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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.

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.

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.

The peroxisomal biogenesis factor 19 (PEX19) is necessary for early peroxisomal biogenesis. PEX19 has been implicated in the replication of a variety of viruses, but the details pertaining to the mechanisms of how PEX19 engages in the life cycle of these viruses still need to be elucidated. Here, we demonstrated that the C terminus of PEX19 interacted with the cytoplasmic tail region of the M2 protein of the influenza A virus (IAV) and inhibited the viral growth titers. IAV infection or PEX19 knockdown triggered a reduction in the peroxisome pool and led to the accumulation of ROS and cell damage, thereby creating favorable conditions for IAV replication. Moreover, a reduction in the peroxisome pool led to the attenuation of early antiviral response mediated by peroxisome MAVS and downstream type III interferons. This study also showed that the interaction between IAV M2 and PEX19 affected the binding of PEX19 to the peroxisome-associated protein PEX14 and peroxisome membrane protein 24 (PMP24). Collectively, our data demonstrate that host factor PEX19 suppresses the replication of the IAV, and the IAV employs its M2 protein to mitigate the restricting role of PEX19.

Influenza viruses are the leading cause of upper respiratory tract infections, leading to several global pandemics and threats to public health. Due to the continuous mutation of influenza A viruses, there is a constant need for the development of novel antiviral therapeutics. Recently, natural antimicrobial peptides have provided an opportunity for the discovery of anti-influenza molecules. Here, we designed several peptides based on pheasant cathelicidin and tested their antiviral activities and mechanisms against the H1N1 virus. Of note, the designed peptides Pc-4 and Pc-5 were found to inhibit replication of the H1N1 virus with an IC50 = 8.14 ± 3.94 µM and 2.47 ± 1.95 µM, respectively. In addition, the cyclic peptide Pc-5 was found to induce type I interferons and the expression of interferon-induced genes. An animal study showed that the cyclic peptide Pc-5 effectively inhibited H1N1 virus infection in a mouse model. Taken together, our work reveals a strategy for designing cyclic peptides and provides novel molecules with therapeutic potential against influenza A virus infection.

The floatation capacity of seabed pipelines has long been considered a key risk element during design, especially with the combined loading of waves and currents. This paper presents a two-dimensional coupled approach with a poro-elastoplastic theory to study the floatation of pipelines with the combined loading of waves and currents. The findings suggest that the proposed method is able to capture the mechanical performance of pipeline floatation. Pipeline floatation occurs in two distinct phases. In the initial phases, the pipelines float slowly with the cyclic loadings. In the second stage, when the backfill soil in the middle position of the pipelines begins to liquefy, the floating displacement increases obviously. The boundary constraints provided by the pipelines strengthen the backfill soil as well as accelerate the release of excessive pore water pressure. Meanwhile, a nonliquefiable region is formed under the pipelines. The floating displacement of the pipelines increases as well as current velocity, wave height, and wave period, and reduces with increased backfill soil permeability. Increasing the permeability coefficient of backfill soil can obviously restrain the floatation of pipelines.

Porcine circovirus type 3 (PCV3) infection can cause symptoms similar to those of porcine circovirus type 2 (PCV2) infection, and coinfections with both PCV2 and PCV3 are observed in the swine industry. Consequently, developing chimeric vaccines is essential to prevent and control porcine circovirus infections. In this study, we used both E. coli and mammalian expression systems to express PCV3 Cap (Cap3) and a chimeric gene containing the PCV2-neutralizing epitope within the PCV3 Cap (Cap3-Cap2E), which were assembled into virus-like particle (VLP) vaccines. We found that Cap3 lacking nuclear localization signal (NLS) could not form VLPs, while Cap3 with a His-tag successfully assembled into VLPs. Additionally, the chimeric of PCV2-neutralizing epitopes did not interfere with the assembly process of VLPs. Various immunization approaches revealed that pCap3-Cap2E VLP vaccines were capable of activating high PCV3 Cap-specific antibody levels and effectively neutralizing both PCV3 and PCV2. Furthermore, pCap3-Cap2E VLPs demonstrated a potent ability to activate cellular immunity, protecting against PCV3 infection and preventing lung damage in mice. In conclusion, this study successfully developed a PCV3 Cap VLP vaccine incorporating chimeric PCV2-neutralizing epitope genes, providing new perspectives for PCV3 vaccine development.

[This corrects the article DOI: 10.1371/journal.ppat.1006851.].

