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1.
Anal Chem ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980807

ABSTRACT

Stroke is an acute injury of the central nervous system caused by the disorders of cerebral blood circulation, which has become one of the major causes of disability and death. Hemorrhage, particularly subarachnoid hemorrhage (SAH), is one of the poorest prognostic factors in stroke, which is related to the thrombolytic therapy, and has been considered very dangerous. In this context, the MR angiography with high sensitivity and resolution has been developed based on biocompatible paramagnetic ultrasmall NaGdF4 nanoprobes. Owing to the appropriate hydrodynamic diameter, the nanoprobe can be confined inside the blood vessels and it only extravasates at the vascular injury site when the bleeding occurs. Relying on this property, the three-dimensional (3D) anatomic structures of artery occlusion of stroke rat can be precisely visualized; reperfusion-related SAH has been successfully visualized and identified. Benefiting from the long blood half-life of the nanoprobe, the observation window of MR angiography can last for the whole period of reperfusion, thereby monitoring the probable SAH in real time during thrombolytic therapy. More importantly, through reconstruction of multiparametric MRI, the arterial occlusion, cerebral ischemic region, and SAH can be simultaneously visualized in vivo in a 3D manner for the first time. Therefore, the current study provides a novel approach for both noninvasive 3D vascular visualization and hemorrhage alert, which possesses great prospects for clinical translation.

2.
Front Nutr ; 11: 1383658, 2024.
Article in English | MEDLINE | ID: mdl-38988853

ABSTRACT

Background: High dietary protein intake exacerbates proteinuria in individuals with diabetic kidney disease (DKD). However, studies on the impacts of low protein diet (LPD) on DKD have yielded conflicting results. Furthermore, patient compliance to continuous protein restriction is challenging. Objective: The current study aims to investigate the effects of intermittent protein restriction (IPR) on disease progression of DKD. Methods: Diabetic KK-Ay mice were used in this study. For the IPR treatment, three consecutive days of LPD were followed by four consecutive days of normal protein diet (NPD) within each week. For early intervention, mice received IPR before DKD onset. For late intervention, mice received IPR after DKD onset. In both experiments, age-matched mice fed continuous NPD served as the control group. Kidney morphology, structure and function of mice in different groups were examined. Results: Intermittent protein restriction before DKD onset ameliorated pathological changes in kidney, including nephromegaly, glomerular hyperfiltration, tubular injuries and proteinuria, without improving glycemic control. Meanwhile, IPR initiated after DKD onset showed no renoprotective effects despite improved glucose homeostasis. Conclusion: Intermittent protein restriction before rather than after DKD onset protects kidneys, and the impacts of IPR on the kidneys are independent of glycemic control. IPR shows promise as an effective strategy for managing DKD and improving patient compliance.

3.
J Colloid Interface Sci ; 675: 569-579, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38986330

ABSTRACT

Affinity and storage capacity for zinc ions of the electrode materials are crucial factors on the properties of zinc ion hybrid capacitors (ZHICs). Wasted pulping liquor with abundant carbohydrates, lignin and inorganic matter served as a unique precursor to produce embedded oxygen-doped hierarchical porous carbon directly through a one-step carbonization process in this investigation. In carbonization process, lignin can serve effectively as the carbon framework, carbohydrates not only act as sacrificial templates but also offer a plentiful oxygen source which can increase the affinity for Zn2+, and sodium-containing inorganic substances plays a role as hard templates to optimize the pore structure. The resulting porous carbon under carbonization temperature of 800 °C shows a high specifical area of 2186 m2g-1 with oxygen content of 4.8 %, which can reduce the adsorption energy of Zn2+ from -0.16 eV to -0.32 eV through electrochemical techniques and density functional theory (DFT) calculations, the incorporation of oxygen was demonstrated to enhance the adsorption and desorption kinetics of Zn2+, suggesting a bright future for application in the domain of energy storage. The resulting ZIHC assembly showcases a notable energy density of 84.6 Wh kg-1 at a power density of 359 W kg-1. Remarkably, even after 10,000 charge and discharge cycles, it exhibits exceptional cycle stability with retaining 86.56 % of its capacity. Consequently, this approach provides fresh insights for exploring the facile and commercial fabrication of biomass-derived cathodes for ZIHCs, thereby propelling the progress of eco-friendly energy storage devices.

