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1.
Article in English | MEDLINE | ID: mdl-38744460

ABSTRACT

BACKGROUND: We analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of fatigue and their association with physical disability following start of disease-modifying therapy (DMT). METHODS: Using a group-modelling approach, we assessed trajectories of fatigue with the Fatigue Scale for Motor and Cognitive Functions and physical disability with Expanded Disability Status Scale among 1587 and 1818 individuals who initiated a first DMT and had a first DMT switch, respectively, followed during 2011-2022. We investigated predictors of fatigue trajectories using group membership as a multinomial outcome and calculated conditional probabilities linking membership across the trajectories. RESULTS: We identified five trajectories of fatigue in participants who initiated their first DMT: no fatigue (mean starting values=23.7; 18.2% of population), low (35.5; 23.9%), mild (49.0; 21.6%), moderate (61.3; 20.1%) and severe (78.7; 16.1%). While no, low, mild and severe fatigue trajectories remained stable, the moderate trajectory increased to severe fatigue. Similarly, we identified six fatigue trajectories among participants who did a DMT switch, all indicating stable values over time. Women initiating a first DMT were more likely than men to display a severe fatigue trajectory, relative to the no fatigue one. There was a strong association between fatigue and physical disability trajectories. CONCLUSIONS: In this cohort of people with actively treated RRMS, self-reported fatigue remained stable or increased over the years following DMT start. There was a strong association between fatigue and disability after DMT start.

2.
BMC Psychol ; 12(1): 275, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755667

ABSTRACT

The present study conducted a comprehensive meta-analysis to systematically review the relationship between occupational burnout and work pressure among Chinese police officers. Additionally, the study explored the mediating role of coping styles using a meta-analytic structural equation model. The investigation involved a thorough search of CNKI, PubMed, PsychInfo, Web of Science, and Google Scholar databases, resulting in the identification of a total of 39 studies with 124 effect sizes and 14,089 police officers. The findings revealed a positive correlation between work pressure and occupational burnout among Chinese police officers (r = 0.410, 95% CI = [0.347, 0.469]). Furthermore, negative coping styles mediate the relationship between work pressure and occupational burnout. Importantly, these conclusions held true across various work regions for police officers. These results provide insights into the relationship magnitude between work pressure and occupational burnout in Chinese police work and shed light on the underlying mechanisms. Based on these findings, it is recommended that interventions focusing on reducing work pressure and fostering positive coping styles be implemented to mitigate occupational burnout among police officers.


Subject(s)
Adaptation, Psychological , Burnout, Professional , Police , Humans , Burnout, Professional/psychology , Burnout, Professional/epidemiology , Police/psychology , Police/statistics & numerical data , China/epidemiology , Occupational Stress/psychology , Occupational Stress/epidemiology , East Asian People
3.
Stem Cell Res Ther ; 15(1): 153, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38816870

ABSTRACT

BACKGROUND: The therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem. METHODS: We compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis. RESULTS: The results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group. CONCLUSIONS: Patients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/mortality , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Homologous , Transplantation, Autologous , Stem Cell Transplantation , Disease-Free Survival , Network Meta-Analysis , Treatment Outcome , Male
4.
Article in English | MEDLINE | ID: mdl-38804845

ABSTRACT

BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.

5.
Nanotechnology ; 35(34)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38806011

ABSTRACT

Low temperature has been a major challenge for lithium-ion batteries to maintain satisfied electrochemical performance, as it leads to poor rechargeability and low capacity retention. Traditional carbonate solvents, vinyl carbonate and dimethyl carbonate are indispensable components of commercial electrolytes. However, the higher melting point of these carbonate solvents causes their electrical conductivity to be easily reduced when temperatures drop below zero, limiting their ability to facilitate lithium ion transport. In this work, we demonstrate that the use of methyl propionate (MP) carboxylate and fluorocarbonate vinyl (FEC) electrolytes can overcome the limitations of low temperature cycling. Compared with carbonate electrolyte, MP has the characteristics of low melting point, low viscosity and low binding energy with Li+, which is crucial to improve the low temperature performance of the battery, while FEC is an effective component to inhibit the side reaction between MP and lithium metal. The carefully formulated MP-based electrolyte can generate a solid electrolyte interface with low resistance and rich in inorganic substances, which is conducive to the smooth diffusion of Li+, allowing the battery to successfully cycle at a high rate of 0.5 C at -20 °C, and giving it a reversible capacity retention rate of 65.3% at -40oC. This work designs a promising advanced electrolyte and holds the potential to overcome limitations of lithium-ion batteries in harsh conditions.

