A Biomimetic Nanocarrier Strategy Targets Ferroptosis and Efferocytosis During Myocardial Infarction.

Background: Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI. Methods: In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation. Results: The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function. Conclusion: Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI.

Persistent acute kidney injury biomarkers: A systematic review and meta-analysis.

BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95% CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95% CI 0.71-0.79), 0.71 (95% CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.

Bacterial Iron Siderophore Drives Tumor Survival and Ferroptosis Resistance in a Biofilm-Tumor Spheroid Coculture Model.

Interactions between tumoral cells and tumor-associated bacteria within the tumor microenvironment play a significant role in tumor survival and progression, potentially impacting cancer treatment outcomes. In lung cancer patients, the Gram-negative pathogen Pseudomonas aeruginosa raises questions about its role in tumor survival. Here, a microfluidic-based 3D-human lung tumor spheroid-P. aeruginosa model is developed to study the bacteria's impact on tumor survival. P. aeruginosa forms a tumor-associated biofilm by producing Psl exopolysaccharide and secreting iron-scavenging pyoverdine, which is critical for establishing a bacterial community in tumors. Consequently, pyoverdine promotes cancer progression by reducing susceptibility to iron-induced death (ferroptosis), enhancing cell viability, and facilitating several cancer hallmarks, including epithelial-mesenchymal transition and metastasis. A promising combinatorial therapy approach using antimicrobial tobramycin, ferroptosis-inducing thiostrepton, and anti-cancer doxorubicin could eradicate biofilms and tumors. This work unveils a novel phenomenon of cross-kingdom cooperation, where bacteria protect tumors from death, and it paves the way for future research in developing antibiofilm cancer therapies. Understanding these interactions offers potential new strategies for combatting cancer and enhancing treatment efficacy.

Anchoring Metal-Nitrogen Sites on Porous Carbon Polyhedra with Highly Accessible Multichannels for Efficient Oxygen Reduction.

Transition metal-nitrogen-carbon complexes, featuring single metal atoms embedded in a nitrogen-doped carbon matrix, emerge as promising alternatives to traditional platinum-based catalysts, offering cost-effectiveness, abundance, and enhanced catalytic performance. This work introduces a novel method for the etching and doping of zeolitic imidazolate frameworks (ZIFs) with transition metals, creating a uniform distribution of secondary metal centers on ZIF surfaces. By disrupting the crystalline symmetry of ZIFs through synthetic defect engineering, we gain access to their entire internal volume, creating multichannel pathways. The absorption of metal ions is theoretically simulated, demonstrating their thermodynamically spontaneous nature. The selective removal of defect channels under Lewis acidic conditions, induced by metal ion alcoholysis/hydrolysis, facilitates the introduction of metal atoms into ZIF cavities. The resulting single-atom catalyst, after pyrolysis, features a three-dimensional (3D) multichannel structure, high surface area, and uniformly dispersed metal atoms within the N-doped carbon matrix, establishing it as an exceptional catalyst for the oxygen reduction reaction (ORR). Our findings highlight the potential of using metal etching in defect-engineered metal-organic frameworks (MOFs) for single-atom catalyst preparation, paving the way for the next generation of high-performance, cost-effective ORR catalysts in sustainable energy systems.

[Occupational chronic psychological stress and transaminase, HSP70 gene family and its proteins association of the interaction with metabolic syndrome].

