proposes that combining CAM interventions could enhance outcomes. Due to the preliminary nature of these findings, further high-quality RCTs are essential to confirm these suggestions and provide clearer clinical guidance. PROSPERO REGISTRATION NUMBER: CRD42021252073.

2.
Food Sci Nutr ; 12(5): 3225-3236, 2024 May.
Article En | MEDLINE | ID: mdl-38726419

Hepatic polypeptide nutrient solution (HP) is a mixture of hepatoprotective peptides derived from fresh porcine liver with various effects. However, the role and mechanisms of HP in nonalcoholic fatty liver disease (NAFLD) are still not well understood. We investigated the effects of HP NAFLD rats induced by high-cholesterol diet (HCD) and its underlying mechanisms. Rats were provided with HCD for 4 weeks and then received HP or metformin after 2 weeks of HCD feeding. The study found that HP reduced cholesterol and triglyceride levels in rats with NAFLD (all p < .05). Histopathological examination also showed that HP improved the liver lesions induced by the HCD diet. Furthermore, the oxidative stress and inflammatory responses of NAFLD rats treated with HP were also improved. In addition, it was discovered that HP triggered the activation of AMPK and decreased the expression of SREBP-1c and FAS while enhancing the expression of PPAR α and CPT-1 in liver. These findings indicated that HP might have therapeutic potential for NAFLD, possibly via activating AMPK signaling pathway.

3.
Clin J Am Soc Nephrol ; (0)2024 May 10.
Article En | MEDLINE | ID: mdl-38728096

BACKGROUND: Accurately predicting kidney outcomes in IgA nephropathy is crucial for clinical decision making. Insufficient use of longitudinal data in previous studies has limited the accuracy and interpretability of prediction models for failing to reflect the chronic nature of IgA nephropathy. This study aimed at establishing a multivariable dynamic deep learning model using comprehensive longitudinal data for the prediction of kidney outcomes in IgA nephropathy. METHODS: In this retrospective cohort study of 2,056 IgA nephropathy patients at 18 kidney centers, a total of 28,317 data points were collected by the sliding window method. Among them, 15,462 windows in a single center were randomly assigned to training (80%) and validation (20%) sets while 8797 windows in 18 kidney centers were assigned to an independently test set. Interpretable Multi-Variable Long Short-Term Memory (IMV-LSTM), a deep learning model, was implemented to predict kidney outcomes (kidney failure or 50% decline in kidney function) based on time-invariant variables measured at biopsy and time-variant variables measured during follow-up. Risk performance was evaluated using Kaplan-Meier analysis and the C statistic. Trajectory analysis was performed to assess the various trends of clinical variables during follow-up. RESULTS: The model achieved a higher C statistic (0.93; 95% CI, 0.92-0.95) on the test set than the XGBoost prediction model that we developed in a previous study using only baseline information (C statistic, 0.84; 95% CI, 0.80-0.88). Kaplan-Meier analysis showed that groups with lower predicted risks from the full model survived longer than groups with higher risks. Time-variant variables demonstrated higher importance scores than time-invariant variables. Within time-variant variables, more recent measurements showed higher importance scores. Further interpretation showed that certain trajectory groups of time-variant variables such as serum creatinine and urine protein were associated with elevated risks of adverse outcomes. CONCLUSIONS: In IgA nephropathy, a deep learning model can be used to accurately and dynamically predict kidney prognosis based on longitudinal data, and time-variant variables show strong ability to predict kidney outcome.

