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ABSTRACT: Avian pathogenic Escherichia coli (APEC) is a serious systemic infectious disease in poultry infections, causing severe economic losses to the poultry industry. Previous studies have shown that secretion of virulence proteins was required for the pathogenicity of APEC through the secretion system. Outer membrane vesicles (OMVs) are a generalized secretion system of Gram-negative bacteria that play a key role in the long-distance delivery of virulence factors, but whether they are associated with the pathogenic mechanism of APEC has not been determined. In this study, OMVs were purified and characterized from AE17 (O2 serotype) by ultracentrifugation and density gradient centrifugation and their protein cargo was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, 89Zr was labeled after chelating AE17 OMVs by DFO and positron emission tomography PET imaging was used to track 89Zr-DFO-OMVs in chickens and to pathologically analyze the distribution sites. This study showed that AE17 OMVs were membrane vesicles ranging in size from 20 to 200 nm and proteomic analysis revealed the presence of virulence proteins, including adhesion proteins OmpA, OmpC, OmpF, OmpX, FimH, FimC and FigE, and serum resistance proteins OmpT and MliC and immune response regulator proteins (FliC). In addition, in vivo PET imaging to track the biodistribution of AE17 OMVs showed that AE17 OMVs were taken up by the lung region and the gastrointestinal and renal regions but were not detected in other areas. Pathological analysis of the tissue sites where AE17 OMVs were ingested showed inflammatory responses and damage. These findings suggested that AE17 OMVs not only contained a group of virulence proteins associated with AE17 infection but can also deliver these virulence proteins over long distances and caused tissue inflammatory damage. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of APEC that could aid in the development of vaccines and antibiotics effective against APEC.

Background Continuous cultivation of ginseng crops in fixed plots can lead to disease outbreaks, yield losses and replanting failures. Fallow periods can help restore soil health and increase the sustainability of agricultural systems; however, taking land out of production for extended periods is often not feasible. Short-term fallow periods could restore soil health, but few studies have examined the effects of short-term fallow treatment on the health of soil in ginseng fields. Methods In this preliminary study, we used metagenomic analysis to assess changes in the abundance of major ginseng pathogens and soil health overall following a short-term fallow period in a region in the Changbai Mountains. A sample from a forest plot (Hx0ks), was compared to a sample from a field where ginseng was previously cultivated and then had been left fallow for two years (Hx2), and a sample from a field that had been fallow for two years and was subsequently replanted with ginseng (Clsd). Results Soil that was fallow for two years, and then replanted with ginseng, showed reduced nutrient content and lower diversity of soil bacterial and fungal communities than soil that remained fallow. Candidatus Solibacter (5%) and Rhizomicrobium (3%) were the most abudant bacterial genera in Hx2. Rhizomicrobium (4%) and Gemmatimonas (3%) were the most abundant bacterial genera in Clsd. Mortierella (22%) and Peziza (12%) dominated the fungal community in Hx2. Lecanicillium (38%) and Mortierella (13%) dominated the fungal community in Clsd. Fallow periods also increased the functional diversity of soil as predicted by PICRUSt and decreased the relative abundance of the pathogenic fungi. Conclusions Preliminary findings were consistent with the hypothesis that fallow management in ginseng cultivation can improve soil microbial community structure and function and reduces the number of plant pathogens; however, testing this hypothesis will require replicated plots.

Few studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of the percent visceral adiposity tissue (VAT) area out of the overall abdominal area, averaged across L1-L5 (%VAT), measured by abdominal magnetic resonance imaging (MRI). A genome-wide significant signal was found on chromosome 2q14.3 in the sex-combined GWAS (lead variant rs79837492: Beta per effect allele = -4.76; P = 2.62 × 10-8) and in the male-only GWAS (lead variant rs2968545: (Beta = -6.50; P = 1.09 × 10-9), and one suggestive variant was found at 13q12.11 in the female-only GWAS (rs79926925: Beta = 6.95; P = 8.15 × 10-8). The negatively associated variants were most common in European Americans (T allele of rs79837492; 5%) and African Americans (C allele of rs2968545; 5%) and not observed in Japanese Americans, whereas the positively associated variant was most common in Japanese Americans (C allele of rs79926925, 5%), which was all consistent with the racial/ethnic %VAT differences. In a validation step among UK Biobank participants (N = 23,699 of mainly British and Irish ancestry) with MRI-based VAT volume, both rs79837492 (Beta = -0.026, P = 0.019) and rs2968545 (Beta = -0.028, P = 0.010) were significantly associated in men only (n = 11,524). In the MEC-APS, the association between rs79926925 and plasma sex hormone binding globulin levels reached statistical significance in females, but not in males, with adjustment for total adiposity (Beta = -0.24; P = 0.028), on the log scale. Rs79837492 and rs2968545 are located in intron 5 of CNTNAP5, and rs79926925, in an intergenic region between GJB6 and CRYL1. These novel findings differing by sex and racial/ethnic group warrant replication in additional diverse studies with direct visceral fat measurements.

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. The lack of targeted therapies and poor patient outcome have fostered efforts to discover new molecular targets to treat patients with TNBC. Here, we showed that baculoviral IAP repeat containing 6 (BIRC6) is overexpressed and positively correlated with epidermal growth factor (EGF) receptor (EGFR) in TNBC cells and tissues and that BIRC6 overexpression is associated with poor patient survival. Mechanistic studies revealed that BIRC6 stability is increased by EGF-JNK signaling, which prevents ubiquitination and degradation of BIRC6 mediated by the E3 ubiquitin ligase HECTD1. BIRC6 in turn decreases SMAC expression by inducing the ubiquitin-proteasome pathway, thereby antagonizing apoptosis and promoting the proliferation, colony formation, tumorsphere formation, and tumor growth capacity of TNBC cells. Therapeutically, the PEGylated cationic lipid nanoparticle (pCLN)-assisted delivery of BIRC6 small interfering RNA (siRNA) efficiently silences BIRC6 expression in TNBC cells, thus suppressing TNBC cell growth in vitro and in vivo, and its antitumor activity is significantly superior to that of the EGFR inhibitor gefitinib. Our findings identify an important regulatory mechanism of BIRC6 overexpression and provide a potential therapeutic option for treating TNBC.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.