OBJECTIVE: To explore the association of Occupational chronic psychological stress with transaminase, heat shock protein70(HSP70)gene family and their protein interaction with metabolic syndrome(MS). METHODS: A case-control study was used. According to the inclusion and exclusion criteria, from March 2015 to March 2016, 583 unrelated MS patients were selected as the case group and 585 unrelated healthy people as the control group among hospitalized and physical examination subjects aged 20-60 in Wuzhong People's Hospital and General Hospital of Ningxia Medical University. Questionnaire survey, physical examination, clinical and biochemical indicators, serum HSP70 level and five-locus polymorphism detection of HSP70 gene were carried out. GMDR 0.7 software was used to analyze the relationship between psychological stress, transaminase, HSP70 gene and its protein interaction and MS. RESULTS: After adjusting for age and sex, the rs1008438, rs1061581, rs539689 and rs222795 locus of HSP70 gene in the Co-dominant model and Dominant model and the rs222795 loci in the Over-dominant model carry wild homozygous genotype and heterozygous genotype were all related to the reduction of MS risk(OR<1, P<0.05). GMDR result: the 2-factor interaction model composed of psychological stress and serum HSP70, the 2-3 factor interaction model composed of transaminase activity, and the 2-6 factor interaction model composed of five locus of HSP70 gene, the 2-9 factor interaction model consisting of psychological stress and transaminase activity, HSP70 gene and its protein were all significantly associated with MS(P<0.01, P<0.05), all each factor interaction models were the best, and the 9-factor optimal interaction model had the highest risk of MS(OR=46.51, 95%CI 27.65-78.26), and the risk of MS in high-risk type was 45.23 times higher than that in low-risk type(95%CI 31.29-65.38, P<0.01). CONCLUSION: HSP70 gene family carrying wild-type alleles is a protective factor for MS. The interaction among Occupational chronic psychological stress interacts with transaminases, HSP70 gene and its serum proteins may be associated with MS. With the increase of involvement interaction factors, the risk of MS increased significantly. The interaction of multiple factors can greatly increase its risk.

High-Frequency Hearing Loss, Hippocampal Volume, and Motoric Cognitive Risk Syndrome in Older Adults in China: A Population-Based Study.

Background: Little is known about the associations of hearing loss, hippocampal volume, and motoric cognitive risk syndrome (MCR) in older adults. Objective: We aimed to investigate the associations of hearing loss with MCR and hippocampal volume; and the interaction of hearing loss with hippocampal volume on MCR. Methods: This population-based cross-sectional study included 2,540 dementia-free participants (age≥60 years; 56.5% women) in the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China. Data were collected through face-to-face interviews, clinical examination, and laboratory tests. Hearing function was assessed using pure tone audiometry test. In the subsample (n = 661), hippocampal volume was assessed on structural magnetic resonance images. Data were analyzed with logistic regression models. Results: In the total sample, MCR was diagnosed in 246 persons (9.7%). High-frequency hearing loss was significantly associated with an increased likelihood of MCR and slow gait. In the subsample, the restricted cubic spline plots indicated an inverted U-shaped nonlinear relationship between high-frequency hearing performance and hippocampal volume. Moreover, greater hippocampal volume was significantly associated with a deduced likelihood of MCR and subjective cognitive decline (SCD). In addition, there were statistical interactions of high-frequency hearing loss with hippocampal volume on MCR and slow gait (p for interaction < 0.05), such that the associations were statistically significant only among participants free of high-frequency hearing loss. Conclusions: High-frequency hearing loss was associated with an increased likelihood of MCR in older adults. The hippocampus might play a part in the relationship of high-frequency hearing loss and MCR.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis, prognosis and recurrence risk in patients with cervical epithelioma.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. AIM: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. METHODS: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. RESULTS: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). CONCLUSION: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.

[Spatiotemporal Coupling Analysis of Urbanization and Ecosystem Services in Southeastern Fujian].

