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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.

Ultra-low lattice thermal conductivity has long been a requirement for the high thermoelectric properties of materials. In this work, the novel 1T-Au6Se2 monolayer was obtained by introducing Au6 clusters into the selenide monolayer, and its electrical and thermal transport characteristics are investigated using first-principles computations supplemented with semi-classical Boltzmann transport theory. The calculation shows that the 1T-Au6Se2 monolayer exhibits ultra-low lattice thermal conductivity and excellent thermoelectric properties owing to its low phonon frequency, group velocity, and extremely strong anharmonicity. Based on strain engineering from 0% to 2%, the lattice thermal conductivity further reduces by restricting the thermal transport on the premise of maintaining outstanding electrical transport properties in the p-type doped system. Thence, the value of ZT for the p-type system increases nearly by 70% compared with the non-stressed state at 700 K. Our investigation indicates the ultra-low thermal conductivity and high ZT of the 1T-Au6Se2 monolayer that might be prepared in the lab, providing new insights into enhancing the thermoelectric performance of the material in the future.

BackgroundDiffuse gliomas possess a kind of malignant brain tumor with high mortality. Glutamine represents the most abundant and versatile amino acid in the body. Glutamine not only plays an important role in cell metabolism but also involves in cell survival and malignancies progression. Recent studies indicate that glutamine could also affect the metabolism of immune cells in the tumor microenvironment (TME).Materials and methodsThe transcriptome data and clinicopathological information of patients with glioma were acquired from TCGA, CGGA, and West China Hospital (WCH). The glutamine metabolism-related genes (GMRGs) were retrieved from the Molecular Signature Database. Consensus clustering analysis was used to discover expression patterns of GMRGs, and glutamine metabolism risk scores (GMRSs) were established to model tumor aggressiveness-related GMRG expression signature. ESTIMATE and CIBERSORTx were applied to depict the TME immune landscape. The tumor immunological phenotype analysis and TIDE were utilized for predicting the therapeutic response of immunotherapy.ResultsA total of 106 GMRGs were retrieved. Two distinct clusters were established by consensus clustering analysis, which showed a close association with the IDH mutational status of gliomas. In both IDH-mutant and IDH-wildtype gliomas, cluster 2 had significantly shorter overall survival compared with cluster 1, and the differentially expressed genes between the two clusters enriched in pathways related to malignant transformation as well as immunity. In silico TME analysis of the two IDH subtypes revealed not only significantly different immune cell infiltrations and immune phenotypes between the GMRG expression clusters but also different predicted responses to immunotherapy. After the screening, a total of 10 GMRGs were selected to build the GMRS. Survival analysis demonstrated the independent prognostic role of GMRS. Prognostic nomograms were established to predict 1-, 2-, and 3-year survival rates in the four cohorts.ConclusionDifferent subtypes of glutamine metabolism could affect the aggressiveness and TME immune features of diffuse glioma, despite their IDH mutational status. The expression signature of GMRGs could not only predict the outcome of patients with glioma but also be combined into an accurate prognostic nomogram.

The ever-increasing global energy demand, juxtaposed with critical concerns about greenhouse gas emissions, emphatically underscores the urgency to pivot toward sustainable and eco-friendly energy alternatives. Tapping into microbial metabolism for clean energy generation stands out as a particularly promising avenue in this endeavor. Given this backdrop, we delved deeply into the metabolic engineering potential of Saccharomyces cerevisiae, thereby aiming for the bioconversion of formate and acetate—both CO2 derivatives—into free fatty acids (FFAs) as precursors for biofuel production. Our study not only elucidated the metabolic pathways within S. cerevisiae that are tailored for efficient formate and acetate utilization but also shone a light on the meticulous optimization strategies that amplify FFA synthesis. The engineered strains, under refined conditions, exhibited up to an 8-fold increase in an FFA titer, thus reaching a production level of 6.6 g/L, which showcases the potential of microbial metabolism in clean energy generation. Our findings offer a promising step toward harnessing microbial metabolism for sustainable energy production, thereby bridging the gap between waste carbon utilization and greener fuel alternatives.

Background: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. Methods: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. Results: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919–1), 0.950 (0.877–1), 0.939 (0.845–1), and 0.875 (0.690–1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. Conclusion: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future.

Abstract Spontaneous synchronization over large networks is ubiquitous in nature, ranging from inanimate to biological systems. In the human brain, neuronal synchronization and de-synchronization occur during sleep, with the greatest degree of neuronal synchronization during slow wave sleep (SWS). The current sleep classification schema is based on electroencephalography and provides common criteria for clinicians and researchers to describe stages of non-rapid eye movement (NREM) sleep as well as rapid eye movement (REM) sleep. These sleep stage classifications have been based on convenient heuristic criteria, with little consideration of the accompanying normal physiological changes across those same sleep stages. To begin to resolve those inconsistencies, first focusing only on NREM sleep, we propose a simple cluster synchronization model to explain the emergence of SWS in healthy people without sleep disorders. We apply the empirical mode decomposition (EMD) analysis to quantify slow wave activity in electroencephalograms, and provide quantitative evidence to support our model. Based on this synchronization model, NREM sleep can be classified as SWS and non-SWS, such that NREM sleep can be considered as an intrinsically bistable process. Finally, we develop an automated algorithm for SWS classification. We show that this new approach can unify brain wave dynamics and their corresponding physiologic changes.

Abstract Background Glioblastoma (GBM) is the most frequent and lethal brain tumor, which possesses highly malignant characteristics and predominates in elder patients. Systemic inflammatory response index (SIRI) is a novel prognostic marker from peripheral blood, which is defined as neutrophil count × monocyte count/lymphocyte count. In the current research, we aim to explore the relationship between SIRI and newly diagnosed GBM underwent gross total resection (GTR). Methods A retrospective analysis was conducted on consecutive newly diagnosed GBM patients underwent operation at West China Hospital from March 2015 to January 2019. X-tile software was used to determine the optimal cut-off values of SIRI, and neutrophil to lymphocyte ratio (NLR). All statistical analyses were performed using SPSS software and R software. Propensity score matching (PSM) was conducted to adjust for imbalance of all potential confounding covariates. Results The current research included a total of 291 consecutive newly diagnosed GBM patients underwent gross total resection. Among them, 186 were male patients and 105 were female patients. In original cohort, only gender was evidently related to SIRI level. SIRI and NLR were independent prognostic indicators both in original cohort and PSM cohort. Prognostic models based on the independent prognostic factors were established, and prognostic capacity of Model SIRI was superior to Model NLR. Conclusion In the current research, SIRI was determined to be an independent prognostic indicator for GBM. And the prognostic predictive ability of SIRI was stronger than NLR.

