VirusRecom: an information-theory-based method for recombination detection of viral lineages and its application on SARS-CoV-2.

Genomic recombination is an important driving force for viral evolution, and recombination events have been reported for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Coronavirus Disease 2019 pandemic, which significantly alter viral infectivity and transmissibility. However, it is difficult to identify viral recombination, especially for low-divergence viruses such as SARS-CoV-2, since it is hard to distinguish recombination from in situ mutation. Herein, we applied information theory to viral recombination analysis and developed VirusRecom, a program for efficiently screening recombination events on viral genome. In principle, we considered a recombination event as a transmission process of ``information'' and introduced weighted information content (WIC) to quantify the contribution of recombination to a certain region on viral genome; then, we identified the recombination regions by comparing WICs of different regions. In the benchmark using simulated data, VirusRecom showed a good balance between precision and recall compared to two competing tools, RDP5 and 3SEQ. In the detection of SARS-CoV-2 XE, XD and XF recombinants, VirusRecom providing more accurate positions of recombination regions than RDP5 and 3SEQ. In addition, we encapsulated the VirusRecom program into a command-line-interface software for convenient operation by users. In summary, we developed a novel approach based on information theory to identify viral recombination within highly similar sequences, providing a useful tool for monitoring viral evolution and epidemic control.

Sex, health status and habitat alter the community composition and assembly processes of symbiotic bacteria in captive frogs.

BACKGROUND: Frogs are critical economic animals essential to agricultural ecosystem equilibrium. However, Meningitis-like Infectious Disease (MID) often affects them in agricultural settings. While frog-associated microbiota contribute to elemental cycling and immunity, the effects of frog sex and health on gut bacteria remain understudied, and the relationship between frog habitat and soil microbes is unclear. We aimed to determine how frog sex, health status and habitat influence symbiotic bacteria and community assembly mechanism to provide guidance for sustainable frog farming and conservation. RESULTS: We employed 16S rRNA sequencing to investigate gut microbiota differences in relation to frog sex and health status. We also compared symbiotic communities in frog-aggregation, native and soybean soil on the farm. Results showed that gut bacterial ß-diversity and taxonomy were markedly influenced by frog sex and health. Healthy frogs had more robust gut bacterial metabolism than frogs infected with MID. Cooccurrence network analysis revealed that healthy female frogs had more complex microbial network structure than males; however, diseased males showed the greatest network complexity. The assembly mechanism of gut bacteria in male frogs was dominated by deterministic processes, whereas in female frogs it was dominated by stochastic processes. Among symbiotic bacteria in frog habitat soils, deterministic processes predominantly shaped the community assembly of soybean soil. In particular, soybean soil was enriched in pathogens and nitrogen functions, whereas frog-aggregation soil was markedly increased in sulphur respiration and hydrocarbon degradation. CONCLUSION: Our study reveals that sex mainly alters the interaction network and assembly mechanism of frog intestinal bacteria; MID infection significantly inhibits the metabolic functions of intestinal bacteria. Furthermore, diverse frog habitat soils could shape more symbiotic bacteria to benefit frog farming. Our findings provide new horizons for symbiotic bacteria among frogs, which could contribute to sustainable agriculture and ecological balance.

The insights into the phage communities of fermented foods in the age of viral metagenomics.

Phages play a critical role in the assembly and regulation of fermented food microbiome through lysis and lysogenic lifestyle, which in turn affects the yield and quality of fermented foods. Therefore, it is important to investigate and characterize the diversity and function of phages under complex microbial communities and nutrient substrate conditions to provide novel insights into the regulation of traditional spontaneous fermentation. Viral metagenomics has gradually garnered increasing attention in fermented food research to elucidate phage functions and characterize the interactions between phages and the microbial community. Advances in this technology have uncovered a wide range of phages associated with the production of traditional fermented foods and beverages. This paper reviews the common methods of viral metagenomics applied in fermented food research, and summarizes the ecological functions of phages in traditional fermented foods. In the future, combining viral metagenomics with culturable methods and metagenomics will broaden the scope of research on fermented food systems, revealing the complex role of phages and intricate phage-bacterium interactions.

An integrated finite element method and machine learning algorithm for brain morphology prediction.

