Search

Background: Clostridium perfringens (C. perfringens) is an important zoonotic microorganism that can cause animal and human infections, however information about the prevalence status in wild birds of this pathogenic bacterium is currently limited. Result: In this study, 57 strains of C. perfringens were isolated from 328 fecal samples of wild birds. All the isolates were identified as type A and 70.18% of the isolates carried the cpb2 gene. Antimicrobial susceptibility testing showed that and 22.80% of the isolates were classified as multidrug-resistant strains. The MLST analysis of the 57 isolates from wild birds was categorized into 55 different sequence types (STs) and clustered into eight clonal complexes (CCs) with an average of 20.1 alleles and the Simpson Diversity index (Ds) of 0.9812, and revealed a high level of genetic diversity within the C. perfringens populations. Interestingly, the isolates from swan goose were clustered in the same CC while isolates from other bird species were more scattered suggesting that a potential difference in genetic diversity among the C. perfringens populations associated with different bird species. Conclusion: C. perfringens exhibits a wide range of host adaptations, varying degrees of antimicrobial resistance, and a high degree of genetic diversity in wild birds. Understanding the prevalence, toxin type, antimicrobial resistance, and genetic diversity of C. perfringens in wildlife populations is essential for developing effective strategies for disease control and management. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionsTo compare the 26-week cost-effectiveness of adalimumab-corticosteroids (ADA-CS) and cyclosporine-corticosteroids (CSA-CS) for Vogt-Koyanagi-Harada (VKH).A preplanned cost-effectiveness analysis based on the per-protocol population of a randomized-controlled trial. VKH subjects were randomized to receive either cyclosporine (100-200 mg daily) combined with corticosteroids or adalimumab (40 mg twice monthly) combined with corticosteroids. The primary outcome of this cost-effectiveness study was the incremental cost-effectiveness ratio (ICER). Costs and quality-adjusted life-years (QALYs) data were calculated by the medical records and health utility, respectively. Subgroup (early and late-phase VKH) analysis and sensitivity analyses were performed.The ICER at 26 weeks was $62,425/QALY for the total participants. Compared to the CSA-CS group, costs in the ADA-CS group were more expensive (mean difference [ΔA-C]: $2,497) with more gains in QALYs (mean difference [ΔA-C]: 0.04). The probability of ADA-CS being cost-effective was 0.17 and 0.41 at willingness to pay (WTP) thresholds of $12,000/QALY and $36,000/QALY, respectively. Subgroup analysis and sensitivity analyses showed consistent findings with the primary analysis.Regardless of early or late-phase VKH, the CSA-CS strategy may be recommended as the preferred initial choice for the majority of VKH. [ABSTRACT FROM AUTHOR]

[Display omitted] Angiogenesis plays a pivotal role in tissue development and regeneration, but few safe and efficient pro-angiogenic factors are available for long-term clinical therapy. Although stem cell-derived exosomes exhibit excellent biocompatibility and considerable pro-angiogenic capacity, their low yield extremely limits their clinical potential. Exosome-mimetics (EMs) employ similar features to exosomes and can be produced in a higher yield. In this study, the HY-EMs were produced to enhance in vitro and in vivo pro-angiogenic ability from hypoxia-preconditioned bone marrow mesenchymal stem cells (BMSCs) using a serial extrusion method. The yield of EMs was over 10 times greater than that of exosomes. Furthermore, compared with the EMs group, the tube number of human umbilical vein endothelial cells (HUVECs) in vitro doubled in the HY-EMs treated group, and the number of blood vessels increased by 186% in subcutaneously implanted scaffold with HY-EMs. More importantly, the HY-EMs effectively promoted vascularized osteogenesis in a critical-sized cranial defect model, with the new bone volume and vessel number in regenerated bone increased to 120% and 175%, respectively. Consequently, our current work provides a promising strategy to customize and mass-produce functional EMs for vascularized osteogenesis. [ABSTRACT FROM AUTHOR]

Biophysical cues of the cellular microenvironment tremendously influence cell behavior by mechanotransduction. However, it is still unclear how cells sense and transduce the mechanical signals from 3D geometry to regulate cell function. Here, the mechanotransduction of human mesenchymal stem cells (MSCs) triggered by 3D micropatterns and its effect on the paracrine of MSCs are systematically investigated. Our findings show that 3D micropattern force could influence the spatial reorganization of the cytoskeleton, leading to different local forces which mediate nucleus alteration such as orientation, morphology, expression of Lamin A/C and chromatin condensation. Specifically, in the triangular prism and cuboid micropatterns, the ordered F-actin fibers are distributed over and fully transmit compressive forces to the nucleus, which results in nuclear flattening and stretching of nuclear pores, thus enhancing the nuclear import of YES-associated protein (YAP). Furthermore, the activation of YAP significantly enhances the paracrine of MSCs and upregulates the secretion of angiogenic growth factors. In contrast, the fewer compressive forces on the nucleus in cylinder and cube micropatterns cause less YAP entering the nucleus. The skin repair experiment provides the first in vivo evidence that enhanced MSCs paracrine by 3D geometry significantly promotes tissue regeneration. The current study contributes to understanding the in-depth mechanisms of mechanical signals affecting cell function and provides inspiration for innovative design of biomaterials. [ABSTRACT FROM AUTHOR]

Cancer recurrence and metastasis after surgical resection is a vital reason of treatment failure. The modification of immune cells through implanted biomaterials is a promising postoperative immunotherapy. Herein, an injectable hydrogel scaffold loaded with engineered exosome mimetics that in vivo recruits and programs endogenous macrophages into M1 binding with anti‐CD47 antibody (M1‐aCD47 macrophages) for postoperative cancer immunotherapy is developed. Briefly, M1 macrophages‐derived exosome mimetics co‐modified with vesicular stomatitis virus glycoprotein (VSV‐G) and aCD47 (V‐M1EM‐aCD47) are encapsulated in injectable chitosan hydrogel. Such hydrogel recruits inherent macrophages in situ and releases V‐M1EM‐aCD47 that programs M2 to M1‐aCD47 macrophages. M1‐aCD47 macrophages own dual‐functions of tumor‐homing and enhanced phagocytosis. They can actively target to tumor cells for delivery of aCD47 that blocks the "don't eat me" signal, thereby promoting phagocytosis of macrophages to cancer cells. Furthermore, V‐M1EM‐aCD47 hydrogel implanted into resection site of 4T1 breast tumor inhibits tumor recurrence and metastasis by phagocytosis of M1‐aCD47 macrophages and T cell‐mediated immune responses. The findings demonstrate that biomaterials can be designed in vivo to program inherent macrophages, thereby activating the innate and adaptive immune systems for prevention of postoperative tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Objective The performance of existing diagnostic criteria for Behçet's disease (BD) is usually evaluated by comparison with expert opinions, which may be limited by misclassification and disagreement among experts. We aim to evaluate these criteria in the absence of a gold standard. Methods We obtained two datasets involving possible BD and other mimickers from a uveitis registry using case–cohort and nested case–control analyses, respectively. With a Bayesian inference approach, the sensitivity and specificity of International Study Group (ISG) and International Criteria for Behçet's Disease (ICBD) criteria were simultaneously estimated when true BD state was unknown. Results A total of 2440 and 2224 participants were included in case–cohort and nested case–control analyses, respectively. In case–cohort analysis, with scores of ≥4 for BD diagnosis, ICBD criteria showed higher sensitivity (median 97.6%; 95% credible interval 96.9, 98.2) than ISG criteria (median 90.0%; 95% credible interval 88.8, 91.2) but had lower specificity (median 90.8%; 95% credible interval 89.4, 92.1) than ISG criteria (median 98.8%; 95% credible interval 98.3, 99.3). With scores of ≥5 for diagnosis, ICBD criteria demonstrated higher sensitivity (median 97.5%; 95% credible interval 96.8, 98.1) and specificity (median 99.6%; 95% credible interval 99.3, 99.8) than the sensitivity (median 92.3%; 95% credible interval 91.2, 93.3) and specificity (median 98.8%; 95% credible interval 98.2, 99.2) for ISG criteria. The highest diagnostic consistency was observed between ISG criteria and ICBD criteria with scores of ≥5 for diagnosis (Kappa = 0.999; P  < 0.001). Nested case–control analysis showed similar results. Conclusion ICBD criteria showed optimum discriminatory properties in sensitivity and specificity with scores of ≥5 for BD diagnosis in uveitis. The diagnostic threshold of ICBD criteria could be considered adjustable according to medical specialty, disease prevalence and local practice characteristics. [ABSTRACT FROM AUTHOR]

