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Gold–Platinum (Au–Pt) alloy demonstrates considerable promise as a material for spacecraft proof mass, due to its ultra-low magnetic susceptibility. This study systematically investigates the effect of heat treatment on the microstructure evolution, magnetic properties, and mechanical performance of the Au72Pt28 alloy. The results indicate that the Pt-rich phase can be precipitated by discontinuous precipitation (DP) and continuous precipitation (CP) reactions. There is a competition between the two precipitation behaviors of Pt-rich phase, which is closely related to their diffusion path. With increasing ageing time and temperature, the discontinuous precipitates gradually coarsen and extend from grain boundaries into grain interior, while the Pt-rich phase nanoparticles precipitated by CP reaction uniformly distribute in the grain interior. Besides, the volume fraction of Pt-rich phase gradually increases, resulting in the increase of magnetic susceptibility. The coarsening of discontinuous precipitates is the main reason for the decrease in the nanoindentation hardness, and it increases rapidly due to a large number of intragranular Pt-rich phase nanoparticles.

An in-depth understanding of the bimodal scale particle reinforced composites, including the particle content and size, phase constitution and distribution, and their effects on mechanical properties and deformation mechanisms, is essential to advance the study of high performance high entropy alloys (HEAs). In this study, the bimodal-sized (nano + micron)(N + M)-Al2O3P/CoCrFeMnNi reinforced composites and monomadal-sized micron(M)-Al2O3P/CoCrFeMnNi reinforced composites were successfully fabricated using a two-step ball milling process in conjunction with spark plasma sintering (SPS) technology. Results showed that the Al2O3P/CoCrFeMnNi composites primarily consisted of fcc structure, with Al2O3 and MnAl2O4 as secondary phases. The M-Al2O3P reinforced composites contained obvious heterogeneous structure while (N + M)-Al2O3P reinforced composites exhibited a multi-scale grain structure comprising of double-sized reinforcement and multiple-sized matrix grains. The yield strength (YS) of bimodal-size particle reinforced composites was higher than that of monomadal particle reinforced composites. For example, the YS of (N-5)/(M − 5) and (N-5)/(M − 10) composites was 117% and 133% higher than that of HEA, respectively. Intriguingly, (N + M)-Al2O3P reinforced composites effectively addressed the issue of reduced material strength caused by a high concentration of particles with a monomadal size. Moreover, the composites of (N-5)/(M − 5) and (N-5)/(M − 10) with a high content of lightweight Al2O3P effectively contributed to the reduction in density of HEA, exhibiting a decrease by 11% and 17% compared to pure HEA, respectively.

Abnormal regional variations in electrical and calcium homeostasis properties have been implicated in catecholaminergic polymorphic ventricular tachycardias (CPVT) attributable to abnormal RyR2-mediated store Ca2+ release, but their underlying mechanism have not been well explored in intact hearts. Methods: We performed in vivo and ex vivo studies including high throughput mapping of Ca2+ transients (CaT) and transmembrane voltage (Vm) in murine wild-type (WT) and heterozygous RyR2-R2474S/+ hearts, before and during isoprenaline (ISO) challenge. Results: ISO-challenged RyR2-R2474S/+ showed increased incidence of arrhythmia accompanied by abnormal Ca2+ transients compared to WT. CaT duration (CaTD) in the LV apex amongst regions studied both before and during ISO challenge in both WT and RyR2-R2474S/+ ventricles. RyR2-R2474S/+ ventricles showed prolonged CaTD, both before and during isoprenaline (ISO) challenge. Conversely, action potential durations (APD) were the same in WT and RyR2-R2474S/+ ventricles and identically reduced by ISO challenge. RyR2-R2474S/+ showed Vm-CaT latencies at time to half decay, but not rise time to peak, which were significantly prolonged compared to WT in all ventricular regions examined with ISO challenge. Following burst pacing, ventricular localized concordant alternans in CaT and APD were readily observed in RyR2-R2474S/+ but not in WT mice. Such CaT and APD alternans occurred mostly semiannually in specific regions of the ventricular pre-occurrence of VT. Conclusion: The pro-arrhythmic RyR2-R2474S/+ phenotype in intact hearts thus directly parallels delayed regional CaT recovery properties and alteration of Vm-CaT latencies. Studies suggest that discordant localized calcium alternans are mechanistically responsible for action potential duration alternans and occurrence of VT in RyR2-R2474S/+ mice.

BackgroundPatients with traumatic brain injury (TBI) often experience post-injury anxiety and depression, which can persist over time. However, the relationships between anxiety and depression in TBI patients and delirium, sleep quality, self-efficacy, and serum inflammatory markers require further investigation.ObjectiveThis study aims to explore the associations of delirium, sleep quality, self-efficacy, and serum inflammatory markers with anxiety and depression in TBI patients, and to examine potential influencing factors.MethodsWe conducted a cohort study involving 127 patients with TBI. Delirium was assessed using the Confusion Assessment Method (CAM) and CAM-ICU, while anxiety, depression, sleep quality, self-efficacy, and pain were evaluated using the appropriate tools, respectively. Serum inflammatory markers (CRP, TNF-α, IL-6) were collected within 1 day post-injury. Generalized estimating equations (GEE) were used to analyze the relationships between delirium, sleep, self-efficacy, and anxiety/depression.ResultsThe study identified 56 patients with delirium. Patients with delirium differed significantly from those without delirium in age, TBI classification, sleep duration, CRP levels, TNF-α levels, pain, self-efficacy, and insomnia (P < 0.05). The GEE analysis revealed that delirium, CRP levels, self-efficacy, underlying diseases, insomnia, TBI classification, age, and sleep duration were associated with anxiety symptoms in TBI patients at 6 months post-discharge (P < 0.05). Depression in TBI patients at 6 months post-discharge was not associated with delirium or insomnia but correlated with CRP levels, TBI classification, and self-efficacy (P < 0.05).ConclusionTBI patients who experience delirium, insomnia, and low self-efficacy during the acute phase are likely to exhibit more anxiety at the 6-month follow-up. Depression in TBI patients is not associated with delirium or insomnia but is negatively correlated with self-efficacy. CRP levels post-TBI may serve as a biomarker to identify patients at risk of emotional symptoms and potentially accelerate patient recovery.