Revealing the spatiotemporal coupling relationship between urbanization and ecosystem services can help to clarify regional development differences, optimize the implementation path of urbanization, and improve the quality of ecosystem services. Taking southeastern Fujian, a region with a good ecological foundation and strong urbanization potential, as a case study, the levels of multidimensional urbanization systems and typical ecosystem services of this region in the years 2000, 2010, and 2020 were quantified using the index comprehensive evaluation method and the InVEST model. The Pearson correlation coefficient and the coupling coordination degree model were used to analyze the spatiotemporal coupling relationship between urbanization and ecosystem services, and suggestions for improving regional coordinated development were proposed. The results showed that： ① The comprehensive urbanization level in southeastern Fujian increased continuously, with an average annual growth rate of 7.3%, of which social urbanization was the fastest, followed by economic urbanization and population urbanization, and spatial urbanization was relatively backward. Ecosystem services tended to decline, especially food and water provision services, which decreased by 61.9% and 46.9%, respectively. The spatial distribution showed a mismatch pattern of "high urbanization level and weak ecosystem services" in the southeast coastal area and "low urbanization level and strong ecosystem services" in the northwest inland area. ② The correlation between urbanization and ecosystem services was mainly negative. The negative effect of economic and social urbanization on ecosystem services was weaker than that of population and spatial urbanization, with a clear weakening tendency. As population and spatial urbanization slowed down sharply and economic and social urbanization accelerated, the driving force of urbanization development gradually shifted from "quantitative increase" to "qualitative improvement." Thus, the decline of ecosystem services was alleviated. ③ Comprehensive urbanization and various ecosystem services experienced three stages of "imbalance-transition-reconciliation," with an average increase of 60.5% to 120.6% in the coupling coordination degree. However, highly coordinated regions remained scarce, indicating that there is still significant room for improvement. The relative relationship between urbanization and ecosystem services evolved from urbanization lag to ecosystem services lag. The fluctuation problem of backward coupling coordination level caused by excessive urbanization had initially appeared in the southeastern coastal area. Therefore, in future construction, southeastern Fujian should improve economic quality and social benefits； strengthen the overall management, protection, and restoration of ecological space； and enhance the order and stability of the coordinated development of urbanization and ecosystem services.

Rotation Error Prediction of CNC Spindle Based on Short-Time Fourier Transform of Vibration Sensor Signals and Improved Weighted Residual Network.

The spindle rotation error of computer numerical control (CNC) equipment directly reflects the machining quality of the workpiece and is a key indicator reflecting the performance and reliability of CNC equipment. Existing rotation error prediction methods do not consider the importance of different sensor data. This study developed an adaptive weighted deep residual network (ResNet) for predicting spindle rotation errors, thereby establishing accurate mapping between easily obtainable vibration information and difficult-to-obtain rotation errors. Firstly, multi-sensor data are collected by a vibration sensor, and Short-time Fourier Transform (STFT) is adopted to extract the feature information in the original data. Then, an adaptive feature recalibration unit with residual connection is constructed based on the attention weighting operation. By stacking multiple residual blocks and attention weighting units, the data of different channels are adaptively weighted to highlight important information and suppress redundancy information. The weight visualization results indicate that the adaptive weighted ResNet (AWResNet) can learn a set of weights for channel recalibration. The comparison results indicate that AWResNet has higher prediction accuracy than other deep learning models and can be used for spindle rotation error prediction.

Difluorocarbene-Promoted O-O Bond Activation of Peroxy Acids for Electrophilic Carboxylation of Boronic Acids.

In this study, a difluorocarbene-promoted O-O bond activation of peroxy acids is developed through the insertion of difluorocarbene into O-H bond. This activation strategy in synergy with O-B coordination with boronic acids/ester greatly polarizes the O-O bond for in-situ generation of carboxylium species that reacts with the nucleophilic part of boronic acids in a concerted way to produce esters. Good efficiency and functional group tolerance are demonstrated. Application of this method to the functionalization of a boronic acid drug used as HSL enzyme inhibitor produces smoothly the ester derivative. This difluorocarbene-mediated O-O bond activation strategy is conceptually different from traditional radical type methods, and is also complementary to conventional esterification methods with a distinct retro-synthetic disconnection.

"Hard" Emulsion-Induced Interface Super-Assembly: A General Strategy for Two-Dimensional Hierarchically Porous Metal-Organic Framework Nanoarchitectures.