In this study, we report the effects of hydroxypropyl methylcellulose (HPMC) and KH2PO4 on the water resistance of magnesium oxychloride cement (MOC), a novel bone cement composite. Different MOC samples were soaked in simulated body fluid (SBF). After soaking for 7–56 d, the surfaces of the experimental group (1 wt.% HPMC/2 wt.% KH2PO4-MOC) and control group (2 wt.% KH2PO4-MOC) appeared pores, which grew with increasing immersion time. Compared with the control group, the experimental group had smaller pore sizes and a denser surface. Furthermore, the compressive strength in the experimental group increased from 35.1 ± 1.9 MPa to 41.8 ± 2.3 MPa, and the softening coefficient increased from 0.34 to 0.45. Thus, HPMC could improve the water erosion resistance of the MOC. The implantation study of the femoral defects in rats showed that the sample modified by 1 wt.% HPMC/2 wt.% KH2PO4 had good biocompatibility and biodegradability. The results indicate that the modification of MOC with HPMC and KH2PO4 is a promising technique to form biodegradable bone repair materials and has good application prospects in the field of biomedical materials.

Dental calculus has long been considered as a vital contributing factor of periodontal diseases. Our review focuses on the role of dental calculus as a repository and discusses the bioinformation recently reported to be concealed in dental calculus from three perspectives: time-varying oral condition, systemic diseases, and anthropology at various times. Molecular information representing an individual’s contemporary oral health status could be detected in dental calculus. Additionally, pathogenic factors of systemic diseases were found in dental calculus, including bacteria, viruses and toxic heavy metals. Thus, dental calculus has been proposed to play a role as biological data storage for detection of molecular markers of latent health concerns. Through the study of environmental debris in dental calculus, an overview of an individual’s historical dietary habits and information about the environment, individual behaviors and social culture changes can be unveiled. This review summarizes a new role of dental calculus as a repository of bioinformation, with potential use in the prediction of oral diseases, systemic diseases, and even anthropology.

Dental caries is among the most prevalent chronic oral infectious diseases. Streptococcus mutans, a major cariogenic bacterial species, possesses several cariogenicity-associated characteristics, including exopolysaccharides (EPS) synthesis, biofilm formation, acidogenicity, and aciduricity. Nicotinamide (NAM), a form of vitamin B3, is a non-toxic, orally available, and inexpensive compound. The present study investigated the inhibitory effects of NAM on the cariogenic virulence factors of S. mutans in vitro and in vivo. NAM inhibited the growth of S. mutans UA159 and the clinical isolates. In addition, there was a decrease in the acid production and acid tolerance ability, as well as biofilm formation and EPS production of S. mutans after NAM treatment. Global gene expression profiling showed that 128 and 58 genes were significantly downregulated and upregulated, respectively, in NAM-treated S. mutans strains. The differentially expressed genes were mainly associated with carbohydrate transport and metabolism, glycolysis, acid tolerance. Moreover, in a rat caries model, NAM significantly reduced the incidence and severity of smooth and sulcal-surface caries in vivo. NAM exhibited good antimicrobial properties against S. mutans, indicating its potential value for antibiofilm and anti-caries applications.

RIO kinase 2 has emerged as a critical kinase for ribosome maturation, and recently it has also been found to play a fundamental role in cancer, being involved in the occurrence and progression of glioblastoma, liver cancer, prostate cancer, non-small cell lung cancer, and acute myeloid leukemia. However, our knowledge in this regard is fragmented and limited and it is difficult to determine the exact role of RIO kinase 2 in tumors. Here, we conducted an integrated pan-cancer analysis comprising 33 cancer-types to determine the function of RIO kinase 2 in malignancies. The results show that RIO kinase 2 is highly expressed in all types of cancer and is significantly associated with tumor survival, metastasis, and immune cell infiltration. Moreover, RIO kinase 2 alteration via DNA methylation, and protein phosphorylation are involved in tumorigenesis. In summary, RIO kinase two serves as a promising target for the identification of cancer and increases our understanding of tumorigenesis and cancer progression and enhancing the ultimate goal of improved treatment for these diseases.

A large proportion of bladder cancer (BLCA) patients suffer from malignant progression to life-threatening muscle-invasive bladder cancer (MIBC). Inflammation is a critical event in cancer development, but little is known about the role of inflammation in BLCA. In this study, the expression of the innate immune sensor AIM2 is much lower in high-grade BLCA and positively correlates with the survival rates of the BLCA patients. A novel AIM2 overexpressed BLCA model is proposed to investigate the impact of AIM2 on BLCA development. Mice inoculated with AIM2-overexpressed cells show tumor growth delay and prolonged survival compared to the control group. Meanwhile, CD11b+ cells significantly infiltrate AIM2-overexpressed tumors, and AIM2-overexpression in 5637 cells enhanced the inflammasome activation. In addition, oligodeoxynucleotide (ODN) TTAGGG (A151), an AIM2 inflammasome inhibitor, could abolish the elevation of AIM2-induced cleavage of inflammatory cytokines and pyroptosis. Orthotopic BLCA by AIM2-overexpressed cells exhibits a better response to Bacillus Calmette-Guérin (BCG) immunotherapy. Overall, AIM2 inflammasome activation can inhibit the BLCA tumorigenesis and enhance the therapeutic effect of BCG in BLCA. This study provides new insights into the anti-tumor effect of AIM2 inflammasome activation in BLCA and the immunotherapeutic strategy of BLCA development.

