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1.
Front Microbiol ; 15: 1417404, 2024.
Article in English | MEDLINE | ID: mdl-38962129

ABSTRACT

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission. Methods: In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials. Results: Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-ß (IFN-ß) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs. Discussion: These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection.

2.
Heliyon ; 10(13): e33240, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39050415

ABSTRACT

This study aims to explore the impact of the herbal ointment Chushi Zhiyang Ruangao (CSZYRG) on the skin's microecological environment in a mouse model of atopic dermatitis (AD) and to understand the underlying mechanisms involved. The AD model was established in C57 mice using calpolitol (a hypocalcemic analog of vitamin D3; MC903). Medication-free matrix ointment, CSZYRG, and mometasone furoate cream (positive control group) were applied to the injured areas. The skin lesions of AD model mice were photographed. Skin lesions were applied for the hematoxylin and eosin (H&E) staining to observe any pathological changes. Serum immunoglobulin IgE was detected by enzyme-linked immunosorbent assay (ELISA). The changes in the expression of inflammation-related factors TNF-α, IL-1ß, and IL-6 in mice were detected using ELISA and qRT-PCR. Skin microflora samples were taken for 16S rDNA sequencing and analyzed for changes in the skin flora diversity, abundance, and dominant flora in mice. It was concluded that CSZYRG effectively alleviates skin lesions, serum IgE, and levels of TNF-α, IL-1ß, and IL-6 in AD model mice. However, CSZYRG did not affect the skin microbial diversity of AD model mice but could exert an effect on the skin microbial community in AD mice and the relative abundance of the dominant microflora. CSZYRG may play a therapeutic role in AD by affecting the skin microbial community and relative abundance of dominant microflora in AD mice.

3.
Heliyon ; 10(13): e33470, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39050468

ABSTRACT

China faces a healthcare challenge due to its aging population, necessitating an integrated old-age healthcare system considering multiple stakeholders' interests. Conflict and inequality may arise from varying stakeholder interests. This study develops a conflict resolution strategy for the coordination of stakeholders involved in the old-age healthcare service system, promoting harmonization and minimizing conflict to establish an equitable system meeting elderly needs. It contributes to a robust healthcare system for comprehensive, quality care. The focus of the study is to identify relevant stakeholders and decision-makers involved in developing an integrated old-age healthcare service system and explore a feasible solution through stakeholder analysis using the Mitchell score-based technique and stakeholder theory. Decision-makers' preferences are estimated using the Analytic Hierarchy Process (AHP). Solution strategies are developed through multiple stability concepts within the graph model for conflict resolution (GMCR). The conflict resolution analysis based on the integrated AHP-GMCR approach reveals that the development of an integrated old-age healthcare system is feasible by addressing potential conflicts among the stakeholders. Considering the current predicament of comprehensive medical services in China, governments should distribute authority, simplify procedures, and improve the insurance system. Furthermore, medical institutions should explore funding options, expand services, and enhance accessibility. Elderly individuals should prioritize healthy aging and seek suitable healthcare providers. Stakeholder participation is crucial for effective implementation. These recommendations enable China to advance integrated elderly care successfully, addressing challenges posed by the aging population.