4.
Adv Mater ; : e2401561, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38949414

ABSTRACT

Digital light processing (DLP) is a 3D printing technology offering high resolution and speed. Printable materials are commonly based on multifunctional monomers, resulting in the formation of thermosets that usually cannot be reprocessed or recycled. Some efforts are made in DLP 3D printing of thermoplastic materials. However, these materials exhibit limited and poor mechanical properties. Here, a new strategy is presented for DLP 3D printing of thermoplastics based on a sequential construction of two linear polymers with contrasting (stiff and flexible) mechanical properties. The inks consist of two vinyl monomers, which lead to the stiff linear polymer, and α-lipoic acid, which forms the flexible linear polymer via thermal ring-opening polymerization in a second step. By varying the ratio of stiff and flexible linear polymers, the mechanical properties can be tuned with Young's modulus ranging from 1.1 GPa to 0.7 MPa, while the strain at break increased from 4% to 574%. Furthermore, these printed thermoplastics allow for a variety of reprocessability pathways including self-healing, solvent casting, reprinting, and closed-loop recycling of the flexible polymer, contributing to the development of a sustainable materials economy. Last, the potential of the new material in applications ranging from soft robotics to electronics is demonstrated.

5.
J Chem Phys ; 161(1)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38949588

ABSTRACT

Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.


Subject(s)
Cardiolipins , Fluorescent Dyes , Unilamellar Liposomes , Cardiolipins/chemistry , Fluorescent Dyes/chemistry , Unilamellar Liposomes/chemistry , Surface Properties , Liposomes/chemistry , Sodium Chloride/chemistry , Surface-Active Agents/chemistry , Molecular Structure
6.
Sci Adv ; 10(28): eadn0960, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996025

ABSTRACT

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.


Subject(s)
Adenosine Triphosphate , Pentacyclic Triterpenes , Prodrugs , Reactive Oxygen Species , Pentacyclic Triterpenes/pharmacology , Pentacyclic Triterpenes/chemistry , Prodrugs/chemistry , Prodrugs/pharmacology , Adenosine Triphosphate/metabolism , Humans , Animals , Reactive Oxygen Species/metabolism , Mice , Cell Line, Tumor , Triterpenes/chemistry , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chelating Agents/chemistry , Chelating Agents/pharmacology , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Tumor Microenvironment/drug effects , Drug Liberation , Nanoparticles/chemistry , Xenograft Model Antitumor Assays , Ferric Compounds/chemistry
7.
J Med Chem ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962837

ABSTRACT

Targeting c-Met is a clinical trend for the precise treatment of HCC, but the potential issue of acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease treatment and overcoming drug resistance due to its special mechanism of action. In this study, we designed and synthesized two series of novel c-Met degraders and conducted a systematic biological evaluation of the optimal compound H11. H11 exhibited good c-Met degradation activity and anti-HCC activity. Importantly, H11 also demonstrated more potent inhibitory activity against Ba/F3-TPR-MET-D1228N and Ba/F3-TPR-MET-Y1230H cell lines than did tepotinib. In summary, H11 displayed potent anti-HCC activity as a degrader and may overcome resistance to type Ib inhibitors, making it a new therapeutic strategy for HCC with MET alterations.

8.
Int J Surg ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857504

ABSTRACT

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in cancer tissue. The lack of specific biomarkers makes the diagnosis and prognosis of TNBC challenging. METHOD: A comprehensive literature review and bibliometric analysis was performed using CiteSpace, VOSviewer and Scimago Graphica. RESULTS: TNBC biomarker research has been growing rapidly in recent years, reflecting the enormous academic interest in TNBC biomarker research. A total of 127 journals published relevant studies and 1749 authors were involved in the field, with developed countries such as the United States, France, and the United Kingdom contributing greatly to the field. Collaborative network analysis found that the research in this field has not yet formed good communication and interaction, and the partnership should be strengthened in the future in order to promote the in-depth development of TNBC biomarker research. Comprehensive analysis of keywords and co-cited literature, etc. found that TNBC biomarker research mainly focuses on immune checkpoint markers, microenvironment-related markers, circulating tumour DNA, metabolic markers, genomics markers and so on. These research hotspots will help to better understand the molecular characteristics and biological processes of TNBC, and provide more accurate biomarkers for its diagnosis, treatment and prognosis. CONCLUSIONS: The bibliometric analysis highlighted global trends and key directions in TNBC biomarker research. Future developments in TNBC biomarker research are likely to be in the direction of multi-omics integration, meticulous study of the microenvironment, targeted therapeutic biomarkers, application of liquid biopsy, application of machine learning and artificial intelligence, and individualised therapeutic strategies. Young scholars should learn and collaborate across disciplines, pay attention to new technologies and methods, improve their data analysis skills, and continue to follow up on the latest research trends in order to meet the challenges and opportunities in the field of TNBC biomarkers.