Two-dimensional (2D) hierarchically porous metal-organic framework (MOF) nanoarchitectures with tailorable meso-/macropores hold great promise for enhancing mass transfer kinetics, augmenting accessible active sites, and thereby boosting performance in heterogeneous catalysis. However, achieving the general synthesis of 2D free-standing MOF nanosheets with controllable hierarchical porosity and thickness remains a challenging task. Herein, we present an ingenious "hard" emulsion-induced interface super-assembly strategy for preparing 2D hierarchically porous UiO-66-NH2 nanosheets with highly accessible pore channels, tunable meso-/macropore sizes, and adjustable thicknesses. The methodology relies on transforming the geometric shape of oil droplet templates within appropriate oil-in-water emulsions from conventional zero-dimensional (0D) "soft" liquid spheres to 2D "hard" solid sheets below the oil's melting/freezing point. Subsequent surfactant exchange on the surface of 2D "hard" emulsions facilitates the heterogeneous nucleation and interfacial super-assembly of in situ formed mesostructured MOF nanocomposites, serving as structural units, in a loosely packed manner to produce 2D MOF nanosheets with multimodal micro/meso-/macroporous systems. Importantly, this strategy can be extended to prepare other 2D hierarchically porous MOF nanosheets by altering metal-oxo clusters and organic ligands. Benefiting from fast mass transfer and highly accessible Lewis acidic sites, the resultant 2D hierarchically porous UiO-66-NH2 nanosheets deliver a fabulous catalytic yield of approximately 96% on the CO2 cycloaddition of glycidyl-2-methylphenyl ether, far exceeding the yield of approximately 29% achieved using conventional UiO-66-NH2 microporous crystals. This "hard" emulsion-induced interface super-assembly strategy paves a new path toward the rational construction of elaborate 2D nanoarchitecture of hierarchical MOFs with tailored physicochemical properties for diverse potential applications.

Fluid infusion prior to intubation or anesthesia: A meta-analysis of randomized controlled trials.

BACKGROUND: The results of current randomized controlled trials (RCTs) vary regarding the effectiveness of rehydration prior to anesthesia induction. Our objective was to determine the effectiveness of pre-induction rehydration in patients undergoing tracheal intubation or surgical procedures. METHODS: This meta-analysis followed PRISMA guidelines and was registered in the INPLASY database (registration number: INPLASY2022100099). Two reviewers independently searched PubMed, Embase, The Cochrane Database of Systematic Reviews, and Clinical Trials databases until October 2022, without any restrictions on date. Any randomized controlled trial investigating the administration of intravenous fluids to patients undergoing tracheal intubation or pre-surgical anesthesia induction was considered eligible. Exclusion criteria were applied to exclude certain literature. Data were analyzed using RevMan (5.4.1) software after independent extraction. The primary objective of this study was to determine if intravenous rehydration could reduce the occurrence of hypotensive events and the use of vasoactive drugs following anesthesia induction. RESULTS: This meta-analysis included seven studies with a total of 2850 patients, including 1430 patients who received rehydration and 1420 control patients. Patients who received early rehydration had a lower incidence of hypotensive events compared to those who did not (RR 0.78, 95% CI 0.66-0.92, P = 0.004). No heterogeneity was observed (p = 0.31, I2 = 16%). However, subgroup analysis showed that rehydration before tracheal intubation did not reduce hypotensive events in critically ill patients (RR 0.99, 95% CI 0.61-1.60, P = 0.96). There were no significant differences in the use of vasoactive medications between the two study groups (RR 0.96, 95% CI 0.80-1.16, P = 0.69). No heterogeneity was observed (p = 0.26, I2 = 23%). The funnel plot indicated no evidence of publication bias. CONCLUSIONS: Pre-induction rehydration can reduce the occurrence of hypotensive events, but only in pre-surgical patients, and does not decrease the use of vasoactive medications.