The human brain development experiences a complex evolving cortical folding from a smooth surface to a convoluted ensemble of folds. Computational modeling of brain development has played an essential role in better understanding the process of cortical folding, but still leaves many questions to be answered. A major challenge faced by computational models is how to create massive brain developmental simulations with affordable computational sources to complement neuroimaging data and provide reliable predictions for brain folding. In this study, we leveraged the power of machine learning in data augmentation and prediction to develop a machine-learning-based finite element surrogate model to expedite brain computational simulations, predict brain folding morphology, and explore the underlying folding mechanism. To do so, massive finite element method (FEM) mechanical models were run to simulate brain development using the predefined brain patch growth models with adjustable surface curvature. Then, a GAN-based machine learning model was trained and validated with these produced computational data to predict brain folding morphology given a predefined initial configuration. The results indicate that the machine learning models can predict the complex morphology of folding patterns, including 3-hinge gyral folds. The close agreement between the folding patterns observed in FEM results and those predicted by machine learning models validate the feasibility of the proposed approach, offering a promising avenue to predict the brain development with given fetal brain configurations.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

Aptamer-functionalized gold nanoparticles for mercury ion detection in a colorimetric assay based on color change time as signal readout.

A universal strategy for a rapid colorimetric method for Hg2+ in an aqueous solution is described. The specific binding of Hg2+ (thymine-Hg2+-thymine) with thiolated DNA-functionalized gold nanoparticles (AuNPs) via Au-S bonds increases the spatial hindrance of the AuNP surface, resulting in a weakened catalytic ability of AuNPs to catalyze the reaction between p-nitrophenol and NaBH4. Therefore, the color change time (CCT) of the solution from yellow to colorless becomes longer. Based on the kinetic curve of absorbance over time measured by a UV spectrometer, the level of Hg2+ in aqueous solutions can be easily quantified. A linear relationship between CCT and Hg2+ concentration was obtained in the 10-600-nM range with a detection limit of 0.20 nM, which is much lower than the limit value (10 nM) defined by the US Environmental Protection Agency for Hg2+ in drinking water. The excellent sensitivity comes from CCT as the signal output of the probe, rather than the absorbance or wavelength change used in traditional colorimetric probes as the signal output.

Key mutations in the spike protein of SARS-CoV-2 affecting neutralization resistance and viral internalization.

To control the ongoing COVID-19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin-converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.

Sperm quality impairment in males of couples with pregnancy loss is correlated with sexual dysfunction: a cross-sectional study.

BACKGROUND: Erectile dysfunction is a common problem in males of couples experiencing pregnancy loss. Erectile dysfunction in males with couple infertile has been extensively investigated and found to be closely linked with semen quality impairment and psychological distress, but it is less clear if this relation exists in males of couples experiencing pregnancy loss. METHOD: A cross-sectional analysis of 437 men who attended our outpatient clinic between June 2021 and October 2021 for couple pregnancy loss. All subjects underwent a complete physical examination, palpation, inspection of the male genitalia, and semen analysis. Validated assessment tools for erectile dysfunction (the International Index of Sexual Function5 -IIEF-5) and anxiety (the seven-item Generalized Anxiety Disorder Scale- GAD-7) were used. RESULTS: Among 437 men of couples with pregnancy loss, we found several relevant sperm parameters confirmed a significant correlation between IIEF-5 scores and sperm parameters, including: sperm progressive motility (r = 0.1627, p = 0.001), sperm normal morphology (r = 0.1373, p = 0.004) and sperm DNA fragmentation (r =-0.1248, p = 0.009). Males with an IIEF-5 scores range between 5-11 presented the worst results in terms of sperm progressive motility (p = 0.002), normal morphology (p = 0.001), and SDF levels (p = 0.003). GAD-7 score, as well as anxiety level, was significantly higher in those males with an IIEF-5 score between 5 and 11 (p = 0.000). CONCLUSION: Although current evidence does not demonstrate the importance of spermatozoa in the etiology of pregnancy loss, significant correlations have been observed between impaired sperm quality and low IIEF-5 scores. Also, anxiety is more likely to occur in males with sexual dysfunction.

Purification and characterization of aspartic protease from Aspergillus niger and its efficient hydrolysis applications in soy protein degradation.