ABSTRACT Lysine acetylation, a ubiquitous and dynamic regulatory posttranslational modification (PTM), affects hundreds of proteins across all domains of life. In bacteria, lysine acetylation can be found in many essential pathways, and it is also crucial for bacterial virulence. However, the biological significance of lysine acetylation events to bacterial virulence factors remains poorly characterized. In Streptococcus mutans, the acetylome profiles help identify several lysine acetylation sites of lactate dehydrogenase (LDH), which catalyzes the conversion of pyruvate to lactic acid, causing the deterioration of teeth. We investigated the regulatory mechanism of LDH acetylation and characterized the effect of LDH acetylation on its function. We overexpressed the 15 Gcn5 N-acetyltransferases (GNAT) family members in S. mutans and showed that the acetyltransferase ActA impaired its acidogenicity by acetylating LDH. Additionally, enzymatic acetyltransferase reactions demonstrated that purified ActA could acetylate LDH in vitro, and 10 potential lysine acetylation sites of LDH were identified by mass spectrometry, 70% of which were also detected in vivo. We further demonstrated that the lysine acetylation of LDH inhibited its enzymatic activity, and a subsequent rat caries model showed that ActA impaired the cariogenicity of S. mutans. Collectively, we demonstrated that ActA, the first identified and characterized acetyltransferase in S. mutans, acetylated the LDH enzymatically and inhibited its enzymatic activity, thereby providing a starting point for the further analysis of the biological significance of lysine acetylation in the virulence of S. mutans. IMPORTANCE Lysine acetylation, a dynamic regulatory posttranslational modification, remains poorly characterized in bacteria. Hundreds of proteins have been identified to be acetylated in bacteria, with advances made in acetylome analyses. However, the regulatory mechanisms and functional significance of the majority of these acetylated proteins remain unclear. We analyzed the acetylome profiles of Streptococcus mutans and found that lactate dehydrogenase (LDH) contains several lysine acetylation sites. We also demonstrated that the acetyltransferase ActA, a member of the Gcn5 N-acetyltransferases (GNAT) family in S. mutans, acetylated LDH, inhibited its enzymatic ability to catalyze the conversion of pyruvate to lactic acid, and impaired its cariogenicity in a rat caries model. Therefore, LDH acetylation might be a potential target that can be exploited in the design of novel therapeutics to prevent dental caries.

In order to complete the various tasks in advanced space missions, such as communication, navigation, and remote sensing, single complicated spacecraft and many distributed spacecraft systems have been launched into orbit [...]

Abstract Background Kinases play critical role in clear-cell renal cell carcinoma (ccRCC). We aim to exploit novel kinase that is both protumorigenic and drugable in ccRCC. Methods Reproduction of public datasets with validation using microarray was performed to identify candidate gene. Functionality was studied using multi-omics with validation in vitro and in vivo. Results 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4) was differentially expressed showing significantly higher expression in tumor than in normal kidney. PFKFB4 overexpression was associated with advanced tumor grade, stage and worsened prognosis. PFKFB4-knockdown significantly impaired fitness in cell proliferation, migration and wound healing. Despite being recurrently deleted on 3p, PFKFN4 mRNA remained actively transcribed by HIF1α. Metabolomics showed overexpressed PFKFB4 showed enriched metabolites in pentose phosphate pathway (PPP). Phosphoproteomics and immunoprecipitation showed PFKFB4 also phosphorylated NCOA3 which interacted with FBP1 to counteract overactive PPP flux, forming a regulatory loop. PFKFB4-knockdown overcame resistance to Sunitinib in vitro and in vivo both in xenograft and tail-vein injection murine models. Conclusion We concluded PFKFB4 was associated with PPP activity and the fine-tuning of which was mediated by its phosphorylation of NCOA3. Targeting PFKFB4 held promise to combat resistance to Sunitinib.

Abstract The performance of the distributed coherent aperture radar (DCAR) is heavily influenced by the antenna positions. Therefore, an antenna position optimization method is proposed based on the adaptive genetic algorithm with a self‐supervised differential operator. In the proposed method, the antenna positions are firstly coded as the chromosomes of the population with multiple constraints, and the reciprocal of the peak side lobe level (PSLL) of the beam pattern is calculated as the fitness function for optimization. Then, the adaptive probabilities are calculated for the crossover and mutation of chromosomes and a self‐supervised differential operator is utilized in the mutation. Finally, the optimal antenna positions for DCAR can be obtained with the lowest PSLL compared with the existing methods. The effectiveness of the proposed method is verified by linear and planar DCARs, respectively.

The statics and dynamics of supercooled water in the hydration layer of poly(ethylene glycol) (PEG) were studied by a combination of quasi-elastic neutron scattering (QENS) and molecular dynamics (MD) simulations. Two samples, that is, hydrogenated PEG/deuterated water (h-PEG/D2O) and fully deuterated PEG/hydrogenated water (d-PEG/H2O) with the same molar ratio of ethylene glycol (EG) monomer to water, 1:1, are compared. The QENS data of h-PEG/D2O show the dynamics of PEG, and that of d-PEG/H2O reveals the motion of water. The temperature-dependent elastic scattering intensity of both samples has shown transitions at supercooled temperature, and these transition temperatures depend on the energy resolution of the instruments. Therefore, neither one is a phase transition, but undergoes dynamic process. The dynamic of water can be described as an Arrhenius to super-Arrhenius transition, and it reveals the hydrogen bonding network relaxation of hydration water around PEG at supercooled temperature. Since the PEG-water hydrogen bond structural relaxation time from MD is in good agreement with the average relaxation time from QENS (d-PEG/H2O), MD may further reveal the atomic pictures of the supercooled hydration water. It shows that hydration water molecules form a series of pools around the hydrophilic oxygen atom of PEG. At supercooled temperature, they have a more bond ordered structure than bulk water, proceed a trapping sites diffusion on the PEG surface, and facilitate the structural relaxation of PEG backbone.

In response to strong signals, several types of immune cells release extracellular traps (ETs), which are web-like structures consisting of DNA decorated with various protein substances. This process is most commonly observed in neutrophils. Over the past two decades, ET formation has been recognized as a unique mechanism of host defense and pathogen destruction. However, the role of ETs in sterile inflammation has only been studied extensively in recent years. Ischemia reperfusion injury (IRI) is a type of sterile inflammatory injury. Several studies have reported that ETs have an important role in IRI in various organs. In this review, we describe the release of ETs by various types of immune cells and focus on the mechanism underlying the formation of neutrophil ETs (NETs). In addition, we summarize the role of ETs in IRI in different organs and their effects on tumors. Finally, we discuss the value of ETs as a potential therapeutic target for organ IRI and present possible challenges in conducting studies on IRI-related ETs as well as future research directions and prospects.

