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Abstract Background The clinical features of cerebellar high-grade gliomas (cHGGs) in adults have not been thoroughly explored. This large-scale, population-based study aimed to comprehensively outline these traits and construct a predictive model. Methods Patient records diagnosed with gliomas were collected from various cohorts and analyzed to compare the features of cHGGs and supratentorial HGGs (sHGGs). Cox regression analyses were employed to identify prognostic factors for overall survival and to develop a nomogram for predicting survival probabilities in patients with cHGGs. Multiple machine learning methods were applied to evaluate the efficacy of the predictive model. Results There were significant differences in prognosis, with SEER-cHGGs showing a median survival of 7.5 months and sHGGs 14.9 months (p

Abstract Background The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. Results In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. Conclusion A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.

Abstract Background Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. Methods We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. Results Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. Conclusion The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Abstract Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447–0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327–0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996–1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.

Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

Abstract Due to the BCS theory, hydrogen, the lightest element, would be the prospect of room-temperature superconductor after metallization, but because of the difficulty of the hydrogen metallization, the theory about hydrogen pre-compression was proposed that the hydrogen-rich compounds could be a great option for the high T c superconductors. The superior properties of TmH6, YbH6 and LuH6 indicated the magnificent potential of heavy rare earth elements for low-pressure stability. Here, we designed XTmH12 (X = Y, Yb, Lu, and La) to obtain higher T c while maintaining low pressure stability. Most prominently, YbTmH12 can stabilize at a pressure of 60 GPa. Compared with binary TmH6 hydride, its T c was increased to 48 K. The results provide an effective method for the rational design of moderate pressure stabilized hydride superconductors.

Abstract Background Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)was reported in some studies, while the diagnosis of TdT (terminal deoxynucleotydil transferase) positive high grade B cell lymphoma (HGBL) with MYC and BCL2 rearrangements (“double hit”) transformed from FL/DLBCL has been rarely reported. Herein, we described the clinical features and mutation profiles of a case diagnosed with TdT positive “double hit” HGBL following the treatment of FL/DLBCL. Case presentation This is a 43-year-old Chinese man who was diagnosed with low grade FL (account for 80%) combined with DLBCL (20%) at a stage of IVB. The patient presented with BCL2/IGH translocation without MYC rearrangement, as well as the expressions of CD20, CD19, CD10 and BCL2 at the initial diagnosis of FL/DLBCL. MYC rearrangement and TdT expression occurred after the treatment. The targeted sequencing revealed mutations in KMT2D, FOXO1, CREBBP, ATM, STAT6, BCL7A, DDX3X, MUC4, FGFR3, ARID5B, DDX11 and PRKCSH genes were the co-mutations shared by the FL/DLBCL and TdT positive “double hit” HGBL, while CCND3, BIRC6, ROBO1 and CHEK2 mutations specifically occurred after the treatment. The overall survival time was 37.8 and 17.8 months after the initial diagnosis of FL/DLBCL and TdT positive “double hit” HGBL, respectively. Conclusion This study reports a rare case of TdT positive “double hit” HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive “double hit” HGBL transformed from FL/DLBCL.

River bottom tearing scour (RBTS) has a strong effect on the scouring and moulding of channel in the Yellow River. Due to the special forming conditions, complex influencing factors, and limited observed data, it is difficult to predict whether RBTS will occur accurately. By collecting and disposing of the hydrodynamic, sediment, and initial boundary data of 246 flood events related to RBTS in three typical reaches of the Yellow River basin, the correlation between different characteristic influencing factors and the occurrence and absence of RBTS were analysed, and prediction models based on machine learning algorithms were constructed. The results showed that under the existing data conditions, the maximum sediment concentration Sm, average sediment concentration Sp, flood growth rate ν, and shape coefficient δ were the four key indices to more easily distinguish whether RBTS will occur. The support vector machine algorithm model had the best performance results and exhibited higher accuracy and precision in predicting its occurrence compared with other models under given water and sediment conditions. The method proposed in this study provides a new method for accurately predicting RBTS in the Yellow River. HIGHLIGHTS The maximum sediment concentration, average sediment concentration, flood growth rate, and shape coefficient are the four key indices for distinguishing whether RBTS will occur.; Prediction models of RBTS based on machine learning algorithms were built.; The SVM model showed the best predictive performance in the case study of the middle reach of the Yellow River.;

Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9 calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.

Landslide disasters, due to their widespread distribution and clustered occurrences, pose a significant threat to human society. Rainfall is considered a primary triggering factor, and the frequent clustering of landslides underscores the importance of early warning systems for regional landslide disasters in preventing and mitigating rainfall-induced landslides. Research on early warning models is crucial for accurately predicting rainfall-induced landslides. However, traditional models face challenges such as the complexity of landslide causes, insufficient data, and limited analysis methods, resulting in low accuracy and inadequate precision. This study focuses on Fujian Province, China, proposing a four-step process for building a regional landslide early warning model based on machine learning. The process includes data integration and cleaning, sample set construction, model training and validation, and practical application. By integrating and cleaning the latest and most detailed data, a training sample set (15,589 samples) for the regional landslide disaster early warning model is established. Three machine learning algorithms—Random Forest, Multilayer Perceptron, and Convolutional Neural Network—are employed and compared, the evaluation results indicated that the RF-based warning model achieved an accuracy of 0.930–0.957 and an AUC value of 0.955. The CNN-based warning model demonstrated an accuracy of 0.945–0.948 with an AUC value of 0.940. The MLP-based warning model achieved an accuracy of 0.930–0.953 and an AUC value of 0.930. The results showed comparable accuracy metrics among the three models, with RF exhibiting a significant advantage in AUC values. Finally, the models are applied to the regional landslide disasters induced by heavy rainfall in Fujian Province on 5 August 2021. The results showed that in the binary classification warning strategy, the accuracy of the Random Forest and Convolutional Neural Network was 92.9%, while that of the Multilayer Perceptron was 85.8%, all performing well. In the multi-classification hierarchical warning strategy, the Random Forest excelled, while the performance of the Convolutional Neural Network and Multilayer Perceptron was relatively limited. The findings of this study contribute to valuable attempts in landslide disaster warning model research, with anticipated further improvements through the gradual accumulation of samples and practical application verification.