Abstract Background Oral melanoma (OM) and oral squamous cell carcinoma (OSCC) are frequently diagnosed in dogs, presenting a challenge in distinguishing them from benign oral tumors (BN). Salivary metabolomic biomarkers offer a practical solution because of saliva's direct contact with tumors and the noninvasive nature of collection. Objective Assess the diversity and abundance of the salivary metabolome in dogs with BN, OM, and OSCC using amine/phenol submetabolome analysis and high‐performance chemical isotope labeling liquid chromatography–mass spectrometry (CIL LC‐MS). Animals Study included 11 BN, 24 OM, 10 OSCC, and 20 healthy control dogs. Methods Case‐control cross‐sectional study was conducted to assess salivary submetabolic profiles in dogs with BN, OM, and OSCC and healthy dogs. Samples were labeled with 12C‐dansyl chloride and analyzed using CIL LC‐MS targeted to amine‐ and phenol‐containing metabolites for amine/phenol submetabolome analysis. Results Distinct clusters and significant differences in metabolite concentrations were observed among the oral cancer, BN, and control groups. A total of 154 and 66 metabolites showed significantly altered concentrations, particularly in OM and OSCC, respectively, when compared with BN (Padj < .05). Potential metabolic biomarkers were identified for each cancer, including decreased concentrations of seryl‐arginine and sarcosine in OSCC. Moreover, high‐confidence putative metabolites were identified, including an increase in tryptophyl‐threonine and a decrease in 1,2‐dihydroxynapthalene‐6‐sulfonic acid and hydroxyprolyl‐hydroxyproline for OM. Conclusions and Clinical Importance We identified high coverage of the amine/phenol submetabolome, including seryl‐arginine, and sarcosine, in OSCC. Our findings emphasize the potential of these biomarkers for distinguishing between oral OSCC and BN in dogs.

Abstract To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L− 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L− 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L− 1 IAA.

Abstract Aphanomyces euteiches causes root rot in pea, leading to significant yield losses. However, the metabolites involved in this pathosystem have not been thoroughly studied. This study aimed to fill this gap and explore mechanisms of bacterial suppression of A. euteiches via untargeted metabolomics using pea grown in a controlled environment. Chemical isotope labeling (CIL), followed by liquid chromatography-mass spectrometry (LC–MS), was used for metabolite separation and detection. Univariate and multivariate analyses showed clear separation of metabolites from pathogen-treated pea roots and roots from other treatments. A three-tier approach positively or putatively identified 5249 peak pairs or metabolites. Of these, 403 were positively identified in tier 1; 940 were putatively identified with high confidence in tier 2. There were substantial changes in amino acid pool, and fatty acid and phenylpropanoid pathway products. More metabolites, including salicylic and jasmonic acids, were upregulated than downregulated in A. euteiches-infected roots. 1-aminocyclopropane-1-carboxylic acid and 12-oxophytodienoic acid were upregulated in A. euteiches + bacterium-treated roots compared to A. euteiches-infected roots. A great number of metabolites were up- or down-regulated in response to A. euteiches infection compared with the control and A. euteiches + bacterium-treated plants. The results of this study could facilitate improved disease management.

The paper comprehensively describes the evolution of metastable microstructures in a cast low-Ta-containing γ-TiAl alloy during cooling-tempering-lamellarization heat treatments. The behavior and mechanism of microstructure refinement are discussed. The rapid cooling generates metastable microstructures, including Widmanstätten, feathery, and massive structures, with many γ variants in small sizes and different orientations. It significantly refines the coarsened colonies and randomizes the texture. The tempering can effectively stabilize the metastable microstructures. During tempering, the γ→α phase transformation is more active at higher temperatures while coarsening and recrystallization dominate at lower temperatures. After tempering, a refined microstructure with spherical grains and convoluted structures forms. Subsequent lamellarization treatment optimizes the microstructure and obtains a fine-grained nearly-lamellar microstructure with small colonies (∼70 μm) and dispersed fine γ grains (∼10 vol%), which yielded a 1.0 % elongation with a 487 MPa yield strength (0.2%) and a 589 MPa ultimate tensile strength at room temperature. Finally, the unique promotion effects and mechanism of a small amount of Ta addition on the nucleation, growth, evolution, and stabilization of metastable microstructures are concluded and discussed, which is crucial for the refinement of cast γ-TiAl alloy by heat treatment alone.

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism. Methods and analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score

The effects of Ta alloying on the isothermal oxidation behavior and mechanism of a cast Ti-48Al-3Nb-1.5Ta (at.%) TiAl alloy are investigated. It exhibits excellent oxidation resistance with mass gains of 0.95 and 1.29 mg·cm−2 after 900 °C oxidation for 100/200 h in the air, similar to 8 at.% Nb-containing TiAl alloys. The oxide scale shows a complex multi-layer structure, where the Al2O3 layer and continuous dense nitride layer act as protective layers against diffusion and metal oxidation. The oxidation mechanisms are discussed thermodynamically and kinetically. Compared with Nb, Ta is more significant in inhibiting diffusion and promoting the formation of the protective continuous nitride layer, thus being more effective in improving the oxidation resistance of cast TiAl alloy. Consequently, without considering the influence of microstructure, the oxidation resistance of cast Nb-containing TiAl alloy can be further improved by replacing some Nb with a small amount of Ta. It is supposed to provide new insights into the design of oxidation-resistant TiAl alloys.

Donghua steel continuous casting-rolling (DSCCR) line is a new endless rolling line in which tunnel heating furnace is added before and after roughing mills to change the temperature field of slab and intermediate slab, but this change will affect the microstructure and properties of hot rolled plate. Therefore, the microstructure evolution, mechanical properties, texture analysis, hole expanding and earing test of 2.0 mm thick hot rolled plate produced by DSCCR line at different final rolling temperature of 860°C, 840°C and 820°C are studied. The results show that with the decrease of final rolling temperature, there is an obvious layered microstructure distribution along the thickness direction, and the surface coarse grain area gradually expands inward, at the same time the morphology of cementite also changed from large multi domain lamellar pearlite and long rod cementite to small single domain lamellar pearlite and short rod cementite. The engineering stress-strain curves have discontinuous yield with the yield elongation of 4-5% and the elongations are more than 35%. EBSD analysis shows that small angle grain boundaries and deformed grains increase significantly with the decrease of final rolling temperature, and are mainly distributed in fine grain area. Hole expanding and earing tests show that with the decrease of final rolling temperature, the earing performance decreased but the limiting hole expanding ratio is similar.

Although the catalytic properties of Au–Pt alloys have received widespread attention, there are a few of relevant studies on their microscopic deformation process. Considering that Au–Pt alloys are noble metals, and the costs of experiments are extremely high. Direct research experiments are extremely expensive. So the molecular dynamics method which can directly observe the evolution process of microstructure and analyze the mechanical behavior of each deformation stage of the material was adopted to explore the underlined relationship between the temperature and the compression deformation mechanism. The results show that during the process of compression deformation, lots of atoms in the crystal are converted into boundary atoms, the dislocation multiplication and the grain fragmentation occur. In different temperature intervals, along with the compression deformation, low temperature, medium temperature and high temperature recovery appear. Due to the influence of the dual mechanism of deformation and recovery, the deformation mechanism is different at different temperatures, at low temperature stage is mainly the dislocation multiplication and the grain fragmentation, at middle temperature stage is the combination of the opposite sign dislocation, and at high temperature stage is mainly the merger of the grain.