Abstract Background Homozygous or compound heterozygous variants in the KLHL40 gene cause nemaline myopathy 8 (NEM8), a severe autosomal recessive muscle disorder characterized by prenatal polyhydramnios, fetal akinesia or hypokinesia, joint contractures, fractures, respiratory failure and dysphagia. Currently, 46 individuals with NEM8 have been described in the literature, and 30 variants in KLHL40 have been identified. Results Here, we reported five individuals from four unrelated Chinese families who presented common features of nemaline myopathy and infrequent clinical characteristics. Whole-exome sequencing (WES) was used to identify the causative gene. WES identified a recurrent missense variant c.1516A>C (p.Thr506Pro) and a novel frameshift variant c.543del (p.Ser182Profs*17) in KLHL40 in patient 1, a nonsense variant c.602G>A (p.Trp201*) and a missense variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 2, and homozygous variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 3 and both siblings (patients 4 and 5), all of which were confirmed by Sanger sequencing. Next, we estimated the incidence of this disorder in the southern and northern Chinese population to be 4.59/106 and 2.95/106, respectively, based on the cumulative allele frequency of pathogenic variants in internal database. Conclusion The results of our study expand the mutation spectrum of KLHL40 and enrich our understanding of the clinical characteristics of NEM8. Genetic counseling was provided for the four families involved in this study. Given the severity and the relatively high incidence of this condition, we strongly suggest that KLHL40 be incorporated into a carrier screening panel for the Chinese population.

BackgroundGlioma is the most common primary brain tumor in adults and accounts for more than 70% of brain malignancies. Lipids are crucial components of biological membranes and other structures in cells. Accumulating evidence has supported the role of lipid metabolism in reshaping the tumor immune microenvironment (TME). However, the relationship between the immune TME of glioma and lipid metabolism remain poorly described.Materials and methodsThe RNA-seq data and clinicopathological information of primary glioma patients were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). An independent RNA-seq dataset from the West China Hospital (WCH) also included in the study. Univariate Cox regression and LASSO Cox regression model was first to determine the prognostic gene signature from lipid metabolism-related genes (LMRGs). Then a risk score named LMRGs-related risk score (LRS) was established and patients were stratified into high and low risk groups according to LRS. The prognostic value of the LRS was further demonstrated by construction of a glioma risk nomogram. ESTIMATE and CIBERSORTx were used to depicted the TME immune landscape. Tumor Immune Dysfunction and Exclusion (TIDE) was utilized to predict the therapeutic response of immune checkpoint blockades (ICB) among glioma patients.ResultsA total of 144 LMRGs were differentially expressed between gliomas and brain tissue. Finally, 11 prognostic LMRGs were included in the construction of LRS. The LRS was demonstrated to be an independent prognostic predictor for glioma patients, and a nomogram consisting of the LRS, IDH mutational status, WHO grade, and radiotherapy showed a C-index of 0.852. LRS values were significantly associated with stromal score, immune score, and ESTIMATE score. CIBERSORTx indicated remarkable differences in the abundance of TME immune cells between patients with high and low LRS risk levels. Based on the results of TIDE algorithm, we speculated that the high-risk group had a greater chance of benefiting from immunotherapy.ConclusionThe risk model based upon LMRGs could effectively predict prognosis in patients with glioma. Risk score also divided glioma patients into different groups with distinct TME immune characteristics. Immunotherapy is potentially beneficial to glioma patients with certain lipid metabolism profiles.

An increasing amount of attention has been focused on the issue of the low recruitment and retention of male teachers in early childhood education worldwide. Previous research has indicated that personal perceptions of male preservice teachers’ personal regarding early childhood education could have a major influence on their decision of a future career. This qualitative study aims at promoting the significance of early childhood preservice preparation programs by exploring the perspectives and experiences of male preservice teachers working with infants in China. Using the purposeful sampling method, two male interns in an infant classroom were interviewed individually, and each of them was interviewed three times in total: at the beginning of their professional studies, during their internship, and after completing their studies. Participants’ reflections were also considered as supplementary data. The results underscore the necessity of a comprehensive early childhood preservice preparation program for prospective male teachers, particularly regarding infants’ development. Additionally, the study highlights the crucial role of male preservice teachers’ involvement and perspectives before entering the early childhood education field. The study was limited to one location and may not apply to others. Despite the small sample, it offers valuable perspectives. Future focus should be on attracting males to early childhood education area and exploring useful strategies.

Digital twins (DTs) have a great potential for bridge operation and maintenance. Geometric digital twins (gDTs) are the key component of DTs. At present, a growing number of researchers are using high-precision 3D laser point clouds to generate gDTs. However, for large bridges, such as arch, cable-stayed, and suspension bridges, comprehensive point-cloud collection stations are difficult to set up due to their large span, narrow site, and limited field of vision. Consequently, the complete point clouds of these bridges cannot be easily obtained. Thus, knowing how to process absence point clouds and generate gDTs is an urgent problem. This study proposes a semiautomatic method of extracting geometric information of a bridge’s components in the absence of point clouds. First, an algorithm based on the combination of the iterative polynomial fitting curve and sliding window is developed to extract the arch ring accurately. Second, an improved random sample consensus (RANSAC) algorithm based on distribution density is adopted to extract the cross sections of the arch bridge components, except the arch ring. For cross sections that lack point clouds, a translation strategy is used to supplement the unknown line segment. Finally, for the T-beam, a model alignment method is proposed to best match the characteristic intersections extracted by the improved RANSAC algorithm and the points corresponding to the design model. The quality of the generated models is gauged using a point cloud deviation chromatogram. In addition, the stressed component piers are compared with its design parameters to verify the accuracy of the proposed method. Results show that our method can efficiently and accurately extract geometric information and generate gDT for the bridge.