4.
Article in English | MEDLINE | ID: mdl-38842592

ABSTRACT

PURPOSE: To compare axial growth in pediatric cataract patients who underwent multifocal intraocular lens (IOL) implantation without anterior vitrectomy (AV) with that in pediatric patients who underwent monofocal IOL implantation with or without AV. METHODS: Patients who had unilateral pediatric cataracts and underwent surgery at 3-6 years of age from June 6, 2019, to June 30, 2020, at our institution were prospectively analyzed. The patients were categorized into Group A: multifocal IOL implantation with optic capture in Berger's space without AV; Group B: monofocal IOL implantation with optic capture in Berger's space without AV; and Group C: bag-in-the-lens monofocal IOL implantation with AV. Groups A', B' and C' consisted of the fellow eyes from the respective groups. Axial growth and monthly growth rates were compared among the 3 treatment groups, as well as between the treated eyes and the fellow eyes. RESULTS: Thirty-one, 23, and 14 children fulfilling the inclusion criteria, respectively, were included in the final analysis. There were no significant differences in patient age at the time of surgery or preoperative axial length (P > 0.05). After a mean follow-up of 35.57 ± 3.78 months, significant differences in the axial growth and the monthly growth rate were observed (P < 0.05), and Group A had the least axial elongation. Comparing treated eyes with fellow eyes, the amount and rate of axial growth were lower in Group A than in Group A' (P < 0.05), no significant differences were found in Group B (P > 0.05), and Group C had greater growth than did Group C' (P < 0.05). CONCLUSIONS: The implanting multifocal intraocular lenses and maintenance of vitreous body integrity may be protective factors against excessive axial growth in pediatric cataract patients. Clinical trial registration (prospective study): chiCRT1900023155; 2019-05-14.

5.
Animals (Basel) ; 14(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38891682

ABSTRACT

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2-6.9), 3.8% (44/1155; 95% CI: 2.7-4.9), and 6.5% (75/1155; 95% CI: 5.1-7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

6.
Org Lett ; 26(23): 4986-4991, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38842488

ABSTRACT

We herein disclose a highly efficient protocol for the esterification and etherification of alcohols, leveraging a Sc(OTf)3-catalyzed ring-strain release event in the meticulously designed, chromatographically stable mixed anhydrides or benzyl esters that incorporate an intramolecular donor-acceptor cyclopropane (DAC). This versatile method facilitates the straightforward functionalization of sugar, terpene, and steroid alcohols under mild acidic conditions, as showcased by the single-catalyst-driven, dual protection of sugar diol.

7.
Transl Res ; 272: 54-67, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838852

ABSTRACT

BACKGROUND: Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration. METHODS AND RESULTS: Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype. CONCLUSIONS: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.

8.
PLoS One ; 19(5): e0302061, 2024.
Article in English | MEDLINE | ID: mdl-38805406

ABSTRACT

Malignant melanoma (MM) is a malignant tumor associated with high mortality rates and propensity for metastasis. Despite advancement in treatment, the incidence of MM continue to rise globally. GPR168, also known as MrgprF, is a MAS related GPR family member. The low expression of GPR168 has also been reported in many malignant tumors including MM. In the study, the statistical analysis from The Cancer Genome Atlas (TCGA) revealed a significant down regulation of GPR168 in melanoma compared to normal melanocytes, underscoring its importance in MM. The aim of the present study is to investigate the affect of GPR168 overexpression and elucidate its molecular mechanisms in MM cells. In addition, we used mouse melanoma B16-F10 cell line and xenograph tumor model to explore the function of GPR168 in melanoma. Our findings demonstrate that GPR168 overexpression could inhibit B16-F10 cell proliferation, migration, and xenografts tumor growth. Further, mechanistic studies revealed that GPR168 affected B16-F10 progress through Akt signal pathway with the decreased expression of p-Akt, p-GSK-3ß, ß-catenin, Myc, CyclinD1 and CDK4. In order to validate these findings, a rescue experiment was formulated employing GPR168 polyclonal antibody (Anti-GPR168 pAbs) to block GPR168 functionality. The addition of Anti-GPR168 pAbs into the culture medium restored both cell proliferation and migration. In conclusion, the overexpression of GPR168 in mouse melanoma B16-F10 cells suppressed proliferation and migration through the Akt signaling pathway. These findings collectively propose GPR168 as a promising novel tumor suppressor in MM, suggesting its potential as a therapeutic target in future interventions.


