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Abstract Background Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS). Endothelial mesenchymal transition (EndMT) refers to the process in which endothelial cells lose endothelial cell morphology and characteristic gene expression, and acquire phenotypic characteristics and gene expression related to mesenchymal cells. Numerous studies have confirmed that EndMT is involved in the formation of atherosclerosis. Catalpol is one of the active components of Rehmannia, which has antioxidant, anti-inflammatory, anti-tumor, neuroprotective and other biological activities. Studies have shown that catalpol can reduce atherosclerotic plaque induced by high sugar or fat. However, the effect of catalpol on HHCY-induced EndMT is unclear. Methods and results In vitro HHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a cell model, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. In vivo C57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The results showed that hhcy could induce morphological transformation of endothelial cells into mesenchymal cells, increase intracellular ROS content, up-regulate α-SMA, N-cadherin, p-p65 protein expression, down-regulate VE-cadherin, CD31 protein expression, induce pathological changes of aortic root endothelium, and increase aortic endothelial ROS content. Catalpol reversed these hhcy induced outcomes. Conclusions Catalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS.

Abstract Aims In an era of evolving diagnostic possibilities, existing diagnostic systems are not fully sufficient to promptly recognize patients with early‐stage hypertrophic cardiomyopathy (HCM) without symptomatic and instrumental features. Considering the sudden death of HCM, developing a novel diagnostic model to clarify the patients with early‐stage HCM and the immunological characteristics can avoid misdiagnosis and attenuate disease progression. Methods and results Three hundred eighty‐five samples from four independent cohorts were systematically retrieved. The weighted gene co‐expression network analysis, differential expression analysis (|log2(foldchange)| > 0.5 and adjusted P

Abstract Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia–reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen–glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia–reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia–reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

Abstract Background Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype–phenotype correlations. Methods Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype–phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population. Results Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad. Conclusions We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.

PurposeThe body contour of patients with cervical cancer is prone to change between radiotherapy sessions. This study aimed to investigate the effect of body contour changes on the setup and dosimetric accuracy of radiotherapy.Methods15 patients with cervical cancer after surgery were randomly selected for retrospective analysis. The body contours on the once-per-week cone-beam computed tomography (CBCT) were registered to the planning CT (pCT) for subsequent evaluation. A body contour conformity index (CIbody) was defined to quantify the variation of body changes. The body volume measured by CBCT was collected, and its relative difference in reference with the first CBCT was calculated and denoted by ΔVn. The relative setup errors, denoted by ΔSELR, ΔSEAP, ΔSESI, and ΔSEvec for left–right, anterior–posterior, superior–inferior, and vectorial shifts, respectively, were defined as the difference in measured setup errors between the reference and following CBCTs. The planned dose was calculated on the basis of virtual CT generated from CBCT and pCT by altering the CT body contour to fit the body on CBCT without deformable registration. The correlations between body contour changes and relative setup errors as well as dosimetric parameters were evaluated using Spearman’s correlation coefficient rs.ResultsCIbody was found to be negatively correlated with the superior–inferior and vectorial relative setup errors ΔSESI (rs = −0.448, p = 0.001) and ΔSEvec (rs = −0.387, p = 0.002), and no significant correlation was found between relative setup errors and ΔVn. Moreover, ΔVn was negatively correlated with ΔD2 (rs = −0.829, p < 0.001), ΔD98 (rs = −0.797, p < 0.001), and ΔTVPIV (rs = −0.819, p < 0.001). ΔD2, ΔD98, and ΔTVPIV were negatively correlated with ΔVn (p < 0.005). No correlation was found for other examined dosimetric parameters.ConclusionThe body contour change of patients could be associated with the setup variability. The effect of body contour changes on dose distribution is minimal. The extent of body change could be used as a metric for radiation therapists to estimate the setup errors.

BackgroundPatients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often experience severe symptoms. Resting-state functional MRI (rs-fMRI) has revealed widespread impairment of functional networks in patients. However, the changes in information flow remain unclear. This study aims to investigate the intrinsic functional connectivity (FC) both within and between resting-state networks (RSNs), as well as the alterations in effective connectivity (EC) between these networks.MethodsResting-state functional MRI (rs-fMRI) data were collected from 25 patients with anti-NMDAR encephalitis and 30 healthy controls (HCs) matched for age, sex, and educational level. Changes in the intrinsic functional connectivity (FC) within and between RSNs were analyzed using independent component analysis (ICA). The functional interaction between RSNs was identified by granger causality analysis (GCA).ResultsCompared to HCs, patients with anti-NMDAR encephalitis exhibited lower performance on the Wisconsin Card Sorting Test (WCST), both in terms of correct numbers and correct categories. Additionally, these patients demonstrated decreased scores on the Montreal Cognitive Assessment (MoCA). Neuroimaging studies revealed abnormal intra-FC within the default mode network (DMN), increased intra-FC within the visual network (VN) and dorsal attention network (DAN), as well as increased inter-FC between VN and the frontoparietal network (FPN). Furthermore, aberrant effective connectivity (EC) was observed among the DMN, DAN, FPN, VN, and somatomotor network (SMN).ConclusionPatients with anti-NMDAR encephalitis displayed noticeable deficits in both memory and executive function. Notably, these patients exhibited widespread impairments in intra-FC, inter-FC, and EC. These results may help to explain the pathophysiological mechanism of anti-NMDAR encephalitis.

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, the infection of Mycoplasma pneumoniae (MP) decreased significantly. At the beginning of the summer of 2023, there was an increasing trend of MP infection in China and the MP pneumonia (MPP) is surging when it comes to the school season and lasts for several months which has attracted widespread attention.ObjectiveThis study aims to investigate the prevalent characteristics of the MP and the difference between the COVID-19 pandemic and the post in Shanghai, China.MethodsThe demographic information and the results of laboratory pathogen detection from July 2021 to May 2024 were collected and analyzed to find out the prevalent characteristics of MP. Two periods, during the COVID-19 pandemic and the post-pandemic, were divided and compared. The P1 genotyping and macrolide resistance-associated gene of 23 s rRNA were detected using the remaining MP-positive samples.ResultsDuring the COVID-19 pandemic, the prevalence of the MP has significantly decreased. Female children are more susceptible to MP infection than the male. The school-aged group (>6 years) had the highest infection rate. The rate of MP P1 genotype during post panel is higher than that during COVID-19 pandemic, which is dominant from July 2021 to May 2024, while the macrolide-resistant associated mutations (A2063G) keep high percentage during or post pandemic.ConclusionAfter the COVID-19 pandemic, an outbreak of MP infection occurred from summer onwards in 2023 with children in Shanghai, China. Immunity debt and high rate of macrolide-resistance may take effects in this MP epidemic. Continuous surveillance of MP is necessary to help to alert the prevalence of MPP.

Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently with few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be a potential therapeutic target. Emerging evidence suggests wogonin, the bioactive compound isolated from Scutellaria baicalensis, owns the anti-senescence properties, however, the possible impact of wogonin on PF and the potential mechanisms remain unclear. In this study, a well-established mouse model of PF was utilized which mice were administrated with bleomycin (BLM). Strikingly, wogonin treatment significantly reduced fibrosis deposition in the lung induced by BLM. In vitro, wogonin also suppressed fibrotic markers of cultured epithelial cells stimulated by BLM or hydrogen peroxide. Mechanistic investigation revealed that wogonin attenuated the expressions of DNA damage marker γ-H2AX and senescence-related markers including phosphorylated p53, p21, retinoblastoma protein (pRB), and senescence-associated β-galactosidase (SA-β-gal). Moreover, wogonin, as a direct and selective inhibitor of cyclin-dependent kinase 9 (CDK9), exhibited anti-fibrotic capacity by inhibiting CDK9 and p53/p21 signalling. In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.

ObjectiveA growing body of evidence underscores a significant association between neurological disorders, particularly migraines, and the gut microbiota. However, a research gap persists in understanding the cause-and-effect dynamics between these elements. Therefore, we employed robust methodologies aimed at thoroughly exploring the causal relationship between the gut microbiome and migraines.MethodsEmploying bidirectional Two Sample Mendelian Randomization (TSMR) analysis, we investigated the causal association between the composition of the gut microbiota and migraines. Data summarizing the relationship between gut microbiota and migraines were extracted from one or more genome-wide association studies. The TSMR analysis employed five methods to assess the correlation between the gut microbiota and migraines, with the inverse variance-weighted method serving as the primary approach for analyzing causal links. Sensitivity analyses were applied to address horizontal pleiotropy and heterogeneity. Simultaneously, a meta-analysis was performed to strengthen the robustness of the findings. Additionally, a reverse TSMR was carried out to explore potential occurrences of reverse causal relationships.ResultsThe ongoing TSMR analysis identified a collection of 14 bacterial taxa connected to migraines. Among these, 8 taxa exhibited a protective effect, while 5 taxa had a detrimental impact, and 1 taxon maintained a neutral relationship. The reverse Mendelian randomization analysis highlighted stable outcomes for only one bacterial taxonomic group.ConclusionThe study confirms a causal relationship between the gut microbiota and migraines, offering a new perspective for migraine research. Strategically targeting specific bacterial taxa with dysregulation may be effective in both preventing and treating migraines, thus opening new avenues for therapeutic strategies.

Abstract We study the existence of solutions of the nonlinear second order m-point boundary value problem with p-Laplacian at resonance { ( ϕ p ( x ′ ) ) ′ = f ( t , x , x ′ ) , t ∈ [ 0 , 1 ] , x ′ ( 0 ) = 0 , x ( 1 ) = ∑ i = 1 m − 2 a i x ( ξ i ) , $$ \textstyle\begin{cases} (\phi _{p}(x'))'=f(t,x,x'),\quad t\in [0,1],\\ x'(0)=0, \qquad x(1)=\sum_{i=1}^{m-2}a_{i}x(\xi _{i}), \end{cases} $$ where ϕ p ( s ) = | s | p − 2 s $\phi _{p}(s)=|s|^{p-2}s$ , p > 1 $p>1$ , f : [ 0 , 1 ] × R 2 → R $f:[0,1]\times \mathbb{R}^{2}\to \mathbb{R}$ is a continuous function, a i > 0 $a_{i}>0$ ( i = 1 , 2 , … , m − 2 $i=1,2,\ldots ,m-2$ ) with ∑ i = 1 m − 2 a i = 1 $\sum_{i=1}^{m-2}a_{i}=1$ , 0 < ξ 1 < ξ 2 < ⋯ < ξ m − 2 < 1 $0

Abstract Background Recently, long non-coding RNAs (lncRNAs) have been demonstrated as essential roles in tumor immune microenvironments (TIME). Nevertheless, researches on the clinical significance of TIME-related lncRNAs are limited in lung adenocarcinoma (LUAD). Methods Single-cell RNA sequencing and bulk RNA sequencing data are integrated to identify TIME-related lncRNAs. A total of 1368 LUAD patients are enrolled from 6 independent datasets. An integrative machine learning framework is introduced to develop a TIME-related lncRNA signature (TRLS). Results This study identified TIME-related lncRNAs from integrated analysis of single‑cell and bulk RNA sequencing data. According to these lncRNAs, a TIME-related lncRNA signature was developed and validated from an integrative procedure in six independent cohorts. TRLS exhibited a robust and reliable performance in predicting overall survival. Superior prediction performance barged TRLS to the forefront from comparison with general clinical features, molecular characters, and published signatures. Moreover, patients with low TRLS displayed abundant immune cell infiltration and active lipid metabolism, while patients with high TRLS harbored significant genomic alterations, high PD-L1 expression, and elevated DNA damage repair (DDR) relevance. Notably, subclass mapping analysis of nine immunotherapeutic cohorts demonstrated that patients with high TRLS were more sensitive to immunotherapy. Conclusions This study developed a promising tool based on TIME-related lncRNAs, which might contribute to tailored treatment and prognosis management of LUAD patients.

