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In this article, procedure and efficiency of the reduced-basis approach in structural design computation are studied. As a model order reduction approach, it provides fast evaluation of a structural system in explicitly parameterized formulation. Theoretically, the original structural system is reduced to obtain a reduced system by being projected onto a lower dimensional subspace. However, in practice, it is a time-consuming process due to the iterations of adaptive procedure in subspace construction. To improve the efficiency of the method, some characteristics are analyzed. First, the accuracy of the subspace is evaluated and computational costs of procedures with different approaches are studied. Results show that the subspaces constructed by greedy adaptive procedures with different beginnings have the same accuracy. It is instructive that accuracy of the subspace is guaranteed by adaptive procedure. And the computational costs depend on the number of iterations in adaptive procedure. Thus, a modified adaptive procedure is proposed to reduce the computational costs and guarantee the accuracy. The modified adaptive procedure begins with experimental design methods to obtain a set of samples rather than a single sample and ends with the adaptive procedure. The start set of samples are selected by the following experimental design methods: 2k factorial design, standard Latin design and Latin hypercube design. By being integrated with the experimental design, the modified adaptive procedure saves computational costs and retains the same accuracy as traditional procedure does. As an example, the outputs of a vehicle body front compartment subjected to a bending load are illustrated. It is proved that the proposed procedure is efficient and is applicable to many other structural design contexts. [ABSTRACT FROM PUBLISHER]

Glioblastoma is incurable and in urgent need of improved therapeutics 1 . Here we identify a small compound, gliocidin, that kills glioblastoma cells while sparing non-tumour replicative cells. Gliocidin activity targets a de novo purine synthesis vulnerability in glioblastoma through indirect inhibition of inosine monophosphate dehydrogenase 2 (IMPDH2). IMPDH2 blockade reduces intracellular guanine nucleotide levels, causing nucleotide imbalance, replication stress and tumour cell death 2 . Gliocidin is a prodrug that is anabolized into its tumoricidal metabolite, gliocidin-adenine dinucleotide (GAD), by the enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) of the NAD + salvage pathway. The cryo-electron microscopy structure of GAD together with IMPDH2 demonstrates its entry, deformation and blockade of the NAD + pocket 3 . In vivo, gliocidin penetrates the blood-brain barrier and extends the survival of mice with orthotopic glioblastoma. The DNA alkylating agent temozolomide induces Nmnat1 expression, causing synergistic tumour cell killing and additional survival benefit in orthotopic patient-derived xenograft models. This study brings gliocidin to light as a prodrug with the potential to improve the survival of patients with glioblastoma., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Glioblastoma (GBM) is an incurable disease with high intratumoral heterogeneity. Bioinformatic studies have examined transcriptional heterogeneity with differing conclusions. Here, we characterize GBM heterogeneity and highlight critical phenotypic and hierarchical roles for quiescent cancer stem cells (qCSCs). Unsupervised single-cell transcriptomic analysis of patient-derived xenografts (PDXs) delineates six GBM transcriptional states with unique tumor exclusive gene signatures, five of which display congruence with central nervous system (CNS) cell lineages. We employ a surrogate tumor evolution assay by serial xenograft transplantation to demonstrate faithful preservation of somatic mutations, transcriptome, and qCSCs. PDX chemotherapy results in CSC resistance and expansion, also seen in recurrent patient GBM. In aggregate, these novel GBM transcriptional signatures exclusively identify tumor cells and define the hierarchical landscape as stable biologically discernible cell types that allow capture of their evolution upon recurrence, emphasizing the importance of CSCs and demonstrating general relevance to all GBM., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this note, a novel prescribed fixed-time adaptive tracking control scheme is developed to cope with the fixed-time tracking control issue for a category of constrained MIMO nonlinear cyber-physical systems (CPSs) with exogenous perturbations, which suffer from deception attacks started in controller-actuator (C-A) channel. Distinguished from the conservative dynamic surface control (DSC) schemes with a linear filter, a novel nonlinear filter is designed in our strategy, which can tackle the intrinsic issue of explosion of computational complexity and promote the system performance. Besides, a new barrier Lyapunov function (BLF) is designed to ulteriorly enhance the tracking performance on the basis of the prescribed performance function (PPF) approach. Prominently, the proposed control strategy could accommodate the exogenous interferences and deception attacks simultaneously. Furthermore, we have substantiated that the developed approach can not only make certain that all the tracking errors of the resulting closed-loop system, including output tracking errors and virtual tracking errors, enter a prespecified small region near equilibrium point with fixed-time convergence rate, but also guarantee them obey the corresponding constraints throughout the entire control operation, where the regulation time and the tracking accuracy level keep prior known and could be prespecified arbitrarily. Finally, the validity and effectiveness of the proposed control scheme are illustrated through a representative application instance.

Identifying potential cancer biomarkers is a key task in biomedical research, providing a promising avenue for the diagnosis and treatment of human tumors and cancers. In recent years, several machine learning-based RNA-disease association prediction techniques have emerged. However, they primarily focus on modeling relationships of a single type, overlooking the importance of gaining insights into molecular behaviors from a complete regulatory network perspective and discovering biomarkers of unknown types. Furthermore, effectively handling local and global topological structural information of nodes in biological molecular regulatory graphs remains a challenge to improving biomarker prediction performance. To address these limitations, we propose a multichannel graph neural network based on multisimilarity modality hypergraph contrastive learning (MML-MGNN) for predicting unknown types of cancer biomarkers. MML-MGNN leverages multisimilarity modality hypergraph contrastive learning to delve into local associations in the regulatory network, learning diverse insights into the topological structures of multiple types of similarities, and then globally modeling the multisimilarity modalities through a multichannel graph autoencoder. By combining representations obtained from local-level associations and global-level regulatory graphs, MML-MGNN can acquire molecular feature descriptors benefiting from multitype association properties and the complete regulatory network. Experimental results on predicting three different types of cancer biomarkers demonstrate the outstanding performance of MML-MGNN. Furthermore, a case study on gastric cancer underscores the outstanding ability of MML-MGNN to gain deeper insights into molecular mechanisms in regulatory networks and prominent potential in cancer biomarker prediction., (© The Author(s) 2024. Published by Oxford University Press.)