Abstract Hypoxia‐associated radioresistance in rectal cancer (RC) has severely hampered the response to radioimmunotherapy (iRT), necessitating innovative strategies to enhance RC radiosensitivity and improve iRT efficacy. Here, a catalytic radiosensitizer, DMPtNPS, and a STING agonist, cGAMP, are integrated to overcome RC radioresistance and enhance iRT. DMPtNPS promotes efficient X‐ray energy transfer to generate reactive oxygen species, while alleviating hypoxia within tumors, thereby increasing radiosensitivity. Mechanistically, the transcriptomic and immunoassay analysis reveal that the combination of DMPtNPS and RT provokes bidirectional regulatory effects on the immune response, which may potentially reduce the antitumor efficacy. To mitigate this, cGAMP is loaded into DMPtNPS to reverse the negative impact of DMPtNPS and RT on the tumor immune microenvironment (TiME) through the type I interferon‐dependent pathway, which promotes cancer immunotherapy. In a bilateral tumor model, the combination treatment of RT, DMPtNPS@cGAMP, and αPD‐1 demonstrates a durable complete response at the primary site and enhanced abscopal effect at the distant site. This study highlights the critical role of incorporating catalytic radiosensitizers and STING agonists into the iRT approach for RC.

BackgroundWilson’s disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient.Case presentationA 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19–26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8–5.5 × 104/ml was administrated by IV infusion at a rate of 50–70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson’s Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 μg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration.ConclusionAmniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively.

Disturbance alters environmental conditions in forests. Plants growing in forests with different disturbance histories in diverse environments may adopt varying life history strategies, but few studies focus on this effect. This study comprehensively investigated plant biodiversity, biomass, and functional traits in subtropical forests with two different disturbance histories in east China to explore differences in life history strategies. Biodiversity was slightly higher in disturbed compared to conserved forests. Significantly higher biomass was measured in conserved relative to disturbed evergreen broadleaved forests (P < 0.05). In conserved forests, leaf tissue density (LTD) was significantly higher and leaf thickness (LT), leaf dry matter content (LDMC), twig tissue density (TTD), twig dry matter content (TDMC), bark tissue density (BTD) and dry matter content (BDMC), and stem tissue density (STD) and dry matter content (SDMC) were significantly lower than in disturbed forests (P < 0.05). In terms of associated plant biodiversity, biomass, and functional traits, conserved forests adopted a resource acquisition strategy, reducing biodiversity and developing multiple functional traits such as high leaf area and specific leaf area and low LT, LDMC, TTD, TDMC, BTD, BDMC, STD, and SDMC to support a high biomass accumulation rate. Disturbed forests adopted a resource conservation strategy, enhancing biodiversity and developing converse trait combinations to lower the rate of biomass accumulation. A comprehensive investigation of plant biodiversity, biomass, and functional traits and subsequent assessment of plant life history strategies in conserved and disturbed forests will aid investigations of regional biodiversity and carbon reserves, contribute data to the TRY and Chinese plant trait databases, and improve ecological management and restoration efforts in east China.

Knowledge about the thermodynamic equilibria of the P2O5-Na2O and P2O5-MgO systems is very important for controlling the phosphorus content of steel materials in the process of steelmaking dephosphorization. The phase equilibrium and thermodynamic data of the P2O5-Na2O and P2O5-MgO systems were critically evaluated and re-assessed by the CALPHAD (CAlculation of PHAse Diagram) approach. The liquid phase was described by the ionic two-sublattice model for the first time with the formulas (Na+1)P(O−2, PO3−1, PO4−3, PO5/2)Q and (Mg+2)P(O−2, PO3−1, PO4−3, PO5/2)Q, respectively, and the selection of the species constituting the liquid phase was based on the structure of the phosphate melts. A new and improved self-consistent set of thermodynamic parameters for the P2O5-Na2O and P2O5-MgO systems was finally obtained, and the calculated phase diagram and thermodynamic properties exhibited excellent agreement with the experimental data. The difference in the phase composition of invariant reactions from the experimentally determined values reported in the literature is less than 0.9 mol.%. The present thermodynamic modeling contributes to constructing a multicomponent oxide thermodynamic database in the process of steelmaking dephosphorization.