BACKGROUND: Adding acid protease to feed can enhance protein digestibility, boost feed utilization, and stimulate the growth of animals in breading industry. In order to obtain an acid protease with high hydrolysis efficiency to plant protein, in this study, an aspartic protease from Aspergillus niger was heterologous expressed in Pichia pastoris (P. pastoris). The enzymatic properties and application in soybean protein degradation were also studied. RESULTS: In our investigation, the high aspartic protease (Apa1) activity level of 1500 U/mL was achieved in 3 L bioreactor. After dialysis and anion exchange chromatography, the total enzyme activity and specific enzyme activity were 9412 U and 4852 U/mg, respectively. The molecular weight of the purified protease was 50 kDa, while the optimal pH and temperature were 3.0 and 50 °C, respectively. It was stable at pH 2.0-5.0 and 30-60 °C. Apa1 was used to hydrolyze soybean isolate protein (SPI) at 40 °C and pH 3.0, and a high hydrolysis degree (DH) of 61.65% was achieved. In addition, the molecular weight distribution of SPI hydrolysis products was studied, the result showed that the hydrolysis products were primarily oligopeptides with molecular weights of 189 Da or below. CONCLUSIONS: In this study, Apa1 was successfully expressed in P. pastoris and high expression level was obtained. In addition, the highest protein hydrolysis rate to SPI degradation so far was achieved. The acid protease in this study provides a new protease that is suitable for the feed industry, which will be very helpful to improve the feed utilization and promote the development of the breeding industry.

Alleviating vacuolar transport improves cellulase production in Trichoderma reesei.

Increasing cellulase production in cellulolytic fungus Trichoderma reesei is of interest for biofuels and biorefineries. Previous studies indicated that secreted protein was occasionally accumulated in vacuoles; this phenomenon has also been reported in T. reesei. Therefore, alleviating vacuolar transport seems to be a promising strategy for improving cellulase production in T. reesei. Herein, we found that knockout of vps10, vps13, and vps21, among 11 vacuolar protein sorting factors, improved cellulase production in T. reesei. The filter paper activity in Δvps10, Δvps13, and Δvps21 increased by 1.28-, 2.45-, and 2.11-fold than that of the parent strain. Moreover, the ß-glucosidase activity in Δvps13 and Δvps21 increased by 3.22- and 3.56-fold after 6 days of fermentation. Furthermore, we also found that the vacuolar trafficking towards vacuoles was partially impaired in three knockout mutants, and disruption of vps13 alleviated the autophagy process. These results indicated that alleviated transport and degradation towards vacuole in Δvps10, Δvps13, and Δvps21 might improve cellulase production. Of note, the expression of cellulase genes in Δvps13 and Δvps21 was dramatically increased in the late induction phase compared to the parent. These results suggested that Vps13 and Vps21 might influence the cellulase production at transcription level. And further transcriptome analysis indicated that increased cellulase gene expression might be attributed to the differential expression of sugar transporters. Our study unravels the effect of alleviating vacuolar transport through knockout vps10, vps13, and vps21 for efficient cellulase secretion, providing new clues for higher cellulase production in T. reesei. KEY POINTS: • Disruption of vps10, vps13 or vps21 improves cellulase production • Vacuolar transport is impaired in three vps KO mutants • Deletion of vps13 or vps21 increases the transcript of cellulase genes in late stage.

Patterns of bacterial distance decay and community assembly in different land-use types as influenced by tillage management and soil layers.

Land use and cover change are major factors driving global change and greatly impact terrestrial organisms, especially soil microbial diversity. Little is known, however, about bacterial diversity, distribution patterns and assembly processes across different land use types. In this study, therefore, we conducted a large-scale field survey of 48 sampling sites, encompassing different land use types in Xuancheng city, China, with different degrees of soil disturbance and different soil horizons. The distance-decay relationships (DDRs), assembly processes and the spatial patterns of soil bacterial communities were investigated based on high-throughput sequencing data. We found that the DDRs might be weakened by anthropogenic disturbances, which were not observed in tilled soils, while a decreasing trend was observed along the soil horizon in untilled soils. The relative importance of environmental factors and geographic distance varied with soil tillage. Specifically, bacterial communities in tilled soils were driven by non-spatially autocorrelated environmental factors, while untilled soils were more susceptible to geographic distance. In addition, the heterogeneity of soil properties, as well as the differences in soil bacterial niche width and niche overlap, determined the assembly processes of the bacterial community, resulting in opposite trends along the soil layers in tilled and untilled soils. These findings expand the current understanding of the biogeography of soil bacterial communities across different land use types.

Merlin functions as a critical regulator in Staphylococcus aureus-induced osteomyelitis.

