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A friction draft gear model was developed to assess the degraded dynamic characteristics of worn draft gears in the vehicle impact condition. It presents an approach to simulate multiple typical wear profiles of wedge shoes and reflect their effects on the draft gear performance. Based on the rated design indexes and existing overhaul regulations of MT-2 type friction draft gears in China, the safety wear limits for wedge shoes with different wear profiles were classified and assessed. The results indicate that wedge shoes with uniform or concave wear can significantly worsen draft gear performance, and the existing maintenance limit of 1 mm only applies to wedge shoes with uniform wear but not to the most common wedge shoes with concave wear. Also, for wedge shoes with concave wear, when the wear area covers 50%, 75%, and 100% of the total main friction surface, the corresponding safety wear limits are 0.5 mm, 0.8 mm, and 1.3 mm, respectively. Therefore, it is proposed to design multiple graded and dynamic maintenance limits to ensure the service safety of MT-2 type friction draft gears. [ABSTRACT FROM AUTHOR]

Rapid detection of heparin-binding protein (HBP) is essential for timely intervention in sepsis cases. Current detection techniques are usually antibody-based immunological methods, which have certain problems, such as complexity and slow detection, and fall short in meeting the urgency of clinical needs. The application of an aptamer can address these concerns well. In this study, HBP-specific DNA aptamers were screened first. Among which, Apt-01, Apt−02, and Apt−13 had a high affinity for HBP, exhibiting impressive KD values of 3.42, 1.44, and 1.04 nmol/L, respectively. Then, the aptamer of HBP and its partially complementary primer probe were combined to form double-stranded DNA (dsDNA) and synthesize a circular DNA template. The template is complementary to the primer probe, but due to the presence of dsDNA, ExoIII cleaves C2-13 as an RCA primer probe, rendering the template unable to recognize the primer probe and preventing the RCA reaction from proceeding. When the target is present, it competes with the adapter for recognition and releases C2-13, exposing its 3′ end. After initiating the RCA at room temperature and reacting with SYBR GreenII at 37 °C for 20 min, fluorescence changes can be observed and quantitatively analyzed at a 530 nm wavelength, achieving quantitative biological analysis. Apt-01 was used to develop a fluorescent biosensor for HBP detection, which exhibited a good linear range (0.01 nmol/L to 10 nmol/L) and detection limit (0.0056 nmol/L). This advancement holds the potential to lay a solid groundwork for pioneering sensitive and specific methods for HBP detection and to significantly enhance the diagnostic processes for sepsis. [ABSTRACT FROM AUTHOR]

There has been few research on the affect and distribution of different shapes of nanoparticles inside an organism during extraction and drug targeting. In order to obtain the distribution of magnetic nanoparticles with different morphology and size in vivo, a general method of Re-188 labeled Magnetic Core–Shell Nanoparticles (MNPs) Materials was developed. Based on the prepared magnetic particles with three different morphologies and sizes, including 230 nm spherical Fe3O4@SiO2 particles (S-230), 100 nm spherical Fe3O4@SiO2 particles (S-100) and peanut shaped Fe3O4@SiO2 particles (P-180, the length of the short axis is about 100 nm and the length of the long axis is about 180 nm), the aminated MNPs were labeled with radionuclide Re-188 through the coupling of diethylenetriamine pentaacetic anhydride. The nuclide Re-188 was labeled to investigate their distribution behavior in mice. Most of the small-size particles S-100 can be separated from the capture of the endothelial reticular system and removed by renal metabolism. Most of the larger particles, S-230 and P-180, will be captured by the endothelial reticular system, and the nanoparticles P-180 with large aspect ratio are easier to be captured by the tissue in the spleen and enter the cells through endocytosis. [ABSTRACT FROM AUTHOR]