Abstract Background and Objective High‐grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium‐frequency, low‐intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. Methods We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non‐TTFields group. Progression‐free survival (PFS) and overall survival (OS) were compared between the two groups. Results There were 26 cases in the TTFields group and 26 cases in the non‐TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50–18.90), the median OS was 19.7 months (95% CI: 14.95–24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47–4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57–11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non‐TTFields group, the median PFS was 9.57 months (95% CI: 6.23–12.91) and the median OS was 16.07 months (95% CI: 12.90–19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. Conclusions In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Summary: The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

Abstract Studying complex relaxation behaviors is of critical importance for understanding the nature of glasses. Here we report a Kovacs-like memory effect in glasses, manifested by non-monotonic stress relaxation during two-step high-to-low strains stimulations. During the stress relaxation process, if the strain jumps from a higher state to a lower state, the stress does not continue to decrease, but increases first and then decreases. The memory effect becomes stronger when the atomic motions become highly collective with a large activation energy, e.g. the strain in the first stage is larger, the temperature is higher, and the stimulation is longer. The physical origin of the stress memory effect is studied based on the relaxation kinetics and the in-situ synchrotron X-ray experiments. The stress memory effect is probably a universal phenomenon in different types of glasses.

Abstract Background Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis. Methods Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome‐wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR‐Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave‐one‐out analysis. Results For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011–1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045–1.511, p = .015). Conclusion Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.

Abstract An experimental investigation of circular concrete-filled steel tubular (CFST) columns subjected to very low-elevation lateral impacts was performed. Six circular CFST members were prepared for lateral impact tests according to the typical CFST columns in high-speed railway stations in China, and the impact location was at the height of the 2/9 column. The tests had three variables: the thickness of the steel tube, the impact velocity, and the axial load. The failure modes were determined in the tests, along with the time histories of the impact force and the deflection at the impact location. A finite-element analysis was performed to examine the effects of the axial load and scaling on the maximum deflection. The results show that with the increase of axial compression ratio, the impact resistance of the member first increases and then weakens. According to the travelling plastic hinge theory, a three-stage rigid plastic mechanical model was employed to describe the impact process, in which the impact location was at the non-mid-span, and a deflection calculation method for CFST applicable to any impact position was developed. A comparison with the test results indicated that deflections can be calculated with reasonable accuracy using the proposed method.

Abstract Background Epigenetic clocks constructed from DNA methylation patterns have emerged as excellent predictors of aging and aging-related health outcomes. Iron, a crucial element, is meticulously regulated within organisms, a phenomenon referred as iron homeostasis. Previous researches have demonstrated the sophisticated connection between aging and iron homeostasis. However, their causal relationship remains relatively unexplored. Results Through two-sample Mendelian randomization (MR) utilizing the random effect inverse variance weighted (IVW) method, each standard deviation (SD) increase in serum iron was associated with increased GrimAge acceleration (GrimAA, BetaIVW = 0.27, P = 8.54E−03 in 2014 datasets; BetaIVW = 0.31, P = 1.25E−02 in 2021 datasets), HannumAge acceleration (HannumAA, BetaIVW = 0.32, P = 4.50E−03 in 2014 datasets; BetaIVW = 0.32, P = 8.03E−03 in 2021 datasets) and Intrinsic epigenetic age acceleration (IEAA, BetaIVW = 0.34, P = 5.33E−04 in 2014 datasets; BetaIVW = 0.49, P = 9.94E−04 in 2021 datasets). Similar results were also observed in transferrin saturation. While transferrin manifested a negative association with epigenetic age accelerations (EAAs) sensitivity analyses. Besides, lack of solid evidence to support a causal relationship from EAAs to iron-related biomarkers. Conclusions The results of present investigation unveiled the causality of iron overload on acceleration of epigenetic clocks. Researches are warranted to illuminate the underlying mechanisms and formulate strategies for potential interventions.

Abstract The underlying atomistic mechanism of deformation is a central problem in mechanics and materials science. Whereas deformation of crystalline metals is fundamentally understood, the understanding of deformation of amorphous metals lacks behind, particularly identifying the involved temporal and spatial scales. Here, we reveal that at small scales the size-dependent deformation behavior of amorphous metals significantly deviates from homogeneous flow, exhibiting increasing deformation rate with reducing size and gradually shifted composition. This transition suggests the deformation mechanism changes from collective atomic transport by viscous flow to individual atomic transport through interface diffusion. The critical length scale of the transition is temperature dependent, exhibiting a maximum at the glass transition. While viscous flow does not discriminate among alloy constituents, diffusion does and the constituent element with higher diffusivity deforms faster. Our findings yield insights into nano-mechanics and glass physics and may suggest alternative processing methods to epitaxially grow metallic glasses.

Climate change and human activities exert significant impacts on runoff generation and convergence mechanisms. Understanding the evolution mechanisms and driving forces of runoff is crucial for the sustainable development of water resources. This study is based on the runoff data of the Huayuankou (HYK), Jiahetan (JHT), and Gaocun (GC) stations in the lower reaches of the Yellow River from 1951 to 2019. The objectives are to identify and quantify the hydrological pattern and its driving mechanism of the three stations by the Mann–Kendall test, cumulative deviation method, wavelet analysis, the IHA-RVA method, SCRCO method, and the Budyko method. Our study revealed that the runoff disturbance points at all three stations occurred in 1985. During the two periods before and after the disturbance, the trends and periodicities within the year exhibited high consistency, showing an overall downward trend, with runoff increasing in October and decreasing in June and the primary cycles being 5 and 7 years. All three stations experienced high-degree changes in their hydrological situations, with the high-degree change occupying the largest proportion. At the HYK, JHT, and GC stations, human activities accounted for 66.05%, 71.94%, and 74.38% of runoff changes, respectively. Furthermore, we verified the attribution conclusion of runoff at HYK using the Budyko model, confirming that human activities are the primary factor influencing runoff. Finally, we explored the interactive relationships along the spatial trajectory of runoff at the three stations, analyzed 32 hydrological indicators, and detailed the land use changes in the Yellow River Basin. Our research findings complement the understanding of hydrological change mechanisms in the lower reaches of the Yellow River Basin and provide a scientific basis for future water resource management and flood prevention measures.