Chinese chive (Allium tuberosum Rottler ex Sprengle) cultivation is widespread in China owing to its distinctive flavor and nutritional advantages. Nevertheless, there exists a significant gap in our knowledge concerning bacterial diseases affecting Chinese chive. In this investigation, a novel strain, denoted as MYJC, was isolated and purified from stem and leaf samples of soft rot in Chinese chive plants collected from above the ground in Chengdu City. Subsequent application of Koch's postulates confirmed its pathogenicity in causing Chinese chive soft rot disease. Comprehensive physiological, biochemical, and molecular biology assays unequivocally identified the causative agent as Pantoea eucalypti. Notably, this study represents the inaugural report of Pantoea eucalypti -induced soft rot disease in Chinese chive in China, thereby establishing a critical theoretical foundation for devising preventive and control strategies against this devastating pathogen in the Chinese chive cultivation sector. • Pantoea eucalypti could cause bacterial soft rot in Chinese chive. • The single colonies of Pantoea eucalypti appeared round or oval in shape, and displayed a white or light-yellow color exhibited a short rod-shaped morphology. • Pantoea eucalypti is capable of pectin and gelatin decompose, whereas it does not exhibit the ability to decompose substances such as cellulose and urea. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine possible causal associations between various components of metabolic syndrome and glaucoma‐related phenotypes. Methods: A two‐sample Mendelian randomisation study was conducted with the models of inverse‐variance weighted (IVW), maximum likelihood, weighted median and MR‐Egger regression. We accessed data from publicly available genome‐wide association studies for individual parameters of metabolic syndrome as the exposures and the data for glaucoma and its endophenotypes as the outcomes. Results: Among 11 exposures and 6 outcomes examined in this Mendelian randomisation study, only fasting blood glucose level showed evidence of a causal influence on intraocular pressure. Results analysed by the IVW model suggested that each one‐SD increase in genetically predicted fasting blood glucose level was significantly associated with 0.80 SD elevation in intraocular pressure (β: 0.80, 95% CI: 0.38–1.22, p: 2.12e−4). The maximum likelihood model (β: 0.82, 95% CI: 0.39–1.25, p: 1.616e−4) also supported a significant causal effect. The weighted median model (β: 0.78, 95% CI: 0.17–1.39, p: 0.012) showed a nominally significant effect whereas the MR‐Egger model (β: 0.63, 95% CI: −0.32–1.59, p: 0.212) showed a consistent direction of effect but was not statistically significant. Several sensitivity analyses indicated no evidence of directional horizontal pleiotropy that would bias the result. Conclusions: This Mendelian randomisation study provides evidence for a causal role for genetically determined higher fasting blood glucose level in the development of increased intraocular pressure. This finding could be considered in the monitoring and control of intraocular pressure and may be instrumental in prevention strategies for ocular hypertension. [ABSTRACT FROM AUTHOR]

The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology call for cautious interpretation of variants as causative of a monogenic disorder by stringent standards. We aimed to reclassify the pathogenicity of nucleotide binding oligomerization domain containing 2 (NOD2) variants according to the ACMG guidelines and to characterize clinical features in patients whose ocular disease might actually be explained by Blau syndrome. Genetic analysis and descriptive study. A total of 1003 unrelated healthy individuals and 3921 sporadic patients who presented with uveitis. Whole-exome sequencing was performed on all healthy participants and 551 patients with uveitis, and targeted NOD2 resequencing was performed on the remaining 3370 patients with uveitis. Pathogenicity for Blau syndrome was classified for NOD2 variants identified by sequencing in study participants according to the ACMG guidelines. Clinical manifestations were compared among NOD2 variants of different levels of classification. Pathogenicity of variants. Eight NOD2 gain-of-function mutations, p.R334W, p.R334Q, p.E383K, p.G481D, p.W490S, p.M513T, p.R587C, and p.N670K, were classified as pathogenic, and 66 patients (1.7%) with uveitis were diagnosed with Blau syndrome due to these mutations. Of 66 with Blau syndrome, anterior uveitis accounted for 39.4%, posterior uveitis for 9.1%, and panuveitis for 51.5%. A proportion of 21.2% of Blau syndrome presented as multifocal choroiditis, 48.5% had papillitis, and 74.2% showed retinal microvasculitis detected by fundus fluorescein angiography. Six NOD2 variants, p.P268S, p.R311W, p.R471C, p.A612T, p.R702W, and p.V955I, were considered nonpathogenic for Blau syndrome and were identified in 96 patients with uveitis. The incidence of bilateral uveitis (86.4%), secondary glaucoma (47.0%), epiretinal membrane (7.6%), choroidal neovascularization (4.6%), retinal atrophy (10.6%), arthritis (69.7%), joint deformity (51.5%), and skin rash (40.9%) was higher in Blau syndrome than in patients with uveitis carrying non–Blau-causing NOD2 variants. Patients with Blau syndrome permanently experienced overall poorer best-corrected visual acuity. Several rare NOD2 mutations, p.I722L (2 cases), p.T476P (1 case), p.T476del (1 case), and p.R439H (1 case), were newly identified. Pathogenic NOD2 variants for Blau syndrome were limited to those gain-of-function mutations and were associated with a high risk for arthritis, skin rash, permanent visual loss, and ocular complications in patients with uveitis. [ABSTRACT FROM AUTHOR]

Simple Summary: Enterocytozoon bieneusi is the most prevalent microsporidian species that can cause significant intestinal diseases in both humans and animals worldwide. This study investigated the overall E. bieneusi prevalence of 21.9% (47/215) in captive and free-ranging deer species in Beijing, China. Thirteen E. bieneusi genotypes including six known and seven novel genotypes were identified. These resources will provide the insights to understand the veterinary and public health and the transmission dynamics between animal environments and human ones. Enterocytozoon bieneusi is the most prevalent microsporidian species that can cause zoonotic diseases in humans and animals. Despite receiving increasing attention in relation to domestic animals, there has been limited information on the infection burden of E. bieneusi in cervids. Altogether, 215 fecal samples collected from four deer species in Beijing, China were examined by nested- Polymerase Chain Reaction (PCR)targeting the internal transcribed spacer (ITS) region. The overall prevalence of E. bieneusi in deer was 21.9% (47/215), with 30.0% (24/80) in Pere David's deer, 27.3% (15/55) in fallow deer, 12.5% (5/40) in sika deer, and 7.5% (3/40) in Chinese water deer. Thirteen E. bieneusi genotypes were identified, including six known (HLJD-V, MWC_d1, BEB6, CGC2, JLD-XV, and HND-I) and seven novel genotypes (BJED-I to BJED-V, BJFD, and BJCWD). A phylogenetic analysis showed that 38.3% of the isolates belonged to zoonotic Group 1. In addition, E. bieneusi infection was first detected in fallow deer and Chinese water deer, which could act as potential zoonotic reservoirs. Our findings suggest that E. bieneusi circulates in deer and might be of importance to public health. [ABSTRACT FROM AUTHOR]

