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In this paper, we consider a class of highly oscillatory Hamiltonian systems which involve a scaling parameter $\varepsilon\in(0,1]$. The problem arises from many physical models in some limit parameter regime or from some time-compressed perturbation problems. The solution of the model exhibits rapid temporal oscillations with $\mathcal{O}(1)$-amplitude and $\mathcal{O}(1/\varepsilon)$-frequency, which makes classical numerical methods inefficient. We apply the two-scale formulation approach to the problem and propose two new time-symmetric numerical integrators. The methods are proved to have the uniform second order accuracy for all $\varepsilon$ at finite times and some near-conservation laws in long times. Numerical experiments on a H\'{e}non-Heiles model, a nonlinear Schr\"{o}dinger equation and a charged-particle system illustrate the performance of the proposed methods over the existing ones., Comment: 21 pages

Bin Lu,1 Xinling Pan,2 Bin Wang,3 Chenyuan Jin,1 Chenxin Liu,1 Mengqi Wang,4 Yunzhen Shi1 1Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of China; 2Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 3Department of Emergency, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of China; 4Department of Neurology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yunzhen Shi, Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, No. 60 Wuningxi Road, Dongyang, People’s Republic of China, Email syzwylwmc@163.comPurpose: We attempted to establish a model for predicting the mortality risk of sepsis patients during hospitalization.Patients and Methods: Data on patients with sepsis were collected from a clinical record mining database, who were hospitalized at the Affiliated Dongyang Hospital of Wenzhou Medical University between January 2013 and August 2022. These included patients were divided into modeling and validation groups. In the modeling group, the independent risk factors of death during hospitalization were determined using univariate and multi-variate regression analyses. After stepwise regression analysis (both directions), a nomogram was drawn. The discrimination ability of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and the GiViTI calibration chart assessed the model calibration. The Decline Curve Analysis (DCA) was performed to evaluate the clinical effectiveness of the prediction model. Among the validation group, the logistic regression model was compared to the models established by the SOFA scoring system, random forest method, and stacking method.Results: A total of 1740 subjects were included in this study, 1218 in the modeling population and 522 in the validation population. The results revealed that serum cholinesterase, total bilirubin, respiratory failure, lactic acid, creatinine, and pro-brain natriuretic peptide were the independent risk factors of death. The AUC values in the modeling group and validation group were 0.847 and 0.826. The P values of calibration charts in the two population sets were 0.838 and 0.771. The DCA curves were above the two extreme curves. Moreover, the AUC values of the models established by the SOFA scoring system, random forest method, and stacking method in the validation group were 0.777, 0.827, and 0.832, respectively.Conclusion: The nomogram model established by combining multiple risk factors could effectively predict the mortality risk of sepsis patients during hospitalization.Keywords: severe sepsis, mortality risk prediction, nomogram, SOFA, random forest, stacking

Yuanxiao Li,1,* Ying Tian,2,* Shufen Pei,3 Baoyuan Xie,2 Xiaonan Xu,1 Bin Wang4 1Department of Pediatric Gastroenterology, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 2Department of Clinical Medicine, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 3Department of Clinical Medicine, North Sichuan Medical College, Nanchong, People’s Republic of China; 4Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Wang, 88 Jie Fang Lu, Shangcheng District, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email wangbin2022@zju.edu.cnObjective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice.Methods: A retrospective analysis of 944 studies was performed on February 28, 2023.Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the “Brief Summary”. A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions.Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent.Keywords: real-world data, real-world evidence, real-world study, study design, ClinicalTrials.gov