Pineapple is a globally significant tropical fruit, but its cultivation faces numerous challenges due to abiotic and biotic stresses, affecting its quality and quantity. WRKY transcription factors are known regulators of stress responses, however, their specific functions in pineapple are not fully understood. This study investigates the role of AcWRKY31 by overexpressing it in pineapple and Arabidopsis. Transgenic pineapple lines were obtained using Agrobacterium-mediated transformation methods and abiotic and biotic stress treatments. Transgenic AcWRKY31-OE pineapple plants showed an increased sensitivity to salt and drought stress and an increased resistance to biotic stress from pineapple mealybugs compared to that of WT plants. Similar experiments in AcWRKY31-OE, AtWRKY53-OE, and the Arabidopsis Atwrky53 mutant were performed and consistently confirmed these findings. A comparative transcriptomic analysis revealed 5357 upregulated genes in AcWRKY31-OE pineapple, with 30 genes related to disease and pathogen response. Notably, 18 of these genes contained a W-box sequence in their promoter region. A KEGG analysis of RNA-Seq data showed that upregulated DEG genes are mostly involved in translation, protein kinases, peptidases and inhibitors, membrane trafficking, folding, sorting, and degradation, while the downregulated genes are involved in metabolism, protein families, signaling, and cellular processes. RT-qPCR assays of selected genes confirmed the transcriptomic results. In summary, the AcWRKY31 gene is promising for the improvement of stress responses in pineapple, and it could be a valuable tool for plant breeders to develop stress-tolerant crops in the future.

Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O improves lipopolysaccharide (LPS)-induced macrophage inflammation. In this study, LPS-stimulated mouse RAW264.7 macrophages were used as a model to analyze the effects of T-4-O on macrophage inflammatory factors and related metabolic pathways in an inflammatory environment. The results showed that T-4-O significantly decreased the expression levels of inflammatory cytokines induced by LPS. Cellular metabolism results showed that T-4-O significantly decreased the ratio of the extracellular acidification rate and oxygen consumption rate. Non-targeted metabolomics results showed that T-4-O mainly affected glutamine and glutamate metabolism and glycine, serine, and threonine metabolic pathways. qPCR results showed that T-4-O increased the transcript levels of GLS and GDH and promoted glutamine catabolism. Western blotting results showed that T-4-O inhibited the mTOR and IκB, thereby decreasing NF-κB activity. The overall results showed that T-4-O inhibited mTOR phosphorylation to promote glutamine metabolism and increased cell oxidative phosphorylation levels, thereby inhibiting the expression of LPS-induced inflammatory cytokines.

Brain metastasis is the leading cause of death in most cancer patients; thus, anti‐brain metastasis is a crucial step in cancer treatment. The unique microenvironment and pathophysiological characteristics of brain metastases hamper the development of effective treatment methods, while the advances in nanomedicine demonstrate its immense potential for addressing this challenge. In recent years, due to breakthroughs in nanotechnology, functional and complex nanomedicine is prepared and it has been extensively explored to improve the treatment of brain metastasis. Compared to traditional treatment methods, nanomedicine can combine multiple traditional treatment methods into one single medicinal format and target unique characteristics of brain metastases to enhance the treatment efficacy. This review summarizes the main obstacles in the field of brain metastasis treatment and clinical/preclinical studies and surveys the use of a variety of nanomedicine candidates as antibrain metastasis strategies for different types of brain metastases.

ObjectiveAnalyzing the epidemiological characteristics of influenza cases among children aged 0–17 years in Guangzhou from 2019 to 2022. Assessing the relationships between multiple meteorological factors and influenza, improving the early warning systems for influenza, and providing a scientific basis for influenza prevention and control measures.MethodsThe influenza data were obtained from the Chinese Center for Disease Control and Prevention. Meteorological data were provided by Guangdong Meteorological Service. Spearman correlation analysis was conducted to examine the relevance between meteorological factors and the number of influenza cases. Distributed lag non-linear models (DLNM) were used to explore the effects of meteorological factors on influenza incidence.ResultsThe relationship between mean temperature, rainfall, sunshine hours, and influenza cases presented a wavy pattern. The correlation between relative humidity and influenza cases was illustrated by a U-shaped curve. When the temperature dropped below 13°C, Relative risk (RR) increased sharply with decreasing temperature, peaking at 5.7°C with an RR of 83.78 (95% CI: 25.52, 275.09). The RR was increased when the relative humidity was below 66% or above 79%, and the highest RR was 7.50 (95% CI: 22.92, 19.25) at 99%. The RR was increased exponentially when the rainfall exceeded 1,625 mm, reaching a maximum value of 2566.29 (95% CI: 21.85, 3558574.07) at the highest rainfall levels. Both low and high sunshine hours were associated with reduced incidence of influenza, and the lowest RR was 0.20 (95% CI: 20.08, 0.49) at 9.4 h. No significant difference of the meteorological factors on influenza was observed between males and females. The impacts of cumulative extreme low temperature and low relative humidity on influenza among children aged 0–3 presented protective effects and the 0–3 years group had the lowest RRs of cumulative extreme high relative humidity and rainfall. The highest RRs of cumulative extreme effect of all meteorological factors (expect sunshine hours) were observed in the 7–12 years group.ConclusionTemperature, relative humidity, rainfall, and sunshine hours can be used as important predictors of influenza in children to improve the early warning system of influenza. Extreme weather reduces the risk of influenza in the age group of 0–3 years, but significantly increases the risk for those aged 7–12 years.

Considering the mass reservoirs construction, it is important to study the cascade reservoir construction sequence, which directly affects the water and sediment resource allocation, ecological environment restoration, and socioeconomic development of the basin. Thus, we constructed an evaluation index system by comprehensively considering the basin water and sediment discharge index, basin ecological and environmental maintenance index, and basin social and economic development index. The evaluation model was established to assess the impact of the cascade reservoir construction sequence on basin multifunctional synergy development index. The model was applied to evaluate the cascade reservoir construction sequence in the Yangtze and Yellow River Basin of China. The results revealed that: (1) The basin water and sediment discharge index, basin social and economic development index, and basin multifunctional synergy development index benefits gradually increased, the basin ecological and environmental maintenance index benefits progressively decreased in the Yangtze and Yellow River Basin. (2) The basin water and sediment discharge index, and basin ecological and environmental maintenance index of the planned cascade reservoir construction sequence ranked top in the Yellow River Basin; the basin water and sediment discharge index, and basin social and economic development index of the planned cascade reservoir construction sequence ranked top in the Yangtze River Basin. (3) The cascade reservoir construction sequence focused more on basin social and economic development index benefits when the level of national economic development was low, and more on basin water and sediment discharge index benefits when it was high. (4) Reservoir capacity and installed capacity were the main factors influencing the cascade reservoir construction sequence in the Yangtze and Yellow River Basin, respectively. These findings provide useful information regarding the cascade reservoir construction sequence.