Objective: To explore susceptibility loci associated with uveitis in Behçet's disease (BD). Methods: We conducted a 2‐stage study, consisting of a genome‐wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD‐related uveitis and 4,388 controls, and the replication stage included 953 cases with BD‐related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1. Results: Three independent HLA alleles (HLA–B51 [3.75 × 10−190], HLA–A26 [1.50 × 10−18], and HLA–C0704 [3.44 × 10−16]) were identified as having a genome‐wide association with BD‐related uveitis. In the non‐HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta‐analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome‐wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1‐FIBP‐FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1. Conclusion: This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease. [ABSTRACT FROM AUTHOR]

Introduction: Immunosuppressive therapy for uveitis may cause liver damage. Methods: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. Results: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80–213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79–6.99; p value = 2.8 × 10−4) and in IPPU (aHR, 3.80; 95% CI, 1.61–9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94–10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). Conclusion: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy. [ABSTRACT FROM AUTHOR]

Behçet's disease is a systemic vasculitis frequently associated with intraocular inflammation. Recent findings identified independent clinical clusters in Behçet's disease, each involving distinct combinations of affected organs. Ocular Behçet's disease, mainly manifested as uveitis, is characterized as an independent cluster with a low likelihood of association with other system involvements, such as intestinal, cardiovascular, or central nervous system. A prevailing theory suggests that the pathogenesis of the disease is multifactorial, where a variety of genetic and infectious agents may interact with each other to cause the disease. Among sporadic cases, the human leukocyte antigen (HLA) genes, including HLA-B51, HLA-A26, HLA-B15, and HLA-B5701, have been found to be a key component conferring genetic susceptibility. Outside the HLA region, a set of susceptibility variants are identified, closely related to interleukin (IL)-23/IL-17 pathway, tumor necrosis factor (TNF) signaling, and pattern recognition receptor systems. Microbial infections, such as Streptococcus sanguinis , Mycobacterium tuberculosis , and Herpes simplex virus (HSV), are linked to play the triggering of disease in immunogenetically predisposed individuals. Clinically, due to the notable relapsing-remitting course of ocular Behçet's disease, the prevention of recurrent attack would be the primary treatment goal. Combination of corticosteroids and immunomodulatory drugs, such as anti-TNF agents, interferon, and conventional immunosuppressants (e.g. cyclosporine, azathioprine), have been the mainstream regimen for the disease. Future research may focus on comparing the effectiveness of immunomodulatory drugs and identifying the most suitable subgroups for a specific drug on the basis of the knowledge of the molecular heterogeneity of the disease. [ABSTRACT FROM AUTHOR]

Our previous pilot-scale studies (Bioresource Technology 2018, 267: 102–109) preliminarily demonstrated the feasibility of performing air gasification with a novel two-stage system, including a medium-temperature bubbling fluidized bed (BFB) reactor and a high-temperature swirl-flow furnace reactor, using rice husk as the fuel. As an extension of that work, this study aims to further investigate the reaction mechanism and application prospect of this technology in the use of a more representative biomass fuel, i. e. rice straw. The operation stability, flow behaviors and reaction characteristics in the first-stage medium-temperature gasification reactor are studied in a lab-scale BFB gasifier. The effects of important operating conditions on the syngas quality, tar yield, compositions of carbon residue, and risk of agglomeration are elucidated in depth. The results have shown that an increase in the gasification temperature can promote syngas quality, gasification efficiency, and carbon conversion, but also increases the risk of agglomeration. An increase in the gasification equivalent ratio leads to positive effects on the syngas yield, carbon conversion, and tar concentration, but also has negative effects on the syngas heating value, tar yield, and especially the restrain of agglomeration. An increase in the raw material moisture content has negative influence on the gasification performance of rice straw, in terms of the gasification efficiency, carbon conversion, tar yield, and so on. However, the increase of moisture content can reduce the cost of raw material drying, and avoid the fluctuation of bed temperature, and therefore, a practical gasification system is recommended to be designed and operated under a certain conditions with moderate moisture contents. [ABSTRACT FROM AUTHOR]

Noninvasive neurostimulation plays a pivotal role in the direct control of neural circuits and the modulation of neuronal function. However, it is difficult to balance both spatial resolution and penetration depth when stimulating deep neurons. Here, we designed a multiple (time-division, frequency and polarity) modulation synthesis (MMS) method for noninvasively stimulating deep neurons with low-frequency envelopes. Compared to conventional transcranial electrical stimulation, we demonstrated that it can stimulate deep neurons at the desired firing rate (beat frequency) with higher spatial resolution via a computational model combining finite element analysis and Hodgkin-Huxley action potential model. Additionally, we measured the distribution of stimulus waveforms in saline solution to validate its effect. Taken together, the results of this study indicate that MMS stimulation with higher spatial resolution is steerable and might be a potential alternative to traditional implanted electrodes. [ABSTRACT FROM AUTHOR]

Bio-inspired citrate-hydroxyapatite (HAP) nanoparticles doped with zinc ions were prepared from mussel shells via a rapid method of ultrasonication and microwave irradiation. It was found that zinc ions can interact with citrate ions in the crystallization process of HAP. The growth of nanocrystals in citrate solution was slower than that in HCl solution. The addition of zinc ions reduced the residue of citrate in the products and increased the crystallinity of HAP. Furthermore, mineral platelets with the length of 29 ± 7 nm and the thickness of 3–5 nm were obtained for Zn/(Zn+Ca) = 5 mol%, which displayed similar morphology with HAP platelets in bone. Moreover, the obtained HAP nanoparticles are promising for use as bone graft materials in biomedical applications. [ABSTRACT FROM AUTHOR]