Abstract The intricate crosstalk of various cell death forms was recently implicated in cancers, laying a foundation for exploring the association between cell death and cancers. Recent evidence has demonstrated that biological networks outperform snapshot gene expression profiles at discovering promising biomarkers or heterogenous molecular subtypes across different cancer types. In order to investigate the behavioral patterns of cell death-related interaction perturbation in colorectal cancer (CRC), this study constructed the interaction-perturbation network with 11 cell death pathways and delineated four cell death network (CDN) derived heterogeneous subtypes (CDN1-4) with distinct molecular characteristics and clinical outcomes. Specifically, we identified a subtype (CDN4) endowed with high autophagy activity and the worst prognosis. Furthermore, AOC3 was identified as a potential autophagy-related biomarker, which demonstrated exceptional predictive performance for CDN4 and significant prognostic value. Overall, this study sheds light on the complex interplay of various cell death forms and reveals an autophagy-related gene AOC3 as a critical prognostic marker in CRC.

In order to investigate the effect of coaxial-feed laser cladding with the addition of ZrC and CNTs reinforcing particles, a four-split-beam coaxial-wire-feed system was used for the first time to fabricate the cladding layers. Specifically, the effects of the reinforcing particles on the microstructure, mechanical and corrosion properties of the cladding layers were investigated. On 316L substrates, three types of cladding layers were created: pure Inconel 625, Inconel 625 with ZrC, and Inconel 625 with ZrC-CNTs. The testing findings revealed that the cladding layer with reinforcement particles added possessed the ideal geometrical features of large melt width and low dilution rate. Due to the coaxial action of the laser and the wire, the grains on both sides of the single-bead cladding layer transited from columnar crystals to equiaxial crystals along the temperature gradient, and the grains in the middle of the single-bead cladding layer showed the competing growth of columnar crystals and equiaxial crystals at the fusion line. The addition of ZrC and CNTs particles produced a heterogeneous nucleation effect that refined the grain size and homogenized the grain orientation, which CNTs accentuated. Compared with the pure Inconel 625 cladding, the tensile strength of the ZrC/Inconel 625 cladding increased from 731Mpa to 783Mpa, the hardness increased by 29%, and the electrochemical corrosion rate decreased by 53.6%. The elongation of the ZrC-CNTs/Inconel 625 cladding increased from 13.4% to 24%, but the corrosion resistance decreased significantly.

In this paper, the 14 μm single-mode laser oscillation welding technique was adopted to achieve high-quality welding of 2A12 aluminum alloy. Specifically, its influence on the microstructure and mechanical properties of the joint and the formation mechanism were investigated. The results showed that the ultra-small spot laser (28 μm) was able to achieve sequential oscillation of the molten pool with small amplitude (0.1 mm). The increased frequency caused the average grain size to decrease and the grain boundary length increased in the fusion zone. Meanwhile, the average grain orientation difference increased, and the growth orientation was more dispersed and homogeneous. While reducing weld morphology defects and refining grain microstructure, there was little influence on the penetration and width morphology of the weld. Finally, successfully prepared welds with tensile strength up to 410.4 MPa and elongation simultaneously increased to 4.065 % at 200 Hz. Furthermore, the influence of keyhole oscillation on the molten pool flow at small amplitude was explained by high-speed camera observation, which explored the mechanism of grain growth in the oscillating joints and provided new ideas for the welding of 2xx aluminum alloys.

A wire-based laser directed energy deposition process was developed to repair Q690D steel. The microstructure evolution, phase transformation and mechanical properties of the repaired specimens were investigated in detail. Excellent metallurgical bonding was achieved between the repaired zone and the substrate free of macroscopic defects. Typical columnar dendrites with grains grew perpendicularly from the fusion line to the deposition zone (DZ) centre. Microstructure in the DZ and heat-affected zone (HAZ) of the repaired specimen was predominated by lath martensite. The tensile properties of the repaired specimens were comparable to those of the substrate. The repaired specimens presented ∼200 MPa higher flexural strength than that of the substrates, while they have inferior ductility compared to the substrates under the three-point bend test. The average impact absorbed energy value for the repaired specimens achieved ∼85–90% of the substrates. This study introduces a novel restoration technique for offshore engineering platform maintenance.

This study investigated the instability mechanisms within the blade-tip region of a transonic compressor. The variations in these mechanisms were explored under different operating conditions using methods such as spectral analysis and vortex identification. The results and analysis enhance the comprehension of self-excited unsteadiness in axial compressors, identifying its initiation characteristics and prevalence under different operational conditions. The regular occurrence of self-excited pulsations in transonic rotors was confirmed, especially when the flow rates fall blow specific levels, causing spontaneous pulsations within the tip region that are notably different from the blade-passing frequency. The findings highlight the crucial influence of interactions between separation flow, leakage flow, and shock waves in generating these pulsations. The effects of clearance size on flow structure intensity were also categorized, revealing three distinct self-excited unsteadiness mechanisms. These range from pulsations caused by shock–boundary-layer separation at small clearance sizes to those induced by interactions between leakage flow and shock waves at larger clearances, and finally to pulsations initiated directly by the clearance vortices at significantly larger clearances. This detailed analysis provides valuable insights into the dynamics of self-excited unsteadiness, supporting the advancement of the design and performance optimization of compressors.

Abstract Data mining from RNA-seq or microarray data has become an essential part of cancer biomarker exploration. Certain existing web servers are valuable and broadly utilized, but the meta-analysis of multiple datasets is absent. Most web servers only contain tumor samples from the TCGA database with only one cohort for each cancer type, which also means that the analysis results mainly derived from a single cohort are thin and unstable. Indeed, consistent performance across multiple independent cohorts is the foundation for an excellent biomarker. Moreover, the deeper exploration of specific biomarkers on underlying mechanisms, tumor microenvironment, and drug indications are missing in existing tools. Thus, we introduce BEST (Biomarker Exploration for Solid Tumors), a web application for comprehensive biomarker exploration on large-scale data in solid tumors. To ensure the comparability of genes between different sequencing technologies and the legibility of clinical traits, we re-annotated transcriptome data and unified the nomenclature of clinical traits. BEST delivers fast and customizable functions, including clinical association, survival analysis, enrichment analysis, cell infiltration, immunomodulator, immunotherapy, candidate agents, and genomic alteration. Together, our web server provides multiple cleaned-up independent datasets and diverse analysis functionalities, helping unleash the value of current data resources. It is freely available at https://rookieutopia.com/ .

