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Background: Drug-induced liver injury (DILI) is a leading cause of drug development failures during clinical trials and post-market introduction. Current biomarkers, such as ALT and AST, lack the necessary specificity and sensitivity needed for accurate detection. Exosomes, which protect LncRNAs from RNase degradation, could provide reliable and easily accessible options for biomarkers. Materials and methods: RNA-sequencing was used to identify differentially expressed LncRNAs (DE-LncRNAs), followed by isolation of LncRNAs from plasma exosomes in this study. Exosome characterization was conducted by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). Bioinformatics analysis included functional enrichment and co-expression network analysis. Five rat models were established, and quantitative real-time PCR was used to verify the specificity and sensitivity of two candidate exosomal LncRNAs. Results: The APAP-induced hepatocellular injury model was successfully established for RNA-sequencing, leading to the identification of several differentially expressed exosomal LncRNAs. Eight upregulated exosomal DE-LncRNAs were selected for validation. Among them, NONRATT018001.2 (p

Abstract Background Developmental dysplasia of the hip (DDH) is a common pediatric orthopedic condition characterized by varying degrees of acetabular dysplasia and hip dislocation. Current 2D imaging methods often fail to provide sufficient anatomical detail for effective treatment planning, leading to higher rates of misdiagnosis and missed diagnoses. MRI, with its advantages of being radiation-free, multi-planar, and containing more anatomical information, can provide the crucial morphological and volumetric data needed to evaluate DDH. However, manual techniques for measuring parameters like the center–edge angle (CEA) and acetabular index (AI) are time-consuming. Automating these processes is essential for accurate clinical assessments and personalized treatment strategies. Methods This study employed a U-Net-based CNN model to automate the segmentation of hip MRI images in children. The segmentation process was validated using a leave-one-out method during training. Subsequently, the segmented hip joint images were utilized in clinical settings to perform automated measurements of key angles: AI, femoral neck angle (FNA), and CEA. This automated approach aimed to replace manual measurements and provide an objective reference for clinical assessments. Results The U-Net-based network demonstrates high effectiveness in hip segmentation compared to manual radiologist segmentations. In test data, it achieves average DSC values of 0.9109 (acetabulum) and 0.9244 (proximal femur), with a 91.76% segmentation success rate. The average ASD values are 0.3160 mm (acetabulum) and 0.6395 mm (proximal femur) in test data, with Ground Truth (GT) edge points and predicted segmentation maps having a mean distance of less than 1 mm. Using automated segmentation models for clinical hip angle measurements (CEA, AI, FNA) shows no statistical difference compared to manual measurements (p > 0.05). Conclusion Utilizing U-Net-based image segmentation and automated measurement of morphological parameters significantly enhances the accuracy and efficiency of DDH assessment. These methods improve precision in automatic measurements and provide an objective basis for clinical diagnosis and treatment of DDH.

Normal dynamic mechanical characteristics of the jointed rock mass are of great significance for studying the working state of rock mass with nonpersistent joint. In this paper, combined with the joint normal deformation theory, the rock-like materials with penetration along different normal directions were analyzed under impact tests of different weights and heights. The experimental results show that under the same impact conditions, as the joint penetration length L increases from 0 to 100 mm, the peak load and joint stiffness of the rock mass joint specimen gradually decrease during the impact process, and the normal dynamic compression displacement and the normal closure of the rock mass joint gradually increase. The energy dissipation gradually decreases at the impact heights of 500, 1000, and 1500 mm. When the impact height is 2000 mm, the energy dissipation first increases and then decreases. Under the action of cyclic impact, the crack propagation path of jointed rock mass specimens is that the cracks originate at the loading place and develop to the joint surface and then spread to the weak joint end to form 90° wing cracks. The crack width, propagation scale, and damage degree gradually expand with the increase in joint penetration length L.

Abstract Background Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets. Methods By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST. Results In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P

Abstract We aimed to analyze the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis for cT1-2 breast cancer patients with positivity after sentinel lymph node biopsy (SLNB). A total of 830 breast cancer patients who underwent surgery between 2016 and 2021 at multi-center were included in the retrospective analysis. Patients were divided into training (n = 410), internal validation (n = 298), and external validation cohorts (n = 122) based on periods and centers. A nomogram-based prediction model for the risk of NSLN metastasis was constructed by incorporating independent predictors of NSLN metastasis identified through univariate and multivariate logistic regression analyses in the training cohort and then validated by validation cohorts. The multivariate logistic regression analysis revealed that the number of positive sentinel lymph nodes (SLNs) (P

Introduction: Early risk assessment studies usually based on total heavy metal (loid) contents, inevitably leading to an overestimation of the health risks. In addition, inputs are represented as single-point estimates in deterministic models, leading to underestimation or overestimation of the health risks.Methods: To overcome these barriers, a novel probabilistic risk assessment strategy based on the combinational use of bioaccessibility and Monte Carlo simulation was developed to assess heavy metal (loid) associated health risks of earthworms in this study. To obtain a realistic and robust probabilistic risk assessment, heavy metal (loid) exposure duration and frequency were determined using our questionnaire data.Results: As a result, the mean gastrointestinal bioaccessibility was in the order: Cd > As > Cu > Hg. The mean hazard index (HI) values for investigated metal (loid)s were 0.65 and 0.59 for male and female, respectively, demonstrating an acceptable health risk in an average community. However, the 90th percentile of HI values was 1.87 and 1.65 for male and female, respectively. And the total non-cancer risks of heavy metal (loid) exposure exceeded the acceptable threshold for 19.9% and 17.8% of male and female, respectively. In addition, the total cancer risk (TCR) value through co-exposure to As and Cd suggested that the carcinogenic risks may be of concern for average exposure population. Sensitivity analyses revealed that the exposure frequency and bioaccessible As concentration were the dominant contributors to the total risk variance, which provided meaningful implications for environmental management.Conclusion: Altogether, the refined strategy based on bioaccessibility and Monte Carlo simulation is the first of its kind, such effort attempts to scientifically guide the rational clinic use of TCM and the improvement of population-health.

Abstract Background Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM. Methods Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention. Results Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1β, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway. Conclusions AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.