The existence of glacial lakes in the southeastern Tibetan Plateau (SETP) is a potential hazard to downstream regions, as the outburst of such lakes has the potential to result in disastrous glacial lake outburst floods (GLOFs). In the present study, we conducted a comprehensive investigation of Bienong Co, a moraine-dammed glacial lake in the SETP. First, the lake basin morphology was determined, and the lake volume was estimated, showing that the maximum lake depth is ∼181 m and the lake volume is ∼102.3×106 m3. These scenarios included the possibility of GLOFs being triggered by ice avalanches (Scenarios A1–3) from the mother glacier or by landslides from the lateral moraines (Scenarios B1–3 and C1–3). Avalanche volumes of the nine trigger scenarios were obtained from the Rapid Mass Movement Simulation (RAMMS) modeling results. Next, the Basic Simulation Environment for Computation of Environmental Flow and Natural Hazard Simulation (BASEMENT) model was used to simulate the generation and propagation of the avalanche-induced displacement waves in the lake. With the model, the overtopping flows and erosion on the moraine dam and the subsequent downstream floods were also simulated. The results indicate that the ice avalanche scenario may cause the largest mass volume entering the lake, resulting in a displacement wave up to 25.2 m in amplitude (Scenario A3) near the moraine dam. Landslide scenarios with smaller volumes entering the lake result in smaller displacement waves. Scenarios A1, A2, and A3 result in released water volumes from the lake of 24.1×106, 25.3×106, and 26.4×106 m3, respectively. Corresponding peak discharges at the moraine dam are 4996, 7817, and 13 078 m3 s−1, respectively. These high discharges cause erosion of the moraine dam, resulting in breach widths of 295, 339, and 368 m, respectively, with the generally similar breach depth of approximately 19 m. In landslide scenarios, only overtopping flows generated by Scenarios B3 and C3 cause erosion on the moraine dam, with breach depths of 6.5 and 7.9 m and breach widths of 153 and 169 m, respectively. According to our simulations, GLOFs generated by Scenarios A1–3 all flow through 18 settlements downstream in 20 h, threatening more than half of them. Both Scenarios B3 and C3 produce GLOFs that flow through the first eight settlements downstream in 20 h and have a relatively small impact on them. Comparisons of the area, depth, and volume of glacial lakes for which the bathymetry data are available show that Bienong Co is the deepest known glacial lake with the same surface area on the Tibetan Plateau. This study could provide a new insight into moraine-dammed glacial lakes in the SETP and be a valuable reference for GLOF disaster prevention for the local government.

Ardisia crenata var. bicolor is a multi-purpose plant and has important ornamental and medicinal properties. Conventional methods of propagating the species from seeds and cuttings have low efficiency because of the recalcitrant properties of seeds and low survival rate of high-quality cuttings. This work aims to study the in vitro regeneration protocol for direct organogenesis from nodal segments of A. crenata var. bicolor on Murashige and Skoog (MS) medium, with different combinations and concentrations of plant growth regulators (PGRs). The treatments used for the establishment and proliferation of shoots included MS medium supplemented with different concentrations of Benzyl-aminopurine (BAP) and indole-3-butyric acid (IBA). For rooting, IBA was used in combination with naphthaleneacetic acid (NAA) in full- and half-strength MS media. Maximum shoot establishment (76.67%) and the highest shoot length (6.6 cm) were observed on MS medium with 1.0 mg·L−1 BAP with 0.5 mg·L−1 IBA, while BAP at 1.0 mg·L−1 with 0.25 mg·L−1 IBA obtained the highest shoot proliferation (4.5 ± 1.53). The best rooting response (83.33%) was achieved on half-strength MS including 1.0 mg·L−1 IBA with 0.25 mg·L−1 NAA, and the maximum survival rate of 84.4% was observed after acclimatization under 75% shading. To define their genetic stability, using eleven primers of ISSR markers to assess the genetic stability of the unstable leaf color samples compared with their mother plant, the ISSR markers demonstrated a level of genetic polymorphism in plantlets, but without other morphological variations. This indicates the genetic resemblance to the mother plant and the reliability of this protocol for the efficient micropropagation of A. crenata var. bicolor.

The group intelligence perception privacy protection model is a method to achieve the balance between user privacy and service requests through the cooperation between users using location services and has a good perception effect. In order to better protect the location privacy of network users and improve the stability control effect of fuzzy estimation of location flow, this paper designs a stability control method of fuzzy estimation of location flow in group intelligent perception privacy protection. This method uses the group intelligence aware privacy protection model to obtain the user network location coordinates in the group intelligence aware privacy protection. Taking the user’s network location coordinates as input, the location flow queue of multiple users in the group intelligence aware privacy protection network is obtained by the Lyapunov multiobjective location flow estimation queue model. After the fuzzy processing of the user location flow queue, the online control mechanism of location flow fuzzy estimation stability under different conditions is established. According to the online control mechanism, a stability control method based on access control and group intelligence aware task allocation is used to realize the stability control of location flow fuzzy estimation in group intelligence aware privacy protection. The experimental results show that the method can obtain 100% of the user location integrity in the group intelligence aware privacy protection, and the target location flow estimation queue is more accurate. It can effectively reduce the number of communication rounds of fuzzy estimation of location flow in the group intelligence aware privacy protection and has better stability control ability.

