Search

Abstract Background MutT homolog 1 (MTH1) sanitizes oxidized dNTP pools to promote the survival of cancer cells and its expression is frequently upregulated in cancers. Polyubiquitination stabilizes MTH1 to facilitate the proliferation of melanoma cells, suggesting the ubiquitin system controls the stability and function of MTH1. However, whether ubiquitination regulates MTH1 in gastric cancers has not been well defined. This study aims to investigate the interaction between MTH1 and a deubiquitinase, USP9X, in regulating the proliferation, survival, migration, and invasion of gastric cancer cells. Methods The interaction between USP9X and MTH1 was evaluated by co-immunoprecipitation (co-IP) in HGC-27 gastric cancer cells. siRNAs were used to interfere with USP9X expression in gastric cancer cell lines HGC-27 and MKN-45. MTT assays were carried out to examine the proliferation, propidium iodide (PI) and 7-AAD staining assays were performed to assess the cell cycle, Annexin V/PI staining assays were conducted to examine the apoptosis, and transwell assays were used to determine the migration and invasion of control, USP9X-deficient, and USP9X-deficient plus MTH1-overexpressing HGC-27 and MKN-45 gastric cancer cells. Results Co-IP data show that USP9X interacts with and deubiquitinates MTH1. Overexpression of USP9X elevates MTH1 protein level by downregulating its ubiquitination, while knockdown of USP9X has the opposite effect on MTH1. USP9X deficiency in HGC-27 and MKN-45 cells causes decreased proliferation, cell cycle arrest, extra apoptosis, and defective migration and invasion, which could be rescued by excessive MTH1. Conclusion USP9X interacts with and stabilizes MTH1 to promote the proliferation, survival, migration and invasion of gastric cancer cells.

Conclusions: There was significant correlation between VSR and multiorgan IR, and the risk of multiorgan IR increased with increasing VSR.

This paper conducts an in-depth study and evaluation of pedestrian paths, with a particular focus on the anti-slip performance and walking comfort of wooden chip pedestrian walkways. Through controlled experiments, a comparative analysis was performed between wooden chip pedestrian walkways and ordinary paved brick walkways. The experimental results indicate that under dry conditions, the anti-slip performance of various road surfaces is good. However, in wet environments, the anti-slip performance of paved brick roads deteriorates significantly. In contrast, wooden chip pedestrian walkways, especially those mixed with asphalt and wood chips, exhibit excellent anti-slip properties and comfort. Additionally, the study reveals that the comfort of wooden chip pedestrian walkways is significantly better than that of paved brick walkways, and the comfort of asphalt materials is slightly better than emulsified asphalt. It is worth mentioning that fine wood chips provide less comfort than coarse wood chips. Although reducing the thickness can enhance comfort, considering the service life of the road, a thickness of 4–6 cm is most suitable. Finally, asphalt and wooden chip mixtures with coarse wood chips possess good water permeability, making them suitable for permeable drainage pavement designs, effectively reducing road surface water accumulation.

Abstract Background The association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. We performed a meta-analysis to evaluate the impact of early tracheostomy compared to late tracheostomy on COVID-19 patients’ outcomes. Methods We searched Medline, Embase, Cochrane, and Scopus database, along with medRxiv, bioRxiv, and Research Square, from December 1, 2019, to August 24, 2021. Early tracheostomy was defined as a tracheostomy conducted 14 days or less after initiation of invasive mechanical ventilation (IMV). Late tracheostomy was any time thereafter. Duration of IMV, duration of ICU stay, and overall mortality were the primary outcomes of the meta-analysis. Pooled odds ratios (OR) or the mean differences (MD) with 95%CIs were calculated using a random-effects model. Results Fourteen studies with a cumulative 2371 tracheostomized COVID-19 patients were included in this review. Early tracheostomy was associated with significant reductions in duration of IMV (2098 patients; MD − 9.08 days, 95% CI − 10.91 to − 7.26 days, p