The antidiabetic effects of flavonoids have been reported, but it is still unclear whether 5,7,3′,4′,5′-pentamethoxyflavone, isolated from Bauhinia championii Benth. (Fabaceae), also exhibits such properties. To isolate 5,7,3′,4′,5′-pentamethoxyflavone from B. championii using high-speed countercurrent chromatography and examine its potential in treating diabetic nephropathy. The phytochemical constituents from the stems of B. championii were separated and purified with high-speed countercurrent chromatography; 5,7,3′,4′,5′-pentamethoxyflavone (PMF) was identified by mass spectrum, 1H-NMR, and 13C-NMR. After exposing mesangial cells to 30 mM glucose and either 5 μM or 10 μM PMF for 6 h, the levels of fibronectin (FN) and p-Smad2/3 were analyzed using Western blotting. Male Sprague–Dawley rats were injected intraperitoneally with 55 mg/kg streptozotocin to induce diabetes and then were randomized into three groups (n = 10): vehicle administration, low-dose (5 mg/kg) PMF, and high-dose (25 mg/kg) PMF by intragastric gavage for 3 months. A healthy group was included as the control. Compared to the diabetic group, low-dose and high-dose PMF treatment decreased the phosphorylation of Smad2/3 by 0.54- and 0.52-fold, and the accumulation of FN decreased by 0.82- and 0.77-fold in vitro; the phosphorylation of Smad2/3 was decreased by 0.39- and 0.37-fold, and the accumulation of FN decreased by 0.47- and 0.40-fold in vivo, respectively. Furthermore, PMF alleviated the glomerular basement membrane thickness and foot process fusion. The findings suggest for the first time that PMF may be a promising treatment option for diabetic kidney fibrosis, which warrants additional clinical investigation. [ABSTRACT FROM AUTHOR]

Objectives. To determine the bone metabolic marker changes from childhood to adolescence and to provide reference values for monitoring bone development in children in Southwest China. Methods. We surveyed 703 participants attending physical examinations from April 2019 and August 2021. Twenty-eight participants were excluded for lack of laboratory tests, and 14 people were excluded for diseases that might affect bone metabolism. A total of 661 children were selected for the study. According to the main developmental periods, the children were divided into preschool, preadolescence, and adolescence groups. Serum bone turnover markers including β-isomerized C-terminal telopeptide of type I collagen (β-CTx), N-terminal midfragment of osteocalcin (N-MID), and procollagen type 1 N-propeptide (P1NP) as well as growth and development indices such as serum calcium (Ca), phosphorus (Pi), alkaline phosphatase (ALP), and vitamin D were measured. The changes in bone metabolism-related markers and the correlations between the indices were analyzed. Results. During the development in boys, the levels of β-CTx and N-MID increased with age from preschool to adolescence, while the levels of P1NP decreased and then increased. In girls, the levels of β-CTx and N-MID plateaued in early adolescence and showed little change in subsequent adolescence, while the levels of P1NP exhibited a downward trend. The correlations between bone metabolism markers and vitamin D were not significant. Conclusions. The levels of bone metabolism markers differed between boys and girls. Reference intervals can be used as essential tools to examine the levels of bone metabolism markers reasonably. [ABSTRACT FROM AUTHOR]