BackgroundPostpartum depression (PPD) is a type of depressive episode related to parents after childbirth, which causes a variety of symptoms not only for parents but also affects the development of children. The causal relationship between potential risk factors and PPD remains comprehensively elucidated.MethodsLinkage disequilibrium score regression (LDSC) analysis was conducted to screen the heritability of each instrumental variant (IV) and to calculate the genetic correlations between effective causal factors and PPD. To search for the causal effect of multiple potential risk factors on the incidence of PPD, random effects of the inverse variance weighted (IVW) method were applied. Sensitivity analyses, including weighted median, MR-Egger regression, Cochrane’s Q test, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), were performed to detect potential Mendelian randomization (MR) assumption violations. Multivariable MR (MVMR) was conducted to control potential multicollinearity.ResultsA total of 40 potential risk factors were investigated in this study. LDSC regression analysis reported a significant genetic correlation of potential traits with PPD. MR analysis showed that higher body mass index (BMI) (Benjamini and Hochberg (BH) corrected p = 0.05), major depression (MD) (BH corrected p = 5.04E-19), and schizophrenia (SCZ) (BH corrected p = 1.64E-05) were associated with the increased risk of PPD, whereas increased age at first birth (BH corrected p = 2.11E-04), older age at first sexual intercourse (BH corrected p = 3.02E-15), increased average total household income before tax (BH corrected p = 4.57E-02), and increased years of schooling (BH corrected p = 1.47E-11) led to a decreased probability of PPD. MVMR analysis suggested that MD (p = 3.25E-08) and older age at first birth (p = 8.18E-04) were still associated with an increased risk of PPD.ConclusionIn our MR study, we found multiple risk factors, including MD and younger age at first birth, to be deleterious causal risk factors for PPD.

Abstract Background H3K27M mutation status significantly affects the prognosis of patients with diffuse midline gliomas (DMGs), but this tumor presents a high risk of pathological acquisition. We aimed to construct a fully automated model for predicting the H3K27M alteration status of DMGs based on deep learning using whole‐brain MRI. Methods DMG patients from West China Hospital of Sichuan University (WCHSU; n = 200) and Chengdu Shangjin Nanfu Hospital (CSNH; n = 35) who met the inclusion and exclusion criteria from February 2016 to April 2022 were enrolled as the training and external test sets, respectively. To adapt the model to the human head MRI scene, we use normal human head MR images to pretrain the model. The classification and tumor segmentation tasks are naturally related, so we conducted cotraining for the two tasks to enable information interaction between them and improve the accuracy of the classification task. Results The average classification accuracies of our model on the training and external test sets was 90.5% and 85.1%, respectively. Ablation experiments showed that pretraining and cotraining could improve the prediction accuracy and generalization performance of the model. In the training and external test sets, the average areas under the receiver operating characteristic curve (AUROCs) were 94.18% and 87.64%, and the average areas under the precision‐recall curve (AUPRC) were 93.26% and 85.4%. Conclusions The developed model achieved excellent performance in predicting the H3K27M alteration status in DMGs, and its good reproducibility and generalization were verified in the external dataset.

Abstract Approximately 20% of aged captive giant pandas (Ailuropoda melanoleuca) have cataracts that impair their quality of life. To identify potential biomarkers of cataract formation, we carried out a quantitative proteomics analysis of 10 giant pandas to find proteins differing in abundance between healthy and cataract-bearing animals. We identified almost 150 proteins exceeding our threshold for differential abundance, most of which were associated with GO categories related to extracellular localization. The most significant differential abundance was associated with components of the proteasome and other proteins with a role in proteolysis or its regulation, most of which were depleted in pandas with cataracts. Other modulated proteins included components of the extracellular matrix or cytoskeleton, as well as associated signaling proteins and regulators, but we did not find any differentially expressed transcription factors. These results indicate that the formation of cataracts involves a complex post-transcriptional network of signaling inside and outside lens cells to drive stress responses as a means to address the accumulation of protein aggregates triggered by oxidative damage. The modulated proteins also indicate that it should be possible to predict the onset of cataracts in captive pandas by taking blood samples and testing them for the presence or absence of specific protein markers.

Abstract Background Short-term air pollution exposure and intracerebral hemorrhage (ICH) risk are related. However, the impact of the pollutant levels decline on this relationship, which attributes to clean air policy implementation and the COVID-19 pandemic lockdown, is unclear. In the present research, we explored the influence of different pollutant levels on ICH risk during eight years in a southwestern China megacity. Methods Our research used a time-stratified case-crossover design. We retrospectively analyzed ICH patients in a teaching hospital from January 1, 2014, to December 31, 2021, and divided 1571 eligible cases into two groups (1st group: 2014–2017; 2nd group: 2018–2021). We observed the trend of every pollutant in the entire study period and compared the pollution levels in each group, using air pollutants data (PM2.5, PM10, SO2, NO2, CO, and O3) documented by the local government. We further established a single pollutant model via conditional logistic regression to analyze the association between short-term air pollutants exposure and ICH risk. We also discussed the association of pollution levels and ICH risk in subpopulations according to individual factors and monthly mean temperature. Results We found that five air pollutants (PM2.5, PM10, SO2, NO2, CO) exhibited a continuous downward trend for the whole duration, and the daily concentration of all six pollutants decreased significantly in 2018–2021 compared with 2014–2017. Overall, the elevation of daily PM2.5, SO2, and CO was associated with increased ICH risk in the first group and was not positively associated with risk escalation in the second group. For patients in subgroups, the changes in the influence of lower pollutant levels on ICH risk were diverse. In the second group, for instance, PM2.5 and PM10 were associated with lower ICH risk in non-hypertension, smoking, and alcohol-drinking participants; however, SO2 had associations with increased ICH risk for smokers, and O3 had associations with raised risk in men, non-drinking, warm month population. Conclusions Our study suggests that decreased pollution levels diminish the adverse effects of short-term air pollutants exposure and ICH risk in general. Nevertheless, the influence of lower air pollutants on ICH risk in subgroups is heterogeneous, indicating unequal benefits among subpopulations.

