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1.
Cell Biochem Biophys ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727783

ABSTRACT

Disulfiram/copper complex (DSF/Cu) was found to have anti-tumor effects in a range of malignancies, including oral squamous cell carcinoma (OSCC), yet its precise mechanism remains unknown. It has been shown that ER stress enhances immunogenic cell death (ICD) in tumor cells, as it can influence the anti-cancer immune system favorably. In this study, we reported that DSF/Cu exhibited a marked inhibitory effect on the growth of OSCC cells, accompanied by cell apoptosis. OSCC cells treated with DSF/Cu showed the hallmarks of immunogenic cell death (ICD), including surface expression of calreticulin (CRT), heat shock protein 70 (HSP70), high mobility-group box 1 (HMGB-1) and adenosine triphosphate (ATP), thus, eliciting the maturation and activation of dendritic cells. Furthermore, we showed DSF/Cu-induced endoplasmic reticulum (ER) stress in OSCC cells. In vivo, results demonstrate that DSF/Cu inhibits tumor growth locally and alters the intratumoral immune cell infiltration and response. In conclusion, DSF/Cu suppresses OSCC development by inducing ICD and ER stress. DSF/Cu has the potential to be a new anti-tumor immunotherapy concept because of its ability to elicit ICD.

2.
Materials (Basel) ; 17(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38730915

ABSTRACT

The amount of heat input during welding impacts the weld's thermal and mechanical behavior and the joint's properties. The current study involved conducting AA 6061 and AZ31B Mg dissimilar welding, using friction stir lap welding (FSLW) and ultrasonic vibration-enhanced FSLW (UVeFSLW). The comparison and analysis of the welding load, the weld's macro-microstructure, intermetallic compounds (IMCs), and joint properties were conducted by adjusting the process parameters. The study also examined the effect of ultrasonic vibration (UV) variations on welding heat input. The study demonstrated that it is possible to reduce the welding load by employing UV. Moreover, this impact becomes more pronounced as the welding heat input decreases. Additionally, the material flow in the weld, the width of the weld nugget zone, and the continuous IMC layer are significantly influenced by ultrasonic vibration, irrespective of the heat input during welding. However, the impact on large areas of irregular IMCs or eutectic structures is relatively small. Furthermore, achieving better joint properties becomes more feasible when a higher welding speed is employed for the Al alloy placed on top. Specifically, the impact of UV becomes more evident at higher welding speeds (≥220 mm/min).

3.
Molecules ; 29(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731419

ABSTRACT

It is a valid path to realize the zero discharge of coal chemical wastewater by using the fractional crystallization method to recycle the miscellaneous salt in high-salinity wastewater. In this study, the thermodynamics and nucleation kinetics of sodium chloride (NaCl) and sodium sulfate (Na2SO4) crystallization in coal chemical wastewater were systematically studied. Through analyses of solubility, metastable zone width, and induction period, it was found that the impurity dimethoxymethane would increase the solid-liquid interface energy and critical crystal size during the nucleation of Na2SO4. Ternary phase diagrams of the pseudo-ternary Na2SO4-NaCl-H2O systems in simulated wastewater were plotted in the temperature range of 303.15 to 333.15 K, indicating that a co-ionization effect existed between NaCl and Na2SO4, and NaCl had a strong salting out effect on Na2SO4. Finally, the nucleation rate and growth rate of Na2SO4 crystals under simulated wastewater conditions were determined by the intermittent dynamic method, and the crystallization kinetic models of Na2SO4 were established. The crystallization nucleation of Na2SO4 crystals was found to be secondary nucleation controlled by surface reactions. The basic theoretical research of crystallization in this study is expected to fundamentally promote the application of fractional crystallization to realize the resource utilization of high-salinity wastewater in the coal chemical industry.

