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Abstract Background The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. Methods The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. Results Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. Conclusion A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.

Abstract Background Blood counting and the liver function tests, as the routine examinations, can reflect the immune and nutritional status of the body, our aim is to assess the prognostic significance of serum gamma-glutamyltransferase (GGT) levels and AST/ALT in primary hepatic carcinoma. Methods Clinico-pathological data of 414 patients with primary hepatic carcinoma in the 1st Affiliated Hospital of Anhui Medical College between January 2007 to January 2014 was analyzed retrospectively in this study. Survival curves were described by Kaplan-Meier method and compared by Log-rank test, univariate and multivariate analysis were used to identify the prognostic factors. Results GGT was positively correlated with the tumor size(P = 0.000), tumor volume (P = 0.000), tumor volume percent (P = 0.004), TNM stage(P = 0.009), 1-year survival rate (P = 0.000), 3- years survival rate (P = 0.000) and 5-years survival rate(P = 0.000). The serum ALT/AST was significantly correlated with age (P = 0.047), tumor size(P = 0.002), tumor volume (P = 0.010), tumor volume percent (P = 0.005), TNM stage(P = 0.006), liver cirrhosis(P = 0.003), 3- years survival rate (P = 0.032) and 5-years survival rate(P = 0.000). The Kaplan-Meier curves showed that the patients with primary hepatic carcinoma had a longer time in the low GGT group and low AST/ALT group, showing a significant difference (P

BackgroundThe prognosis of patients with hepatocellular carcinoma (HCC) remains difficult to accurately predict. The purpose of this study was to establish a prognostic model for HCC based on a novel scoring system.MethodsFive hundred and sixty patients who underwent a curative hepatectomy for treatment of HCC at our hospital between January 2007 and January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. The nomogram construction was based on Cox proportional hazard regression models, and the development of the new scoring model was analyzed using receiver operating characteristic (ROC) curve analysis and then compared with other clinical indexes. The novel scoring system was then validated with an external dataset from a different medical institution.ResultsMultivariate analysis showed that tumor size, portal vein tumor thrombus (PVTT), invasion of adjacent tissues, microvascular invasion, and levels of fibrinogen and total bilirubin were independent prognostic factors. The new scoring model had higher area under the curve (AUC) values compared to other systems, and the C-index of the nomogram was highly consistent for evaluating the survival of HCC patients in the validation and training datasets, as well as the external validation dataset.ConclusionsBased on serum markers and other clinical indicators, a precise model to predict the prognosis of patients with HCC was developed. This novel scoring system can be an effective tool for both surgeons and patients.

Background: The prognostic prediction after radical resection of pancreatic ductal adenocarcinoma (PDAC) has not been well-established. We aimed to establish a prognostic model for PDAC based on a new score system, which included a clinical routine serum marker.Methods: A total of 438 patients who underwent curative PDAC at the First Affiliated Hospital of Anhui Medical University from January 2007 to January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. We constructed the nomogram based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operator characteristic curve (ROC curve), which were compared with other clinical indexes.Results: Multivariate analysis showed that TNM stage, CA199, CEA, globulin, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were independent prognostic factors. The new score system had a higher AUC value than other risk factors, and the C-index of the nomogram was highly consistent for evaluating survival of PDAC patients in the validation groups and training group, and the external population also verified the nomogram.Conclusions: For the patients with PDAC after radical surgery, we developed a precise model to predict the prognosis based on the serum markers and other clinical indicators. For surgeons and patients, this score system can be an effective help.

Ginsenosides has been extensively used in clinical settings to treat various inflammatory diseases. At present, the anti-inflammatory effect of ginsenosides is mainly focused on monomeric ginsenosides, while the total saponins of ginseng and their synergistic effect with probiotic fermentation products are rarely studied. This study aimed to investigate the mitigative effects of fermented ginsenosides with Pediococcus acidilactici on Enterotoxigenic Escherichia coli diarrhea in mice. P. acidilactici XM-06 and ginsenoside fermentation products demonstrated significant pre-protection against ETEC-induced diarrhea by mitigating inflammation, inhibited the ERK and upregulated the Z0–1, 0ccludin and Claudin-1 levels, and reducing oxidative stress. These products not only repaired intestinal mucosal damage caused by ETEC-induced diarrhea in mice but also positively influenced gut microbiota dysbiosis by increasing the abundance of Lactobacillus and Bacteroides while decreasing the abundance of Enterobacter, potentially providing a new natural product for the prevention of ETEC-associated diarrheal diseases in humans.

BACKGROUND: The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC. METHODS: We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed. RESULTS: A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65-1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20-3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment. CONCLUSIONS: NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.