Abstract N 6-methyladenosine (m6A), the most prevalent mRNA modification, has an important function in diverse biological processes. However, the involvement of m6A in allergic asthma and macrophage homeostasis remains largely unknown. Here we show that m6A methyltransferases METTL3 is expressed at a low level in monocyte-derived macrophages from childhood allergic asthma patients. Conditional knockout of Mettl3 in myeloid cells enhances Th2 cell response and aggravates allergic airway inflammation by facilitating M2 macrophage activation. Loss and gain functional studies confirm that METTL3 suppresses M2 macrophage activation partly through PI3K/AKT and JAK/STAT6 signaling. Mechanistically, m6A-sequencing shows that loss of METTL3 impairs the m6A-YTHDF3-dependent degradation of PTX3 mRNA, while higher PTX3 expression positively correlates with asthma severity through promoting M2 macrophage activation. Furthermore, the METTL3/YTHDF3-m6A/PTX3 interactions contribute to autophagy maturation in macrophages by modulating STX17 expression. Collectively, this study highlights the function of m6A in regulating macrophage homeostasis and identifies potential targets in controlling allergic asthma.

Two-dimensional MXenes are generally prepared by the etching of acid solutions. The as-synthesized MXenes are terminated by acid group anions (F–, Cl–, etc.), which affect the electrochemical performance of MXenes. Here, we report a novel method to prepare Mo2C MXene from Mo2Ga2C by the hydrothermal etching of alkali solutions. Highly pure Mo2C MXene was successfully synthesized by the etching of NaOH, while the etchings of LiOH and KOH were failed. The concentration of NaOH, temperature, and time strongly affect the purity of as-prepared MXene. Pure Mo2C MXene could be synthesized by the etching of 20 M NaOH at 180 ℃ for 24 h. After intercalation by hexadecyl trimethyl ammonium bromide at 90 ℃ for 96 h, few-layer Mo2C MXene was obtained. The Mo2C MXene made by NaOH etching after intercalation exhibited excellent performance as anode of lithium-ion battery, compared with general Mo2C MXene made by HF etching and the Mo2C MXene reported in literature. The final discharge specific capacity was 266.73 mAh·g−1 at 0.8 A·g−1, which is 52% higher than that Mo2C made by HF etching (175.77 mAh·g−1). This is because Mo2C MXene made by NaOH etching has lager specific surface area, lower resistance, and pure O/OH termination without acid anion termination. This is the first report to make Mo2C MXene by alkali etching and the samples made by this method exhibited significantly better electrochemical performance than the samples made by general HF etching.

With the increasing awareness of health, more people have shown a preference for low-alcohol beverages. Seeking various methods to improve the quality of kiwi wine is now a major research interest in the wine industry. In this study, kiwi wine was fermented by Saccharomyces cerevisiae and different non-Saccharomyces strains (Torulaspora delbrueckii, Kluyveromyces thermotolerans, Pichia fermentans) in three methods (pure fermentation, simultaneous, and sequential co-fermentation). The physicochemical characteristics, color parameters, phenolic profiles, total phenolic content (TPC), antioxidant activities, organic acids, and taste sense of the different wines were evaluated to determine the effects of different yeasts and fermentation methods on the quality of the kiwi wine. Results indicated that co-fermentation reduced the contents of alcohol while enhancing the lightness of the kiwi wine. The TPC of sequential co-fermentation with K. thermotolerans/S. cerevisiae was significantly higher than that of their simultaneous co-fermentation. Compared to K. thermotolerans/S. cerevisiae, the antioxidant activities were increased by co-fermentation of T. delbrueckii/S. cerevisiae and P. fermentans/S. cerevisiae. Principal component analysis showed that kiwi wines fermented by different yeasts and inoculation methods could be separated and grouped. Correlation analysis presented positive correlations of phenolic composition, antioxidant activities, and color intensity. This study provided theoretical guidance for co-fermentation of non-Saccharomyces/S. cerevisiae and accelerated the industrialization process of kiwi wine.

To explore the creep characteristics of geomembrane under different tensile stresses, a series of creep tests were carried out on high-density polyethylene (HDPE) geomembrane specimens. For the interpretation and fitting of the experimental data, refined approximation functions were proposed. Particular attention was paid to the creep failure behavior under high tensile stresses, i.e., 70%, 80%, and 90% of maximum peak stress. To investigate the effects of size on the mechanical response, experiments with two different membrane thicknesses were conducted. The results obtained under high stress levels were compared with creep tests at medium and low stress levels. Depending on load level, different creep characteristics can be distinguished. In the secondary creep state, the creep velocity is higher for higher load levels. In contrast to the medium and low load levels, the geomembrane under high stresses underwent the tertiary creep stage after instantaneous deformation and primary and secondary creep stages. In some tests, it was observed that under very high stress levels, creep velocity does not necessarily follow the expected trend and creep rupture can occur within a short time. For numerical simulation, an improved mathematical model was proposed to reproduce in a unified manner the experimental data of the whole non-linear evolution of creep elongation under different stress levels.

In this study, the effects of dandelion polysaccharide (DP) and its carboxymethylated derivative (CMDP) on the emulsifying characteristics and antioxidant capacities of emulsions stabilized by whey protein isolate (WPI) were determined. The addition of both DP and CMDP reduced the particle size and zeta potential of the emulsions. Using 1.0 % WPI and 1.0 % CMDP as emulsifier, the emulsifying activity index (EAI) and emulsifying stability index (ESI) were 32.61 ± 0.11 m2/g and 42.58 ± 0.13 min, respectively, which were higher than the corresponding values of 27.19 ± 0.18 m2/g and 36.17 ± 0.15 min with 1.0 % WPI and 1.0 % DP. Fourier-transform infrared spectroscopy (FT-IR), far-ultraviolet circular dichroism (Far-UV CD), and fluorescence (FS) spectra analyses confirmed that the α-helix and β-sheet structures in WPI-polysaccharide complexes were reduced compared with those in pure WPI, whereas the random-coil content was enhanced by the addition of polysaccharides. Moreover, DP and CMDP effectively improved the antioxidant capacity and inhibited oxidation of the emulsions during storage. Therefore, DP and its carboxymethylated derivative exhibit great potential to be applied in the emulsion-based delivery system.