4.
Mol Med Rep ; 30(1)2024 Jul.
Article in English | MEDLINE | ID: mdl-38785151

ABSTRACT

Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti­inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase­1 (HO­1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription­quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)­2, TNF­α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ­2, TNF­α, RANKL and OPG. Following HO­1 knockdown, the same treatment was performed. The expression of COX­2 in rat gingival tissue was observed by immunohistochemistry. One­way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. With increase of Oroxylin A dose, the expression of HO­1 was gradually upregulated. When HO­1 was knocked down, Oroxylin A did not downregulate the expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. Immunohistochemical results showed that expression of COX­2 was downregulated by Oroxylin A, and the expression of TNF­α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS­induced RGFs and had a good inhibitory effect on periodontitis in rats.


Subject(s)
Cyclooxygenase 2 , Fibroblasts , Flavonoids , Periodontitis , RANK Ligand , Animals , Rats , Flavonoids/pharmacology , Periodontitis/metabolism , Periodontitis/drug therapy , Periodontitis/pathology , RANK Ligand/metabolism , RANK Ligand/genetics , Male , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Fibroblasts/metabolism , Fibroblasts/drug effects , Osteoprotegerin/metabolism , Osteoprotegerin/genetics , Lipopolysaccharides , Gingiva/metabolism , Gingiva/drug effects , Tumor Necrosis Factor-alpha/metabolism , Cytokines/metabolism , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/genetics , Cells, Cultured , Rats, Sprague-Dawley
5.
Adv Sci (Weinh) ; : e2309185, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741387

ABSTRACT

Quasi-2D perovskite quantum wells are increasingly recognized as promising candidates for direct-conversion X-ray detection. However, the fabrication of oriented and uniformly thick quasi-2D perovskite films, crucial for effective high-energy X-ray detection, is hindered by the inherent challenges of preferential crystallization at the gas-liquid interface, resulting in poor film quality. In addressing this limitation, a carbonyl array-synergized crystallization (CSC) strategy is employed for the fabrication of thick films of a quasi-2D Ruddlesden-Popper (RP) phase perovskite, specifically PEA2MA4Pb5I16. The CSC strategy involves incorporating two forms of carbonyls in the perovskite precursor, generating large and dense intermediates. This design reduces the nucleation rate at the gas-liquid interface, enhances the binding energies of Pb2+ at (202) and (111) planes, and passivates ion vacancy defects. Consequently, the construction of high-quality thick films of PEA2MA4Pb5I16 RP perovskite quantum wells is achieved and characterized by vertical orientation and a pure well-width distribution. The corresponding PEA2MA4Pb5I16 RP perovskite X-ray detectors exhibit multi-dimensional advantages in performance compared to previous approaches and commercially available a-Se detectors. This CSC strategy promotes 2D perovskites as a candidate for next-generation large-area flat-panel X-ray detection systems.

6.
Int J Mol Sci ; 25(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38732181

ABSTRACT

B cell receptor-associated protein 31 (BAP31) is a transmembrane protein that is widely expressed and primarily located in the endoplasmic reticulum (ER). B cells play a crucial role in the immune system, and BAP31 significantly contributes to the functions of various immune cells. However, the specific role of BAP31 in B lymphocytes development remains unknown. In this study, we utilized a mouse model with BAP31 deleted from B cells to investigate its effects. Our findings reveal a block in early B cell development in the bone marrow and a significant decrease in the number of B cells in peripheral lymphoid organs taken from BAP31 B cell conditional knockout (BAP31-BCKO) mice. B cell receptor (BCR) signaling is crucial for the normal development and differentiation of B lymphocytes. BAP31, an endoplasmic reticulum membrane protein, directly regulates the BCR signaling pathway and was shown to be significantly positively correlated with B cell activation and proliferation. These findings establish BAP31 as a crucial regulator of early B cell development.