9.
Int J Biol Macromol ; 274(Pt 1): 133243, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901507

ABSTRACT

To enhance the DNA/RNA amplification efficiency and inhibitor tolerance of Bst DNA polymerase, four chimeric Bst DNA polymerase by fusing with a DNA-binding protein Sto7d and/or a highly hydrophobic protein Hp47 to Bst DNA polymerase large fragment. One of chimeric protein HpStBL exhibited highest inhibitor tolerance, which retained high active under 0.1 U/µL sodium heparin, 0.8 ng/µL humic acid, 2.5× SYBR Green I, 8 % (v/v) whole blood, 20 % (v/v) tissue, and 2.5 % (v/v) stool. Meanwhile, HpStBL showed highest sensitivity (93.75 %) to crude whole blood infected with the African swine fever virus. Moreover, HpStBL showed excellent reverse transcriptase activity in reverse transcription loop-mediated isothermal amplification, which could successfully detect 0.5 pg/µL severe acute respiratory syndrome coronavirus 2 RNA in the presence of 1 % (v/v) stools. The fusion of two domains with different functions to Bst DNA polymerase would be an effective strategy to improve Bst DNA polymerase performance in direct loop-mediated isothermal amplification and reverse transcription loop-mediated isothermal amplification detection, and HpStBL would be a promising DNA polymerase for direct African swine fever virus/severe acute respiratory syndrome coronavirus 2 detection due to simultaneously increased inhibitor tolerance and reverse transcriptase activity.

10.
Virulence ; 15(1): 2367671, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38910312

ABSTRACT

Viral diseases are among the main threats to public health. Understanding the factors affecting viral invasion is important for antiviral research. Until now, it was known that most viruses have very low plaque-forming unit (PFU)-to-particle ratios. However, further investigation is required to determine the underlying factors. Here, using quantitative single-particle analysis methods, the invasion of Semliki Forest virus (SFV), Japanese encephalitis virus (JEV), and influenza A virus (IAV) containing attachment to the cell surface, entry into the cell, transport towards the cell interior, and fusion with endosomes to release nucleocapsids were quantitatively analysed in parallel. It was found that for SFV with an PFU-to-particle ratio of approximately 1:2, an entry efficiency of approximately 31% limited infection. For JEV, whose PFU-to-particle ratio was approximately 1:310, an attachment efficiency of approximately 27% and an entry efficiency of 10% were the main factors limiting its infection. Meanwhile, for IAV with PFU-to-particle ratios of 1:8100, 5% attachment efficiency, 9% entry efficiency, and 53% fusion efficiency significantly limited its infection. These results suggest that viruses with different infectivities have different limited steps in the invasion process. Moreover, there are significant differences in attachment efficiencies among viruses, emphasizing the pivotal role of attachment in viral invasion. The influence of the virus purification method on virus invasion was also investigated. This study, for the first time, reports the efficiencies of different stages of virus invasion, leading to a better understanding of virus invasion and providing a protocol to quantitatively analyse the virus invasion efficiency.


Subject(s)
Influenza A virus , Semliki forest virus , Virus Internalization , Influenza A virus/physiology , Animals , Semliki forest virus/physiology , Humans , Encephalitis Virus, Japanese/physiology , Cell Line , Virus Attachment , Endosomes/virology
11.
J Chem Theory Comput ; 20(12): 5043-5057, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38836623