Accumulating evidences indicate that circular RNAs (circRNAs) play a vital role in modulating gene expression. However, the mechanisms underlying circRNAs remain largely elusive. Here, we screened circRNA and mRNA expression profiles of bladder carcinoma (BC) using microarray analysis. We found that circRNA-MYLK and VEGFA were significantly up-regulated and co-expressed in BC. Importantly, circRNA-MYLK levels were related to the progression of stage and grade of BC. Mechanistically, we demonstrated that circRNA-MYLK could directly bind to miR-29a and relieve suppression for target VEGFA, which activated VEGFA/VEGFR2 signaling pathway. Functionally, we found that ectopically expressing circRNA-MYLK accelerated cell proliferation, migration, tube formation of HUVEC and rearranged cytoskeleton. Moreover, up-regulating circRNA-MYLK promoted epithelial-mesenchymal transition (EMT). Whereas circRNA-MYLK knockdown decreased cell proliferation, motility, and induced apoptosis. Finally, up-regulating circRNA-MYLK promoted the growth, angiogenesis and metastasis of BC xenografts. Taken together, this study demonstrated for the first time that circRNA-MYLK might function as competing endogenous RNA (ceRNA) for miR-29a, which could contribute to EMT and the development of BC through activating VEGFA/VEGFR2 and downstream Ras/ERK signaling pathway. Our data suggest that circRNA-MYLK would be a promising target for BC diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Zinc substituted hydroxyapatite/silk fibroin composite coatings were deposited on titanium substrates at room temperature by electrophoretic deposition. Microscopic characterization of the synthesized composite nanoparticles revealed that the particle size ranged 50–200 nm, which increased a little after zinc substitution. The obtained coatings maintained the phase of hydroxyapatite and they could induce fast apatite formation in simulated body fluid, indicating high bone activity. The cell culturing results showed that the biomimetic hydroxyapatite coatings could regulate adhesion, spreading, and proliferation of osteoblastic cells. Furthermore, the biological behavior of the zinc substituted hydroxyapatite coatings was found to be better than the bare titanium without coatings and hydroxyapatite coatings without zinc, increasing MC3T1-E1 cell differentiation in alkaline phosphatase expression. [ABSTRACT FROM AUTHOR]

Several studies suggested that coronavirus disease 2019 (COVID-19) vaccination may lead to uveitis, a vision-threatening condition often associated with a variety of autoimmune or autoinflammatory diseases. This study aims to explore factors that influence the risk of uveitis relapse after COVID-19 vaccination to guide the prevention of disease. Uveitis relapse was evidenced by worsening activity of intraocular inflammation (e.g. anterior chamber cells, vitreous haze) as defined by the Standardization of Uveitis Nomenclature Working Group. Time to uveitis relapse since the administration of each dose of COVID-19 vaccine was compared across participants with modifiable variables. The primary analysis included 438 non-COVID-19 participants with 857 doses of COVID-19 vaccine administered in total. The median age was 41 years (interquartile range, 30 to 51), and 57.3% were female. A total of 39 episodes of uveitis relapse events occurred in 34 patients after the receipt of a dose of COVID-19 vaccine within 30 days. The median time to relapse after vaccination was 5 days (interquartile range, 1 to 14). Concomitant use of systemic glucocorticoids at the time of vaccination was independently associated with a decrease in risk of relapse after vaccination (HR, 0.23 [95% CI, 0.07–0.74]; P value = 0.014). There was a trend in attenuating the risk of relapse with increasing prednisone dose from none to less than 20 mg per day and then to 20 mg per day or greater (P value for trend = 0.029). Concomitant treatment with systemic glucocorticoids for uveitis at the time of COVID-19 vaccination was associated with a dose-dependent lower risk of uveitis relapse after vaccination. • COVID-19 vaccination increased the risk of newly active uveitis, but the underlying factors modifying the risk are unclear. • Systemic glucocorticoid use at the time of COVID-19 vaccination reduced the risk of uveitis relapse after vaccination. • The inverse relationship between glucocorticoid use and uveitis relapse after COVID-19 vaccination was dose-dependent. [ABSTRACT FROM AUTHOR]

Autophagy, a cellular waste disposal process, has well-established tumor-suppressive properties. New studies indicate that, in addition to its cell-autonomous anti-tumorigenic functions, autophagy inhibits cancer development by orchestrating inflammation and immunity. While attenuating tumor-promoting inflammation, autophagy enhances the processing and presentation of tumor antigens and thereby stimulates anti-tumor immunity. Although cancer cells can escape immunosurveillance by tuning down autophagy, certain chemotherapeutic agents with immunogenic properties may enhance anti-tumor immunity by inducing autophagic cell death. Understanding the intricate and complex relationships within this troika and how they are affected by autophagy enhancing drugs should improve the efficacy of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

To evaluate the effects of segmental vitiligo (SV) on nerve conduction velocity (NCV) in different nerves, we compared the patient's lesional side of their body to the contralateral normal side. The 106 participants were selected from outpatients visiting the dermatological clinics of Huashan Hospital, Fudan University, from November 2011 to March 2014. NCVs were measured on the limbs and the face, including both motor and sensory nerves. The parameters for NCVs included motor nerve conduction velocity ( MCV) and its distal conduction latency, sensory nerve conduction velocity, sensory nerve action potentials amplitude, and compound muscle action potential amplitude. MCV on the limbs was compromised by SV state, which was significantly slower on the lesional side of the body compared with the normal contralateral side ( P = 0.006). Furthermore, SV at the stable stage significantly impaired MCV compared with the SV at progressive stage. There was no significant difference in the other parameters of NCV between lesional and normal sides of the body. Compound muscle action potentials in the face did not differ between lesional and healthy sides. Motor nerves in the limbs were compromised by SV, particularly when the disease was at the stable stage. [ABSTRACT FROM AUTHOR]

A biomimetic method was used to prepare hybrid hydroxyapatite (HAP) nanoparticles with chitosan/polyacrylic acid (CS-PAA) nanogel. The morphology, structure, crystallinity, thermal properties and biocompatibility of the obtained hybrid nanogel-HAP nanoparticles have been characterized. In addition, bovine serum albumin (BSA) was used as a model protein to study the loading and release behaviors of the hybrid nanogel-HAP nanoparticles. The results indicated that the obtained HAP nanoparticles were agglomerated and the nanogel could regulate the formation of HAP. When the nanogel concentration decreased, different HAP crystal shapes and agglomerate structures were obtained. The loading amount of BSA reached 67.6 mg/g for the hybrid nanoparticles when the mineral content was 90.4%, which decreased when the nanogel concentration increased. The release profile of BSA was sustained in neutral buffer. Meanwhile, an initial burst release was found at pH 4.5 due to the desorption of BSA from the surface, followed by a slow release. The hemolysis percentage of the hybrid nanoparticles was close to the negative control, and these particles were non-toxic to bone marrow stromal stem cells. The results suggest that these hybrid nanogel-HAP nanoparticles are promising candidate materials for biocompatible drug delivery systems. [ABSTRACT FROM AUTHOR]

In this paper, three types of sand-casting M2052 alloys subjected to different heat treatments have been designed and prepared in order to investigate the relationship between Mn segregation and damping capacity using dynamic mechanical analysis, optical microscopy, X-ray diffraction, scanning electron microscopy, and energy dispersive spectroscopy. The results show that damping capacity has a crucial dependence on the Mn segregation in as-cast M2052 alloy. The original as-cast alloy without subsequent heat treatment shows its internal friction (Q −1 ) is 1.52×10 −2 at a strain amplitude of γ=2×10 −4 , while a remarkable enhancement (2.6×10 −2 ) of Q −1 can be obtained by ageing of the as-cast alloy at 435 °C for 4 h. This is mainly ascribed to the further formation of nanoscale Mn segregation in the Mn dendrites (so-called Mn macrosegregation) by spinodal decomposition during the ageing. On the contrary, performing the additional homogenization treatment at 850 °C for 24 h prior to the ageing at 435 °C for 4 h for the as-cast M2052 alloy can result in the obvious reduction of damping capacity (only 6.5×10 −3 for Q −1 ), which is closely associated with the distinct decrement of lattice distortion of γ′-Mn during f.c.c-f.c.t phase transformation caused by weakening of Mn segregation at the macro/nano-scale. [ABSTRACT FROM AUTHOR]