4.
Tree Physiol ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38728368

Flavonoids are crucial medicinal active ingredients in Ginkgo biloba. However, the effect of protein post-translational modifications (PTMs) on flavonoid biosynthesis remains poorly explored. Lysine acetylation, a reversible PTM, plays a crucial role in metabolic regulation. This study aims to investigate the potential role of acetylation in G. biloba flavonoid biosynthesis. Through comprehensive analysis of transcriptomes, metabolomes, proteomes, and acetylated proteins in different tissues, a total of 11,788 lysine acetylation sites were identified on 4324 acetylated proteins, including 89 acetylation sites on 23 proteins. Additionally, 128 types of differentially accumulated flavonoids were identified among tissues, and a dataset of differentially expressed genes related to the flavonoid biosynthesis pathway was constructed. Twelve (CHI, C3H1, ANR, DFR, CCoAOMT1, F3H1, F3H2, CCoAOMT2, C3H2, HCT, F3'5'H, and FG2) acetylated proteins that might be involved in flavonoid biosynthesis were identified. Specifically, we found that the modification levels of CCoAOMT1 and F3'5'H sites correlated with the catalytic production of homoeriodictyol and dihydromyricetin, respectively. Inhibitors of lysine deacetylase (trichostatin A, TSA) impacted total flavonoid content in different tissues and increased flavonoid levels in G. biloba roots. Treatment with TSA revealed that expression levels of GbF3'5'H and GbCCoAOMT1 in stems and leaves aligned with total flavonoid content variations, while in roots, expression levels of GbC3H2 and GbFG2 corresponded to total flavonoid content changes. Collectively, these findings reveal for the first time the important role of acetylation in flavonoid biosynthesis.

5.
Food Res Int ; 186: 114331, 2024 Jun.
Article En | MEDLINE | ID: mdl-38729716

Peach fruit is prone to chilling injury (CI) during low-temperature storage, resulting in quality deterioration and economic losses. Our previous studies have found that exogenous trehalose treatment can alleviate the CI symptoms of peach by increasing sucrose accumulation. The purpose of this study was to explore the potential molecular mechanism of trehalose treatment in alleviating CI in postharvest peach fruit. Transcriptome analysis showed that trehalose induced gene expression in pathways of plant MAPK signaling, calcium signaling, and reactive oxygen species (ROS) signaling. Furthermore, molecular docking analysis indicated that PpCDPK24 may activate the ROS signaling pathway by phosphorylating PpRBOHE. Besides, PpWRKY40 mediates the activation of PpMAPKKK2-induced ROS signaling pathway by interacting with the PpRBOHE promoter. Accordingly, trehalose treatment significantly enhanced the activities of antioxidant-related enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and gluathione reductase (GR), as well as the transcription levels AsA-GSH cycle related gene, which led to the reduction of H2O2 and malondialdehyde (MDA) content in peach during cold storage. In summary, our results suggest that the potential molecular mechanism of trehalose treatment is to enhance antioxidant capacity by activating CDPK-mediated Ca2 + -ROS signaling pathway and WRKY-mediated MAPK-WRKY-ROS signaling pathway, thereby reducing the CI in peach fruit.


Antioxidants , Cold Temperature , Fruit , Gene Expression Profiling , Gene Expression Regulation, Plant , Prunus persica , Reactive Oxygen Species , Signal Transduction , Trehalose , Trehalose/pharmacology , Trehalose/metabolism , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Signal Transduction/drug effects , Gene Expression Regulation, Plant/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Molecular Docking Simulation , Malondialdehyde/metabolism
6.
Anal Chem ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38730304

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

7.
Bioresour Technol ; 402: 130800, 2024 May 09.
Article En | MEDLINE | ID: mdl-38734259

A sulfur-iron coupled ecological floating bed (EFB-SFe) was developed to enhance the denitrification capability of sulfur-based ecological floating beds (EFB-S). The denitrification performance, kinetic process and microbial community composition were explored. Results showed that sulfur-iron coupling effectively enhanced the denitrification performance of EFB, surpassing the sum of their individual effects. The average total nitrogen removal rate ranged from 1.56 to 4.56 g·m-2·d-1, with a removal efficiency of 22-84 %. The k value for the S + Fe group increased from 0.04 to 0.18 d-1 to 0.40-0.46 d-1 relative to the S group. The sulfur-iron coupling promoted the enrichment of denitrifying bacteria (Thiobacillus and Ferritrophicum). The denitrification genes in EFB-SFe were upregulated, being 12-22 times more abundant than in EFB-S. Sulfur and iron autotrophic denitrification were identified as the main nitrogen removal processes in EFB-SFe. Overall, sulfur-iron coupling showed the potential to enhance the denitrification capacity of EFB-S for treating low-pollution water.