During the use of optical gun scopes, slight movements between the human eye and the instrument can cause the pupil to offset from the optical axis, resulting in a dynamic distortion effect. This affects the accuracy and stability of aiming. Based on the mechanism, this study established parameters of the centroid’s deviation of image spots for marginal field points under pupil decentering and centering conditions and their differences to quantitatively evaluate the distortion. These evaluation parameters were obtained by performing a double integral calculation of the ray aberration distribution function over the entire designed exit pupil. Based on this evaluation method, three optical design strategies for reducing the distortion were proposed: optimizing ray aberrations, optimizing centroid shift of image spots, and utilizing vignetting effects. An optimization process was established by combining increasing vignetting and suppressing centroid shift. For a gun scope with significant distortion, the distortion effect was significantly weakened by increasing the vignetting factor and optimizing the centroid shift of image spots. This proved the effectiveness of the proposed analysis, evaluation, and optimization design methods.

Today due to the development of technologies a new economy, network economy is formed. The network business is an economic activity carried out through digital networks. The introduction of the network economy into production at the present stage is conditioned by a special economic category or form of industrial relations in cooperation with the development of productive forces and economic phenomena. In the context of digitalization, contradictory requirements are beginning to be placed on production. In the first case, it is about low costs and high variability, in the other case, the life cycle of a product is beginning to shorten rapidly. All of these problems can be solved at different stages of digital transformation. Continued innovation is needed today, as progress in the existence and effectiveness of some organizations becomes almost impossible without technological innovation. Flexibility of reaction of people to changes and development of new methods of activity are the leading conditions of competitiveness of modern enterprise. The object of this study is new opportunities, various aspects of digitalization of production, optimization of enterprise resources. The key aspect is to increase the productivity of the enterprise by reducing the time of the development of new products marketed and delivered to the consumer. As a result, the reduction contributes to overall efficiency. The authors substantiate that digitalization of production is the consolidation of all business processes at the enterprise using computer and information technologies. The basis of the introduction of the latest technologies is the desire of any company to comprehensively increase the efficiency of production, demand among customers and competitiveness. Keywords: economy, production, process, technology, digitalization, labor productivity, efficiency.

Low temperature inhibits the regeneration of amputated tails of Gekko japonicus by influencing the energy sensory Akt/mTOR pathway, which is also modulated by injury-induced Wnt signal.

Background: The CTNND2 gene which encodes a δ-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of CTNND2 in spatial cognition and related mechanisms remains obscure. Methods: In this study, we generated a new line of Ctnnd2-Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism. Results: Ctnnd2-KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both Ctnnd2-KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of Ctnnd2-KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice. Conclusion: The CTNND2 gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the Ctnnd2 gene in cognition at the molecular and synaptic levels. Highlights: 1. Ctnnd2−/− mice exhibited autism-like behaviors and impaired spatial learning and memory. 2. Rictor was involved in the regulation of Ctnnd2-associated spatial cognition but not autism-like behaviors. 3. Rictor played a crucial role in spatial learning and memory by modulating postsynaptic changes in hippocampal neurons of Ctnnd2-⁣/- mice.

Stenotrophomonas maltophilia (S. maltophilia) is an emerging opportunistic pathogen that exhibits resistant to a majority of commonly used antibiotics. Phages have the potential to serve as an alternative treatment for S. maltophilia infections. In this study, a lytic phage, A1432, infecting S. maltophilia YCR3A-1, was isolated and characterized from a karst cave. Transmission electron microscopy revealed that phage A1432 possesses an icosahedral head and a shorter tail. Phage A1432 demonstrated a narrow host range, with an optimal multiplicity of infection of 0.1. The one-step growth curve indicated a latent time of 10  min, a lysis period of 90  min, a burst size of 43.2 plaque-forming units per cell. In vitro bacteriolytic activity test showed that phage A1432 was capable to inhibit the growth of S. maltophilia YCR3A-1 in an MOI-dependent manner after 2  h of co-culture. BLASTn analysis showed that phage A1432 genome shares the highest similarity (81.46%) with Xanthomonas phage Xoo-sp2 in the NCBI database, while the query coverage was only 37%. The phage contains double-stranded DNA with a genome length of 61,660  bp and a GC content of 61.92%. It is predicted to have 79 open reading frames and one tRNA, with no virulence or antibiotic resistance genes. Phylogenetic analysis using terminase large subunit and DNA polymerase indicated that phage A1432 clustered with members of the Bradleyvirinae subfamily but diverged into a distinct branch. Further phylogenetic comparison analysis using Average Nucleotide Identity, proteomic phylogenetic analysis, genomic network analysis confirmed that phage A1432 belongs to a novel genus within the Bradleyvirinae subfamily, Mesyanzhinovviridae family. Additionally, phylogenetic analysis of the so far isolated S. maltophilia phages revealed significant genetic diversity among these phages. The results of this research will contribute valuable information for further studies on their morphological and genetic diversity, will aid in elucidating the evolutionary mechanisms that give rise to them. [ABSTRACT FROM AUTHOR]

