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Abstract Background Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Owing to label-free modeling of complex heterogeneity, self-supervised heterogeneous graph representation learning (SS-HGRL) has been widely studied in recent years. The goal of SS-HGRL is to design an unsupervised learning framework to represent complicated heterogeneous graph structures. However, based on contrastive learning, most existing methods of SS-HGRL require a large number of negative samples, which significantly increases the computation and memory costs. Furthermore, many methods cannot fully extract knowledge from a heterogeneous graph. To learn global and local information simultaneously at low time and space costs, we propose a novel Siamese Network based Multi-scale bootstrapping contrastive learning approach for Heterogeneous graphs (SNMH). Specifically, we first obtain views under the meta-path schema and the 1-hop relation type schema through dual-schema view generation. Then, we propose cross-schema and cross-view bootstrapping contrastive objectives to maximize the similarity of node representations between different schemas and views. By integrating and optimizing the above objectives, we can extract local and global information and eventually obtain the node representations for downstream tasks. To demonstrate the effectiveness of our model, we conduct experiments on several public datasets. Experimental results show that our model is superior to the state-of-the-art methods on the premise of lower time and space complexity. The source code and datasets are publicly available at https://github.com/lorisky1214/SNMH.

Objective The aim of the present study was to evaluate the 10‐year outcomes of cementless total hip arthroplasty (THA) in adult patients with the late sequelae of septic arthritis of the hip. Methods We followed 166 consecutive patients (168 hips) who underwent cementless THA between March 2001 and December 2011. There were 79 men and 87 women, with a mean age of 50.4 years (range 21–76 years) at the time of index THA, all of whom had hip osteoarthritis secondary to hip pyogenic infection. The average duration of follow up was 10.6 years (range 6.9–17.2 years). Preoperative and postoperative clinical ratings were evaluated, including the hip dysfunction and osteoarthritis outcome score (HOOS), the Harris hip score (HHS), range of motion, a 100‐point visual analog scale for hip pain, and the severity of limp and limb length discrepancy (LLD). The anteroposterior and lateral radiographs of the hip and full‐length view of the lower extremities were obtained to assess the position of the components, radiolucent lines, osteolysis, loosening of components, and heterotopic ossification. The intraoperative and postoperative complications were also recorded. Results The mean HSS and hip pain score were 44.2 points (range 29–66 points) and 42.5 points (range 32–64 points), respectively, before the index surgery and significantly improved to 88.1 points (range 78–96 points) and 15.1 points (range 10–26 points), respectively, at final follow‐up examination. The HOOS and range of motion also improved significantly. The mean limb length discrepancy was reduced from 2.6 to 0.8 cm. The limp at last follow‐up examination was moderate in 3 cases because of hip osteoarthritis in the other limb, slight in 26, and absent in 137. A radiolucent line was observed in 12 hips (7.1%) around the acetabular or femoral components. A progressive radiolucent line around the undersized femoral stem in all zones was seen in 1 hip, resulting in aseptic loosening and breakage of the femoral component. There were 8 cases of intraoperative fracture, 7 cases of dislocation, and 7 cases of transient nerve palsy. Recurrence of infection occurred in 2 hips. Revision surgery was conducted in 2 hips because of isolated loosening of the acetabular cup and the femoral stem, respectively. Kaplan–Meier survival was 97% at 10 years, with revision for any reason with any component as an end‐point. Conclusion Improved surgical techniques and development of components with various sizes provided favorable results for cementless THA conducted for late sequelae of sepsis in these young and active patients. Although the incidence of complications was relatively high, the complications were treated successfully.

Transmembrane proteins have exhibited a significant correlation with glioblastoma multiforme (GBM). The current study elucidates the roles of transmembrane protein 150A (TMEM150A) in GBM. Data on patients with GBM were collected from The Cancer Genome Atlas and Xena databases. The objective was to identify the expression levels of TMEM150A in patients with GBM, and evaluate its diagnostic and prognostic values, accomplished using the receiver operating characteristic and survival analyses. On a cellular level, Cell Counting Kit-8, Wound healing, and Transwell experiments were performed to gauge the impact of TMEM150A on cell growth and migration. The study further investigated the correlation between TMEM150A expression and immune status, along with ribonucleic acid (RNA) modifications in GBM. The findings demonstrated TMEM150A overexpression in the cancerous tissues of patients with GBM, with an area under the curve value of 0.95. TMEM150A overexpression was significantly correlated with poor prognostic indicators. TMEM150A overexpression and isocitrate dehydrogenase (IDH) mutation status were predictive of poor survival time among patients with GBM. In vitro experiments indicated that suppressing TMEM150A expression could inhibit GBM cell proliferation, migration, and invasion. Moreover, TMEM150A overexpression was associated with stromal, immune, and estimate scores, immune cells (such as the T helper (Th) 17 cells, Th2 cells, and regulatory T cells), cell markers, and RNA modifications. Therefore, TMEM150A overexpression might serve as a promising biomarker for predicting poor prognosis in patients with GBM. Inhibiting TMEM150A expression holds the potential for improving the survival time of patients with GBM.

Cyclic injection hydraulic fracturing is a promising way for the geothermal energy exploitation by reactivating the fractures in geothermal reservoir. However, fracture initiation and growth induced by cyclic injection schemes have been inadequately studied for hot dry rock (HDR), and the cyclic injection fracturing optimized often by experience. For this reason, the initiation and propagation of hydraulic fractures in the HDR under different cyclic injection methods were determined by experiment research for hydraulic fracturing. The results show that the cyclic frequency and injection rate play different roles in the stimulation of HDR. The cyclic injection with low frequency-low pressure can create more branched fractures, forming a short but complex hydraulic fracture network. However, when high flow-high frequency injection method is subjected, the branch fractures formed are significantly reduced, but each branch fracture can be fully expanded. To fully exploit the advantages of different injection methods, a numerical model that contains a fracture network was established with PFC software, and an alternating cyclic injection scheme with synergistic control of the cyclic frequency and injection rate was proposed. The comparison results indicated that the alternating cyclic injection method can effectively improve the fracturing effect in the HDR. The stimulation area of the alternating cyclic injection method is about 2.3 times and 2.7 times that of the low flow-low frequency and high flow-high frequency injection methods, respectively. The method presented here can be adopted to optimize the fracture growth regime and provide a scientific basis for EGS hydraulic fracturing design.

BackgroundSerum lactate dehydrogenase levels reflect disease status in a variety of organs, but its role in indicating pulmonary function is not yet clear. Therefore, this study explored the correlation between pulmonary function and serum lactate dehydrogenase, and investigated thresholds for changes in pulmonary function indicators in the total population as well as in different strata of the population.MethodsBased on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 (n = 3453), univariate and stratified analyses were performed to investigate factors associated with pulmonary function, and multiple regression analysis was used to further investigate the specific relationship with serum lactate dehydrogenase. Smoothed curve fitting, threshold effect and saturation effect analysis were used to explore the threshold level of serum lactate dehydrogenase at the onset of changes in pulmonary function indicators.ResultsAdjusted smoothed curve fit plots showed a linear relationship between serum lactate dehydrogenase levels and forced vital capacity and forced expiratory volume in one second: for each 1 U/L increase in serum lactate dehydrogenase levels, forced vital capacity decreased by 1.24 mL (95% CI = -2.05, -0.42, P = 0.0030) and forced expiratory volume in one second by 1.11 mL (95% CI = -1.82, -0.39, P = 0.0025).ConclusionsSerum lactate dehydrogenase was negatively and linearly correlated with pulmonary function indices in the total population analyzed. Based on the total population and different population stratifications, this study determined the threshold values of serum lactate dehydrogenase at the onset of decline of pulmonary function in different populations. This provides a new serological monitoring indicator for patients suffering from respiratory diseases and has implications for patients with possible clinical impairment of pulmonary function. However, our cross-sectional study was not able to determine a causal relationship between these two factors, and further research is needed.