8.
Mol Med Rep ; 30(1)2024 Jul.
Article En | MEDLINE | ID: mdl-38695251

Although exogenous calcitonin gene­related peptide (CGRP) protects against hyperoxia­induced lung injury (HILI), the underlying mechanisms remain unclear. The present study attempted to elucidate the molecular mechanism by which CGRP protects against hyperoxia­induced alveolar cell injury. Human alveolar A549 cells were treated with 95% hyperoxia to establish a hyperoxic cell injury model. ELISA was performed to detect the CGRP secretion. Immunofluorescence, quantitative (q)PCR, and western blotting were used to detect the expression and localization of CGRP receptor (CGRPR) and transient receptor potential vanilloid 1 (TRPV1). Cell counting kit­8 and flow cytometry were used to examine the proliferation and apoptosis of treated cells. Digital calcium imaging and patch clamp were used to analyze the changes in intracellular Ca2+ signaling and membrane currents induced by CGRP in A549 cells. The mRNA and protein expression levels of Cyclin D1, proliferating cell nuclear antigen (PCNA), Bcl­2 and Bax were detected by qPCR and western blotting. The expression levels of CGRPR and TRPV1 in A549 cells were significantly downregulated by hyperoxic treatment, but there was no significant difference in CGRP release between cells cultured under normal air and hyperoxic conditions. CGRP promoted cell proliferation and inhibited apoptosis in hyperoxia, but selective inhibitors of CGRPR and TRPV1 channels could effectively attenuate these effects; TRPV1 knockdown also attenuated this effect. CGRP induced Ca2+ entry via the TRPV1 channels and enhanced the membrane non­selective currents through TRPV1 channels. The CGRP­induced increase in intracellular Ca2+ was reduced by inhibiting the phospholipase C (PLC)/protein kinase C (PKC) pathway. Moreover, PLC and PKC inhibitors attenuated the effects of CGRP in promoting cell proliferation and inhibiting apoptosis. In conclusion, exogenous CGRP acted by inversely regulating the function of TRPV1 channels in alveolar cells. Importantly, CGRP protected alveolar cells from hyperoxia­induced injury via the CGRPR/TRPV1/Ca2+ axis, which may be a potential target for the prevention and treatment of the HILI.


Alveolar Epithelial Cells , Apoptosis , Calcitonin Gene-Related Peptide , Calcium , Cell Proliferation , Receptors, Calcitonin Gene-Related Peptide , TRPV Cation Channels , Humans , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/pharmacology , Apoptosis/drug effects , A549 Cells , Calcium/metabolism , Cell Proliferation/drug effects , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/drug effects , Receptors, Calcitonin Gene-Related Peptide/metabolism , Hyperoxia/metabolism , Signal Transduction/drug effects , Calcium Signaling/drug effects
9.
BMC Cancer ; 24(1): 573, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724951

BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.


Biomarkers, Tumor , Colorectal Neoplasms , Disease Progression , Microsatellite Instability , Phosphopyruvate Hydratase , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Prognosis , Female , Male , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Middle Aged , Nomograms , Single-Cell Analysis , DNA Copy Number Variations
10.
Front Med (Lausanne) ; 11: 1393734, 2024.
Article En | MEDLINE | ID: mdl-38765255