Parvoviruses are single-stranded DNA viruses, infecting many animals from insects to humans. Human parvovirus B19 (B19V) causes erythema infectiosum, arthropathy, anemia, and fetal death, and human bocavirus (HBoV) 1 causes respiratory tract infections, while HBoV2-4 are enteric. Parvoviral genomes can persist in diverse non-permissive tissues after acute infection, but the host-cell tropism and the impact of their tissue persistence are poorly studied. We searched for parvoviral DNA in a total of 427 intestinal biopsy specimens, as paired disease-affected and healthy mucosa, obtained from 130 patients with malignancy, ulcerative colitis (UC), or adenomas, and in similar intestinal segments from 55 healthy subjects. Only three (1.6%) individuals exhibited intestinal HBoV DNA (one each of HBoV1, 2, and 3). Conversely, B19V DNA persisted frequently in the intestine, with 50, 47, 31, and 27% detection rates in the patients with malignancy, UC, or adenomas, and in the healthy subjects, respectively. Intra-individually, B19V DNA persisted significantly more often in the healthy intestinal segments than in the inflamed colons of UC patients. The highest loads of B19V DNA were seen in the ileum and colon specimens of two healthy individuals. With dual-RNAscope in situ hybridization and immunohistochemistry assays, we located the B19V persistence sites of these intestines in mucosal B cells of lymphoid follicles and vascular endothelial cells. Viral messenger RNA transcription remained, however, undetected. RNA sequencing (RNA-seq) identified 272 differentially expressed cellular genes between B19V DNA-positive and -negative healthy ileum biopsy specimens. Pathway enrichment analysis revealed that B19V persistence activated the intestinal cell viability and inhibited apoptosis. Lifelong B19V DNA persistence thus modulates host gene expression, which may lead to clinical outcomes.

Background: Neurosyphilis is a serious complication caused by the invasion of the central nervous system by Treponema pallidum subsp. pallidum (T. pallidum). However, the molecular mechanism by which T. pallidum crosses the blood-brain barrier has not been fully elucidated. Objectives: The primary purpose of this experimental design was to explore the effect of the T. pallidum adhesion protein Tp0751 on the blood-brain barrier and cerebrovascular endothelial cells. Methods: BEnd3 cells were used to construct a monolayer blood-brain barrier model in vitro. The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. The expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 at the transcription and translation levels were detected by qRT-PCR and ELISA, respectively. Results: The results showed that, the tight junction structures between cells showed no obvious fragmentation, but the levels of the tight junction proteins zonula occludens-1 and occludin were reduced by the effects of Tp0751 on bEnd3 cells. In addition, further research demonstrated that after incubation with bEnd3 cells, Tp0751 induced cell apoptosis in a concentration- and time-dependent manner via the caspase 8/caspase 3 pathway. These apoptotic processes may have contributed to the changes in tight junction proteins expression. Furthermore, the Tp0751 protein may be involved in the pathogenic process by which T. pallidum crosses the blood-brain barrier by promoting secretion of the proinflammatory factor interleukin-6. Conclusions: On the whole, this study is the first to reveal and highlight that Tp0751 may affect the expression of tight junction proteins by inducing apoptosis and promoting the secretion of the inflammatory cytokine IL-6, thus playing a role in the progression of neurosyphilis caused by T. pallidum.

From the standpoint of chemical structures, the organic backbones of energetic materials can be classified into aromatic rings, nonaromatic rings, and open chains. Although the category of aromatic energetic compounds exhibits several advantages in the regulation of energetic properties, the nonaromatic heterocycles, assembling nitramino explosophores with simple alkyl bridges, still have prevailed in benchmark materials. The methylene bridge plays a pivotal role in the constructions of the classic nonaromatic heterocycle-based energetic compounds, e.g., hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), whereas ethylene bridge is the core moiety of state-of-the-art explosive 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20). In this context, it is of great interest to employ simple and practical bridges to assemble aromatic and nonaromatic nitrogen-rich heterocycles, thereby expanding the structural diversity of energetic materials, e.g., bridged and fused nitrogen-rich poly-heterocycles. Furthermore, alkyl-bridged poly-heterocycles highlight the potential for the open chain type of energetic materials. In this review, the development of alkyl bridges in linking nitrogen-rich heterocycles is presented, and the perspective of the newly constructed energetic backbones is summarized for the future design of advanced energetic materials. [ABSTRACT FROM AUTHOR]

Among the bioactive compounds, lipid-soluble tanshinone is present in Salvia miltiorrhiza, a medicinal plant species. While it is known that ethephon has the ability to inhibit the tanshinones biosynthesis in the S. miltiorrhiza hairy root, however the underlying regulatory mechanism remains obscure. In this study, using the transcriptome dataset of the S. miltiorrhiza hairy root induced by ethephon, an ethylene-responsive transcriptional factor EIN3-like 1 (SmEIL1) was identified. The SmEIL1 protein was found to be localized in the nuclei, and confirmed by the transient transformation observed in tobacco leaves. The overexpression of SmEIL1 was able to inhibit the tanshinones accumulation to a large degree, as well as down-regulate tanshinones biosynthetic genes including SmGGPPS1, SmHMGR1, SmHMGS1, SmCPS1, SmKSL1 and SmCYP76AH1. These are well recognized participants in the tanshinones biosynthesis pathway. Further investigation on the SmEIL1 was observed to inhibit the transcription of the CPS1 gene by the Dual-Luciferase (Dual-LUC) and yeast one-hybrid (Y1H) assays. The data in this work will be of value regarding the involvement of EILs in regulating the biosynthesis of tanshinones and lay the foundation for the metabolic engineering of bioactive ingredients in S. miltiorrhiza. [ABSTRACT FROM AUTHOR]