Background: Ultrasound-triggered sonodynamic therapy (SDT), as a non-invasive approach, has attracted considerable attention in a wide variety of malignant tumors and other diseases. Over the past 2 decades, the number of scientific publications on SDT has increased rapidly. However, there is still a lack of one comprehensive report that summarizes the global research trends and knowledge landscapes in the field of SDT in detail. Thus, we performed a bibliometric analysis on SDT from 2000 to 2021 to track the current hotspots and highlight future directions.Methods: We collected publications on SDT research from the Web of Science Core Collection database. The annual number of publications and citations, major contributors, popular journals, international collaborations, co-cited references and co-occurrence keywords were analyzed and visualized with CiteSpace, VOSviewer, and R-bibliometrix.Results: A total of 701 publications were included. The annual publication output increased from 5 in 2000 to 175 in 2021, and the average growth rate was 18.4%. China was the most productive country with 463 documents (66.05%), and Harbin Medical University was the most prolific institution (N = 73). Ultrasound in Medicine and Biology published the most papers related to SDT. Materials Science, and Chemistry were the research areas receiving the most interest. All the keywords were divided into four different clusters including studies on mechanisms, studies on drug delivery and nanoparticles, studies on cancer therapy, as well as studies on ultrasound and sonosensitizers. In addition to nanomaterials-related studies including nanoparticles, mesoporous silica nanoparticles, nanosheets, liposomes, microbubble and TiO2 nanoparticle, the following research directions such as immunogenic cell death, metal-organic framework, photothermal therapy, hypoxia, tumor microenvironment, chemodynamic therapy, combination therapy, tumor resistance, intensity focused ultrasound, drug delivery, and Staphylococcus aureus also deserve further attention and may continue to explode in the future.Conclusion: SDT has a bright future in the field of cancer treatment, and nanomaterials have increasingly influenced the SDT field with the development of nano-technology. Overall, this comprehensive bibliometric study was the first attempt to analyze the field of SDT, which could provide valuable references for later researchers to better understand the global research trends, hotspots and frontiers in this domain.

The KCNK4 gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously, only two variants were identified to be associated with human disease, facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG) syndrome. In this study, we performed trio-based whole exon sequencing (WES) in a cohort of patients with epilepsy. Two de novo likely pathogenic variants were identified in two unrelated cases with heterogeneous phenotypes, including one with Rolandic epilepsy and one with the FHEIG syndrome. The two variants were predicted to be damaged by the majority of in silico algorithms. These variants showed no allele frequencies in controls and presented statistically higher frequencies in the case cohort than that in controls. The FHEIG syndrome-related variants were all located in the region with vital functions in stabilizing the conductive conformation, while the Rolandic epilepsy-related variant was distributed in the area with less impact on the conductive conformation. This study expanded the genetic and phenotypic spectrum of KCNK4. Phenotypic variations of KCNK4 are potentially associated with the molecular sub-regional effects. Carbamazepine/oxcarbazepine and valproate may be effective antiepileptic drugs for patients with KCNK4 variants.

Aiming at the impulsive noise occurring in MIMO-OFDM systems， a joint channel and impulsive noise estimation method based on the multiple measurement vector compressed sensing theory was proposed.The channel impulse response and the impulsive noise were combined to form a row sparse matrix to be estimated， and a multiple measurement vector compressed sensing model based on all subcarriers was constructed.As the measurement matrix was partially unknown due to the presence of unknown transmitted symbols in data tones， the multiple response sparse Bayesian learning theory and expectation maximization framework were adopted to jointly estimate the channel impulse response， the impulsive noise， and the data symbols which were regarded as unknown parameters.Compared with the existing methods， the proposed method not only utilizes all subcarriers but also does not use any a priori information of the channel and impulsive noise.The simulation results show that the proposed method achieves significant improvement on the channel estimation and bit error rate performance.

Peri-implantitis are a major problem causing implant failure these days. Accordingly, anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue. Micro-arc oxidation (MAO) treatment is a way to form an oxidation film on the surface of metallic materials. The method shows good osteogenic properties but weak antibacterial effect. Therefore, we developed combined strategies to combat severe peri-implantitis, which included the use of a novel compound, PD, comprising dendrimers poly(amidoamine) (PAMAM) loading dimethylaminododecyl methacrylate (DMADDM) as well as MAO treatment. Here, we explored the chemical properties of the novel compound PD, and proved that this compound was successfully synthesized, with the loading efficiency and encapsulation efficiency of 23.91% and 31.42%, respectively. We further report the two-stage double benefits capability of PD + MAO: (1) in the first stage, PD + MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo; (2) in the second stage, PD + MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo. This study first reports the two-staged, double benefits of PD + MAO, and demonstrates its potential in clinical applications for inhibiting peri-implantitis, especially in patients with severe infection risk.

Purpose: The deregulation of miRNA-218 has been found in a number of cancers. Using miRNA-218 as a target for Runt-related transcription factor 2 (Runx2), we sought to understand the role of miRNA-218 in osteosarcoma (OS). Methods: The expression of miRNA-218 was detected in the OS tumor tissues and OS cells. The Runx2 expression level was evaluated in Saos-2, 143B, U2OS, and MG-63. miRNA-218 overexpressed U2OS cells were achieved by transfection with miRNA-218 mimics. The role of miRNA-218 in inhibiting OS tumorigenesis was explored by CCK8, colony formation, cell wound scratch and Transwell assay. TargetScan and dual-luciferase reporter assay identified the interaction between miRNA-218 and Runx2. The inhibitive effect of miRNA-218 on OS through targeting Runx2 was also evaluated. Results: MiRNA-218 levels were remarkably down-regulated in OS tumor tissues and cell lines. The overexpression of miRNA-218 suppressed U2OS cell development and metastasis. The target interaction between miRNA-218 and Runx2 was validated, and their expression showed a negative correlation in U2OS cells. The suppressed U2OS cell development and metastasis were remarkably reversed by Runx2 overexpression. Conclusion: MiRNA-218 showed an inhibitive effect on the development and metastasis of osteosarcoma cell proliferation by targeting Runx2. Our findings may provide novel clues for OS treatment.

Abstract Crowd counting is still a practical and challenging problem owing to scale variations and information loss. Most existing methods based on the straightforward fusion of different features from a deep neural network seem to eliminate this limitation. However, these features are difficult to be fused since they often differ significantly in modality and dimensionality. Unlike previous works, a multi‐level features extraction network with gating mechanism for crowd counting is proposed. Specifically, a multi‐channel gated unit to adaptively extract features in different levels of the network is proposed, which can avoid interference from confusing information. To fully aggregate features via multi‐level fusion, multi‐level features extraction scheme is presented. The multi‐level features extraction network learns to fuse features from multiple levels and reduce false predictions. Extensive experiments and evaluations clearly illustrate that the proposed approach achieves state‐of‐the‐art counting performance against other methods on four mainstream crowd counting benchmarks.

Immunotherapy can improve the survival of patients with advanced lung squamous cell carcinoma (LUSC). T cytotoxic cells are one of the main members of the immune microenvironment. Herein, we aimed to identify the roles of T-cell cytotoxic markers interleukin 18 (IL18) receptor 1 (IL18R1) in the LUSC progression using bioinformatics, clinical tissue specimen, and cell experiment. We assessed the association between the IL18R1 expression and immune infiltration and IL18R1-related competing RNA network. The IL18R1 expression was downregulated in the LUSC tissues. The IL18R1 expression downregulation was associated with diagnosis and short overall survival and disease-specific survival, and it was also an independent risk factor for dismal survival time in LUSC. IL18R1-related nomograms predicted the survival time of patients with LUSC. IL18R1 overexpression inhibited the proliferation, migration, and invasion of LUSC cells. The IL18R1 expression was significantly associated with the microenvironment (stromal, immune, and estimate scores), immune cells (such as the T cells, cytotoxic cells, CD8 T cells), and immune cell markers (such as the CD8A, PD-1, and CTLA4) in LUSC. AC091563.1 and RBPMS-AS1 downregulation was positively associated with the IL18R1 expression, negatively associated with the miR-128-3p expression, and associated with short disease-specific survival and progression in LUSC. In conclusion, IL18R1 was significantly downregulated and associated with the prognosis and immune microenvironment. IL18R1 overexpression inhibits the growth and migration of cancer cells in LUSC. Furthermore, AC091563.1 and RBPMS-AS1 might compete with IL18R1 to bind miR-128-3p for participating in LUSC progression. These results showed that IL18R1 is a biomarker for evaluating the prognosis of patients with LUSC.