We propose a novel framework for computing the medial axis transform of 3D shapes while preserving their medial features via restricted power diagram (RPD). Medial features, including external features such as the sharp edges and corners of the input mesh surface and internal features such as the seams and junctions of medial axis, are important shape descriptors both topologically and geometrically. However, existing medial axis approximation methods fail to capture and preserve them due to the fundamentally under-sampling in the vicinity of medial features, and the difficulty to build their correct connections. In this paper we use the RPD of medial spheres and its affiliated structures to help solve these challenges. The dual structure of RPD provides the connectivity of medial spheres. The surface restricted power cell (RPC) of each medial sphere provides the tangential surface regions that these spheres have contact with. The connected components (CC) of surface RPC give us the classification of each sphere, to be on a medial sheet, a seam, or a junction. They allow us to detect insufficient sphere sampling around medial features and develop necessary conditions to preserve them. Using this RPD-based framework, we are able to construct high quality medial meshes with features preserved. Compared with existing sampling-based or voxel-based methods, our method is the first one that can preserve not only external features but also internal features of medial axes., Comment: 18 pages, 26 figures, SIGGRAPH Asia 2022

This paper is concerned with geometric exponential energy-preserving integrators for solving charged-particle dynamics in a magnetic field from normal to strong regimes. We firstly formulate the scheme of the methods for the system in a uniform magnetic field by using the idea of continuous-stage methods, and then discuss its energy-preserving property. Moreover, symmetric conditions and order conditions are analysed. Based on those conditions, we propose two practical symmetric continuous-stage exponential energy-preserving integrators of order up to four. Then we extend the obtained methods to the system in a nonuniform magnetic field and derive their properties including the symmetry, convergence and energy conservation. Numerical experiments demonstrate the efficiency of the proposed methods in comparison with some existing schemes in the literature., 21 pages,36 figures

We aim to investigate the potential role and underlying mechanisms of linc00174 on pyroptosis in the pathogenesis of DR.Expression patterns of linc00174, miR-26a-5p and PTEN in human retinal microvascular endothelial cells (hRMECs) were detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Biological functions of linc00174 on cell proliferation and pyroptosis were evaluated by CCK-8, flow cytometry, caspase-1 activity assays, respectively. Luciferase reporter assay was employed to verify the interaction between miR-26a-5p and linc00174/PTEN. Streptozotocin (STZ)-induced DR in mice was further constructed to verify the potential role of linc00174 in vivo. Hematoxylin and eosin (HE) and immunohistochemical staining were performed to assess the pathological changes and caspase-1 expression in retinal tissues.Up-regulated linc00174 and PTEN and down-regulated miR-26a-5p were uncovered in hRMECs treated with high glucose (HG). Mechanistically, linc00174 served as a sponge of miR-26a-5p to facilitate PTEN expression. Functionally, knockdown of linc00174 inhibited HG-induced pyroptosis of hRMECs via targeting miR-26a-5p. Moreover, linc00174/miR-26a-5p axis participated in HG-induced pyroptosis via PTEN/Akt signaling cascade. Further, silencing of linc00174 attenuated pyroptosis via regulating miR-26a-5p/PETN axis in DR mice.Collectively, our study reveals that linc10074 deteriorates the pathogenesis of DR via miR-26a-5p/PTEN/Akt signalling cascade, which may shed light on the discovery of potential therapeutic agents for DR treatment.

The strain variations in Elm earlywood and latewood during drying were studied with digital image correlation method. Also, the moisture contents of different water states were quantified based on time-domain nuclear magnetic resonance technique to reveal the strain-water relationships. Although the shrinkage strains gradually increased with increasing drying time, there was a significant difference in the strain distribution of the earlywood and latewood. Owing to latewood large stress, the earlywood was pulled by it to shrink together, and the earlywood maximum shrinkage appeared in the early/latewood junction, while the maximum shrinkage of latewood happened in its middle part. Wood shrinkage strain increased fast in the early-drying stage, mainly influenced by moisture content variation; in the mid-drying stage, the shrinkage increased slowly due to the synergistic effect of free and bound water migration; in the late-drying stage, the bound water variation led to a mild shrinkage.