Cucumber (Cucumis sativus L.) is an important horticultural crop worldwide. Sodium (Na+) and chloride (Cl−) in the surface soil are the major limiting factors in coastal areas of Shandong Province in China. Therefore, to understand the mechanism used by cucumber to adapt to sodium chloride (NaCl), we analyzed the phenotypic and physiological indicators of eighteen cucumber germplasms after three days under 100 and 150 mM NaCl treatment. A cluster analysis revealed that eighteen germplasms could be divided into five groups based on their physiological indicators. The first three groups consisted of seven salt-tolerant and medium salt-tolerant germplasms, including HLT1128h, Zhenni, and MC2065. The two remaining groups consisted of five medium salt-sensitive germplasms, including DM26h and M1-2-h-10, and six salt-sensitive germplasms including M1XT and 228. A principal component analysis revealed that the trend of comprehensive scores was consistent with the segmental cluster analysis and survival rates of cucumber seedlings. Overall, the phenotype, comprehensive survival rate, cluster analysis, and principal component analysis revealed that the salt-tolerant and salt-sensitive germplasms were Zhenni, F11-15, MC2065, M1XT, M1-2-h-10, and DM26h. The results of this study will provide references to identify or screen salt-tolerant cucumber germplasms and lay a foundation for breeding salt-tolerant cucumber varieties.

Abstract Background Cirrhosis can be complicated by electrolyte abnormalities, but the major focus has been concentrated on the clinical significance of serum sodium levels. Emerging studies have identified hypochloremia as an independent prognostic marker in patients with chronic heart failure and chronic kidney disease. The aim of this study was to investigate whether serum chloride levels were associated with mortality of critically ill cirrhotic patients. Methods Critically ill cirrhotic patients were identified from the Multi-parameter Intelligent Monitoring in Intensive Care III Database. The primary outcome was ICU mortality. Logistic regression was used to explore the association between serum chloride levels and ICU mortality. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of serum chloride levels for predicting ICU mortality. Results A total of 1216 critically ill cirrhotic patients were enrolled in this study. The overall ICU mortality rate was 18.8%. Patients with hypochloremia had a higher ICU mortality than those with non-hypochloremia (34.2% vs. 15.8%; p

Diabetic ketoacidosis (DKA), an acute and life-threatening complication of diabetes, is a metabolic disorder caused by insulin deficiency and an increase in counter-regulatory hormones. Several cases of DKA without marked hyperglycemia have been reported and are defined as euglycemic DKA (eu-DKA). The use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) is associated with the occurrence of eu-DKA, of which, dapagliflozin is one of the agents. In this study, we report a case of dapagliflozin-associated eu-DKA following surgery for pancreatic carcinoma. A 57-year-old woman presented with acute abdominal pain after surgery for pancreatic carcinoma. Emergency exploratory laparotomy was performed because of suspicion of gastrointestinal perforation based on a CT scan. The surgeons observed that the stomach was significantly dilated but not perforated. Meanwhile, the patient developed shock and severe acidosis. A further examination confirmed the diagnosis of dapagliflozin-associated eu-DKA. We reviewed the precipitating factors and mechanisms of SGLT2i-associated eu-DKA and discussed the treatment and prevention of this condition. Clinicians need to be alert of the occurrence of SGLT2i-associated eu-DKA in patients treated with this drug in the perioperative period.

The study aims to analyze the influence of complex service factors on ravelling resistance performance for large-void asphalt pavements by carrying out tests on environmental and vehicle factors, conducting ultraviolet aging, freeze–thaw cycles, as well as vehicle speed simulated tests with the Rotating Surface Abrasion Test, vehicle tests, and traffic volume tests, and by making a correlation analysis between the Cantabro Abrasion test and Rotating Surface Abrasion Test. The result shows that environmental factors significantly affect the ravelling resistance performance of drainage asphalt pavements. With the increase in the times of UV aging and freeze–thaw cycles, the ravelling loss rate of asphalt specimens shows a tendency to increase, and the combined test of UV aging and freeze–thaw cycles aggravated the ravelling damage of asphalt specimens. Meanwhile, vehicle factors have a significant attenuation effect on the ravelling resistance performance of drainage asphalt pavements. With the increase in the speed, pressure, and times of the Rotating Surface Abrasion, the ravelling loss rate of asphalt specimens shows a steady tendency to increase. Furthermore, there exists a good correlation between the Rotating Surface Abrasion speed, pressure, times, and the ravelling loss rate. Finally, the two test results of the Cantabro Abrasion test and Rotating Surface Abrasion test are consistent in their changes during single/composite factor analysis, confirming the feasibility of using the Rotating Surface Abrasion test index to characterize the change in the ravelling resistance performance of drainage asphalt pavements.