Mg3Sb2-based materials, part of the Zintl compound family, are known for their low thermal conductivity but face challenges in thermoelectric applications due to their low energy conversion efficiency. This study addressed these limitations through first-principles calculations using the CASTEP module in Materials Studio 8.0, aiming to enhance the thermoelectric performance of Mg3Sb2 via strategic doping. Density functional theory (DFT) calculations were performed to analyze electronic properties, including band structure and density of states (D.O.S.), providing insights into the influence of various dopants. The semiclassical Boltzmann transport theory, implemented in BoltzTrap (version 1.2.5), was used to evaluate key thermoelectric properties such as the Seebeck coefficient, electrical conductivity, electronic thermal conductivity, and electronic figure of merit (eZT). The results indicate that doping significantly improved the thermoelectric properties of Mg3Sb2, facilitating a transition from p-type to n-type behavior. Bi doping reduced the band gap from 0.401 eV to 0.144 eV, increasing carrier concentration and mobility, resulting in an electrical conductivity of 1.66 × 106 S/m and an eZT of 0.757. Ge doping increased the Seebeck coefficient to −392.1 μV/K at 300 K and reduced the band gap to 0.09 eV, achieving an electronic ZT of 0.859 with low thermal conductivity (11 W/mK). Si doping enhanced stability and achieved an electrical conductivity of 1.627 × 106 S/m with an electronic thermal conductivity of 11.3 W/mK, improving thermoelectric performance. These findings established the potential of doped Mg3Sb2 as a highly efficient thermoelectric material, paving the way for future research and applications in sustainable energy solutions.

Background: To determine the effect of continuous care based on mobile application on patients' quality of life and self-care ability after mechanical heart valve replacement. Methods: Ninety patients who underwent cardiac mechanical valve replacement in the cardiovascular surgery department of a tertiary general hospital in Guizhou Province from September 2020 to January 2022 were selected for the study. The subjects were randomly divided into a control group and an intervention group using the SPSS25.0 software, with 45 patients in the two groups. The control group received routine nursing care during hospitalization, health education the day before discharge, and regular telephone and outpatient follow-up 6 months after discharge. Based on the control group's care, the intervention group received Mobile APP continuous care for 6 months. The effectiveness of patient's quality of life, medication adherence, international normalized ratio (INR) value compliance rates and self-care ability following mechanical heart valve replacement were evaluated the day before discharge and at the 1, 3 and 6 months after discharge. Results: Scores of quality of life, warfarin medication adherence, and self-care ability rose considerably in the intervention group compared to the control group, and the differences were statistically significant. Conclusion: The mobile phone application (APP) 's continuity of care could improve patients' quality of life, medication adherence, INR value compliance rates, and self-care ability. Clinical Trial Registration: No: ChiCTR2400081250. Registered 27 February, 2024, https://www.chictr.org.cn.

Abstract Left ventricular diastolic dysfunction (LVDD) is an early event associated with cardiovascular complications and poor prognosis in chronic kidney disease patients undergoing dialysis. In this study, we investigated whether diastolic dysfunction, measured by the E/E′ ratio, affects adverse outcomes in peritoneal dialysis (PD) patients (n = 148). Our results showed that patients with an E/E′ ratio ≥ 15 were more likely to be female, have a longer dialysis vintage, have significantly higher left atrial volume index and left atrial kinetic energy levels, have lower E′ levels and LV hypertrophy (LVH) degree, and have higher volume markers. Kaplan–Meier curves revealed that patients with a higher E/E′ ratio had worse survival and a higher risk of heart failure than those with a lower E/E′ ratio. Subgroup analysis demonstrated that non-diabetic patients with a higher E/E′ ratio had a higher risk of heart failure than those with a lower E/E′ ratio. Cox proportional hazard regression analysis indicated that the ECW/ICW ratio was strongly associated with LVDD and confirmed that the E/E′ ratio was an independent risk factor for overall death. Our study suggests that monitoring the E/E′ ratio in PD patients is important for improving their prognosis.

In the present work, novel nano-Al2O3p reinforced heterogeneous CoCrFeMnNi matrix composites with 0–7.5 wt% Al2O3p were fabricated by mechanical alloying (MA) and spark plasma sintering (SPS) method. The microstructure evolution and properties, i.e., density, hardness and room temperature compression were systematically studied. The results show that different degrees of heterogeneous matrix organization occurred in the composites. The CoCrFeMnNi-2.5 wt%Al2O3p composite consists of CG region and UFG region of uniformly distributed nano-Al2O3p. And the addition of nano-Al2O3p can effectively refine the matrix grains. Compared to pure HEA, the grain size of CoCrFeMnNi-5.0 wt%Al2O3p composite is refined by 48.5%. With the increase of nano-Al2O3 content, the hardness values of the composites increased by 23.6%–56.7% than those of pure HEA. Among the nanocomposites, the CoCrFeMnNi-5.0 wt%Al2O3p composite exhibits the best strengthening effect, while the CoCrFeMnNi-2.5 wt%Al2O3p composite shows a superior strong-plastic synergistic effect with yield strength, ultimate compressive strength and fracture strain of 913 MPa, 1935 MPa and 38%, respectively. However, with the Al2O3p content further increases to 7.5 wt%, both the strength and plasticity of the composite decrease due to the serious agglomeration of nanoparticles.

The Ni61Fe10Cr10Al17Mo2 high-entropy alloys (HEAs) with low density have been developed with great potentials for applications. The forging process is one of the important methods for fabricating components. Accordingly, the study of the deformation behavior of HEAs is the essence in the processing and molding of this material for using in industry. Moreover, there are multiple phases with hierarchical structures in the as-cast Ni61Fe10Cr10Al17Mo2 alloys, with the face-centered cubic (FCC) phase as the matrix phase accompanied with hard body-centered cubic (BCC) B2 phase. Here, the hot deformation behaviors of the homogenized Ni61Fe10Cr10Al17Mo2 alloy were investigated at strain rates ranging from 0.001 to 1.0 s−1 and temperatures ranging from 1000 to 1200 °C via isothermal compression tests. The true stress-strain curves were used to reveal the relationship between the flow stress and the deformation temperature and strain rate. The constitutive equations describing the correlations between the flow stress and hot compression parameters were constructed. At the same time, the dynamic material model and instability criterion were used to plot the hot processing map. Furthermore, the deformed microstructures and the dynamic recrystallization of alloy were investigated. Combined with the processing map, the optimal processing route is obtained.

BackgroundPatients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH.MethodsPatients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated.ResultsA total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55–0.77] and 0.72 (95% CI: 0.63–0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40–0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72–0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value.ConclusionARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment.