Vestibular schwannoma (VS), the most common intercranial schwannoma, originates from the sheath of the vestibular nerve. The growth rate of VS varies greatly, with the tumor enlarging gradually, which can compress the peripheral nerve tissue and reveal corresponding symptoms. This study was aimed to elucidate the growth mechanism of VS by analyzing cellular changes at protein, messenger ribonucleic acid (mRNA), and other molecular levels.We determined mRNA and protein levels of β 2 -microglobulin (β 2 -M) and nuclear factor κB (NF-κB) in tumors of different sizes using the real-time polymerase chain reaction and Western blotting, respectively. The relationship between these factors was verified in VS primary cells cultured in vitro, and the potential role of β 2 -M and NF-κB in VS growth was elucidated.In the secretions of freshly isolated tumor tissue cultured for 72 h, the concentration of β 2 -M was positively correlated with the tumor diameter. Furthermore, tumors with larger diameter showed higher expressions of β 2 -M and NF-κB at protein and mRNA level. β 2 -M treatment resulted in elevated protein expression of NF-κB and also its phosphorylated form in vitro.β 2 -M may participate in VS growth by regulating NF-κB and act as a key regulatory molecule in VS tumor growth.

IntroductionNonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are both chronic multisystem diseases that cause tremendous health burdens worldwide. Previous epidemiological studies have found a bidirectional relationship between these two diseases; however, their causality remains largely unknown. We aim to examine the causal relationship between NAFLD and T2DM.MethodsThe observational analysis included 2,099 participants from the SPECT-China study and 502,414 participants from the UK Biobank. Logistic regression and Cox regression models were used to examine the bidirectional association between NAFLD and T2DM. Two-sample Mendelian randomization (MR) analyses were conducted to investigate the causal effects of the two diseases using summary statistics of genome-wide association studies from the UK Biobank for T2DM and the FinnGen study for NAFLD.ResultsDuring the follow-up, 129 T2DM cases and 263 NAFLD cases were observed in the SPECT-China study, and 30,274 T2DM cases and 4,896 NAFLD cases occurred in the UK Biobank cohort. Baseline NAFLD was associated with an increased risk of incident T2DM in both studies (SPECT-China: OR: 1.74 (95% confidence interval (CI): 1.12–2.70); UK Biobank: HR: 2.16 (95% CI: 1.82–2.56)), while baseline T2DM was associated with incident NAFLD in the UK Biobank study only (HR: 1.58). Bidirectional MR analysis showed that genetically determined NAFLD was significantly associated with an increased risk of T2DM (OR: 1.003 (95% CI: 1.002–1.004, p< 0.001)); however, there was no evidence of an association between genetically determined T2DM and NAFLD (OR: 28.1 (95% CI: 0.7–1,143.0)).ConclusionsOur study suggested the causal effect of NAFLD on T2DM development. The lack of a causal association between T2DM and NAFLD warrants further verification.

Long non-coding RNAs (lncRNAs) play vital roles in regulating epigenetic mechanisms and gene expression levels, and their dysregulation is closely associated with a variety of diseases such as cancer. Several studies have demonstrated that lncRNAs are dysregulated during tumor progression. Recently, the MYC-induced long non-coding RNA MINCR, a newly identified lncRNA, has been demonstrated to act as an oncogene in different cancers, including gallbladder cancer, hepatocellular cancer, colorectal cancer, non-small cell lung cancer, oral squamous cell carcinoma, nasopharyngeal cancer, and glioma. Moreover, MINCR has been reported to act as a biomarker in the prognosis of patients with different cancers. In this review, we summarize and analyze the oncogenic roles of MINCR in a variety of human cancers in terms of its clinical significance, biological functions, cellular activities, and regulatory mechanism. Our analysis of the literature suggests that MINCR has potential as a novel biomarker and therapeutic target in human cancers.