Subject(s)
B-Lymphocytes , Cell Differentiation , Mice, Knockout , Receptors, Antigen, B-Cell , Signal Transduction , Animals , B-Lymphocytes/metabolism , Mice , Receptors, Antigen, B-Cell/metabolism , Receptors, Antigen, B-Cell/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Cell Proliferation , Lymphocyte Activation , Mice, Inbred C57BL
7.
Cell Rep ; 43(5): 114194, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38735043

ABSTRACT

Class switch recombination (CSR) diversifies the effector functions of antibodies and involves complex regulation of transcription and DNA damage repair. Here, we show that the deubiquitinase USP7 promotes CSR to immunoglobulin A (IgA) and suppresses unscheduled IgG switching in mature B cells independent of its role in DNA damage repair, but through modulating switch region germline transcription. USP7 depletion impairs Sα transcription, leading to abnormal activation of Sγ germline transcription and increased interaction with the CSR center via loop extrusion for unscheduled IgG switching. Rescue of Sα transcription by transforming growth factor ß (TGF-ß) in USP7-deleted cells suppresses Sγ germline transcription and prevents loop extrusion toward IgG CSR. Mechanistically, USP7 protects transcription factor RUNX3 from ubiquitination-mediated degradation to promote Sα germline transcription. Our study provides evidence for active transcription serving as an anchor to impede loop extrusion and reveals a functional interplay between USP7 and TGF-ß signaling in promoting RUNX3 expression for efficient IgA CSR.

8.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(6): 159498, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38703945

ABSTRACT

The biosynthetic capability of the long-chain polyunsaturated fatty acids (LC-PUFA) in teleosts are highly diversified due to evolutionary events such as gene loss and subsequent neo- and/or sub-functionalisation of enzymes encoded by existing genes. In the present study, we have comprehensively characterised genes potentially involved in LC-PUFA biosynthesis, namely one front-end desaturase (fads2) and eight fatty acid elongases (elovl1a, elovl1b, elovl4a, elovl4b, elovl5, elovl7, elovl8a and elovl8b) from an amphidromous teleost, Ayu sweetfish, Plecoglossus altivelis. Functional analysis confirmed Fads2 with Δ6, Δ5 and Δ8 desaturase activities towards multiple PUFA substrates and several Elovl enzymes exhibited elongation capacities towards C18-20 or C18-22 PUFA substrates. Consequently, P. altivelis possesses a complete enzymatic capability to synthesise physiologically important LC-PUFA including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) from their C18 precursors. Interestingly, the loss of elovl2 gene in P. altivelis was corroborated by genomic and phylogenetic analyses. However, this constraint would possibly be overcome by the function of alternative Elovl enzymes, such as Elovl1b, which has not hitherto been functionally characterised in teleosts. The present study contributes novel insights into LC-PUFA biosynthesis in the relatively understudied teleost group, Osmeriformes (Stomiati), thereby enhancing our understanding of the complement of LC-PUFA biosynthetic genes within teleosts.

9.
Mar Environ Res ; 198: 106547, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38739970

ABSTRACT

Micro/nanoplastics in aquatic environments is a noteworthy environmental problem. Zooplankton, an important biological group in aquatic ecosystems, readily absorb micro/nanoplastics and produce a range of toxic endpoints due to their small size. This review summarises relevant studies on the effects of micro/nanoplastics on zooplankton, including combined effects with conventional pollutants. Frequently reported adverse effects include acute/chronic lethal effects, oxidative stress, gene expression, energetic homeostasis, and growth and reproduction. Obstruction by plastic entanglement and blockage is the physical mechanism. Genotoxicity and cytotoxicity are molecular mechanisms. Properties of micro/nanoplastics, octanol/water partition coefficients of conventional pollutants, species and intestinal environments are important factors influencing single and combined toxicity. Selecting a wider range of micro/nanoplastics, focusing on the aging process and conducting field studies, adopting diversified zooplankton models, and further advancing the study of mechanisms are the outstanding prospects for deeper understanding of impacts of micro/nanoplastics on aquatic ecosystem.