Dislocation is a common extended defect in crystalline silicon solar cells, which affects the recombination characteristics of solar cells by forming deep‐level defect states in the silicon bandgap, thereby reducing the lifetime of minority carrier. Hence, reducing the impact of defects on device performance is an effective strategy to optimize the performance of photovoltaic devices. This article reviews the observation and engineering of dislocation in Si solar cell. The structure and deformation of Si can be directly observed by chemical etching combined with electron microscopy. Also, more information about dislocation is obtained indirectly by monitoring the electrical and optical properties of Si. The classification, density, distribution of dislocations, and their interactions with other defects in Si can affect the lifetime of minority carriers and thereby reduce the performance of Si solar cells. In order to achieve higher cell efficiency, crystals with less or even no dislocation should be obtained. In addition to the specification of controlling the relevant parameters during the growth of silicon ingots to obtain the minimum dislocation density, it is necessary to study the behavior of dislocation in Si wafers under the combined action of external stress, temperature, and other defects.

China’s northern Hulun Lake is a significant body of water internationally. The issue of eutrophication has gained prominence in recent years. The achievement of precise chlorophyll-a (Chl-a) monitoring is crucial for safeguarding Hulun Lake’s ecosystem. The machine learning-based remote sensing inversion method has been shown to be effective in capturing the intricate relationship between independent and dependent variables; however, it lacks a priori knowledge and is limited by the quality of remote sensing data sources. The relationship between independent and dependent variables can be more accurately simulated with the use of suitable auxiliary variables. Therefore, three machine learning models—random forest (RF), adaptive boosting (AdaBoost), and extreme gradient boosting (XGBoost)—were established in this study using meteorological observation parameters as auxiliary variables combined with Sentinel-2 satellite image remote sensing band combinations as independent variables and measured Chl-a data as dependent variables. The estimation effects before and after the fusion of meteorological ground observation data were compared, and the best model was used to estimate the spatial–temporal variation trend of Chl-a in the regional water body. The results show that (1) the addition of meteorological parameters as auxiliary variables improved the precision of the three machine models; the decision coefficient (R2) rose by 7.25%, 5.71%, and 7.20%, respectively, to 0.76, 0.66, and 0.73. (2) The concentration of Chl-a in the lake region was projected from June to October 2019 to October 2021 using the RF optimal estimating model of meteorological fusion. The northeast, southwest, and south of the lake were where the comparatively high concentration values of Chl-a were located, whereas the lake’s center had a generally low concentration of the substance. Chromatically, Chl-a typically peaked in August after initially increasing and then declining. (3) The three rivers that feed into the river have varying levels of water pollution, with chemical oxygen demand (COD) and total nitrogen (TN) pollution being the most severe. This is what primarily caused the higher levels of Chl-a in the northeast, southwest, and south. This study is crucial for the preservation and restoration of Hulun Lake’s natural ecosystem and offers some technical support for the monitoring of the lake’s concentration of Chl-a.

In this paper, hyperspectral imaging technology, combined with chemometrics methods, was used to detect the nitrogen content of soybean leaves, and to achieve the rapid, non-destructive and in situ detection of the nitrogen content in soybean leaves. Soybean leaves under different fertilization treatments were used as the research object, and the hyperspectral imaging data and the corresponding nitrogen content data of soybean leaves at different growth stages were obtained. Seven spectral preprocessing methods, such as Savitzky–Golay smoothing (SG), first derivative (1-Der), and direct orthogonal signal correction (DOSC), were used to establish the quantitative prediction models for soybean leaf nitrogen content, and the quantitative prediction models of different spectral preprocessing methods for soybean leaf nitrogen content were analyzed and compared. On this basis, successive projections algorithm (SPA), genetic algorithm (GA) and random frog (RF) were employed to select the characteristic wavelengths and compress the spectral data. The results showed the following: (1) The full-spectrum prediction model of soybean leaf nitrogen content based on DOSC pretreatment was the best. (2) The PLS model of soybean leaf nitrogen content based on the five characteristic wavelengths had the best prediction performance. (3) The spatial distribution map of soybean leaf nitrogen content was generated in a pixel manner using the extracted five characteristic wavelengths and the DOSC-RF-PLS model. The nitrogen content level of soybean leaves can be quantified in a simple way; this provides a foundation for rapid in situ non-destructive detection and the spatial distribution difference detection of soybean leaf nitrogen. (4) The overall results illustrated that hyperspectral imaging technology was a powerful tool for the spatial prediction of the nitrogen content in soybean leaves, which provided a new method for the spatial distribution of the soybean nutrient status and the dynamic monitoring of the growth status.

Abstract Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, and epigenetic alterations are striking features of immunosenescence. Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells, and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging. Although the underlying molecular mechanisms remain to be addressed, it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence. Potential counteractive measures will be discussed, including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence. In recent years, immunosenescence has attracted increasing attention for its role in tumor development. As a result of the limited participation of elderly patients, the impact of immunosenescence on cancer immunotherapy is unclear. Despite some surprising results from clinical trials and drugs, it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.

Abstract Background Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract which seriously endangers the health of human beings worldwide. Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of GC. This study aimed to investigate the impact of epigenetically regulated genes on the prognosis, immune microenvironment, and potential treatment of GC. Results Under the premise of verifying significant co-regulation of the aberrant frequencies of microRNA (miRNA) correlated (MIRcor) genes and DNA methylation-correlated (METcor) genes. Four GC molecular subtypes were identified and validated by comprehensive clustering of MIRcor and METcor GEPs in 1521 samples from five independent multicenter GC cohorts: cluster 1 was characterized by up-regulated cell proliferation and transformation pathways, with good prognosis outcomes, driven by mutations, and was sensitive to 5-fluorouracil and paclitaxel; cluster 2 performed moderate prognosis and benefited more from apatinib and cisplatin; cluster 3 was featured by an up-regulated ligand–receptor formation-related pathways, poor prognosis, an immunosuppression phenotype with low tumor purity, resistant to chemotherapy (e.g., 5-fluorouracil, paclitaxel, and cisplatin), and targeted therapy drug (apatinib) and sensitive to dasatinib; cluster 4 was characterized as an immune-activating phenotype, with advanced tumor stages, benefit more from immunotherapy and displayed worst prognosis. Conclusions According to the epigenetically regulated GEPs, we developed four robust GC molecular subtypes, which facilitated the understanding of the epigenetic mechanisms underlying GC heterogeneity, offering an optimized decision-making and surveillance platform for GC patients.