Summary Nuclear factor κB (NF-κB), a key activator of inflammation, primes the NLRP3-inflammasome for activation by inducing pro-IL-1β and NLRP3 expression. NF-κB, however, also prevents excessive inflammation and restrains NLRP3-inflammasome activation through a poorly defined mechanism. We now show that NF-κB exerts its anti-inflammatory activity by inducing delayed accumulation of the autophagy receptor p62/SQSTM1. External NLRP3-activating stimuli trigger a form of mitochondrial (mt) damage that is caspase-1- and NLRP3-independent and causes release of direct NLRP3-inflammasome activators, including mtDNA and mtROS. Damaged mitochondria undergo Parkin-dependent ubiquitin conjugation and are specifically recognized by p62, which induces their mitophagic clearance. Macrophage-specific p62 ablation causes pronounced accumulation of damaged mitochondria and excessive IL-1β-dependent inflammation, enhancing macrophage death. Therefore, the “NF-κB-p62-mitophagy” pathway is a macrophage-intrinsic regulatory loop through which NF-κB restrains its own inflammation-promoting activity and orchestrates a self-limiting host response that maintains homeostasis and favors tissue repair. [ABSTRACT FROM AUTHOR]

Because of the superior properties of copper, it has been of great interest as a conducting material to replace aluminum in device manufacturing. In this study, we investigated the influence of substrate temperature, film thickness, and rapid thermal annealing (RTA) on the deposition of Cu films of thickness less than 10 nm. Compared to thicker films, the electrical properties of nanometer-thick films were found to be very sensitive to the deposition temperature. Further, we determined the optimal deposition temperature to obtain low-resistivity nanometer-thick Cu films. The Cu films were deposited with island-type growth, and the interconnection between grains plays a major role in the resistivity of the films. We also determined the critical thickness at which Cu films exhibit continuous growth as 8 nm. After RTA, the film color darkened, electron scattering became weak, and the resistivity reduced more than 20% with annealing at 300–350 °C, because of the growth of Cu grains. The results of this study indicate that thermal ALD can be used in conjunction with RTA to produce low-resistivity Cu thin films, the thickness, uniformity, and conformality of which can be easily controlled. [ABSTRACT FROM AUTHOR]

In this study, a biomimetic method was used to prepare hydroxyapatite (HAP) and zinc substituted HAP (ZnHAP) nanoparticles, in which silk fibroin was used as template. The morphology of HAP is rod-like, while ZnHAP changes to wrinkled sheets. HAP and ZnHAP nanoparticles were used to coat titanium by EPD with additional chitosan and multiwalled carbon nanotubes. Phase composition, morphology and structure were studied using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared and Raman spectroscopy. The results showed that the composite coatings containing HAP and ZnHAP had homogeneous morphology and good apatite formation ability. The ZnHAP composite coating possessed class 5B adhesive strength using tape test. Furthermore, the ZnHAP composite coating had better corrosion resistance compared to the HAP composite coatings. [ABSTRACT FROM AUTHOR]

Cellulose acetate (CA) nanofibers were deposited on stainless steel plates by electrospinning technique. The composite of hydroxyapatite (HAP) nanoparticles and chitosan (CHI) was coated subsequently by dip-coating. The structure and morphology of the obtained coatings were investigated by Fourier transform infrared spectroscopy and scanning electron microscopy. The stability of the coatings in physiological environment was studied using electrochemical polarization and impedance spectroscopy. The CA nanofibers were embedded in the HAP/CHI coating and the resulted composite film was densely packed and uniform on the substrate. The in vitro biomineralization study of the coated samples immersed in simulated body fluid (SBF) confirmed the formation ability of bone-like apatite layer on the surface of HAP-containing coatings. Furthermore, the coatings could provide corrosion resistance to the stainless steel substrate in SBF. The electrochemical results suggested that the incorporation of CA nanofibers could improve the corrosion resistance of the HAP/CHI coating. Thus, biocompatible CA/HAP/CHI coated metallic implants could be very useful in the long-term stability of the biomedical applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chimeric BPV VLP vaccines were constructed to present HIV-1 MPER epitopes. [•] The induction of systemic and mucosal antibody responses was assessed in mice. [•] The induced IgG and sIgA recognized the MPER epitopes presented by HIV-1. [•] IgG and sIgA induced by L1-MPER are able to neutralize clade B and clade C HIV-1. [Copyright &y& Elsevier]

Abstract: Cryopreservation of animal or human peripheral blood mononuclear cells (PBMC) is a commonly used technique. Effects of cryopreservation on functional capacity, especially the cytokine production of human PBMCs, have been extensively defined. However, certain animals, such as livestock, are a shortage of these information. Here we investigated the effects of cryopreservation on cytokine (IL-4, IFNγ and IL-6) production of porcine PBMC. The porcine PBMCs were cryopreserved at −196°C for a variety time periods for 2, 5, 25 and 50days. Viability and cytokine production of the porcine PBMCs were measured before and after cryopreservation. The results showed that about 90% cell recovery rate was obtained at each storage time, indicating that about 10% loss of PBMCs in this short-term cryopreservation was due to the freezing process rather than the duration of cryopreservation. The fresh or frozen resting porcine PBMCs produced little cytokines in the absence of stimulation. However, three cytokines were apparently increased after PMA stimulation in both fresh and frozen porcine PBMCs. The sensitivity of frozen cells to PMA simulation for IFNγ and IL-6 production was different from that of the fresh ones. IFNγ production from the frozen PBMCs was significantly higher than that from the fresh ones (P <0.01). In contrast, IL-6 level from the frozen sample was significantly lower than that from the fresh one (P <0.05). Those results indicate that cryopreservation can increase the sensitivity of porcine PBMCs stimulated by PMA for IFNγ production but not for IL-6 production. There was no significant difference of IL-4 production between fresh and frozen cells either stimulated (P >0.05) or un-stimulated (P >0.05). [Copyright &y& Elsevier]

Although it has long been recognized that air pollution can affect the immune system and human ocular symptoms, it is uncertain whether air pollutants may also contribute to the development of uveitis. This study aimed to quantify the association of particulate matters less than 2.5 μm (PM2.5) with uveitis onset. We combined monthly averages of PM2.5 concentrations, with data from the largest database of uveitis cases to assess the association between PM2.5 and uveitis onset. We further estimated the uveitis burden that was attributed to PM2.5 exposure and used choropleth maps to precisely characterize geographical variations. We found that a 10 μg/m3 increase in PM2.5 concentration was associated with a one-case per 10 individuals increase in uveitis onset across the dataset. Our results further suggest that PM2.5 concentrations above the level of the minimum exposure are responsible for 13% of novel uveitis cases in our cohort. Conclusion: These findings provide evidence supporting the association between fine particulate air pollution and uveitis onset. [ABSTRACT FROM AUTHOR]