10.
J Environ Manage ; 360: 121159, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38759549

ABSTRACT

Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO2-based ICPB system has been widely studied. There are many ways to improve the degradation efficiency of the ICPB process, but no crystal facet engineering method has been reported yet. In this work, a new ICPB system coated with NaF-TiO2 exposing high energy facets was designed to degrade biorecalcitrant psychotropic drug - venlafaxine (VNF). Initially, the TiO2 crystal surface was modified with NaF, resulting in the formation of NaF-TiO2 with a 14.4% increase in the exposure ratio of (001). The contribution rate of ·OH was increased by 9.5%, and the contribution rate of h+ was increased by 33.2%. Next, NaF-TiO2 was loaded onto the surface of the sponge carrier, and then the ICPB system was constructed after about 15 days of biofilm formation. After the ICPB system was acclimated with VNF, the removal rate of COD decreased significantly (the lowest was 62.7%), but that of ammonia nitrogen remained at 50.5 ± 6.0% and the extracellular polymeric substance (EPS) secretion increased by 84.1 mg/g VSS. According to the high throughput results, at the phylum level, Proteobacteria and Chloroflexi together maintain the nitrogen removal capability and structural stability of the ICPB system. The relative abundance of Bacteroidota was significantly increased by 14.2%, suggesting that there may be some correlation between Bacteroidota and certain metabolites of the anti-depressant active ingredients. At the genus level, the Thauera (3.1%∼11.5%) is the major bacterial group that secretes EPS, protecting biofilm against external influences. Most of the changes in microorganisms are consistent with the decontamination properties and macroscopic appearance of EPS in the ICPB system. Finally, the degradation efficiency of ICPB system for VNF was investigated (92.7 ± 3.8%) and it was mostly through hydroxylation and demethylation pathways, with more small molecular products detected, providing the basis for biological assimilation of VNF. Collectively, the NaF-TiO2 based ICPB system would be lucrative for the future degradation of venlafaxine.

11.
Bioresour Technol ; : 130853, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38759895

ABSTRACT

This study introduces a two-stage hydrogen production enhancement mechanism using natural particle additives, with a focus on the effects of thermally modified maifanite (TMM) and pH self-regulation on dark fermentation (DF). Initial single-factor experiments identified preliminary parameters for the addition of TMM, which were further optimized using a Box-Behnken design. The established optimal conditions which include mass of 5.5 g, particle size of 120 mesh, and temperature of 324 °C, resulted in a 28.7 % increase in cumulative hydrogen yield (CHY). During the primary hydrogen production stage, TMM significantly boosted the growth and activity of Clostridium_sensu_stricto_1, enhancing hydrogen output. Additionally, a pH self-regulating phenomenon was observed, capable of initiating secondary hydrogen production and further augmenting CHY. These findings presented a novel and efficient approach for optimizing biohydrogen production, offering significant implications for future research and application in sustainable energy technologies.

12.
Transl Oncol ; 45: 101986, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38723299

ABSTRACT

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

13.
PLoS One ; 19(5): e0300263, 2024.
Article in English | MEDLINE | ID: mdl-38758775

ABSTRACT

China eliminated rural poverty under current poverty standards in 2020. However, compared with rural poverty, urban poverty in China has been somewhat neglected. This paper aims to discover the changes and determinants of multidimensional urban poverty in Shandong Province, a representative province in Eastern China. Using a nationally representative panel dataset, the China Family Panel Studies, and the Dual Cutoff method, this study creates a multidimensional poverty index with four dimensions and 11 indicators to measure urban poverty in Shandong Province. This paper discovers that while the incidence of multidimensional urban poverty in Shandong Province decreased from 47.62% in 2010 to 36.45% in 2018, the intensity of multidimensional poverty only decreased from 41.27% to 37.25%, which indicates the inadequacy of urban anti-poverty efforts in Shandong Province. This paper also uses logistic regression to identify the determinants of multidimensional urban poverty. The findings suggest that income, health, drinking water, and durable goods are the main determinants of multidimensional urban poverty in Shandong Province. Based on these findings, this study provides targeted recommendations for future urban anti-poverty policies in Shandong Province.


Subject(s)
Poverty , Urban Population , China , Humans , Urban Population/statistics & numerical data , Income , Socioeconomic Factors , Rural Population
14.
Sci Data ; 11(1): 416, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38653806

ABSTRACT

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.


Subject(s)
Cochlea , Animals , Mice , Guinea Pigs , Humans , Rats , Swine , Hair Cells, Auditory , Microscopy, Fluorescence , Machine Learning
15.
Zhen Ci Yan Jiu ; 49(4): 376-383, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38649205

ABSTRACT

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time;the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.