The purpose of this study is to confirm whether the 'cold-hot properties' of traditional Chinese medicine (TCM) have modern scientific connotations on the molecular level of compounds using machine learning (ML).In this study, 393 Chinese herbs were selected, modeling was based on three ML algorithms, and the voting fusion algorithm was used to construct the fusion model. According to the ROC area under the curve (AUC), the cold-hot herb property classification model was screened. The a priori and K-means algorithms were used to mine key molecules related to cold-hot properties.The AUC of the ML models and fusion models under the ROC curve after 10 rounds of folding cross-verification was above 0.75. Mining obtained 15 cold key compounds (CKCs), 26 hot key compounds (HKCs), a CKC structure similarity of 0.75 on average, and an HKC structure similarity of 0.69 on average. The average similarity between the molecular structures of CKCs compounds and HKCs compounds was 0.18, lower than 0.5. Twelve physical and chemical indices, such as molecular weight (MW) and molecular hydrophobicity (Alogp), had a statistically significant difference in molecular characteristics (P

The global industrialization accelerates the use of fossil fuels and hence the excessive emissions of greenhouse gasses, especially carbon dioxide (CO2), which poses a serious threat to the ecological environment. CO2 capture is considered as a potential strategy to reduce the amount of CO2 released into the atmosphere. The development of adsorption materials that are both economically feasible and effective is the most critical issue. Biochar is a promising candidate for CO2 capture among the capture materials. It offers a diverse range of raw materials and a lower environmental impact than other adsorbent materials. Even though pristine biochar could be employed directly to CO2 capture, it generally exhibits a poor adsorption performance. Therefore, biochar needs to be modified in practical applications to improve physicochemical properties such as specific surface area, pore structure, and surface functional groups. This paper summaries recent research advances in biochar-based adsorbents for CO2 adsorption. Pre-combustion capture technology and post-combustion capture technology are investigated. The production of biochar and the influence of raw materials and process conditions on the adsorption capacity of CO2 are described in detail. The mechanism of CO2 adsorption on biochar is also discussed, which summarized physical and chemical adsorption, respectively, as well as the corresponding presentation of some current methods of physical/chemical modification of biochar. Finally, the future prospects are proposed in order to provide a guideline for the adsorption of CO2 by biochar. Despite the progress made in the production of biochar for CO2 adsorption, more efforts are needed to produce biochar with higher adsorption capacity and long-term stability for large-scale CO2 capture.

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS.

Despite promising breakthroughs in diagnosing and treating acute coronary syndromes, cardiovascular disease’s high global mortality rate remains indisputable. Nearly half of these patients died of ischemic heart disease. Primary percutaneous coronary intervention (PCI) and coronary artery bypass grafting can rapidly restore interrupted blood flow and become the most effective method for salvaging viable myocardium. However, restoring blood flow could increase the risk of other complications and myocardial cell death attributed to myocardial ischemia-reperfusion injury (IRI). How to reduce the damage of blood reperfusion to ischemic myocardium has become an urgent problem to be solved. In preclinical experiments, many treatments have substantial cardioprotective effects against myocardial IRI. However, the transition from these cardioprotective therapies to clinically beneficial therapies for patients with acute myocardial infarction remains elusive. The reasons for the failure of the clinical translation may be multi-faceted, and three points are summarized here: (1) Our understanding of the complex pathophysiological mechanisms of myocardial IRI is far from enough, and the classification of specific therapeutic targets is not rigorous, and not clear enough; (2) Most of the clinical patients have comorbidities, and single cardioprotective strategies including ischemia regulation strategies cannot exert their due cardioprotective effects under conditions of hyperglycemia, hypertension, hyperlipidemia, and aging; (3) Most preclinical experimental results are based on adult, healthy animal models. However, most clinical patients had comorbidities and received multiple drug treatments before reperfusion therapy. In 2019, COST Action proposed a multi-target drug combination initiative for prospective myocardial IRI; the optimal cardioprotective strategy may be a combination of additive or synergistic multi-target therapy, which we support. By establishing more reasonable preclinical models, screening multi-target drug combinations more in line with clinical practice will benefit the translation of clinical treatment strategies.

The alteration of glycometabolism is a characteristic of cancer cells. Long non-coding RNAs (lncRNAs) have been documented to occupy a considerable position in glycometabolism regulation. This research aims to construct an effective prediction model for the prognosis of bladder cancer (BC) based on glycometabolism-associated lncRNAs (glyco-lncRNAs). Pearson correlation analysis was applied to get glyco-lncRNAs, and then, univariate cox regression analysis was employed to further filtrate survival time-associated glyco-lncRNAs. Multivariate cox regression analysis was utilized to construct the prediction model to divide bladder cancer (BC) patients into high- and low-risk groups. The overall survival (OS) rates of these two groups were analyzed using the Kaplan–Meier method. Next, gene set enrichment analysis and Cibersortx were used to explore the enrichment and the difference in immune cell infiltration, respectively. pRRophetic algorithm was applied to explore the relation between chemotherapy sensitivity and the prediction model. Furthermore, reverse transcriptase quantitative polymerase chain reaction was adopted to detect the lncRNAs constituting the prediction signature in tissues and urine exosomal samples of BC patients. A powerful model including 6 glyco-lncRNAs was proposed, capable of suggesting a risk score for each BC patient to predict prognosis. Patients with high-risk scores demonstrated a shorter survival time both in the training cohort and testing cohort, and the risk score could predict the prognosis without depending on the traditional clinical traits. The area under the receiver operating characteristic curve of the risk score was higher than that of other clinical traits (0.755 > 0.640, 0.485, 0.644, or 0.568). The high- and low-risk groups demonstrated very distinct immune cells infiltration conditions and gene set enriched terms. Besides, the high-risk group was more sensitive to cisplatin, docetaxel, and sunitinib. The expression of lncRNA AL354919.2 featured with an increase in low-grade patients and a decrease in T3-4 and Stage III–IV patients. Based on the experiment results, lncRNA AL355353.1, AC011468.1, and AL354919.2 were significantly upregulated in tumor tissues. This research furnishes a novel reference for predicting the prognosis of BC patients, assisting clinicians with help in the choice of treatment.