Subject(s)
Cell Proliferation , Melanoma, Experimental , Proto-Oncogene Proteins c-akt , Receptors, G-Protein-Coupled , Signal Transduction , Animals , Proto-Oncogene Proteins c-akt/metabolism , Mice , Melanoma, Experimental/pathology , Melanoma, Experimental/metabolism , Melanoma, Experimental/genetics , Cell Line, Tumor , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Cell Movement , Humans , Gene Expression Regulation, Neoplastic , Mice, Inbred C57BL
9.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2138-2146, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812229

ABSTRACT

In this study, four Atractylodes chinensis(A. chinensis) with different leaf shapes, such as the split leaf, long and narrow leaf, oval leaf, and large round leaf, were used as experimental materials to establish a method for simultaneously determining atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in the rhizome of A. chinensis. The expression of key enzyme genes for biosynthesis of acetyl-CoA carboxylase(ACC), 3-hydroxy-3-methylglutaryl-CoA reductase(HMGR), and farnesyl pyrophosphate synthase(FPPS) was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR). High performance liquid chromatography(HPLC) was used to compare the difference in the content of four active components in A. chinensis with different leaf shapes, and the correlation between the content of active components and the expression of key enzyme genes in biosynthesis was discussed. The results show that there was good linearity among atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in the range of 3.30-33.00 µg·mL~(-1)(r =0.999 7), 12.04-120.40 µg·mL~(-1)(r =0.999 5), 29.16-291.60 µg·mL~(-1)(r =0.999 5), and 14.20-142.00 µg·mL~(-1)(r =0.999 5), respectively. The average recoveries were 99.77%(RSD=2.1%), 98.56%(RSD=1.2%), 103.0%(RSD=1.2%), and 100.6%(RSD=1.5%), respectively. The method was accurate and had good reproducibility, which could be used to simultaneously detect atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon. The results showed that there were significant differences in the content of four active components in A. chinensis with different leaf shapes. The content of atractylodin, atractylenolide Ⅰ, and ß-eudesmol in A. chinensis with split leaves was the highest, which were 1.341 9, 5.237 2, and 12.084 3 mg·g~(-1), respectively. The content of atractylon in A. chinensis with long and narrow leaves was the highest(5.470 1 mg·g~(-1)). The content of atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in A. chinensis with oval leaves was the lowest. The total content of the four effective components in descending order was A. chinensis with split leaves > A. chinensis with long and narrow leaves > A. chinensis with large round leaves > A. chinensis with oval leaves. The gene expression levels of key enzymes ACC, HMGR, and FPPS in A. chinensis with split leaves were the highest(P < 0.05), and the gene expression levels of key enzymes ACC and HMGR in A. chinensis with oval leaves were the lowest(P < 0.05). The gene expression level of key enzyme FPPS in A. chinensis with large round leaves was the lowest. In A. chinensis with different leaf shapes, the key enzyme gene ACC was significantly positively correlated with the polyacetylene component, namely atractylodin(P < 0.01), and the key enzyme genes HMGR and FPPS were positively correlated with the sesquiterpene components, namely atractylenolide Ⅰ, ß-eudesmol, and atractylon. In summary, the quality of A. chinensis with split leaves is the best, and the biosynthesis of atractylodin is significantly correlated with the gene expression of key enzyme ACC, which provides a theoretical basis for screening and optimizing the germplasm resources of A. chinensis and improving the quality of medicinal materials.


Subject(s)
Atractylodes , Lactones , Plant Leaves , Sesquiterpenes , Atractylodes/genetics , Atractylodes/chemistry , Atractylodes/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Leaves/chemistry , Sesquiterpenes/metabolism , Sesquiterpenes/analysis , Lactones/metabolism , Lactones/analysis , Plant Proteins/genetics , Plant Proteins/metabolism , Furans/metabolism , Drugs, Chinese Herbal , Gene Expression Regulation, Plant , Rhizome/genetics , Rhizome/chemistry , Rhizome/metabolism , Sesquiterpenes, Eudesmane
10.
J Diabetes ; 16(6): e13567, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769875

ABSTRACT

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.