ABSTRACT

We present an open-source MLatom@XACS software ecosystem for on-the-fly surface hopping nonadiabatic dynamics based on the Landau-Zener-Belyaev-Lebedev algorithm. The dynamics can be performed via Python API with a wide range of quantum mechanical (QM) and machine learning (ML) methods, including ab initio QM (CASSCF and ADC(2)), semiempirical QM methods (e.g., AM1, PM3, OMx, and ODMx), and many types of ML potentials (e.g., KREG, ANI, and MACE). Combinations of QM and ML methods can also be used. While the user can build their own combinations, we provide AIQM1, which is based on Δ-learning and can be used out-of-the-box. We showcase how AIQM1 reproduces the isomerization quantum yield of trans-azobenzene at a low cost. We provide example scripts that, in dozens of lines, enable the user to obtain the final population plots by simply providing the initial geometry of a molecule. Thus, those scripts perform geometry optimization, normal mode calculations, initial condition sampling, parallel trajectories propagation, population analysis, and final result plotting. Given the capabilities of MLatom to be used for training different ML models, this ecosystem can be seamlessly integrated into the protocols building ML models for nonadiabatic dynamics. In the future, a deeper and more efficient integration of MLatom with Newton-X will enable a vast range of functionalities for surface hopping dynamics, such as fewest-switches surface hopping, to facilitate similar workflows via the Python API.

12.
Water Sci Technol ; 89(11): 2907-2920, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38877621

ABSTRACT

In this study, three sequencing batch biofilter granular reactors (SBBGRs) were employed to treat model lignin wastewater containing different lignin models (2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin). After 40 days of cultivation, uniform-shaped aerobic granular sludge (AGS) was successfully developed through nutrient supplementation with synthetic wastewater. During the acclimation stage, the chemical oxygen demand (COD) reduction efficiencies of the three reactors showed a trend of initial decreasing (5-20%) and then recovering to a high reduction efficiency (exceeding 90%) in a short period of time. During the stable operation stage, all three reactors achieved COD reduction efficiencies exceeding 90%. These findings indicated the cultivated AGS's robust resistance to changes in lignin models in water. UV-Vis spectra analysis confirmed the effective degradation of the three lignin models. Microbiological analysis showed that Proteobacteria and Bacteroidetes were always the dominant phyla. At the genus level, while Acinetobacter (15.46%) dominated in the inoculation sludge, Kapabacteriales (7.93%), SBR1031 (11.77%), and Chlorobium (25.37%) were dominant in the three reactors (for 2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin) after degradation, respectively. These findings demonstrate that AGS cultured with SBBGR effectively degrades lignin models, with different dominant strains observed for various lignin models.


Subject(s)
Bioreactors , Lignin , Sewage , Sewage/microbiology , Lignin/metabolism , Lignin/chemistry , Aerobiosis , Filtration/methods , Waste Disposal, Fluid/methods , Bacteria/metabolism
13.
ACS Omega ; 9(24): 26708-26718, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38911737

ABSTRACT

Y-H bond functionalization has always been the focus of research interest in the area of organic synthesis. Direct hydrogen atom transfer (HAT) from the Y-H bond is one of the most efficient and practical methods to activate the Y-H bond. Recently, nitrogen centered radical cations were broadly utilized as H-abstraction catalysts to activate Y-H bonds via the HAT process. As a type of HAT catalyst, the H-affinity of nitrogen centered radical cations is a significant thermodynamic parameter to quantitatively evaluate the thermodynamic H-abstraction potentials of nitrogen centered radical cations. In this work, the pK a values of 120 protonated N-containing compounds in acetonitrile (AN) are predicted, and the H-affinities of 120 nitrogen centered radical cations in AN are derived from the reduction potentials of nitrogen centered radical cations and pK a of protonated N-containing compounds using Hess' law. This work focuses on the H-abstraction abilities of 120 nitrogen centered radical cations in AN to enrich the molecule library of novel HAT catalysts or H-abstractors and provides valuable thermodynamic guidelines for the application of nitrogen centered radical cations in Y-H bond functionalization.

14.
BMC Infect Dis ; 24(1): 578, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862881

ABSTRACT

BACKGROUND: Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. METHODS: From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. RESULTS: Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p < 0.001). Male, re-treated and smear-positive groups were high-burden carriers of MTBC. Individuals aged > 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged < 61 years in the county and township areas. The detection of multidrug-resistant TB (MDR-TB) was higher in the main urban area than in the county and township areas (13.9% vs. 7.8%, p < 0.001). In all areas, MDR-TB groups were dominated by males, patients with a history of TB treatment, and patients aged < 61 years. Stratified analysis of MDR-TB epidemiology showed that MDR4 (INH þ RIF þ EMB þ SM) was predominant in the main urban area, while MDR3 (INH þ RIF þ SM) was predominant in the county and township areas. MDR-TB detection rate and epidemiology differed among the county and township areas. CONCLUSIONS: For local TB control, it is necessary to plan more appropriate and accurate prevention and control strategies according to the regional distribution of MTBC infection.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Male , Middle Aged , Female , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Adult , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , COVID-19/epidemiology , Aged , Adolescent , Young Adult , Drug Resistance, Multiple, Bacterial/genetics , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Child , Sputum/microbiology , SARS-CoV-2/genetics , SARS-CoV-2/drug effects , Child, Preschool , Aged, 80 and over , Infant , Epidemics
15.
Materials (Basel) ; 17(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38894015