Introduction Immunosuppressive therapy (IST) for acquired hemophilia A (AHA) results in remission within days to months in 60% to 80% of patients. However, little is known regarding the predictors of response. Aim This study aimed to identify the factors that influence response to treatment. Methods The data of 42 patients with AHA from three hospitals were retrospectively analyzed. Results All 42 AHA patients received IST; complete treatment data were available for 34 patients. The response rate was 60% among the 5/34 (14.7%) patients who received steroids alone, 70.8% among the 24/34 (70.6%) patients who received steroids plus cyclophosphamide, and 80% among the 5/34 (14.7%) patients who received steroids plus cyclophosphamide and rituximab. Overall, 29/34 (85.3%) patients achieved CR; 4/34 (13.8%) of them relapsed after a median time of 410 (21–1279) days. Adverse events occurred in 14/34 (41.2%) patients: 13/34 (38.2%) had infections and 1/34 (2.9%) developed pancytopenia. In univariate and multivariate Cox regression analyses, FVIII inhibitor titer ≥20 BU/mL was the only significant prognostic factor affecting time to CR. No variable had significant effect on OS. Conclusion FVIII inhibitory antibody titer ≥20 BU/mL appears to be an important predictor of time to complete response in patients with acquired hemophilia A treated with immunosuppressive therapy.

BackgroundCases of lateral ventricular ectopic schwannomas (LVES) are extremely rare, with only 23 cases reported thus far. This study aimed to obtain a better understanding of the disease.MethodsWe reported a rare case of LVES, in which the patient was admitted to our hospital, and reviewed the relevant literature on LVES to summarize and analyze the clinical manifestations, pathologies, imaging features and progress.ResultsOf the 23 patients, LVES was more common in men (74%, 17/23) than in women and was mostly located on the right side (78%, 18/23). The average age at clinical presentation was 28 years, with an age range between 8 and 68 years. Moreover, most cases were histologically benign, except in one case of malignancy. In all the benign cases, there were 2 cases of subtotal resection, but no recurrence was found during follow-up.ConclusionsThe origin of LVES could be the tumor transformation of autonomic nerve tissue in the perivascular choroid plexus. For lateral ventricle tumors,which are rare benign lesions with good prognosis after surgical resection, LVES should be considered in the differential diagnosis. Moreover, whether LVES could be considered for gamma knife treatment, similar to a small acoustic neuromas,requires further investigation.

Abstract Background Conventional MR imaging has limited value in identifying H3 K27M mutations. We aimed to investigate the capacity of quantitative MR imaging variables in identifying the H3 K27M mutation status of diffuse midline glioma. Materials and Methods Twenty‐three patients with H3 K27M mutation and thirty‐two wild‐type patients were recruited in this retrospective study, all of whom underwent multimodal MR imaging. Clinical data and quantitative MR imaging variables were explored by subgroup analysis stratified by age (juveniles and adults). Then, a logistic model for all patients was constructed to identify potential variables for predicting K27M mutation status. Besides, a retrospective validation set including 13 patients was recruited. The C‐index and F1 score were used to evaluate the performance of the prediction model. Results It turned out that patients with H3 K27M mutation were younger in the adult subgroup. In the mutation group, some relative apparent diffusion coefficient (rADC) histogram parameters and myo‐inositol/creatine plus phosphocreatine (Ins/tCr) ratio were lower than in the wild‐type group of both juveniles and adults (p

Background and Aim: Postoperative radiotherapy with concomitant temozolomide (TMZ) followed by ≤ six cycles of adjuvant TMZ chemotherapy (Stupp regimen) is the standard treatment for newly diagnosed glioblastoma (GBM); however, its effectiveness is limited. Anlotinib inhibits both tumor angiogenesis and tumor cell proliferation by targeting multiple kinases, and showing promising results in preclinical GBM models. We designed a Phase II trial to assess the efficacy and safety of the Stupp regimen plus anlotinib. Methods/Design: This is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib (Stupp regimen + anlotinib) or placebo (Stupp regimen + placebo). Postoperative patient recruitment will begin in July 2021, the analysis of primary outcome measures will be completed in July 2023, and the study will finish in July 2024. Major eligibility criteria include histologically confirmed newly diagnosed GBM and an Eastern Cooperative Oncology Group performance score ≤2. Other criteria for inclusion include age ≥18 years and lack of significant comorbidity. In this study, the primary endpoint will be the median progression-free survival (PFS). Secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity. The protocol has received approval from Sun Yat-sen University Cancer Center Ethics Committee (Approval No. B2021-073-01; approved on April 19, 2021). Discussion: Updated treatment modalities are required for newly diagnosed GBM. Our proposed treatment modality of the Stupp regimen combined with anlotinib therapy are waiting conclusion. Trial Registration: This study was registered with ClinicalTrials.gov under identifier NCT04959500 on July 13, 2021.

Precision medicine, particularly therapeutic drug monitoring (TDM), is essential for optimizing drug dosage and minimizing toxicity. However, current TDM methods have limitations, including the need for skilled operators, patient discomfort, and the inability to monitor dynamic drug level changes. In recent years, wearable sensors have emerged as a promising solution for drug monitoring. These sensors offer real-time and continuous measurement of drug concentrations in biofluids, enabling personalized medicine and reducing the risk of toxicity. This review provides an overview of drugs detectable by wearable sensors and explores biosensing technologies that can enable drug monitoring in the future. It presents a comparative analysis of multiple biosensing technologies and evaluates their strengths and limitations for integration into wearable detection systems. The promising capabilities of wearable sensors for real-time and continuous drug monitoring offer revolutionary advancements in diagnostic tools, supporting personalized medicine and optimal therapeutic effects. Wearable sensors are poised to become essential components of healthcare systems, catering to the diverse needs of patients and reducing healthcare costs.