Objective. Previous studies suggested that the level of bone turnover markers (BTMs) could be altered in patients with nonalcoholic fatty liver disease (NAFLD). We aim to provide a comprehensive understanding on the associations between BTMs and NAFLD in adults with a meta-analysis. Methods. Articles published up to January 31, 2023, were systematically searched in PubMed, Web of Science, Cochrane database, Embase, and CNKI. The search formula is as follows: "nonalcoholic fatty liver disease" combined with the terms that bone turnover markers such as "osteocalcin," "collagen type I trimeric cross-linked peptide," and "procollagen type I N-terminal peptide." Stata 15.0 software was used to calculate the pooled OR (95% CI) and perform the heterogeneity test, sensitivity analysis, and publication bias. Results. We identified 18 studies with a total of 12,310 participants. Statistical differences were found between patients with NAFLD compared to the control group for osteocalcin (n = 15 studies; SMD: −0.69; 95% CI: −0.73–−0.64; P = 0.002), procollagen type I N-terminal propeptide (n = 5 studies; SMD: −0.40; 95% CI: −0.80−−0.00; P = 0.049), and collagen type I cross-linked C-telopeptide (n = 7 studies; SMD: −0.16; 95% CI: −0.23−−0.09); P < 0.001). Conclusion. Bone turnover markers were lower in patients with NAFLD compared to the control group. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is an important pathogen causing high morbidity and high mortality in children and undergoes frequent recombination for capsule switching to neutralize the 13-valent pneumococcal conjugate vaccine (PCV13). This study aimed to investigate the prevalence, and molecular characteristics including serotypes and antibiotic susceptibility of S. pneumoniae isolated from children living in Southwest China from 2017 to 2019 to facilitate the selection of effective vaccine formulations and appropriate antibiotic treatment regimens. Methods: This study was conducted at West China Second University Hospital (Chengdu, Sichuan Province, China), Zunyi Medical University Third Affiliated Hospital/First People's Hospital of Zunyi (Zunyi, Guizhou Province, China) and Chengdu Jinjiang District Maternal and Child Healthcare Hospital (Chengdu, Sichuan Province, China). Demographic and clinical characteristics of children infected with S. pneumoniae were collected and analysed. Next-generation sequencing and sequence analysis were used to determine the serotypes, sequence types, antibiotic resistance and potential protein vaccine target genes of the pneumococcal isolates. The coverage rate provided by PCV13 was estimated by calculating the percentage of the specific serotypes that were specifically the PCV13-included serotypes. Antimicrobial susceptibility was determined by the microdilution broth method. Results: The most prevalent pneumococcal serotypes were 19F (25.8%), 19A (14.1%), 6B (12.5%), 6A (9.4%) and 14 (7.8%). The predominant STs were ST271 (23.3%), ST320 (15.5%) and ST90 (8.6%), dominated by the clonal complex Taiwan19F-14 (39.1%). The coverage rate of PCV13 was 77.3% in all the isolates, with relatively higher values in invasive isolates (86.4%). Over the decade, the rates of resistance to penicillin, amoxicillin and cefotaxime were 5.6%, 5.3% and 5.1%, respectively, with significantly higher values in invasive isolates (22.4%, 14.9% and 11.9%). Almost all the isolates were resistant to erythromycin (99.1%) and clindamycin (95.9%). All isolates carried virulence-related genes, including ply, psaA, piaA, piuA, phtE, nanA, pepO, danJ, pvaA, clpP, pcsB, stkP, potD , and strH. The carriage of virulence and resistance genes varied among serotypes and clades, with serotype 19F/ST271 showing higher resistance to antibiotics and being more likely to carry pilus genes and other virulence genes. Conclusion: These data provide valuable information for the understanding of pneumococcal pathogenesis, antimicrobial resistance and the development of protein-based vaccines against pneumococcal infection. [ABSTRACT FROM AUTHOR]

Infectious diseases are a long-standing and severe global public health problem. The rapid diagnosis of infectious diseases is an urgent need to solve this problem. MicroRNA (miRNA) plays an important role in the intervention of some infectious diseases and is expected to become a potential biomarker for the diagnosis and prognosis of infectious diseases. It is of great significance to develop rapid and sensitive methods for detecting miRNA for effective control of infectious diseases. In this study, a simple and highly sensitive homogeneous electrochemical method for microRNAs using enzyme-driven cascaded signal amplification has been developed. In the presence of target miRNA, the reaction system produced plenty of MB-labeled single-nucleotide fragments (MB-MF) containing a few negative charges, which can diffuse to the negative surface of the ITO electrode easily, so an obvious electrochemical signal enhancement was obtained. Without the target, MB-HP contains a relatively large amount of negative charges due to the phosphates on the DNA chain, which cannot be digested by the enzyme and cannot diffuse freely to the negatively charged ITO electrode, so only a small signal was detected. The enhanced electrochemical response has a linear relationship with the logarithm of miRNA concentration in the range of 10 fM to 10 nM and the limit of detection as low as 3.0 fM. Furthermore, the proposed strategy showed the capability of discriminating single-base mismatch and performed eligibly in the analysis of miRNA in cell lysates, exhibiting great potential for disease diagnosis and biomedical research. [ABSTRACT FROM AUTHOR]