Motivation: Research shows that competing endogenous RNA is widely involved in gene regulation in cells, and identifying the association between circular RNA (circRNA), microRNA (miRNA), and cancer can provide new hope for disease diagnosis, treatment, and prognosis. However, affected by reductionism, previous studies regarded the prediction of circRNA-miRNA interaction, circRNA-cancer association, and miRNA-cancer association as separate studies. Currently, few models are capable of simultaneously predicting these three associations., Results: Inspired by holism, we propose a multi-task prediction method based on neighborhood structure embedding and signed graph representation learning, CMCSG, to infer the relationship between circRNA, miRNA, and cancer. Our method aims to extract feature descriptors of all molecules from the circRNA-miRNA-cancer regulatory network using known types of association information to predict unknown types of molecular associations. Specifically, we first constructed the circRNA-miRNA-cancer association network (CMCN), which is constructed based on the experimentally verified biomedical entity regulatory network; next, we combine topological structure embedding methods to extract feature representations in CMCN from local and global perspectives, and use denoising autoencoder for enhancement; then, combined with balance theory and state theory, molecular features are extracted from the point of social relations through the propagation and aggregation of signed graph attention network; finally, the GBDT classifier is used to predict the association of molecules. The results show that CMCSG can effectively predict the relationship between circRNA, miRNA, and cancer. Additionally, the case studies also demonstrate that CMCSG is capable of accurately identifying biomarkers across various types of cancer. The data and source code can be found at https://github.com/1axin/CMCSG., (© The Author(s) 2024. Published by Oxford University Press.)

The discovery of diagnostic and therapeutic biomarkers for complex diseases, especially cancer, has always been a central and long-term challenge in molecular association prediction research, offering promising avenues for advancing the understanding of complex diseases. To this end, researchers have developed various network-based prediction techniques targeting specific molecular associations. However, limitations imposed by reductionism and network representation learning have led existing studies to narrowly focus on high prediction efficiency within single association type, thereby glossing over the discovery of unknown types of associations. Additionally, effectively utilizing network structure to fit the interaction properties of regulatory networks and combining specific case biomarker validations remains an unresolved issue in cancer biomarker prediction methods. To overcome these limitations, we propose a multi-view learning framework, CeRVE, based on directed graph neural networks (DGNN) for predicting unknown type cancer biomarkers. CeRVE effectively extracts and integrates subgraph information through multi-view feature learning. Subsequently, CeRVE utilizes DGNN to simulate the entire regulatory network, propagating node attribute features and extracting various interaction relationships between molecules. Furthermore, CeRVE constructed a comparative analysis matrix of three cancers and adjacent normal tissues through The Cancer Genome Atlas and identified multiple types of potential cancer biomarkers through differential expression analysis of mRNA, microRNA, and long noncoding RNA. Computational testing of multiple types of biomarkers for 72 cancers demonstrates that CeRVE exhibits superior performance in cancer biomarker prediction, providing a powerful tool and insightful approach for AI-assisted disease biomarker discovery., (© The Author(s) 2024. Published by Oxford University Press.)

State-of-the-art optical cavities are pivotal in pushing the envelope of laser frequency stability below 10-16. This is often achieved by extending the cavity length or cooling the system to cryogenic temperatures to reduce the thermal noise floor. In our study, we present a 30-cm-long cavity that operates at room temperature and is outfitted with crystalline coatings. The system has a predicted ultralow thermal noise floor of 4.4 × 10-17, comparable to what is observed in cryogenic silicon cavities. A 1397-nm laser is stabilized in this advanced cavity, and the stable frequency is then transferred to the clock transition in strontium optical lattice clocks via a frequency-doubling process. We have meticulously minimized and assessed the technical noise contributions through comparisons with an ultrastable reference laser that is locked to a commercially available 30-cm cavity. The frequency instability of the system is rigorously evaluated using a three-cornered-hat method. The results demonstrate that the laser frequency instability remains below 2 × 10-16 for averaging times ranging from 1 to 50 s. These findings underscore the significant potential of room-temperature cavities with crystalline coatings in high-precision metrology and pave the way for further improvements in optical lattice clocks., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: The use of machine learning(ML) methods would improve the diagnosis of small airway dysfunction(SAD) in subjects with chronic respiratory symptoms and preserved pulmonary function(PPF). This paper evaluated the performance of several ML algorithms associated with the impulse oscillometry(IOS) analysis to aid in the diagnostic of respiratory changes in SAD. We also find out the best configuration for this task., Methods: IOS and spirometry were measured in 280 subjects, including a healthy control group (n = 78), a group with normal spirometry (n = 158) and a group with abnormal spirometry (n = 44). Various supervised machine learning (ML) algorithms and feature selection strategies were examined, such as Support Vector Machines (SVM), Random Forests (RF), Adaptive Boosting (ADABOOST), Navie Bayesian (BAYES), and K-Nearest Neighbors (KNN)., Results: The first experiment of this study demonstrated that the best oscillometric parameter (BOP) was R5, with an AUC value of 0.642, when comparing a healthy control group(CG) with patients in the group without lung volume-defined SAD(PPFN). The AUC value of BOP in the control group was 0.769 compared with patients with spirometry defined SAD(PPFA) in the PPF population. In the second experiment, the ML technique was used. In CGvsPPFN, RF and ADABOOST had the best diagnostic results (AUC = 0.914, 0.915), with significantly higher accuracy compared to BOP (p < 0.01). In CGvsPPFA, RF and ADABOOST had the best diagnostic results (AUC = 0.951, 0.971) and significantly higher diagnostic accuracy (p < 0.01). In the third, fourth and fifth experiments, different feature selection techniques allowed us to find the best IOS parameters (R5, (R5-R20)/R5 and Fres). The results demonstrate that the performance of ADABOOST remained essentially unaltered following the application of the feature selector, whereas the diagnostic accuracy of the remaining four classifiers (RF, SVM, BAYES, and KNN) is marginally enhanced., Conclusions: IOS combined with ML algorithms provide a new method for diagnosing SAD in subjects with chronic respiratory symptoms and PPF. The present study's findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients., (© 2024. The Author(s).)