Merlin is known as a tumor suppressor, while its role in osteomyelitis remains unclear. This study aimed to investigate the role of Merlin in Staphylococcus aureus-induced osteomyelitis and its underlying mechanisms. S. aureus-induced osteomyelitis mouse model was established in Merlinfl/fl Lyz2cre/+ and Merlinfl/fl Lyz2+/+ mice. Bone marrow-derived macrophages (BMDMs) were isolated and stimulated by lipopolysaccharide (LPS). Bioassays, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays, were conducted to determine the levels of target genes or proteins. Immunoprecipitation was applied to determine the interactions between proteins. DCAF1fl/fl mice were further crossed with Lyz2-Cre mice to establish myeloid cell conditional knockout mice (DCAF1fl/fl Lyz2cre/+ ). It was found that the level of Merlin was elevated in patients with osteomyelitis and S. aureus-infected BMDMs. Merlin deficiency in macrophages suppressed the production of inflammatory cytokines and ameliorated the symptoms of osteomyelitis induced by S. aureus. Merlin deficiency in macrophages also suppressed the production of proinflammatory cytokines in BMDMs induced by LPS. The inhibitory effects of Merlin deficiency on the inflammatory response were associated with DDB1-Cul4-associated factor 1 (DCAF1). In summary, Merlin deficiency ameliorates S. aureus-induced osteomyelitis through the regulation of DCAF1.

Psychological stress induces moderate pathology in the ganglion cell layer in mice.

Purpose: Primary open-angle glaucoma (POAG) is a condition with unclear pathogenesis. Researchers have observed an increased incidence of young Chinese POAG patients who manifest significant psychological stress while their intraocular pressure (IOP) is normal or close to normal; we hypothesize that psychological stress may play a causal role in initiating POAG. Methods: Twenty-four male C57BL/6 mice were included and divided randomly into two groups. A chronic unpredictable mild stress (CUMS) mouse model was established to evaluate the effect of psychological stress on glaucoma-related retinal pathologies. Body weight and IOP were recorded weekly. At 5 weeks after the CUMS procedure, a behavior test, serum corticosterone level, retinal nerve fiber layer (RNFL) thickness, retinal ganglion cell (RGC) number and neurotrophic factor expression were evaluated and compared between the CUMS group and the control group. Results: CUMS exposure induced depression-like behaviors, lighter body weight, and increased serum corticosterone levels in mice. RNFL thinning and neural cell loss in the ganglion cell layer (GCL) were observed in CUMS mice without significant IOP elevation. Decreased mRNA expression and protein levels of neurotropic factors in retinas of CUMS mice were observed, especially brain-derived neurotrophic factor (BDNF). Conclusions: The CUMS mouse model demonstrated that psychological stress induced glaucoma-like changes in the retinas of CUMS mice. The mechanism by which psychological stress induces retina defects may be due to a reduced expression of retinal neurotropic factors. Thus, we conclude that psychological stress is causally associated with POAG.

High incidence of sexual dysfunction and timed intercourse was found only in infertile males who with known impairment of sperm quality for a long period: evidence from a hospital-based cross-sectional study.

BACKGROUND: Infertile men with higher sexual dysfunction risk and increased psychological burden, were also associated with more inclined to timed intercourse. Decreased semen quality may have adverse effects on male sexual function. However, it is also likely that many of these sequences do not play a direct role, those negative consequences may depend mainly on the later failed attempting pregnancy. Research is limited in this area. METHODS: This cross-sectional study was based on a group of 509 men who were assessed for couple's infertility at the First Hospital of Jilin University between June 2021 and October 2021. All the men completed a comprehensive questionnaire, and then were divided in two groups. Group A included patients who either never received a routine infertility work-up or done so recently within the last 6 months. Group B included patients who previously received a sperm quality assessment at least 6 months or more prior. Patients were further categorized into three subgroups according to the severity of the decreases in their sperm parameters: severe, mild-moderate, and normozoospermic. RESULTS: The prevalence of erectile dysfunction was higher in Group B Mild-Moderate and Group B Severe in comparison to Group A (OR=1.86 [1.07-3.24], P = 0.027; OR=5.312 [2.69-10.49], P < 0.001, respectively). No significant differences were found between Group A and Group B-normozoospermic. Similar results were observed in the prevalence of premature ejaculation between the groups. Timed intercourse was seen in 11.8% (20/170) of men in Group A and 16.2% (19/117) in Group B-normozoospermic. It was more commonly practiced among infertile men in Group B-Mild-Moderate and Group B Severe, as 28.2% (44/156) and 25.7% (17/66) of these couples had attempted to conceive through timed intercourse (P < 0.001). CONCLUSIONS: Our findings indicate that the severity of sperm quality impairment was negatively associated with sexual dysfunction only in infertile men who with known impairment of sperm quality for a long period. Timed intercourse was more common among these couples. For those individuals had never test their sperm quality, although more than half of these patients showed a decrease in sperm quality, the incidence of sexual dysfunction is relatively low and were comparable to those men examined previously known as normozoospermic.