Abstract Background Self-management (SM) is the key factor in controlling the progression of chronic obstructive pulmonary disease (COPD). Previous studies have reported that majority of COPD patients later presented with frailty and mental health diseases, which affect self-management. This study attempted to explore the mediation role of depression and frailty between social support and self-management in elderly COPD population. Methods Six hundred twenty-seven stable elderly COPD patients admitted to 5 public hospitals in Ningxia, China were selected as study subjects by convenience sampling method. Self-management, frailty, depression and social support were assessed using the COPD Self-management Scale (COPD-SMS), Frail Scale (FS), 15-item Geriatric Depression Scale (GDS-15), and Social Support Rating Scale (SSRS) respectively. The Pearson correlation analysis was used to assess the correlation between variables. Additionally, SPSS25.0 PROCESS plugin Model 6 was used to explore the mediating effects of frailty and depression in the relationship between social support and self-management. Results The mean participant age was 72.87 ± 7.03 years, 60.4% of participants were male. The mean total score of the COPD-SMS was 156.99 ± 25.15. Scores for the SSRS, FS, and GDS-15 were significantly correlated with COPD-SMS (p

Abstract Neuroblastoma (NB) is a challenging pediatric extracranial solid tumor characterized by a poor prognosis and resistance to chemotherapy. Identifying targets to enhance chemotherapy sensitivity in NB is of utmost importance. Increasing evidence implicates long noncoding RNAs (lncRNAs) play important roles in cancer, but their functional roles remain largely unexplored. Here, we analyzed our RNA sequencing data and identified the upregulated lncRNA ZNF674-AS1 in chemotherapy non-responsive NB patients. Elevated ZNF674-AS1 expression is associated with poor prognosis and high-risk NB. Importantly, targeting ZNF674-AS1 expression in NB cells suppressed tumor growth in vivo. Further functional studies have revealed that ZNF674-AS1 constrains cisplatin sensitivity by suppressing pyroptosis and promoting cell proliferation. Moreover, ZNF674-AS1 primarily relies on CA9 to fulfill its functions on cisplatin resistance. High CA9 levels were associated with high-risk NB and predicted poor patient outcomes. Mechanistically, ZNF674-AS1 directly interacted with the RNA binding protein IGF2BP3 to enhance the stability of CA9 mRNA by binding with CA9 transcript, leading to elevated CA9 expression. As a novel regulator of CA9, IGF2BP3 positively upregulated CA9 expression. Together, these results expand our understanding of the cancer-associated function of lncRNAs, highlighting the ZNF674-AS1/IGF2BP3/CA9 axis as a constituting regulatory mode in NB tumor growth and cisplatin resistance. These insights reveal the pivotal role of ZNF674-AS1 inhibition in recovering cisplatin sensitivity, thus providing potential therapeutic targets for NB treatment.

In recent years, significant breakthroughs have been made in the field of gene therapy. Adeno-associated virus (AAV) is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of interest. Among the AAV vectors, AAV serotype 8 (AAV8) has attracted much attention for its efficient and stable gene transfection into specific tissues. Currently, recombinant AAV8 has been widely used in gene therapy research on a variety of diseases, including genetic diseases, cancers, autoimmune diseases, and viral diseases. This paper reviewed the applications and challenges of using AAV8 as a vector for gene therapy, with the aim of providing a valuable resource for those pursuing the application of viral vectors in gene therapy.

In the intricate and dynamic infrared imaging environment, the detection of infrared dim and small targets becomes notably challenging due to their feeble radiation intensity, intricate background noise, and high interference characteristics. To tackle this issue, this paper introduces a lightweight detection and recognition algorithm, named YOLOv5-IR, and further presents an even more lightweight version, YOLOv5-IRL. Firstly, a lightweight network structure incorporating spatial and channel attention mechanisms is proposed. Secondly, a detection head equipped with an attention mechanism is designed to intensify focus on small target information. Lastly, an adaptive weighted loss function is devised to improve detection performance for low-quality samples. Building upon these advancements, the network size can be further compressed to create the more lightweight YOLOv5-IRL version, which is better suited for deployment on resource-constrained mobile platforms. Experimental results on infrared dim and small target detection datasets with complex backgrounds indicate that, compared to the baseline model YOLOv5, the proposed YOLOv5-IR and YOLOv5-IRL detection algorithms reduce model parameter counts by 42.9% and 45.6%, shorten detection time by 13.6% and 16.9%, and enhance mAP0.5 by 2.4% and 1.8%, respectively. These findings demonstrate that the proposed algorithms effectively elevate detection efficiency, meeting future demands for infrared dim and small target detection.

Background: The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. Methods: Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56bright, and CD56dim NK cell subsets after in vitro stimulation. Results: The frequencies of TIGIT+ cells in total NK, CD56bright, and CD56dim NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT+ cells than the corresponding TIGIT− cells in all HDs, whereas those for TIGIT+ to TIGIT− cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients’ TIGIT+ NK cells displayed lower K562 cell-killing activity than their TIGIT− NK cells. In addition, high frequencies of TIGIT+ cells in total NK and CD56dim NK cells were associated with poor RFS. Conclusions: TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32–72.49% and 4.98–51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were

C17H18F6N6O, monoclinic, P21/n (no. 14), a = 9.9491(11) Å, b = 18.1523(17) Å, c = 11.7703(15) Å, β = 113.473(14)°, V = 1949.8(4) Å3, Z = 4, Rgt(F) = 0.0606, wRref(F2) = 0.1876, T = 169.99(10) K.

Objectives: This study seeks to investigate the willingness of medical professionals to embrace training in sports medicine integrated talents, as well as the factors that influence their decision-making process. By utilizing technology acceptance models, the objective is to gain a comprehensive understanding of this phenomenon and provide valuable recommendations to facilitate the development of proficient integration of sports and medicine (ISM) talents. Methods: The questionnaire was developed through a comprehensive review of relevant literature and consultation with experts in the field. A cluster sampling method was employed to select medical professionals from various medical institutions in Guangxi Zhuang Autonomous Region (Guangxi) who had participated in ISM talent training. The collected data were analyzed using the AMOS structural equation model, ensuring a rigorous and systematic approach to data analysis. Results: A total of 403 questionnaires were collected in this survey, and 8 out of the 9 research hypotheses formulated for the model variables were found to be supported. Perceived usefulness, perceived ease of use, subjective norm and training satisfaction were identified as significant factors influencing the behavioral intention of medical professionals to engage in ISM talent training (P