PurposeThe purpose of this study was to explore the factors influencing PRL levels in patients with prolactinoma and to investigate the correlations between anxiety, depression, sleep, self-efficacy, and PRL levels.MethodsThis retrospective study included 176 patients with prolactinoma who received outpatient treatment at the Affiliated Hospital of Zunyi Medical University from May 2017 to August 2022. The general information questionnaire, Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and General Self-Efficacy Scale (GSES) were used for data collection. A generalized estimating equation (GEE) model was used to analyze the factors influencing PRL levels in patients with prolactinoma. GEE single-effect analysis was used to compare PRL levels at different time points between anxiety group and nonanxiety group, between insomnia group and normal group, and between low, medium, and high self-efficacy groups.ResultsThe median baseline PRL level and the PRL levels at 1, 3, 6, and 12 months of follow-up were 268.50 ng/ml, 122.25 ng/ml, 21.20 ng/ml, 19.65 ng/ml, and 16.10 ng/ml, respectively. Among patients with prolactinoma, 59.10% had anxiety (HADS-A score = 7.35 ± 3.34) and 28.98% had depression (HADS-D score = 5.23 ± 3.87), 9.10% had sleep disorders (AIS score = 6.10 ± 4.31) and 54.55% had low self-efficacy (GSES score = 2.13 ± 0.83). Educational level, tumor size, number of visits, sleep quality, anxiety level, and self-efficacy level were found to be factors influencing PRL levels in patients with prolactinoma (P

The novel loquat cultivar ‘Chunhua No.1′ (CH1) is a promising commercial cultivar. However, CH1 has texture characteristics different from those of common loquat, and its formation mechanism remains unclear. Here, we first identified the phenolic compounds of CH1 and its parent (‘Dawuxing’, DWX) and the effect on texture formation. The special presence of stone cells explained the flavor differences in CH1. Chlorogenic acid, neochlorogenic acid, and coniferyl alcohol were the main phenolic compounds in loquat, and the high content of coniferyl alcohol was a potential factor for the rough texture of CH1. Transcriptome reveals that phenylpropanoid metabolism was activated during CH1 fruit texture formation. Kyoto Encyclopedia of Genes and Genomes (KEGG) identified 51 structural genes involved in phenylpropanoid biosynthesis, and Weighted Gene Co-expression Network Analysis (WGCNA) identified four structural genes and 88 transcription factors. These findings provide new insights into the phenolic metabolism and flavor formation of loquat fruit.

The Al2O3 coating on continuous TiNb fiber can effectively suppress the interfacial reaction in TiNbf/TiAl composites. Some phase transitions in fiber have been founded and their formation reason was analyzed. The micromechanical properties of each phase and macroscopic mechanical properties of the composites were also systematically studied. The α+β duplex structure exhibiting texture feature was found in the most regions of TiNb fiber. Meanwhile α+δ layer, σ layer, outer α layer, and β layer would be formed respectively within 10 μm of the fiber surface whose formation reasons were explained from thermodynamics dominated by Al element. Nanoindentation tests indicated the deformation capacity of each phase satisfied: β＞δ＞σ＞α (outer)＞α (inner)＞Al2O3 coating. The composite with coated fibers has excellent fracture strength of 498 MPa and the fracture toughness of 18.72 MPa m, which was benefited from the fine grain strengthening and precipitation strengthening mechanisms. The Al2O3 coating can significantly improve the thermal stability of the composites during thermal exposure below 1250 °C, and keep the mechanical properties from degradation. This work is of great significance for understanding the phase transformation and deformation process of innovative Al2O3 coated TiNb fiber reinforced TiAl matrix composites.

IntroductionA group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.MethodsWe identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).ResultsThrough these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.ConclusionOur study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Juxtaglomerular cell tumor (JCT) is an endocrine tumor marked by elevated renin levels and high blood pressure. This case report presents the clinical findings of a 47-year-old woman with a history of recurrent hypokalemia, headaches, hypertension, and increased plasma renin activity (PRA). Dynamic enhanced magnetic resonance imaging (MRI) revealed a small nodule on the upper part of the right kidney. Selective renal venous sampling indicated a higher PRA only in the right upper pole renal vein. The patient underwent surgical removal of the right kidney mass, and the pathology results confirmed the diagnosis of JCT. This case underscores the importance of conducting selective renal venous sampling for accurate JCT diagnosis.

The unique cellular structure has been reported to be the dominant reason for the remarkable mechanical properties in laser powder-bed fusion (LPBF) superalloys. However, the specific strengthening mechanism of the cellular structure needs to be further researched. In this study, the microstructure and tensile properties of a composition-optimized Haynes 230 alloy fabricated by the LPBF method were systematically investigated. The post-heated HT1 and HT2 samples with different cellular and grain structures served as the reference. The results show that the micron-scale grain and submicron-scale cellular structures are present in the as-built (AB) sample. The cellular boundaries are characterized by solute Nb segregation and high-density dislocations. The tensile tests show that the AB sample illustrates excellent tensile properties with ultimate tensile strength (UTS) of 1180.2 MPa, yield strength (YS) of 842.5 MPa and elongation (EL) of 29.3 %. The high YS mainly results from the strengthening effects of the cellular structure, which can be considered as a combination of dislocation and elemental segregation strengthening. The contribution of cellular structure to YS is much higher than that of GB strengthening. Furthermore, the deformation incompatibility of heterogeneous grain and cellular structures leads to high hetero-deformation induced (HDI) strengthening, which is also the primary reason for the abnormal upturn of strain hardening rate (SHR) in the AB sample.

Titanium dioxide (TiO2) is widely used in various fields, and doped TiO2 exhibits different characteristics in different fields. Although numerous studies of Fe-doped TiO2 have been reported, they mainly analyze the influence of Fe on TiO2. The behavior of Fe during the phase transition of TiO2 has been rarely studied. To explore the continuous behavior of Fe during the phase transition of Fe-doped TiO2, the real-time phase transitions of Fe-doped and pure TiO2 at 300–1000 °C were characterized using high-temperature in-situ X-ray diffraction (XRD). Based on the experimental results, models of Fe-doped TiO2 were established using density functional theory (DFT). By comparing the calculated and refined values of the in-situ XRD data of Fe-doped TiO2 and an analysis of the defect formation energies, the evolution of Fe was as follows: Fe is located at a lattice interstice of anatase with an oxygen vacancy → Fe at a Ti site in anatase with an oxygen vacancy → Fe at a Ti site in rutile with an oxygen vacancy → Fe at a Ti site in rutile without an oxygen vacancy. This study reveals the deep connection between the microscopic properties of Fe and the phase transition of Fe-doped TiO2 and clarifies the states of Fe. It provides a theoretical basis for determining the states of doped atoms during the phase transition of TiO2 and theoretical guidance for research regarding the phase transitions of doped TiO2 systems.