The WRKY proteins constitute a large family of transcription factors that have been known to play a wide range of regulatory roles in multiple biological processes. Over the past few years, many reports have focused on analysis of evolution and biological function of WRKY genes at the whole genome level in different plant species. However, little information is known about WRKY genes in melon (Cucumis melo L.). In the present study, a total of 56 putative WRKY genes were identified in melon, which were randomly distributed on their respective chromosomes. A multiple sequence alignment and phylogenetic analysis using melon, cucumber and watermelon predicted WRKY domains indicated that melon WRKY proteins could be classified into three main groups (I-III). Our analysis indicated that no recent duplication events of WRKY genes were detected in melon, and strong purifying selection was observed among the 85 orthologous pairs of Cucurbitaceae species. Expression profiles of CmWRKY derived from RNA-seq data and quantitative RT-PCR (qRT-PCR) analyses showed distinct expression patterns in various tissues, and the expression of 16 CmWRKY were altered following powdery mildew infection in melon. Besides, we also found that a total of 24 WRKY genes were co-expressed with 11 VQ family genes in melon. Our comparative genomic analysis provides a foundation for future functional dissection and understanding the evolution of WRKY genes in cucurbitaceae species, and will promote powdery mildew resistance study in melon.

We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS) permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol) was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (t(max) of 5 min) and a C(max) of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted C(max) for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results are being utilized to design prototype dosage forms for initial human pharmacokinetic studies.

We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918) to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute) confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health), Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown). These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1) bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2) partition into the basolateral membrane and directly reduce membrane permeability; (3) aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while highly permeable P-gp substrates such as amprenavir, quinidine, ketoconazole and verapamil do not, regardless of whether they actually use the basolateral transporter.

A comprehensive understanding of the diffusion coefficients and atomic mobilities in the Ti–Cr–Mo system is crucial for establishing an atomic mobility database for titanium-based high-strength titanium alloys. In the present work, nine sets of solid/solid diffusion couples were prepared and measured in bcc Ti–Cr–Mo alloys, with the temperatures ranging from 1373 to 1473 K. Scanning electron microscopy (SEM), and Electro Probe Micro-Analysis (EPMA) techniques were used to respectively test its microstructure and composition distance. The diffusion coefficients in bcc Ti–Cr–Mo alloys were determined using the Matano-Kirkaldy method and numerical inverse method respectively. The diffusion coefficients obtained from the above two methods exhibit good consistency. The atomic mobility parameters for the Ti–Cr–Mo systems were provided with the assistance of HitDIC software. A three-dimensional plot of interdiffusivities was generated for chromium and molybdenum contents ranging from 0 to 20 mol % and 0–14 mol %. Moreover, the application of the Arrhenius equation enabled the determination of changes in frequency factors and activation energies concerning temperature and composition.

The H9N2 subtype of avian influenza virus (AIV) is widely prevalent in poultry and wild birds globally, and has become the predominant subtype circulating in poultry in China. The H9N2 AIV can directly or indirectly (by serving as a “donor virus”) infect humans, posing a significant threat to public health. Currently, there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province, central China. In this study, we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province, and genetic analysis revealed that these viruses belonged to 7 different genotypes. Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations, and exhibited diverse replication abilities within these birds. These viruses could replicate efficiently in the lungs of mice, with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys. At the cellular level, the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays, revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level. The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters. Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China. It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.