Abstract Background Human bocavirus 1 is a commonly detected human parvovirus. Many studies have shown human bocavirus 1 as a pathogen in association with acute respiratory tract infections in children. However, because human bocavirus 1 persists in the upper airways for extensive time periods after acute infection, the definition and diagnostics of acute human bocavirus 1 infection is challenging. Until now, detection of human bocavirus 1 exclusively, high viral load in respiratory samples, and viremia have been associated with a clinical picture of acute respiratory illness. There are no studies showing detection of human bocavirus 1 messenger ribonucleic acid in the peripheral blood mononuclear cells as a diagnostic marker for acute lower respiratory tract infection. Case presentation We report the case of a 17-month-old Latvian boy who presented in intensive care unit with acute bilateral bronchiolitis, with a history of rhinorrhea and cough for 6 days and fever for the last 2 days prior to admission, followed by severe respiratory distress and tracheal intubation. Human bocavirus 1 was the only respiratory virus detected by a qualitative multiplex polymerase chain reaction panel. For the diagnosis of acute human bocavirus 1 infection, both molecular and serological approaches were used. Human bocavirus 1 deoxyribonucleic acid (DNA) was detected simultaneously in nasopharyngeal aspirate, stool, and blood, as well as in the corresponding cell-free blood plasma by qualitative and quantitative polymerase chain reaction, revealing high DNA-copy numbers in nasopharyngeal aspirate and stool. Despite a low-load viremia, human bocavirus 1 messenger ribonucleic acid was found in the peripheral blood mononuclear cells. For detection of human bocavirus 1-specific antibodies, non-competitive immunoglobulin M and competitive immunoglobulin G enzyme immunoassays were used. The plasma was positive for both human bocavirus 1-specific immunoglobulin M and immunoglobulin G antibodies. Conclusions The presence of human bocavirus 1 genomic DNA in blood plasma and human bocavirus 1 messenger ribonucleic acid in peripheral blood mononuclear cells together with human bocavirus 1-specific immunoglobulin M are markers of acute human bocavirus 1 infection that may cause life-threatening acute bronchiolitis.

Background Cardiac remodeling predisposes individuals to heart failure if the burden is not solved, and heart failure is a growing cause of morbidity and mortality worldwide. The cardiac extracellular matrix not only provides structural support, but also is a core aspect of the myocardial response to various biomechanical stresses and heart failure. MFAP4 (microfibrillar‐associated protein 4) is an integrin ligand located in the extracellular matrix, whose biological functions in the heart remain poorly understood. In the current study we aimed to test the role of MFAP4 in cardiac remodeling. Methods and Results MFAP4‐deficient (MFAP4−/−) and wild‐type mice were subjected to aortic banding surgery and isoproterenol to establish models of cardiac remodeling. We also evaluated the functional effects of MFAP4 on cardiac hypertrophy, fibrosis, and cardiac electrical remodeling. The expression of MFAP4 was increased in the animal cardiac remodeling models induced by pressure overload and isoproterenol. After challenge of 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol, MFAP4−/− mice exhibited lower levels of cardiac fibrosis and fewer ventricular arrhythmias than wild‐type mice. However, there was no significant effect on cardiomyocyte hypertrophy. In addition, there was no significant difference in cardiac fibrosis severity, hypertrophy, or ventricular arrhythmia incidence between wild‐type‐sham and knockout‐sham mice. Conclusions These findings are the first to demonstrate that MFAP4 deficiency inhibits cardiac fibrosis and ventricular arrhythmias after challenge with 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol but does not significantly affect the hypertrophy response. In addition, MFAP4 deficiency had no significant effect on cardiac fibrosis, hypertrophy, or ventricular arrhythmia in the sham group in this study.

Oral squamous cell carcinoma (OSCC) has always been one of the most aggressive and invasive cancers among oral and maxillofacial malignancies. As the morbidity and mortality of the disease have increased year by year, the search for a promising diagnostic and prognostic biomarker for the disease is becoming increasingly urgent. Tumorous and adjacent tissues were collected from three OSCC sufferers and we obtained 229 differentially expressed genes (DEGs) between tumor and normal tissues via high-throughput RNA sequence. Function and pathway enrichment analyses for DEGs were conducted to find a correlation between tumorigenesis status and DEGs. Protein interaction network and molecular complex detection (MCODE) were constructed to detect core modules. Two modules were enriched in MCODE. The diagnostic and prognostic values of the candidate genes were analyzed, which provided evidence for the candidate genes as new tumor markers. Small Proline Rich Protein 3 (SPRR3), a potential tumor marker that may be useful for the diagnosis of OSCC, was screened out. The survival analysis showed that SPRR3 under expression predicted the poor prognosis of OSCC patients. Further experiments have also shown that the expression of SPRR3 decreased as the malignancy of OSCC increased. Therefore, we believe that SPRR3 could be used as a novel diagnostic and prognostic tumor marker.