Hypobiosis (facultative developmental arrest) is the most important life-cycle adaptation ensuring survival of parasitic nematodes under adverse conditions. Little is known about such survival mechanisms, although ascarosides (ascarylose with fatty acid-derived side chains) have been reported to mediate the formation of dauer larvae in the free-living nematode Caenorhabditis elegans. Here, we investigated the role of a key gene acox-1, in the larval development of Haemonchus contortus, one of the most important parasitic nematodes that employ hypobiosis as a routine survival mechanism. In this parasite, acox-1 encodes three proteins (ACOXs) that all show a fatty acid oxidation activity in vitro and in vivo, and interact with a peroxin PEX-5 in peroxisomes. In particular, a peroxisomal targeting signal type1 (PTS1) sequence is required for ACOX-1 to be recognised by PEX-5. Analyses on developmental transcription and tissue expression show that acox-1 is predominantly expressed in the intestine and hypodermis of H. contortus, particularly in the early larval stages in the environment and the arrested fourth larval stage within host animals. Knockdown of acox-1 and pex-5 in parasitic H. contortus shows that these genes play essential roles in the post-embryonic larval development and likely in the facultative arrest of this species. A comprehensive understanding of these genes and the associated β-oxidation cycle of fatty acids should provide novel insights into the developmental regulation of parasitic nematodes, and into the discovery of novel interventions for species of socioeconomic importance. Author summary: Haemonchus contortus is one of the most pathogenic nematodes causing substantial economic losses worldwide that undergo facultative arrest (diapause) to survive harsh environmental and host conditions. However, the molecular basis (e.g., fatty acid oxidation and dauer pheromone synthesis) underlying such survival mechanisms has not yet been elucidated in parasitic nematodes. Here, we show that an acyl-CoA oxidase ACOX-1 interacts with a peroxin PEX-5 and functions in fatty acid oxidation in peroxisomes. Further, knockdown of ACOX-1 and PEX-5 results in a lethal phenotype of the infective stage and likely developmental parasitic larval stage within host animals. This data demonstrates an essential role of ACOX-1-PEX-5 and potentially ascarosides signalling in the facultative arrested larval development of parasitic nematodes, and suggests possible intervention targets. [ABSTRACT FROM AUTHOR]

Nuclear factor kappa B p50 (NF-κB p50) induces various biological processes. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor for the detection of NF-κB p50 has been developed, which combines the high selectivity of the proximity hybridization assay (PHA) with the high efficiency of the hybridization chain reaction (HCR). [ABSTRACT FROM AUTHOR]

A highly sensitive homogeneous electrochemiluminescence (ECL) biosensor for folate receptor (FR) has been developed based on hyperbranched rolling circle amplification (HRCA) and terminal protection. FR was combined to folic acid modified single stranded DNA (FA‐ssDNA) through the strong affinity between FA and FR, which prevented ssDNA from enzymolysis of exonuclease I (Exo I). The protected ssDNA was then applied as a template of padlock looping to trigger the HRCA proceeding. The products of HRCA contains large amount of double strand DNA (dsDNA), which provided excellent carries for Ru(phen)32+ intercalation. The extra free Ru(phen)32+ was removed by ultrafiltration and the Ru(phen)32+ embedded into dsDNA can act as a high‐efficiency ECL indicator to quantify the FR concentration. The enhanced ECL intensity had a linear relationship with logarithm of FR concentration in the range of 4 fM to 120 pM with a correlation coefficient of 0.998. Furthermore, the proposed ECL biosensor has been applied to detect FR in Hela cells and showed a linear relationship with the logarithm of cell concentration ranging from 100–5000 cell/mL. Compared to other FR biosensors, the proposed ECL biosensor presents the merits of the simplicity, high sensitivity and specificity, which shows the great potential application in the field of early cancers diagnosis. Let there be light: an electrochemiluminescence (ECL) biosensor for detection of the folate receptor is fabricated in a homogeneous system. The combination of an effective ECL indicator (Ru(phen)32+) and the hyperbranched rolling circle amplification (HRCA) technique promotes the high sensitivity of the fabricated biosensor. [ABSTRACT FROM AUTHOR]