Subject(s)
Hyperglycemia , Independent Living , Nutrition Surveys , Humans , Male , Female , Middle Aged , Independent Living/statistics & numerical data , Hyperglycemia/mortality , Hyperglycemia/blood , Hyperglycemia/epidemiology , Adult , Aged , Cause of Death , Risk Factors , Mortality/trends , Stress, Physiological , United States/epidemiology , Prognosis , Kaplan-Meier Estimate
11.
ACS Appl Mater Interfaces ; 16(21): 27419-27428, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38743926

ABSTRACT

Phenolic resin (PF) is considered a promising precursor of hard carbon (HC) for advanced-performance anodes in sodium-ion batteries (SIBs) because of its facile designability and high residual carbon yield. However, understanding how the structure of PF precursors influences sodium storage in their derived HC remains a significant challenge. Herein, the microstructure of HC is controlled by the degree of cross-linking of resorcinol-benzaldehyde (RB) resin. We reveal that robust molecular cross-linking in RB resin induced by hydrothermal treatment promotes closed-pore formation in the derived HC. The mechanism is devised for the decomposition of a highly cross-linked RB three-dimensional network into randomly stacked short-range graphitic microcrystals during high-temperature carbonization, contributing to the abundant closed pores in the derived HC. In addition, the high cross-linking degree of RB resin endows its derived HC with a small-sized spherical morphology and large interlayer spacing, which improves the rate performance of HC. Consequently, the optimized hydrothermal treatment HC anode shows a higher specific capacity of 372.7 mAh g-1 and better rate performance than the HC anode without hydrothermal treatment (276.0 mAh g-1). This strategy can provide feasible molecular cross-linking engineering for the development of closed pores in PF-based HC toward enhanced sodium storage.

12.
Transl Vis Sci Technol ; 13(5): 12, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38758570

ABSTRACT

Purpose: To evaluate the visual performance in adolescents undergoing orthokeratology (OrthoK) treatment with two different optical zone diameters (OZDs). Methods: This randomized, double-masked, self-controlled prospective study was conducted at Tianjin Eye Hospital (Tianjin, China) in June 2022. Thirty-six eligible schoolchildren were enrolled and fitted with corneal refractive therapy lenses with two sizes of OZDs (5 mm [5OZ] and 6 mm [6OZ]). Each participant was randomized to wear the 5OZ in one eye and the 6OZ in the contralateral eye. Subjective visual quality was assessed using visual acuity, refraction, contrast sensitivity function, and visual symptoms, and the objective optical quality was assessed using ocular higher order aberrations (HOAs) and modulation transfer function (MTF). Results: Thirty-five myopic children completed a 1-month follow-up visit. The 5OZ lens induced significantly smaller treatment zone diameters than the 6OZ lens (P < 0.001). Subjective visual quality did not differ significantly between the two groups. Compared to baseline, aberrations of Z40, coma-like, spherical-like, and total HOAs in both groups increased significantly (P < 0.05). For the 3-mm pupils, spherical aberration in the 5OZ group was significantly higher than that in the 6OZ group (P < 0.05). The MTF value of the 6OZ group was significantly higher than that of 5OZ group for 0.3 and 1.5 cycles per degree for the 3-mm pupils (P = 0.006 and P = 0.026, respectively). However, HOAs or MTF did not differ significantly between the two groups for the 5-mm pupils. Conclusions: The difference induced by varying OZD was significant only in the smaller pupil condition. The selection of OZD in OrthoK designs in real-world patient management should be done while considering individual pupil size. Translational Relevance: This study revealed that the objective visual quality of small OZD lenses was only slightly affected for the small pupil size.


Subject(s)
Myopia , Orthokeratologic Procedures , Refraction, Ocular , Visual Acuity , Humans , Female , Orthokeratologic Procedures/methods , Male , Visual Acuity/physiology , Prospective Studies , Adolescent , Myopia/therapy , Myopia/physiopathology , Child , Double-Blind Method , Refraction, Ocular/physiology , Contrast Sensitivity , Contact Lenses
13.
Postgrad Med J ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796714

ABSTRACT

Cardiovascular diseases (CVDs) present a significant global public health threat, contributing to a substantial number of cases involving morbidity and mortality. Therefore, the early and accurate detection of CVDs plays an indispensable role in enhancing patient outcomes. Decades of extensive research on electrocardiography at high frequencies have yielded a wealth of knowledge regarding alterations in the QRS complex during myocardial ischemia, as well as the methodologies to assess and quantify these changes. In recent years, the analysis of high-frequency QRS (HF-QRS) components has emerged as a promising non-invasive approach for diagnosing various cardiovascular conditions. Alterations in HF-QRS amplitude and morphology have demonstrated remarkable sensitivity as diagnostic indicators for myocardial ischemia, often surpassing measures of ST-T segment changes. This comprehensive review aims to provide an intricate overview of the current advancements, challenges, and prospects associated with HF-QRS analysis in the field of CVDs.