Face gear drive has been widely investigated in the aviation field as a power split device on the helicopter main reducer. However, high-speed and heavy-load condition makes the face gear prone to tooth surface pitting, leading to deterioration of transmission performance. To improve the load-bearing capacity of face gear, this paper proposes a design and modification method based on gear skiving process for face gear drives. First, gear skiving mathematical models for a face gear pair are established, and a continuously profile-shifted modification method is presented based on these mathematical models. Then, the load-bearing capacity of the modified face gear pair is minutely analyzed and discussed through contact analysis. The contact stress of the modified face gear is reduced by 47.78% on the right side and 41.1% on the left side compared with an unmodified face gear. Finally, gear skiving experiments and meshing performance tests of face gear pairs are conducted. The measurement results show consistency with the calculation results. Thus, the proposed design and continuously profile-shifted modification method based on the gear skiving process is feasible and contributes to load-bearing capacity improvement. [ABSTRACT FROM AUTHOR]

Polymyxin B, produced by Paenibacillus polymyxa, is used as the last line of defense clinically. In this study, exogenous mixture of precursor amino acids increased the level and proportion of polymyxin B1 in the total of polymyxin B analogs of P. polymyxa CJX518-AC (PPAC) from 0.15 g/L and 61.8 % to 0.33 g/L and 79.9 %, respectively. The co-culture of strain PPAC and recombinant Corynebacterium glutamicum-leu01, which produces high levels of threonine, leucine, and isoleucine, increased polymyxin B1 production to 0.64 g/L. When strains PPAC and C. glu-leu01 simultaneously inoculated into an optimized medium with 20 g/L peptone, polymyxin B1 production was increased to 0.97 g/L. Furthermore, the polymyxin B1 production in the co-culture of strains PPAC and C. glu-leu01 increased to 2.21 g/L after optimized inoculation ratios and fermentation medium with 60 g/L peptone. This study provides a new strategy to improve polymyxin B1 production. [ABSTRACT FROM AUTHOR]

Background and aims: Amnestic mild cognitive impairment (aMCI) is the most common subtype of MCI, which carries a significantly high risk of transitioning to Alzheimer's disease. Recently, increasing attention has been given to remnant cholesterol (RC), a non-traditional and previously overlooked risk factor. The aim of this study was to explore the association between plasma RC levels and aMCI. Methods: Data were obtained from Brain Health Cognitive Management Team in Wuhan (https://hbtcm.66nao.com/admin). A total of 1,007 community-dwelling elders were recruited for this project. Based on ten tools including general demographic data, cognitive screening and some exclusion scales, these participants were divided into the aMCI (n = 401) and normal cognitive groups (n = 606). Physical examinations were conducted on all participants, with clinical indicators such as blood pressure, blood sugar, and blood lipids collected. Results: The aMCI group had significantly higher RC levels compared to the normal cognitive group (0.64 ± 0.431 vs. 0.52 ± 0.447 mmol/L, p<0.05). Binary logistics regression revealed that occupation (P<0.001, OR = 0.533, 95%CI: 0.423-0.673) and RC (p = 0.014, OR = 1.477, 95% CI:1.081-2.018) were associated factors for aMCI. Partial correlation analysis, after controlling for occupation, showed a significant negative correlation between RC levels and MoCA scores (r = 0.059, p = 0.046), as well as Naming scores (r = 0.070, p = 0.026). ROC curve analysis demonstrated that RC levels had an independent predictive efficacy in predicting aMCI (AUC = 0.580, 95%CI: 0.544 ~ 0.615, P <0.001). Conclusion: Higher RC levels were identified as an independent indicator for aMCI, particularly in the naming cognitive domain among older individuals. Further longitudinal studies are necessary to validate the predictive efficacy of RC. [ABSTRACT FROM AUTHOR]

In a previously published clinical trial, we demonstrated that tirofiban was effective and safe in acute ischemic stroke (AIS) patients who did not undergo early recanalization treatments. We aimed to evaluate neuroimaging characteristics and their clinical significance to guide tirofiban treatment. In this post hoc analysis, location of infarcts (anterior circulation stroke [ACS] vs. posterior circulation stroke [PCS]), degree of cerebral artery stenosis (≤69% vs. ≥70% or occlusion), total infarct volume, and ASPECTS were used to predict the treatment effects of tirofiban, defined as the proportions of excellent and favorable functional outcome (modified Rankin Scale [mRS] score of 0–1, 0–2) at 90 days. ACS patients were more likely to achieve excellent (OR 2.08; 95% CI 1.25–3.45; p = 0.004) and favorable functional outcome (OR 2.28; 95% CI 1.24–4.22; p = 0.008) when treated with tirofiban. However, there was no significant difference in PCS patients between tirofiban and the control group. For patients with severe stenosis (≥70% or occlusion), tirofiban treatment improved the proportion of good outcomes (OR 2.84; 95% CI 1.44–5.60; p = 0.002 for mRS 0–1; OR 2.42; 95% CI 1.22–4.77; p = 0.011 for mRS 0–2). Meanwhile, we found that tirofiban improved outcome in patients with ASPECTS 8–10 and was independent of total infarct volume. These findings support the hypothesis that patients with ACS and severe stenosis may be recommended for tirofiban treatment, which can be predicted independent of total infarct volume. [ABSTRACT FROM AUTHOR]