Abstract The most commercialized kiwifruit, Actinidia chinensis var. deliciosa (Acd), is an allohexaploid (2n = 6x = 174), making high-quality assemblage genome challenging. We previously discovered a rare naturally occurring diploid Acd plant. Here, chromosome-level de novo genome assembly for this diploid Acd was reported, reaching approximately 621.98 Mb in length with contig and scaffold N50 values of 10.08 and 21.09 Mb, respectively, 99.66% of the bases anchored to 29 pseudochromosomes, and 38,990 protein-coding genes and 42.29% repetitive elements annotated. The divergence time of A. chinensis cv. ‘Red5’ and ‘Hongyang’ (11.1–27.7 mya) was more recent compared with the divergence time of them and Acd (19.9–41.2 mya), with the divergence time of A. eriantha cv. ‘White’ being the earliest (22.9–45.7 mya) among that of the four Actinidia species. The 4DTv distance distribution highlighted three recent whole-genome duplication events in Acd. This is the first high-quality diploid Acd genome, which lays an important foundation for not only kiwifruit functional genomics studies but also further elucidating genome evolution of allohexaploid Acd.

Microstructural development and mechanical properties of tungsten heavy alloy, WHA, with FeNiCoCrMn high entropy alloy, HEA, binder were investigated and compared to conventional WHA using Fe–Ni binder. Both WHAs, with HEA and conventional Fe–Ni binders, were fabricated by hot isostatic pressing at a temperature of 1450 °C in an argon environment. Scanning electron microscopy revealed that WHA with HEA and conventional binders possessed uniform and well-refined microstructures. Energy dispersive spectroscopy and X-ray diffraction, XRD, spectroscopy validated the formation and composition of HEA, existing as a skeletal network surrounding tungsten grains. HEA binder exhibited an overall increase of 42% in micro Vickers hardness values. Furthermore, hardness values of the tungsten heavy alloy were also seen to rise when fabricated with HEA binder. However, WHA sample with HEA binder was seen to undergo faster strain hardening and a premature failure, leading to lower values of ultimate strength and reduced ductility.

Cas12a-mediated cytosine (CBE) and adenine base editor (ABE) systems with elevated efficiencies and expanded target scopes are developed, by combining highly active deaminases with Cas12a variants, enCas12a, RR and RVR, recognizing non-TTTV PAMs.

Abstract The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron‐based metal organic framework (Fe‐MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer‐specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non‐targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule‐associated protein 1A/1B‐light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy‐dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.

Abstract Tumor stemness is associated with the recurrence and incurability of colorectal cancer (CRC), which lacks effective therapeutic targets and drugs. Glycinamide ribonucleotide transformylase (GART) fulfills an important role in numerous types of malignancies. The present study aims to identify the underlying mechanism through which GART may promote CRC stemness, as to developing novel therapeutic methods. An elevated level of GART is associated with poor outcomes in CRC patients and promotes the proliferation and migration of CRC cells. CD133+ cells with increased GART expression possess higher tumorigenic and proliferative capabilities both in vitro and in vivo. GART is identified to have a novel methyltransferase function, whose enzymatic activity center is located at the E948 site. GART also enhances the stability of RuvB‐like AAA ATPase 1 (RUVBL1) through methylating its K7 site, which consequently aberrantly activates the Wnt/β‐catenin signaling pathway to induce tumor stemness. Pemetrexed (PEM), a compound targeting GART, combined with other chemotherapy drugs greatly suppresses tumor growth both in a PDX model and in CRC patients. The present study demonstrates a novel methyltransferase function of GART and the role of the GART/RUVBL1/β‐catenin signaling axis in promoting CRC stemness. PEM may be a promising therapeutic agent for the treatment of CRC.

The RAN Guanine Nucleotide Release Factor (RANGRF) gene encodes the protein MOG1, which binds to Nav1.5 and facilitates its transport to the cell membrane. Nav1.5 mutations have been linked to various cardiac arrhythmias and cardiomyopathy. To investigate the role of RANGRF in this process, we utilized the CRISPR/Cas9 gene editing system to generate a homozygous RANGRF knockout hiPSC line. The availability of the cell line will prove to be an invaluable asset in the study of disease mechanisms and the testing of gene therapies for cardiomyopathy.

Pomegranate (Punica granatum L.), with its abundant phenolic substances and strong antioxidant activity, holds significant research and utilization potential across various organs. However, there have been few studies on the phenolic content and antioxidant activity of different parts of pomegranate, especially the placenta. This study investigated the phenolic content and antioxidant activity of fruits, flowers, and leaves of two pomegranate varieties, ‘Tunisia’ and ‘Qingpi’, throughout their growth and development. Results indicated significant variations in phenolic content among different organs, with petals exhibiting the highest total polyphenol content (TPC, 49.40 mg GAE/g FW) and total anthocyanin content (TMAC, 1938.54 nmol/g FW). Placenta contained the highest levels of total flavonoids (TFC, 173.58 mg RE/g FW) and punicalagin (109.30 mg/g FW). The peel had the highest content of total flavanols (TFAC, 19.42 mg CE/g FW). Over the course of pomegranate development, total polyphenols, total flavonoids, total flavanols, punicalagin, and antioxidant activity declined in different organs. Antioxidant activity followed the order: fruit > flower > leaf, with the placenta exhibiting the highest antioxidant activity among fruits. Antioxidant activity showed a significant positive correlation with total polyphenols (R2 = 0.77-1.00), total flavonoids (R2 = 0.71-0.99, except tegmens), and punicalagin (R2 = 0.71-1.00). This study provides a comparative analysis of the phenolic content and antioxidant activity in different organs of pomegranate, highlighting the placenta as the primary source of punicalagin. This study provides a theoretical basis for the development and utilization of pomegranate phenolic compounds.

Within the double-sided countersunk riveting process of aircraft wings with a composite wedge structure, riveting consistency is poor, and composite damage is severe, which seriously affects the performance and reliability of the aircraft structure. This paper used the principal stress method to establish a stress model of countersunk riveting, and, based on the analysis of the stress on the structure during the pressure-riveting process, a composite structure rivet was designed. A finite element simulation model of the double-sided countersunk riveting of composite wedge structures’ composite rivets was established. The influences of the structure and the matching parameters of composite rivets on both the plastic flow of pressure riveting and the compressive stress of the structure during the pressure-riveting process were analyzed. The structural parameters and riveting process of composite rivets were optimized. The results show that the composite rivet structure could significantly reduce the contact-compressive stress at the riveting joint by more than 20%, thereby reducing the damage caused by the riveting to the composite material. For 4 mm rivets, an aperture of 4.04~4.06 mm can achieve precise relative interference riveting at 0.6% to 1.0%. Employing a 2.6 mm rivet elongation can exactly fill the countersunk hole of the wedge.