ABSTRACT

Steel with a combination of strength and plasticity is prevalently demanded for lightweight design and emission reductions in manufacturing. In this study, a high-strength Cr-Ni-Mo martensitic steel treated by quenching and partitioning (Q&P) and ultrasonic surface rolling (USR) processes was studied for both strength and plasticity enhancement. Specimens were austenitized at 850 °C and then quenched to 240 °C via cooling by water, oil, and normalization in quenching. This was followed by partitioning, in which two groups of specimens were heated to 370 °C and 350 °C for 45 min, respectively. At last, all the specimens were quenched to room temperature with the same methods of quenching. The highest tensile strength increased from 681.73 MPa to 1389.76 MPa when compared to as-received (AR) steel after the Q&P process. The USR process with a static force of 800 N further improved the tensile strength of specimens with high tensile strength after the Q&P process, which improved from 1389.76 MPa to 1586.62 MPa and the product's strength and elongation (PSE) increased from 15.76 GPa% to 15.9 GPa%, while the total elongation showed a mitigatory decrease from 11.34% to 10.02%. Tensile fractures were also studied and verified using a combination of strength and plasticity after a combined process of Q&P and USR.

16.
World J Hepatol ; 16(5): 809-821, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38818287

ABSTRACT

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

17.
Biomed Pharmacother ; 176: 116802, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38795643

ABSTRACT

Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/ß-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.


Subject(s)
Hydrogen , Oxidation-Reduction , Oxidative Stress , Renal Insufficiency, Chronic , Signal Transduction , Oxidative Stress/drug effects , Humans , Hydrogen/pharmacology , Hydrogen/therapeutic use , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Oxidation-Reduction/drug effects , Signal Transduction/drug effects , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Reactive Oxygen Species/metabolism
18.
Int Heart J ; 65(3): 548-556, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38749748

ABSTRACT

Inflammation plays a pathophysiological role in atherosclerosis and its clinical consequences. In addition to glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are of wide concern for cardioprotective effects. The structure, half-life, homology, and clinical efficacy of GLP-1RAs exhibit remarkable disparity. Several studies have compared the disparities in anti-inflammatory effects between daily and weekly GLP-1RAs. This study aimed to compare the similarities and differences between liraglutide and dulaglutide in terms of inhibiting atherosclerotic inflammation and improving co-cultured endothelial cell function. The expression of inflammation markers was examined by immunofluorescence, Western blotting, and real-time PCR. The tube-forming ability of endothelial cells was tested on Matrigel. The results verify that 10/50/100 nmol/L liraglutide and 100 nmol/L dulaglutide markedly suppressed the expression of inflammatory factors in LPS-induced atherosclerosis after 24 and 72 hours, respectively. Moreover, they promoted the polarization of M1 macrophages toward the M2 phenotype and improved the function of co-cultured endothelial cells. Both liraglutide and dulaglutide ameliorate atherosclerosis development. The difference between the two resided in the extended intervention duration required to observe the effect of dulaglutide, and liraglutide demonstrated a superior dose-dependent manner. We provide a potential strategy to understand the dynamics of drug action and possible timing administration.