Abstract H3 K27M-mutant diffuse midline glioma (H3 K27M-mt DMG) is a rare, highly invasive tumor with a poor prognosis. The prognostic factors of H3 K27M-mt DMG have not been fully identified, and there is no clinical prediction model for it. This study aimed to develop and validate a prognostic model for predicting the probability of survival in patients with H3 K27M-mt DMG. Patients diagnosed with H3 K27M-mt DMG in the West China Hospital from January 2016 to August 2021 were included. Cox proportional hazard regression was used for survival assessment, with adjustment for known prognostic factors. The final model was established using the patient data of our center as the training cohort and data from other centers for external independent verification. One hundred and five patients were ultimately included in the training cohort, and 43 cases from another institution were used as the validation cohort. The factors influencing survival probability in the prediction model included age, preoperative KPS score, radiotherapy and Ki-67 expression level. The adjusted consistency indices of the Cox regression model in internal bootstrap validation at 6, 12, and 18 months were 0.776, 0.766, and 0.764, respectively. The calibration chart showed high consistency between the predicted and observed results. The discrimination in external verification was 0.785, and the calibration curve showed good calibration ability. We identified the risk factors that affect the prognosis of H3 K27M-mt DMG patients and then established and validated a diagnostic model for predicting the survival probability of these patients.

Glucose transporter 1 (GLUT1) overexpression in tumor cells is a potential target for drug therapy, but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds. With current analysis techniques, it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time. We developed a cell membrane-based glucose sensor (CMGS) that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines (TCMs). CMGS is compatible with cell membranes of various origins, including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules. Based on CMGS continuous monitoring technique, we investigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression. We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families. Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation. CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1, providing a new strategy for studying transmembrane protein-receptor interactions.

Somaclonal variation in tissue culture is a common phenomenon induced by various external or internal environmental conditions, resulting in heritable or non-heritable alterations in gene expression. One crucial mechanism involved in plant growth and development is epigenetic regulation. A highly dynamic epigenome can respond to environmental changes by regulating gene expression. DNA methylation is one of these epigenetic modifications that can alter gene expression in tissue-cultured pineapple plants. The underlying mechanism of such somaclonal variations in pineapple and the epigenetic regulation involvement in somaclonal variations has not been studied. This study performed DNA methylome and transcriptome sequencing of wild-type (WT) and mutant pineapple plants (WS, HW, and TW). We observed altered DNA methylation patterns in chlorophyll development in the mutants. Specifically, we noticed that the methylation levels in the CHG and CHH contexts were lower in the gene body regions compared to the upstream and downstream regions. We identified several thousand differentially methylated regions (DMRs) located at the gene body regions, some of which overlapped with the differentially expressed genes (DEGs). Functional enrichment analyses suggested that these genes were involved in chlorophyll metabolism. Thus, our results revealed that the transcriptional regulation of many chlorophyll metabolic essential genes could be regulated by DNA methylation caused by somaclonal variations and provided insights into epigenetic mechanisms underlying the regulation of chlorosis in pineapple plants.

Abstract Aim To explore the experiences of healthcare workers (HCWs) following occupational exposure to coronavirus disease 2019 (COVID‐19) during the early stage of the pandemic. Design A Husserl descriptive phenomenological study design was employed. Methods Convenient and snowball sampling was used. In‐depth semi‐structured telephone interviews were conducted from February to March 2020 with the frontline HCWs who were exposed to COVID‐19 during work. Data analysis was conducted following the 7‐step analysis method developed by Colaizzi. Results Fifteen HCWs participated in the study. Four themes were identified, including (1) traumatic experiences since the occupational exposure; (2) getting through the hard time; (3) struggling to return to work; (4) reflections on occupational exposures. Conclusion The HCWs had traumatic and painful experiences after the occupational exposure. But they returned to work with strong resilience, professional obligation and social support. Training and supervision, and adequate supply of personal protective equipment are suggested to prevent professional exposure. Social and organizational support should be provided for the exposed HCWs.

Abstract Background The current molecular classifications cannot completely explain the polarized malignant biological behavior of low‐grade gliomas (LGGs), especially for tumor recurrence. Therefore, we tried to identify suspicious hub genes related to tumor recurrence in LGGs. Methods In this study, we constructed a gene‐miRNA‐lncRNA co‐expression network for LGGs by a weighted gene co‐expression network analysis (WGCNA). GDCRNATools and the WGCNA R package were mainly used in data analysis. Results Sequencing data from 502 LGG patients were analyzed in this study. Compared with recurrent glioma tissues, we identified 774 differentially expressed (DE) mRNAs, 49 DE miRNAs, and 129 DE lncRNAs in primary LGGs and ultimately determined that the expression of MKLN1 was related to tumor recurrence in LGG. Conclusion This study identified the potential biomarkers for the pathogenesis and recurrence of LGGs and proposed that MKLN1 could be a potential therapeutic target.

Background: Immunosenescence, an age-related deficit in immunity, associated with multiple disorders and making the successful aging a challenge. Although nearly 4000 articles have been published, only few review articles have summarized the research status. In order to better understand the most recent advances, hotspots and development trends in immunosenescence, it is very necessary to conduct a comprehensive bibliometric analysis. Hence, commonly used bibliometric analysis software CiteSpace and VOSviewer were employed to conduct a quantitative analysis and critical evaluation of publications in this study. Methods: Immunosenescence publications were screened from the Web of Science Core Collection (WoSCC). Microsoft Excel 2021, CiteSpace 5.8.R3, and VOSviewer 1.6.17 were used for bibliometric study. Results: A total of 3875 publications were retrieved from WoSCC. After screening by document type (article or review) (352 publications were excluded) and language of English (85 were excluded), 3438 studies were finally used for bibliometric analysis. The literature on immunosenescence had been continuously growing since 1991, and by 2020 it has skyrocketed 312 publications from 240 in 2019. USA (1111 publications, 35.01%) was the leading country of publications, followed by ITALY (379, 11.94%) and ENGLAND (366, 11.53%). Of the authors, Pawelec G from the Tubingen University of GERMANY contributed the greatest articles (93 publications). All the keywords could be divided into five clusters, and additional potent visualization bursts revealed that “gut microbiota,” “health,” “dysfunction,” and “nivolumab” were the active hotspots presently. Conclusion: Based on the current data, we firstly concluded that there will be a dramatically rising publications on immunosenescence, and research teams from USA or GERMANY might be the best chooses for collaboration. Moreover, We particularly emphasized the development potential of mechanism and intervening strateges like “gut microbiota” and “nivolumab” in immunosenescence. We hope to provide new ideas for promoting the basic research and clinical application of immunosenescence.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory disease characterized by a slow progression and caused by the inhalation of harmful particulate matter. Cigarette smoke and air pollutants are the primary contributing factors. Currently, the pathogenesis of COPD remains incompletely understood. The PI3K/Akt signaling pathway has recently emerged as a critical regulator of inflammation and oxidative stress response in COPD, playing a pivotal role in the disease’s progression and treatment. This paper reviews the association between the PI3K/Akt pathway and COPD, examines effective PI3K/Akt inhibitors and novel anti-COPD agents, aiming to identify new therapeutic targets for clinical intervention in this disease.