Objective: This retrospective study aims to identify risk factors for urogenic sepsis in patients with upper urinary tract stones following ureteral flexible lithotripsy (FURL). Additionally, we analyze the clinical characteristics of bacterial infections post-surgery. Methods: A total of 759 patients who underwent FURL at the Urology Department of Zunyi Medical University were included. Univariate and multivariate Logistic regression analyses were conducted to identify independent risk factors for urogenic sepsis post-FURL. The distribution of bacteria based on preoperative urine cultures was also analyzed. Statistical analysis was performed using R4.2.2 software. Results: Of the 759 patients, positive preoperative urine culture, urine nitrite positivity, urine white blood cell count (WBC) ≥ 200 cells/µL, residual stones, and neutrophil-to-lymphocyte ratio (NLR) were found to be independent risk factors for urogenic sepsis after FURL. Among the 164 patients with positive preoperative urine cultures, 32 developed urogenic sepsis post-surgery, with 68.75% having positive preoperative cultures. The leading pathogens causing postoperative urogenic sepsis were Escherichia coli (E. coli), Enterococcus faecium, Proteus mirabilis, and Klebsiella pneumoniae. The probabilities of progression to urogenic sepsis were as follows: E. coli 19% (n = 12), Enterococcus faecium 43% (n = 3), Proteus mirabilis 33.3% (n = 1), and Klebsiella pneumoniae 33.3% (n = 1). The ages of affected patients were 47.17 ± 13.2, 53.7, 41, and 79 years, respectively. Rates of comorbid diabetes were 36.4, 66.7, 50, 100%, with nitrite positivity rates at 72.7, 33.3, 50, 0%. Ten female patients were infected with E. coli, while patients infected with Klebsiella pneumoniae had an NLR of 7.62. Conclusion: Positive preoperative urine culture, urine nitrite positivity, urine WBC ≥ 200 cells/µL, residual stones, and NLR are independent risk factors for urogenic sepsis after FURL. Escherichia coli is the predominant pathogen post-FURL, with notable female prevalence and nitrite-positive urine in infections. Enterococcus faecium infections are associated with diabetes.

11.
BMC Cancer ; 24(1): 617, 2024 May 21.
Article En | MEDLINE | ID: mdl-38773511

BACKGROUND: Hepatocellular carcinoma (HCC) presents a significant threat to individuals and healthcare systems due to its high recurrence rate. Accurate prognostic models are essential for improving patient outcomes. Gamma-glutamyl transpeptidase (GGT) and prealbumin (PA) are biomarkers closely related to HCC. This study aimed to investigate the predictive value of the GGT to PA ratio (GPR) and to construct prognostic nomograms for HCC patients without microvascular invasion. METHODS: We retrospectively analyzed data from 355 HCC patients who underwent radical hepatectomy at Shengjing Hospital of China Medical University between December 2012 and January 2021. Patients were randomly assigned to a training cohort (n = 267) and a validation cohort (n = 88). The linearity of GPR was assessed using restricted cubic spline (RCS) analysis, and the optimal cut-off value was determined by X-tile. Kaplan-Meier survival curves and log-rank tests were used to investigate the associations between GPR and both progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis identified independent risk factors, enabling the construction of nomograms. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the accuracy of the nomograms. Decision curve analysis (DCA) assessed the predictive value of the models. RESULTS: Patients were categorized into GPR-low and GPR-high groups based on a GPR value of 333.33. Significant differences in PFS and OS were observed between the two groups (both P < 0.001). Cox multivariate analysis identified GPR as an independent risk factor for both PFS (OR = 1.80, 95% CI: 1.24-2.60, P = 0.002) and OS (OR = 1.87, 95% CI: 1.07-3.26, P = 0.029). The nomograms demonstrated good predictive performance, with C-index values of 0.69 for PFS and 0.76 for OS. Time-dependent ROC curves and calibration curves revealed the accuracy of the models in both the training and validation cohorts, with DCA results indicating notable clinical value. CONCLUSIONS: GPR emerged as an independent risk factor for both OS and PFS in HCC patients without microvascular invasion. The nomograms based on GPR demonstrated relatively robust predictive efficiency for prognosis.