This paper aims to introduce a new approach to enhance college English learning through an intelligent method that constructs a learning environment from a demand analysis perspective. The proposed model utilizes a bionic algorithm to structure the algorithm and adopts a highly efficient energy generation method to calculate the interaction energy. This study aims to find the optimal solution to the constraint problem by using a process of continuous generation, expansion, and replacement of magnetosomes. The methodology employed in this research involved constructing the college English learning environment in colleges and universities from a demand analysis perspective. This was achieved by analyzing the needs and requirements of college students and designing an ecological virtual learning environment (EVLE) that meets their demands. The findings of this study indicate that the proposed EVLE for college English is effective in improving the effectiveness of college English learning. The experimental verification results support the effectiveness of the proposed model in creating an interactive and engaging learning environment that facilitates the acquisition of English language skills. It is an innovative approach to college English learning that utilizes intelligent methods to construct a demand-driven learning environment that enhances students’ learning outcomes.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and irreversible airflow obstruction with abnormal lung function. Because its pathogenesis involves multiple aspects of oxidative stress, immunity and inflammation, apoptosis, airway and lung repair and destruction, the clinical approach to COPD treatment is not further updated. Therefore, it is crucial to discover a new means of COPD diagnosis and treatment. COPD etiology is associated with complex interactions between environmental and genetic determinants. Numerous genes are involved in the pathogenic process of this illness in research samples exposed to hazardous environmental conditions. Among them, Long non-coding RNAs (lncRNAs) have been reported to be involved in the molecular mechanisms of COPD development induced by different environmental exposures and genetic susceptibility encounters, and some potential lncRNA biomarkers have been identified as early diagnostic, disease course determination, and therapeutic targets for COPD. In this review, we summarize the expression profiles of the reported lncRNAs that have been reported in COPD studies related to environmental risk factors such as smoking and air pollution exposure and provided an overview of the roles of those lncRNAs in the pathogenesis of the disease.

Background: Magnetoencephalography (MEG) is a non-invasive imaging technique for directly measuring the external magnetic field generated from synchronously activated pyramidal neurons in the brain. The optically pumped magnetometer (OPM) is known for its less expensive, non-cryogenic, movable and user-friendly custom-design provides the potential for a change in functional neuroimaging based on MEG. Methods: An array of OPMs covering the opposite sides of a subject’s head is placed inside a magnetically shielded room (MSR) and responses evoked from the auditory cortices are measured. Results: High signal-to-noise ratio auditory evoked response fields (AEFs) were detected by a wearable OPM-MEG system in a MSR, for which a flexible helmet was specially designed to minimize the sensor-to-head distance, along with a set of bi-planar coils developed for background field and gradient nulling. Neuronal current sources activated in AEF experiments were localized and the auditory cortices showed the highest activities. Performance of the hybrid optically pumped magnetometer-magnetoencephalography/electroencephalography (OPM-MEG/EEG) system was also assessed. Conclusions: The multi-channel OPM-MEG system performs well in a custom built MSR equipped with bi-planar coils and detects human AEFs with a flexible helmet. Moreover, the similarities and differences of auditory evoked potentials (AEPs) and AEFs are discussed, while the operation of OPM-MEG sensors in conjunction with EEG electrodes provides an encouraging combination for the exploration of hybrid OPM-MEG/EEG systems.

Pediatric tuberculosis (TB) is a serious infectious disease that affects many children worldwide and is more likely to be extrapulmonary than adult TB. However, the clinical and epidemiological profile, and cost burden of pediatric extrapulmonary TB (EPTB) in China remain unknown. Here, we conducted a descriptive, multicenter study of pediatric TB patients from 22 hospitals across all six regions in China from October 2015 to December 2018. Of 4,654 patients, 54.23% (2,524) had pulmonary TB (PTB), 17.76% (827) had EPTB, and 28.00% (1,303) had concurrent extrapulmonary and pulmonary TB (combined TB). Compared with PTB, EPTB and combined TB were associated with lower hospitalization frequency (2.43 and 2.21 vs. 3.16 times), longer length of stay (10.61 and 11.27 vs. 8.56 days), and higher rate of discharge against medical advice (8.46% and 9.44% vs. 5.67%). EPTB was associated with higher mortality (0.97% vs. 0.24% and 0.31%), higher rate of low birth weight (17.69% vs. 6.79% and 6.22%), worse diagnosis at the first visit (21.16% vs. 34.67% and 44.47%), and worse hospitalization plan situation (4.35% vs. 7.81% and 7.44%), compared with PTB and combined TB. EPTB and combined TB had higher financial burdens (17.67% and 16.94% vs. 13.30%) and higher rates of catastrophic expenditure (8.22% and 9.59% vs. 5.03%), compared with PTB. Meningitis TB (34.18%) was the most frequent form of total extrapulmonary infection and had the highest cost burden and rate of catastrophic expenditure. In conclusion, improved screening approaches for pediatric EPTB are needed to reduce diagnostic challenges and financial burden.

Abstract The coronavirus disease 2019 (COVID-19) pandemic has devastated global health. Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks. Here, we have identified host proteins that associate with nonstructural protein 12 (nsp12), the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 using a mass spectrometry (MS)-based proteomic approach. Among the candidate factors, CDK2 (Cyclin-dependent kinase 2), a member of cyclin-dependent kinases, interacts with nsp12 and causes its phosphorylation at T20, thus facilitating the assembly of the RdRp complex consisting of nsp12, nsp7 and nsp8 and promoting efficient synthesis of viral RNA. The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection. Taken together, we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex, thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors.

Abstract Background Ventilator-associated pneumonia (VAP) is one of the most common intensive care unit (ICU)-acquired infections, which can cause multiple adverse events. Due to bacterial mutation and overuse of antimicrobial drugs, multidrug-resistant organisms (MDRO) has become one of the major causes of postoperative VAP infections in cardiac patients. Therefore, this study aims to explore the risk factors for VAP with MDRO following cardiac surgery in adults. Methods The clinical data of adult VAP patients following cardiac surgery in the hospital from Jan 2017 to May 2021 were analyzed retrospectively, and the patients were divided into the MDRO VAP group and the non-MDRO VAP group. Univariable and multivariable logistic regression analyses were performed on risk factors in patients with MDRO VAP. The species and drug sensitivity of pathogens isolated from the VAP patients were also analyzed. Results A total of 61 VAP cases were involved in this study, with 34 cases in the MDRO VAP group (55.7%) and 27 cases in the non-MDRO VAP group (44.3%). Multivariable logistic regression analysis showed that independent risk factors for MDRO VAP included preoperative creatinine clearance rate (CCR) ≥ 86.6ml, intraoperative cardiopulmonary bypass (CPB) time ≥ 151 min, postoperative acute kidney injury (AKI) and nasal feeding. Gram-negative bacilli were the main pathogens in VAP patients (n = 54, 90.0%), with the highest rate of Acinetobacter baumannii (n = 24, 40.0%). Additionally, patients with MDRO VAP had a significantly longer postoperative intensive care unit (ICU) duration and higher hospitalization costs than non-MDRO VAP patients, but there was no notable difference in the 28-day mortality rate between the two groups. Conclusion Based on implementing measures to prevent VAP, clinicians should pay more attention to patients with kidney disease, longer intraoperative CPB time, and postoperative nasal feeding to avoid MDRO infections.