AIM: To study the application of macular ganglion cell complex(mGCC)and peripapillary retinal nerve fiber layer thickness(pRNFL)measured by optical coherence tomography(OCT)in the early diagnosis of glaucoma. METHODS: Case-control study. Eighty-six subjects, including 30 eyes in normal subjects, 27 eyes in suspected primary open angle glaucoma, 29 eyes in primary open angle glaucoma were enrolled in this study. The thickness of mGCC and pRNFL were measured by OCT. The area under the receiver operating characteristic(AROC)curve at fixed specificities were calculated for each parameter. RESULTS: There were significant differences in mean pRNFL thickness, superior pRNFL thickness and inferior pRNFL thickness between normal group, suspected glaucoma group and early glaucoma group(P=0.001, 0.004, 0.011). The mean mGCC thickness, the thickness of the top mGCC, the thickness of the lower mGCC were statistically significant(P=0.008, 0.002, 0.003); the difference of general loss of volume(GLV)and focal loss of volume(FLV)between the three groups was statistically significant(P=0.002). Compared with the normal group, all the pRNFL and the mGCC parameters were higher in the suspected glaucoma group, and the FLV had the highest AROC(0.801), all the remaining AROC was >0.700 except above Prnlf(0.688). Compared with the normal group and the early glaucoma group, all the pRNFL and the mGCC had higher AROC, average mGCC was hightest(0.804), all parameters AROC were >0.700 except mean pRNFL(0.683). In suspected glaucoma group, 58% patients had abnormal mGCC thickness and 23% had abnormal pRNFL thickness; in early glaucoma group, 98%patients had abnormal mGCC thickness and 90% had abnormal pRNFL thickness; in normal group, 93%patients had abnormal mGCC thickness and 93%had abnormal pRNFL thickness, the correlation between the three groups was statistically significant(χ2=12.11, PCONCLUSION: OCT measurement of mGCC thickness and pRNFL thickness in early glaucoma have good diagnostic ability; mGCC thickness measurement can be used as an effective method for early diagnosis of glaucoma.

AIM:To investigate the efficacy of subthreshold micropulse 577nm laser photocoagulation with intravitreous anti-vascular endothelial growth factor(anti-VEGF)treatment for macular edema secondary to branch retinal vein occlusion(BRVO). METHODS: A retrospective case series study was sixteen patients(16 eyes)of macular edema secondary to BRVO whose course was not more than 3mo were examined by fundus fluoresceine angiography(FFA)and optical coherence tomography(OCT). Eight eyes were given subthreshold micropulse 577nm laser with anti-VEGF treatment(micropulse laser group). Meantime another 8 eyes were given conventional grid laser photocoagulation with anti-VEGF treatment(grid laser group). The followed up was 6mo. The best corrected visual acuity(BCVA)and central foveal thickness(CFT)were analyzed.RESULTS: The baseline BCVA of the micropulse laser group was 0.34±0.18(LogMAR)and was improved to 0.07±0.01(PPPPP>0.05).CONCLUSION: Subthreshold micropulse 577nm laser with anti-VEGF and conventional grid laser photocoagulation with anti-VEGF had equivalent effects on the treatment of macular edema secondary to BRVO.

Background: Whether keratoconus (KC) is an inflammatory disease is currently debated. Hence, we aimed to investigate the immune-related features of KC based on single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data. Methods: scRNA-seq data were obtained from the Genome Sequence Archive (GSA), bulk RNA-seq data were obtained from the Gene Expression Omnibus (GEO), and immune-associated genes(IAGs) were obtained from the ImmPort database. Cell clusters of KC were annotated, and different cell clusters were then selected. The IAG score of each cell was calculated using the AUCell package. Three bulk RNA-seq datasets were merged and used to identify the differentially expressed genes (DEGs), biological functions, and immune characteristics. Weighted gene coexpression network analysis (WGCNA) was used to select the IAG score-related hub genes. Based on scRNA-seq and bulk RNA-seq analyses, three machine learning algorithms, including random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) regression analysis, were used to identify potential prognostic markers for KC. A predictive nomogram was developed based on prognostic markers. Results: Six cell clusters were identified in KC, and decreased corneal stromal cell-5 (CSC-5) and increased CSC-6 were found in KC. CSC and immune cell clusters had the highest IAG scores. The bulk RNA-seq analysis identified 1362 DEGs (553 upregulated and 809 downregulated) in KC. We found different immune cell populations and differentially expressed cytokines in KC. More than three key IAG score-related modules and 367 genes were identified. By integrating the scRNA-seq and bulk RNA-seq analyses, 250 IAGs were selected and then incorporated into three machine learning models, and 10 IAGs (CEP112, FYN, IFITM1, IGFBP5, LPIN2, MAP1B, RNASE1, RUNX3, SMIM10, and SRGN) were identified as potential prognostic genes that were significantly associated with cytokine and matrix metalloproteinase(MMP)1-14 expression. Finally, a predictive nomogram was constructed and validated. Conclusion: Taken together, our results identified CSCs and immune cell clusters that may play a key role during KC progression by regulating immunological features and maintaining cell stability. [ABSTRACT FROM AUTHOR]