Uveitis is a group of diseases characterized by intraocular inflammation, of which some are driven by autoinflammatory or autoimmune responses, such as Vogt-Koyanagi-Harada disease, Behçet's disease, uveitis associated with spondyloarthritis, ocular sarcoidosis, sympathetic ophthalmia and birdshot chorioretinopathy. These entities have various clinical forms, but genetic and biomarker data suggest that they share a common molecular basis, activation of the Interleukin (IL)-23/IL-17 pathway. Multiple factors including genetic predisposition, various cytokine imbalances, infectious agents and gut alterations are found to trigger an aberrant response of this pathway. The enhanced activity of the IL-23/IL-17 pathway is committed to the expansion and pathogenicity of Th17 cells. Evidence from animal models demonstrates that the development of pathogenic Th17 cells is responsible for the induction of experimental autoimmune uveitis. Further findings indicate that retinal pigment epithelium (RPE) cells may be a target of IL-17. IL-17 triggers downstream inflammatory cascades and causes dysfunction of RPE cells, which may affect retinal barrier function and thereby promote intraocular inflammation. Currently, several emerging drugs blocking the IL-23/IL-17 pathway have been assessed for the treatment of uveitis in pilot studies. The purpose of this is to summarize updated biological knowledge and preliminary clinical data, providing the rationale for further development and evaluation of novel drugs targeting the IL-23/IL-17 pathway in autoinflammatory and autoimmune uveitis. Future studies may focus on translational medicine targeting the IL-23/IL-17 pathway for the improvement of diagnosis and treatment of uveitis. In conclusion, activation of the IL-23/IL-17 pathway is a critical biological event and can be an important target for the treatment of autoinflammatory and autoimmune uveitis. [ABSTRACT FROM AUTHOR]

This paper proposes a new car-following model for electric vehicle traffic flow in order to minimize the energy consumption. In particular, the energy consumption model is introduced for electric vehicles to capture the energy consumption at every moment. Then, the new car-following models with zero initial state and non-zero initial state are derived from the optimal energy consumption model by using the minimum principle theory. The theoretical analysis shows that the model with the zero initial state condition is a special case of the model with the non-zero initial state condition. Finally, the numerical experiments are conducted with three scenarios: acceleration process, deceleration process and evolution process. Results from numerical experiments demonstrate the effectiveness of the proposed model in terms of position, velocity, and acceleration profiles. [ABSTRACT FROM AUTHOR]

In the global transition towards sustainable energy, microgrids are emerging as a core component of distributed energy systems and a pivotal technology driving this transformation. By integrating renewable energy sources such as solar and wind power, microgrids not only enhance energy efficiency and reduce reliance on traditional energy sources but also bolster grid stability and mitigate the risk of widespread power outages. Consequently, microgrids demonstrate significant potential in improving the reliability of power supply and facilitating flexibility in energy consumption. However, the operational planning and optimization of microgrids are faced with complex challenges characterized by multiple objectives and constraints, making the reduction in operational costs a focal point of research. This study fully considers an operational model for a microgrid that incorporates distributed energy resources and comprehensive costs, integrating a battery storage system to ensure three-phase balance. The microgrid model includes photovoltaic power generation, wind power generation, fuel cells, micro-gas turbines, energy storage systems, and loads. The objectives of operating and maintaining this microgrid primarily involve optimizing dispatch, energy consumption, and pollution emissions, aiming to reduce carbon emissions and minimize total costs. To achieve these goals, the study introduces a carbon emission constraint strategy and proposes an improved Multi-Strategy Integrated Sparrow Search Algorithm (MISSA). By applying the MISSA to solve the operational problems of the microgrid and comparing it with other algorithms, the results demonstrate the effectiveness of the carbon emission constraint strategy in the microgrid's operation. Furthermore, the results prove that the MISSA can achieve the lowest comprehensive operational costs for the microgrid, confirming its effectiveness in addressing the operational challenges of the microgrid. [ABSTRACT FROM AUTHOR]

Extracellular vesicle (EV)-based liquid biopsies have been proposed to be a readily obtainable biological substrate recently for both profiling and diagnostics purposes. Development of a fast and reliable preparation protocol to enrich such small particles could accelerate the discovery of informative, disease-related biomarkers. Though multiple EV enrichment protocols are available, in terms of efficiency, reproducibility and simplicity, precipitation-based methods are most amenable to studies with large numbers of subjects. However, the selectivity of the precipitation becomes critical. Here, we present a simple plasma EV enrichment protocol based on pluronic block copolymer. The enriched plasma EV was able to be verified by multiple platforms. Our results showed that the particles enriched from plasma by the copolymer were EV size vesicles with membrane structure; proteomic profiling showed that EV-related proteins were significantly enriched, while high-abundant plasma proteins were significantly reduced in comparison to other precipitation-based enrichment methods. Next-generation sequencing confirmed the existence of various RNA species that have been observed in EVs from previous studies. Small RNA sequencing showed enriched species compared to the corresponding plasma. Moreover, plasma EVs enriched from 20 advanced breast cancer patients and 20 age-matched non-cancer controls were profiled by semi-quantitative mass spectrometry. Protein features were further screened by EV proteomic profiles generated from four breast cancer cell lines, and then selected in cross-validation models. A total of 60 protein features that highly contributed in model prediction were identified. Interestingly, a large portion of these features were associated with breast cancer aggression, metastasis as well as invasion, consistent with the advanced clinical stage of the patients. In summary, we have developed a plasma EV enrichment method with improved precipitation selectivity and it might be suitable for larger-scale discovery studies. [ABSTRACT FROM AUTHOR]

• An interference-resistant gear defect detection method is proposed based on improved YOLOv5. • Ability of the network to extract defect features is enhanced by new module CBAMC3. • Combined module BiFPN_concat makes the network capable of fusing the features. • Cosine annealing function is used to improve the learning ability of the network. • Improved YOLOv5 network enhances the recall rate by 13.1% and the mAP @0.5 by 12%. Automatically detecting the metallic gear defects may encounter the misdetected and undetected errors when the defect features are very close to the interferences of oil stains and image shadow. To address these challenges, in this paper an industrial interference-resistant gear surface defect detection method is presented based on the improved YOLOv5 network. The method combines the approach using the attention module CBAMC3 constituted by CBAM and C3 modules together with the analysis of the module BiFPN_concat, which makes the network capable of extracting and fusing defect features, respectively. The cosine annealing function is then employed to improve the learning ability of the network by modifying the learning rate. The experimental results indicate that the improved YOLOv5 network enhances both the recall rate by 13.1% and the mAP @0.5 by 12% compared with the original YOLOv5 network, and also outweighs the classical algorithms in detection speed with average 25 frames per second. [ABSTRACT FROM AUTHOR]

Clostridium perfringens is a highly versatile pathogen of humans and animals. Rapid and sensitive detection methods for C. perfringens are urgently needed for the timely implementation of control. In this study, to provide novel promising methods for the detection of C. perfringens, two rapid, sensitive, and instrument-free C. perfringens detection methods based on recombinase-aided amplification (RAA) assay and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 12a (CRISPR/Cas12a) system were developed depending on fluorescence signal (RAA-CRISPR/Cas12a-FL) and lateral flow strip (RAA-CRISPR/Cas12a-LFS), respectively. The limit of detection of the RAA-CRISPR/Cas12a-FL and RAA-CRISPR/Cas12a-LFS methods is 2 copies and 20 copies of C. perfringens genomic DNA per reaction, respectively, and the whole process can be completed in 1 hr. Moreover, these two methods show no cross-reactivity with nontarget bacteria, which were used as a negative control to evaluate the specificity of two developed methods in the detection of C. perfringens and have 100% consistent with real-time polymerase chain reaction tests for 12 clinical samples collected from 2 Chinese Milu at Beijing Milu Ecological Research Center and 6 spiked samples from human blood and stool. Overall, the constructed C. perfringens detection methods, RAA-CRISPR/Cas12a-FL and RAA-CRISPR/Cas12a-LFS, have great potential as a novel detection scheme for the early diagnosis of C. perfringens infection in humans and animals. [ABSTRACT FROM AUTHOR]