Corynebacterium matruchotii is a reported calcifying bacterium that can usually be isolated from dental calculus and induce mineralization in vitro. In recent years, based on in situ hybridization probe and sequencing technology, researchers have discovered the central “pillar” role of C. matruchotii in supragingival plaque, and many studies focused on bacterial interactions in the biofilm structure dominated by C. matruchotii have been conducted. Besides, C. matruchotii seems to be an indicator of “caries-free” oral status according to imaging and sequencing studies. Therefore, in this review, we summarize C. matruchotii ‘s role in supragingival plaque based on the structure, interactions, and potential connections with oral diseases.

Porcine circovirus type 4 (PCV4) is a newly emerging pathogen that was first detected in 2019 and is associated with diverse clinical signs, including respiratory and gastrointestinal distress, dermatitis and various systemic inflammations. It was necessary to develop a sensitive and specific diagnostic method to detect PCV4 in clinical samples, so in this study, a multienzyme isothermal rapid amplification (MIRA) assay was developed for the rapid detection of PCV4 and evaluated for sensitivity, specificity and applicability. It was used to detect the conserved Cap gene of PCV4, operated at 41°C and completed in 20 min. With the screening of MIRA primer-probe combination, it could detect as low as 101 copies of PCV4 DNA per reaction and was highly specific, with no cross-reaction with other pathogens. Further assessment with clinical samples showed that the developed MIRA assay had good correlation with real-time polymerase chain reaction assay for the detection of PCV4. The developed MIRA assay will be a valuable tool for the detection of the novel PCV4 in clinical samples due to its high sensitivity and specificity, simplicity of operation and short testing time.

Ciliates are unique in having nuclear dimorphism (i.e., possessing both a germline micronucleus and a somatic macronucleus in one cell), and undergo dramatic changes during their sexual process (known as conjugation). Here we investigate the nuclear events and morphogenetic processes during conjugation in the freshwater species Euplotes aediculatus. In addition, three conjugation-related pheromone genes were sequenced and analyzed. The results indicate that: (i) the 65-hour-long conjugation process includes five nuclear divisions, i.e., three prezygotic divisions (mitosis, meiosis I and II) and two postzygotic divisions; (ii) the ciliature reorganizes twice during conjugation with the frontoventral-transverse cirral anlagen regenerating during both morphogenetic events and breaking apart in a 3:3:3:2:2 pattern; and (iii) each of three pheromone genes contains a 444 bp coding region and encodes 147 amino acid polypeptides. These results suggest a broadly shared morphogenetic pattern during conjugation in Euplotes species and provide new information for studies on the evolutionary history of pheromone genes.

Abstract Background The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women. Methods We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHMmolar) and adjusted for creatinine and potential confounders. Results Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04–1.68) and 1.26 (95% CI 0.96–1.66) (P trend = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA ORT3 vs T1 = 2.66, 95% CI 1.39–5.12, P trend = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05–1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (ORabove vs below median = 1.59, 95% CI 1.01–2.48). Conclusions Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.

Herein, we describe a yeast cell-based assay system to analyze SNAP25-targeting botulinum neurotoxins (BoNTs). BoNTs are protein toxins, and, upon incorporation into neuronal cells, their light chains (BoNT-LCs) target specific synaptosomal N-ethylmaleimide-sensitive attachment protein receptor (SNARE) proteins, including synaptosomal-associated protein 25 (SNAP25). BoNT-LCs are metalloproteases, and each BoNT-LC recognizes and cleaves conserved domains in SNAREs termed the SNARE domain. In the budding yeast Saccharomyces cerevisiae, the SNAP25 ortholog Spo20 is required for production of the spore plasma membrane; thus, defects in Spo20 cause sporulation deficiencies. We found that chimeric SNAREs in which SNARE domains in Spo20 are replaced with those of SNAP25 are functional in yeast cells. The Spo20/SNAP25 chimeras, but not Spo20, are sensitive to digestion by BoNT-LCs. We demonstrate that spo20∆ yeasts harboring the chimeras exhibit sporulation defects when various SNAP25-targeting BoNT-LCs are expressed. Thus, the activities of BoNT-LCs can be assessed by colorimetric measurement of sporulation efficiencies. Although BoNTs are notorious toxins, they are also used as therapeutic and cosmetic agents. Our assay system will be useful for analyzing novel BoNTs and BoNT-like genes, as well as their manipulation.

Chronic obstructive pulmonary disease (COPD) is one of the most common pulmonary diseases. Evidence suggests that dysbiosis of pulmonary microbiota leads to the COPD pathological process. Yifei Sanjie Formula (YS) is widely used to treat diseases in respiratory systems, yet little is known about its mechanisms. In the present study, we first established the fingerprint of YS as the background for UHPLC-QTOF-MS. Components were detected, including alkaloids, amino acid derivatives, phenylpropanoids, flavonoids, terpenoids, organic acids, phenols, and the like. The therapeutic effect of YS on COPD was evaluated, and the pulmonary function and ventilatory dysfunction (EF50, TV, and MV) were improved after the administration of YS. Further, the influx of lymphocytes was inhibited in pulmonary parenchyma, accompanied by down-regulation of inflammation cytokines via the NLRP3/caspase-1/IL-1β signaling pathway. The severity of pulmonary pathological damage was reversed. Disturbed pulmonary microbiota was discovered to involve an increased relative abundance of Ralstonia and Mycoplasma and a decreased relative abundance of Lactobacillus and Bacteroides in COPD animals. However, the subversive effect was shown. The abundance and diversity of pulmonary microflora were remodeled, especially increasing beneficial genua Lactobacillus and Bacteroides, as well as downregulating pathogenic genua Ralstonia and Mycoplasma in the YS group. Environmental factor correlation analysis showed that growing pulmonary microbiota was positively correlated with the inflammatory factor, referring to Ralstonia and Mycoplasma, as well as negatively correlated with the inflammatory factor, referring to Lactobacillus and Bacteroides. These results suggest that the effects of YS involved remodeling lung microbes and anti-inflammatory signal pathways, revealing that intervention microbiota and an anti-inflammatory may be a potential therapeutic strategy for COPD.