Yan Xuan,1,2,&ast; Wen Zhang,1,&ast; Yuying Wang,1 Bin Wang,1 Yi Chen,1 Fangzhen Xia,1 Kun Zhang,1 Qing Li,1 Ningjian Wang,1 Yingli Lu1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China, Tel +86-13636352507, Fax +86-21-63136856, Email luyingli2008@126.comBackground: The aim of this study was measuring the association between the hypertriglyceridemic-waist (HTGW) phenotype and chronic kidney disease in a large type 2 diabetes population.Methods: A total of 4254 diabetic patients from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study were enrolled. The hypertriglyceridemic-waist (HTGW) phenotype was defined as the presence of an elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 or urinary albumin creatinine ratio (uACR) more than 30 mg/g. Linear and multiple logistic regression models were used for measuring the association between HTGW phenotype and chronic kidney disease.Results: The prevalence of CKD was 29% and 35.8% in total participants and participants with HTGW phenotype, respectively. Subjects in the HTGW phenotype group were more likely to have CKD (OR 1.47, 95% CI: 1.11, 1.95) compared with subjects in the normal waist circumference and normal triglycerides (NTNW) group. HTGW phenotype was both associated with the increasing risk of decreased eGFR (OR 1.31, 95% CI: 1.02, 1.75) and elevated uACR (OR 1.57, 95% CI: 1.18, 2.11). Furthermore, the stratified analysis showed that the strongest positive association between HTGW phenotype and CKD presence was found in the subgroup of presence of hypertension. The associations were all fully adjusted for age, sex, BMI, current smoking, current drinking and other confounding factors.Conclusion: Our study suggested a positive association between the HTGW phenotype and CKD in Chinese type 2 diabetes patients. Further prospective studies are needed to confirm our findings and to investigate the underlying biological mechanisms.Keywords: central obesity, type 2 diabetes mellitus, hypertriglyceridemia waist phenotype, chronic kidney disease

Rhizosphere microbes have an extremely close relationship with plants and the study on the relationship between rhizosphere microorganisms and their influencing factors is conducive to the protection of vegetation and the maintenance of biodiversity. Here we investigated how plant species, slope positions and soil types affect the rhizosphere microbial community. Slope positions and soil types were collected from northern tropical karst and non-karst seasonal rainforests. The results indicated that soil types played a predominant role in the development of rhizosphere microbial communities (28.3% of separate contribution rate), more than plant species identity (10.9% of separate contribution rate) and slope position (3.5% of separate contribution rate). Notably, environmental factors closely related to soil properties were the major influence factors that controlling the rhizosphere bacterial community structure in the northern tropical seasonal rainforest, especially pH. Additionally, plant species also influenced the rhizosphere bacterial community. In low nitrogen content soil environments, rhizosphere biomarkers of dominant plant species were often nitrogen-fixing strains. It suggested that plants might have a selective adaptation mechanism to rhizosphere microorganisms to obtain the advantages of nutrient supply. Overall, soil types exerted the biggest influence on rhizosphere microbial community structure, followed by plant species and finally slope positions.

ObjectiveThe study aims to explore the possibility of prelaryngeal and/or pretracheal lymph node metastasis in identifying papillary thyroid carcinoma with more than 5 metastatic central lymph nodes from unilateral lobe cT1-2N0 papillary thyroid carcinoma.MethodsA retrospective analysis was conducted on patients who underwent the initial thyroid surgery for unilateral lobe cT1-2N0 PTC in a single tertiary center between July 2018 to December 2022. Multivariable binary logistic regression analysis was used to identify risk factors for unilateral lobe cT1-2N0 papillary thyroid carcinoma with more than 5 metastatic central lymph nodes.ResultsA total of 737 patients were included in the study and 399 patients were confirmed to suffer from occult central lymph node metastasis. The larger size of the largest diameter of tumor (> 1cm; OR = 3.3, 95%CI 1.6 – 6.83; p = 0.001), pretracheal lymph node metastasis (OR = 5.91, 95%CI 2.73 – 12.77; p < 0.001), prelaryngeal lymph node metastasis (OR = 3.74, 95%CI 1.73 – 8.1; p = 0.001), ipsilateral paratracheal lymph node metastasis (OR = 12.22, 95%CI 3.43 – 43.48; p < 0.001), and contralateral paratracheal lymph node metastasis (OR = 7.68, 95%CI 3.86 – 15.3; p < 0.001) were confirmed to be risk factors for unilateral lobe cT1-2N0 PTC with more than 5 metastatic central lymph nodes. When more than two metastatic prelaryngeal and/or pretracheal lymph nodes occurred, the incidence of more than 5 metastatic central lymph nodes was 71.2%.ConclusionPrelaryngeal and/or pretracheal lymph node metastasis could help to identify papillary thyroid carcinoma with more than 5 metastatic central lymph nodes from unilateral lobe cT1-2N0 papillary thyroid carcinoma. When more than two metastatic pretracheal and/or prelaryngeal lymph nodes occurred, total thyroidectomy and ipsilateral central lymph node dissection should be performed and contralateral paratracheal lymph node dissection might be also necessary.