14.
Int J Infect Dis ; 144: 107055, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723889

ABSTRACT

OBJECTIVES: To investigate cases of five Campylobacter jejuni outbreaks and describe laboratory characteristics of these infections. METHODS: Whole-genome sequencing and conventional methods were combined to thoroughly investigate the outbreaks, and data of contemporaneous sporadic cases was included for comparison. RESULTS: Seven sequence types (STs) of C. jejuni caused 83 cases, including ST9079 which recurred across 2 years. Trace-back investigation could not identify any food items of infection but detected identical campylobacters from food contacts. Phylogenetic analysis unveiled genetic closeness between outbreak strains and some concurrent sporadic strains, indicating local campylobacteriosis may not be wholly sporadic but rather a series of linked cases. Virulence genes disclosed species/case-specific signatures to differentiate outbreaks from truly non-outbreak strains. Resistance to fluoroquinolones and/or macrolides was prevalent (90.8%, 108/119), with a noteworthy portion exhibiting multidrug resistance (31.1%, 37/119). Five types of plasmids were harbored among outbreak isolates, of which one plasmid harboring anti-stress and resistant genes was rarely found in C. jejuni. CONCLUSIONS: This is the first reported sequential outbreak of C. jejuni in China. Our observations help to define the genomic landscape and antimicrobial resistance patterns of Campylobacter, emphasizing the need for a broader 'One Health' perspective to combat the threats posed by campylobacteriosis.


Subject(s)
Anti-Bacterial Agents , Campylobacter Infections , Campylobacter jejuni , Disease Outbreaks , Phylogeny , Whole Genome Sequencing , Campylobacter jejuni/genetics , Campylobacter jejuni/drug effects , Campylobacter jejuni/isolation & purification , Campylobacter jejuni/classification , Humans , China/epidemiology , Campylobacter Infections/epidemiology , Campylobacter Infections/microbiology , Adult , Child , Male , Female , Anti-Bacterial Agents/pharmacology , Adolescent , Middle Aged , Drug Resistance, Multiple, Bacterial/genetics , Young Adult , Child, Preschool , Microbial Sensitivity Tests , Plasmids/genetics , Genome, Bacterial
15.
Viruses ; 16(4)2024 04 22.
Article in English | MEDLINE | ID: mdl-38675986

ABSTRACT

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial cells (PIECs) infected with PCV2, can inhibit the maturation of monocyte-derived dendritic cells (MoDCs). Here, we established a co-culture system of MoDCs and different groups of PIECs to further investigate the PCV2-induced endothelial IL-8 signaling pathway that drives the inhibition of MoDC maturation. The differentially expressed genes related to MoDC maturation were mainly enriched in the NF-κB and JAK2-STAT3 signaling pathways. Both the NF-κB related factor RELA and JAK2-STAT3 signaling pathway related factors (IL2RA, JAK, STAT2, STAT5, IL23A, IL7, etc.) decreased significantly in the IL-8 up-regulated group, and increased significantly in the down-regulated group. The expression of NF-κB p65 in the IL-8 up-regulated group was reduced significantly, and the expression of IκBα was increased significantly. Nuclear translocation of NF-κB p65 was inhibited, while the nuclear translocation of p-STAT3 was increased in MoDCs in the PCV2-induced endothelial IL-8 group. The results of treatment with NF-κB signaling pathway inhibitors showed that the maturation of MoDCs was inhibited and the expression of IL-12 and GM-CSF at mRNA level were lower. Inhibition of the JAK2-STAT3 signaling pathway had no significant effect on maturation, and the expression of IL-12 and GM-CSF at mRNA level produced no significant change. In summary, the NF-κB signaling pathway is the main signaling pathway of MoDC maturation, and is inhibited by the PCV2-induced up-regulation of endothelial-derived IL-8.