The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.

Abstract Objectives Gliomas with comutations of isocitrate dehydrogenase (IDH) genes and telomerase reverse transcriptase (TERT) gene promoter (IDHmut pTERTmut) show distinct biological features and respond to first‐line treatment differently in comparison with other gliomas. This study aimed to characterize the IDHmut pTERTmut gliomas in multimodal MRI using the radiomic method and establish a precise diagnostic model identifying this group of gliomas. Methods A total of 140 patients with untreated primary gliomas were admitted between 2016 and 2020 to West China Hospital as a discovery cohort, including 22 IDHmut pTERTmut patients. Thirty‐four additional cases from a different hospital were included in the study as an independent validation cohort. A total of 3654 radiomic features were extracted from the preoperative multimodal MRI images (T1c, FLAIR, and ADC maps) and filtered in a data‐driven approach. The discovery cohort was split into training and test sets by a 4:1 ratio. A diagnostic model (multilayer perceptron classifier) for detecting the IDHmut pTERTmut gliomas was trained using an automatic machine‐learning algorithm named tree‐based pipeline optimization tool (TPOT). The most critical radiomic features in the model were identified and visualized. Results The model achieved an area under the receiver‐operating curve (AUROC) of 0.971 (95% CI, 0.902–1.000), the sensitivity of 0.833 (95% CI, 0.333–1.000), and the specificity of 0.966 (95% CI, 0.931–1.000) in the test set. The area under the precision‐recall curve (AUCPR) was 0.754 (95% CI, 0.572–0.833) and the F1 score was 0.833 (95% CI, 0.500–1.000). In the independent validation set, the model reached 0.952 AUROC, 0.714 sensitivity, 0.963 specificity, 0.841 AUCPR, and 0.769 F1 score. MR radiomic features of the IDHmut pTERTmut gliomas represented homogenous low‐complexity texture in three modalities. Conclusions An accurate diagnostic model was constructed for detecting IDHmut pTERTmut gliomas using multimodal radiomic features. The most important features were associated with the homogenous simple texture of IDHmut pTERTmut gliomas in MRI images transformed using Laplacian of Gaussian and wavelet filters.

Phased array antennas (PAAs) with flexible and agile wide-angle beam scanning (WABS) abilities have drawn rapidly increasing attentions in recent years. They have found significant applications in beyond fifth-generation (B5G) and sixth-generation (6G) wireless communications, satellite communications, sensing, etc., for their outstanding capability to achieve wide spatial coverage, enable critical frequency reuse, and improve the system capacity. In this review, we aim to investigate and discuss several challenges that hinder WABS for conventional PAAs, including the strong mutual coupling, narrow beamwidth of the element antenna, etc. We then review and summarize a variety of innovative techniques to overcome these challenges. Subsequently, we discuss and analyze potential research gaps of WABS PAAs for future emerging applications. This timely review fulfills the demand of a thorough and detailed investigation on WABS technologies for PAAs and provides detailed introduction and guidance for interested researchers and engineers.

High-quality, normalized differential vegetation index (NDVI) time-series data are fundamental for environmental remote sensing applications; however, their quality is often influenced by complicated factors such as atmospheric aerosols and cloud coverage. Hence, in the current study, a robust reconstruction method based on envelope detection and the Savitzky-Golay filter (ED-SG) was developed to reduce noise in the NDVI time-series. To verify the performance of ED-SG, simulation experiments were implemented and NDVI time-series samples were selected for different land cover types derived from MOD09GQ, Sentinel-2 and Landsat 8 OLI of Yangtze River Basin, between December 2018 and December 2019. The experimental results yielded an agreement coefficient and variance of 0.9599 and 0.0006, respectively on simulated time-series, Additionally, the smoothness metrics of evergreen broadleaf forests, evergreen needleleaf forests, deciduous broadleaf forests, herbaceous, and croplands were 0.0019, 0.0017, 0.0012, 0.0012, and 0.0013, respectively. Ultimately, the reconstructed time-series metrics showed significant improvements in robustness and smoothness over conventional methods. Moreover, the simplistic mechanisms of the ED-SG model enabled it to run effectively in the Google Earth Engine over the NDVI time-series of the whole Yangtze River Basin.

Magnesium–lithium alloys are arguably the lightest metal structural materials but have low strength. In order to increase strength, friction stir processing (FSP) is applied to a hot-rolled Mg-10Li-3Al-3Zn (LA103Z) sheet to study the effects on the microstructure and mechanical properties. In this study, the strengthening mechanisms of various FSP regions of an Mg-Li alloy were clarified by a combination of numerical simulation and experimental method. Based on ANSYS APDL, a finite element model with a moving heat source is established. Rotational speeds of 800, 1000, and 1200 rpm and traverse speeds of 100, 110, and 120 mm/min were used in this research. The simulation results confirm that the influence of the rotation speed on the alloy temperature field is greater than that of the travel speed. The temperature of the processing area increases with an increase in rotation speed and decreases with an increase in travel speed. Then, hot-rolled LA103Z alloy plates are processed by FSP. The correspondence between the numerical simulation and experiment was verified by infrared thermography. The results indicate that FSP decreases the grain size significantly for the dynamic recrystallization and dramatic mechanical crushing of the stirring pin. The α-Mg and AlLi are solid soluted in the β-Li matrix. The tensile strength of the processing zone is 260.67 MPa (1000 rpm, 110 mm/min) versus the 170.47 MPa of the base metal. The SZ has the highest microhardness of 77.8 HV (800 rpm, 120 mm/min) and decreases gradually to the BM. The severe deformation, recrystallization, and solid solution of the α-Mg are important factors contributing to the improved mechanical properties.