Carcinoma, Hepatocellular , Liver Neoplasms , Nomograms , Prealbumin , gamma-Glutamyltransferase , Humans , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Liver Neoplasms/blood , Liver Neoplasms/surgery , Female , Male , Middle Aged , gamma-Glutamyltransferase/blood , gamma-Glutamyltransferase/metabolism , Retrospective Studies , Prognosis , Prealbumin/analysis , Prealbumin/metabolism , Biomarkers, Tumor/blood , Biomarkers, Tumor/metabolism , Hepatectomy , Adult , Aged , ROC Curve , Neoplasm Invasiveness , Kaplan-Meier Estimate , Microvessels/pathology , Predictive Value of Tests
12.
Front Pharmacol ; 15: 1336347, 2024.
Article En | MEDLINE | ID: mdl-38774215

Objective: This study aimed to elucidate the therapeutic effects of Huaier granules on hepatocellular carcinoma (HCC) within the Milan criteria in patients who underwent microwave ablation (MWA). Materials and methods: A total of 228 patients were included, with 97 in the Huaier group and 131 in the control group. We evaluated progression-free survival (PFS), overall survival (OS), and extrahepatic metastasis survival (EMS) using Kaplan-Meier (KM) curves with a log-rank test. Propensity Score Matching (PSM) and Stabilized Inverse Probability of Treatment Weighting (IPTW) were performed to minimize selection and confounding biases. Results: Following PSM, the 1-, 3-, and 5-year PFS rates in the Huaier and control groups were 83.5% vs 70.7%, 57.7% vs 42.6%, and 43.6% vs 31.9% (p = 0.030), respectively. The 1-, 3-, and 5-year OS rates were 98.9% vs 95.6%, 83.9% vs 72.3%, and 72.2% vs 53.7% (p = 0.023), respectively. The corresponding 1-, 3-, and 5-year EMS rates were 98.9% vs 93.4%, 91.7% vs 83.7%, and 91.7% vs 78.5% (p = 0.039), respectively. Stabilized IPTW analysis of KM curves yielded results similar to those of the PSM analysis. Additionally, administering Huaier granules for at least 6 months significantly improved PFS and OS. Conclusion: Huaier granules can reduce the risk of recurrence and improve the OS of patients with HCC within the Milan criteria following MWA. Administering Huaier granules for over 6 months proved beneficial.

13.
RSC Adv ; 14(23): 16379-16388, 2024 May 15.
Article En | MEDLINE | ID: mdl-38774610

An FeN4 single-atom catalyst (SAC) embedded in a graphene matrix is considered an oxygen reduction reaction (ORR) catalyst for its good activity and durability, and decoration on the Fe active site can further modulate the performance of the FeN4 SAC. In this work, the axial heteroatom (L = P, S and Cl)-decorated FeN4 SAC (FeN4L) and pure FeN4 were comparatively studied using density functional theory (DFT) calculations. It was found that the rate-determining step (RDS) in the ORR on pure FeN4 is the reduction of OH to H2O in the last step with an overpotential of 0.58 V. However, the RDS of the ORR for the axial heteroatom-decorated FeN4L is the reduction of O2 to OOH in the first step. The axial P and S heteroatom-decorated FeN4P and FeN4S exhibit lower activity than pure FeN4 since the overpotentials of the ORR on FeN4P and FeN4S are 1.02 V and 1.09 V, respectively. Meanwhile, FeN4Cl exhibits the best activity towards the ORR since it possesses the lowest overpotential (0.51 V). The main reason is that the axial heteroatom decoration alleviates the adsorption of all the species in the whole ORR, thus modulating the free energy in every elementary reaction step. A volcano relationship between the d band center and the ORR activity can be determined among the axial heteroatom-decorated FeN4L SACs. The d band center of the Fe atom in various FeN4L SACs follows the order of FeN4 > FeN4Cl > FeN4S > FeN4P, whereas the overpotential of the ORR on various catalysts follows the order of FeN4Cl > FeN4 > FeN4S ≈ FeN4P. ΔG(*OH) is a simple descriptor for the prediction of the ORR activity of various axial heteroatom-decorated FeN4L, although the RDS in the ORR is either the first step or the last step. This paper provides a guide to the design and selection of the ORR over SACs with different axial heteroatom decorations, contributing to the rational design of more powerful ORR electrocatalysts and achieving advances in electrochemical conversion and storage devices.