Efficient protein secretion is closely correlated with vesicle sorting and packaging, especially with cargo receptor-mediated selective transport for ER exit. Even though Aspergillus niger is considered an industrially natural host for protein production due to its exceptional secretion capacity, the trafficking mechanism in the early secretory pathway remains a black box for us to explore. Here, we identified and characterized all putative ER cargo receptors of the three families in A. niger. We successfully constructed overexpression and deletion strains of each receptor and compared the colony morphology and protein secretion status of each strain. Among them, the deletion of Erv14 severely inhibited mycelial growth and secretion of extracellular proteins such as glucoamylase. To gain a comprehensive understanding of the proteins associated with Erv14, we developed a high-throughput method by combining yeast two-hybrid (Y2H) with next-generation sequencing (NGS) technology. We found Erv14 specifically interacted with transporters. Following further validation of the quantitative membrane proteome, we determined that Erv14 was associated with the transport of proteins involved in processes such as cell wall synthesis, lipid metabolism, and organic substrate metabolism.

Clays have considerable influence on the electrical properties of hydrate-bearing sediments. It is desirable to understand the electrical properties of hydrate-bearing clayey sediments and to build hydrate saturation (Sh) models for reservoir evaluation and monitoring. The electrical properties of tetrahydrofuran-hydrate-bearing sediments with montmorillonite are characterized by complex conductivity at frequencies from 0.01 Hz to 1 kHz. The effects of clay and Sh on the complex conductivity were analyzed. A decrease and increase in electrical conductance result from the clay-swelling-induced blockage and ion migration in the electrical double layer (EDL), respectively. The quadrature conductivity increases with the clay content up to 10% because of the increased surface site density of counterions in EDL. Both the in-phase conductivity and quadrature conductivity decrease consistently with increasing Sh from 0.50 to 0.90. Three sets of models for Sh evaluation were developed. The model based on the Simandoux equation outperforms Archie’s formula, with a root-mean-square error (ERMS) of 1.8% and 3.9%, respectively, highlighting the clay effects on the in-phase conductivity. The frequency effect correlations based on in-phase and quadrature conductivities exhibit inferior performance (ERMS = 11.6% and 13.2%, respectively) due to the challenge of choosing an appropriate pair of frequencies and intrinsic uncertainties from two measurements. The second-order Cole-Cole formula can be used to fit the complex-conductivity spectra. One pair of inverted Cole-Cole parameters, i.e., characteristic time and chargeability, is employed to predict Sh with an ERMS of 5.05% and 9.05%, respectively.

Periprosthetic osteolysis (PPO) induced by wear particles is an important cause of aseptic loosening after artificial joint replacement, among which the imbalance of osteogenesis and osteoclastic processes occupies a central position. The cells involved in PPO mainly include osteoclasts (macrophages), osteoblasts, osteocytes, and fibroblasts. RANKL/RANK/OGP axis is a typical way for osteolysis. Autophagy, a mode of regulatory cell death and maintenance of cellular homeostasis, has a dual role in PPO. Although autophagy is activated in various periprosthetic cells and regulates the release of inflammatory cytokines, osteoclast activation, and osteoblast differentiation, its beneficial or detrimental role remains controversy. In particular, differences in the temporal control and intensity of autophagy may have different effects. This article focuses on the role of autophagy in PPO, and expects the regulation of autophagy to become a powerful target for clinical treatment of PPO.