Towards realizing the future quantum internet 1,2 , a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory 3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis., Design: Prospective multicentre diagnostic accuracy study., Setting: 14 medical centres in China., Participants: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1., Main Outcome Measures: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices., Results: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE., Conclusion: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis., Trial Registration: ClinicalTrials.gov NCT03748563., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the “Ten Thousand Plan”-National High-Level Talents Special Support Plan and Shanghai Municipal Hospital Emerging Frontier Technology Joint Project for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H 22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation., Methods: Sixty H 22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 10 6 T cells from HIFU treated-mice were intravenously injected into each syngeneic H 22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer., Results: T cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs ( p < 0.001), with a significant increase of TNF-α ( p < 0.001) and IFN-γ secretion ( p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand + and perforin + tumor-infiltrating lymphocytes (TILs) and apoptotic H 22 tumor cells were significantly higher ( p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand + TILs (r = 0.9145, p < 0.001) and perforin + TILs (r = 0.9619, p < 0.001)., Conclusion: T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ran, Xie, Xia, Xie, Fan and Wu.)

Objective: The aim of this study is to explore the early diagnostic value of contrast-enhanced ultrasound (CEUS)-related quantitative parameter and its relationship with the micro-perfusion of nontraumatic necrosis of the femoral head., Patients and Methods: According to the random and double-blind method, the patients with non-traumatic femoral head necrosis diagnosed and treated in our hospital from July 2019 to January 2022 were selected as the subjects (the research group). According to the staging of the International Society of Bone Circulation for Femoral Head Necrosis, 89 patients with stage Ⅱ and Ⅲ A were included (39 patients with stage Ⅱ and 50 patients with stage Ⅲ A). 25 patients who conducted physical examination in our hospital during the same time were taken as the control group. Quantitative parameters of CEUS were analyzed. The content of serum vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) were evaluated. The relationship among the quantitative parameters of CEUS, the expression of VEGF and BMP-2 in serum and the patient's condition, and the value for assisting the early diagnosis of nontraumatic femoral head necrosis were analyzed., Results: The body mass, body mass index (BMI), blood lipid, and cholesterol levels were much higher in the research group than in the control group (p < 0.05). The research group had a markedly higher slope of ascending branch (AS), strength enhancement index (EI), and VEGF and obviously lower decay slope (DS), mean transit time (MTT), and time to peak (TTP) than the control group (p < 0.05). In the research group, compared to stage Ⅱ, the levels of AS, EI, and VEGF in stage Ⅲ A patients were memorably higher, and the levels of DS, MTT, TTP and BMP-2 were dramatically lower (p < 0.05). Pearson's correlation test showed that AS, EI, and VEGF were positively correlated with the patients' condition, while DS, MTT, TTP and BMP-2 were negatively correlated with the patients' condition (p < 0.05). The receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of quantitative parameters of CEUS was 0.961, with sensitivity and specificity of 88.0% and 97.4%, respectively. The AUC of the combined detection of VEGF and BMP-2 was 0.945 with sensitivity and specificity of 82.3% and 87.5%, respectively, and the combined detection had a high diagnostic value (p < 0.05)., Conclusions: The quantitative parameters of CEUS were of great value in the early diagnosis of nontraumatic necrosis of the femoral head with microvascular perfusion and the patients' condition, and provided a reference for the clinical treatment of non-traumatic necrosis of the femoral head. These parameters were expected to be useful indicators for judging the efficacy before and after treatment.

In order to explore the impact of antibiotics (enrofloxacin) on microbial community in aquatic environment, an indoor aquatic ecological model was built, and different concentrations of enrofloxacin (0.05, 0.5, 5, and 50 mg/L) were added in the aquatic ecological model. In addition, the water and sediment samples were collected on the 0, 7, 30, and 60 days, and the changes in microbial community were studied through 16S rDNA high-throughput sequencing. The results showed that when the concentration of enrofloxacin was 50 mg/L, the relative abundance of Actinomycetes was increased. In the water, the bacterial richness and diversity communities first decreased and then gradually recovered with the passage of time; On the 7th day, the diversity and richness index of species in the treatment groups with enrofloxacin at 5 and 50 mg/L decreased to the lowest; On the 30th day, the diversity and richness index of species began to rise; On the 60th day, the diversity index and richness index of water species began to increase, while the diversity index and richness index of sediment species decreased. In conclusion, the addition of enrofloxacin negatively affected the microbial community structure in an indoor aquatic ecological model, 50 mg/L enrofloxacin could increase the relative abundance of Actinomycetes, and decrease the diversity and richness index of water and sediment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dai, Peng, Zhang, Xie, Luo, Liu and Ma.)

Background: Through significant advances in the treatment of peripheral arterial occlusive disease, acute ischemia of the lower extremity is still associated with significant morbidity, limb threat and mortality. The two main causes of acute ischemia in lower extremities are arterial embolism and atherosclerotic arteries. Timely recognition and treatment of acute limb ischemia in emergency situations is essential in order to minimize the duration of ischemia., Aim: To investigate the application effect of angiojet thrombolysis in the treatment of acute lower extremity arterial embolization., Methods: Sixty-two patients with acute lower extremity arterial embolization admitted to our hospital from May 2018 to May 2020 were selected. Among them, the observation group (twenty-eight cases) had received angiojet thrombolysis, and the control group (thirty-four cases) had received femoral artery incision and thrombectomy. After thrombus clearance, significant residual stenosis of the lumen was combined with balloon dilation and/or stent implantation. When the thrombus removal was not satisfactory, catheter-directed thrombolysis was performed. The incidence of postoperative complications, recurrence rate and recovery of the two groups were compared., Results: There were no significant differences in postoperative recurrence (target vessel reconstruction rate), anklebrachial index and the incidence of postoperative complications between the two groups ( P > 0.05); there were statistically significant differences in postoperative pain score and postoperative rehabilitation between the two groups ( P < 0.05)., Conclusion: The application of angiojet in the treatment of acute lower limb artery thromboembolism disease is safe and effective, minimally invasive, quicker recovery after operation, less postoperative complications, which is more suitable for the treatment of femoral popliteal arterial thromboembolism lesions. If the thrombus removal is not satisfactory, the combination of coronary artery aspiration catheter and catheterized directed thrombolysis can be used. Balloon dilation and stent implantation can be considered for obvious lumen stenosis., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The problem of enhancing the robust performance of nonlinear fault estimation (FE) is addressed by proposing a novel real-time gain-scheduling mechanism for discrete-time Takagi-Sugeno fuzzy systems. The real-time status of the operating point for the considered nonlinear plant is characterized by using these available normalized fuzzy weighting functions at both the current and the past instants of time. To achieve this, the developed fuzzy real-time gain-scheduling mechanism produces different switching modes by introducing key tunable parameters. Thus, a pair of exclusive FE gain matrices is designed for each switching mode on the strength of time-varying balanced matrices developed in this study, respectively. Since the implementation of more FE gain matrices can be scheduled according to the real-time status of the operating point at each sampling instant, the robust performance of nonlinear FE will be enhanced over the previous methods to a great extent. Finally, considerable numerical comparisons are implemented in order to illustrate that the proposed method is much superior to those existing ones reported in the literature.