Schizophrenia is a group of common psychosis of unknown etiology and GRIN2A gene has been a risk gene for schizophrenia. In order to understand the relationship between the GRIN2A and schizophrenia, we generated a GRIN2A-KO human embryonic stem cell line by CRISPR/Cas9 system, which could provide a valuable resource for investing pathogenic mechanisms underlying schizophrenia and facilitating the development of targeted medicine.

MADS-box is a large transcription factor family in plants and plays a crucial role in various plant developmental processes; however, it has not been systematically analyzed in kiwifruit. In the present study, 74 AcMADS genes were identified in the Red5 kiwifruit genome, including 17 type-I and 57 type-II members according to the conserved domains. The AcMADS genes were randomly distributed across 25 chromosomes and were predicted to be mostly located in the nucleus. A total of 33 fragmental duplications were detected in the AcMADS genes, which might be the main force driving the family expansion. Many hormone-associated cis-acting elements were detected in the promoter region. Expression profile analysis showed that AcMADS members had tissue specificity and different responses to dark, low temperature, drought, and salt stress. Two genes in the AG group, AcMADS32 and AcMADS48, had high expression levels during fruit development, and the role of AcMADS32 was further verified by stable overexpression in kiwifruit seedlings. The content of α-carotene and the ratio of zeaxanthin/β-carotene was increased in transgenic kiwifruit seedlings, and the expression level of AcBCH1/2 was significantly increased, suggesting that AcMADS32 plays an important role in regulating carotenoid accumulation. These results have enriched our understanding of the MADS-box gene family and laid a foundation for further research of the functions of its members during kiwifruit development.

In present work, a novel γ′′-strengthened Nb-alloyed medium-entropy alloy (MEA) was successfully fabricated and systematically investigated. Our results evidence that the γ′′ phase brings out significant precipitation hardening effect (∼10.2 %volume fraction contributes ∼ 685 MPa strength enhancement). The metastable γ′′ phase could abnormally transform to ε phase, and the morphology and distribution of ε phase shows great impacts on mechanical properties. A hetero-lamellae grain coupling with dual-precipitation (HLG + dual-P) structure was successfully constructed in this Nb-alloyed MEA, which could effectively combine precipitation hardening and hetero-deformation induced (HDI) hardening effects. Deformation characters investigations reveals that the absence of mechanical twinning in γ′′-strengthened MEA originates from the improved critical twinning stress related to the fine dislocation source size and the difficulty of high-energy complex SFs reordering. The combination of massive stacking-faults, Lomer-Cottrell locks and dynamically reinforced HDI hardening contribute to the excellent ductility and work-hardening capacity at high-level strength in the HLG + dual-P structural alloy. Our work provides a useful insight and helpful guidance for developing high-performance precipitation-hardened multi-principal element alloys.

Pre-existing and gestationally-developed diabetes mellitus have been linked with impairments in placental villous trophoblast cell metabolic function, that are thought to underlie the development of metabolic diseases early in the lives of the exposed offspring. Previous research using placental cell lines and ex vivo trophoblast preparations have highlighted hyperglycemia is an important independent regulator of placental function. However, it is poorly understood if hyperglycemia directly influences aspects of placental metabolic function, including nutrient storage and mitochondrial respiration, that are altered in term diabetic placentae. The current study examined metabolic and mitochondrial function as well as nutrient storage in both undifferentiated cytotrophoblast and differentiated syncytiotrophoblast BeWo cells cultured under hyperglycemia conditions (25 mM glucose) for 72 hours to further characterize the direct impacts of placental hyperglycemic exposure. Hyperglycemic-exposed BeWo trophoblasts displayed increased glycogen and triglyceride nutrient stores, but real-time functional readouts of metabolic enzyme activity and mitochondrial respiratory activity were not altered. However, specific investigation into mitochondrial dynamics highlighted increased expression of markers associated with mitochondrial fission that could indicate high glucose-exposed trophoblasts are transitioning towards mitochondrial dysfunction. To further characterize the impacts of independent hyperglycemia, the current study subsequently utilized a multi-omics approach and evaluated the transcriptomic and metabolomic signatures of BeWo cytotrophoblasts. BeWo cytotrophoblasts exposed to hyperglycemia displayed increased mRNA expression of ACSL1, HSD11B2, RPS6KA5, and LAP3 and reduced mRNA expression of CYP2F1, and HK2, concomitant with increased levels of: lactate, malonate, and riboflavin metabolites. These changes highlighted important underlying alterations to glucose, glutathione, fatty acid, and glucocorticoid metabolism in BeWo trophoblasts exposed to hyperglycemia. Overall, these results demonstrate that hyperglycemia is an important independent regulator of key areas of placental metabolism, nutrient storage, and mitochondrial function, and these data continue to expand our knowledge on mechanisms governing the development of placental dysfunction.

Cellular metabolomics provides insights into the metabolic processes occurring within cells and can help researchers understand how these processes are regulated and how they relate to cellular function, health, and disease. In this technical note, we investigated the effects of solvent evaporation equipment and storage condition on high-coverage cellular metabolomics. We previously introduced a robust CIL LC-MS-based cellular metabolomics workflow that encompasses various steps, including cell harvest, metabolic quenching, cell lysis, metabolite extraction, differential chemical isotope labeling, and LC-MS analysis. This workflow has consistently served as the cornerstone of our collaborative research and service projects. As a core facility catering to users with diverse research needs and financial resources, we have encountered scenarios requiring short-term sample storage. For example, the need often arises to transport samples at room temperature from user sites to our core facility. Herein, we present a study in which we compared different solvent evaporation methods (specifically, the nitrogen blowdown evaporator, SpeedVac concentrator, and lyophilizer) and diverse storage conditions (including dried samples stored in a freezer, samples stored in a freezer with methanol, dried samples stored at room temperature, and samples stored at room temperature with methanol). Our findings indicate that the choice of solvent evaporation equipment did not significantly impact the cellular metabolome. However, we observed a noteworthy change in the metabolome after 7 days of storage when cells were stored with methanol, regardless of whether they were kept at −80 °C or room temperature, in contrast to cells that were dried and frozen. Importantly, we detected no significant alterations in cells that were dried and stored at room temperature. In conclusion, to ensure the production of high-quality CIL LC-MS metabolomics results, we strongly recommend that, in situations where low-temperature storage is not feasible, cell samples should be thoroughly dried before storage or shipment at room temperature.