6.
Clin Med Insights Case Rep ; 17: 11795476241253107, 2024.
Article in English | MEDLINE | ID: mdl-38746687

ABSTRACT

Excessive water consumption is an extremely rare and potential asthma risk factor with very few cases reported in the literature. Common triggers of asthma include genetic factors, smoking, allergens, and viral respiratory infections. The adult patient with asthma reportedly drank too much water and was unable to get relief from his asthma while hospitalized. The patient's asthma was better controlled with the use of diuretics and control of the patient's fluid intake and output. This case explores asthma induced by excessive drinking of water.

7.
Sci Rep ; 14(1): 10106, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38697999

ABSTRACT

Previous studies have shown that a higher intensity of physical activity (PA) is associated with a lower risk of cognitive impairment (CI), whereas hypertension is associated with higher CI. However, there are few studies on the association between PA intensity and cognitive function in hypertensive patients. This study investigated the association between PA intensity and cognitive function in hypertensive patients. A total of 2035 hypertensive patients were included in this study, including 407 hypertensive patients with CI and 1628 hypertensive patients with normal cognitive function matched 1:4 by age and sex. The International Physical Activity Questionnaire-Long Form and the Mini-mental State Examination were used to evaluate PA intensity, total metabolic equivalents, and cognitive function in patients with hypertension. Multivariate logistic regression was used to analyze the correlation between PA intensity and CI in hypertensive patients. The Spearman correlation coefficient was used to analyze the correlation between PA intensity and the total score of each component of the MMSE and the correlation between PA total metabolic equivalents and cardiac structure in hypertensive patients. After adjusting for all confounding factors, PA intensity was negatively associated with CI in hypertensive patients (OR = 0.608, 95% CI: 0.447-0.776, P < 0.001), and this association was also observed in hypertensive patients with education level of primary school and below and junior high school and above (OR = 0.732, 95% CI: 0.539-0.995, P = 0.047; OR = 0.412, 95% CI: 0.272-0.626, P < 0.001). The intensity of PA in hypertensive patients was positively correlated with orientation (r = 0.125, P < 0.001), memory (r = 0.052, P = 0.020), attention and numeracy (r = 0.151, P < 0.001), recall ability (r = 0.110, P < 0.001), and language ability (r = 0.144, P < 0.001). PA total metabolic equivalents in hypertensive patients were negatively correlated with RVEDD and LAD (r = - 0.048, P = 0.030; r = - 0.051, P = 0.020) and uncorrelated with LVEDD (r = 0.026, P = 0.233). Higher PA intensity reduced the incidence of CI in hypertensive patients. Therefore, hypertensive patients were advised to moderate their PA according to their circumstances.


Subject(s)
Cognition , Cognitive Dysfunction , Exercise , Hypertension , Humans , Hypertension/physiopathology , Male , Female , Exercise/physiology , Middle Aged , Case-Control Studies , Cognition/physiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Aged , Surveys and Questionnaires , Adult
8.
Proc Natl Acad Sci U S A ; 121(15): e2309087121, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38557184

ABSTRACT

Africa carries a disproportionately high share of the global malaria burden, accounting for 94% of malaria cases and deaths worldwide in 2019. It is also a politically unstable region and the most vulnerable continent to climate change in recent decades. Knowledge about the modifying impacts of violent conflict on climate-malaria relationships remains limited. Here, we quantify the associations between violent conflict, climate variability, and malaria risk in sub-Saharan Africa using health surveys from 128,326 individuals, historical climate data, and 17,429 recorded violent conflicts from 2006 to 2017. We observe that spatial spillovers of violent conflict (SSVCs) have spatially distant effects on malaria risk. Malaria risk induced by SSVCs within 50 to 100 km from the households gradually increases from 0.1% (not significant, P>0.05) to 6.5% (95% CI: 0 to 13.0%). SSVCs significantly promote malaria risk within the average 20.1 to 26.9 °C range. At the 12-mo mean temperature of 22.5 °C, conflict deaths have the largest impact on malaria risk, with an approximately 5.8% increase (95% CI: 1.0 to 11.0%). Additionally, a pronounced association between SSVCs and malaria risk exists in the regions with 9.2 wet days per month. The results reveal that SSVCs increase population exposure to harsh environments, amplifying the effect of warm temperature and persistent precipitation on malaria transmission. Violent conflict therefore poses a substantial barrier to mosquito control and malaria elimination efforts in sub-Saharan Africa. Our findings support effective targeting of treatment programs and vector control activities in conflict-affected regions with a high malaria risk.