Abstract Most metals and alloys suffer from high friction and wear due to their low hardness and lack of self‐lubrication. Although plenty of strategies have been proposed, it is still a long‐standing challenge to achieve diamond‐like wear in metals. Metallic glasses (MGs) are supposed to possess low coefficient of friction (COF) because of their high hardness and fast surface mobility. However, their wear rate is larger than that of diamond‐like materials. Here, this work reports the discovery of Ta‐rich MGs that exhibit diamond‐like wear. This work develops an indentation approach for high‐throughput characterization of crack resistance. By employing deep indentation loading, this work is able to efficiently identify the alloys that exhibit better plasticity and crack resistance according to the differences of indent morphology. With high temperature stability, high hardness, improved plasticity, and crack resistance, the discovered Ta‐based MGs exhibit diamond‐like tribological properties, featured by COF as low as ≈0.05 for diamond ball test and ≈0.15 for steel ball test, and specific wear rate of only ≈10−7 mm3 N−1m−1. The discovery approach and the discovered MGs exemplifie the promise to substantially reduce friction and wear of metals and may unleash the potential of MGs in tribological applications.

BackgroundDeveloping Internet+home care (IHC) services is a promising way to address the problems related to population aging, which is an important global issue. However, IHC services are in their infancy in China. Limited studies have investigated the willingness and demand of nurses in municipal hospitals to provide IHC services. ObjectiveThis study aims to investigate the willingness and demand of nurses in municipal hospitals in China to provide IHC services and analyze the factors to promote IHC development in China. MethodsThis cross-sectional study used multistage sampling to recruit 9405 nurses from 10 hospitals in 5 regions of China. A self-designed questionnaire with good reliability and validity was used to measure nurses’ willingness and demand for providing IHC services. Data analysis used the chi-square test, Welch t test, binary logistic regression analysis, and multiple linear regression analysis. ResultsNurses were highly willing to provide IHC services and preferred service distances of 60% was the expected service pay sharing. Job title, educational level, monthly income, and marital status were associated with nurses’ willingness to provide IHC services in binary logistic regression analysis. Supervising nurses were 1.177 times more likely to express a willingness to provide IHC services than senior nurses. Nurses with a bachelor's degree had a 1.167 times higher likelihood of expressing willingness to provide IHC services than those with a junior college education or lower. Married nurses were 1.075 times more likely to express a willingness than unmarried nurses. A monthly income >¥10,000 increased the likelihood of nurses’ willingness to provide IHC services, by 1.187 times, compared with an income ¥10,000 (B=1.335, P

Background: Using epigenetic markers and fragmentomics of cell-free DNA for cancer detection has been proven applicable. Methods: We further investigated the diagnostic potential of combining two features (epigenetic markers and fragmentomic information) of cell-free DNA for detecting various types of cancers. To do this, we extracted cfDNA fragmentomic features from 191 whole-genome sequencing data and studied them in 396 low-pass 5hmC sequencing data, which included four common cancer types and control samples. Results: In our analysis of 5hmC sequencing data from cancer samples, we observed aberrant ultra-long fragments (220–500 bp) that differed from normal samples in terms of both size and coverage profile. These fragments played a significant role in predicting cancer. Leveraging the ability to detect cfDNA hydroxymethylation and fragmentomic markers simultaneously in low-pass 5hmC sequencing data, we developed an integrated model that incorporated 63 features representing both fragmentomic features and hydroxymethylation signatures. This model achieved high sensitivity and specificity for pan-cancer detection (88.52% and 82.35%, respectively). Conclusion: We showed that fragmentomic information in 5hmC sequencing data is an ideal marker for cancer detection and that it shows high performance in low-pass sequencing data.

The investigation of the low-cost deoxygenation of guaiacol (GUA, a model bio-oil compound) is of importance for upgrading bio-oil. At present, common sulfide catalysts for GUA deoxygenation reactions cause contamination of the liquid product, and noble metal catalysts are economically disadvantageous. In this study, four reduced Fe-based oxides with different Ce doping ratios were prepared and their effects on the in-situ deoxygenation performance of GUA in aqueous/methanol hydrogen donor solvents were explored. The results based on the deoxygenation degree, conversion degree, and higher heating value (HHV) of the products showed that the oxide catalyst with a Fe/Ce molar ratio of 2:1 in the methanol solvent performed very well. After selecting an excellent catalyst and a better hydrogen donor solvent, four factors (reaction temperature, reaction time, volume ratio of GUA dosage and methanol dosage, and the ratio of catalyst dosage at the bottom of the reactor to that at the top) in the deoxygenation degree of GUA were investigated using an orthogonal experimental method to further explore the performance of the catalyst. The results showed that the reaction temperature and time greatly influenced GUA deoxygenation. Under optimal experimental conditions, the deoxygenation degree and conversion degree of GUA could reach 34.36% and 92.56%, respectively, based on the relative peak area of gas chromatography–mass spectrometry, and the HHV of the liquid product was 32.27 MJ/kg. Although Fe/Ce catalysts mainly promote demethoxylation, demethylation, and methylation, the stability and quality of the liquid products were improved compared with GUA owing to the reduction in phenolic hydroxyl and ether content. The reduced catalyst in the process of GUA in-situ deoxygenation reactions in methanol maintained a steady performance, as revealed by X-ray diffraction and X-ray fluorescence.

Abstract The brachistochrone (shortest-time) curve is the path connecting two points that enables the shortest travel time. This work explores the “brachistochrone path” of fire spread connecting two points at the same altitude and with a fixed path length. The starting and ending points are connected by both thermally thin fuels (thin wires) and thermally thick fuels (PMMA bars). Flame-spread paths of triangular, rectangular, and circular shapes with different heights and inclinations are explored. Results show that having a local maximum flame-spread rate does not result in the shortest overall travel time. For thin-wire paths, the fastest overall-path fire spread occurs, when the upward spread path is vertical, and the path height reaches a maximum, as demonstrated by the theoretical analysis. Differently, for thick PMMA-bar paths, the brachistochrone condition occurs when the path length of the vertical upward spread reaches the maximum, because the upward spread is about ten times faster than the downward spread. This study extends the conventional problem of the fastest fire spread to the shortest-time problem of the whole fire path, and it may help optimize the fuel distribution inside the built environment and estimate available safe egress time in building and wildland fires.