Clinical drug interactions between linezolid and other antibiotics: For adverse drug event monitoring.

Detailed data on safety associated with drug-drug interactions (DDIs) between Linezolid (LZD) and other antibiotics are limited. The aim of this study was to investigate the safety signals related to these DDIs and to provide a reference for clinically related adverse drug event monitoring. Adverse event (AE) information from 1 January 2004 to 16 June 2022 of the target antibiotics including LZD using alone or in combination with LZD was extracted from the OpenVigil FDA data platform for safety signal analysis. The combined risk ratio model, reporting ratio method, Ω shrinkage measure model, and chi-square statistics model were used to analyze the safety signals related to DDIs. Meanwhile, we evaluated the correlation and the influence of sex and age between the drug(s) and the target AE detected. There were 18991 AEs related to LZD. There were 2293, 1726, 4449, 821, 2431, 1053, and 463 AE reports when LZD was combined with amikacin, voriconazole, meropenem, clarithromycin, levofloxacin, piperacillin-tazobactam, and azithromycin, respectively. Except for azithromycin, there were positive safety signals related to DDIs between LZD and these antibiotics. These DDIs might influence the incidence of 13, 16, 7, 7, 6, and 15 types of AEs, respectively, and is associated with higher reporting rates of AEs compared with use alone. Moreover, sex and age might influence the occurrence of AEs. We found that the combinations of LZD and other antibiotics are related to multiple AEs, such as hepatotoxicity, drug resistance and electrocardiogram QT prolonged, but further research is still required to investigate their underlying mechanisms. This study can provide a new reference for the safety monitoring of LZD combined with other antibiotics in clinical practice.

A Comparative Analysis of the Anti-Tumor Activity of Sixteen Polysaccharide Fractions from Three Large Brown Seaweed, Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida.

Searching for natural products with anti-tumor activity is an important aspect of cancer research. Seaweed polysaccharides from brown seaweed have shown promising anti-tumor activity; however, their structure, composition, and biological activity vary considerably, depending on many factors. In this study, 16 polysaccharide fractions were extracted and purified from three large brown seaweed species (Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida). The chemical composition analysis revealed that the polysaccharide fractions have varying molecular weights ranging from 8.889 to 729.67 kDa, and sulfate contents ranging from 0.50% to 10.77%. Additionally, they exhibit different monosaccharide compositions and secondary structures. Subsequently, their anti-tumor activity was compared against five tumor cell lines (A549, B16, HeLa, HepG2, and SH-SY5Y). The results showed that different fractions exhibited distinct anti-tumor properties against tumor cells. Flow cytometry and cytoplasmic fluorescence staining (Hoechst/AO staining) further confirmed that these effective fractions significantly induce tumor cell apoptosis without cytotoxicity. qRT-RCR results demonstrated that the polysaccharide fractions up-regulated the expression of Caspase-3, Caspase-8, Caspase-9, and Bax while down-regulating the expression of Bcl-2 and CDK-2. This study comprehensively compared the anti-tumor activity of polysaccharide fractions from large brown seaweed, providing valuable insights into the potent combinations of brown seaweed polysaccharides as anti-tumor agents.

Genome-Wide Identification and Interaction Analysis of Turbot Heat Shock Protein 40 and 70 Families Suggest the Mechanism of Chaperone Proteins Involved in Immune Response after Bacterial Infection.