Background: To investigate the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy on brain glucose metabolism in patients with diffuse large B cell lymphoma (DLBCL). Methods: Seventy-two patients with newly diagnosed DLBCL underwent FDG PET/CT brain and whole-body scans at baseline (PET0), in the interim of chemotherapy (PET2), and at the end (PET6) of chemotherapy. All three brain scans of each patient were analyzed using statistical parametric mapping software. Results: Compared with the PET0 scan, the PET2 and PET6 scans revealed a significantly higher glucose metabolism throughout the whole brain, with the PET6 scan revealing a higher metabolism than the PET2 scan. Patients with a complete response (CR) displayed decreased glucose metabolism in the lingual gyrus and increased glucose metabolism in the pons after chemotherapy compared with the findings in patients with partial responses or progressive disease. Conclusions: Brain glucose metabolism was affected by R-CHOP treatment throughout the entire chemotherapy protocol.

ObjectiveSpinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a rare neurodegenerative disease for which there is no specific treatment. Very few cases have been treated with single-target deep brain stimulation (DBS), and the results were not satisfactory. We applied multi-target DBS to an SCA3/MJD patient and performed positron emission computed tomography (PET) before and after DBS to explore the short-term clinical therapeutic effect.Materials and methodsA 26-year-old right-hand-dominant female with a family history of SCA3/MJD suffered from cerebellar ataxia and dystonia. Genetic testing indicated an expanded CAG trinucleotide repeat in the ATXN3 gene and a diagnosis of SCA3/MJD. Conservative treatment had no obvious effect; therefore, leads were implanted in the bilateral dentate nucleus (DN) and the globus pallidus internus (GPi) and connected to an external stimulation device. The treatment effect was evaluated in a double-blind, randomized protocol in five phases (over a total of 15 days): no stimulation, GPi, DN, or sham stimulation, and combined GPi and DN stimulation. 18F-fluoro-2-deoxy-d-glucose and dopamine transporter PET, Scale for the Assessment and Rating of Ataxia, Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and SF-36 quality of life scores were compared before and after DBS.ResultsThe Total Scale for the Assessment and Rating of Ataxia scores improved by ~42% (from 24 to 14). The BFMDRS movement scores improved by ~30% (from 40.5 to 28.5). The BFMDRS disability scores improved by ~12.5% (from 16 to 14). Daily living activities were not noticeably improved. Compared with the findings in pre-DBS imaging, 18F-fluoro-2-deoxy-d-glucose uptake increased in the cerebellum, while according to dopamine transporter imaging, there were no significant differences in the bilateral caudate nucleus and putamen.ConclusionMulti-target acute stimulation (DN DBS and GPi DBS) in SCA3/MJD can mildly improve cerebellar ataxia and dystonia and increase cerebellar metabolism.

Magnetoencephalography is a non-invasive technology for brain function imaging, which is of enormous value to brain science research and clinical application due to its ultra-high temporal and spatial trace resolution. In this paper, we introduce a self-built and atomic magnetometer based wearable magnetoencephalography system. By designing bi-planar coils system and combining with reference sensor array, the residual magnetic field in the subject's head movement area is controlled to be within ±1 nT, which ensures the sensors are maintained within their dynamic range during the moving measurement. At the same time, a virtual gradiometer-based noise reduction method is proposed to suppress the common-mode magnetic-field noise. Finally, the alpha rhythm and auditory evoked magnetic field signals with high signal-to-noise ratio are successfully detected under the subject's natural head movement and the effectiveness of the system is confirmed. This study could provide more possibilities for the application and promotion of moving wearable magnetoencephalography.

Abstract Objective To investigate the circumstances that lead to acute exacerbation readmission of elderly patients with chronic obstructive pulmonary disease (COPD) within 30 days and to explore the influencing factors of readmission using a structural equation model to provide evidence for medical staff so that effective intervention measures can be taken. Methods The convenience sampling method was used to select 1120 elderly patients with COPD from the respiratory departments of thirteen general hospitals in the Ningxia region, China, from April 2019 to August 2020, who then completed a survey questionnaire. The survey questionnaire contained a general data questionnaire and the modified Medical Research Council, activities of daily living, geriatric depression scale and COPD assessment test scales. Results The readmission rate of patients with COPD presenting with acute exacerbation within 30 days was determined to be 21.52%. Therefore, the modified model measures data accurately. The results showed that seasonal factors, family rehabilitation, age factors and overall health status were direct factors in the acute exacerbation readmission of patients with COPD within 30 days of hospital discharge. Smoking is not only a direct factor for acute exacerbation readmission within 30 days but also an indirect factor through disease status; disease status and chronic disease are not only direct factors for acute exacerbation readmission within 30 days but also indirect factors through the patient’s overall health status. Conclusions The rate of patients with COPD presenting with acute exacerbation within 30 days is high; while taking measures to prevent readmission based on influencing factors that directly impact admission rates, attention should also be paid to the interaction between these factors.

Abstract Background Salmonella is a common foodborne pathogen, which can cause intestinal diseases. In the last decades, the overuse of antibiotics has led to a pandemic of drug-resistant bacterial infections. To tackle the burden of antimicrobial resistant pathogens, it is necessary to develop new antimicrobial drugs with novel modes of action. However, the research and development of antibiotics has encountered bottlenecks, scientific hurdles in the development process, as well as safety and cost challenges. Phages and phage endolysins are promising antibacterial agents that can be used as an alternative to antibiotics. In this context, the expression of endolysin derived from different phages through microbial cells as a chassis seems to be an attractive strategy. Results In this study, a new endolysin from the Salmonella phage XFII-1, named XFII, was screened and obtained. The endolysin yield exceeded 100 mg/mL by heterologous expression from E. coli BL21 and short induction. The endolysin XFII exhibited high bactericidal activity at a concentration of 0.5 μg/mL and reduced the OD600 nm of EDTA-pretreated E. coli JM109 from 0.8 to 0.2 within 5 min. XFII exhibited good thermo-resistance, as it was very stable at different temperatures from 20 to 80℃. Its bactericidal activity could keep constant at 4 °C for 175 days. In addition, the endolysin was able to exert lytic activity in eutrophic conditions, including LB medium and rabbit serum, and the lytic activity was even increased by 13.8% in 10% serum matrices. XFII also showed bactericidal activity against many Gram-negative bacteria, including Salmonella, E. coli, Acinetobacter baumannii, and Klebsiella pneumoniae. Surprisingly, the combination of endolysin XFII and chitosan showed a strong synergy in lysing E. coli and Salmonella without EDTA-pretreatment, and the OD600 nm of E. coli decreased from 0.88 to 0.58 within 10 min. Conclusions The novel globular endolysin XFII was screened and successfully expressed in E. coli BL21. Endolysin XFII exhibits a broad lysis spectrum, a rapid and strong bactericidal activity, good stability at high temperatures and under eutrophic conditions. Combined with chitosan, XFII could spontaneously lyse Gram-negative bacteria without pretreatment. This work presented the first characterization of combining endolysin and chitosan in spontaneously lysing Gram-negative bacteria in vitro.