14.
Adv Healthc Mater ; : e2401020, 2024 May 14.
Article En | MEDLINE | ID: mdl-38742703

Chemotherapy is widely used for cancer therapy but with unsatisfied efficacy, mainly due to the inefficient delivery of anticancer agents. Among the critical "five steps" drug delivery process, internalization into tumor cells and intracellular drug release are two important steps for the overall therapeutic efficiency. Strategy based on active targeting or TME-responsive is developed individually to improve therapeutic efficiency, but with limited improvement. However, the combination of these two strategies could potentially augment the drug delivery efficiency and therapeutic efficiency, consequently. Therefore, this work constructs a library of stimuli-responsive aptamer-drug conjugates (srApDCs), as "dual-targeted" strategy for cancer treatment that enables targeted drug delivery and controlled drug release. Specifically, this work uses different stimuli-responsive linkers to conjugate a tumor-targeting aptamer (i.e., AS1411) with drugs, forming the library of srApDCs for targeted cancer treatment. This design hypothesis is validated by the experimental data, which indicated that the aptamer could selectively enhance uptake of the srApDCs and the linkers could be cleaved by pathological cues in the TME to release the drug payload, leading to a significant enhancement of therapeutic efficacy. These results underscore the potential of the approach, providing a promising methodology for cancer therapy.

15.
Magn Reson Med ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38748853

PURPOSE: To develop a 3D, high-sensitivity CEST mapping technique based on the 3D stack-of-spirals (SOS) gradient echo readout, the proposed approach was compared with conventional acquisition techniques and evaluated for its efficacy in concurrently mapping of guanidino (Guan) and amide CEST in human brain at 3 T, leveraging the polynomial Lorentzian line-shape fitting (PLOF) method. METHODS: Saturation time and recovery delay were optimized to achieve maximum CEST time efficiency. The 3DSOS method was compared with segmented 3D EPI (3DEPI), turbo spin echo, and gradient- and spin-echo techniques. Image quality, temporal SNR (tSNR), and test-retest reliability were assessed. Maps of Guan and amide CEST derived from 3DSOS were demonstrated on a low-grade glioma patient. RESULTS: The optimized recovery delay/saturation time was determined to be 1.4/2 s for Guan and amide CEST. In addition to nearly doubling the slice number, the gradient echo techniques also outperformed spin echo sequences in tSNR: 3DEPI (193.8 ± 6.6), 3DSOS (173.9 ± 5.6), and GRASE (141.0 ± 2.7). 3DSOS, compared with 3DEPI, demonstrated comparable GuanCEST signal in gray matter (GM) (3DSOS: [2.14%-2.59%] vs. 3DEPI: [2.15%-2.61%]), and white matter (WM) (3DSOS: [1.49%-2.11%] vs. 3DEPI: [1.64%-2.09%]). 3DSOS also achieves significantly higher amideCEST in both GM (3DSOS: [2.29%-3.00%] vs. 3DEPI: [2.06%-2.92%]) and WM (3DSOS: [2.23%-2.66%] vs. 3DEPI: [1.95%-2.57%]). 3DSOS outperforms 3DEPI in terms of scan-rescan reliability (correlation coefficient: 3DSOS: 0.58-0.96 vs. 3DEPI: -0.02 to 0.75) and robustness to motion as well. CONCLUSION: The 3DSOS CEST technique shows promise for whole-cerebrum CEST imaging, offering uniform contrast and robustness against motion artifacts.