Hsp40-Hsp70 typically function in concert as molecular chaperones, and their roles in post-infection immune responses are increasingly recognized. However, in the economically important fish species Scophthalmus maximus (turbot), there is still a lack in the systematic identification, interaction models, and binding site analysis of these proteins. Herein, 62 Hsp40 genes and 16 Hsp70 genes were identified in the turbot at a genome-wide level and were unevenly distributed on 22 chromosomes through chromosomal distribution analysis. Phylogenetic and syntenic analysis provided strong evidence in supporting the orthologies and paralogies of these HSPs. Protein-protein interaction and expression analysis was conducted to predict the expression profile after challenging with Aeromonas salmonicida. dnajb1b and hspa1a were found to have a co-expression trend under infection stresses. Molecular docking was performed using Auto-Dock Tool and PyMOL for this pair of chaperone proteins. It was discovered that in addition to the interaction sites in the J domain, the carboxyl-terminal domain of Hsp40 also plays a crucial role in its interaction with Hsp70. This is important for the mechanistic understanding of the Hsp40-Hsp70 chaperone system, providing a theoretical basis for turbot disease resistance breeding, and effective value for the prevention of certain diseases in turbot.

Advances in multiparametric magnetic resonance imaging combined with biomarkers for the diagnosis of high-grade prostate cancer.

Clinical decisions based on the test results for prostate-specific antigen often result in overdiagnosis and overtreatment. Multiparametric magnetic resonance imaging (mpMRI) can be used to identify high-grade prostate cancer (HGPCa; Gleason score ≥3 + 4); however, certain limitations remain such as inter-reader variability and false negatives. The combination of mpMRI and prostate cancer (PCa) biomarkers (prostate-specific antigen density, Proclarix, TMPRSS2:ERG gene fusion, Michigan prostate score, ExoDX prostate intelliscore, four kallikrein score, select molecular diagnosis, prostate health index, and prostate health index density) demonstrates high accuracy in the diagnosis of HGPCa, ensuring that patients avoid unnecessary prostate biopsies with a low leakage rate. This manuscript describes the characteristics and diagnostic performance of each biomarker alone and in combination with mpMRI, with the intension to provide a basis for decision-making in the diagnosis and treatment of HGPCa. Additionally, we explored the applicability of the combination protocol to the Asian population.

Association of late-life blood pressure change with cerebral small vessel disease in the MIND-China study.

OBJECTIVES: This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). METHODS: This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. RESULT: The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. CONCLUSIONS: CSVDs are associated with increased exposure to elevated BP later in life.

A robust ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of 10 components in glutathione cycle.

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.

Aerobic mechanochemical reversible-deactivation radical polymerization.

Polymer materials suffer mechano-oxidative deterioration or degradation in the presence of molecular oxygen and mechanical forces. In contrast, aerobic biological activities combined with mechanical stimulus promote tissue regeneration and repair in various organs. A synthetic approach in which molecular oxygen and mechanical energy synergistically initiate polymerization will afford similar robustness in polymeric materials. Herein, aerobic mechanochemical reversible-deactivation radical polymerization was developed by the design of an organic mechano-labile initiator which converts oxygen into activators in response to ball milling, enabling the reaction to proceed in the air with low-energy input, operative simplicity, and the avoidance of potentially harmful organic solvents. In addition, this approach not only complements the existing methods to access well-defined polymers but also has been successfully employed for the controlled polymerization of (meth)acrylates, styrenic monomers and solid acrylamides as well as the synthesis of polymer/perovskite hybrids without solvent at room temperature which are inaccessible by other means.

Advanced Nanomedicine Approaches for Myocardial Infarction Treatment.

Myocardial infarction, usually caused by the rupture of atherosclerotic plaque, leads to irreversible ischemic cardiomyocyte death within hours followed by impaired cardiac performance or even heart failure. Current interventional reperfusion strategies for myocardial infarction still face high mortality with the development of heart failure. Nanomaterial-based therapy has made great progress in reducing infarct size and promoting cardiac repair after MI, although most studies are preclinical trials. This review focuses primarily on recent progress (2016-now) in the development of various nanomedicines in the treatment of myocardial infarction. We summarize these applications with the strategy of mechanism including anti-cardiomyocyte death strategy, activation of neovascularization, antioxidants strategy, immunomodulation, anti-cardiac remodeling, and cardiac repair.