Subject(s)
Anti-Inflammatory Agents , Atherosclerosis , Glucagon-Like Peptides , Immunoglobulin Fc Fragments , Liraglutide , Recombinant Fusion Proteins , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/pharmacology , Glucagon-Like Peptides/therapeutic use , Liraglutide/pharmacology , Liraglutide/therapeutic use , Immunoglobulin Fc Fragments/pharmacology , Immunoglobulin Fc Fragments/therapeutic use , Recombinant Fusion Proteins/pharmacology , Recombinant Fusion Proteins/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Humans , Atherosclerosis/drug therapy , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Inflammation/drug therapy , Cells, Cultured , Coculture Techniques , Human Umbilical Vein Endothelial Cells/drug effects
19.
Small ; : e2402371, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597692

ABSTRACT

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation displays, but suffer from carrier imbalance arising from lower hole injection compared to electron injection. A defect engineering strategy is reported to tackle transport limitations in nickel oxide-based inorganic hole-injection layers (HILs) and find that hole injection is able to enhance in high-performance InP QLEDs using the newly designed material. Through optoelectronic simulations, how the electronic properties of NiOx affect hole injection efficiency into an InP QD layer, finding that efficient hole injection depends on lowering the hole injection barrier and enhancing the acceptor density of NiOx is explored. Li doping and oxygen enriching are identified as effective strategies to control intrinsic and extrinsic defects in NiOx, thereby increasing acceptor density, as evidenced by density functional theory calculations and experimental validation. With fine-tuned inorganic HIL, InP QLEDs exhibit a luminance of 45 200 cd m-2 and an external quantum efficiency of 19.9%, surpassing previous inorganic HIL-based QLEDs. This study provides a path to designing inorganic materials for more efficient and sustainable lighting and display technologies.

20.
Front Neurol ; 15: 1361037, 2024.
Article in English | MEDLINE | ID: mdl-38562427

ABSTRACT

Objective: This study aims to evaluate the efficacy and safety of various acupuncture treatments in conjunction with multimodal analgesia (MA) for managing postoperative pain and improving knee function in patients undergoing total knee arthroplasty (TKA), based on the findings from clinical research indicating the potential benefits of acupuncture-related therapies in this context. Methods: We searched Web of Science, PubMed, SCI-hub, Embase, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials of acupuncture-related therapies for post-TKA pain. After independent screening and data extraction, the quality of the included literature was evaluated. The potential for bias in the studies incorporated in the analysis was assessed according to the guidelines outlined in the Cochrane Handbook 5.1. Network meta-analysis (NMA) was conducted using RevMan 5.4 and Stata 16.0 software, with primary outcome measures including visual analog scale (VAS), pain pressure threshold (PPT), hospital for special surgery knee score (HSS), and knee joint range of motion (ROM). Furthermore, the interventions were ranked based on the SUCRA value. Results: We conducted an analysis of 41 qualifying studies encompassing 3,003 patients, examining the efficacy of four acupuncture therapies (acupuncture ACU, electroacupuncture EA, transcutaneous electrical acupoint stimulation TEAS, and auricular acupoint therapy AAT) in conjunction with multimodal analgesia (MA) and MA alone. The VAS results showed no significant difference in efficacy among the five interventions for VAS-3 score. However, TEAS+MA (SMD: 0.67; 95%CI: 0.01, 1.32) was more effective than MA alone for VAS-7 score. There was no significant difference in PPT score among the three interventions. ACU + MA (SMD: 6.45; 95%CI: 3.30, 9.60), EA + MA (SMD: 4.89; 95%CI: 1.46, 8.32), and TEAS+MA (SMD: 5.31; 95%CI: 0.85, 9.78) were found to be more effective than MA alone for HSS score. For ROM score, ACU + MA was more efficacious than EA + MA, TEAS+MA, and AAT + MA, MA. Regarding the incidence of postoperative adverse reactions, nausea and vomiting were more prevalent after using only MA. Additionally, the incidence of postoperative dizziness and drowsiness following ACU + MA (OR = 4.98; 95%CI: 1.01, 24.42) was observed to be higher compared to that after AAT + MA intervention. Similarly, the occurrence of dizziness and drowsiness after MA was found to be significantly higher compared to the following interventions: TEAS+MA (OR = 0.36; 95%CI: 0.18, 0.70) and AAT + MA (OR = 0.20; 95%CI: 0.08, 0.50). The SUCRA ranking indicated that ACU + MA, EA + MA, TEAS+MA, and AAT + MA displayed superior SUCRA scores for each outcome index, respectively. Conclusion: For the clinical treatment of post-TKA pain, acupuncture-related therapies can be selected as a complementary and alternative therapy. EA + MA and TEAS+MA demonstrate superior efficacy in alleviating postoperative pain among TKA patients. ACU + MA is the optimal choice for promoting postoperative knee joint function recovery in TKA patients. AAT + MA is recommended for preventing postoperative adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/, identifier (CRD42023492859).

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