16.
SLAS Technol ; : 100138, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38692508

This research presents a novel method for objectively evaluating college badminton players' physical function levels. It examines current evaluation methods before proposing a novel model that combines Particle Swarm Optimization (PSO) with Backpropagation (BP) neural networks and data mining. The model establishes an evaluation index system that considers physical form, function, quality, and neural mechanisms. The study uses PSO-BP neural networks to adjust indicator weights for more accurate ratings. This recurrent improvement reduces errors while increasing prediction ability, resulting in accurate assessments of athletes' physical talents and neurological insights. The model's efficiency is proved by low mistakes and high accuracy results, which are critical for training optimization and injury avoidance. The combination of PSO optimization and BP neural networks offers robustness across various athlete profiles and training scenarios. This method improves physical function evaluation in badminton and has wider implications for sports science and performance analytics. This study uses bio-inspired computing and machine learning to emphasize the relevance of data-driven techniques in enhancing athlete assessments for better training outcomes and general well-being.

18.
PLoS One ; 19(5): e0302386, 2024.
Article En | MEDLINE | ID: mdl-38713669

BACKGROUND: The purpose of this study was to evaluate the relationship between hyperuricemia and the risks of all-cause mortality and cardiovascular disease (CVD) mortality in patients with osteoarthritis (OA). METHODS: A retrospective cohort study was performed on 3,971 patients using data from the National Health and Nutrition Examination Survey database between 1999 and 2018. OA was diagnosed through specific questions and responses. The weighted COX regression models were used to explore the factors associated with all-cause mortality/CVD mortality in OA patients. Subgroup analyses were conducted based on age, gender, hypertension, dyslipidemia, CVD, and chronic kidney disease (CKD). Hazard ratio (HR) and 95% confidence interval (95% CI) were measured as the evaluation indexes. RESULTS: During the duration of follow-up time (116.38 ± 2.19 months), 33.69% (1,338 patients) experienced all-cause mortality, and 11.36% (451 patients) died from CVD. Hyperuricemia was associated with higher risks of all-cause mortality (HR: 1.22, 95% CI: 1.06-1.41, P = 0.008) and CVD mortality (HR: 1.32, 95% CI: 1.02-1.72, P = 0.036) in OA patients. Subgroup analyses showed that hyperuricemia was related to the risk of all-cause mortality in OA patients aged >65 years (HR: 1.17, 95% CI: 1.01-1.36, P = 0.042), in all male patients (HR: 1.41, 95% CI: 1.10-1.80, P = 0.006), those diagnosed with hypertension (HR: 1.17, 95% CI: 1.01-1.37, P = 0.049), dyslipidemia (HR: 1.18, 95% CI: 1.01-1.39, P = 0.041), CVD (HR: 1.30, 95% CI: 1.09-1.55, P = 0.004), and CKD (HR: 1.31, 95% CI: 1.01-1.70, P = 0.046). The association between hyperuricemia and a higher risk of CVD mortality was found in OA patients aged ≤ 65 years (HR: 1.90, 95% CI: 1.06-3.41, P = 0.032), who did not suffer from diabetes (HR: 1.36, 95% CI: 1.01-1.86, P = 0.048), who did not suffer from hypertension (HR: 2.56, 95% CI: 1.12-5.86, P = 0.026), and who did not suffer from dyslipidemia (HR: 2.39, 95% CI: 1.15-4.97, P = 0.020). CONCLUSION: These findings emphasize the importance of monitoring serum uric acid levels in OA patients for potentially reducing mortality associated with the disease.


Cardiovascular Diseases , Hyperuricemia , Nutrition Surveys , Osteoarthritis , Humans , Hyperuricemia/complications , Hyperuricemia/mortality , Hyperuricemia/epidemiology , Male , Female , Osteoarthritis/mortality , Osteoarthritis/complications , Osteoarthritis/epidemiology , Middle Aged , Retrospective Studies , Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/complications , Risk Factors , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Databases, Factual , Proportional Hazards Models , Hypertension/complications , Hypertension/mortality , Hypertension/epidemiology , Adult , Dyslipidemias/mortality , Dyslipidemias/complications , Dyslipidemias/epidemiology
19.
iScience ; 27(4): 109506, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38715945

It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/µL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/µL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.

20.
Small ; : e2309907, 2024 May 07.
Article En | MEDLINE | ID: mdl-38712486

The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.

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