Abstract Background Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. Methods In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. Results As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p

Background: Despite substantial resources deployed to curb SARS-CoV-2 transmission, controlling the COVID-19 pandemic has been a major challenge. New variants of the virus are frequently emerging leading to new waves of infection and re-introduction of control measures. In this study, we assessed the effectiveness of containment strategies implemented in the early phase of the pandemic. Methods: Real-world data for COVID-19 cases was retrieved for the period Jan 1 to May 1, 2020 from a number of different sources, including PubMed, MEDLINE, Facebook, Epidemic Forecasting and Google Mobility Reports. We analyzed data for 18 countries/regions that deployed containment strategies such as travel restrictions, lockdowns, stay-at-home requests, school/public events closure, social distancing, and exposure history information management (digital contact tracing, DCT). Primary outcome measure was the change in the number of new cases over 30 days before and after deployment of a control measure. We also compared the effectiveness of centralized versus decentralized DCT. Time series data for COVID-19 were analyzed using Mann-Kendall (M-K) trend tests to investigate the impact of these measures on changes in the number of new cases. The rate of change in the number of new cases was compared using M-K z-values and Sen’s slope. Results: In spite of the widespread implementation of conventional strategies such as lockdowns, travel restrictions, social distancing, school closures, and stay-at-home requests, analysis revealed that these measures could not prevent the spread of the virus. However, countries which adopted DCT with centralized data storage were more likely to contain the spread. Conclusions: Centralized DCT was more effective in containing the spread of COVID-19. Early implementation of centralized DCT should be considered in future outbreaks. However, challenges such as public acceptance, data security and privacy concerns will need to be addressed.

In this case report, we present an extremely rare and previously unreported case of skull osteoma relapse without any attachment to the skull after hydroxyapatite cement (HAC) cranioplasty. The 49-year-old male patient was admitted with recurrence of the left frontal skull lesion; he underwent craniectomy and HAC cranioplasty for a left frontal osteoma 14 years before. Intraoperative findings disclosed multiple irregular lesions located on the HAC flap without any attachment to the bony structure and the roots of the lesions originating from the outer layer of the dura through several reserved holes. Pathological diagnosis was osteoma. The purpose of this report is to document this rare occurrence and provide the most probable pathogenesis for this rare event.

IntroductionHigh-grade glioma (HGG) defines a group of brain gliomas characterized by contrast enhancement, high tumor heterogeneity, and poor clinical outcome. Disturbed reduction–oxidation (redox) balance has been frequently associated with the development of tumor cells and their microenvironment (TME).MethodsTo study the influence of redox balance on HGGs and their microenvironment, we collected mRNA-sequencing and clinical data of HGG patients from TCGA and CGGA databases and our own cohort. Redox-related genes (ROGs) were defined as genes in the MSigDB pathways with keyword “redox” that were differentially expressed between HGGs and normal brain samples. Unsupervised clustering analysis was used to discover ROG expression clusters. Over-representation analysis (ORA), gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were also employed to understand the biological implication of differentially expressed genes between HGG clusters. CIBERSORTx and ESTIMATE were used to profile the immune TME landscapes of tumors, and TIDE was used to evaluated the potential response to immune checkpoint inhibitors. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression was used to construct HGG-ROG expression risk signature (GRORS).ResultsSeventy-five ROGs were found and consensus clustering using the expression profile of ROGs divided the both IDH-mutant (IDHmut) and IDH-wildtype (IDHwt) HGGs into subclusters with different prognosis. Functional enrichment analysis revealed that the differential aggressiveness between redox subclusters in IDHmut HGGs were significantly associated with cell cycle regulation pathways, while IDHwt HGG redox subclusters showed differentially activated immune-related pathways. In silico TME analysis on immune landscapes in the TME showed that the more aggressive redox subclusters in both IDHmut and IDHwt HGGs may harbor a more diverse composition of tumor-infiltrating immune cells, expressed a higher level of immune checkpoints and were more likely to respond to immune checkpoint blockade. Next, we established a GRORS which showed AUCs of 0.787, 0.884, and 0.917 in predicting 1–3-year survival of HGG patients in the held-out validation datasets, and the C-index of a nomogram combining the GRORS and other prognostic information reached 0.835.ConclusionBriefly, our results suggest that the expression pattern of ROGs was closely associated with the prognosis as well as the TME immune profile of HGGs, and may serve as a potential indicator for their response to immunotherapies.

Introduction: Glioblastoma is one of the most lethal cancers and leads to more than 200,000 deaths annually. However, despite lots of researchers devoted to exploring novel treatment regime, most of these attempts eventually failed to improve the overall survival of glioblastoma patients in near 20 years. Immunotherapy is an emerging therapy for cancers and have succeeded in many cancers. But most of its application in glioblastoma have been proved with no improvement in overall survival, which may result from the unique immune microenvironment of glioblastoma. Arginine is amino acid and is involved in many physiological processes. Many studies have suggested that arginine and its metabolism can regulate malignancy of multiple cancers and influence the formation of tumor immune microenvironment. However, there is hardly study focusing on the role of arginine metabolism in glioblastoma.Methods: In this research, based on mRNA sequencing data of 560 IDH-wildtype glioblastoma patients from three public cohorts and one our own cohort, we aimed to construct an arginine metabolism-related genes signature (ArMRS) based on four essential arginine metabolism-related genes (ArMGs) that we filtered from all genes with potential relation with arginine metabolism. Subsequently, the glioblastoma patients were classified into ArMRS high-risk and low-risk groups according to calculated optimal cut-off values of ArMRS in these four cohorts.Results: Further validation demonstrated that the ArMRS was an independent prognostic factor and displayed fine efficacy in prediction of glioblastoma patients’ prognosis. Moreover, analyses of tumor immune microenvironment revealed that higher ArMRS was correlated with more immune infiltration and relatively “hot” immunological phenotype. We also demonstrated that ArMRS was positively correlated with the expression of multiple immunotherapy targets, including PD1 and B7-H3. Additionally, the glioblastomas in the ArMRS high-risk group would present with more cytotoxic T cells (CTLs) infiltration and better predicted response to immune checkpoint inhibitors (ICIs).Discussion: In conclusion, our study constructed a novel score system based on arginine metabolism, ArMRS, which presented with good efficacy in prognosis prediction and strong potential to predict unique immunological features, resistance to immunotherapy, and guide the application of immunotherapy in IDH-wild type glioblastoma.