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Quantum internet gives the promise of getting all quantum resources connected, and it will enable applications far beyond a localized scenario. A prototype is a network of quantum memories that are entangled and well separated. In this Letter, we report the establishment of postselected entanglement between two atomic quantum memories physically separated by 12.5 km directly. We create atom-photon entanglement in one node and send the photon to a second node for storage via electromagnetically induced transparency. We harness low-loss transmission through a field-deployed fiber of 20.5 km by making use of frequency down-conversion and up-conversion. The final memory-memory entanglement is verified to have a fidelity of 90% via retrieving to photons. Our experiment makes a significant step forward toward the realization of a practical metropolitan-scale quantum network.

We test the hypothesis that glioblastoma harbors quiescent cancer stem cells that evade anti-proliferative therapies. Functional characterization of spontaneous glioblastomas from genetically engineered mice reveals essential quiescent stem-like cells that can be directly isolated from tumors. A derived quiescent cancer-stem-cell-specific gene expression signature is enriched in pre-formed patient GBM xenograft single-cell clusters that lack proliferative gene expression. A refined human 118-gene signature is preserved in quiescent single-cell populations from primary and recurrent human glioblastomas. The F3 cell-surface receptor mRNA, expressed in the conserved signature, identifies quiescent tumor cells by antibody immunohistochemistry. F3-antibody-sorted glioblastoma cells exhibit stem cell gene expression, enhance self-renewal in culture, drive tumor initiation and serial transplantation, and reconstitute tumor heterogeneity. Upon chemotherapy, the spared cancer stem cell pool becomes activated and accelerates transition to proliferation. These results help explain conventional treatment failure and lay a conceptual framework for alternative therapies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Recently, the coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several studies indicate that the digestive system can also be affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, patients with digestive symptoms should have a capsule endoscopy (CE). COVID-19 patients with gastrointestinal (GI) symptoms who underwent CE were recruited from March 2020 to April 2020. We collected patients' data and performed a prospective follow-up study for 6 months. All 11 COVID-19 cases with GI symptoms who underwent CE presented gastritis. Eight cases (72.7%) had intestinal mucosa inflammation. Among them, two cases showed intestinal ulcers or erosions. Moreover, two cases displayed colonic mucositis. One case was lost during follow-up. At 3-6 months after hospital discharge, five patients underwent CE again, presenting gastrointestinal lesions. Five of the 10 cases had GI symptoms, such as abdominal pain, diarrhea, constipation, and others. Among these five cases, the GI symptoms of three patients disappeared at the last follow-up and two patients still presented diarrhea symptoms. Overall, we observed damaged digestive tract mucosa that could be caused by SARS-CoV-2. Moreover, after discharge, some patients still presented intestinal lesions and GI symptoms., (© 2021 Wiley Periodicals LLC.)

In this article, an adaptive fuzzy tracking control scheme is developed for a class of uncertain switched nonlinear systems with input saturations and full-state constraints. First to surmount the design difficulty with respect to a saturation nonlinearity controller, a nonlinear smooth function approximating the nondifferential saturation function is introduced to establish a standard switched adaptive tracking control strategy based on the mean-value theorem and the input compensation technique. Then, invoking fuzzy-logic systems (FLSs), a novel analysis method of average dwell time for switched nonlinear systems with full-state constraints is proposed by using an artful logarithmic inequality. Furthermore, the designed adaptive controller can ensure that all the states of uncertain switched nonlinear systems are not to violate the set constraint bounds by employing barrier Lyapunov functions (BLFs), and that the system output tracking error can converge to a desired neighborhood of the origin within a suitable compact set. Finally, the simulation results are given to demonstrate the validity of the presented approach.

Interferometers are widely used in imaging technologies to achieve enhanced spatial resolution, but require that the incoming photons be indistinguishable. In previous work, we built and analyzed color erasure detectors, which expand the scope of intensity interferometry to accommodate sources of different colors. Here we demonstrate experimentally how color erasure detectors can achieve improved spatial resolution in an imaging task, well beyond the diffraction limit. Utilizing two 10.9-mm-aperture telescopes and a 0.8 m baseline, we measure the distance between a 1063.6 and a 1064.4 nm source separated by 4.2 mm at a distance of 1.43 km, which surpasses the diffraction limit of a single telescope by about 40 times. Moreover, chromatic intensity interferometry allows us to recover the phase of the Fourier transform of the imaged objects-a quantity that is, in the presence of modest noise, inaccessible to conventional intensity interferometry.

NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discover and characterize a rare MPNST cell population with stem-cell-like properties, including quiescence, that is essential for tumor initiation and relapse. Following isolation of these cells, we derive a cancer-stem-cell-specific gene expression signature that includes consensus embryonic neural crest genes and identify Nestin as a marker for the MPNST cell of origin. Combined targeting of cancer stem cells along with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development., Competing Interests: Declaration of interests The authors declare no competing interests, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Non-line-of-sight (NLOS) imaging enables monitoring around corners and is promising for diverse applications. The resolution of transient NLOS imaging is limited to a centimeter scale, mainly by the temporal resolution of the detectors. Here, we construct an up-conversion single-photon detector with a high temporal resolution of ∼1.4  ps and a low noise count rate of 5 counts per second (cps). Notably, the detector operates at room temperature, near-infrared wavelength. Using this detector, we demonstrate high-resolution and low-noise NLOS imaging. Our system can provide a 180  μm axial resolution and a 2 mm lateral resolution, which is more than 1 order of magnitude better than that in previous experiments. These results open avenues for high-resolution NLOS imaging techniques in relevant applications.

To realize the large-scale and high-precision co-phasing adjustment of synthetic-aperture telescopes, we propose a multichannel left-subtract-right feature vector piston error detection method based on a convolutional neural network, which inherits the high precision and strong noise resistance of the DFA-LSR method while achieving a detection range of (-139λ, 139λ) (λ = 720 nm). In addition, a scheme to build large training datasets was proposed to solve the difficulty in collecting datasets using traditional neural network methods. Finally, simulations verified that this method can guarantee at least 94.96% accuracy with large samples, obtaining a root mean square error of 10.2 nm when the signal-to-noise ratio is 15.