Engineering the optimum pH of ß-galactosidase from Aspergillus oryzae for efficient hydrolysis of lactose.

ß-Galactosidase (lacA) from Aspergillus oryzae is widely used in the dairy industry. Its acidic pH optimum and severe product inhibition limit its application for lactose hydrolysis in milk. In the present study, structure-based sequence alignment was conducted to determine the candidate mutations to shift the pH optimum of lacA to the neutral range. The Y138F and Y364F mutants shifted the pH optimum of lacA from 4.5 to 5.5 and 6.0, respectively. The acid dissociation constant (pKa) values of catalytic acid/base residues with upwards shift were consistent with the increased pH optimum. All variants in the present study also alleviated galactose inhibition to various extents. Molecular dynamics demonstrated that the less rigid tertiary structures and lower galactose-binding free energy of Y138F and Y364F might facilitate the release of the end product. Both Y138F and Y364F mutants exhibited better hydrolytic ability than lacA in milk lactose hydrolysis. The higher pH optimum and lower galactose inhibition of Y138F and Y364F may explain their superiority over lacA. The Y138F and Y364F mutants in the present study showed potential in producing low-lactose milk, and our studies provide a novel strategy for engineering the pH optimum of glycoside hydrolase.

Subacute dermal toxicity study of bensulfuron-methyl in Sprague-Dawley rats.

Background: Bensulfuron-methyl has recently attracted attention given its widespread use as an herbicide in crops, especially its transdermal safety. However, no dermal toxicity study of this pesticide to mammals has been reported. The present study aims to investigate subacute dermal toxicity of bensulfuron-methyl following repeated doses exposure.Methods: Forty-eight Sprague-Dawley rats were randomly divided into four groups: a normal control group and bensulfuron-methyl groups of different concentrations (250, 500, 1000 mg/kg.bw/day). The rats were topically applied with the substance dermally for 6 h per day for 28 days. At the end of the experiment, all rats were monitored for any changes in their hematological, biochemical parameters, and pathological and histological sections.Results: There were no statistically significant differences (P ≥ 0.05) in the hematological parameters and biochemical parameters. The pathological histological results of rats in the control and the highest concentration group showed no significant abnormalities. The NOAEL of subacute dermal toxicity study was found to be 1000 mg/kg.bw/day in both female and male rats.Conclusion: The result indicated that bensulfuron-methyl is probably safe for humans as a pesticide.

Involvement of mechanosensitive ion channels in the effects of mechanical stretch induces osteogenic differentiation in mouse bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) can be induced to process osteogenic differentiation with appropriate mechanical and/or chemical stimuli. The present study described the successful culture of murine BMSCs under mechanical strain. BMSCs were subjected to 0%, 3%, 8%, 13%, and 18% cyclic tensile strain at 0.5 Hz for 8 hr/day for 3 days. The expression of osteogenic markers and mechanosensitive ion channels was evaluated with real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot. The expression of alkaline phosphatase (ALP) and matrix mineralization were evaluated with histochemical staining. To investigate the effects of mechanosensitive ion channel expression on cyclic tensile strain-induced osteogenic differentiation, the expression of osteogenic markers was evaluated with real-time RT-PCR in the cells without mechanosensitive ion channel expression. This study revealed a significant augment in osteogenic marker in BMSC strained at 8% compared to other treatments; therefore, an 8% strain was used for further investigations. The ALP expression and matrix mineralization were enhanced in osteogenic induced BMSCs subjected to 8% strain after 7 and 14 days, respectively. Under the same conditions, the osteogenic marker and mechanosensitive ion channel expression were significantly promoted. However, the loss function of mechanosensitive ion channels resulted in the inhibition of osteogenic marker expression. This study demonstrated that strain alone can successfully induce osteogenic differentiation in BMSCs and the expression of mechanosensitive ion channels was involved in the process. The current findings suggest that mechanical stretch could function as efficient stimuli to induce the osteogenic differentiation of BMSCs via the activation of mechanosensitive ion channels.

Carbon Dots-in-EuAPO-5 Zeolite: Triple-Emission for Multilevel Luminescence Anti-Counterfeiting.