Abstract Aim The aim of this study was to explore the relationship between chronic illness resources, patient activation and self‐management behaviour among middle‐aged and older patients with CHD. Design A cross‐sectional, descriptive correlational study was performed. Methods A convenience sample of 296 participants were recruited in Tianjin, China. Data were collected by using the Chronic Illness Resource Survey (CIRS), Patient Activation Measure (PAM) and Coronary Artery Disease Self‐Management Scale (CSMS). Descriptive statistics and Pearson's correlation analysis were used to data analysis. Linear regression analysis was performed to explore the mediating role of patient activation. Results The results showed that chronic illness resources and patient activation were significantly and positively correlated with self‐management behaviours (p

Abstract Background SQUAMOSA promoter binding proteins (SBPs) genes encode a family of plant-specific transcription factors involved in various growth and development processes, including flower and fruit development, leaf initiation, phase transition, and embryonic development. The SBP gene family has been identified and characterized in many species, but no systematic analysis of the SBP gene family has been carried out in sugarcane. Results In the present study, a total of 50 sequences for 30 SBP genes were identified by the genome-wide analysis and designated SsSBP1 to SsSBP30 based on their chromosomal distribution. According to the phylogenetic tree, gene structure and motif features, the SsSBP genes were classified into eight groups (I to VIII). By synteny analysis, 27 homologous gene pairs existed in SsSBP genes, and 37 orthologous gene pairs between sugarcane and sorghum were found. Expression analysis in different tissues, including vegetative and reproductive organs, showed differential expression patterns of SsSBP genes, indicating their functional diversity in the various developmental processes. Additionally, 22 SsSBP genes were predicted as the potential targets of miR156. The differential expression pattern of miR156 exhibited a negative correlation of transcription levels between miR156 and the SsSBP gene in different tissues. Conclusions The sugarcane genome possesses 30 SsSBP genes, and they shared similar gene structures and motif features in their subfamily. Based on the transcriptional and qRT-PCR analysis, most SsSBP genes were found to regulate the leaf initial and female reproductive development. The present study comprehensively and systematically analyzed SBP genes in sugarcane and provided a foundation for further studies on the functional characteristics of SsSBP genes during different development processes.

Zhimin Hou, Yanhui Liu et al. used single cell RNA-seq to analyze the model organism, Arabidopsis thaliana, at three stages during female germline differentiation. They reconstructed the continuous trajectory of female germline differentiation, providing a valuable reference for future investigation of germline cell fate determination in A. thaliana.

Primary pulmonary venous malformation is rare and usually presents as single or multiple round masses or nodules. Here, we present the first report of a case of venous malformation presenting as Mauritia arabica -like bronchial wall thickness that was initially misdiagnosed as bronchiectasis. A Chinese man in his late 20s presented complaining of hemoptysis for 10 days. Computed tomography demonstrated bronchiectasis and M. arabica -like bronchial wall thickening in the left lower lobe. He was unresponsive to medical treatment for bronchiectasis and underwent thoracoscopic left lower lobectomy. Histopathological examination revealed venous malformation around the bronchial walls with no bronchiectasis. Venous malformation should be considered in the differential diagnosis of bronchiectasis, especially in patients with the following triad of signs: no response to antibiotics, M. arabica -like bronchial wall thickness, and normal accompanying arteries.

Glioma is one of the most lethal cancers and causes more than 200,000 deaths every year. Immunotherapy was an inspiring therapy for multiple cancers but failed in glioma treatment. The importance of serine and glycine and their metabolism has been well-recognized in the physiology of immune cells and microenvironment in multiple cancers. However, their correlation with prognosis, immune cells, and immune microenvironment of glioma remains unclear. In this study, we investigated the relationships between the expression pattern of serine and glycine metabolism-related genes (SGMGs) and clinicopathological features, prognosis, and tumor microenvironment in glioma based on comprehensive analyses of multiple public datasets and our cohort. According to the expression of SGMGs, we conducted the consensus clustering analysis to stratify all patients into four clusters with remarkably distinctive clinicopathological features, prognosis, immune cell infiltration, and immune microenvironment. Subsequently, a serine and glycine metabolism-related genes signature (SGMRS) was constructed based on five critical SGMGs in glioma to stratify patients into SGMRS high- and low-risk groups and tested for its prognostic value. Higher SGMRS expressed genes associated with the synthesis of serine and glycine at higher levels and manifested poorer prognosis. Besides, we confirmed that SGMRS was an independent prognostic factor and constructed nomograms with satisfactory prognosis prediction performance based on SGMRS and other factors. Analyzing the relationship between SGMRS and immune landscape, we found that higher SGMRS correlated with ‘hotter’ immunological phenotype and more immune cell infiltration. Furthermore, the expression levels of multiple immunotherapy-related targets, including PD-1, PD-L1, and B7-H3, were positively correlated with SGMRS, which was validated by the better predicted response to immune checkpoint inhibitors. In conclusion, our study explored the relationships between the expression pattern of SGMGs and tumor features and created novel models to predict the prognosis of glioma patients. The correlation of SGMRS with immune cells and microenvironment in gliomas suggested an essential role of serine and glycine metabolism in reforming immune cells and microenvironment. Finally, the results of our study endorsed the potential application of SGMRS to guide the selection of immunotherapy for gliomas.

Glioma is the most common malignant tumor in the central nervous system. The impact of metabolism on cancer development and the immune microenvironment landscape has recently gained broad attention. Purines are involved in multiple metabolic pathways. It has been proved that purine metabolism could regulate malignant biological behaviors and response to immune checkpoint inhibitors in multiple cancers. However, the relationship of purine metabolism with clinicopathological features and the immune landscape of glioma remains unclear. In this study, we explored the relationships between the expression of purine metabolism-related genes (PuMGs) and tumor features, including prognosis and microenvironment of glioma, based on analyses of 1,523 tumors from 4 public databases and our cohort. Consensus clustering based on 136 PuMGs classified the glioma patients into two clusters with significantly distinguished prognosis and immune microenvironment landscapes. Increased immune infiltration was associated with more aggressive gliomas. The prognostic Purine Metabolism-Related Genes Risk Signature (PuMRS), based on 11 critical PuMGs, stratified the patients into PuMRS low- and high-risk groups in the training set and was validated by validation sets from multiple cohorts. The high-risk group presented with significantly shorter overall survival, and further survival analysis demonstrated that the PuMRS was an independent prognostic factor in glioma. The nomogram combining PuMRS and other clinicopathological factors showed satisfactory accuracy in predicting glioma patients’ prognosis. Furthermore, analyses of the tumor immune microenvironment suggested that higher PuMRS was correlated with increased immune cell infiltration and gene expression signatures of “hotˮ tumors. Gliomas in the PuMRS high-risk group presented a higher expression level of multiple immune checkpoints, including PD-1 and PD-L1, and a better-predicted therapy response to immune checkpoint inhibitors. In conclusion, our study elucidated the relationship between the expression level of PuMGs and the aggressiveness of gliomas. Our study also endorsed the application of PuMRS to construct a new robust model for the prognosis evaluation of glioma patients. The correlations between the profiles of PuMGs expression and tumor immune microenvironment potentially provided guidance for immunotherapy in glioma.