Abstract X-ray computed tomography (CT) has been widely used in clinical practice, and contrast agents such as Iohexol are often used to enhance the contrast of CT imaging between normal and diseased tissue. However, such contrast agents can have some toxicity. Thus, new CT contrast agents are urgently needed. Owing to the high atomic number (Z = 83), low cost, good biological safety, and great X-ray attenuation property (5.74 cm2 kg−1 at 100 keV), bismuth has gained great interest from researchers in the field of nano-sized CT contrast agents. Here, we synthesized BiF3: Ln@PVP nanoparticles (NPs) with an average particle size of about 380 nm. After coating them with polyvinylpyrrolidone (PVP), the BiF3: Ln@PVP NPs possessed good stability and great biocompatibility. Meanwhile, compared with the clinical contrast agent Iohexol, BiF3: Ln@PVP NPs showed superior in vitro CT imaging contrast. Subsequently, after in situ injection with BiF3: Ln@PVP NPs, the CT value of the tumor site after the injection was significantly higher than that before the injection (the CT value of the pre-injection and post-injection was 48.9 HU and 194.58 HU, respectively). The morphology of the gastrointestinal (GI) tract can be clearly observed over time after oral administration of BiF3: Ln@PVP NPs. Finally, the BiF3: Ln@PVP NPs were completely discharged from the GI tract of mice within 48 h of oral administration with no obvious damage to the GI tract. In summary, our easily synthesized BiF3: Ln@PVP NPs can be used as a potential clinical contrast agent and may have broad application prospects in CT imaging.

Background: Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouring MET exon 14 skipping alteration ( MET ex14). Objective: To analyse post hoc , the association between circulating tumour DNA (ctDNA) biomarkers and clinical outcomes, including resistance, with savolitinib. Design: A multicentre, single-arm, open-label phase 2 study. Methods: All enrolled patients with baseline plasma samples were included. Outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) by baseline MET ex14 and post-treatment clearance, coexisting gene alterations at baseline and disease progression. Results: Among 66 patients with baseline ctDNA sequencing, 46 (70%) had detectable MET ex14. Frequent coexisting baseline gene alterations included TP53 and POT1 mutations. Patients with detectable baseline MET ex14 exhibited worse PFS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 0.88–3.57; p = 0.108] and OS (HR, 3.26; 95% CI, 1.35–7.89; p = 0.006) than those without, despite showing a numerically higher ORR. Among 24 patients with baseline detectable MET ex14 and evaluable postbaseline samples, 13 achieved MET ex14 clearance post-treatment. Median time to first clearance was 1.3 months (range, 0.7–1.5). MET ex14 post-treatment clearance was associated with better ORR (92.3%; 95% CI, 64.0–99.8 versus 36.4%; 95% CI, 10.9–69.2; p = 0.0078), PFS (HR, 0.44; 95% CI, 0.2–1.3; p = 0.1225) and OS (HR, 0.31; 95% CI, 0.1–1.0; p = 0.0397) versus non-clearance. Among 22 patients with disease progression, 10 acquired pathway alterations (e.g. in RAS/RAF and PI3K/PTEN) alone or with secondary MET mutations (D1228H/N and Y1230C/H/S). Conclusion: ctDNA biomarkers may allow for longitudinal monitoring of clinical outcomes with savolitinib in patients with MET ex14-positive PSC and other NSCLC subtypes. Specifically, undetectable baseline MET ex14 or post-treatment clearance may predict favourable clinical outcomes, while secondary MET mutations and other acquired gene alterations may explain resistance to savolitinib. Registration: The trial was registered with ClinicalTrials.gov (NCT02897479) on 13 September 2016.

Cadmium (Cd) contamination of paddy soil affects safe crop production. This study aimed to evaluate the effects of plant biostimulant amino acid fertilizer on the phytoremediation capability of an emergent accumulator plant Nasturtium officinale R. Br. for Cd-contaminated paddy soils. A pot study was carried out to study the effects of different concentrations of amino acid fertilizer on the Cd accumulation of N. officinale grown in Cd-contaminated paddy soil. The amino acid fertilizer increased the biomass of N. officinale. The amino acid fertilizer concentration exhibited a quadratic polynomial regression relationship with the root and shoot biomass. The fertilizer also increased the photosynthetic pigment (chlorophyll and carotenoid) contents, peroxidase (POD; EC 1.11.1.7) activity, and catalase (CAT; EC 1.11.1.6) activity of N. officinale, but decreased the soluble protein content and had no significant effect on the superoxide dismutase (SOD; EC 1.15.1.1) activity. Furthermore, the amino acid fertilizer increased the Cd content and Cd extraction of N. officinale. The shoot Cd extraction increased by 29.06%, 63.05%, 77.22%, and 17.40% at 1500-, 1200-, 900-, and 600-fold dilutions of the amino acid fertilizer, respectively, compared with the control. Moreover, the amino acid fertilizer promoted the Cd transport from the roots to shoots of N. officinale. The amino acid fertilizer concentration also exhibited a quadratic polynomial regression relationship with the root Cd content, shoot Cd content, root Cd extraction, and shoot Cd extraction, respectively. The correlation, grey relational, and path analyses revealed that the root biomass, shoot biomass, chlorophyll content, catalase activity, shoot Cd content, and root Cd extraction were closely associated with the shoot Cd extraction. Therefore, the amino acid fertilizer can promote Cd uptake and improve the phytoremediation capability of N. officinale to remediate Cd-contaminated paddy soils, and 900-fold dilution is the most suitable concentration.

Introduction: Savolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with MET exon 14 skipping alterations (MET ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses. Methods: This multicenter, single-arm, open-label, phase 2 study in the People’s Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic METex14-positive NSCLC (NCT02897479). Oral savolitinib at a dose of 400 or 600 mg was administered once daily (body weight dependent). The primary objectives of the final analysis were long-term overall survival (OS) and subgroup analyses by previous systemic treatment, NSCLC subtypes, and brain metastases. Results: At the final analysis cutoff date (June 28, 2021), a total of 70 patients were enrolled and receiving savolitinib, and median follow-up was 28.4 (interquartile range: 26.2–36.3) months. The median OS was 12.5 months (95% confidence interval [CI]: 10.5–21.4 [18- and 24-mo OS rates, 42.1% and 31.5%, respectively]). Median OS in pretreated or treatment-naive patients was 19.4 (95% CI: 10.5–31.3) and 10.9 (95% CI: 7.5–14.0) months, respectively; it was 10.6 months (95% CI: 4.6–14.0) in patients with pulmonary sarcomatoid carcinoma, 17.3 months (95% CI: 10.6–23.6) in other NSCLC subtypes, and 17.7 months (95% CI: 10.5–not evaluable) in patients with brain metastases. No new safety signals emerged with prolonged follow-up and exposure. Conclusions: The updated results further confirm the favorable benefit and acceptable safety of savolitinib in Chinese patients with METex14-positive NSCLC.