Objectives: To describe the epidemiological, clinical, and household transmission characteristics of pediatric COVID-19 cases in Shanghai, China. Methods: Pediatric patients with COVID-19 hospitalized in Shanghai from March-May 2022 were enrolled in this retrospective, multicenter cohort study. The symptoms and the risk factors associated with disease severity were analyzed. Results: In total, 2620 cases (age range, 24 days-17 years) were enrolled in this study. Of these, 1011 (38.6%) were asymptomatic, whereas 1415 (54.0%), 190 (7.3%), and 4 (0.2%) patients developed mild, moderate, and severe illnesses, respectively. Household infection rate was negatively correlated with household vaccination coverage. Children aged 0-3 years, those who are unvaccinated, those with underlying diseases, and overweight/obese children had a higher risk of developing moderate to severe disease than children aged 12-17 years, those who were vaccinated, those without any underlying disease, and those with normal weight, respectively (all P

Background Chronic kidney disease (CKD) is closely associated with cardiovascular disease. We aimed to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of CKD among US adults. Methods and Results This population‐based cross‐sectional study used data from the National Health and Nutrition Examination Survey from 2007 to 2018 and included adults aged ≥20 years. Multivariable logistic and restricted cubic spline models were used to assess the associations between LE8 and CKD. Among 24 960 participants, 4437 were determined to have CKD (weighted percentage, 14.11%). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of CKD (odds ratio for each 10‐point increase, 0.79 [95% CI, 0.76–0.83]), and a nonlinear dose–response relationship was observed. Similar patterns were also identified in the associations of health behavior and health factor scores with CKD. Meanwhile, higher scores for blood glucose (odds ratio, for each 10‐point increase, 0.88 [95% CI, 0.87–0.90]) and blood pressure (odds ratio, for each 10‐point increase, 0.92 [95% CI, 0.91–0.94]) in the LE8 component are significantly associated with a lower prevalence of CKD. The inversed association of LE8 score and CKD was significantly stronger among middle‐aged, male, and coupled participants. Conclusions LE8 was negatively associated with the prevalence of CKD in a nonlinear fashion. Promoting adherence to optimal cardiovascular health levels may be beneficial to reduce the burden of CKD.

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.

PurposeThis study aimed to evaluate the robustness with respect to the positional variations of five planning strategies in free-breathing breast hypofractionated radiotherapy (HFRT) for patients after breast-conserving surgery.MethodsTwenty patients who received breast HFRT with 42.72 Gy in 16 fractions were retrospectively analyzed. Five treatment planning strategies were utilized for each patient, including 1) intensity-modulated radiation therapy (IMRT) planning (IMRTpure); 2) IMRT planning with skin flash tool extending and filling the fluence outside the skin by 2 cm (IMRTflash); 3) IMRT planning with planning target volume (PTV) extended outside the skin by 2 cm in the computed tomography dataset (IMRTePTV); 4) hybrid planning, i.e., 2 Gy/fraction three-dimensional conformal radiation therapy combined with 0.67 Gy/fraction IMRT (IMRThybrid); and 5) hybrid planning with skin flash (IMRThybrid-flash). All plans were normalized to 95% PTV receiving 100% of the prescription dose. Six additional plans were created with different isocenter shifts for each plan, which were 1 mm, 2 mm, 3 mm, 5 mm, 7 mm, and 10 mm distally in the X (left-right) and Y (anterior-posterior) directions, namely, (X,Y), to assess their robustness, and the corresponding doses were recalculated. Variation of dosimetric parameters with increasing isocenter shift was evaluated.ResultsAll plans were clinically acceptable. In terms of robustness to isocenter shifts, the five planning strategies followed the pattern IMRTePTV, IMRThybrid-flash, IMRTflash, IMRThybrid, and IMRTpure in descending order. V95% of IMRTePTV maintained at 99.6% ± 0.3% with a (5,5) shift, which further reduced to 98.2% ± 2.0% with a (10,10) shift. IMRThybrid-flash yielded the robustness second to IMRTePTV with less risk from dose hotspots, and the corresponding V95% maintained >95% up until (5,5).ConclusionConsidering the dosimetric distribution and robustness in breast radiotherapy, IMRTePTV performed best at maintaining high target coverage with increasing isocenter shift, while IMRThybrid-flash would be adequate with positional uncertainty

Summary: Most gastric cancer (GC) subtypes are identified through transcriptional profiling overlooking dynamic changes and interactions in gene expression. Based on the background network of global immune genes, we constructed sample-specific edge-perturbation matrices and identified four molecular network subtypes of GC (MNG). MNG-1 displayed the best prognosis and vigorous cell cycle activity. MNG-2 was enriched by immune-hot phenotype with the potential for immunotherapy response. MNG-3 and MNG-4 were identified with epithelial-mesenchymal transition (EMT) peculiarity and worse prognosis, termed EMT subtypes. MNG-3 was characterized by low mutational burden and stromal cells and considered a replica of previous subtypes associated with poor prognosis. Notably, MNG-4 was considered a previously undefined subtype with a dismal prognosis, characterized by chromosomal instability and immune-desert microenvironment. This subtype tended to metastasize and was resistant to respond to immunotherapy. Pharmacogenomics analysis showed three therapeutic agents (NVP-BEZ235, LY2606368, and rutin) were potential interventions for MNG-4.