To explore the strength characteristics of anisotropic rocks caused by mineral directional arrangement during progressive failure process, biotite quartz schist was taken as an example, and triaxial compression tests were carried out on samples with schistosity angles of 0°, 45° and 90°. The macro and micro failure characteristics and progressive failure strength index of the specimens were analyzed, and the differences with other types of anisotropic rock were discussed. The results show that the failure characteristics of biotite quartz schist are closely related to its schistosity. With the schistosity angle increasing from 0° to 90°, the main macro and micro fracture modes of the specimens change from tensile to shear, and then to co-existence of tensile and shear. The strength characteristic values of biotite quartz schist show significant anisotropy. With the increase of schistosity angle, the strengthening effect caused by confining pressure increase on the strength characteristic values weakens, but the change of the strength value has a trend of acceleration. The anisotropic variation law of the ratio of strength characteristic value is not obvious, which gradually weakens and even disappears under high confining pressure. The fracture modes, variations of strength characteristic values and their ratios of anisotropic rocks with directional arrangement of minerals are different from those of rocks with stratified structure. A thorough understanding of the mechanical properties of rocks with directional arrangement of minerals will be helpful to guide the related engineering practice.

Abstract Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) is an important event in the process of disease management. Early identification of high-risk groups for readmission and appropriate measures can avoid readmission in some groups, but there is still a lack of specific prediction tools. The predictive performance of the model built by support vector machine (SVM) has been gradually recognized by the medical field. This study intends to predict the risk of acute exacerbation of readmission in elderly COPD patients within 30 days by SVM, in order to provide scientific basis for screening and prevention of high-risk patients with readmission. Methods A total of 1058 elderly COPD patients from the respiratory department of 13 general hospitals in Ningxia region of China from April 2019 to August 2020 were selected as the study subjects by convenience sampling method, and were followed up to 30 days after discharge. Discuss the influencing factors of patient readmission, and built four kernel function models of Linear-SVM, Polynomial-SVM, Sigmoid-SVM and RBF-SVM based on the influencing factors. According to the ratio of training set and test set 7:3, they are divided into training set samples and test set samples, Analyze and Compare the prediction efficiency of the four kernel functions by the precision, recall, accuracy, F1 index and area under the ROC curve (AUC). Results Education level, smoking status, coronary heart disease, hospitalization times of acute exacerbation of COPD in the past 1 year, whether long-term home oxygen therapy, whether regular medication, nutritional status and seasonal factors were the influencing factors for readmission. The training set shows that Linear-SVM, Polynomial-SVM, Sigmoid-SVM and RBF-SVM precision respectively were 69.89, 78.07, 79.37 and 84.21; Recall respectively were 50.78, 69.53, 78.74 and 88.19; Accuracy respectively were 83.92, 88.69, 90.81 and 93.82; F1 index respectively were 0.59, 0.74, 0.79 and 0.86; AUC were 0.722, 0.819, 0.866 and 0.918. Test set precision respectively were86.36, 87.50, 80.77 and 88.24; Recall respectively were51.35, 75.68, 56.76 and 81.08; Accuracy respectively were 85.11, 90.78, 85.11 and 92.20; F1 index respectively were 0.64, 0.81, 0.67 and 0.85; AUC respectively were 0.742, 0.858, 0.759 and 0.885. Conclusions This study found the factors that may affect readmission, and the SVM model constructed based on the above factors achieved a certain predictive effect on the risk of readmission, which has certain reference value.

Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies.

The model outputs from the sixth phase of the International Coupled Model Intercomparison Project （CMIP6） are used to diagnose the near-surface permafrost on the Qinghai-Xizang Plateau in this study.The models' ability to simulate climate variables related to permafrost and permafrost for the current period （1985 -2014） was assessed in comparison with observations and permafrost maps of the Qinghai-Xizang Plateau， and the multi-model ensemble averaging method was applied to predict the future trends of near-surface permafrost on the Plateau under four SSP scenarios for the periods 2021 -2040， 2041 -2060 and 2081 -2100.The results show that all CMIP6 models can simulate the distribution characteristics and trends of climate variables related to permafrost well， but， the simulation of air temperature has more obvious cold bias， and the simulation of snow is significantly larger.The current permafrost distribution calculated using the surface frost index （SFI） is in good agreement with the permafrost map of the Qinghai-Xizang Plateau， and the surface permafrost area from 1985 to 2014 is about 134.52×104 km2 （including the area of lakes and glaciers）.With increasing temperatures， the permafrost on the Tibetan Plateau shows a regional degradation trend in the 21st century.Under the SSP1-2.6， SSP2-4.5， SSP3-7.0， and SSP5-8.5 scenarios， permafrost in the eastern， southern and northern margins of the Qinghai-Xizang Plateau showed regional degradation.Between 2041 to 2060， the permafrost area decreases by 13.81×104 km2， 19.51×104 km2， 18.02×104 km2， and 24.84×104 km2， respectively， and by the end of the 21st century， the plateau permafrost is severely degraded on a large scale， with only 69.3%， 52.5%， 34.4%， and 26.3% of the current permafrost area remaining.

This paper is concerned with the inverse problem of determining an obstacle and the corresponding incident point sources in the Helmholtz equation from near-field scattering data. An optimization method is proposed to simultaneously recover both the obstacle and source locations. Moreover, a two-step sampling scheme with novel indicator functions is proposed to produce a good initial guess for solving the optimization problem. Theoretically, we analyze the convergence properties of the optimization method and the behaviors of the indicator functions. Several numerical examples are presented to show the effectiveness of the proposed method.