Among the major abiotic stresses, salt and drought have considerably affected agricultural development globally by interfering with gene expression profiles and cell metabolism. Transcription factors play crucial roles in activating or inhibiting the expression of stress-related genes in response to abiotic stress in plants. In this study, the Zea mays L. SQUAMOSA promoter-binding protein gene (ZmSBP17) was identified, and the molecular regulatory mechanism of osmotic stress tolerance was analyzed. Phylogenetic analysis confirmed that ZmSBP17 is part of the SBP gene family and is closely related to OsSBP17. The ZmSBP17-GFP fusion protein exhibited green fluorescence in the nucleus, as determined via tobacco epidermal transient transformation system. Acting as a transcriptional activator, the overexpression of ZmSBP17 in Arabidopsis significantly enhanced the expression of genes encoding superoxide dismutases (CSD1/2, MSD1), catalases (CAT1/2), ascorbate peroxidase 1 (APX1), and myeloblastosis transcription factors (AtMYB53/65), which increased the activity of reactive oxygen species (ROS)-scavenging enzymes and reduced ROS levels. Additionally, the expression of abiotic stress-related genes, such as AtDREB2A and AtNHX1, was significantly upregulated by ZmSBP17. Furthermore, ZmSBP17 specifically bound to cis-acting elements containing GTAC core sequences in the promoters of stress-related genes, suggesting that ZmSBP17 regulates the transcription of certain genes by recognizing these sequences. These results indicate that the overexpression of ZmSBP17 in Arabidopsis thaliana significantly increased tolerance to osmotic stress during the germination and seedling stages, which may enhance our understanding of the biological functions of SBPs in maize under abiotic stresses.

Objective: The aim was to predict the effectiveness of using frailty, defined by the frailty index (FI), for predicting recurrent pneumonia and death in patients 50 years and older with vascular cognitive impairment (VCI) during long-term hospitalization. Measurements: This retrospective cohort study was conducted at a teaching hospital in western China and included VCI patients aged ≥50 years undergoing long-term hospitalization. The relevant data were collected from the electronic medical record system. The FI was based on 31 parameters and groups were defined using a cutoff value (0.2) as robust (FI

Numerous studies highlight the significance of biomimetic metallic implant surfaces for enhancing osseointegration through synergistic regulation of osteogenesis-angiogenesis. However, achieving clinical demands through singular structural or compositional biomimicry poses challenges. Therefore, the integration of both structural and compositional biomimicry, to closely emulate the host bone surface, is crucial for maximizing the biological activity of metallic implants. We synthesized a micro/nano hierarchical SrSi-codoped hydroxyapatite coating on Zr16Nb12Ti alloy through a simple microarc oxidation-hydrothermal reaction. Results revealed that Si doping enhances hydroxyapatite (HA) growth along the c-axis, forming large-sized nanorods. However, co-doping of Sr and Si inhibits grain growth by reducing crystal growth freedom, yielding a finer HA nanowire coating (MH-SrSi). MH-SrSi exhibits outstanding hydrophilicity attributed to the finer HA nanowires on the coating surface, promoting the adhesion of proteins and cells. Additionally, the released Sr and Si from MH-SrSi stimulate the secretion of osteogenesis-related proteins in osteoblasts and angiogenesis-related factors in endothelial cells, exhibiting a synergistic effect on promoting osteogenesis and angiogenesis. In vivo evaluation mirrors these results and shows that the micro/nano hierarchical structures of MH-SrSi elicited inward bone growth. Overall, MH-SrSi, combining structural biomimicry and compositional biomimicry, exhibits excellent osseointegration capability, making it a promising candidate for implant materials.

This paper presents a novel hybrid algorithm that combines the Butterfly Optimization Algorithm (BOA) and Quantum-behavior Particle Swarm Optimization (QPSO) algorithms, leveraging $ gbest $ to establish an algorithm communication channel for cooperation. Initially, the population is split into two equal subgroups optimized by BOA and QPSO respectively, with the latter incorporating the Lévy flight for enhanced performance. Subsequently, a hybrid mechanism comprising a weight hybrid mechanism, a elite strategy, and a diversification mechanism is introduced to blend the two algorithms. Experimental evaluation on 12 benchmark test functions and the Muskin model demonstrates that the synergy between BOA and QPSO significantly enhances algorithm performance. The hybrid mechanism further boosts algorithm performance, positioning the new algorithm as a high-performance method. In the Muskingum model experiment, the algorithm proposed in this article can give the best sum of the square of deviation (SSQ) and is superior in the comparison of other indicators. Overall, through benchmark test function experiments and Muskin model evaluations, it is evident that the algorithm proposed in this paper exhibits strong optimization capabilities and is effective in addressing practical problems.