This study was conducted to investigate the visual appearance and physicochemical changes of postharvest jujube fruits (Ziziphus jujuba Mill. cv. Shucuizao) stored under 0 °C for 15 days. The fruits were dipped in 0 (control), 50, 100, 200 and 400 µM melatonin solutions after harvest. The results showed that treatment with a suitable melatonin concentration improved the rate of crisp fine fruits, delayed weight loss and firmness decline, and suppressed changes in total soluble solids (TSS) and titratable acidity (TA) contents of jujube fruits compared with the control. In addition, jujube fruits soaked with melatonin showed improved antioxidant capacity through increased ascorbic acid (AsA) content, enhanced superoxide dismutase (SOD) activity, and decreased malonaldehyde (MDA) content. As a result, 50 µM melatonin showed the greatest improvement of visual appearance and quality maintenance, and could be used as an effective treatment to preserve postharvest jujube fruit.

The selenium (Se) deficiency is threatening the human health, and the increase of Se content in food can prevent the Se deficiency of human body. To increase the Se content in fruit trees and alleviate the Se stress to fruit trees, the effects of gibberellic acid (GA) on the growth and Se accumulation in Cyphomandra betacea under Se stress were studied. Although GA increased the biomass of C. betacea, it did not significantly affect the root/shoot ratio. The root and shoot biomass had a quadratic polynomial regression relationship with the GA concentration. Furthermore, GA increased the photosynthetic pigment content, photosynthetic parameters, and antioxidant enzyme activity of C. betacea. GA also increased the Se content in C. betacea, peaking at 300 mg/L GA. For instance, GA (300 mg/L) increased the Se contents in roots and shoots of C. betacea by 70.31 and 22.02%, respectively, compared with the control. Moreover, the root Se and shoot Se contents had a quadratic polynomial regression relationship with the GA concentration. Correlation and gray relational analyses showed that the carotenoid, chlorophyll a, and chlorophyll b contents were closely related to the Se uptake in C. betacea under the GA application. These results show that GA (300 mg/L) can promote the growth and Se uptake of C. betacea under Se stress.

ABSTRACT: Background: Generalized anxiety disorder (GAD) is a common chronic mental disorder, and it also can cause depressive symptoms and cognitive impairment. The primary aim of this study was to determine whether inflow-frequency transcranial magnetic stimulation (ILF-TMS) improves anxiety symptoms in patients with GAD. Methods: Sixty-two patients with GAD were randomly divided into 2 groups. Thirty-one patients in the active ILF-TMS group and 31 patients in the sham ILF-TMS group. All participants were assessed at baseline, week 2, week 4 and week 12. The intention-to-treat methodology was used for the analysis. Results: The response rate was higher in the active group than in the sham group, with a significant difference at week 12 (response rate: 80.6% vs. 54.8%, respectively; P = 0.03). Although the remission rate was higher in the active group at week 12, there was no statistically significant difference between the groups (remission rate: 71.0% vs. 48.4%; P > 0.05). No statistically significant differences on the Hamilton Depression Rating Scale, Clinical Global Impression scale, and neurocognitive test between groups were observed (overall P > 0.05). Adverse events that occurred in the active group were similar to those in the sham group, with no significant differences (P > 0.05). Conclusion: The response rate was higher in the active group at the end of the trial, which indicated that ILF-TMS may be an effective and safe adjunctive tool to improve anxiety symptoms in patients with GAD.

Aims: The causal relationship between COVID-19 infection and stroke has not yet been fully established. This study aimed to explore this causality using two-sample Mendelian randomization (MR).Materials and Methods: Genetic variants associated with COVID-19 infection and stroke were both obtained from genome-wide association study (GWAS) summary data. The single nucleotide polymorphisms (SNPs) were selected as instrumental variables. The standard inverse variance weighted (IVW) was primarily used to assess this causality. Finally, sensitivity analysis was performed to evaluate the reliability and stability.Results: The results showed that being hospitalized due to COVID-19 had a positive effect on stroke [OR = 1.05; 95% CI= (1.01, 1.10); p = 2.34 × 10−5] and ischemic stroke [OR = 1.06; 95% CI= (1.02, 1.11); p = 2.28 × 10−6] analyzed by inverse variance weighted. Moreover, the results revealed that severe respiratory symptoms due to COVID-19 had a positive effect on stroke [OR = 1.04; 95% CI= (1.00, 1.06); p = 0.04] and that the causal effect of severe respiratory symptoms due to COVID-19 on ischemic stroke estimated by IVW suggested a positive effect [OR = 1.06; 95% CI= (1.02, 1.09); p = 0.0068], too.Conclusion: In summary, this study showed that severe COVID-19 might increase the risk of stroke, thus much more attention should be paid to patients with severe COVID-19.

Ultrasonic surface rolling technology is a new mechanical surface treatment technology that can improve the surface integrity, increase the amplitude and depth of the residual compressive stress layer and improve the fatigue property of metal materials. In this paper, the effect of ultrasonic rolling on the surface layer's microstructure and properties of Ti6Al4V alloys is investigated. The microstructure, surface roughness, surface topography, microhardness and residual stress were used to characterise the surface-modified layer. Specimens treated by ultrasonic surface rolling obtained the smallest surface roughness (0.231 μm) and largest plastic deformation depth (304.38 μm), simultaneously, under sixteen processing stage numbers. The rule of surface compressive residual stress distribution had a similar tendency to the law of surface microhardness distribution. Furthermore, the grain size of the strengthened surface layer decreased, the texture type changed and the Schmidt factor increased compared with the matrix. The increase of microhardness and residual stress is due to grain refinement and dislocation strengthening.

In this study, Ti-48Al-3Nb-1.5Ta powders were manufactured from cast bars by the supreme-speed plasma rotating electrode process (SS-PREP) and used to prepare hot isostatically pressed (HIPed) material at 1050–1260 °C with 150 MPa for 4 h. The phase, microstructure and mechanical performance were analyzed by XRD, SEM, electrical universal material testing machine and other methods. The results revealed that the phase constitution changed from γ phase to α2 phase and then to γ phase with the material changing from as-cast to powders and then to as-HIPed. Compared with the as-cast material, the grain size and element segregation were significantly reduced for both powders and as-HIPed. When the hot isostatic pressing (HIP) temperature was low, the genetic characteristics of the powder microstructure were evident. With the HIP temperature increasing, the homogeneity of the composition and microstructure increased, and the prior particle boundaries (PPBs) gradually disappeared. The elastic moduli of powder and as-HIPed were superior to those of as-cast, which increased with the HIP temperature increasing. The hardness of as-HIPed was lower than that of the powder. The compressive strength, compressive strain, bending strength, and tensile strength of as-HIPed were higher than those of as-cast. With an increase in the HIP temperature, the compressive strength decreased gradually, and the compressive strain first decreased and then increased.