In this research, the diffusion behaviors within the Ti-Fe-Cr ternary system were examined at the temperatures of 1273 K and 1373 K through the diffusion couple technique. This study led to the determination of both ternary inter-diffusion and impurity diffusion coefficients in the body-centered cubic (bcc) phase for the Ti-Fe-Cr alloy, utilizing the Whittle–Green and Hall methods. The statistics show that the average diffusion coefficients D˜FeFeTi and D˜CrCrTi measured at 1273 K were 1.34 × 10−12 and 3.66 × 10−13, respectively. At 1373 K, the average values of D˜FeFeTi and D˜CrCrTi were 4.89 × 10−12 and 1.43 × 10−12. By adopting the CALPHAD method, a self-consistent database for atomic mobility in the bcc phase of the Ti-Fe-Cr system was established. This database underwent refinement by comparing the newly acquired diffusion coefficients with data from the existing literature. Diffusion simulations for the diffusion couples were performed, drawing on the established database. The error between the simulated diffusion coefficient and the experimental measurement data is within 15%, and the simulated data of the component distance distribution and diffusion path are in good agreement with the experimental data. The simulations generated results that aligned well with the observed experimental diffusion characteristics, thereby affirming the reliability and accuracy of the database.

Background Preoperative radiation therapy (preRT) is a fundamental aspect of neoadjuvant treatment for rectal cancer (RC), but the response to this treatment remains unsatisfactory. The combination of radiation therapy (RT) and immunotherapy (iRT) presents a promising approach to cancer treatment, though the underlying mechanisms are not yet fully understood. The gut microbiota may influence the response to RT and immunotherapy. Therefore, we aimed to identify the metabolism of gut microbiota to reverse radioresistance and enhance the efficacy of iRT.Methods Fecal and serum samples were prospectively collected from patients with locally advanced rectal cancer (LARC) who had undergone pre-RT treatment. Candidate gut microbiome-derived metabolites linked with radiosensitization were screened using 16s rRNA gene sequencing and ultrahigh-performance liquid chromatography-mass coupled with mass spectrometry. In vitro and in vivo studies were conducted to assess the radiosensitizing effects of the metabolites including the syngeneic CT26 tumor model and HCT116 xenograft tumor model, transcriptomics and immunofluorescence. The CT26 abscopal effect modeling was employed to evaluate the combined effects of metabolites on iRT.Results We initially discovered the gut microbiota-associated metabolite, methylglyoxal (MG), which accurately predicts the response to preRT (Area Under Curve (AUC) value of 0.856) among patients with LARC. Subsequently, we observed that MG amplifies the RT response in RC by stimulating intracellular reactive oxygen species (ROS) and reducing hypoxia in the tumor in vitro and in vivo. Additionally, our study demonstrated that MG amplifies the RT-induced activation of the cyclic guanosine monophosphate AMP synthase-stimulator of interferon genes pathway by elevating DNA double-strand breaks. Moreover, it facilitates immunogenic cell death generated by ROS-mediated endoplasmic reticulum stress, consequently leading to an increase in CD8+ T and natural killer cells infiltrated in the tumor immune microenvironment. Lastly, we discovered that the combination of anti-programmed cell death protein 1 (anti-PD1) therapy produced long-lasting complete responses in all irradiated tumor sites and half of the non-irradiated ones.Conclusions Our research indicates that MG shows promise as a radiosensitizer and immunomodulator for RC. Furthermore, we propose that combining MG with iRT has great potential for clinical practice.

The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity (MVPA) time and sedentary (SED) time with a history of cardiovascular disease (CVD) and multifactorial (i.e., blood pressure (BP), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin A1c (HbA1c)) control status among type 2 diabetes mellitus (T2DM) patients in China. A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes (MIDiab) study was performed. Patients were grouped according to their self-reported MVPA time (low, < 150 min·week−1; moderate, 150 to < 450 min·week−1; high, ≥ 450 min·week−1) and SED time (low, < 4 h·d–1; moderate, 4 to < 8 h·d–1; high, ≥ 8 h·d–1). Participants who self-reported a history of CVD were identified as having a CVD risk. Odds ratios (ORs) and 95% confidence intervals (CIs) of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models, adjusting for China’s geographical region characteristics. The participants had a mean ± standard deviation (SD) age of (60.87 ± 8.44) years, 44.5% were women, and 25.1% had CVD. After adjustment for potential confounding factors, an inverse association between high MVPA time and CVD risk that was independent of SED time was found, whereas this association was not observed in the moderate-MVPA group. A higher MVPA time was more likely to have a positive effect on the control of BMI. Compared with the reference group (i.e., those with MVPA time ≥ 450 min·week−1 and SED time

A good understanding of failure mechanisms can help us improve the lifetime of the dies. This paper presents a case study investigating the wear behaviour of a QRO90 die insert utilized for stamping uncoated boron-alloyed high-strength steel sheets. Topography and microstructure were characterized by means of scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), hardness measurement and X-ray photoelectron spectroscopy (XPS). Severe galling due to accumulated layers transferred from the boron-alloyed steel workpieces occurred on the die surface. Material softening was detected in the sublayer of the tool steel (up to ∼200 μm). In addition, white layers with a in a thickness of 1–2 μm were frequently observed on the surface of the round corner of the tool. The main wear mechanisms are discussed. Galling caused by surface softening and the spallation of white layers are considered to be the primary wear mechanisms for the tool.