In this study, we presented an investigation into a newly developed metastable Zr–10Nb–6Sn alloy meticulously tailored to fulfill the demanding requisites of magnetic resonance imaging (MRI)-compatible hard implants. The effect of cold rolling reduction (0%, 10%, 20% and 40%) on the mechanical properties and magnetic susceptibility of the alloy has been systematically studied. With the increase of cold rolling reduction, the yield strength and tensile strength of the alloy increase, while the elastic modulus decreases first and then increases slightly. The sample with 40% cold rolling (CR40%) exhibits excellent matching of yield strength ∼ 905 MPa and elastic modulus ∼55.8 GPa, with a superior yield strength-to-elastic modulus ratio than that of other reported metallic biomedical materials. The deformation mechanism of Zr–10Nb–6Sn alloy during cold rolling includes stress-induced α'' phase, kink bands and dislocation slip. Due to the addition of Sn element with low magnetic susceptibility (0.03× 10−6 cm3g−1) and the formation of ω phase, the solution-treated sample (CR0%) has a low magnetic susceptibility ∼ 0.77 × 10−6 cm3g−1, which is significantly lower than that of other reported titanium and zirconium based biomedical alloys. The magnetic susceptibility of the samples increases from 0.77× 10−6 cm3g−1 to 1.35 × 10−6 cm3g−1 as the cold rolling reduction increases, which may be attributed to the decrease in ω-phase content and the increase in α''-phase content during cold rolling. Hence, the cold-workable Zr–10Nb–6Sn alloy, exhibiting exceptional mechanical compatibility and low magnetic susceptibility, holds promise as a potential alloy for MRI-compatible hard tissue replacements.

Objective: This study aimed to explore the factors influencing false-positive results for rifampicin resistance (RIF-R) detected using Xpert MTB/RIF (Xpert). Methods: This retrospective analysis included the clinical data of patients from September 2019 to February 2023. The chi-square and rank sum tests were used to compare differences in patient characteristics between the true-positive and false-positive groups. Logistic regression was used to analyze the factors influencing false positives in the detection of RIF-R by Xpert. Results: A total of 384 patients were included. Logistic regression analysis revealed that, with mutation of probe E as the reference, mutations on probe A or C (OR = 72.68, P

Pigeon Newcastle disease, caused by pigeon paramyxovirus type 1 (PPMV-1), is a significant infectious disease in pigeons that can result in substantial mortality and poses a severe threat to the pigeon industry. The rapid and accurate onsite diagnosis of pigeon disease is crucial for timely diagnosis and the implementation of effective prevention and control measures. In this study, we established a rapid detection method for PPMV-1 based on recombinase-aided amplification (RAA) and CRISPR/Cas12a. The RAA primers target the conserved regions of the L gene for preamplification in clinical nucleic acid samples, followed by CRISPR/Cas12a detection of the target gene. Visualization could be achieved by combination with a lateral flow dipstick (LFD). This method demonstrated high specificity, showing no cross-reactivity with non-PPMV-1 samples. The sensitivity of the method assessed by fluorescence analysis reached 100 copies/µL, and when it was combined with an LFD, the sensitivity was 103 copies/µL. The constructed RAA-CRISPR/Cas12a-LFD visual detection method was applied to clinical sample testing and was found to enable the rapid and accurate detection of swab samples and tissue specimens. Its sensitivity was consistent with the current gold standard, quantitative real-time PCR results. The RAA-CRISPR/Cas12a-LFD detection method we developed provides a novel approach for the rapid, simple, precise, and specific onsite diagnosis of pigeon Newcastle disease.