Glioma is the most common malignant tumor in the central nervous system with no significant therapeutic breakthrough in recent years. Most attempts to apply immunotherapy in glioma have failed. Tryptophan and its metabolism can regulate malignant features of cancers and reshape immune microenvironment of tumors. However, the role of tryptophan metabolism in glioma remains unclear. In current study, we explored the relationships between the expression pattern of tryptophan metabolism-related genes (TrMGs) and tumor characteristics, including prognosis and tumor microenvironment of gliomas through analyzing 1,523 patients’ samples from multiple public databases and our own cohort. Based on expression of TrMGs, K-means clustering analysis stratified all glioma patients into two clusters with significantly different TrMG expression patterns, clinicopathological features and immune microenvironment. Furthermore, we constructed a tryptophan metabolism-related genes signature (TrMRS) based on seven essential TrMGs to classify the patients into TrMRS low- and high-risk groups and validated the prognostic value of the TrMRS in multiple cohorts. Higher TrMRS represented for potentially more active tryptophan catabolism, which could subsequently lead to less tryptophan in tumor. The TrMRS high-risk group presented with shorter overall survival, and further analysis confirmed TrMRS as an independent prognostic factor in gliomas. The nomograms uniting TrMRS with other prognostic factors manifested with satisfactory efficacy in predicting the prognosis of glioma patients. Additionally, analyses of tumor immune landscapes demonstrated that higher TrMRS was correlated with more immune cell infiltration and “hot” immunological phenotype. TrMRS was also demonstrated to be positively correlated with the expression of multiple immunotherapy targets, including PD1 and PD-L1. Finally, the TrMRS high-risk group manifested better predicted response to immune checkpoint inhibitors. In conclusion, our study illustrated the relationships between expression pattern of TrMGs and characteristics of gliomas, and presented a novel model based on TrMRS for prognosis prediction in glioma patients. The association between TrMRS and tumor immune microenvironment of gliomas indicated an important role of tryptophan and its metabolism in reshaping immune landscape and the potential ability to guide the application of immunotherapy for gliomas.

Angioimmunoblastic T-cell lymphoma (AITL) is a common type of nodal peripheral T-cell lymphoma, which always presents with extensive follicular dendritic cell (FDC) meshwork. Here, we report a case of AITL combined with extensive spindle cell meshwork. Spindle cells occupied were positive for the FDC markers CD21, CD23, and CD35. Furthermore, some cells were positive for desmin and smooth muscle actin (SMA), suggesting the differentiation of fibroblastic reticular cell (FRC). Interestingly, the proliferation of spindle cells was so extensive that was easily misdiagnosed as FDC sarcoma (FDCS). Next-generation sequencing showed that the common mutations reported in AITL, including RHOA, TET2, and IDH2, were also detected in this case, while the genes that are recurrently mutated in FDCS were not detected. Regrettably, the patient died 19 months later. Overall, we highlight the unusual morphologic features in an AITL patient with extensive FDC and FRC network that may be misdiagnosed as FDCS, and careful morphological observation and immunochemical and molecular examinations are crucial for an accurate diagnosis.

Glioma is the most prevalent malignancy in the central nervous system. The impact of ion-induced cell death on malignant tumors’ development and immune microenvironment has attracted broad attention in recent years. Cuproptosis is a novel copper-dependent mechanism that could potentially regulate tumor cell death by targeting mitochondria respiration. However, the role of cuproptosis in gliomas remains unclear. In the present study, we investigated the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of glioma, by analyzing multiple public databases and our cohort. Consensus clustering based on the expression of twelve CRGs stratified the glioma patients into three subgroups with significantly different prognosis and immune microenvironment landscapes. Reduced immune infiltration was associated with the less aggressive CRG cluster. A prognostic CRGs risk signature (CRGRS), based on eight critical CRGs, classified the patients into low- and high-risk groups in the training set and was endorsed by validation sets from multiple cohorts. The high-risk group manifested a shorter overall survival, and further survival analysis demonstrated that the CRGRS was an independent prognostic factor. The nomogram combining CRGRS and other clinicopathological factors exhibited good accuracy in predicting the prognosis of glioma patients. Moreover, analyses of tumor immune microenvironment indicated that higher CRGRS was correlated with increased immune cell infiltration but diminished immune function. Gliomas in the high-risk group exhibited higher expression of multiple immune checkpoints, including PD-1 and PD-L1, and a better predicted therapy response to immune checkpoint inhibitors. In conclusion, our study elucidated the connections between CRGs expression and the aggressiveness of gliomas, and the application of CRGRS derived a new robust model for prognosis evaluation of glioma patients. The correlations between the profiles of CRGs expression and immune tumor microenvironment illuminated prospects and potential indications of immunotherapy for glioma.

Glioma is one of the most malignant intracerebral tumors, whose treatment means was limited, and prognosis was unsatisfactory. Lactate metabolism patterns have been shown to be highly heterogenous among different tumors and produce diverse impact on the tumor microenvironment. To understand the characteristics and implications of lactate metabolism gene expression, we developed a lactate metabolism-related gene expression signature of gliomas based on RNA-sequencing data of a total of 965 patient samples from TCGA, CGGA, and our own glioma cohort. Sixty-three lactate metabolism-related genes (LMGs) were differentially expressed between glioma and normal brain tissue, and consensus clustering analysis identified two clusters distinct LMG expression patterns. The consensus clusters differed in prognosis, molecular characteristics and estimated immune microenvironment landscape involving immune checkpoint proteins, T cell dysfunction and exclusion, as well as tumor purity. Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox hazard regression was applied in determining of prognosis-related lactate metabolism genes (PRLMGs), on which prognostic lactate metabolism risk score (PLMRS) was constructed. The high PLMRS group was associated with significantly poorer patient outcome. A nomogram containing PLMRS and other independent prognostic variables was established with remarkable predictive performance on patient survival. Exploration on the somatic mutations and copy number variations of the high- and low-PLMRS groups demonstrated their distinct genetic background. Together, our results indicated that the expression signature of LMG was associated with the prognosis of glioma patients and influenced the activity of immune cells in the tumor microenvironment, which may serve as a potential biomarker for predicting response of gliomas to immunotherapy.