The KIAA0100 gene was identified in the human immature myeloid cell line cDNA library. Recent studies have shown that its expression is elevated in breast cancer and associated with more aggressive cancer types as well as poor outcomes. However, its cellular and molecular function is yet to be understood. Here we show that silencing KIAA0100 by siRNA in the breast cancer cell line MDA-MB-231 significantly reduced the cancer cells’ aggressive behavior, including cell aggregation, reattachment, cell metastasis and invasion. Most importantly, silencing the expression of KIAA0100 particularly sensitized the quiescent cancer cells in suspension culture to anoikis. Immunoprecipitation, mass spectrometry and immunofluorescence analysis revealed that KIAA0100 may play multiple roles in the cancer cells, including stabilizing microtubule structure as a microtubule binding protein, and contributing to MDA-MB-231 cells Anoikis resistance by the interaction with stress protein HSPA1A. Our study also implies that the interaction between KIAA0100 and HSPA1A may be targeted for new drug development to specifically induce anoikis cell death in the cancer cell. [ABSTRACT FROM AUTHOR]

Extracellular vesicle (EV)-based liquid biopsies have been proposed to be a readily obtainable biological substrate recently for both profiling and diagnostics purposes. Development of a fast and reliable preparation protocol to enrich such small particles could accelerate the discovery of informative, disease-related biomarkers. Though multiple EV enrichment protocols are available, in terms of efficiency, reproducibility and simplicity, precipitation-based methods are most amenable to studies with large numbers of subjects. However, the selectivity of the precipitation becomes critical. Here, we present a simple plasma EV enrichment protocol based on pluronic block copolymer. The enriched plasma EV was able to be verified by multiple platforms. Our results showed that the particles enriched from plasma by the copolymer were EV size vesicles with membrane structure; proteomic profiling showed that EV-related proteins were significantly enriched, while high-abundant plasma proteins were significantly reduced in comparison to other precipitation-based enrichment methods. Next-generation sequencing confirmed the existence of various RNA species that have been observed in EVs from previous studies. Small RNA sequencing showed enriched species compared to the corresponding plasma. Moreover, plasma EVs enriched from 20 advanced breast cancer patients and 20 age-matched non-cancer controls were profiled by semi-quantitative mass spectrometry. Protein features were further screened by EV proteomic profiles generated from four breast cancer cell lines, and then selected in cross-validation models. A total of 60 protein features that highly contributed in model prediction were identified. Interestingly, a large portion of these features were associated with breast cancer aggression, metastasis as well as invasion, consistent with the advanced clinical stage of the patients. In summary, we have developed a plasma EV enrichment method with improved precipitation selectivity and it might be suitable for larger-scale discovery studies. [ABSTRACT FROM AUTHOR]

Inflammation benefits the host by promoting the elimination of invading pathogens and clearance of cellular debris after tissue injury. Inflammation also stimulates tissue repair and regeneration to restore homeostasis and organismal health. Emerging evidence suggests that mitochondrial DNA (mtDNA), the only form of non-nuclear DNA in eukaryotic cells, is a major activator of inflammation when leaked out from stressed mitochondria. Here, we review the current understanding on the role of mtDNA in innate immunity, discussing how dysregulated mtDNA metabolism can promote chronic inflammation and disease progression. mtDNA possesses unique features that are 'immunostimulatory'. mtDNA escaping from stressed mitochondria can activate inflammasomes, triggering IL-1β and IL-18 production. mtDNA also engages the cGAS-STING pathway to induce type I IFN production. mtDNA activates the TLR9 pathway to induce proinflammatory cytokine and chemokine production. Dysregulation of mtDNA metabolism can promote inflammation and disease development. [ABSTRACT FROM AUTHOR]

To characterize the clinical features of sympathetic ophthalmia (SO) and compare SO and Vogt–Koyanagi–Harada (VKH) disease in Chinese patients. Retrospective case series. A total of 131 consecutive SO and 500 VKH disease patients randomly selected from among those referred to our uveitis center from April 2008 through June 2018. History, extraocular and ocular findings, best-corrected visual acuity (BCVA), auxiliary examination findings, complications, and therapeutic effects were analyzed retrospectively in SO and VKH disease patients. Visual outcome, extraocular and ocular findings, and therapeutic effects. Sympathetic ophthalmia manifested as posterior uveitis (68.8%) within 2 weeks and equal involvement of anterior and posterior segment (44.4%), respectively, was observed between 2 weeks and 2 months after disease onset. Two months after disease onset, SO patients showed sunset glow fundus (51.2%) and granulomatous anterior uveitis (27.3%). Vogt–Koyanagi–Harada disease patients mainly showed posterior uveitis (100%), anterior segment involvement (92.4%) associated with posterior uveitis (84.9%), and granulomatous anterior uveitis (97.4%) accompanying sunset glow fundus (91.5%) in the 3 periods mentioned above. The frequencies of extraocular manifestations were lower in SO patients (24.4%) as compared with VKH disease patients (84.8%; P < 0.001). Best-corrected visual acuity of SO patients improved from 0.68±0.86 logarithm of the minimum angle of resolution (logMAR) to 0.47±0.78 logMAR (P = 0.01), and BCVA of VKH disease patients improved from 0.67±0.79 logMAR to 0.24±0.53 logMAR (P < 0.001) at 12 months of follow-up. A worse BCVA was noted in SO patients compared with VKH disease patients after treatment (P = 0.003). Kaplan-Meier survival analysis showed that the risk of loss of useful vision in SO patients was significantly higher than that of VKH disease patients (P < 0.001). Chinese SO and VKH disease patients have a different evolutionary process. The frequency of extraocular manifestations in SO patients is much lower as compared with VKH disease patients. Visual outcome is worse in SO as compared with VKH disease. [ABSTRACT FROM AUTHOR]

Purpose: To depict a whole spectrum of clinical feartures and visual prognosis among pediatric, adult, and elderly Vogt-Koyanagi-Harada disease (VKH) patients. Methods: Retrospective chart review was conducted in 2571 VKH patients diagnosed from April 2008 to January 2022. Based on age of disease onset, patients were divided into pediatric (age ≤ 16 years), adult (16 < age < 65 years), and elderly (age ≥ 65 years) VKH group. Ocular and extraocular manifestations were compared among these patients. Visual outcomes and complications were evaluated using logistic regression models and restricted cubic splines analysis. Results: The median follow-up time was 48 (IQR, 12–60) months. Pediatric, adult and elderly VKH were found in 106 (4.1%), 2355 (91.6%), and 110 (4.3%) patients, respectively. All of the patients showed similar ocular manifestations in the context of disease phasing. The proportion of neurological and auditory manifestations in pediatric (42.3% and 7.5%) VKH patients was significantly lower than that in adults (66.5% and 47.9%) and elderly (68.2% and 50%) (both p < 0.0001). An increased risk of macular abnormalities was seen in adults (OR, 3.43; 95% CI, 1.62–7.29) compared with elderly VKH. An inverted-U-shaped pattern was observed between disease onset age and a poor visual outcome (visual acuity 6/18 or worse) according to OR value in VKH patients. The highest risk of BCVA ≤ 6/18 was observed in 32 years at disease onset (OR, 1.51; 95% CI, 1.18–1.94). A higher risk of visual loss was observed in adult VKH patients (OR, 9.06; 95% CI, 2.18–37.6) compared with elderly VKH patients. And stratified by macular abnormalities, the interaction test was not significant (P = 0.634). Conclusion: Our study identified, for the first time, a whole spectrum of clinical features of VKH based on a large cohort of Chinese patients. Adult VKH patients have an increased risk of poor visual outcomes, possibly due to increased frequency of macular abnormalities. [ABSTRACT FROM AUTHOR]

Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ~1011 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 106 enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients. [ABSTRACT FROM AUTHOR]

Background: Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. Methods: In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut‐off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan–Meier method, and significant differences were evaluated by the log‐rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early‐stage disease (stage 0‐II) for sensitivity analysis. Results: Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19‐9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p < 0.05). These prognostic factors were used to establish and verify the OS nomogram. Poorer OS was linked to higher RDW (HR = 1.52; 95% CI, 1.11–2.08; p < 0.01) and ΔRDW (HR = 1.65; 95% CI, 1.19–2.28; p < 0.01) in all‐stage patients, and was only linked to higher RDW in early‐stage patients. In competing risk model, H‐RDW and H‐ΔRDW were confirmed to be independent risk factors for CSS in CRC patients. Conclusions: High preoperative RDW and ΔRDW are both risk factors for OS and CSS in CRC. [ABSTRACT FROM AUTHOR]

Accumulating evidences indicate that long noncoding RNAs (lncRNAs) might play important roles in tumorigenesis and metastasis. EMT (epithelial-to-mesenchymal transition) is considered as a critical step in invasion and metastasis of various tumors including bladder cancer (BC). Recent researches have showed that lncRNA H19 is implicated in metastasis through regulating EMT and the reverse MET (mesenchymal-to-epithelial transition). However, underlying mechanisms remain largely unknown. Here, we screened lncRNA and mRNA expression profiles of BC with microarray assay. We found that H19 and DNMT3B displayed a higher co-expression in BC tissues and cells. Functionally, we demonstrated that H19 could increase proliferation, invasion and migration, regulate EMT as well as rearrange cytoskeleton of BC cells in vitro . Moreover, ectopic expression of H19 promoted tumorigenesis, angiogenesis and pulmonary metastasis in vivo , whereas knockdown of H19 has a contrary role in vivo and in vitro . Mechanistically, we proved that H19 could directly bind to miR-29b-3p (miR-29b) and derepress the expression of target DNMT3B. H19 and miR-29b-3p showed a co-localization. More importantly, up-regulating H19 antagonized miR-29b-3p-mediated proliferation, migration and EMT suppression in BC cells. Furthermore, H19 knockdown partially reversed the function of miR-29b-3p inhibitor on DNMT3B and facilitated miR-29b-3p-induced MET. Taken together, we demonstrated for the first time that H19 might function as ceRNA (competing endogenous RNA) for miR-29b-3p and relieve the suppression for DNMT3B, which led to EMT and metastasis of BC. Our findings highlight a novel mechanism of H19 in progression of BC and provide H19/miR-29b-3p/DNMT3B axis as a promising therapeutic target for BC. [ABSTRACT FROM AUTHOR]

Novel cast-aged Mn-26.0Cu-2.0Ni-2.0Fe-2.0Zn-3.0Al (wt.%) alloy with good damping capacity and high usage temperature has been well designed and developed in this work, which can act as a promising candidate toward engineering applications. The microstructure, damping capacity and usage temperature were investigated systematically by X-ray diffraction, optical microscopy, scanning electron microscopy, energy dispersive spectroscopy, and dynamic mechanical analyzer. The results show that heat treatment has a significant influence on the damping capacity and usage temperature of as-cast MnCuNiFeZnAl alloy. Compared to the original as-cast alloy with internal friction (Q − 1 ) of 3.0 × 10 − 2 at a strain amplitude ε = 2 × 10 − 4 and usage temperature of 43 °C, the largest Q − 1 (5.0 × 10 − 2 ) and highest usage temperature (70 °C) can be obtained simultaneously by ageing treatment at 435 °C for 2 h, while homogenization-ageing, solution-ageing and overageing can just result in the limited improvement of damping capacity and usage temperature. This is because the highest nanoscale Mn segregation in Mn dendrites can be formed by spinodal decomposition during ageing, while carrying out the homogenization or solution treatment prior to the ageing, as well as overageing treatment can cause the weakening of Mn segregation at the macro/nano-scale and even the precipitation of α-Mn, thus leading to the undesirable damping capacity and usage temperature. [ABSTRACT FROM AUTHOR]

Sorptive removal of hexavalent chromium (Cr(VI)) bears the advantages of simple operation and easy construction. Customized polymeric materials are the attracting adsorbents due to their selectivity, chemical and mechanical stabilities. The mostly investigated polymeric materials for removing Cr(VI) were reviewed in this work. Assembling of robust functional groups, reduction of self-aggregation, and enhancement of stability and mechanical strength, were the general strategies to improve the performance of polymeric adsorbents. The maximum adsorption capacities of these polymers toward Cr(VI) fitted by Langmuir isotherm model ranged from 3.2 to 1185 mg/g. Mechanisms of complexation, chelation, reduction, electrostatic attraction, anion exchange, and hydrogen bonding were involved in the Cr(VI) removal. Influence factors on Cr(VI) removal were itemized. Polymeric adsorbents performed much better in the strong acidic pH range (e.g., pH 2.0) and at higher initial Cr(VI) concentrations. The adsorption of Cr(VI) was an endothermic reaction, and higher reaction temperature favored more robust adsorption. Anions inhibited the removal of Cr(VI) through competitive adsorption, while that was barely affected by cations. Factors that affected the regeneration of these adsorbents were summarized. To realize the goal of industrial application and environmental protection, removal of the Cr(VI) accompanied by its detoxication through reduction is highly encouraged. Moreover, development of adsorbents with strong regeneration ability and low cost, which are robust for removing Cr(VI) at trace levels and a wider pH range, should also be an eternally immutable subject in the future. Work done will be helpful for developing more robust polymeric adsorbents and for promoting the treatment of Cr(VI)-containing wastewater. [ABSTRACT FROM AUTHOR]

Aim: To explore the feasibility of applying artificial intelligence in nurse–patient interaction to assist nurses in grasping patient status and reducing their working hours. Background: Artificial intelligence has been reshaping the health care industry and has immense potential in nursing care, but there is still a lack of suitable artificial intelligence methods to improve the efficiency of the nurse–patient interaction that takes much time of nurses. Methods: An artificial intelligence‐based intelligent surveillance system was developed to reduce nurses' working hours in nurse–patient interaction, and a two‐wave follow‐up design was adopted in this study. The data were collected in a nursing home in Guangzhou, China. The first and second waves of data were recorded in the same format on the same patients by the same nurses. The only difference is the deployment of artificial intelligence technology between the two waves of data. Results: Artificial intelligence‐based intelligent surveillance can provide statistical health data for nurses to grasp the patients' status more intuitively, reducing the average nurse–patient interaction time per patient from 18 to 10 min. In addition, artificial intelligence's real‐time response to the abnormal health status of patients not only avoids more serious secondary injuries for patients but also prevents nurses from consuming energy in detecting emergencies. Conclusion: The application of artificial intelligence has great potential to reduce nurses' working hours in nurse–patient interaction. There are still many limitations in artificial intelligence technology at this stage, and it is not feasible to completely rely on artificial intelligence. However, as a tool to assist decision‐making, it can still have beneficial impacts on nursing management. Implications for Nursing Management: Artificial intelligence has great potential in daily nurse–patient interaction, and nursing facility managers and nurses need to be more open to this new technology. [ABSTRACT FROM AUTHOR]