ObjectiveWe investigated the effects of COVID-19 fear on negative moods among college students, and assessed the efficacy of physical exercise behavior as a moderator variable.MethodsThis was a cross-sectional study. Students from three colleges and universities in Shangqiu City, Henan Province and Yangzhou City, Jiangsu Province were enrolled in this study, which was performed during the COVID-19 pandemic using an online questionnaire. A total of 3,133 college students completed the questionnaire. Measurement tools included the COVID-19 Phobia Scale (C19P-S), Depression-Anxiety-Stress Self-Rating Scale (DASS), and the Physical Activity Behavior Scale (PARS-3).ResultsDuring the COVID-19 pandemic, the rates of depression, anxiety, and stressful negative moods among college students were 35.5, 65.5, and 10.95%, respectively; there was a positive correlation between COVID-19 fear and negative moods among college students (r = 0.479, p < 0.001), which was negatively correlated with physical exercise behavior (r = −0.4, p < 0.001); the regulating effects of physical exercise behavior were significant (ΔR2 = 0.04, p < 0.001).ConclusionThe rate of negative moods among college students is high, and the fear for COVID-19 is one of the key factors that lead to negative moods. Physical exercise can modulate the impact of COVID-19 fear among college students on negative moods. Studies should elucidate on mental health issues among different populations during the COVID-19 pandemic.

Summary: Background: The E2F family of transcription factors play a crucial role in the development of various cancers. However, E2F members lack targetable binding pockets and are typically considered “undruggable”. Unlike canonical small-molecule therapeutics, molecular glues mediate new E3 ligase–protein interactions to induce selective proteasomal degradation, which represents an attractive option to overcome these limitations. Methods: Human proteome microarray was utilized to identify a natural product-derived molecular glue for targeting E2F2 degradation. Co-IP analysis with stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics was carried out to further explore the E3 ligase for E2F2 degradation. Findings: In this study, we identified a molecular glue bufalin, which significantly promoted E2F2 degradation. Unexpectedly, E2F2 underwent ubiquitination and proteasomal degradation via a previously undisclosed atypical E3 ligase, zinc finger protein 91 (ZFP91). In particular, we observed that bufalin markedly promoted E2F2-ZFP91 complex formation, thereby leading to E2F2 polyubiquitination via K48-linked ubiquitin chains for degradation. E2F2 degradation subsequently caused transcriptional suppression of multiple oncogenes including c-Myc, CCNE1, CCNE2, MCM5 and CDK1, and inhibited hepatocellular carcinoma growth in vitro and in vivo. Interpretation: Collectively, our findings open up a new direction for transcription factors degradation by targeting atypical E3 ligase ZFP91. Meanwhile, the chemical knockdown strategy with molecular glue may promote innovative transcription factor degrader development in cancer therapy. Funding: This work was financially supported by the National Key Research and Development Project of China (2022YFC3501601), National Natural Sciences Foundation of China (81973505, 82174008, 82030114), and China Postdoctoral Science Foundation (2019M650396), the Fundamental Research Funds for the Central Universities.

Abstract Background We aimed to build a common terminology in the domain of cervical cancer, named Cervical Cancer Common Terminology (CCCT), that will facilitate clinical data exchange, ensure quality of data and support large scale data analysis. Methods The standard concepts and relations of CCCT were collected from ICD-10-CM Chinese Version, ICD-9-PC Chinese Version, officially issued commonly used Chinese clinical terms, Chinese guidelines for diagnosis and treatment of cervical cancer and Chinese medical book Lin Qiaozhi Gynecologic Oncology. 2062 cervical cancer electronic medical records (EMRs) from 16 hospitals, belong to different regions and hospital tiers, were collected for terminology enrichment and building common terms and relations. Concepts hierarchies, terms and relationships were built using Protégé. The performance of natural language processing results was evaluated by average precision, recall, and F1-score. The usability of CCCT were evaluated by terminology coverage. Results A total of 880 standard concepts, 1182 common terms, 16 relations and 6 attributes were defined in CCCT, which organized in 6 levels and 11 classes. Initial evaluation of the natural language processing results demonstrated average precision, recall, and F1-score percentages of 96%, 72.6%, and 88.5%. The average terminology coverage for three classes of terms, clinical manifestation, treatment, and pathology, were 87.22%, 92.63%, and 89.85%, respectively. Flexible Chinese expressions exist between regions, traditions, cultures, and language habits within the country, linguistic variations in different settings and diverse translation of introduced western language terms are the main reasons of uncovered terms. Conclusions Our study demonstrated the initial results of CCCT construction. This study is an ongoing work, with the update of medical knowledge, more standard clinical concepts will be added in, and with more EMRs to be collected and analyzed, the term coverage will be continuing improved. In the future, CCCT will effectively support clinical data analysis in large scale.

Abstract Background The high signal of paravertebral muscle (PVM) on T2-weighted image (T2WI) is usually considered to be fatty degeneration. However, it is difficult to distinguish inflammatory edema from fatty degeneration on T2WI. The purpose of this study was to identify different types of PVM high signal in patients with low back pain (LBP) through magnetic resonance imaging (MRI) and histology. Methods Seventy patients with LBP underwent MRI. The signal change of multifidus both on T2WI and fat suppression image (FSI) was quantified by Image J. Furthermore, 25 of the 70 patients underwent surgery for degenerative lumbar disease and their multifidus were obtained during the operation. Histological analysis of the samples was performed by HE staining. Result Three types of PVM signal changes were identified from the MRI. Type 1 (n = 36) indicated fatty degeneration characterized by a high signal on T2WI and low signal on FSI. High signal on both T2WI and FSI, signifying type 2 meant inflammatory edema (n = 9). Type 3 (n = 25) showed high signal on T2WI and partial signal suppression on FSI, which meant a combination of fatty degeneration and inflammatory edema. Histological results were consistent with MRI. Among the 25 patients who underwent surgery, type 1 (n = 14) showed adipocytes infiltration, type 2 (n = 3) showed inflammatory cells infiltration and type 3 (n = 8) showed adipocytes and inflammatory cells infiltration. Conclusion From our results, there are three types of pathological changes in patients with PVM degeneration, which may help to decide on targeted treatments for LBP.

Space-time shift keying (STSK) is a modulation scheme used in multi-input multi-output (MIMO) communication systems.It uses a pre-designed dispersion matrix set (DMS) to realize the flexible design of the system between multiplexing and diversity.An improved genetic algorithm (GA) was proposed to assist the joint optimization of DMS and 3D constellations, that is, the DMS and 3D constellations were jointly coded as the chromosome of GA , and the coding gain corresponding to the rank and determinant criterion was adopted as the overall fitness value.Through efficient selection and improved mutation and crossover strategies, DMS and 3D constellations with low bit error rate (BER) can be obtained.At the same time, the symmetry of the 3D constellation was used to greatly reduce the computational complexity of according to the fitness value the coding gain.The theoretical average paired error probability (ABEP) of the 3D STSK scheme was deducted.The simulation results show that, compared with the traditional GA and random search schemes, the improved GA proposed can significantly reduce the complexity of system implementation while ensuring BER performance.

While incomplete non-medical data has been integrated into prediction models for epidemics, the accuracy and the generalizability of the data are difficult to guarantee. To comprehensively evaluate the ability and applicability of using social media data to predict the development of COVID-19, a new confirmed case prediction algorithm improving the Google Flu Trends algorithm is established, called Weibo COVID-19 Trends (WCT), based on the post dataset generated by all users in Wuhan on Sina Weibo. A genetic algorithm is designed to select the keyword set for filtering COVID-19 related posts. WCT can constantly outperform the highest average test score in the training set between daily new confirmed case counts and the prediction results. It remains to produce the best prediction results among other algorithms when the number of forecast days increases from one to eight days with the highest correlation score from 0.98 (P ​< 0.01) to 0.86 (P ​< 0.01) during all analysis period. Additionally, WCT effectively improves the Google Flu Trends algorithm's shortcoming of overestimating the epidemic peak value. This study offers a highly adaptive approach for feature engineering of third-party data in epidemic prediction, providing useful insights for the prediction of newly emerging infectious diseases at an early stage.