The Al–Cr–Mo–Ni system is of technical interest because it is an essential system for the thermodynamic modeling of systems related to the Ni- and NiAl-based superalloys. The knowledge of phase behaviors and thermodynamic properties of this system will be greatly helpful for the development of related alloys. Thermodynamic modeling of the Al–Cr–Mo–Ni system in the previous effort is not satisfactory. In this study, the Cr–Mo–Ni system was re-optimized with more sophisticated binary databases, and a new thermodynamic database of the Al–Cr–Mo–Ni system was established. A satisfactory agreement between calculated results and experimental data was obtained. The thermodynamic database developed in this study is suitable for assisting the design of both Ni- and NiAl-based superalloys. [ABSTRACT FROM AUTHOR]

We report an effective approach on improving the electrical strength and mechanical impact toughness in polyethylene blends by locating the composition on a submicroscopic supramolecular structure turning point. The designed linear low density polyethylene (LLDPE)-high density polyethylene (HDPE) blends exhibit the enhanced electrical breakdown strength and toughness with the optimal value of E0=95.48kV/mm and G=54.67 kJ·m-2 respectively, which is around 6% and 18% higher than pure LLDPE. The scanning electron microscopic (SEM) investigation and X-ray diffraction (XRD) study show no obvious variation in mesoscopic and microscopic structure with the change of HDPE content. Further differential scanning calorimetric (DSC) study using successive self-nucleation/annealing (SSA) method reveals that the turning point with optimal performance corresponds with a peculiar supramolecular structure with a high density of tie molecules, which enhances the toughness and the electromechanical breakdown strength. Our work provides a new insight on improving electrical strength and toughness for dielectric polymers, and may aid to enhance the electric insulation performance for dielectric materials in power equipment.

AIM:To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE+/- mice (AChE knockout mice) of various ages.METHODS:Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 μmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE+/- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.RESULTS:Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE+/- mice retina were thinner than those in wild-type mice (PP+/- mice developed more slowly than wild-type mice (PP>0.05).CONCLUSION:In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.

The self-centering buckling-restrained brace (SC-BRB) may achieve self-restoration for structures and, to a certain degree, diminish the substantial seismic residual deformation following rare earthquakes when compared to the usage of the conventional buckling-restrained brace (BRB). It may be possible to reduce the abrupt change in stiffness at the location of the strengthened stories and make the outrigger better at dissipating energy by improving the design of the energy-dissipation outrigger. This study compares the seismic performances of two types of energy-dissipation outriggers with BRB and SC-BRB web member designs during rare earthquakes so that the changes can be measured. The results show that using the SC-BRB web member design reduces the maximum inter-story drift ratio by an average of 7.68% and increases the average plastic-energy dissipation of the outrigger truss by 8.75%. The evaluation results showthat the SC-BRB outrigger truss structure has better structural regularity and energy-dissipation performance. It has the ability to efficiently regulate the structural seismic response and lessen primary-structure damage. [ABSTRACT FROM AUTHOR]

Highly efficient drinking water purification is still an important challenge for membrane techniques where high flux, high rejection, and low fouling are highly emphasized. In the present work, a porous network surface with carbon nanotubes (CNTs) was in situ constructed on hierarchically-structured mullite ceramic membranes. Interestingly, such a composite structure was demonstrated to effectively remove bacteria from drinking water with a highly stable long-term flux. After membrane structure characterizations, separation performance, such as flux and rejection, was assessed by the purification of bacteria-contaminated drinking water. The results confirmed that the mullite-CNT composite membrane claimed a complete removal of two model bacteria (100% rejection of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus)), driven by a trans-membrane pressure of 0.1 MPa, where a surface sieving mechanism was dominant. A highly stable long-term flux for the 24 h filtration process was achieved, which can be attributed to the porous membrane surface with a special randomly-oriented CNTs network structure, featuring very high three-dimensional open porosity, allowing water to rapidly transport. The bacteria were only trapped on the CNTs network surface via surface filtration, without pore plugging, endowing the mullite-CNT membrane with unprecedentedly low fouling propensity to keep high flux with long-term operation time.