In recent years, unprecedented progress has been achieved regarding black holes' observation through the electromagnetic channel. The images of the supermassive black holes M87$^{*}$ and Sgr A$^{*}$ released by the Event Horizon Telescope (EHT) Collaboration provided direct visual evidence for their existence, which has stimulated further studies on various aspects of the compact celestial objects. Moreover, the information stored in these images provides a new way to understand the pertinent physical processes that occurred near the black holes, to test alternative theories of gravity, and to furnish insight into fundamental physics. In this review, we briefly summarize the recent developments on the topic. In particular, we elaborate on the features and formation mechanism of black hole shadows, the properties of black hole images illuminated by the surrounding thin accretion disk, and the corresponding polarization patterns. The potential applications of the relevant studies are also addressed., 17 pages, 8 figures, Acepted by Sci. China-Phys. Mech. Astron

ObjectivesTo evaluate the diagnostic efficacy of a modified thyroid imaging reporting and data system (TI-RADS) in combination with contrast-enhanced ultrasound (CEUS) for differentiating between benign and malignant thyroid nodules and to assess inter-observer concordance between different observers.MethodsThis study included 3353 patients who underwent thyroid ultrasound (US) and CEUS in ten multi-centers between September 2018 and March 2020. Based on a modified TI-RADS classification using the CEUS enhancement pattern of thyroid lesions, ten radiologists analyzed all US and CEUS examinations independently and assigned a TI-RADS category to each thyroid nodule. Pathology was the reference standard for determining the diagnostic performance (accuracy (ACC), sensitivity (SEN), specificity (SPN), positive predictive value (PPV), and negative predictive value (NPV)) of the modified TI-RADS for predicting malignant thyroid nodules. The risk of malignancy was stratified for each TI-RADS category-based on the total number of benign and malignant lesions in that category. ROC curve was used to determine the cut-off value and the area under the curve (AUC). Cohen’s Kappa statistic was applied to assess the inter-observer agreement of each sonological feature and TI-RADS category for thyroid nodules.ResultsThe calculated malignancy risk in the modified TI-RADS categories 5, 4b, 4a, 3 and 2 nodules was 95.4%, 86.0%, 12.0%, 4.1% and 0%, respectively. The malignancy risk for the five categories was in agreement with the suggested malignancy risk. The ROC curve showed that the AUC under the ROC curve was 0.936, and the cutoff value of the modified TI-RADS classification was >TI-RADS 4a, whose SEN, ACC, PPV, NPV and SPN were 93.6%, 91.9%, 90.4%, 93.7% and 88.5% respectively. The Kappa value for taller than wide, microcalcification, marked hypoechoic, solid composition, irregular margins and enhancement pattern of CEUS was 0.94, 0.93, 0.75, 0.89, 0.86 and 0.81, respectively. There was also good agreement between the observers with regards to the modified TI-RADS classification, the Kappa value was 0.80.ConclusionsThe actual risk of malignancy according to the modified TI-RADS concurred with the suggested risk of malignancy. Inter-observer agreement for the modified TI-RADS category was good, thus suggesting that this classification was very suitable for clinical application.

Purpose: To investigate the potential protective effect of hydrogen sulfide against neural cell damage induced by a high-concentration of adenosine triphosphate (ATP).Methods: PC12 cells were incubated with ATP in order to induce cell damage. The extracellular level of H2S and protein expression of cystathionine-β-synthase (CBS) were determined. The PC12 cells pretreated with NaHS, aminooxyacetic acid (AOAA) and KN-62, prior to further incubation with ATP, and the effect of the treatments on cell viability was investigated.Results: High-concentration ATP induced cell death in PC12 cells, and this was accompanied by markedly increased contents of extracellular H2S and CBS expression (p < 0.05). The ATP-induced cytotoxicity was significantly compromised after pretreatment with H2S. (p < 0.05). The viability of PC12 cells pretreated with NaHS and AOAA was significantly higher than that of PC12 cells treated with ATP alone. In addition, the viability of ATP-treated PC12 cells was further markedly increased after pretreatment with NaHS and KN-62 (p < 0.05).Conclusion: ATP induced a concentration- and time-dependent cytotoxicity in PC12 cells via theendogenous H2S/CBS system. Supplementation with exogenous H2S mitigated the cell damageinduced by high concentration of ATP via a specific mechanism which may be specifically related to P2X7R.

Aryl sulfonates were developed by ssing an energy-saving and eco-friendly approach, through ultrasound-assisted coupling reaction of readily sodium sulfinates with N-hydroxyphthalimide, under metal-free and mild conditions within 10 min at room temperature.