The landslide disaster in China is widespread and serious. Regional landslide risk assessment has always been one of the most important contents of landslide disaster prevention and mitigation. In recent years, with the rapid development of big data and artificial intelligence technology, machine learning technology has gradually been widely used in landslide hazard assessment andachieved good results. Based on a large number of literatures, this paper systematically expounds the research status of landslide risk assessment methods based on machine learning technology. This paper reviews and analyzes the existing research results from three key links: evaluation factor selection and quantization normalization, data cleaning and sample set construction, model selection and training evaluation, and finally puts forward some suggestions on the development trend of machine learning landslide risk evaluation methods.

Abstract Acoustic wave can destabilize the flame and has a potential in firefighting, but the influences of the sound source and its frequency are still poorly understood. This work applies a loudspeaker to extinguish a laminar diffusion propane flame of 5–25 mm high, where the local sound frequency is 50–70 Hz and sound pressure is 0.8–3.2 Pa (92.0–104.1 dB). Results reveal a constant flame pulsating displacement at the extinction limit, independent of the sound environment used. Such a flame pulsating displacement is found to be caused by the motion of the speaker membrane (or diaphragm) and its induced wind, which could be two orders of magnitude larger than the displacement of the air that transmits acoustic wave. Thus, under the influence of sound source, a critical flame strain rate, stretched by the pulsating airflow, can be formulated to characterize the blow-off limit better than the local sound pressure. The sound source with a lower frequency can produce larger pulsating displacements of both membrane and flame, and thus promoting extinction. This work improves the understanding of flame dynamics under the external sound field and source, and it helps establish a scientific framework for acoustic-based fire suppression technologies.

Ultrastable metallic glasses form by surface diffusion on a substrate during deposition. Here, this process is shown to involve the collective diffusion of atoms in a cyclic process, involving the formation of islands, their coalescence into a layer, followed by further island formation.

BackgroundGlioblastoma (GBM) accounts for approximately 80% of malignant gliomas and is characterized by considerable cellularity and mitotic activity, vascular proliferation, and necrosis. Naples prognostic score (NPS), based on inflammatory markers and nutritional status, has a prognostic ability in various cancers. In the current study, we aim to explore the prognostic value of operative NPS in GBM patients and compare the prognostic ability between NPS and controlling nutritional status (CONUT).Materials and methodsThe retrospective analysis was carried out on consecutive newly diagnosed GBM patients who had underwent tumor resection at West China Hospital from February 2016 to March 2019. All statistical analyses were conducted using SPSS software and R software.ResultsA total of 276 newly diagnosed GBM patients were enrolled in the current study. Overall survival (OS) (p < 0.001) and tumor location (p = 0.007) were significantly related to NPS. Serum albumin concentrate, cholesterol concentrate, neutrophil-to-lymphocyte ratio, lymphocyte ratio, and CONUT score were all significantly associated with NPS (p < 0.001). The Kaplan–Meier curve indicated that NPS (log-rank test, p < 0.001) and CONUT score (log-rank test, p = 0.023) were significantly associated with OS. Multivariate Cox regression revealed that both NPS and CONUT score served as independent prognostic indicators. The prognostic model with NPS had the strongest prognostic capability and best model-fitting.ConclusionIn the current study, NPS is found as an independent prognostic indicator for patients with newly diagnosed GBM, and the prognostic ability of NPS is superior to CONUT score.

The rapid expansion of electric vehicles (EVs) in China will induce a potential imbalance in the demand and supply of critical metals, which emphasized the importance of recycling critical metals. Evaluating their stock and recycling potential is essential to the electrification transformation in the automobile industry and provides references to the overall national resource strategy. In this study, we identified the critical metals in the electrification transformation of the automobile industry, estimated the stock of critical metals from 2022 to 2050 under multiple scenarios in China, and assessed the recycling potential of critical metals in EVs as well as their economic value. The results show that China’s passenger vehicles will reach 547.5–623.8 million in 2050. According to China’s current energy conservation and emission reduction policies, fuel vehicle (FV) ownership will peak in 2042, at 488.2 million. If strict energy conservation and emission reduction policies are adopted, electric vehicle ownership will increase from 148.3 million to 293.9 million by 2050, leading to a rapid increase in the stock of critical metals. The total stock of key critical metals under the scenario with stringent policies will be 29.27 million tons in 2050, 10.55 million higher compared to the scenario with no ban on fuel vehicles. Based on our results, the recycling of critical metals can be an effective option for the inadequate critical metal supply, especially given the policy context of increasingly expanding EV ownership in the near-term future.

On rare occasions, secondary Epstein–Barr virus (EBV)-associated B-cell lymphoma can develop in patients with angioimmunoblastic T-cell lymphoma (AITL). Here, we describe the tumor microenvironment and mutation features of a patient with EBV + large B-cell lymphoma (LBCL) secondary to AITL. He was admitted to hospital due to a 1-year history of fever and enlarged right inguinal lymph nodes. A biopsy of the right inguinal lymph node demonstrated that numerous diffuse medium-sized atypical lymphocytes proliferated, together with increased extrafollicular follicular dendritic cell meshwork, and the lymphocytes expressed CD3, CD4, BCL6, CD10, PD-1, CXCL13, and Ki-67 (75%). Thus, a diagnosis of AITL was made. However, the disease progressed following treatment by CHOP regimen (cyclophosphamide, adriamycin, vincristine, and prednisone). Biopsy showed that most of the cells were positive for CD20 staining and IgH rearrangement. Analysis of 22 kinds of immune cells showed that the numbers of activated NK cells and activated memory T cells increased, while the T-follicular helper population decreased in the transformed sample. In addition, compared with the primary sample, RHOA (G17V) mutation was not detected, while JAK2 and TRIP12 gene mutations were detected in the transformed sample. Overall, we described the immune microenvironment and mutation features of a patient with EBV + LBCL secondary to AITL. This study will help us to understand the mechanisms by which AITL transforms to B-cell lymphoma.