Multilevel luminescence materials have aroused wide attention for their advanced anti-counterfeiting abilities. However, various complicated stimuli factors involved in multilevel luminescence anti-counterfeiting (MlLA) limit the practical applications of such materials. Herein, carbon dots (CDs) are in situ introduced into Eu-substituted AlPO4 -5 zeolite (named CDs@EuAPO-5) via a solvent-free thermal crystallization method, which exhibits triple emissions including pink fluorescence mainly associated with Eu3+ in the zeolite framework, blue fluorescence and green room temperature phosphorescence (RTP) associated with CDs. CDs are uniformly embedded in the EuAPO-5 zeolite matrix. Such composite displays excellent photo-, thermo-, and solvent resistance, as well as long-term storage-stability. Moreover, the triple emissions of the composite only need two kinds of common excitation lights to trigger, without involving other complicated stimuli. A triple-level luminescence anti-counterfeiting (TlLA) label has been built, realizing facile, quick, and advanced luminescence anti-counterfeiting that is hard to copy.

Evaluation of MYRF as a candidate gene for primary angle closure glaucoma.

PURPOSE: Primary angle-closure glaucoma (PACG) is a leading cause of blindness. Despite tremendous human effort and financial input, no definitive causative gene has been identified either through genome-wide association or Mendelian family studies. In the current study, novel candidate genes for PACG were investigated by studying the variants of nanophthalmos-associated genes. METHODS: A case-control study was conducted that included 45 PACG patients and 12 normal controls with short axial length (AL, less than 23.5 mm but more than 20.5 mm). Whole-exome sequencing (WES) was performed to screen the variants in previously identified nanophthalmos-associated genes, as well as other risk genes. RESULTS: The age range of the 45 PACG patients was 24 to 80 years, with an average AL of 21.87±0.65 mm (range: 20.54-23.45 mm) in the right eye and 21.89±0.64 mm (range 20.60-23.23 mm) in the left eye. Four novel myelin regulatory factor (MYRF) gene missense variants (p.G117S, p.H1057R, p.H230R, and p.R316C) were identified in four out of the 45 enrolled PACG patients, respectively. No MYRF or other nanophthalmos-associated gene variants were detected in the 12 normal controls. CONCLUSIONS: An appropriate approach was adopted to investigate the genetics of PACG through nanophthalmos-associated genes. A genetic variant, MYRF, was identified in four out of 45 PACG patients, which might be a novel candidate gene for PACG.

Naringin inhibits titanium particles-induced up-regulation of TNF-α and IL-6 via the p38 MAPK pathway in fibroblasts from hip periprosthetic membrane.

AIMS: Inflammatory responses to wear debris cause osteolysis that leads to aseptic loosening and hip arthroplasty failure. Wear debris stimulate macrophages and fibroblasts to secret proinflammatory cytokines, including TNF-α and IL-6, which have been specifically implicated in periprosthetic osteolysis and osteoclast differentiation. Naringin has anti-inflammatory effect in macrophages. Moreover, naringin inhibited osteoclastogenesis and wear particles-induced osteolysis. In this study, we examined the potential inhibitory effects of naringin on titanium (Ti) particle-induced proinflammatory cytokines secretion in fibroblasts and the possible underlying molecular mechanisms. MATERIALS AND METHODS: Fibroblasts were isolated from periprosthetic membrane at the time of revision surgery performed due to aseptic loosening after hip arthroplasty and were cultured in the presence or absence of Ti particles, naringin and mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (a selective inhibitor of ERK), SP600125 (a selective inhibitor of JNK), and SB203580 (a selective inhibitor of p38). TNF-α and IL-6 assays were performed using enzyme-linked immunosorbent assay kits. The phosphorylation levels of p38 and nuclear factor kappa B p65 (NF-κB p65) were examined by western blot. RESULTS: Naringin or SB203580 pretreatment significantly suppressed the secretion of TNF-α and IL-6 induced by titanium particles in fibroblasts, while inhibition of ERK or JNK pathways showed no effect on production of TNF-α and IL-6. Moreover, naringin inhibited Ti particle-induced phosphorylation of p38 and p65. CONCLUSIONS: These results indicated that naringin could inhibit Ti particle-induced inflammation in fibroblasts by inhibiting p38 MAPK/NF-κB p65 activity and might be a potential drug for the treatment of inflammatory periprosthetic osteolysis after arthroplasty.