Abstract Background PI3K pathway is the most frequently mutated pathway in head and neck squamous cell carcinoma (HNSC), which plays a crucial role in tumorigenesis and progression. In the present study, we aimed to investigate the role of PI3K pathway mutation in clinical prognosis prediction and the relationship with immune microenvironment and response rate to immunotherapy. Methods We collected 129 samples with immunotherapy information from MSKCC-2019 cohort as well as 501 and 40 samples from TCGA-HNSC and MD-Anderson non-immunotherapy cohorts, respectively. Somatic mutation data was utilized to characterize the mutational status of the PI3K pathway. Subsequently, we further analyzed the differences in prognosis, immunotherapy response, genomic alterations, functional characteristics, and immune microenvironment between the mutation and wild groups. Results The Kaplan-Meier survival curves displayed that PI3K pathway mutation predicted observably prolonged overall survival (OS) in the immunotherapy cohort MSKCC-2019 (p = 0.012) but did not reach statistical significance in the non-immunotherapy cohorts TCGA-HNSC (p = 0.68) and MD-Anderson (p = 0.68). After incorporating several clinicopathologic features such as age, gender, and tumor mutation burden (TMB), the results of multivariate Cox regression analysis also demonstrated that the PI3K pathway mutation could indicate better immunotherapy outcomes in HNSC patients with a hazard ratio (HR) of 0.533 (95% CI: 0.313–0.910; p = 0.021) in the immunotherapy cohort MSKCC-2019, compared with 0.888 (95% CI: 0.636–1.241; p = 0.487) and 1.939 (95% CI: 0.483–7.781; p = 0.351) in the non-immunotherapy cohorts TCGA-HNSC and MD-Anderson. In addition, the results of the subclass mapping (SubMap) and the tumor immune dysfunction and exclusion (TIDE) also consistently suggested that patients in the mutation group are more likely to benefit from immunotherapy. And further studies showed that the mutation group owned significantly higher TMB, activated immune-related pathways, richer abundance of immune cells, and higher expression levels of immunomodulators. To improve the prognosis of the wild group, we identified five relatively sensitive potential drugs for the wild group, including “BMS-536924,” “linsitinib,” “NVP-TAE684,” “PLX-4720,” and “clonazepam.” Conclusions The PI3K pathway mutation status could be considered as a potential biomarker to predict better immunotherapeutic efficacy and clinical outcomes after immunotherapy in HNSC patients.

Abstract Background Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease of nonspecific origin. This study used an RNA-Sequencing (RNA-Seq) approach to evaluate the transcriptomic landscape of a well-stratified treatment-naïve pediatric UC patient population by comparing them with healthy control children. The data were analyzed to evaluate the mechanisms driving UC-related intestinal inflammation and fibrosis. Methods Intestinal mucosal samples from five pediatric UC patients and five healthy controls were analyzed by RNA-Seq, and results were verified by qPCR. A CRISPR/Cas9 approach was used to knock out the expression of HLA-DRB5, and molecular biology techniques were used for additional mechanistic studies. Results In these analyses, 2290 genes were found to be differentially expressed between the UC and control samples, of which 1258 and 1032 were upregulated and downregulated, respectively. Gene Ontology analysis showed that these genes were enriched in extracellular matrix (ECM)-related processes and that 7 of 8 differentially expressed genes of interest (PIK3CD, IL1β, IL1α, TIMP1, MMP1, MMP12, COL6A3, and HLADRB5) were upregulated and involved in ECM-receptor interaction and inflammatory bowel disease-related pathways. Increased HLA-DRB5 expression driven by intestinal bacteria was found to promote IL-1α secretion, leading to intestinal inflammation and fibrosis, suggesting a possible target for the treatment of UC. Conclusion These data suggest that intestinal inflammation is present in pediatric UC patients for extended periods before the onset of symptoms, and intestinal fibrosis begins even during the early stages of UC. Intestinal bacteria were also found to trigger intestinal inflammation and fibrosis, with HLA-DRB5 playing a central role in this process.

Abstract The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.

Abstract In this paper, we consider the following singular third-order two-point boundary value problem on the half-line of the form { x ‴ + ϕ ( t ) f ( t , x , x ′ , x ″ ) = 0 , 0 < t < + ∞ , x ( 0 ) = 0 , x ′ ( 0 ) = a 1 , x ′ ( + ∞ ) = b 1 , $$ \textstyle\begin{cases} x'''+\phi (t)f(t,x,x',x'')=0, \quad 0< t< +\infty , \\ x(0)=0, \qquad x'(0)=a_{1},\qquad x'(+\infty )=b_{1}, \end{cases} $$ where ϕ ∈ C [ 0 , + ∞ ) $\phi \in C[0,+\infty )$ , f ∈ C ( [ 0 , + ∞ ) × ( 0 , + ∞ ) × R 2 , R ) $f\in C([0,+\infty )\times (0,+\infty )\times \mathbb{R}^{{2}},\mathbb{R})$ may be singular at x = 0 $x=0$ , and a 1 $a_{1}$ , b 1 $b_{1}$ are positive constants. Using the Leray–Schauder nonlinear alternative and the diagonalization method together with the truncation function technique, we obtain the existence and qualitative properties of positive solutions for the problem. As applications, an example is given to illustrate our result.

The most common primary cardiac tumors in adults are atrial myxomas, with adolescent-onset being uncommon. In this case report, a 15-year-old female was hospitalized with cerebrovascular embolism and later diagnosed with a left atrial myxoma. She had previously shown signs of distal vascular micro thrombosis, including recurring bilateral lower extremity rash, which are crucial for the early diagnosis and differential diagnosis of atrial mucinous neoplasm. We reviewed the various clinical symptoms and diagnostic approaches to identify left atrial mucinous neoplasm. This patient also had a combination of endocrine-related diseases. We reviewed the diagnostic approach for the Carney Complex (CNC) and discussed the role of thyroid disease in diagnosing CNC.

Abstract Canada's boreal forests and tundra ecosystems are responding to unprecedented climate change with implications for the global carbon (C) cycle and global climate. However, our ability to model the response of Canada's terrestrial ecosystems to climate change is limited and there has been no comprehensive, process‐based assessment of Canada's terrestrial C cycle. We tailor the Canadian Land Surface Scheme Including Biogeochemical Cycles (CLASSIC) to Canada and evaluate its C cycling performance against independent reference data. We utilize skill scores to assess model performance against reference data alongside benchmark scores that quantify the level of agreement between the reference data sets to aid in interpretation. Our results demonstrate CLASSIC's sensitivity to prescribed vegetation cover. They also show that the addition of five region‐specific Plant functional types (PFTs) improves CLASSIC's skill at simulating the Canadian C cycle. CLASSIC performs well when tailored to Canada, falls within the range of the reference data sets, and meets or exceeds the benchmark scores for most C cycling processes. New region‐specific land cover products, well‐informed PFT parameterizations, and more detailed reference data sets will facilitate improvements to the representation of the terrestrial C cycle in regional and global land surface models. Incorporating a parameterization for boreal disturbance processes and explicitly representing peatlands and permafrost soils will improve CLASSIC's future performance in Canada and other boreal regions. This is an important step toward a comprehensive process‐based assessment of Canada's terrestrial C cycle and evaluating Canada's net C balance under climate change.