ObjectivesThe aim of this study is to investigate the clinical significance of myeloperoxidase (MPO)–antineutrophil cytoplasmic antibody (ANCA) on eosinophilic granulomatosis with polyangiitis (EGPA) from a longitudinal Chinese cohort.MethodsA total of 120 patients with EGPA were consecutively enrolled and followed up. Two patients with PR3 ANCA was excluded and our analysis focused on the 118 patients with EGPA. On the basis of MPO-ANCA status, baseline clinical manifestations, treatment, and outcomes were analyzed. Logistic regression analysis was performed to analyze the independently associated factors for renal involvement.ResultsANCA positivity was observed in 24.2% of patients with EGPA. Patients with MPO-ANCA accounted for 20.8%. Patients with positive MPO-ANCA had higher levels of erythrocyte sedimentation rate (ESR), C-reactive protein, Birmingham Vasculitis Activity Score (BVAS), higher ratios of fever, myalgia, renal involvement, and biopsy-proven vasculitis. Heart manifestations and asthma were more common in patients with negative ANCA. Baseline MPO-ANCA titers positively correlated with ESR, eosinophil count, and BVAS and were higher in patients with methylprednisolone pulse. Among patients with renal involvement, patients with positive MPO-ANCA had higher proportions of female, fever, biopsy-proven vasculitis, and faster ESR; patients with negative ANCA developed more skin and cardiac involvement. MPO-ANCA positivity, male, and ear involvement were the independent factors associated with renal involvement. Intravenous cyclophosphamide and immunoglobulins were prescribed more frequently in patients with positive MPO-ANCA.ConclusionIn this cohort, patients with positive MPO-ANCA and negative ANCA displayed distinct clinical features, suggesting that MPO-ANCA might be a valuable biomarker for EGPA stratification. Baseline MPO-ANCA level correlated positively with disease activity of EGPA. MPO-ANCA was a significant independent factor associated with renal involvement.

Abstract Background To analyze the epidemic characteristics of the human rhinovirus (HRV) outbreaks in Guangzhou, China, in 2020. Methods Descriptive epidemiological methods were used to analyze the HRV‐related outbreaks in Guangzhou, 2020. Results Seventeen outbreaks were reported in 2020 during the coronavirus disease 2019 (COVID‐19) pandemic in Guangzhou, a total of 465 patients (290 males and 175 females) were enrolled, with a median age of 10. A total of 223 (47.96%) had been tested for HRV, 89 (39.91%) of which were positive; 344/465 (73.98%) had a fever, 138/465 (29.68%) had a runny nose, 139/465 (29.89%) had a sore throat, 86/465 (18.49%) had a cough, 41/465 (8.82%) had a headache, and 37/465 (7.96%) had a sneeze. Patients at age of 13–15 had the highest rate of sore throat and runny nose, patients aged 11–12 had the highest rate of sneezing, and patients at age of 12–14 had the highest rate of positive rate. Patients tested positive had a higher rate of fever (χ2 = 11.271, p = .001), cough (χ2 = 6.987, p = .008), runny nose (χ2 = 7.980, p = .005), and sneeze (χ2 = 4.676, p = .031). Conclusion The HRV was restored during the fighting of the COVID‐19 pandemic. The conventional COVID‐19 control measures were not effective enough in preventing rhinovirus. More appropriate control measures should be used to control HRV.

Abstract Background Sixty five percent of procyanidins in grape seeds is polymeric procyanidins (PPC), and they could not be assimilated directly by human. To enhance procyanidin assimilation, steam explosion treatment (SE) was used to facilitate the preparation of oligomeric procyanidins (OPC) from grape seeds. Results The results indicate that SE treatment made grape seeds loose and porous, and decreased the mean degree of polymerization (mDP) of procyanidins. The procyanidins content and total phenolic content (TPC) were decreased with the increase of SE severity, while the amount of catechin (CA), epicatechin (EC) and epicatechin-3-O-gallate (ECG) were increased, resulting in significant increase of antioxidant activity. Conclusions Although SE treatment could depolymerize PPC and produce CA/EC/ECG with high yield, it caused the yield loss of total procyanidins. SE treatment is a potential effective method to prepare procyanidins with low degree of polymerization and high antioxidant activity. However, it still needs to study further how to balance the yield of total procyanidins and catechin monomers (CA/EC/ECG).

Abstract Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.

Background:ZEB2 gene mutations or deletions cause Mowat-Wilson syndrome (MWS), which is characterized by distinctive facial features, global developmental delay, intellectual disability, epilepsy, friendly and happy personalities, congenital heart disease, Hirschsprung disease and multiple congenital anomalies. Currently, more than 300 MWS patients have been described in the literature, and nearly 280 variants in ZEB2 have been identified.Methods: In this study, we report three unrelated Chinese patients presenting multiple congenital anomalies that were consistent with those of MWS. Whole-exome sequencing (WES) was used to identify the causative variants.Results: WES identified two novel de novo frameshift variants in ZEB2 (NM_014795.4:c.2136delC, p. Lys713Serfs*3 and c.2740delG, p. Gln914Argfs*16) in patients 1 and 2, respectively, and a novel de novo splicing variant in ZEB2 (NM_014795.4:c.808-2delA) in patient 3, all of which were confirmed by Sanger sequencing. Next, we systematically reviewed the clinical characteristics of Chinese and Caucasian MWS patients. We revealed a higher incidence of constipation in Chinese MWS patients compared to that previously reported in Caucasian cohorts, while the incidence of Hirschsprung disease and happy demeanor was lower in Chinese MWS patients and that epilepsy in Chinese MWS patients could be well-controlled compared to that in Caucasian MWS individuals.Conclusion: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical characteristics of MWS. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with MWS.

BackgroundF-box and WD repeat domain-containing 7 (Fbw7) is well known as a tumor suppressor and ubiquitin ligase which targets a variety of oncogenic proteins for proteolysis. We previously reported that Fbw7 promotes apoptosis in diffuse large B-cell lymphoma (DLBCL) through Fbw7-mediated ubiquitination of Stat3. This study aimed to identify the mechanism of Fbw7-mediated aerobic glycolysis reprogramming in DLBCL.MethodsExpression levels of Fbw7 and Lactate Dehydrogenase A (LDHA) in human DLBCL samples were evaluated by immunohistochemistry. Crosstalk between Fbw7 and LDHA signaling was analyzed by co-immunoprecipitation, ubiquitination assay, western blotting and mRNA quanlitative analyses. In vitro and in vivo experiments were used to assess the effect of the Fbw7-mediated LDHA/lactate/miR-223 axis on DLBCL cells growth.ResultsFbw7 could interact with LDHA to trigger its ubiquitination and degradation. Inversely, lactate negatively regulated Fbw7 via trigging the expression of miR-223, which targeted Fbw7 3’-UTR to inhibit its expression. In vivo and in vitro experiments revealed that miR-223 promoted tumor growth and that the effects of miR-223 on tumor growth were primarily related to the inhibition of Fbw7-mediated LDHA’s ubiquitination.ConclusionsWe demonstrated that the ubiquitin-ligase Fbw7 played a key role in LDHA-related aerobic glycolysis reprogramming in DLBCL. Our study uncovers a negative functional loop consisting of a Fbw7-mediated LDHA/lactate/miR-223 axis, which may support the future ABC-DLBCL therapy by targeting LDHA-related inhibition.