Abstract Miscanthus spp. are increasingly cultivated in cropland worldwide due to their bioenergy potential and multiple ecological services. Effects of long‐term cropland‐to‐Miscanthus conversion without N fertilizer on soil microbiome and N cycling largely remain unknown. We aimed to explore the effects of Miscanthus conversion on soil microbiome and N cycling over a 15‐year period. We analyzed diversity, composition, and abundance of bacterial and archaeal communities using 16S rRNA amplicon sequencing, and abundances of N‐cycling‐related genes using quantitative polymerase chain reaction of 0–10 cm soils collected from bare land, cropland, 10‐year Miscanthus × giganteus, and 15‐year Miscanthus sacchriflorus land in Beijing. Conversion decreased soil sand and micro‐aggregate proportion, nitrate N (NiN), available phosphorus levels, conductivity, temperature, and pH, while increasing proportion of soil clay and macro‐aggregate (MAA), soil organic C (SOC), available N (AN), exchangeable Mg2+ (EMg2+), and available potassium (AK) contents as well as microbial C/N. Consequently, diversity, composition, and abundance of soil bacterial community exhibited larger changes than those values of archaeal community after conversion. Soil AP, EMg2+, AK, and SOC were key factors in shifting microbiome from the cropland to Miscanthus pattern. Moreover, abundances of bacterial and archaeal communities and the N fixer gene nifH increased, whereas that of the bacterial ammonia monooxygenase gene decreased. The copies of other N‐cycling‐related genes in the two Miscanthus lands seemed similar to those values of cropland. The nifH copies negatively correlated with soil NiN and positively correlated with AN, EMg2+, ECa2+, SOC, AK, and MAA. We conclude that changes in soil microbiome pattern induced by the variation of soil properties enhance microbial N fixation potential, maintaining stable N levels and robust N cycling with lower N leakage risk after conversion. These results should inspire farmers and governments to large‐scale use Miscanthus on marginal cropland in Northern China.

Stock movement prediction has received growing interest in the deep learning community. However, the generalization ability of some existing prediction models is weak due to the highly stochastic property of stock market, and some models suffer from the problem of gradient explosion or gradient vanishing in the training process. To solve the above issues, in this paper, we propose a novel stock movement prediction model based on gated orthogonal recurrent units (GORU) and variational auto-encoder (VAE). Specifically, GORU encodes the text information, and then VAE infers and decodes the market information formed by concatenating encoded text information with normalized historical price information. Meanwhile, orthogonality introduced by GORU can alleviate the problem of gradient explosion or gradient vanishing and enhance the generalization ability of the model. We evaluate the relative contributions of text information and historical prices with respect to prediction accuracy by the results of an ablation study. The experimental results on publicly available datasets show that the proposed model is better than several state-of-the-art models, which indicates that the GORU and VAE can effectively improve the model's generalization ability and accuracy for predicting stock trends.

Background: In the emergent situation of COVID-19, off-label therapies and newly developed vaccines may bring the patients more adverse drug event (ADE) risks. Data mining based on spontaneous reporting systems (SRSs) is a promising and efficient way to detect potential ADEs to help health professionals and patients get rid of the risk.Objective: This pharmacovigilance study aimed to investigate the ADEs of some attractive drugs (i.e., “hot drugs” in this study) in COVID-19 prevention and treatment based on the data from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS).Methods: The FAERS ADE reports associated with COVID-19 from the 2nd quarter of 2020 to the 2nd quarter of 2022 were retrieved with hot drugs and frequent ADEs were recognized. A combination of support, lower bound of 95% confidence interval (CI) of the proportional reporting ratio (PRR) was applied to detect significant hot drug and ADE signals by the Python programming language on the Jupyter notebook.Results: A total of 66,879 COVID-19 associated cases were retrieved with 22 hot drugs and 1,109 frequent ADEs on the “preferred term” (PT) level. The algorithm finally produced 992 significant ADE signals on the PT level among which unexpected signals such as “hypofibrinogenemia” of tocilizumab and “disease recurrence” of nirmatrelvir\ritonavir stood out. A picture of signals on the “system organ class” (SOC) level was also provided for a comprehensive understanding of these ADEs.Conclusion: Data mining is a promising and efficient way to assist pharmacovigilance work, and the result of this study could help timely recognize ADEs in the prevention and treatment of COVID-19.

Previous studies have shown that complement syntax is closely associated with false belief (FB) in children with autism spectrum disorder (ASD). However, the relationship between different types of complement syntax and FB remains unclear. This study examined the relationship between different types of complement syntax and FB in both ASD and typically developing (TD) children. Thirty Mandarin-speaking ASD and TD children, each matched for language ability, were included. Children completed different types of complement syntax tasks, verbal and nonverbal FB. For the ASD children, results demonstrated that sentential complement syntax independently predicted verbal and nonverbal FB, while phrasal complement syntax only predicted nonverbal FB. For the TD children group, sentential complement syntax only predicted verbal FB. This indicates that as the language demands of the FB task decrease, ASD children can use both types of complement syntax for its prediction. Moreover, the characteristics of ASD children differ from TD children in terms of the relationship between different types of complement syntax and FB. The results of this study support de Villiers’ point of view from the Mandarin perspective and provide evidence for the social-cognitive component of the theory of mind.

BackgroundHelicobacter pylori (H. pylori) eradication has been reported to cause short-term disruption of gut microbiota. It is acknowledged that probiotics supplementation mitigates side effects induced by H. pylori eradication, yet its role on alleviating dysbiosis of microbiota is obscure.ObjectivesTo evaluate the impact of probiotics on gastrointestinal microbiota after eradication therapy.MethodsThis was a multicenter, double-blinded, randomized trial done at seven centers in China. A total of 276 treatment-naïve H. pylori-positive patients were randomly assigned to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, furazolidone) combined with probiotics (Bifidobacterium Tetragenous viable Bacteria Tablets) (n=140) or placebo (n=136) for 28 days. Saliva, gastric mucosa and fecal samples were collected before and after therapy for 16S rRNA gene sequencing.ResultsThe incidence of gastrointestinal adverse events was lower in probiotics group compared to placebo group (23.6% vs 37.7%, p=0.016), while there was no significant difference in eradication rate. We found dramatic perturbations of gut microbiota immediately following eradication, with the predominance of Proteobacteria in replacement of commensal Firmicutes and Bacteroidetes, and gradually restored after two weeks. The reduction of gut Bacteroidetes caused by eradication drugs was neutralized with probiotics supplementation. The gastric microbiota was completely reconstituted with H. pylori depleted and other taxa flourished. Of note, patients treated with probiotics showed smaller fluctuations of gastric microbiota compared to those with placebo. We also observed changes of saliva microbiota after H. pylori eradication, illustrated by the overgrowth of Neisseria and depletion of Streptococcus. The expansion of some pathogenic genera, including Porphyromonas, Leptotrichia, in the mouth was suppressed by probiotics.ConclusionThis study not only demonstrated the beneficial effect of probiotics implementation on side events during H. pylori eradication but also provided a comprehensive profile of microbiome alterations along gastrointestinal tract that modulated by probiotics.

To explore the characteristics of kindergarten teachers’ occupational beliefs in China, 24 public and private kindergarten teachers were interviewed, their teaching was observed, and teaching reflection notes and educational essays were collected. A structural model was subsequently developed. Based on grounded theory, the information was coded at three levels and tested for theoretical saturation. The results demonstrated that the occupational beliefs of kindergarten teachers consisted of occupational cognition, occupational endurance, occupational expectation, and occupational intention, and these four core elements were not independent. Although there were characteristics common to public and private kindergarten teachers’ occupational beliefs, they also had distinct characteristics. The occupational beliefs of public kindergarten teachers were relatively stable, yet those of private kindergarten teachers were not. Moreover, most public kindergarten teachers were willing to stay in their teaching jobs. These findings reveal the composition and characteristics of Chinese kindergarten teachers’ occupational beliefs and the relationship between kindergarten teachers’ turnover and occupational beliefs.

Background: Hydrophilic dental implants are gaining increasing interest for their ability to accelerate bone formation. However, commercially available hydrophilic implants, such as SLActive™, have some major limitations due to their time-dependent biological aging and lower cost-effectiveness. The non-thermal atmospheric plasma (NTAP) treatment is a reliable way to gain a hydrophilic surface and enhance osseointegration. However, a few studies have been carried out to compare the osseointegration of NTAP-functionalized titanium implants and commercially available hydrophilic implants.Purpose: In this study, we compare the osseointegration abilities of the NTAP-functionalized titanium implant and Straumann SLActive.Material and methods: The NTAP effectiveness was examined using in vitro cell experiments. Then, six beagle dogs were included in the in vivo experiment. Straumann SLActive implants, SLA implants, and SLA implants treated with NTAP were implanted in the mandibular premolar area of dogs. After 2 w, 4 w, and 8 w, the animals were sacrificed and specimens were collected. Radiographic and histological analyses were used to measure osseointegration.Results: NTAP treatment accelerated the initial attachment and differentiation of MC3T3-E1 cells. In the in vivo experiment, bone parameters (e.g., BIC value and BV/TV) and volume of new bone of NTAP groups were close to those of the SLActive group. Additionally, although there was no statistical difference, the osseointegration of SLActive and NTAP groups was evidently superior to that of the SLA group.Conclusion: NTAP-functionalized implants enhanced cell interaction with material and subsequent bone formation. The osseointegration of the NTAP-functionalized implant was comparable to that of the SLActive implant at the early osseointegration stage.