Taxadiene is an important precursor for the biosynthesis of highly effective anticancer drug paclitaxel, but its microbial biosynthesis yield is very low. In this study, we employed Yarrowia lipolytica as a microbial host to produce taxadiene. First, a "push-pull" strategy was adopted to increase taxadiene production by 234%. Then taxadiene synthase was fused with five solubilizing tags respectively, leading a maximum increase of 62.3% in taxadiene production when fused with SUMO. Subsequently, a multi-copy iterative integration method was used to further increase taxadiene titer, achieving the maximum titer of 23.7 mg/L in shake flask culture after three rounds of integration. Finally, the taxadiene titer was increased to 101.4 mg/L by optimization of the fed-batch fermentation conditions. This is the first report of taxadiene biosynthesis accomplished in Y. lipolytica, serving as a good example for the sustainable production of taxadiene and other terpenoids in this oleaginous yeast. [ABSTRACT FROM AUTHOR]

The infructescence of Platycarya strobilacea is a rich source of ellagic acid (EA) which has shown antioxidant, anticancer and antimutagen properties. Response surface methodology (RSM) was used to optimize the conditions for ultrasonic extraction of EA from infructescence of P. strobilacea. A central composite design (CCD) was used for experimental design and analysis of the results to obtain the optimal processing parameters. The content of EA in the extracts was determined by HPLC with UV detection. Three independent variables such as ultrasonic extraction temperature (°C), liquid:solid ratio (mL/g), and ultrasonic extraction time (min) were investigated. The experimental data obtained were fitted to a quadratic equation using multiple regression analysis and also analyzed by appropriate statistical methods. The 3-D response surface and the contour plots derived from the mathematical models were applied to determine the optimal conditions. The optimum ultrasonic extraction conditions were as follows: ultrasonic extraction temperature 70 °C, liquid:solid ratio 22.5, and ultrasonic extraction time 40 min. Under these conditions, the experimental percentage value was 1.961%, which is in close agreement with the value predicted by the model.

Background: We aimed to investigate the feasibility and application of using the zoomed diffusion-weighted echo-planar imaging (z-EPI DWI) sequences for hilar cholangiocarcinoma assessment compared with conventional single-shot EPI diffusion-weighted imaging (c-EPI DWI). Methods: Both c-EPI DWI and z-EPI DWI were preoperatively performed in 16 patients with histopathologically-confirmed hilar cholangiocarcinoma. A two-dimensional spatial-selective radiofrequency (RF) pulse was applied to the z-EPI DWI using an echo-planar transmit trajectory. Anatomic structural visualization, lesion conspicuity, artifact presence and overall image quality were evaluated and compared between the two sequence images. The ratio of differences regarding hilar cholangiocarcinoma lesion sizes measured on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) were compared from both EPI techniques. The DW images for tumor involvement of the bile duct were reviewed based on histopathological examination of the surgical intraoperative evaluation. ADC measurements of DWIs in the hilar cholangiocarcinoma lesions were conducted. Results: The hepatic hilar region was better delineated by visualization of anatomical structures, lesion conspicuity and overall image quality using the z-EPI DWI and these analyses were compared with the c-EPI DWI method (all p<0.05). Better lesion delineation of bile duct walls and lumens was noted in four patients with z-EPI DWI compared with those of c-EPI DWI. No significant differences were noted between the two image datasets for artifacts (p=0.876). The ratio of differences regarding hilar cholangiocarcinoma lesion sizes was significantly lower (p= 0.018) on T2WI and DWI, as determined by the z-EPI DWI than that determined by the c-EPI method. The use z-EPI DWI resulted in the accurate diagnosis of the Bismuth-Corlette classification of 15 tumors (15/16, 93.75%), whereas the use of c-EPI DWI resulted in correct diagnosis of 12 tumors (12/16, 75.00%). There were no significant differences between c-EPI DWI and z-EPI DWI in the ADC values of hilar cholangiocarcinoma lesions (p= 0.48). Conclusion: z-EPI DWI resulted in remarkable image quality improvements for hilar cholangiocarcinoma. The ability to detect and delineate lesions using z-EPI DWI was superior to that of c-EPI DWI. [ABSTRACT FROM AUTHOR]

The Arakawa-Schubert (A-S) cumulus parameterization is evaluated by performing semiprognostic tests against data simulated by a cumulus ensemble model (CEM). The CEM is a two-dimensional cloud model for simulating the formation of an ensemble of cumulus clouds under prescribed large-scale conditions. Three simulations, two with vertical wind shear and one without, are performed with identical (time-varying) large-scale advective effects. The semiprognostic tests follow a procedure similar to that used by Lord except that simulated data averaged over the entire domain or selected subdomains of the CEM provide the 'observed' large-scale conditions. Detailed comparisons were made between the results of simulation and parameterization. The results include comparisons of surface precipitation rate, apparent heat source, apparent moisture sink, updraft mass flux, and downdraft mass flux. Two different sets of tests were performed. One is the standard A-S parameterization with the cloud work function (CWF) quasi equilibrium, and the other allows CWF nonequilibrium by taking into account the simulated time change of the CWF. The tests show that the A-S parameterization is basically valid in spite of the existence of mesoscale organization in cumulus convection. In particular, the assumption of CWF quasi equilibrium is more accurate for inputs averaged over smaller subdomain sizes that resolve some mesoscale processes. On the other hand, errors due to the nondiagnostic aspect of cumulus convection are more significant for inputs averaged over larger subdomain sizes. Errors due to the inherent nondeterministic aspect of cumulus convection appear to be more significant for inputs averaged over smaller subdomain sizes. A modified A-S parameterization with a convective-scale downdraft formulation was also tested against the simulated data. The inclusion of downdrafts slightly improves the results of semiprognostic tests. The impact of downdrafts on the subcloud layer may depend significantly on the subdomain size.