PurposeThe aim of this study was to retrospectively analyze 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/ computed tomography (CT) images of non-infected hip arthroplasty patients and summarize findings that may be useful for clinical practice.Methods18F-FDG PET/CT images of non-infected hip arthroplasty patients were collected from September 2009 to August 2021. The region of interest was independently delineated by two physicians and maximum standardized uptake values (SUVmax) were recorded and compared. Serologic data were also collected and the correlation between SUVmax and serologic parameters was analyzed, while the images were classified based on the 18F-FDG uptake pattern in the images using the diagnostic criteria proposed by Reinartz et al. (9). The interval between hip replacement and PET/CT was classified by year and the characteristics of the two groups were compared. The images of patients who underwent PET/CT multiple times were analyzed dynamically.ResultsA total of 121 examinations were included; six patients underwent PET/CT twice and two patients had three scans. There were no significant correlations between SUVmax and serologic results. The interobserver agreement between the two physicians in the classification according to the criteria of Reinartz et al. (9) was 0.957 (P < 0.005). Although there was non-specific uptake in cases with an arthroplasty-to-PET/CT interval this was non-significant. Additionally, 18F-FDG showed potential utility for dynamic observation of the condition of the hip.ConclusionSUVmax provided information independent of serologic results, meanwhile 18F-FDG showed potential applicability to the dynamic monitoring of hip arthroplasty-related diseases. However, the presence of blood vessels and muscles affected image interpretation and the specificity of 18F-FDG was not optimal. A more specific radionuclide is needed to maximize the benefits of using PET/CT for the assessment of periprosthetic joint infection (PJI).

Human CLCA2 regulates store-operated calcium entry (SOCE) by interacting with Orai1 and STIM1. It is expressed as a 943aa type I transmembrane protein that is cleaved at amino acid 708 to produce a diffusible 100 kDa product. The N-terminal ectodomain contains a hydrolase-like subdomain with a conserved HEXXH zinc-binding motif that is proposed to cleave the precursor autoproteolytically. Here, we tested this hypothesis and its link to SOCE. We first studied the conditions for autocleavage in isolated membranes and then in a purified protein system. Cleavage was zinc-dependent and abolished by mutation of the E in the HEXXH motif to Q, E165Q. Cleavage efficiency increased with CLCA2 concentration, implying that it occurs in trans. Accordingly, the E165Q mutant was cleaved by co-transfected wildtype CLCA2. Moreover, CLCA2 precursors with different epitope tags co-immunoprecipitated. In a membrane-free system utilizing immunopurified protease and target, no cleavage occurred unless the target was first denatured, implying that membranes provide essential structural or conformational cues. Unexpectedly, cleavage caused a conformational shift: an N-terminal antibody that immunoprecipitated the precursor failed to precipitate the N-terminal product unless the product was first denatured with an ionic detergent. The E165Q mutation abolished the stimulation of SOCE caused by wildtype CLCA2, establishing that the metalloprotease activity is required for this regulatory function.

Abstract Background Tumor necrosis factor (TNF)-α inhibitors represented by Etanercept (a fusion protein containing soluble TNF receptor II (sTNFRII) and the Fc segment of human IgG1) play a pivotal role in Rheumatoid arthritis (RA) treatment. However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-α, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their “homing” and immune-regulation capacities, whereas inflammatory environment (especially TNF-α) is not conducive to MSCs' therapeutic effects by inducing apoptosis/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions. Methods Constructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence. Results sTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis/autophagy induced by TNF-α. Conclusion sTNFRII-Fc modification protects MSCs against apoptosis/autophagy induced by TNF-α, in addition to releasing sTNFRII-Fc neutralizing TNF-α to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis.

Description of immune landscapes in malignant microenvironment is critical to the improvement of therapeutic strategies for various tumors. Acute myeloid leukemia (AML) remains a severe life-threatening malignancy and often confronts treatment dilemma in clinic. Although γδ T cells exhibit independent and potent cytotoxicity against leukemic cells in vitro and in the mouse models, efficacy of γδ T cell-based immunotherapy on AML patients has seemed unsatisfying so far. How the anti-AML capacity of γδ T cells is suppressed in vivo remains elusive. Herein, we found an aberrant γδ T cells subset expressing CD25+CD127lowVδ2+ in the bone marrows of patients with newly diagnosed AML. The emergence of this subset was significantly associated with disease status and risk stratification as well as with the abnormally increased bone morphogenetic protein 2 (BMP2). Mechanistically, BMP2 could directly induce CD25+CD127lowVδ2+ γδ T cells (named as Reg-Vδ2) in vitro. The immunosuppressive features of Reg-Vδ2 cells were identified by combining immunophenotypical and functional data. Furthermore, inhibition of BMP2 pathway significantly blocked the emergence of Reg-Vδ2 cells and enhanced the anti-AML immunity in humanized mice. These findings not only provide a novel insight into the mechanisms of immunosuppression in the context of leukemia, but also suggest potential targets for the treatment of AML and other hematopoietic malignancies.

BackgroundAcute myeloid leukemia (AML) with t(8;21) needs to be further stratified. In addition to leukemia cells, immune cells in tumor microenvironment participate in tumor initiation, growth and progression. Interleukins (ILs)/interleukin receptors (ILRs) interaction plays important roles in the antitumor immune response. IL7R is reported to be relevant to prognosis in solid tumor and acute lymphoblastic leukemia. However, the prognostic significance of IL7R in t(8;21) AML remains to be clarified.MethodsBone marrows collected from 156 newly diagnosed t(8;21) AML patients were used for testing IL7R transcript level by TaqMan-based real-time quantitative PCR (RQ-PCR), and RNAseq were performed in 15 of them. Moreover, IL7R expression at diagnosis were measured by RQ-PCR and flow cytometry (FCM) simultaneously in other 13 t(8;21) AML patients.Resultst(8;21) AML patients had varied IL7R transcript levels and were categorized into low-expression (IL7R-L) and high-expression (IL7R-H) groups; IL7R-L was significantly associated with a lower relapse-free survival (RFS) rate (P=0.0027) and KITD816/D820 mutation (P=0.0010). Furthermore, IL7R-L was associated with a lower RFS rate in KITD816/D820 group (P=0.013) and IL7R-H/KITD816/D820 patients had similar RFS to KITN822/e8/WT patients (P=0.35). GO analysis enrichment showed that down-regulated genes were predominantly involved in the regulation of T cell and leukocyte activation, proliferation and differentiation in IL7R-L group. IL7R-L had significantly lower levels of Granzymes A/B, CCR7, CD28 and CD27 than IL7R-H group (all P

The scientific prediction of the TBM penetration rate is of great significance to the selection of hydraulic tunnel construction methods, construction schedule and cost estimation. In view of the high nonlinearity, fuzziness and complexity of TBM excavation process, and in order to improve the prediction accuracy and computational efficiency, the partial least squares regression (PLSR) has been applied to extract the principal components of the influencing parameters. Then the deep neural network (DNN) is employed to train and forecast the TBM penetration rate. A prediction model of TBM penetration rate based on the coupled method of PLSR and DNN is proposed. Based on the measured data of the double-shield TBM construction of a water conveyance tunnel in the Lanzhou water source construction project, six impact parameters including the rock uniaxial compressive strength, rock uniaxial tensile strength, cutter head thrust, cutter head speed, rock mass integrity coefficient and rock Cerchar abrasiveness index are selected to verify the prediction reasonability of the model. The fitting and prediction accuracy of the different prediction methods are compared and analyzed. The research results show that the PLSR can effectively overcome the problem of multiple collinearity between the independent variables. The extracted principal components are trained as the input layer of the DNN, which simplifies the structure of the neural network. The PLSR-DNN coupled model effectively avoids the over-fitting and inadequate fitting problems. It has the characteristics of fast convergence, stable solution and high fitting accuracy. The average relative fitting error of the PLSR-DNN prediction model is 2.96%, and the average relative prediction error is 3.27%. The fitting accuracy and prediction accuracy of the PLSR-DNN prediction model is significantly higher than those of PLSR model alone, BP neural network model and SVR model, respectively.