Subject(s)
Apolipoproteins E , Atherosclerosis , Forkhead Box Protein O3 , Moxibustion , Sirtuin 1 , Animals , Humans , Male , Mice , Acupuncture Points , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/therapy , Forkhead Box Protein O3/metabolism , Forkhead Box Protein O3/genetics , Mice, Inbred C57BL , Mice, Knockout , Signal Transduction , Sirtuin 1/metabolism , Sirtuin 1/genetics , Triglycerides/blood , Triglycerides/metabolism
16.
Biomacromolecules ; 25(5): 3112-3121, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38651274

ABSTRACT

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Escherichia coli/drug effects , Animals , Microbial Sensitivity Tests , Polyelectrolytes/chemistry , Polyelectrolytes/pharmacology , Peptides/chemistry , Peptides/pharmacology , Protein Conformation, alpha-Helical , Micelles , Escherichia coli Infections/drug therapy , Hemolysis/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Mice , Polyglutamic Acid/chemistry , Polyglutamic Acid/analogs & derivatives , Polyglutamic Acid/pharmacology , Humans
17.
Sci Total Environ ; 930: 172731, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38663605

ABSTRACT

Soil ecoenzymatic stoichiometry reflects the dynamic equilibrium between microorganism's nutrient requirements and resource availability. However, uncertainties persist regarding the key determinants of nutrient restriction in relation to microbial metabolism under varying degrees of warming. Our long-term and multi-level warming field experiment (control treatment, +0.42 °C, +1.50 °C, +2.55 °C) in a typical alpine meadow unveiled a decline in carbon (C)- and nitrogen (N)-acquired enzymes with escalating warming magnitudes, while phosphorus (P)-acquired enzymes displayed an opposite trend. Employing enzymatic stoichiometry modeling, we assessed the nutrient limitations of microbial metabolic activity and found that C and N co-limited microbial metabolic activities in the alpine meadow. Remarkably, high-level warming (+2.55 °C) exacerbated microbe N limitation, but alleviate C limitations. The structural equation modeling further indicated that alterations in soil extracellular enzyme characteristics (SES) were more effectively elucidated by microbial characteristics (microbial biomass C, N, P, and their ratios) rather than by soil nutrients (total nutrient contents and their ratios). However, the microbial control over SES diminished with higher levels of warming magnitude. Overall, our results provided novel evidence that the factors driving microbe metabolic limitation may vary with the degree of warming in Tibet alpine grasslands. Changes in nutrient demand for microorganism's metabolism in response to warming should be considered to improve nutrient management in adapting to different future warming scenarios.


Subject(s)
Grassland , Nitrogen , Soil Microbiology , Soil , Tibet , Nitrogen/metabolism , Soil/chemistry , Climate Change , Global Warming , Carbon/metabolism , Phosphorus/metabolism
18.
Front Psychiatry ; 15: 1354999, 2024.
Article in English | MEDLINE | ID: mdl-38563028

ABSTRACT

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

20.
Chemistry ; : e202400333, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639068

ABSTRACT

The selective hydrogenation of furfural (FFA) to furfuryl alcohol (FA) is regarded as attractive transformation to achieve the sustainable synthesis of value-added chemicals from biomass resources. However, the conventional supported catalysts are significantly restricted by their narrow pore size, ununiform dispersion and easy leaching or aggregation of catalytic sites. Herein, we designed hollow UiO-66-NH2 as the support to encapsulate Pd nanoparticles (Pd@H-UiO-66-NH2) to achieve the highly active and selective conversion of FFA to FA. Benefiting from the void-confinement effect and substrate enrichment of hollow structure, as well as the surface wrinkles, the as-prepared catalyst Pd@H-UiO-66-NH2 exhibited 96.8 % conversion of FFA with satisfactory selectivity reaching up to 92.4 % at 80 °C, 0.5 MPa H2 in isopropanol solvent within 6 h. More importantly, as-prepared Pd@H-UiO-66-NH2 catalyst exhibited excellent long-term stability, as well as good universality toward a series of hydrogenation of unsaturated hydrocarbons.

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