Subject(s)
Circovirus , Interleukin-8 , Signal Transduction , Swine Diseases , Animals , Cell Differentiation , Cells, Cultured , Circoviridae Infections/virology , Circoviridae Infections/immunology , Circoviridae Infections/veterinary , Circovirus/physiology , Circovirus/immunology , Coculture Techniques , Dendritic Cells/immunology , Dendritic Cells/metabolism , Endothelial Cells/virology , Endothelial Cells/metabolism , Interleukin-8/metabolism , Interleukin-8/genetics , NF-kappa B/metabolism , Swine , Swine Diseases/virology , Swine Diseases/immunology , Swine Diseases/metabolism
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 337-345, 2024 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-38645867

ABSTRACT

Objective: To screen for the key characteristic genes of the psoriasis vulgaris (PV) patients with different Traditional Chinese Medicine (TCM) syndromes, including blood-heat syndrome (BHS), blood stasis syndrome (BSS), and blood-dryness syndrome (BDS), through bioinformatics and machine learning and to provide a scientific basis for the clinical diagnosis and treatment of PV of different TCM syndrome types. Methods: The GSE192867 dataset was downloaded from Gene Expression Omnibus (GEO). The limma package was used to screen for the differentially expressed genes (DEGs) of PV, BHS, BSS, and BDS in PV patients and healthy populations. In addition, KEGG (Kyoto Encyclopedia of Genes and Genes) pathway enrichment analysis was performed. The DEGs associated with PV, BHS, BSS, and BDS were identified in the screening and were intersected separately to obtain differentially characterized genes. Out of two algorithms, the support vector machine (SVM) and random forest (RF), the one that produced the optimal performance was used to analyze the characteristic genes and the top 5 genes were identified as the key characteristic genes. The receiver operating characteristic (ROC) curves of the key characteristic genes were plotted by using the pROC package, the area under curve (AUC) was calculated, and the diagnostic performance was evaluated, accordingly. Results: The numbers of DEGs associated with PV, BHS, BSS, and BDS were 7699, 7291, 7654, and 6578, respectively. KEGG enrichment analysis was focused on Janus kinase (JAK)/signal transducer and activator of transcription (STAT), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), apoptosis, and other pathways. A total of 13 key characteristic genes were identified in the screening by machine learning. Among the 13 key characteristic genes, malectin (MLEC), TUB like protein 3 (TULP3), SET domain containing 9 (SETD9), nuclear envelope integral membrane protein 2 (NEMP2), and BTG anti-proliferation factor 3 (BTG3) were the key characteristic genes of BHS; phosphatase 15 (DUSP15), C1q and tumor necrosis factor related protein 7 (C1QTNF7), solute carrier family 12 member 5 (SLC12A5), tripartite motif containing 63 (TRIM63), and ubiquitin associated protein 1 like (UBAP1L) were the key characteristic genes of BSS; recombinant mouse protein (RRNAD1), GTPase-activating protein ASAP3 Protein (ASAP3), and human myomesin 2 (MYOM2) were the key characteristic genes of BDS. Moreover, all of them showed high diagnostic efficacy. Conclusion: There are significant differences in the characteristic genes of different PV syndromes and they may be potential biomarkers for diagnosing TCM syndromes of PV.