The toxic heavy metal cadmium (Cd) is easily absorbed and accumulated in crops and affects human health through the food chains. Sunflower (Helianthus annuus L.) is a globally important oil crop. In this study, two sunflower cultivars 62\3 (high Cd) and JB231AC (low Cd), were chosen to compare physiological and transcriptomic responses at different Cd concentrations (0, 25, 50, and 100 μM). The results showed that JB231AC had better Cd tolerance than 62\3. The contents of H2O2 and MDA (malondialdehyde) in 62\3 were lower than that in JB231AC under Cd stress, but the activities of SOD (superoxide dismutase) and POD (peroxidase) in JB231AC were higher than in 62\3, which indicated that JB231AC had a strong ability to remove reactive oxygen species (ROS)-induced toxic substances. Many deferentially expressed ABC (ATP-binding cassette) and ZIP (Zn-regulated transporter, Iron-regulated transporter-like protein) genes indicated that the two gene families might play important roles in different levels of Cd accumulation in the two cultivars. One up-regulated NRAMP (Natural resistance-associated macrophage protein) gene was identified and had a higher expression level in 62\3. These results provide valuable information to further understand the mechanism of Cd accumulation and provide insights into breeding new low Cd sunflower cultivars.

AimThe action of immune checkpoint inhibition (ICI) largely depends on antibody-dependent cellular phagocytosis (ADCP). We thus aim to develop ADCP-based ccRCC risk stratification as both prognostic and therapeutic markers of ICI.MethodGenomic data from multiple public datasets (TCGA, etc.) were integrated. A cancer-intrinsic ADCP gene set for ccRCC tailored from a recent report was constructed based on the association with prognosis, immune infiltrates, and response to ICI. Therapeutic potential was profiled using genome-drug sensitivity datasets.ResultsADCP genes were selected from a recent CRISPR/Cas9 screen report. Following a four-module panel based on clinical traits, we generated a six-gene signature (ARPC3, PHF19, FKBP11, MS4A14, KDELR3, and CD1C), which showed a strong correlation with advanced grade and stage and worsened prognosis, with a nomogram showing predictive efficacies of 0.911, 0.845, and 0.867 (AUC) at 1, 3, and 5 years, respectively. Signatures were further dichotomized, and groups with a higher risk score showed a positive correlation with tumor mutation burden, higher expressions of inhibitory checkpoint molecules, and increased antitumor immune infiltrates and were enriched for antitumor immune pathways. The high risk-score group showed better response to ICI and could benefit from TKIs of axitinib, tivozanib, or sorafenib, preferentially in combination, whereas sunitinib and pazopanib would better fit the low risk-score group.ConclusionHere we showed a six-gene ADCP signature that correlated with prognosis and immune modulation in ccRCC. The signature-based risk stratification was associated with response to both ICI and tyrosine kinase inhibition in ccRCC.

Tuberculosis (TB) is a life-threatening infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). Timely diagnosis and effective treatment are essential in the control of TB. Conventional smear microscopy still has low sensitivity and is unable to reveal the drug resistance of this bacterium. The traditional culture-based diagnosis is time-consuming, since usually the results are available after 3–4 weeks. Molecular biology methods fail to differentiate live from dead M. tuberculosis, while diagnostic immunology methods fail to distinguish active from latent TB. In view of these limitations of the existing detection techniques, in addition to the continuous emergence of multidrug-resistant and extensively drug-resistant TB, in recent years there has been an increase in the demand for simple, rapid, accurate and economical point-of-care approaches. This review describes the development, evaluation, and implementation of conventional diagnostic methods for TB and the rapid new approaches for the detection of M. tuberculosis.

Abstract Background We aim to explore association between copy number alteration (CNA) and sensitivity to common tyrosine kinase inhibitors (TKIs) used in clear-cell renal cell carcinoma (ccRCC) treatment. Methods CNA with related sensitivity profiles were extracted from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and was cross-referenced with common CNA in ccRCC in the Cancer Genome Atlas (TCGA) dataset. Functional annotation was profiled using GSEA and NET-GE. Target genes within cytobands of interest were screened in silico and validated in vitro using proliferation assays in A498 and 786-O ccRCC cells. Results Four TKIs (Sunitinib, Cabozantinib, Axitinib and Sorafenib) that were clinically used in ccRCC were selected. In silico analysis showed gain of 20q (+20q) occurred in ~ 23% of cases and was associated with resistance to all four TKIs; loss of 14q (−14q) occurred in ~ 39% of cases and was associated with resistance to Sunitinib and Sorafenib; loss of 18p (−18p) occurred in ~ 39% of cases and was associated with sensitivity to Sunitinib and Sorafenib. All 3 CNAs were associated with worsened prognosis, respectively. Candidate target genes included of RBL1 on 20q, KLHL33 on 14q and ARHGAP28 on18q. In vitro validation showed RBL1 overexpression induced resistance to Sunitinib and Cabozantinib; KLHL33 silencing induced resistance to Sunitinib; ARHGAP28 silencing induced sensitivity to Cabozantinib. Functional annotation indicated FoxO signaling, hypoxic response and Wnt pathway, and Rho-related cellular adhesion were mechanistically associated with +20q, −14q and −18p, respectively. Conclusion Common CNAs in ccRCC are associated with cancer-intrinsic cross-sensitivity to common TKIs. Further validation and functional analyses are therefore needed.

Abstract Background Heterotrichous ciliates are common members of microeukaryote communities which play important roles in both the transfer of material and the flow of energy in aquatic food webs. This group has been known for over two centuries due to their large body size and cosmopolitan distribution. Nevertheless, species identification and phylogenetic relationships of heterotrichs remain challenging due to the lack of accurate morphological information and insufficient molecular data. Results The morphology and phylogeny of two heterotrichous ciliates, namely Gruberia foissneri spec. nov. and Linostomella vorticella (Ehrenberg, 1833) Aescht in Foissner et al., 1999, were studied using rigorous methods (living morphology, stained preparations, and small subunit rDNA sequence data). Gruberia foissneri spec. nov. is morphologically very similar to G. uninucleata Kahl, 1932, however, it can be distinguished from the latter by having more ciliary rows (about 32 vs. about 20) and macronuclear shape (sausage-shaped vs. ellipsoid). Based on a combination of previous and present studies, an improved diagnosis of L. vorticella is supplied and several taxonomic anomalies are clarified. In addition, phylogenetic analyses based on SSU rDNA sequence data support the generic assignment of these two species. Conclusions Modern ciliate taxonomy should be performed by means of detailed living observation, stained preparations and molecular information. For those species that have been reported in previous studies, it is necessary to provide as much useful information as possible using state-of-the-art methods in order to resolve taxonomic anomalies.