Abstract Background The developmental dysplasia of the hip (DDH) can cause a wide range of pathological changes, and often requires surgical treatment. Preoperative evaluation is very important for DDH. We aimed to assess the diagnostic capability of magnetic resonance imaging (MRI) for irreducible aspects preventing hip reduction in DDH. Methods A total of 39 pediatric patients who received DDH evaluation in pediatric orthopedics from January 2015 to December 2019 were included. The samples included 4 cases of bilateral DDH and 35 cases of unilateral DDH, a total of 43 hip joint samples. All patients underwent surgical treatment, pathological examination and MRI of hip joint. Results With pathological results or intraoperative findings as the gold standard, the sensitivity and specificity of MRI were 90.3% and 83.3% for the affected labrum, 92% and 83.3% for thickening of the round ligament, 90.0% and 91.3% for atrophy of the iliopsoas muscle, and 100% and 100% for fibrofatty pulvinar tissue and joint effusion, respectively. Conclutions The MRI showed an extraordinary capability of detecting these irreducible factors and helped surgeon choose the appropriate treatment strategies.

G protein-coupled receptor kinase 2 (GRK2) is one of the cytosolic enzymes, and GRK2 translocation induces prostaglandin E2 receptor 4 (EP4) over-desensitization and reduces the level of cyclic adenosine monophosphate (cAMP) to regulate macrophage polarization. However, the role of GRK2 in the pathophysiology of ulcerative colitis (UC) remains unclear. In this study, we investigated the role of GRK2 in macrophage polarization in UC, using biopsies from patients, a GRK2 heterozygous mouse model with dextran sulfate sodium (DSS)-induced colitis, and THP-1 cells. The results showed that a high level of prostaglandin E2 (PGE2) stimulated the receptor EP4 and enhanced the transmembrane activity of GRK2 in colonic lamina propria mononuclear cells (LPMCs), resulting in a down-regulation of membrane EP4 expression. Then, the suppression of cAMP–cyclic AMP responsive element-binding (CREB) signal inhibited M2 polarization in UC. Paroxetine is acknowledged as one of the selective serotonin reuptake inhibitors (SSRI), which is also considered as a potent GRK2 inhibitor with a high selectivity for GRK2. We found that paroxetine could alleviate symptoms of DSS-induced colitis in mice by regulating GPCR signaling to affect macrophage polarization. Taken together, the current results show that GRK2 may act as a novel therapeutic target in UC by regulating macrophage polarization, and paroxetine as a GRK2 inhibitor may have therapeutic effect on mice with DSS-induced colitis.

Most of the existing quantum-inspired models are based on amplitude-phase embedding to model natural language, which maps words into Hilbert space. In quantum-computing theory, the vectors corresponding to quantum states are all complex values, so there is a gap between these two areas. Presently, complex-valued neural networks have been studied, but their practical applications are few, let alone in the downstream tasks of natural language processing such as sentiment analysis and language modeling. In fact, the complex-valued neural network can use the imaginary part information to embed hidden information and can express more complex information, which is suitable for modeling complex natural language. Meanwhile, quantum-inspired models are defined in Hilbert space, which is also a complex space. So it is natural to construct quantum-inspired models based on complex-valued neural networks. Therefore, we propose a new quantum-inspired model for NLP, ComplexQNN, which contains a complex-valued embedding layer, a quantum encoding layer, and a measurement layer. The modules of ComplexQNN are fully based on complex-valued neural networks. It is more in line with quantum-computing theory and easier to transfer to quantum computers in the future to achieve exponential acceleration. We conducted experiments on six sentiment-classification datasets comparing with five classical models (TextCNN, GRU, ELMo, BERT, and RoBERTa). The results show that our model has improved by 10% in accuracy metric compared with TextCNN and GRU, and has competitive experimental results with ELMo, BERT, and RoBERTa.

Epirubicin (EPI) is one of the most widely used anthracycline chemotherapy drugs, yet its cardiotoxicity severely limits its clinical application. Altered intracellular Ca2+ homeostasis has been shown to contribute to EPI-induced cell death and hypertrophy in the heart. While store-operated Ca2+ entry (SOCE) has recently been linked with cardiac hypertrophy and heart failure, its role in EPI-induced cardiotoxicity remains unknown. Using a publicly available RNA-seq dataset of human iPSC-derived cardiomyocytes, gene analysis showed that cells treated with 2 µM EPI for 48 h had significantly reduced expression of SOCE machinery genes, e.g., Orai1, Orai3, TRPC3, TRPC4, Stim1, and Stim2. Using HL-1, a cardiomyocyte cell line derived from adult mouse atria, and Fura-2, a ratiometric Ca2+ fluorescent dye, this study confirmed that SOCE was indeed significantly reduced in HL-1 cells treated with EPI for 6 h or longer. However, HL-1 cells presented increased SOCE as well as increased reactive oxygen species (ROS) production at 30 min after EPI treatment. EPI-induced apoptosis was evidenced by disruption of F-actin and increased cleavage of caspase-3 protein. The HL-1 cells that survived to 24 h after EPI treatment demonstrated enlarged cell sizes, up-regulated expression of brain natriuretic peptide (a hypertrophy marker), and increased NFAT4 nuclear translocation. Treatment by BTP2, a known SOCE blocker, decreased the initial EPI-enhanced SOCE, rescued HL-1 cells from EPI-induced apoptosis, and reduced NFAT4 nuclear translocation and hypertrophy. This study suggests that EPI may affect SOCE in two phases: the initial enhancement phase and the following cell compensatory reduction phase. Administration of a SOCE blocker at the initial enhancement phase may protect cardiomyocytes from EPI-induced toxicity and hypertrophy.