Facial paralysis is negatively associated with functional, aesthetic, and psychosocial consequences. The masseteric-to-facial nerve transfer (MFNT) has many advantages in facial reanimation. The aim is to evaluate the effectiveness of our MFNT technique and define the potential factors predictive of outcome. The authors conducted a retrospective review of 20 consecutive patients who underwent MFNT using the temporofacial trunk of facial nerve. Videotapes and images were documented and evaluated according to Facial Nerve Grading Scale 2.0 (FNGS2.0) and Sunnybrook Facial Grading System (FGS). The quality-of-life was obtained using the Facial Clinimetric Evaluation (FaCE) Scale. Moreover, Facial Asymmetry Index (FAI), quantitative measurement of the width of palpebral fissure, deviation of the philtrum, and angles or excursions of the oral commissure were applied to explore the effect of the transfer metrically. Multivariable logistic regression models and Cox regression were prepared to predict the effect of MFNT by preoperative clinical features. The patients showed favorable outcomes graded by FNGS2.0, and experienced significantly improved scores in static and dynamic symmetry with slightly elevated scores in synkinesis evaluated by the Sunnybrook FGS. The score of FaCE Scale increased in all domains after reanimation. The quantitative indices indicated the symmetry restoration of the middle and lower face after MFNT. Regression analysis revealed that younger patients with severe facial paralysis are preferable to receive MFNT early for faster and better recovery, especially for traumatic causes. The findings demonstrate that MFNT is an effective technique for facial reanimation, and case screening based on clinical characteristics could be useful for surgical recommendation.

Searchable symmetric encryption (SSE) provides an effective way to search encrypted data stored on untrusted servers. When the server is not trusted, it is indispensable to verify the results returned by it. However, the existing SSE schemes either lack fairness in the verification of search results, or do not support the verification of multiple keywords. To address this, we designed a multi-keyword verifiable searchable symmetric encryption scheme based on blockchain, which provides an efficient multi-keyword search and fair verification of search results. We utilized bitmap to build a search index in order to improve search efficiency, and used blockchain to ensure fair verification of search results. The bitmap and hash function are combined to realize lightweight multi-keyword search result verification, compared with the existing verification schemes using public key cryptography primitives, our scheme reduces the verification time and improves the verification efficiency. In addition, our scheme supports the dynamic update of files and realizes the forward security in update. Finally, formal security analysis proves that our scheme is secure against Chosen-Keyword Attacks (CKA), experimental analysis demonstrations that our scheme is efficient and viable in practice.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.

In Qingchuan County of Sichuan Province, landslide disasters occur in a large number of places and cover a wide range of areas. Early warning of regional landslide disaster is an important means of effective disaster prevention and mitigation, and an early warning model is the core of successful early warning. The traditional regional geological disaster warning model is limited by the lack of big data and analysis methods of the complicated investigation and monitoring mechanism of the landslide in the study areas, and it has some problems, such as limited warning precision and insufficient refinement. In this paper, the training sample set of landslide disaster in Qingchuan County is constructed on the basis of the integrated collation and data cleaning of the results of geological disaster investigation and monitoring and precipitation monitoring. The sample set includes 27 input feature attributes such as geological environment rainfall and 1 output feature attribute, covering the total number of the samples in Qingchuan County in the past 9 years (2010—2018) up to 1826 (613 positive samples, 1213 negative samples). Based on the logistic regression algorithm, the study and training of the sample set is carried out with a 50%-fold cross validation. The Bayesian optimization algorithm is used for model optimization, and the accuracy and model generalization ability of the model are verified by such indicators as accuracy, ROC curve and AUC value. The ROC curve is also known as the “Receiver Operating Characteristic” curve. AUC value represents the area under the ROC curve. The verification results show that the training result model based on logistic regression algorithm is of good accuracy and generalization ability (accuracy 94.3% and AUC 0.980). Finally, it is proposed that in the actual warning of regional landslide, 27 characteristic attributes of each warning unit in the research area are input according to the format of characteristic attributes of training samples, and the pre-learned and trained model is called to output the probability of occurrence of landslide disaster, and the warning level of landslide disaster is segmented according to the output probability. A yellow alert is issued when the output probability P is greater than or equal to 40% and P is less than 60%. An orange alert is issued when the output probability P is greater than or equal to 60% and P is less than 80%. A red alert is issued when the output probability P is greater than or equal to 80%. In the next step, the accuracy of the model will be further verified in the landslide disaster early warning business in Qingchuan county.

Abstract Background Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported. Case presentation We present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening. Conclusions This case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.

Abstract Background Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. Methods Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. Results Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling. Conclusion Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.

Reactive oxygen species (ROS), a type of oxygen monoelectronic reduction product, play integral roles in root growth and development. The epigenetic mechanism plays a critical role in gene transcription and expression; however, its regulation of ROS metabolism in root development is still limited. We found that the chromatin remodeling complex SWR1 regulates root length and lateral root formation in Arabidopsis. Our transcriptome results and gene ontology (GO) enrichment analysis showed that the oxidoreductase activity-related genes significantly changed in mutants for the Arabidopsis SWR1 complex components, such as arp6 and pie1, and histone variant H2A.Z triple mutant hta8 hta9 hta11. The three encoding genes in Arabidopsis are the three H2A.Z variants hta8, hta9, and hta11. Histochemical assays revealed that the SWR1 complex affects ROS accumulation in roots. Furthermore, chromatin immunoprecipitation quantitative real-time PCR (ChIP-qPCR) analysis showed that the reduced H2A.Z deposition in oxidoreductase activity-related genes caused ROS to accumulate in arp6, pie1, and hta8 hta9 hta11. H2A.Z deposition-deficient mutants decreased after the trimethylation of lysine 4 on histone H3 (H3K4me3) modifications and RNA polymerase II (Pol II) enrichment, and increased after the trimethylation of lysine 27 on histone H3 (H3K27me3) modifications, which may account for the expression change in oxidoreductase activity-related genes. In summary, our results revealed that the chromatin complex SWR1 regulates ROS accumulation in root development, highlighting the critical role of epigenetic mechanisms.