Abstract Background Chronic kidney disease (CKD) patients, especially those with end stage renal disease (ESRD) undergoing hemodialysis (HD), exhibit high prevalence of periodontitis. This cross-sectional study aimed to investigate the periodontal status of HD patients and its relationship with salivary microbiome. Methods One hundred eight HD patients and one hundred healthy control individuals were recruited. They were subjected to periodontal examination followed by saliva samples collection for 16S rRNA gene sequencing. Results The HD patients were with worse periodontal health status, and exhibited higher salivary microbial diversity and lower richness. The periodontal pathogens were significantly enriched in the HD patients. The inferred functional analyze showed microbes enriched in the HD patients were mainly related to metabolism. Despite the periodontal status and overall structure of the microbiome were not significantly altered as the HD duration prolonged, the abundance of Lachnospiraceae [G-2] sp. |HMT_096| is positively correlated with the duration of HD and the community periodontal index (CPI). Five OTUs (operational taxonomic units) belonging to the phyla Firmicutes were enriched as the duration prolonged, and four OTUs originated from the phyla Proteobacteria were negatively related with the CPI index. ESRD patients undergoing HD exhibited microbiota structural, compositional and functional differences compared with the healthy controls. And the species changed as the duration of hemodialysis prolonged. Conclusions End stage renal disease changes salivary microbiome and is a risk factor for oral dysbiosis.

Abstract Background Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive. Methods We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro. Results ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest. Conclusion Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed.

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population‐specific genetic variants associated with liver fat. We conducted a genome‐wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population‐based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin‐like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10−15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA‐IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10−8) was also observed. Rs7724941 was associated with HOMA‐IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high‐density lipoprotein (beta = −0.046; P = 0.04), and sex hormone binding globulin (beta = −0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

Abstract In this paper, a delayed virus model with two different transmission methods and treatments is investigated. This model is a time-delayed version of the model in (Zhang et al. in Comput. Math. Methods Med. 2015:758362, 2015). We show that the virus-free equilibrium is locally asymptotically stable if the basic reproduction number is smaller than one, and by regarding the time delay as a bifurcation parameter, the existence of local Hopf bifurcation is investigated. The results show that time delay can change the stability of the endemic equilibrium. Finally, we give some numerical simulations to illustrate the theoretical findings.

Fabry-Perot (F-P) filter based fiber Bragg grating (FBG) demodulation has been widely applied in many areas. However, the F-P filter suffers from random fluctuation in wavelength scanning when the ambient temperature changes severely, which reduces the demodulation accuracy inevitably. In this paper, a demodulation method based on an etalon and a fiber-optic Michelson interferometer is proposed to improve the demodulation accuracy in an environment with variable temperature. The experiment is carried out by constructing an interferometer with long-optical path difference (OPD). When the environment temperature increases from 20 °C to 60 °C in 30 minutes, the results show that the error of the proposed method is reduced from ± 20.39 pm to ± 6.89 pm. The standard deviation is 3.11 pm, which is reduced by 43.92% compared with the etalon-based demodulation method.

In recent years, Convolutional neural networks (CNNs) have achieved start-of-art performance in the fault diagnosis field. If there is no available information on the unseen operating conditions, the model trained on the seen operating condition cannot perform well. One of the feasible strategies is to enhance the generalization ability of the network on various seen operating conditions. We introduce the center loss to the traditional CNN and build an end-to-end fault diagnosis framework (called CNN-C). By minimizing the intra-class variations, center loss cluster the learned features across various seen operating conditions. With the joint supervision of the center loss and the softmax loss, the learned features of the same class could minimize the domain difference across various seen operating conditions while the features of different classes are separable. The generalization ability of network is improved on unseen operating conditions. Compared with the shallow methods and traditional CNN, the proposed method is promising to deal with the fault diagnosis tasks of the bearing and gearbox.

Calibration by hydrogen cyanide (HCN) absorption spectrum can make the fiber Bragg grating (FBG) demodulation system immune to environment temperature changes. The transmittance function of Fabry-Perot (F-P) filter will result in the distortion of the HCN absorption peaks. A demodulation scheme based on deconvolution is proposed to eliminate the impact of the F-P filter. A recovered HCN absorption spectrum with deeper, narrower and more symmetrical absorption peaks is obtained for the Bragg wavelength calibration. It is proved experimentally that this method can reduce the standard deviation of demodulated FBG wavelengths by at least 45.9% at a constant temperature, and 42.9% in the environment of varying temperature from 10 °C to 60 °C. Compared with the method of Bragg wavelength calibration based on the original HCN absorption spectrum, the spectral bandwidth that can be accurately demodulated is also expanded to the whole C-band.

Background: Bladder urothelial carcinoma (BLCA) is one of the most common malignant tumors with high morbidity and recurrence rate. The study aims to establish a prediction model to elaborate the relation between inflammatory response and prognosis of BLCA and thus to evaluate the potential prognostic value of inflammatory response–related genes (IRGs) in therapeutic choices.Methods: The study utilized the gene expression profiles from the The Cancer Genome Atlas and Gene Expression Omnibus (GSE32894) datasets. Differentially expressed IRGs between normal and tumor tissues were identified, and 10 of them were correlated with overall survival (OS) (p < 0.05). Then, the LASSO–Cox regression analysis was applied to optimize the signature. RNA sequencing data of patients with BLCA from GSE32894 were applied as a validation set. Cox regression analyses of the seven-gene signature were performed to examine the efficiency of signature in predicting prognosis. Receiver operating characteristic curve analysis was applied to measure the predictive performance of the risk score for OS. Analysis of independent prognostic factors, downstream functional enrichment, drug sensitivity, and immune features were included in this study.Results: The IRG signature (LDLR, ROS1, MMP14, TNFAIP6, MYC, PTGER4, and RIPK2) was used to divide patients into high- and low-risk groups. Cox regression analyses revealed that the risk score was an independent predictive factor. Functional enrichment analysis revealed that genes were enriched in prognosis-related molecular functions and immune-related biological processes. Drug sensitivity and tumor microenvironment correlation analysis indicated that the signature was related to immunotherapy effect.Conclusion: The study defined a new prognostic signature consisting of seven IRGs, which could effectively predict the prognosis of patients with BLCA and reveal relationship of immune features in BLCA with different risk scores. The study also provided a possible indicator for targeted therapy.