The National Science and Technology Award is a recognition of the highest level of science and technology projects in China, which has an extraordinary incentive effect on science and technology innovation. By referring to Michael Porter diamond model, the incentive diamond model of science and technology awards is constructed. It is considered that the incentive effect of science and technology awards on enterprise science and technology innovation is mainly through influencing the foundation and motivation of science and technology innovation, which is thus implemented in four aspects: leading the advancement of technology, promoting economic development, supporting policy implementation, and cultivating research teams. Based on the case of “Qinshan 600 MW Nuclear Power Plant Design and Construction” project in the power industry, the model is confirmed. It is argued that the superiority and inferiority effect brought by national science and technology rewards can help China build a leading science and technology enterprise and build a world science and technology power.

A full scale water-cooled Passive Residual Heat Removal System was designed and built for a 2 MW Molten Salt Reactor. In the process of heating the water tank, the heat transfer characteristics of the condenser in the system had an important impact on the temperature distribution and the development of thermal stratification in the water tank. Therefore, the heat transfer characteristics of the condenser at single-phase natural convection stage need to be experimentally researched and theoretically analyzed. Aiming at the condenser in the system, a series of experiments were carried out. Considering the influence of tube bundle effect on natural convection heat transfer, a set of theories using hydraulic diameter as characteristic length were put forward and applied to analyze the experimental results, which indicated the good agreement with the previous correlations consequently. This study can provide theoretical feasibility and experimental reference for the design of commercial molten salt reactor system in the future.

Objective: We aimed to compare amyloid deposition at the lobar cerebral microbleed (CMB) sites of cerebral amyloid angiopathy (CAA), Alzheimer’s disease (AD), and cognitively normal healthy controls (NC) and to propose a novel diagnostic method for differentiating CAA patients from AD patients with integrated 11C-Pittsburgh compound B (PIB) positron emission tomography (PET)/magnetic resonance (MR) and assess its diagnostic value.Methods: Nine CAA, 15 AD patients, and 15 NC subjects were enrolled in this study. Each subject underwent an 11C-PIB brain PET/MR examination. Susceptibility weighted imaging was assessed to detect CMB locations, and standardized uptake value ratios (SUVRs) were measured at these sites. Cortical PIB distributions were quantitatively evaluated. Patients with CAA, AD, and NC subjects were compared with global and regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated.Results: Lobar CMBs were detected in all the CAA patients, eight of the 15 AD patients (53.3%), and four of the 15 NC subjects (26.7%), respectively. The PIB deposition at CMB sites was significantly higher in CAA patients compared with AD patients and NC subjects in terms of SUVR (1.72 ± 0.10 vs. 1.42 ± 0.16 and 1.17 ± 0.08; p < 0.0001). The PIB deposition was associated with CMB locations and was greatest in the occipital and temporal regions of CAA patients. The global cortical PIB deposition was significantly higher in CAA than in NC subjects (1.66 ± 0.06 vs. 1.21 ± 0.06; p < 0.0001) and significantly lower than in AD patients (1.66 ± 0.06 vs. 1.86 ± 0.17; p < 0.0001). In contrast, the occipital/global PIB uptake ratio was significantly increased in CAA (occipital/global ratio, 1.05 ± 0.02) relative to AD patients (1.05 ± 0.02 vs. 0.99 ± 0.04; p < 0.001). PET/MR had a higher accuracy (sensitivity, 88.9%; specificity, 93.3%) than separate PET and MR.Conclusion: Our results indicate that the CMBs occur preferentially at loci with concentrated amyloid. By combining lobar CMBs with regional cortical amyloid deposition, the proposed workflow can further improve CAA diagnostic accuracy compared to each method alone. These findings improve our knowledge regarding the pathogenesis of CMBs and highlight the potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.

Abstract To improve the computing efficiency, a fourth-order difference scheme is proposed and a fast algorithm is designed to simulate the nonlinear fractional Schrödinger (FNLS) equation oriented from the fractional quantum mechanics. The numerical analysis and experiments conducted in this article show that the proposed difference scheme has the optimal second-order and fourth-order convergence rates in time and space respectively, reduces its computation cost to O(MlogM) $\mathcal{O}(M\log M)$, and recognizes accurately its physical feature of FNLS such as the mass balance.

Abstract Background Previous studies have demonstrated that the common laryngoscopic approach (right-sided) and midline approach are both used for endotracheal intubation by direct laryngoscopy. Although the midline approach is commonly recommended for video laryngoscopy (VL) in the clinic, there is a lack of published evidences to support this practice. This study aimed to evaluate the effects of different video laryngoscopic approaches on intubation. Methods Two hundred sixty-two patients aged 18 years who underwent elective surgery under general anaesthesia and required endotracheal intubation were included in the present prospective, randomized, controlled study. The participants were randomly and equally allocated to the right approach (Group R) or midline approach (Group M). All the intubations were conducted by experienced anaesthetists using GlideScope video laryngoscopy. The primary outcomes were Cormack-Lehane laryngoscopic views (CLVs) and first-pass success (FPS) rates. The secondary outcomes were the time to glottis exposure, time to tracheal intubation, haemodynamic responses and other adverse events. Comparative analysis was performed between the groups. Results Finally, 262 patients completed the study, and all the tracheas were successfully intubated. No significant differences were observed in the patient characteristics and airway assessments (P > 0.05). Compared with Group R, Group M had a better CLV (χ2 = 14.706, P = 0.001) and shorter times to glottis exposure (8.82 ± 2.04 vs 12.38 ± 1.81; t = 14.94; P 0.05). Conclusion Although the FPS rate did not differ based on the laryngoscopic approach, the midline approach could provide better glottis exposure and shorter times to glottis exposure and intubation. The midline approach should be recommended for teaching in VL-assisted endotracheal intubation. Trial registration The study was registered on May 18, 2019 in the Chinese Clinical Trial Registry (ChiCTR1900023252).

Abstract Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Although the detection of minimal residual disease (MRD), which is indicated by RUNX1‐RUNX1T1 transcript levels, plays a key role in directing treatment, risk stratification needs to be improved, and other markers need to be assessed. A total of 66 t(8;21) AML patients were tested for aldehyde dehydrogenase (ALDH) activity by flow cytometry at diagnosis, and 52 patients were followed up for a median of 20 (1‐34) months. The median percentage of CD34+ALDH+, CD34+CD38‐ALDH+, and CD34+CD38+ALDH+ cells among nucleated cells were 0.028%, 0.012%, and 0.0070%, respectively. The CD34+ALDH+‐H, CD34+CD38‐ALDH+‐H, and CD34+CD38+ALDH+‐H statuses (the percentage of cells that were higher than the individual cutoffs) were all significantly associated with a lower 2‐year relapse‐free survival (RFS) rate in both the whole cohort and adult patients (P = .015, .016, and .049; P = .014, .018, and .032). Patients with