Subject(s)
Exposure to Violence , Malaria , Humans , Malaria/epidemiology , Africa South of the Sahara/epidemiology , Temperature
9.
J Environ Manage ; 356: 120652, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38531139

ABSTRACT

The increasing volume of electronic waste (e-waste) poses significant challenges for efficient collection in China. Despite many measures were taken over the past two decades, the e-waste collection rate was still not high. To this end, the Chinese government issued a new policy, the collection target responsibility (CTR) policy. Under the CTR policy, however, it is essential for participants to know how to share the responsibility of collection and how much reasonable targets are set to ensure the efficiency of the collection models. Therefore, the purpose of this paper is to explore the determination of optimal collection targets and the corresponding performance from the perspective of responsibility sharing to support the successful implementation of the CTR. Firstly, the study focuses on participants including the government, manufacturers, and recyclers, and develops three CTR models, independent collection model, government cost-sharing model, and enterprise collaboration model. Secondly, collection target equations for each model are established by employing dynamic differential game analysis, and corresponding collection performances are derived. Thirdly, through practical case simulations, the evolution of collection performance is dynamically analyzed to determine reasonable collection targets for the three models, as 23.8%, 32.3%, and 34.4%, respectively. The findings highlight the effectiveness of CTR in improving e-waste collection targets and performance, with the highest levels attained when the collection responsibilities are shared by government cost-sharing and enterprise collaboration. This study provides theoretical support for setting reasonable collection targets under CTR, and assists decision-makers in developing targeted CTR implementation measures.


Subject(s)
Electronic Waste , Waste Management , Humans , Recycling , China
10.
J Gene Med ; 26(3): e3680, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38448368

ABSTRACT

BACKGROUND: Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients. METHODS: YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity. RESULTS: YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response. CONCLUSIONS: YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Prognosis , Liver Neoplasms/genetics , Algorithms , Tumor Microenvironment/genetics , Y-Box-Binding Protein 1/genetics
11.
Front Psychol ; 15: 1323784, 2024.
Article in English | MEDLINE | ID: mdl-38384354

ABSTRACT

Corporal punishment is believed to precede various forms of violent behavior, yet prior research has yielded inconsistent findings, partly due to variations in violent types and other factors. This meta-analysis systematically reviewed 35 studies including 144 effect sizes (comprising a total sample size of 159,213) investigating the association between corporal punishment and a spectrum of violent behaviors called Violent Behavior Spectrum (VBS). Additionally, meta-regressions were conducted to explore the moderating impact of punishment severity, violence type and cultural context. Our findings indicated a significant positive relationship between corporal punishment and VBS (r = 0.238, 95%, CI [0.176, 0.300]). Notably, punishment severity was found to influence the strength of this association. Namely, The more severe the corporal punishment, the more likely it is to lead to VBS. These results enhance our understanding of the intricate connection between corporal punishment and various forms of violence, providing valuable insights for both parenting practices and policy development.

12.
Environ Res ; 250: 118495, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38367837

ABSTRACT

Methanogens are the main participants in the carbon cycle, catalyzing five methanogenic pathways. Methanogens utilize different iron-containing functional enzymes in different methanogenic processes. Iron is a vital element in methanogens, which can serve as a carrier or reactant in electron transfer. Therefore, iron plays an important role in the growth and metabolism of methanogens. In this paper, we cast light on the types and functions of iron-containing functional enzymes involved in different methanogenic pathways, and the roles iron play in energy/substance metabolism of methanogenesis. Furthermore, this review provides certain guiding significance for lowering CH4 emissions, boosting the carbon sink capacity of ecosystems and promoting green and low-carbon development in the future.