This article is concerned with a neural adaptive tracking control scheme for a class of multiinput and multioutput (MIMO) nonaffine nonlinear systems with event-triggered mechanisms, which include the fixed thresholds, triggering control inputs, and decreasing functions of tracking errors. Unlike the existing results of nonaffine nonlinear controller decoupling, a novel nonlinear multiple control inputs separated design method is proposed based on the mean-value theorem and the Taylor expansion technique. By this way, a weaker condition of nonlinear decoupling is provided to instead of the previous ones. Then, introducing a prescribed performance barrier Lyapunov function (PPBLF) and using neural networks (NNs), the presented event-triggered controller can maintain better tracking performance and effectively alleviate the computation burden of the communication procedure. Furthermore, it is proved that all the closed-loop signals are bounded and the system output tracking errors are confined within the prescribed bounds. Finally, the simulation results are given to demonstrate the validity of the developed control scheme.

Adult neural stem cells (NSC) serve as a reservoir for brain plasticity and origin for certain gliomas. Lineage tracing and genomic approaches have portrayed complex underlying heterogeneity within the major anatomical location for NSC, the subventricular zone (SVZ). To gain a comprehensive profile of NSC heterogeneity, we utilized a well-validated stem/progenitor-specific reporter transgene in concert with single-cell RNA sequencing to achieve unbiased analysis of SVZ cells from infancy to advanced age. The magnitude and high specificity of the resulting transcriptional datasets allow precise identification of the varied cell types embedded in the SVZ including specialized parenchymal cells (neurons, glia, microglia) and noncentral nervous system cells (endothelial, immune). Initial mining of the data delineates four quiescent NSC and three progenitor-cell subpopulations formed in a linear progression. Further evidence indicates that distinct stem and progenitor populations reside in different regions of the SVZ. As stem/progenitor populations progress from neonatal to advanced age, they acquire a deficiency in transition from quiescence to proliferation. Further data mining identifies stage-specific biological processes, transcription factor networks, and cell-surface markers for investigation of cellular identities, lineage relationships, and key regulatory pathways in adult NSC maintenance and neurogenesis., Competing Interests: The authors declare no competing interest.

Background: Genes are regulated by various types of regulators and most of them are still unknown or unobserved. Current gene regulatory networks (GRNs) reverse engineering methods often neglect the unknown regulators and infer regulatory relationships in a local and sub-optimal manner., Results: This paper proposes a global GRNs inference framework based on dictionary learning, named dlGRN. The method intends to learn atomic regulators (ARs) from gene expression data using a modified dictionary learning (DL) algorithm, which reflects the whole gene regulatory system, and predicts the regulation between a known regulator and a target gene in a global regression way. The modified DL algorithm fits the scale-free property of biological network, rendering dlGRN intrinsically discern direct and indirect regulations., Conclusions: Extensive experimental results on simulation and real-world data demonstrate the effectiveness and efficiency of dlGRN in reverse engineering GRNs. A novel predicted transcription regulation between a TF TFAP2C and an oncogene EGFR was experimentally verified in lung cancer cells. Furthermore, the real application reveals the prevalence of DNA methylation regulation in gene regulatory system. dlGRN can be a standalone tool for GRN inference for its globalization and robustness.

High-performance single-photon detectors (SPDs) at 1550-nm band are critical for fiber-based quantum communications. Among many types of SPDs, the up-conversion SPDs based on periodically poled lithium niobate waveguides are of great interest. Combined with a strong pump laser, the telecom single-photons are converted into short wavelength ones and detected by silicon-based SPDs. However, due to the difficulty of precise controlling waveguide profile, the direct coupling between a single-mode fiber and the waveguide is not efficient. Here by utilizing fiber taper with proper diameter, optimal mode-matching is achieved and coupling efficiency up to 93% is measured. With an optimized design, a system detection efficiency of 36% and noise counting rate of 90 cps are realized. The maximum detection efficiency is characterized as 40% with a noise counting rate of 200 cps. Numerical simulation results indicate that our device can significantly improve the performance of QKD and extend the communication distance longer than 200 km.

Background: The clinical effects and safety over the treatment of tibia intercondylar eminence fracture (TIEF) with cannulated screw and suture fixation were evaluated under arthroscope systematically, providing evidence-based medical support for the selection of surgical methods in terms of minimally invasive arthroscopic treatment for TIEF., Methods: The English databases of PubMed, EMBASE, Cochrane Library, CNKI, SinoMed, VIP, and Wanfang databases were searched by computer. The randomized controlled trials were conducted to compare the clinical effects of TIEF with cannulated screw and suture fixation under arthroscope. The retrieval period is from the beginning of database building to January 2020. There is no language restriction. Chinese databases are searched by keywords, while English databases are searched by the combination of subject words and free words. According to the retrieval strategy, the two evaluators will lead the conforming documents into Note Express for repeated literature screening, and the two evaluators will extract and cross-check the conforming documents according to the pre-designed data extraction table. Two researchers adopted the modified Jadad scale independently to evaluate the quality of the literature. The RevMan 5.3 version software provided by the Cochrane Collaboration Network was adopted for statistical analysis., Results: The study will strictly review and extract the data included in the literature, and scientifically make statistical analysis for the pre-set outcome indicators. All the research processes will be conducted in strict accordance with the guidance of system evaluation. In this study, the differences between cannulated screw fixation and suture fixation under arthroscopy will be evaluated by comparing the relevant outcome indicators. All the results of this study will be published openly in a highly influential professional academic journal., Conclusion: The paper adopted Cochrane system evaluation method to collect and sort out the published literature about the treatment of tibial eminence fracture between cannulated screw fixation and suture fixation under arthroscopy, and to compare the clinical efficacy and safety of the two fixation methods utilizing meta-analysis and comparison of related outcome indicators. Through this study, we will draw a positive conclusion, which will provide a basis for the better treatment of tibial eminence fracture., Prospero Registration Number: PROSPERO CRD42020168433.