D-Allose is a potential alternative to sucrose in the food industries and a useful additive for the healthcare products in the future. At present, the methods for large-scale production of D-allose are still under investigation, most of which are based on in vitro enzyme-catalyzed Izumoring epimerization. In contrast, fermentative synthesis of D-allose has never been reported, probably due to the absence of available natural microorganisms. In this work, we co-expressed D-galactose: H+ symporter (GalP), D-glucose isomerase (DGI), D-allulose 3-epimerase (DAE), and ribose-5-phosphate isomerase (RPI) in Escherichia coli, thereby constructing an in vivo Izumoring pathway for yielding D-allose from D-glucose. The carbon fluxes and carbon catabolite repression (CCR) were rationally regulated by knockout of FruA, PtsG, Glk, Mak, PfkA, and PfkB involved in the pathways capable of phosphorylating D-fructose, D-glucose, and fructose-6-phosphate. Moreover, the native D-allose transporter was damaged by inactivation of AlsB, thus driving the reversible Izumoring reactions towards the target product. Fermentation was performed in the M9 medium supplemented with glycerol as a carbon source and D-glucose as a substrate. The results show that the engineered E. coli cell factory was able to produce approximately 127.35 mg/L of D-allose after 84 h. Our achievements in the fermentative production of D-allose in this work may further promote the green manufacturing of rare sugars.

The roles and mechanisms of T-cell receptor (TCR)-associated transmembrane adaptor 1 (TRAT1) in lung adenocarcinoma (LAC) have not yet been reported in the relevant literature. Therefore, this study aimed to understand the roles and mechanisms of TRAT1 in LAC using bioinformatics and in vitro experiments. TRAT1 expression levels in LAC samples were analysed using various databases. TRAT1 co-expressed genes were acquired by the correlation analysis of LAC tissues. The functional mechanisms and protein network of TRAT1 co-expressed genes were analysed using bioinformatics analysis. The expression of TRAT1 was activated in LAC cells, and the roles of TRAT1 overexpression in the growth and migration of cancer cells was investigated using flow cytometry, Cell Counting Kit-8 (CCK-8), and migration and invasion assays. The relationship between TRAT1 overexpression, the immune microenvironment, and RNA modification was evaluated using correlation analysis. TRAT1 expression levels were significantly abnormal at multiple mutation sites and were related to the prognosis of LAC. TRAT1 co-expressed genes were involved in cell proliferation, adhesion, and differentiation, and TRAT1 overexpression significantly inhibited cell viability, migration, and invasion and promoted apoptosis of A549 and H1299 cells, which might be related to the TCR, B cell receptor (BCR), MAPK, and other pathways. TRAT1 expression levels were significantly correlated with the ESTIMATE, immune, and stromal scores in the LAC microenvironment. Additionally, TRAT1 expression levels were significantly correlated with the populations of B cells, CD8 T cells, cytotoxic cells, and other immune cells. TRAT1 overexpression was significantly correlated with the expression of immune cell markers (such as PDCD1, CD2, CD3E) and genes involved in RNA modification (such as ALKBH1, ALKBH3, ALKBH5). In conclusions, TRAT1 overexpression inhibited the growth and migration of LAC cells, thereby delaying cancer progression, and was correlated with the LAC microenvironment and RNA modifications.

ObjectiveElderly people are less likely than younger patients to undergo curative surgery for early-stage lung cancer because of the greater risk of surgery and postoperative complications. We investigated the relationship between treatment modality and the risk of all-cause and lung cancer-specific mortality to compare the efficacy of surgical treatment with radiotherapy in patients with stage I and II non-small cell lung cancer (NSCLC) who were ≥80 years old.MethodsWe extracted data from the most recent Surveillance, Epidemiology, and End Results 9 registry study database (2010–2017). We mainly selected patients with stage I and II NSCLC who were ≥80 years old, and after screening, 7,045 cases were selected for our study. We used univariate analysis, stratified analysis, and multiple regression equation analysis to examine all-cause mortality and lung cancer-specific mortality in different treatment modalities. The overall and stratified populations' survival curves were plotted using the Kaplan–Meier method. The competing risk regression method of Fine and Gray was used to estimate mortality specific to lung cancer.ResultsIn the fully adjusted model, all-cause mortality was 1.97 times higher in the radiotherapy-only group (hazard ration (HR) = 1.97, 95% confidence interval (CI) = 1.81–2.14, p

Osteosarcoma (OS) is one of the most prevalent primary bone tumors at all ages of human development. The objective of our study was to develop a model of Cuproptosis-Related Genes (CRGs) for predicting prognosis in OS patients. All datasets of OS patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and Gene Expression Omnibus (GEO) database. We obtained the gene set (81 CRGs) related to cuproptosis by accessing the database and previous literature. All the CRGs were analyzed by univariate COX regression, least absolute shrinkage and selection operator (LASSO) COX regression analysis to screen for CRGs associated with prognosis in OS patients. Then these CRGs were used to construct a prognostic signature, which was further verified by independent cohort (GSE21257) and clinical correlation analysis. Afterward, to identify underlying mechanisms, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for the high-risk group by using the GSEA method. The association between the prognostic signature and 28 types of immune infiltrating cells in the tumor microenvironment was assessed. Ultimately, Lipoic Acid Synthetase (LIAS) (HR=0.632, P=0.004), Lipoyltransferase 1 (LIPT1) (HR=0.524, P=0.011), BCL2 Like 1 (BCL2L1/BCL-XL) (HR=0.593, P=0.022), and Pyruvate Dehydrogenase Kinase 1 (PDK1) (HR=0.662, P=0.025) were identified. Subsequently, they were used to calculate the risk score and build a prognostic model. In the training cohort, risk score (HR=1.878, P=0.003) could be considered as an independent prognostic factor, and OS patients with high-risk scores showed lower survival rates. Biological pathways related to substance metabolism and transport were enriched. There were significant differences in immune infiltrating cells in the tumor microenvironment. All in all, The CRGs signature is related to the tumor immune microenvironment and could be used as a credible predictor of the prognostic status in OS patients.

Background: The serum albumin level is reflective of the function of multiple organs, such as the liver and kidneys. However, the association between serum albumin and pulmonary function is unclear; therefore, this study aimed to determine the relationship between pulmonary function and serum albumin, including the threshold of serum albumin at the changes of the pulmonary function in the total population and in different strata of population.Methods: In this cross-sectional study, We examined the relationship between serum albumin and two independent indicators of pulmonary function: forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1), using data from National Health and Nutrition Examination Survey (NHANES 2013–2014) (n = 3286). We used univariate analysis, stratified analysis, and multiple regression equation analysis to examine the correlation between serum albumin levels and FVC and FEV 1, and performed smoothed curve fitting, threshold effect, and saturation effect analysis (for stratification) to determine the threshold serum albumin level at which FVC and FEV 1 begin to change.Results: The adjusted smoothed curve fit plot showed a linear relationship between serum albu-min levels and FVC: for every 1 g/dl increase in the serum albumin level, FVC increased by 80.40 ml (11.18, 149.61). Serum albumin and FEV 1 showed a non-linear relationship. When serum al-bumin reached the inflection point (3.8 g/dl), FEV 1 increased with increasing serum albumin and the correlation coefficient β was 205.55 (140.15, 270.95).Conclusion: Serum albumin is a core indicator of liver function, and abnormal liver function has a direct impact on pulmonary function. In the total population, serum albumin levels were linearly and positively correlated with FVC. Above 3.6 g/dl, serum albumin was positively correlated with FEV 1. Based on the total population and different population strata, this study revealed a positive association between the serum albumin level and pulmonary function, and identified the threshold of serum albumin when Indicators of pulmonary function tests starts to rise, providing a new early warning indicator for people at high risk of pulmonary insufficiency and has positive implications for the prevention of combined respiratory failure in patients with liver insufficiency.