BackgroundNoninvasive positive-pressure ventilation (NPPV) can be effective in children with acute asthma. However, clinical evidence remains limited. The objective of the meta-analysis was to systematically assess NPPV's effectiveness and safety in treating children with acute asthma.MethodsRelevant randomized controlled trials were obtained from electronic resources, including PubMed, Embase, Cochrane's Library, Wanfang, and CNKI databases. The influence of potential heterogeneity was taken into account before using a random-effect model to pool the results.ResultsA total of 10 RCTs involving 558 children with acute asthma were included in the meta-analysis. Compared to conventional treatment alone, additional use of NPPV significantly improved early blood gas parameters such as the oxygen saturation (mean difference [MD]: 4.28%, 95% confidence interval [CI]: 1.51 to 7.04, p = 0.002; I2 = 80%), partial pressure of oxygen (MD: 10.61 mmHg, 95% CI: 6.06 to 15.16, p

Bonding technology can be an important component of packaging for photonic chips, such as electro-optic (EO) modulators and other active function devices. In general, an EO modulator chip can achieve a broader 3 dB EO bandwidth than its packaging device, as the packaging design and structure can technically limit modulation performance. Recently, bump bonding has been shown to be a good candidate for the EO interconnection technique, which has a higher transmission bandwidth than wire bonding. In this article, we propose a design for radio frequency (RF) interconnection of bump bonding with a dislocation packaging (BBDP) structure. Through simulation calculations and analysis, the proposed BBDP structure shows a 3 dB transmission bandwidth of approximately 145 GHz, which is 52.6% better than one using optimized wire-bonding structures (95 GHz). The proposed packaging structure presents an important alternative method for ultrahigh speed optical modulation applications.

This paper investigated evolutions of α-Al sub-grains’ morphology and crystalline orientation in the fusion zone during laser welding of 2A12 aluminum alloys. Based on this, a new method for assessing the weldability of materials was proposed. In laser deep-penetration welding, in addition to the conventional columnar and equiaxed dendrites, there also exhibited a corrugated structure with several ‘fine-coarse-fine’ transformations. In such regions, an abnormal α-Al coarsening phenomenon was encountered, with a more dispersed crystalline orientation arrangement and a decreased maximum pole density value. Particularly, structural alterations appeared more frequently in the weld bottom than the top. The above results indicated that the laser-induced keyhole presented a continually fluctuating state. Under such a condition, the solid–liquid transformation exhibited an unstable solidification front, a fluctuant undercooling, and a variational solidification rate. Meanwhile, the welding quality of this material is in a critical state to generate pores. Therefore, the appearance and relevant number of corrugated regions can be considered as a new way for judging the weldability, which will help to narrow the processing window with better welding stability.

Abstract Background Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD). Methods PubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3rd 2021. Results Ten studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events. Conclusions According to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.

Abstract In order to improve the high‐temperature friction and wear properties of polyimide (PI), Mo2CTx/PI nanocomposite materials are prepared by using 2D Mo2CTx MXene as reinforcement. Compared with the properties of pure PI, Mo2CTx/PI nanocomposites exhibit significant improvement on thermal stability, hardness, and tribological performance. Especially, the addition of Mo2CTx can reduce friction coefficient and wear rate of PI significantly at different temperatures ranging from room temperature (RT) to 200 °C. The hardness and the thermo‐degradation temperature of composites increase due to the formation of an organic inorganic structure. In addition, this structure helps to form a protective film containing Mo2CTx nanoflakes, iron oxide, molybdenum oxide, and organic compounds during friction, and improve the tribological properties of PI composite.

Myocardial remodeling refers to structural and functional disorders of the heart caused by molecular biological changes in the cardiac myocytes in response to neurological and humoral factors. A variety of heart diseases, such as hypertension, coronary artery disease, arrhythmia, and valvular heart disease, can cause myocardial remodeling and eventually lead to heart failure. Therefore, counteracting myocardial remodeling is essential for the prevention and treatment of heart failure. Sirt1 is a nicotinamide adenine dinucleotide+-dependent deacetylase that plays a wide range of roles in transcriptional regulation, energy metabolism regulation, cell survival, DNA repair, inflammation, and circadian regulation. It positively or negatively regulates myocardial remodeling by participating in oxidative stress, apoptosis, autophagy, inflammation, and other processes. Taking into account the close relationship between myocardial remodeling and heart failure and the involvement of SIRT1 in the development of the former, the role of SIRT1 in the prevention of heart failure via inhibition of myocardial remodeling has received considerable attention. Recently, multiple studies have been conducted to provide a better understanding of how SIRT1 regulates these phenomena. This review presents the progress of research involving SIRT1 pathway involvement in the pathophysiological mechanisms of myocardial remodeling and heart failure.

Summary: Striving to optimize surgical outcomes, the Enhanced Recovery After Surgery (ERAS) pathway mitigates patients’ stress through the implementation of evidence-based practices during the pre-, intra-, and postoperative periods. Intestinal flora is a sophisticated ecosystem integrating with the host and the external environment, which serves as a mediator in diverse interventions of ERAS to regulate human metabolism and inflammation. This review linked gut microbes and their metabolites with ERAS interventions, offering novel high-quality investigative proponents for ERAS. ERAS could alter the composition and function of intestinal flora in patients by alleviating various perioperative stress responses. Modifying gut flora through multiple modalities, such as diet and nutrition, to accelerate recovery might be a complementary approach when exploring novel ERAS initiatives. Meanwhile, the pandemic of COVID-19 and the availability of promising qualitative evidence created both challenges and opportunities for the establishment of ERAS mode.