Subject(s)
Iron , Methane , Methane/metabolism , Iron/metabolism , Archaea/metabolism
13.
RSC Adv ; 14(10): 7157-7171, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38419673

ABSTRACT

Constructing a synergistic multiple-modal antibacterial platform for multi-drug-resistant (MDR) bacterial eradication and effective treatment of infected wounds remains an important and challenging goal. Herein, we developed a multifunctional Cu/Mn dual single-atom nanozyme (Cu/Mn-DSAzymes)-based synergistic mild photothermal/nanocatalytic-therapy for a MDR bacterium-infected wound. Cu/Mn-DSAzymes with collaborative effects exhibit remarkable dual CAT-like and OXD-like enzyme activities and could efficiently catalyze cascade enzymatic reactions with a low level of H2O2 as an initial reactant to produce reparative O2 and lethal ˙O2-. Moreover, a black N-doped carbon nanosheet supports of Cu/Mn-DSAzymes show superior NIR-II-triggered photothermal performance, endowing them with photothermal-enhanced dual enzyme catalysis. In addition, such enhanced dual enzyme catalysis likely improves the susceptibility and lethality of photothermal effects on MDR bacteria. In vitro and in vivo studies demonstrate that Cu/Mn-DSAzyme-mediated synergistic nanocatalytic and photothermal effects possess dramatic antibacterial outcomes against MDR bacteria and evidently reduced inflammation at wound sites. Moreover, the combined photothermal effect and O2 release mediated by Cu/Mn-DSAzymes promotes macrophage polarization to reparative M2 phenotype, collagen deposition, and angiogenesis, considerably accelerating wound healing. Therefore, Cu/Mn-DSAzyme-based synergetic dual-modal antibacterial therapy is a promising strategy for MDR bacterium-infected wound treatment, owing to their excellent antibacterial ability and significant tissue remodeling effects.

14.
Small Methods ; 8(1): e2300843, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37800985

ABSTRACT

Bone defects in osteoporosis usually present excessive reactive oxygen species (ROS), abnormal inflammation levels, irregular shapes and impaired bone regeneration ability; therefore, osteoporotic bone defects are difficult to repair. In this study, an injectable thermosensitive hydrogel poly (D, L-lactide)-poly (ethylene glycol)- poly (D, L-lactide) (PLEL) system containing resveratrol (Res) and dexamethasone (DEX) is designed to create a microenvironment conducive to osteogenesis in osteoporotic bone defects. This PLEL hydrogel is injected and filled irregular defect areas and achieving a rapid sol-gel transition in situ. Res has a strong anti-inflammatory effects that can effectively remove excess free radicals at the damaged site, guide macrophage polarization to the M2 phenotype, and regulate immune responses. Additionally, DEX can promote osteogenic differentiation. In vitro experiments showed that the hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, removed excess intracellular ROS, and regulated macrophage polarization to reduce inflammatory responses. In vivo experiments showed that the hydrogel promoted osteoporotic bone defect regeneration and modulated immune responses. Overall, this study confirmed that the hydrogel can treat osteoporotic bone defects by synergistically modulating bone damage microenvironment, alleviating inflammatory responses, and promoting osteogenesis; thus, it represents a promising drug delivery strategy to repair osteoporotic bone defects.


Subject(s)
Hydrogels , Osteoporosis , Humans , Osteogenesis , Resveratrol/pharmacology , Durapatite/pharmacology , Microspheres , Reactive Oxygen Species/pharmacology , Polyethylene Glycols/pharmacology , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Osteoporosis/drug therapy
15.
Clin Pharmacol Ther ; 115(5): 993-1006, 2024 May.
Article in English | MEDLINE | ID: mdl-38037868

ABSTRACT

Circulating tumor DNA (ctDNA) analysis increasingly provides a promising minimally invasive alternative to tissue biopsies in precision oncology. However, there are no ctDNA analysis approaches available in nasopharyngeal carcinoma (NPC) and current methods of ctDNA mutation profiling have limited resolution because of the high background noise and false-positive rate caused by benign variants in plasma cell-free DNA (cfDNA), majorly generated during clonal hematopoiesis. Although personalized parallel white blood cell genome sequencing suppresses the noise of clonal hematopoiesis variances, the system cost and complexity restrict its extensive application in clinical settings. We developed Matched WBC Genome sequencing Independent CtDNA profiling (MaGIC) approaches, which synergically integrated a ctDNA capturing panel for a hybrid capture cfDNA deep sequencing, in silico background elimination, and a reliable readout measurement. We profiled the ctDNAs of 80 plasma samples from 40 patients with NPC before and during chemotherapy by MaGICs. In addition, the public cfDNA sequencing data and The Cancer Genome Atlas project data were analyzed by MaGICs to evaluate their application in other scenarios of patient classification. The MaGIC version-2 has the ability to predict the chemosensitivity of patients with NPC with high accuracy by utilizing a single sample of liquid biopsy from each patient prior to a standardized treatment regimen. Moreover, both versions of MaGICs are of ideal performance in the diagnosis of patients with prostate cancer by liquid biopsy and prognosis prediction of multiple cancers by tissue biopsy. This study has the potential to enhance the sensitivity and expand the application scope of ctDNA detection, independently of other paired genome sequencing methods. As a result, it might further increase the clinical utilization of liquid biopsy based on ctDNA.