Magnetically controlled capsule endoscopy (MCE) system has been used to screen gastric lesions. However, the visualization performance of MCE in the esophagus has not been investigated systematically. String method improved the ability of capsule endoscopy (CE) for esophageal observing; however, the string attachment is complicated and cannot be detached with the CE inside the esophagus. We used a modified string, called detachable string attached to MCE. The aim of the study was to compare the observation performance of MCE with and without the detachable string. A total of 238 participants with upper gastrointestinal symptoms and a healthy check who refused esophagogastroduodenoscopy examination were retrospectively divided into the detachable string MCE group and the MCE alone group from June 2016 to May 2018. A suction cap with a thin, hollow string was attached to the MCE system in the detachable string group. Circumferential visualization of the esophagus including the upper, middle, and lower esophagus and Z-line, and esophageal focal lesion, as well as the recording time, safety and tolerability of the procedure, were assessed. The circumferential visualization of the upper, middle, and lower esophagus and Z-line was more efficient in the detachable string MCE group than in the MCE alone group (P < 0.001). In all, 31 esophageal lesions were detected in the detachable string MCE group, which was more than that in the MCE alone group (10, P < 0.001). The mean recording time was 305 seconds in the string MCE group, which was longer than that in the MCE alone group (48.5 seconds, P < 0.001). In seven participants (6.1%) in the detachable string MCE group, the capsule could not be separated from the string. Detachable string MCE showed better performance in terms of observation of the esophagus. Detachable string MCE can be used to screen for esophageal diseases as an alternative method in the future., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Weightlessness exposure conduces to substantial vascular remodeling, mechanisms behind which remain unclear. Acid sphingomyelinase (ASM) catalyzed ceramide (Cer) generation accounts for multiple vascular disorders, so the role of it in adjustment of cerebral artery (CA) and small mesenteric artery (MA) was investigated in simulated weightless rats., Main Methods: Rats were hindlimb unloaded tail suspended (HU) to simulate the effect of weightlessness. Arterial morphology was examined by hematoxylin-eosin staining. Cer abundance was measured by immunohistochemistry. Western blotting was used to detect protein content. Apoptosis was detected by transferase-mediated dUTP nick end labeling., Key Findings: During 4 weeks of tail suspension, intima-media thickness (IMT) and media cross section area (CSA) were increased gradually in CA but decreased gradually in MA (P < 0.05). Correspondingly, the apoptosis and proliferation of vascular smooth muscle cells were reduced and enhanced respectively in CA (P < 0.05), while promoted and restrained in MA (P < 0.05). As compared to control, both ASM protein expression and Cer content were lowered in CA and elevated in MA of HU rats (P < 0.05). Permeable Cer incubation reversed the change of apoptosis and proliferation in CA of HU rats, while ASM inhibition recapitulated it in control rats. On the contrary, ASM inhibitors restored the alteration of apoptosis and proliferation in MA of HU., Significance: The results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer exerts an important role in structural adaptation of CA and MA to simulated weightlessness., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A quantum internet that connects remote quantum processors 1,2 should enable a number of revolutionary applications such as distributed quantum computing. Its realization will rely on entanglement of remote quantum memories over long distances. Despite enormous progress 3-12 , at present the maximal physical separation achieved between two nodes is 1.3 kilometres 10 , and challenges for longer distances remain. Here we demonstrate entanglement of two atomic ensembles in one laboratory via photon transmission through city-scale optical fibres. The atomic ensembles function as quantum memories that store quantum states. We use cavity enhancement to efficiently create atom-photon entanglement 13-15 and we use quantum frequency conversion 16 to shift the atomic wavelength to telecommunications wavelengths. We realize entanglement over 22 kilometres of field-deployed fibres via two-photon interference 17,18 and entanglement over 50 kilometres of coiled fibres via single-photon interference 19 . Our experiment could be extended to nodes physically separated by similar distances, which would thus form a functional segment of the atomic quantum network, paving the way towards establishing atomic entanglement over many nodes and over much longer distances.

Aim: To investigate the effectiveness of over-the-scope-clip (OTSC)-based endoscopic closure in patients with perforated peptic ulcer (PPU)., Methods: One hundred six patients diagnosed with PPU were treated with either OTSC (n = 26) or conservative treatments (n = 80), respectively. The outcome assessments included technical success rate, clinical success rate, post-treatment complications after 1 month, mortality rate, time to resume oral feeding, length of hospital stay, and the administration of antibiotics., Results: In the OTSC group, technical and clinical success was achieved in 100% of patients without any complications, including death, incomplete closure, duodenal obstruction, and gastrointestinal bleeding, with a median operation time of 10 min. All patients in the OTSC group were discharged, while the mortality rate in the control group was 13.8%. Subsequent surgeries were required in 30% of patients in the control group. The median times to resume oral feeding were 3.5 (interquartile range [IQR] 2.0-5.25) days in the OTSC group and 7.0 (IQR 5.0-9.0) days in the control group (p < 0.001). One month post-procedure, 30% (24/80) of patients in the control group and 0 (0/26) in the OTSC group required additional operations (p < 0.001). No significant difference was found in the length of the hospital stay and the administration of antibiotics between the two groups (p > 0.05)., Conclusions: OTSC-based endoscopic technique, with a high clinical success rate and a shorter time to resume oral feeding, was effective in achieving closure of PPU with a diameter < 15 mm.

Noise-induced hearing loss (NIHL) relates closely to auditory cortex (AC) injury, so countermeasures aiming at the AC recovery would be of benefit. In this work, the effect of hyperbaric oxygen treatment on NIHL was elucidated, which was imposed on mice before (HBOP), during (HBOD) or after (HBOA) noise exposure. Morphology of neurons was assayed by hematoxylin-eosin or Nissl staining. Ceramide (Cer) level was measured through immunohistochemistry analysis. Apoptotic neurons were counted using transferase-mediated dUTP nick end labeling (TUNEL) staining. We demonstrated that the intense, broad band noise raised the threshold of auditory brainstem response, evoked neuronal degeneration or apoptosis and triggered the Cer accumulation in AC, all of which were restored significantly by HBOP, but not HBOD or HBOA. Cer over-generation reversed the advantages of HBOP significantly, while its curtailment recapitulated the effect. Next, noise exposure raised the superoxide or malondialdehyde (MDA) production which was blocked by HBOP or Cer repression. Oxidative control not only attenuated the hearing loss or neurodegeneration but, in turn, reduced the Cer formation significantly. In summary, mutual regulation between Cer and oxidative stress underlies the HBOP's curative effect on hearing loss and neuronal damage in noise-exposed mice.