When measuring plant functional traits across geomorphologies, 5–10 healthy individuals of a plant species are commonly sampled. However, whether more individuals should be sampled in habitat-heterogeneous karst vegetation remains unknown. In this study, two dominant tree species (Clausena dunniana and Platycarya strobilacea) in karst evergreen and broadleaved mixed forests in Southwestern China were selected. On the basis of a large quantity of individuals of the two species grown in different peak clumps and slope positions, variations of 10 morphological traits in the two species were statistically analyzed. The suggested sampling number of individuals, which could mostly represent the common trait characteristics, was further explored. All traits showed significant differences between the two species (p

Background: Anoikis is a type of apoptosis associated with cell detachment. Resistance to anoikis is a focal point of tumor metastasis. This study aimed to explore the relationship among anoikis-related genes (ARGs), immune infiltration, and prognosis in colorectal cancer (CRC).Methods: The transcriptome profile and clinical data on patients with CRC were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Patients were divided into two clusters based on the expression of ARGs. Differences between the two ARG molecular subtypes were analyzed in terms of prognosis, functional enrichment, gene mutation frequency, and immune cell infiltration. An ARG-related prognostic signature for predicting overall survival in patients with CRC was developed and validated using absolute value convergence and selection operator (LASSO) regression analysis. The correlation between the signature risk score and clinicopathological features, immune cell infiltration, immune typing, and immunotherapy response was analyzed. The risk score combined with clinicopathological characteristics was used to construct a nomogram to assess CRC patients’ prognosis.Results: Overall, 151 ARGs were differentially expressed in CRC. Two ARG subtypes, namely, ARG-high and ARG-low groups, were identified and correlated with CRC prognosis. The gene mutation frequency and immune, stromal, and ESTIMATE scores of the ARG-high group were higher than those of the ARG-low group. Moreover, CD8, natural killer cells, M1 macrophages, human leukocyte antigen (HLA), and immune checkpoint-related genes were significantly increased in the ARG-high group. An optimized 25-gene CRC prognostic signature was successfully constructed, and its prognostic predictive ability was validated. The high-risk score was correlated with T, N, M, and TNM stages. Risk scores were negatively correlated with dendritic cells, eosinophils, and CD4 cells, and significantly positively correlated with regulatory T cells. Patients in the high-risk group were more likely to exhibit immune unresponsiveness. Finally, the nomogram model was constructed and showed good prognostic predictive power.Conclusion: ARGs are associated with clinicopathological features and the prognosis of CRC, and play important roles in the immune microenvironment. Herein, we underpinned the usefulness of ARGs in CRC to develop more effective immunotherapy techniques.

High-sugar and high-fat diets cause significant harm to health, especially via metabolic diseases. In this study, the protective effects of the antidiabetic drug exenatide (synthetic exendin-4), a glucagon-like peptide 1 (GLP-1) receptor agonist, on high-fat and high-glucose (HFHG)-induced renal injuries were investigated in vivo and in vitro. In vivo and in vitro renal injury models were established. Metabolomic analysis based on 1H-nuclear magnetic resonance was performed to examine whether exenatide treatment exerts a protective effect against kidney injury in diabetic rats and to explore its potential molecular mechanism. In vivo, 8 weeks of exenatide treatment resulted in the regulation of most metabolites in the diabetes mellitus group. In vitro results showed that exendin-4 restored the mitochondrial functions of mesangial cells, which were perturbed by HFHG. The effects of exendin-4 included the improved antioxidant capacity of mesangial cells, increased the Bcl-2/Bax ratio, and reduced protein expression of cyt-c and caspase-3 activation. In addition, exendin-4 restored mesangial cell energy metabolism by increasing succinate dehydrogenase and phosphofructokinase activities and glucose consumption while inhibiting pyruvate dehydrogenase E1 activity. In conclusion, GLP-1 agonists improve renal injury in diabetic rats by ameliorating metabolic disorders. This mechanism could be partially related to mitochondrial functions and energy metabolism.