The halophyte Karelinia caspia has not only fodder and medical value but also can remediate saline-alkali soils. Our previous study showed that salt-secreting by salt glands is one of main adaptive strategies of K. caspia under high salinity. However, ROS scavenging, ion homeostasis, and photosynthetic characteristics responses to high salinity remain unclear in K. caspia. Here, physio-biochemical responses and gene expression associated with ROS scavenging and ions transport were tested in K. caspia subjected to 100–400 mM NaCl for 7 days. Results showed that both antioxidant enzymes (SOD, APX) activities and non-enzymatic antioxidants (chlorogenic acid, α-tocopherol, flavonoids, polyamines) contents were significantly enhanced, accompanied by up-regulating the related enzyme and non-enzymatic antioxidant synthesis gene (KcCu/Zn-SOD, KcAPX6, KcHCT, KcHPT1, Kcγ-TMT, KcF3H, KcSAMS and KcSMS) expression with increasing concentrations of NaCl. These responses are beneficial for removing excess ROS to maintain a stable level of H2O2 and O2− without lipid peroxidation in the K. caspia response to high salt. Meanwhile, up-regulating expression of KcSOS1/2/3, KcNHX1, and KcAVP was linked to Na+ compartmentalization into vacuoles or excretion through salt glands in K. caspia. Notably, salt can improve the function of PSII that facilitate net photosynthetic rates, which is helpful to growing normally in high saline. Overall, the findings suggested that ROS scavenging systems and Na+/K+ transport synergistically contributed to redox equilibrium, ion homeostasis, and the enhancement of PSII function, thereby conferring high salt tolerance.

The direct coal liquefaction process usually produces a liquefaction residue of about 30% of its coal feed. The effective utilization of the coal liquefaction residue (CLR), which contains about 80% organic matter, is of great significance for improving the oil yield of the direct liquefaction process and reducing the amount of pollution emitted from this oil-containing organic solid waste. In this study, the CLR fluidized bed pyrolysis process was studied through a fluidized bed reactor pyrolysis experiment and steady-state thermal analysis. The characteristics of CLR were first analyzed, and then the pyrolysis experiment was conducted in a fluidized bed reactor system. The experiment results show that the oil yield is 34.81% at 540°C for an ash-free feedstock using a fluidized bed pyrolysis reactor. Based on the pyrolysis experimental data and the Aspen Plus software platform, the fluidized bed pyrolysis reactor, fractionation column, coke burner, gasifier, and other equipment were modeled to compare four different process schemes. CLR pyrolysis is an endothermic reaction, and its heat is usually supplied by coke combustion, which produces significant CO2 emissions. Case studies of the pyrolysis process were performed in detail in order to reduce CO2 emissions. Thermal efficiency, carbon efficiency, solid waste discharge, and CO2 emissions of the different schemes were compared, and a flexible fluidized pyrolysis (FFP) process coupled with water electrolysis was proposed. The introduction of green hydrogen and green oxygen to the process can realize near-complete utilization of carbon and hydrogen elements in the CLR and produce high-quality liquid fuels and syngas (for further chemical synthesis), and this new process can achieve almost near-zero CO2 emission in the entire unit. This process principle can also be applied to the CO2 emission reduction of organic solid waste pyrolysis, catalytic fluid cracking, fluid coking, and so on.

This study described the natural circulation and heat transfer of a molten pool in a specifically designed core catcher conceived for a pressurized water reactor. In addition to external cooling, the core catcher features internal cooling tubes embedded in the molten pool. To investigate the coolability in such a configuration, first, a full-scale core catcher simulation is conducted to give a preliminary study under a real SA situation. Results illustrated that cooling efficiency can be remarkably enhanced due to the inner tubes. Then a test facility of the 2D slice with the geometrical scaled factor of 1:4 has been developed, and molten salt (NaNO3–KNO3) experiments will be implemented in the near future. This study also performed a pre-test simulation using molten NaNO3–KNO3 as a stimulant to study the heat transfer and flow characteristics of the salt pool. The melt convection in the test section was represented by a two-dimensional mesh with a WMLES turbulence model using the FLUENT code. The simulation captured the heat transfer enhancement by the cooling tubes as expected, and the results would help decide the proper test matrix and improvement of instrumentation required to obtain the necessary data for code validation.

Introduction: Epidermolysis bullosa (EB) is a skin fragility disorder that is caused by molecular aberrations in the epidermal basement membrane zone. Based primarily on the cleavage plane within the skin, EB is classified into four major subtypes: EB simplex; junctional EB (JEB); dystrophic EB; and Kindler EB. The junctional form (JEB) can lead to blistering and a variety of extracutaneous complications, including genitourinary tract involvement. Despite therapeutic progress, treatment modalities for urological complications of JEB are currently limited.Results: We present the case of a Chinese male with intermediate JEB and profound urinary tract stenosis. Due to the progression of the urinary tract stenosis, he presented with repeated urological symptoms, such as high frequency of urination, painful urination, and difficult voiding. After birth, multiple blisters on the fingers, feet, and limbs, as well as nail dystrophies and spare hair were noted. Mutation analysis revealed that the patient carried a homozygous frameshift mutation in the LAMB3 gene [c.1172_1179delinsTGTGTGTGCAAGGAG/p. (P391Lfs*23)]. After receiving treatment for urethral dilatation, lingual mucosa for anterior urethroplasty, and repair of urethral stricture using a ventral onlay penile skin flap, the patient still experienced a relapse of urinary tract stenosis. Finally, the patient underwent perineal urethrostomy. In contrast, his older brother with similar urological symptoms received regular urethral dilatation, and the curative effect was positive.Conclusion: Here we report on a case with a novel LAMB3 mutation that led to JEB with profound urinary tract stenosis, which has expanded our experience in the treatment of EB urological complications.

BackgroundCentral nervous system tumor (CNST) is one of the most complicated and lethal forms of human tumors with very limited treatment options. In recent years, growing evidence indicates that oncolytic virotherapy (OVT) has emerged as a promising therapeutic strategy for CNSTs. And a considerable amount of literature on OVT-CNSTs has been published. However, there are still no studies summarizing the global research trends and hotspots of this field through a bibliometric approach. To fulfill this knowledge gap, bibliometric analysis was conducted based on all publications relating to OVT-CNSTs since 2000s.MethodsWe searched the Web of Science Core Collection for all relevant studies published between 2000 and 2022. Four different tools (online analysis platform, R-bibliometrix, CiteSpace and VOSviewer) were used to perform bibliometric analysis and network visualization, including annual publication output, active journals, contribution of countries, institutions, and authors, references, as well as keywords.ResultsA total of 473 articles and reviews were included. The annual number of publications on OVT-CNSTs showed a significant increasing trend. Molecular Therapy and Cancer Research were the most active and co-cited journals, respectively. In terms of contributions, there is no doubt that the United States occupied a leading position with the most publications (n=307, 64.9%) and the highest H-index (57). The institution and author that contributed the largest number of publications were Ohio State University and Chiocca EA, respectively. As can be seen from citation analysis, the current studies mainly focused on preclinical and phase I/II clinical results of various oncolytic virus for CNSTs treatment. Keywords co-occurrence and burst analysis revealed that the following research topics including immunotherapy, T-cells, tumor microenvironment, vaccine, blood-brain-barrier, checkpoint inhibitors, macrophage, stem cell, and recurrent glioblastoma have been research frontiers of this field and also have great potential to continue to be research hotspots in the future.ConclusionThere has been increasing attention on oncolytic viruses for use as CNSTs therapeutics. Oncolytic immunotherapy is a topic of great concern in this field. This bibliometric study provides a comprehensive analysis of the knowledge base, research hotspots, development perspective in the field of OVT-CNSTs, which could become an essential reference for scholars in this area.

The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both periodontal diseases and respiratory diseases show high prevalence worldwide and have a marked influence on the quality of life for the patients. Accumulating studies are establishing a compelling association between periodontal diseases and respiratory diseases. Here, in this review, we specifically focus on the key periodontal pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum and dissect their roles in the onset and course of respiratory diseases, mainly pneumonia, chronic obstructive pulmonary disease, lung cancer, and asthma. The mechanistic underpinnings and molecular processes on how P. gingivalis and F. nucleatum contribute to the progression of related respiratory diseases are further summarized and analyzed, including: induction of mucus hypersecretion and chronic airway inflammation; cytotoxic effects to disrupt the morphology and function of respiratory epithelial cells; synergistic pathogenic effects with respiratory pathogens like Streptococcus pneumoniae and Pseudomonas aeruginosa. By delving into the complex relationship to periodontal diseases and periodontopathogens, this review helps unearth novel insights into the etiopathogenesis of respiratory diseases and inspires the development of potential therapeutic avenues and preventive strategies.