Subject(s)
Circulating Tumor DNA , Nasopharyngeal Neoplasms , Prostatic Neoplasms , Male , Humans , Circulating Tumor DNA/genetics , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/genetics , Precision Medicine , Mutation , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/genetics , Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing/methods
16.
Bioorg Chem ; 143: 107036, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38141330

ABSTRACT

This study reports a thermostable glucose-stimulated ß-glucosidase, BglY442, from hot-spring metagenomic data that was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of recombinant BglY442 was 69.9 kDa and was used in the production of gardenia blue. The recombinant BglY442 showed its maximum activity at pH 6.0 and 75 °C, maintained 50 % activity at 70 °C for 36 h, presented over 90 % activity in a broad pH range and a wide range of pH stability. Moreover, BglY442 exhibited excellent tolerance toward methanol and ethanol. The specific activity of BglY442 was 235 U/mg at pH 6.0 and 75 °C with 10 mM pNPG as substrate. BglY442 activity increased by over fourfold with 2 M glucose or xylose. Specifically, the enzyme kinetics of BglY442 seem to be non-Michaelis-Menten kinetics or atypical kinetics because the Michaelis-Menten saturation kinetics were not observed with pNPG, oNPG or geniposide as substrates. Under optimum conditions, geniposide was dehydrated by BglY442 and reacted with nine amino acids respectively by the one-pot method. Only the Arg or Met derived pigments showed bright blue, and these two pigments had similar ultraviolet absorption spectra. The OD590 nm of GB was detected to be 1.06 after 24 h with the addition of Arg and 1.61 after 36 h with the addition of Met. The intermediate was elucidated and identified as ginipin. Molecular docking analysis indicated that the enzyme had a similar catalytic mechanism to the reported GH1 Bgls. BglY442 exhibited potential for gardenia blue production by the one-pot method. With outstanding thermostability and glucose tolerance, BglY442 should be considered a potential ß-glucosidase in biotechnology applications.


Subject(s)
Gardenia , Glucose , Iridoids , Glucose/pharmacology , Recombinant Proteins/metabolism , beta-Glucosidase/metabolism , Metagenome , Molecular Docking Simulation , Hydrogen-Ion Concentration , Enzyme Stability , Substrate Specificity , Temperature , Kinetics
17.
Small Methods ; : e2301271, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38085682

ABSTRACT

Camptothecin (CPT) is a highly cytotoxic molecule with excellent antitumor activity against various cancers. However, its clinical application is severely limited by poor water solubility, easy inactivation, and severe toxicity. Structural modifications and nanoformulations represent two crucial avenues for camptothecin's development. However, the potential for further structural modifications is limited, and camptothecin nanoparticles fabricated via physical loading have the drawbacks of low drug loading and leakage. Prodrug-based CPT nanoformulations have shown unique advantages, including increased drug loading, reduced burst release, improved bioavailability, and minimal toxic side effects. Stimulus-responsive CPT nano-prodrugs that respond to various endogenous or exogenous stimuli by introducing various activatable linkers to achieve spatiotemporally responsive drug release at the tumor site. This review comprehensively summarizes the latest research advances in stimulus-responsive CPT nano-prodrugs, including preparation strategies, responsive release mechanisms, and their applications in cancer therapy. Special focus is placed on the release mechanisms and characteristics of various stimulus-responsive CPT nano-prodrugs and their application in cancer treatment. Furthermore, clinical applications of CPT prodrugs are discussed. Finally, challenges and future research directions for CPT nano-prodrugs are discussed. This review to be valuable to readers engaged in prodrug research is expected.