Nanocomposite magnets have attracted much attention because of their ultra-high theoretical magnetic energy product and saving rare earth resources. In this study, the Fe93.5Si6.5 with higher hardness than the most common soft magnetic phase (α-Fe) was used to synthesize SmCo5/Fe-Si nanocomposite magnets, and its nanosized process was studied. The results showed that Fe-Si can be well dispersed into SmCo5 matrix through 12 hours of ball milling, and appeared in fine and evenly distributed grains in the SmCo5/Fe-Si nanocomposites, indicating it is suitable for soft magnetic phase. The nanosized process of Fe-Si phase can be summarized as from the irregular shape of agglomeration, to long chain, and finally too uniformly dispersed Fe-Si particles with increased milling time. As a result, the SmCo5/Fe-Si nanocomposite magnet with the optimal maximum magnetic energy product was 14.3 MGOe, accompanied by remanence of 9.5 kG and coercivity of 8.2 kOe. Our results show that by using Fe-Si with high hardness as the soft magnetic phase, the prepared nanocomposite magnet not only has good properties, but also can be expected that the two phases with closer mechanical properties can be deformed harmoniously.

Forming cysts is a common and important bionomic strategy for microorganisms to persist in harsh environments. In ciliated protists, many species have been reported to form cysts when facing unfavorable conditions. Despite traditional studies on the morphological features of cysts and the chemical composition of cyst wall, recent research has focused more on the molecular mechanisms of encystment. The present work reviews studies on developmental features and molecular information of resting cysts in ciliates, and pays more attention to the following questions: what are the inducing factors of encystment and excystment? How does the cell change morphologically during these dynamic processes? And what molecular mechanisms underlie those changes? We also present and summarize the characteristics of cysts from diverse ciliate lineages in a phylogenetic framework, aiming to provide new perspectives for studies on adaptive evolution of unicellular eukaryotes.

Bladder cancer is a highly metastatic tumor and one of the most common malignancies originating in the urinary tract. Despite the efficacy of immune checkpoints, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the effect of immunotherapy for bladder cancer remains unsatisfactory. Therefore, it is urgent to develop new targets to expand immunotherapeutic options. In this study, we utilized single-cell sequencing to explore the cell composition of tumors and detected a subset of Treg cells with high expression of T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and interleukin (IL)-32. The antitumor immune response was suppressed by this subset of Treg cells, while IL-32 promoted bladder cancer metastasis. Nevertheless, targeting TIGIT not only reversed immunosuppression by restoring the antitumor immune response mediated by T cells but also suppressed the secretion of IL-32 and inhibited the metastasis of bladder cancer cells. Thus, our study provided novel insights into immunosuppression in bladder cancer and highlighted TIGIT as a novel target for immunotherapy of bladder cancer. We also illustrated the mechanism of the dual effect of targeting TIGIT and revealed the metastasis-promoting effect of IL-32 in bladder cancer. Collectively, these findings raise the possibility of utilizing TIGIT as a target against bladder cancer from the bench to the bedside.

A more efficient attention recovery of workers during their break time is essential for achieving higher productivity and wellness. In recent years, the biophilic design that introduces indoor plants has become one of the solutions to these problems. This study aims to determine the impact factors and corresponding levels related to indoor planting design concerning workers’ attention recovery. Firstly, the volume ratio, layout, and leaf size of indoor plants and the corresponding levels were put forward by a focus group study with ten participants. Secondly, the orthogonal experiment method established nine virtual recovery scenarios based on characteristics extraction of staff break areas in the factory. Thirdly, eighteen participants were guided to feel fatigued by experiencing the sustained attention to response test to measure the baseline attention level of participants. Then, participants rested in the virtual scenarios. Lastly, the attention test was conducted again to observe participants’ attention recovery degree. The difference values of participants’ sensitivity, reaction times, and the number of correct responses between the two detection targets were applied to evaluate the attention recovery. Results showed that the volume ratio of indoor plants had the most significant effect on workers’ attention recovery; 3% by volume ratio, mixed floor and wall plants and floor planting with large leaves were demonstrated as the optimal indoor planting design for attention recovery.

Oral bacteria colonize the oral cavity, surrounding complex and variable environments. Post-translational modifications (PTMs) are an efficient biochemical mechanism across all domains of life. Oral bacteria could depend on PTMs to quickly regulate their metabolic processes in the face of external stimuli. In recent years, thanks to advances in enrichment strategies, the number and variety of PTMs that have been identified and characterized in oral bacteria have increased. PTMs, covalently modified by diverse enzymes, occur in amino acid residues of the target substrate, altering the functions of proteins involved in different biological processes. For example, Ptk1 reciprocally phosphorylates Php1 on tyrosine residues 159 and 161, required for Porphyromonas gingivalis EPS production and community development with the antecedent oral biofilm constituent Streptococcus gordonii, and in turn Php1 dephosphorylates Ptk1 and rapidly causes the conversion of Ptk1 to a state of low tyrosine phosphorylation. Protein acetylation is also widespread in oral bacteria. In the acetylome of Streptococcus mutans, 973 acetylation sites were identified in 445 proteins, accounting for 22.7% of overall proteins involving virulence factors and pathogenic processes. Other PTMs in oral bacteria include serine or threonine glycosylation in Cnm involving intracerebral hemorrhage, arginine citrullination in peptidylarginine deiminases (PADs), leading to inflammation, lysine succinylation in P. gingivalis virulence factors (gingipains, fimbriae, RagB, and PorR), and cysteine glutathionylation in thioredoxin-like protein (Tlp) in response to oxidative stress in S. mutans. Here we review oral bacterial PTMs, focusing on acetylation, phosphorylation, glycosylation, citrullination, succinylation, and glutathionylation, and corresponding modifying enzymes. We describe different PTMs in association with some examples, discussing their potential role and function in oral bacteria physiological processes and regulatory networks. Identification and characterization of PTMs not only contribute to understanding their role in oral bacterial virulence, adaption, and resistance but will open new avenues to treat oral infectious diseases.