This study aims to investigate the critical state of the saddle-shaped unstable region of the axial-flow pump and propose a suitable criterion for identifying this state. The bifurcation SST k–ω model considered the rotation effect is used in the present work and verified in the numerical calculation of a water jet pump. Then, it is used to simulate the critical state of the axial-flow pump. Results show that the leading-edge separation vortex generates at 0.6Qd, while the head declines only at 0.55Qd. Therefore, using the inflection point of the head-flow curve as the critical state criterion is unsuitable. In addition, the fixed monitoring point is unsuitable for identifying the critical state due to the insensitivity to the amplitude, main frequency, and periodicity changes at the critical state. Finally, to identify the critical state, it is essential to arrange a monitoring point at the leading edge of the blade suction near the shroud, which should rotate with the impeller. The critical state criterion is that the main frequency position of the pressure fluctuation signal is offset at the monitoring point, and the amplitude is increased by 10 times.

In this paper, the spatial spectral characteristics of partial discharge (PD) under different electrode models are mainly studied. In the initial corona discharge stage, the emission spectrum is mainly emitted by the N2(C3IIu→B3IIg) energy level transition of the N2 second positive band system. The spectrum is in the ultraviolet range of 294–436 nm, and its main peak is at 337 nm. The streamer discharge stage spectrum is mainly emitted by the energy level transition of the second positive band system of N2, N+, NO, and O+ and the first positive band system of N2(B3IIg→A3Σu+). In the gap of different polarity electrodes, the ultraviolet spectrum content near the positive polarity is more abundant. The UV spectra ranges are 202–225 nm and 229–292 nm, respectively. The discharge of the needle–sphere system is more intense in visible light and near-infrared light, with peaks at 500 nm and 777 nm, respectively. In addition, the PD process based on the finite element method is simulated by COMSOL Multiphysics software. The simulation results show that the distribution of high-energy electron density varies with the electrode spacing and discharge model. The influence of particle energy level transition on the spatial spectral characteristics of PD is verified. This work provides important insights and possibilities for future fluorescent fiberoptic sensing and positioning for spatial PD detection and positioning using spectral characteristic peaks as detection quantities or excitations.

Abstract Background Systemic inflammation relates to the initiation and progression of acute respiratory distress syndrome (ARDS). Neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW)/albumin ratio have been reported to be predictive prognostic biomarkers in ARDS patients. However, the role of monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in a variety of diseases is rarely mentioned in ARDS. In this study, we explored the relationship between MLR and disease severity in ARDS patients and compared it with other indicators associated with 28-day mortality in patients with ARDS. Methods We retrospectively included 268 patients who fulfilled the Berlin definition of ARDS and were admitted to a single institute from 2016 to 2020. Clinical characteristics and experimental test data were collected from medical records within 24 h after the ARDS diagnosis. MLR, NLR, and RDW/albumin ratio levels were calculated. The primary clinical outcome was 28-day mortality. Logistic regression analysis was used to illustrate the relationship between indicators and 28-day mortality. Receiver operating characteristic (ROC) curve was used to evaluate the area under the curve (AUC), and propensity score matching (PSM) was employed to validate our findings. Results The median MLR values were higher for non-survivors than for survivors before and after matching (P

A high-accuracy source-independent radiometric calibration (SIRC) methodology with low complexity for both photoconductive and photovoltaic infrared photonic sensors is proposed to provide an easier SI-traceable way for global observation systems.

Background: Forkhead box F2, a member of the Forkhead box transcription factor superfamily, plays an important role in several types of cancer. However, the mechanisms of Forkhead box F2 in the progression of colorectal cancer remain unclear. PRUNE2 is closely associated with prostate cancer, neuroblastoma, glioblastoma, and melanoma. The relationship between Forkhead box F2 and PRUNE2 in colorectal cancer remains unknown. Method: We investigated the effects of Forkhead box F2 upregulation on colorectal cancer cell behavior in vitro using Cell Counting Kit-8, colony formation, flow cytometry, Transwell, reverse transcription quantitative polymerase chain reaction and Western blot analyses. Nude mouse xenografts were established to investigate the effect of Forkhead box F2 upregulation on the growth of colorectal cancer cells. Dual-luciferase reporter assays were performed to confirm the Forkhead box F2 regulation of PRUNE2 transcription. A series of in vitro assays was performed in cells with Forkhead box F2 upregulation and PRUNE2 knockdown to elucidate the function and regulatory effects of Forkhead box F2 on PRUNE2 transcription in colorectal cancer. Results: Forkhead box F2 was downregulated in colorectal cancer tissues compared with adjacent tissues. Forkhead box F2 overexpression significantly suppressed the proliferation and invasion of colorectal cancer cells in vitro and in vivo . Moreover, Forkhead box F2 directly targeted PRUNE2 to promote its transcription in colorectal cancer cells. Furthermore, PRUNE2 mediated the Forkhead box F2-regulated proliferation and invasion of colorectal cancer cells. Additionally, we demonstrated a significant positive correlation between Forkhead box F2 and PRUNE2 mRNA levels in colorectal cancer tissues. Conclusion: These results indicated that Forkhead box F2 and PRUNE2 in combination may serve as a prognostic biomarker for colorectal cancer and that Forkhead box F2 upregulation inhibits the proliferation and invasion of colorectal cancer cells by upregulating PRUNE2.

According to Hund’s multiplicity rule, the energy of the lowest excited triplet state (T1) is always lower than that of the lowest excited singlet state (S1) in organic molecules, resulting in a positive singlet-triplet energy gap (ΔEST). Therefore, the up-converted reverse intersystem crossing (RISC) from T1 to S1 is an endothermic process, which may lead to the quenching of long-lived triplet excitons in electroluminescence, and subsequently the reduction of device efficiency. Interestingly, organic molecules with inverted singlet-triplet (INVEST) gaps in violation of Hund’s multiplicity rule have recently come into the limelight. The unique feature has attracted extensive attention in the fields of organic optoelectronics and photocatalysis over the past few years. For an INVEST molecule possessing a higher T1 with respect to S1, namely a negative ΔEST, the down-converted RISC from T1 to S1 does not require thermal activation, which is possibly conducive to solving the problems of fast efficiency roll-off and short lifetime of organic light-emitting devices. By virtue of this property, INVEST molecules are recently regarded as a new generation of organic light-emitting materials. In this review, we briefly summarized the significant progress of INVEST molecules in both theoretical calculations and experimental studies, and put forward suggestions and expectations for future research.

In recent years, ferroptosis has become a research hotspot in programmed cell death. Since the concept of ferroptosis was proposed, a growing number of articles have been published on this topic. Nevertheless, to our knowledge, these ferroptosis-related publications that have received a great deal of attention have not been quantitatively evaluated. In this study, we analyzed the top 100 most influential articles over the past decade through a bibliometric method to characterize the research status and trends in this field. Web of Science Core Collection was searched to identify relevant studies. After being manually screened, the top 100 most cited studies with original data were identified and analyzed. Bibliometric software including VOSviewer and R-Bibliometrix were used to perform visualization analysis. The citation frequency for the top 100 selected articles ranged from 135 to 3603 (326.6 citations on average). These articles originated from 25 countries/regions, with more than half originating from the United States and China. The most frequently nominated author was Stockwell BR from the Columbia University, and of the top 100 articles, 19 listed his name. Three core journals were Nature, Cell and Proceedings of the National Academy of Sciences of the United States of America. In addition to term of ferroptosis, these terms or phrases including cell death, cancer cell, GPX4, pathway, inhibitor, mechanism, iron, lipid peroxidation, resistance, erastin, sorafenib, P53, reactive oxygen species, necroptosis, apoptosis, glutathione peroxidase, ACSL4, autophagy, and SLC7A11 appeared more frequently in the top 100 articles. Overall, although much progress has been made, the research on ferroptosis is still at an early stage. The current attention in this field mainly focuses on potential regulatory mechanism and pathways including key ferroptosis-related genes/molecules, oxidant and antioxidant system, ferroptosis-inducing agents or nanomedicine for cancer therapy, as well as the role of ferroptosis in non-neoplastic disorders. Meanwhile, combination therapeutic strategies targeting ferroptosis in radiotherapy or immunotherapy also deserve further attention.