18.
BMC Public Health ; 23(1): 2431, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38057774

ABSTRACT

BACKGROUND: Hypertensive patients are likelier to have cognitive function decline (CFD). This study aimed to explore physical activity level, sleep disorders, and type of work that influenced intervention effects on cognitive function decline in hypertensive patients and to establish a decision tree model to analyze their predictive significance on the incidence of CFD in hypertensive patients. METHODS: This cross-sectional study recruited patients with essential hypertension from several hospitals in Shandong Province from May 2022 to December 2022. Subject exclusion criteria included individuals diagnosed with congestive heart failure, valvular heart disease, cardiac surgery, hepatic and renal dysfunction, and malignancy. Recruitment is through multiple channels such as hospital medical and surgical outpatient clinics, wards, and health examination centers. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Moreover, we obtained information on the patients' type of work through a questionnaire and their level of physical activity through the International Physical Activity Questionnaire (IPAQ). RESULTS: The logistic regression analysis results indicate that sleep disorder is a significant risk factor for CFD in hypertension patients(OR:1.85, 95%CI:[1.16,2.94]), mental workers(OR:0.12, 95%CI: [0.04,0.37]) and those who perform both manual and mental workers(OR: 0.5, 95%CI: [0.29,0.86]) exhibit protective effects against CFD. Compared to low-intensity, moderate physical activity(OR: 0.53, 95%CI: [0.32,0.87]) and high-intensity physical activity(OR: 0.26, 95%CI: [0.12,0.58]) protects against CFD in hypertension patients. The importance of predictors in the decision tree model was ranked as follows: physical activity level (54%), type of work (27%), and sleep disorders (19%). The area under the ROC curves the decision tree model predicted was 0.72 [95% CI: 0.68 to 0.76]. CONCLUSION: Moderate and high-intensity physical activity may reduce the risk of developing CFD in hypertensive patients. Sleep disorders is a risk factor for CFD in hypertensive patients. Hypertensive patients who engage in mental work and high-intensity physical activity effectively mitigate the onset of CFD in hypertensive patients.


Subject(s)
Exercise , Hypertension , Sleep Wake Disorders , Humans , Cognition , Cross-Sectional Studies , Hypertension/epidemiology , Sleep , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/prevention & control
19.
Small Methods ; : e2301178, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38037521

ABSTRACT

Inflammation-associated diseases are very common clinically with a high incidence; however, there is still a lack of effective treatments. Cell-biomimetic nanoplatforms have led to many breakthroughs in the field of biomedicine, significantly improving the efficiency of drug delivery and its therapeutic implications especially for inflammation-associated diseases. Macrophages are an important component of immune cells and play a critical role in the occurrence and progression of inflammation-associated diseases while simultaneously maintaining homeostasis and modulating immune responses. Therefore, macrophage-biomimetic nanoplatforms not only inherit the functions of macrophages including the inflammation tropism effect for targeted delivery of drugs and the neutralization effect of pro-inflammatory cytokines and toxins via membrane surface receptors or proteins, but also maintain the functions of the inner nanoparticles. Macrophage-biomimetic nanoplatforms are shown to have remarkable therapeutic efficacy and excellent application potential in inflammation-associated diseases. In this review, inflammation-associated diseases, the physiological functions of macrophages, and the classification and construction of macrophage-biomimetic nanoplatforms are first introduced. Next, the latest applications of different macrophage-biomimetic nanoplatforms for the treatment of inflammation-associated diseases are summarized. Finally, challenges and opportunities for future biomedical applications are discussed. It is hoped that the review will provide new ideas for the further development of macrophage-biomimetic nanoplatforms.

20.
Appl Opt ; 62(33): 8749-8759, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38038020

ABSTRACT

Since there are usually multiple layers present in a real-world sea fog environment, and because previous studies have tended to analyze sea fog as a single layer rather than as refined layered sea fog, this paper splits sea fog into two categories: water fog and salt fog double-layer environments. By adjusting the optical thickness of the two layers of media, we may investigate the issue of the law governing the transmission of polarized light. In this paper, the analysis is mainly carried out through a simulation and experimental tests. The simulation portion is based mostly on the improved layered Monte Carlo approach, which builds a simulation model more appropriate for multilayer non-spherical media by using the accumulation principle to determine the scattering and transmission properties between layers. The tests are conducted by altering the double-layer medium's optical thickness, incoming wavelength, and polarization state, and then getting the polarization information of visible light after transmission through the complicated environment. The findings demonstrate that the optical thickness of the sea fog double-layer media affects polarized light transmission in a non-negligible way. Longer wavelength polarized light may keep polarization information better as the optical thickness increases, and circularly polarized light has polarization-preserving properties that are superior to linearly polarized light. By contrasting the simulation findings with the experimental data, the consistency of the two conclusions is confirmed, and the study offers a helpful resource for the transmission of polarized light in the sea fog environment.

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