Abstract: Objective To analyze a knowledge web of the literature published by Journal of Forensic Medicine from its founding in 1985 to 2018, describe the evolving process of forensic science research and explore the research hotspots and frontiers at present. Methods The literature that was published by Journal of Forensic Medicine from 1985 to 2018 was collected and analyzed in terms of elements, such as emerging research hotspots, high frequency keywords, authors, dispatching units, location of institution and funding, by CiteSpace5.3 information visualization analysis software. Results All disciplines of forensic medicine were continually developing and maturing, and the publication volume of the literature on forensic pathology had the highest weight; in research hotspots, the two categories, research and identification each had their own emphasis; as the main source of contributions to the journal, research institutes accounted for 38.99% of the total number of publications; Shanghai ranked first among all regions with 1 046 articles published. The number of funded articles was generally on the rise, with the number of funded articles published largest in 2015. Conclusion As an authoritative academic journal in the field of forensic science in China, Journal of Forensic Medicine carries the development of forensic science and witnesses the institutional reform of universities and colleges, and offers a wide range of communication and cooperation in terms of technicality and application. Many scholars and scientific research institutions have gained progress continually in various research directions in the form of teamwork; and emerging research hotspots will continue to play a huge role in future practical applications., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: Identifying cancer biomarkers from transcriptomics data is of importance to cancer research. However, transcriptomics data are often complex and heterogeneous, which complicates the identification of cancer biomarkers in practice. Currently, the heterogeneity still remains a challenge for detecting subtle but consistent changes of gene expression in cancer cells., Results: In this paper, we propose to adaptively capture the heterogeneity of expression across samples in a gene regulation space instead of in a gene expression space. Specifically, we transform gene expression profiles into gene regulation profiles and mathematically formulate gene regulation probabilities (GRPs)-based statistics for characterizing differential expression of genes between tumor and normal tissues. Finally, an unbiased estimator (aGRP) of GRPs is devised that can interrogate and adaptively capture the heterogeneity of gene expression. We also derived an asymptotical significance analysis procedure for the new statistic. Since no parameter needs to be preset, aGRP is easy and friendly to use for researchers without computer programming background. We evaluated the proposed method on both simulated data and real-world data and compared with previous methods. Experimental results demonstrated the superior performance of the proposed method in exploring the heterogeneity of expression for capturing subtle but consistent alterations of gene expression in cancer., Conclusions: Expression heterogeneity largely influences the performance of cancer biomarker identification from transcriptomics data. Models are needed that efficiently deal with the expression heterogeneity. The proposed method can be a standalone tool due to its capacity of adaptively capturing the sample heterogeneity and the simplicity in use., Software Availability: The source code of aGRP can be downloaded from https://github.com/hqwang126/aGRP .

Although a number of methods have been proposed for identifying differentially expressed pathways (DEPs), few efforts consider the dynamic components of pathway networks, i.e., gene links. We here propose a signaling dynamics detection method for identification of DEPs, DynSig, which detects the molecular signaling changes in cancerous cells along pathway topology. Specifically, DynSig relies on gene links, instead of gene nodes, in pathways, and models the dynamic behavior of pathways based on Markov chain model (MCM). By incorporating the dynamics of molecular signaling, DynSig allows for an in-depth characterization of pathway activity. To identify DEPs, a novel statistic of activity alteration of pathways was formulated as an overall signaling perturbation score between sample classes. Experimental results on both simulation and real-world datasets demonstrate the effectiveness and efficiency of the proposed method in identifying differential pathways., Competing Interests: The authors declare no conflict of interest.

The paper provides relaxed designs of fault estimation observer for nonlinear dynamical plants in the Takagi-Sugeno form. Compared with previous theoretical achievements, a modified version of fuzzy fault estimation observer is implemented with the aid of the so-called maximum-priority-based switching law. Given each activated switching status, the appropriate group of designed matrices can be provided so as to explore certain key properties of the considered plants by means of introducing a set of matrix-valued variables. Owing to the reason that more abundant information of the considered plants can be updated in due course and effectively exploited for each time instant, the conservatism of the obtained result is less than previous theoretical achievements and thus the main defect of those existing methods can be overcome to some extent in practice. Finally, comparative simulation studies on the classical nonlinear truck-trailer model are given to certify the benefits of the theoretic achievement which is obtained in our study., (Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.)

To report a rare case of multiple primary carcinoma：laryngeal neuroendocrine carcinoma complicated with splenic mantle cell lymphoma to improve the understanding of multiple primary carcinoma. The incidence rate of multiple primary carcinoma was low. Laryngeal neuroendocrine carcinoma with mantle cell lymphoma has not been reported yet. Early diagnosis and antidiastole is very important for MPC. Pathological examination and immunohistochemistry plays an important role in the diagnosis of multiple primary carcinoma, laryngeal neuroendocrine carcinoma and mantle cell lymphoma., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20-20 KHz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg kg -1  days -1 . Morphology of neurons was examined using hematoxylin-eosin (HE) and Nissl staining. Apoptosis was assayed through transferase-mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4-32 KHz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P < 0.05). DOX partly restored noise-caused hearing loss alleviating morphologic changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were elevated significantly by noise which was reversed upon DOX treatment (P < 0.05), but neither noise nor DOX altered AC content. DOX had no influence on hearing, neuronal morphology or ASM/Cer in control mice. Our result suggests DOX palliates noise induced hearing loss and neuronal damage in auditory cortex by correcting over-activation of ASM/Cer without hampering intrinsic behavior of it. Anat Rec, 300:2220-2232, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Based on the land-use satellite image datasets of 2000, 2010 and 2015, the landscape index, dynamic change model, landscape transfer matrix and CLUE-S model were integrated to analyze the dynamic evolution of the landscape spatial pattern of Taihu Lake basin. The results showed that the landscape type of the basin was dominated by cultivated land and construction land, and the degree of landscape fragmentation was strengthened from 2000 to 2015, and the distribution showed a uniform trend. From the point of transfer dynamic change, the cultivated land and construction land changed significantly, which was reduced by 6761 km 2 (2.1%) and increased by 6615.33 km 2 (8.4%), respectively. From the landscape transfer, it could be seen that the main change direction of the cultivated land reduction was the construction land, and the cultivated land with 7866.30 km 2 was converted into construction land, accounting for 91.6% of the cultivated land change, and the contribution to the construction land was 96.5%. The trend of dynamic changes of cultivated and construction land in the counties and cities was the same as that of the whole Taihu Lake basin. For Shanghai Central Urban, as well as Pudong District, Lin'an City, Baoshan District, Minhang District, Jiading District and Changzhou City, the area of the cultivated land and construction land changed more prominently. However, compared with the CLUE-S model for the landscape pattern change in 2030, the change of cultivated and construction lands would be the largest in the natural development scenario. Under the ecological protection scenario, the area of grassland would increase and the dynamic degree would reach 54.5%. Under the situation of cultivated land protection, the conversion of cultivated land to construction land would be decreased.