Subject(s)
Computational Biology , Machine Learning , Medicine, Chinese Traditional , Psoriasis , Humans , Psoriasis/genetics , Psoriasis/diagnosis , Medicine, Chinese Traditional/methods , Computational Biology/methods , Gene Expression Profiling/methods , Support Vector Machine , Algorithms
17.
Small ; : e2401669, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573947

ABSTRACT

The anti-solvent-free fabrication of high-efficiency perovskite solar cells (PSCs) holds immense significance for the transition from laboratory-scale to large-scale commercial applications. However, the device performance is severely hindered by the increased occurrence of surface defects resulting from the lack of control over nucleation and crystallization of perovskite using anti-solvent methods. In this study, 2-(naphthalen-2-yl)ethylamine hydriodide (NEAI) is employed as the surface passivator for perovskite films without using any anti-solvent. Naphthalene demonstrates strong π-π conjugation, which aids in the efficient extraction of charge carriers. Additionally, the naphthalene-ring moieties form a tight attachment to the perovskite surface. After NEAI treatment, FA and I vacancies are selectively occupied by NEA+ and I- in NEAI respectively, thus effectively passivating the surface defects and isolating the surface from moisture. Ultimately, the optimized NEAI-treated device achieves a promising power conversion efficiency (PCE) of 24.19% (with a certified efficiency of 23.94%), featuring a high fill factor of 83.53%. It stands out as one of the reported high PCEs achieved for PSCs using the spin-coating technique without the need for any anti-solvent so far. Furthermore, the NEAI-treated device can maintain ≈87% of its initial PCE after 2000 h in ambient air with a relative humidity of 30% ± 5%.

18.
J Am Chem Soc ; 146(17): 11811-11822, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38635880

ABSTRACT

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.


Subject(s)
Anti-Inflammatory Agents , Glycosides , Steroids , Glycosides/chemistry , Glycosides/chemical synthesis , Glycosides/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemical synthesis , Steroids/chemistry , Steroids/pharmacology , Steroids/chemical synthesis , Mice , Animals , Humans , Density Functional Theory , Molecular Structure , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Macrophages/drug effects
19.
ACS Nano ; 18(18): 11941-11954, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38652811

ABSTRACT

Closed pores play a crucial role in improving the low-voltage (<0.1 V) plateau capacity of hard carbon anodes for sodium-ion batteries (SIBs). However, the lack of simple and effective closed-pore construction strategies, as well as the unclear closed-pore formation mechanism, has severely hindered the development of high plateau capacity hard carbon anodes. Herein, we present an effective closed-pore construction strategy by one-step pyrolysis of zinc gluconate (ZG) and elucidate the corresponding mechanism of closed-pore formation. The closed-pore formation mechanism during the pyrolysis of ZG mainly involves (i) the precipitation of ZnO nanoparticles and the ZnO etching on carbon under 1100 °C to generate open pores of 0.45-4 nm and (ii) the development of graphitic domains and the shrinkage of the partial open pores at 1100-1500 °C to convert the open pores to closed pores. Benefiting from the considerable closed-pore content and suitable microstructure, the optimized hard carbon achieves an ultrahigh reversible specific capacity of 481.5 mA h g-1 and an extraordinary plateau capacity of 389 mA h g-1 for use as the anode of SIBs. Additionally, some in situ and ex situ characterizations demonstrate that the high-voltage slope capacity and the low-voltage plateau capacity stem from the adsorption of Na+ at the defect sites and Na-cluster formation in closed pores, respectively.

20.
Chem Sci ; 15(10): 3711-3720, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38455029

ABSTRACT

We herein present a strain-release glycosylation method employing a rationally designed ortho-2,2-dimethoxycarbonylcyclopropylbenzyl (CCPB) thioglycoside donor. The donor is activated through the nucleophilic ring-opening of a remotely activable donor-acceptor cyclopropane (DAC) catalyzed by mild Sc(OTf)3. Our new glycosylation method efficiently synthesizes O-, N-, and S-glycosides, providing facile chemical access to the challenging S-glycosides. Because the activation conditions of conventional glycosyl donors and our CCPB thioglycoside are orthogonal, our novel donor is amenable to controlled one-pot glycosylation reactions with conventional donors for expeditious access to complex glycans. The strain-release glycosylation is applied to the assembly of a tetrasaccharide of O-polysaccharide of Escherichia coli O-33 in one pot and the synthesis of a 1,1'-S-linked glycoside oral galectin-3 (Gal-3) inhibitor, TD139, to demonstrate the versatility and effectiveness of the novel method for constructing both O- and S-glycosides.

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