Pipe vibration induced by water hammer frequently emerges in water conveyance system, especially in the hydropower plant or pumped storage power station with long diversion pipelines. This vibration in turn affects the hydraulic pulsation so that undesired fluid-structure interaction (FSI) arises. In this research, attention is given to a pipeline embedded in concrete. A six-equation model was derived to describe the fluid-pipe-concrete interaction considering Poisson coupling and junction coupling. With the elastic and homogeneous hypotheses, an iterative approach was proposed to solve this model, and the results were validated by experiment and classical water-hammer theory. Then dynamic FSI responses to water hammer were studied in a reservoir-pipe-valve physical system. Hydraulic pressure, pipe wall stress and axial motion were discussed with respect to different parameters of concrete. Results obtained by the two-equation model, four-equation model and six-equation model show characteristics of pressure wave and stress wave separately with and without FSI.

Extracellular vesicles from adipose-derived mesenchymal stem cells (ADSCs) play an important role in lymphangiogenesis; however, the underlying mechanisms are not fully understood. In this study, we aimed to investigate the function of extracellular vesicles secreted by hypoxia-conditioned ADSCs in lymphangiogenesis and explore the potential molecular mechanisms. Extracellular vesicles were extracted from ADSCs cultured under hypoxia or normoxia conditions. The uptake of extracellular vesicles by lymphatic endothelial cells (LECs) was detected by immunofluorescence staining. The effects of extracellular vesicles on the viability, migration, and tube formation of LECs were determined by CCK-8 assay, migration assay, and tube formation assay, respectively. Molecules and pathway involved in lymphangiogenesis mediated by ADSC-derived extracellular vesicles were analyzed by luciferase reporter assay, qRT-polymerase chain reaction (PCR), and Western blot. Hypoxia ADSC-derived extracellular vesicles (H-ADSC/evs) significantly enhanced the proliferation, migration, and tube formation of LECs. Hypoxia decreased the expression of miR-129 in ADSC-derived extracellular vesicles. Overexpression of miR-129 counteracted the promoting effect of H-ADSC/evs on lymphangiogenesis. In addition, decreased exosomal miR-129 expression resulted in upregulation of HMGB1 in LECs, which led to AKT activation and lymphangiogenesis enhancement. Our data reveal that extracellular vesicles derived from hypoxia-conditioned ADSCs induce lymphangiogenesis, and this effect is mediated by miR-129/HMGB1/AKT signaling. Our findings imply that hypoxia ADSC-isolated extracellular vesicles may represent as a valuable target for the treatment of diseases associated with lymphatic remodeling.

Introduction: The pathological rare category of thyroid is a type of lesion with a low incidence rate and is easily misdiagnosed in clinical practice, which directly affects a patient’s treatment decision. However, it has not been adequately investigated to recognize the rare, benign, and malignant categories of thyroid using the deep learning method and recommend the rare to pathologists.Methods: We present an empirical decision tree based on the binary classification results of the patch-based UNet model to predict rare categories and recommend annotated lesion areas to be rereviewed by pathologists.Results: Applying this framework to 1,374 whole-slide images (WSIs) of frozen sections from thyroid lesions, we obtained an area under a curve of 0.946 and 0.986 for the test datasets with and without WSIs, respectively, of rare types. However, the recognition error rate for the rare categories was significantly higher than that for the benign and malignant categories (p < 0.00001). For rare WSIs, the addition of the empirical decision tree obtained a recall rate and precision of 0.882 and 0.498, respectively; the rare types (only 33.4% of all WSIs) were further recommended to be rereviewed by pathologists. Additionally, we demonstrated that the performance of our framework was comparable to that of pathologists in clinical practice for the predicted benign and malignant sections.Conclusion: Our study provides a baseline for the recommendation of the uncertain predicted rare category to pathologists, offering potential feasibility for the improvement of pathologists’ work efficiency.

Exciplexes possessing thermally activated delayed fluorescence (TADF) characteristics have received much attention in the fields of organic light-emitting materials and devices over the past decade. In general, an exciplex is a physical mixture between a donor (D) with hole transport properties and an acceptor (A) with electron transport characteristics, and the energy difference between the lowest excited singlet state and the lowest excited triplet state is usually fairly small in terms of the long-range charge-transfer process from D to A. In the processes of photoluminescence and electroluminescence, triplet excitons can be converted to singlet excitons through reverse intersystem crossing and then radiate photons to achieve TADF. As a consequence, triplet excitons can be effectively harvested, and the exciton utilization can be significantly enhanced. Up to now, a large number of exciplexes have been developed and applied to organic light-emitting devices. Notably most of them showed green or red emission, while blue exciplexes are relatively few owing to the spectrum characteristics of the large red-shift and broadened emission. In this study, the latest progress of blue exciplex–based organic light-emitting materials and devices is briefly reviewed, and future research is prospected.

BackgroundDiabetes mellitus (DM) have become seriously threatens to human health and life quality worldwide. As a systemic metabolic disease, multiple studies have revealed that DM is related to metabolic bone diseases and always induces higher risk of fracture. In view of this, the links between bone metabolism (BM) and DM (BMDM) have gained much attention and numerous related papers have been published. Nevertheless, no prior studies have yet been performed to analyze the field of BMDM research through bibliometric approach. To fill this knowledge gap, we performed a comprehensive bibliometric analysis of the global scientific publications in this field.MethodsArticles and reviews regarding BMDM published between 2000 and 2021 were obtained from the Web of Science after manually screening. VOSviewer 1.6.16, CiteSpace V 5.8.R3, Bibliometrix, and two online analysis platforms were used to conduct the bibliometric and visualization analyses.ResultsA total of 2,525 documents including 2,255 articles and 270 reviews were retrieved. Our analysis demonstrated a steady increasing trend in the number of publications over the past 22 years (R2 = 0.989). The United States has occupied the leading position with the largest outputs and highest H-index. University of California San Francisco contributed the most publications, and Schwartz AV was the most influential author. Collaboration among institutions from different countries was relatively few. The journals that published the most BMDM-related papers were Bone and Osteoporosis International. Osteoporosis and related fractures are the main bone metabolic diseases of greatest concern in this field. According to co-cited references result, “high glucose environment,” “glycation end-product” and “sodium-glucose co-transporter” have been recognized as the current research focus in this domain. The keywords co-occurrence analysis indicated that “diabetic osteoporosis,” “osteoarthritis,” “fracture risk,” “meta-analysis,” “osteogenic differentiation,” “bone regeneration,” “osteogenesis,” and “trabecular bone score” might remain the research hotspots and frontiers in the near future.ConclusionAs a cross-discipline research field, the links between bone metabolism and diabetes mellitus are attracting increased attention. Osteoporosis and related fractures are the main bone metabolic diseases of greatest concern in this field. These insights may be helpful for clinicians to recognize diabetic osteopenia and provide more attention and support to such patients.

D-Allulose is an ultra-low calorie sweetener with broad market prospects. As an alternative to Izumoring, phosphorylation-dephosphorylation is a promising method for D-allulose synthesis due to its high conversion of substrate, which has been preliminarily attempted in enzymatic systems. However, in vitro phosphorylation-dephosphorylation requires polyphosphate as a phosphate donor and cannot completely deplete the substrate, which may limit its application in industry. Here, we designed and constructed a metabolic pathway in Escherichia coli for producing D-allulose from D-fructose via in vivo phosphorylation-dephosphorylation. PtsG-F and Mak were used to replace the fructose phosphotransferase systems (PTS) for uptake and phosphorylation of D-fructose to fructose-6-phosphate, which was then converted to D-allulose by AlsE and A6PP. The D-allulose titer reached 0.35 g/L and the yield was 0.16 g/g. Further block of the carbon flux into the Embden-Meyerhof-Parnas (EMP) pathway and introduction of an ATP regeneration system obviously improved fermentation performance, increasing the titer and yield of D-allulose to 1.23 g/L and 0.68 g/g, respectively. The E. coli cell factory cultured in M9 medium with glycerol as a carbon source achieved a D-allulose titer of ≈1.59 g/L and a yield of ≈0.72 g/g on D-fructose.