Taihu Lake basin was selected as the study site. Based on the landscape data of 2000, 2005, 2010 and 2015, the Markov and CLUE-S models were used to simulate the landscape types with different scenarios in 2030, and landscape ecological risk index was constructed. The shift of gravity center and spatial statistics were used to reveal landscape ecological risk of Taihu Lake basin with temporal and spatial characteristics. The results showed that the ecological risk mainly was at medium and low levels in Taihu Lake basin, and the higher ecological risk areas were mainly distributed at the Taihu Lake area during 2000 to 2015, and the low ecological risk was transferred from the southwest and south of Taihu Lake to the developed areas in the northern part of Taihu Lake area. Spatial analysis showed that landscape ecological risk had negative correlation with natural factors, which was weakened gradually, while the correlation with socioeconomic factors trended to become stronger, with human disturbance affecting the landscape ecological risk significantly. The impact of socioeconomic factors on landscape ecological risks differed in different urbanization stages. In the developing area, with the economic development, the landscape was increasingly fragmented and the ecological risk was correspondingly increased. While in the developed area, with the further development of the economy, the aggregation index was increased, and fragmentation and separation indexes were decreased, ecological construction was restored, and the landscape ecological risk began to decline. CLUE-S model simulation showed that the ecological risk of Taihu Lake basin would be reduced in future, mainly on the low and relatively low levels. Taihu Lake area, both in history and the future, is a high ecological risk zone, and its management and protection should be strengthened.

Identifying differentially expressed pathways (DEPs) plays important roles in understanding tumor etiology and promoting clinical treatment of cancer or other diseases. By assuming gene expression to be a sparse non-negative linear combination of hidden pathway signals, we propose a pathway crosstalk-based transcriptomics data analysis method (ctPath) for identifying differentially expressed pathways. Biologically, pathways of different functions work in concert at the systematic level. The proposed method interrogates the crosstalks between pathways and discovers hidden pathway signals by mapping high-dimensional transcriptomics data into a low-dimensional pathway space. The resulted pathway signals reflect the activity level of pathways after removing pathway crosstalk effect and allow a robust identification of DEPs from inherently complex and noisy transcriptomics data. CtPath can also correct incomplete and inaccurate pathway annotations which frequently occur in public repositories. Experimental results on both simulation data and real-world cancer data demonstrate the superior performance of ctPath over other popular approaches. R code for ctPath is available for non-commercial use at the URL http://micblab.iim.ac.cn/Download/., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Large-scale accumulation of omics data poses a pressing challenge of integrative analysis of multiple data sets in bioinformatics. An open question of such integrative analysis is how to pinpoint consistent but subtle gene activity patterns across studies. Study heterogeneity needs to be addressed carefully for this goal., Results: This paper proposes a regulation probability model-based meta-analysis, jGRP, for identifying differentially expressed genes (DEGs). The method integrates multiple transcriptomics data sets in a gene regulatory space instead of in a gene expression space, which makes it easy to capture and manage data heterogeneity across studies from different laboratories or platforms. Specifically, we transform gene expression profiles into a united gene regulation profile across studies by mathematically defining two gene regulation events between two conditions and estimating their occurring probabilities in a sample. Finally, a novel differential expression statistic is established based on the gene regulation profiles, realizing accurate and flexible identification of DEGs in gene regulation space. We evaluated the proposed method on simulation data and real-world cancer datasets and showed the effectiveness and efficiency of jGRP in identifying DEGs identification in the context of meta-analysis., Conclusions: Data heterogeneity largely influences the performance of meta-analysis of DEGs identification. Existing different meta-analysis methods were revealed to exhibit very different degrees of sensitivity to study heterogeneity. The proposed method, jGRP, can be a standalone tool due to its united framework and controllable way to deal with study heterogeneity.

Objective: To evaluate the efficacy and safety of testa triticum tricum purif for the treatment of functional constipation(FC) in the late middle-aged and elderly patients. Methods: This study was designed as a multicenter randomized controlled trial. Patients who met Rome Ⅲ diagnostic criteria of FC were enrolled, with age between 55-85 years old. Those with organic diseases were excluded. The patients were randomly allocated to receive testa triticum tricum purif (3.5 g bid) or polyethylene glycol 4000 powder (PEG4000, 10g bid) for 8 weeks, followed by single dose of maintenance therapy for 4 weeks. Follow-up visits were at 4 and 12 weeks after treatment discontinuation. The independent investigators in each center evaluated the constipation symptoms scores. The primary endpoints included rates of significant improvement, improvement and overall improvement at the end of 2, 4 and 8 weeks of therapy, which were calculated by the reduction of symptom scores ≥75%, 50%-74%, ≥25% respectively. Results: A total of 127 FC subjects were enrolled from 3 centers, and 122 cases valid for final analysis. The mean age was (69.4±6.9) years old, including 62 cases in testa triticum tricum purif group and 60 cases in PEG4000 group. The demographic data, constipated symptoms scores and proportion of FC subtypes at baseline were comparable. The rates of significant improvement, improvement and overall improvement in testa triticum tricum purif and PEG4000 groups at the end of 2, 4 and 8 weeks were 37.70% (23/61) vs 59.32% (35/59) ( P =0.018), 57.38% (35/61) vs 74.14% (43/58) ( P =0.054), and 64.41% (38/59) vs 79.31% (46/58) ( P =0.073) respectively. Testa triticum tricum purif therapy significantly improved the proportion of spontaneous bowel movement(SBM) ≥3 times/week from 43.55% (27/62) to 80.33% (49/61), 83.61% (51/61) and 93.22% (55/59) at 2, 4, and 8 weeks respectively (all P <0.01), which were comparable with PEG4000 group (all P >0.05). The proportion of normalized stool forms in study group was significant higher than that of control group at the end of 8 weeks [86.44% (51/59) vs 67.24% (39/58), P =0.014]. Only one patient complained mild abdominal distension during testa triticum tricum purif therapy. Conclusions: The efficacy of testa triticum tricum purif for the treatment of FC in late middle-aged and older patients is comparable with osmotic laxatives PEG4000, which has significant effect on normalization of fecal forms and reliable safety.