Seco-tetracyclic and seco-pentacyclic triterpenoids are a special class of triterpenoids with ring/rings cleaved on the original skeleton structures. A class of important triterpene derivatives, secotetracyclic and seco-pentacyclic triterpenoids, have long stimulated the interest and attention of botanists and natural products chemists. There is no systematic and comprehensive review for them. This review is focused on the phytochemical investigations and biological activities of seco-tetracyclic and seco-pentacyclic triterpenoids from nature, covering the literature from 2000-2019. This review describes 310 seco-tetracyclic and 139 seco-pentacyclic triterpenoids discovered from 154 species belong to 97 genera, which cover the chemical structures, types, sources, and bioactivities of compounds. The literature from 2000-2019 is reviewed and 208 references are cited.

Cephalosporin antibiotics, a group of widely prescribed antibiotics, are frequently detected in wastewater effluent and in the natural aquatic environment. Materials have been sought to effectively degrade the antibiotics. In this study, a novel high-iron clay was prepared with potassium ferrate and montmorillonite via a strong alkaline in-situ synthesis method. Degradation of cefazolin sodium (CFZ) by this novel Fe (VI)-clay was investigated. The optimal conditions for the degradation of CFZ were determined using a single factor experiment and response surface optimization method. We found that 89.84 % removal efficiency was obtained in 137 min when pH value was 5.16 and Fe (VI)-clay dosage was 0.79 g/100mL. The CFZ degradation mechanism was studied by the Density Functional Theory (DFT) in combination with spectroscopic and mass spectroscopic analysis. The spectroscopic characteristics of the products at different stages showed that the oxidation decomposition reaction occurred during the degradation of CFZ by Fe(VI) -clay. Further, DFT calculation combined with GC-MS results showed that the degradation pathways of CFZ by the Fe (VI)-clay was mainly the cleavage of β-lactam, thiadiazole, tetrazole and dihydrothiazine rings.

To improve the toughness and friction properties of carbon fiber reinforced ceramic matrix composite, a Cu alloy modified carbon fiber reinforced TiC based ceramic matrix composite was designed and prepared by TiCu alloy melt infiltration at low temperatures up to 1100 °C. The as-produced composite was mainly composed of carbon, TiC, Ti3Cu4, TiCu4 and Cu phases. Due to the ductile Cu alloy introduced into the matrix, the composite showed good mechanical performance especially the fracture toughness. The flexural strength reached about 248.36 MPa while the fracture toughness was up to 15.78 MPa·m1/2. The high toughness of the composite was mainly attributed to the fiber bridging, fiber pull-out, interface debonding, crack propagation and deflection. The tribological performance of the as-produced composite was measured using SiC and 440C stainless steel balls as counterparts, respectively. The as-prepared composite exhibited good wear resistance and the wear mechanism was discussed based on the microstructural observations.

The summer hypoxia off the Changjiang Estuary is one of the largest coastal hypoxic systems in the world and has displayed spatial heterogeneity in recent years. Based on observation data in the summer of 2014, hypoxia was identified both in the bottom and mid-layers. Except for the typical bottom hypoxia in the submarine canyon, the subsurface oxygen minima (SOM) were captured in the mid-layer of 10~15 m, with lower dissolved oxygen in the mid-layer than at the bottom (30–50 m). This SOM phenomenon was located in the lower boundary of the pycnocline and above the Taiwan warm current (TWC) and Kuroshio subsurface water (KSSW). Due to the southern expansion of Changjiang diluted water (CDW), a high phytoplankton biomass (the maximum chlorophyll a of 25 μg L−1, pH of 8.6, and DO of 11 mg L−1) band occupied the surface area along 123°E. By analyzing the 24-h continuous observation and high-resolution profile data, we revealed that the subsurface oxygen minima were predominantly controlled by remineralization and bottom-flushing effects. Fast local consumption occurred near the pycnocline layer, while the lateral transport of oxygen-rich ambient water replenished the bottom oxygen deficit from south to north. We summarize and contextualize three hot spots of hypoxia into a conceptual diagram and emphasize the influences of advection, mixing, and respiration on their location and severity. Overall, compared with the discussion about the low DO background of TWC/KSSW, this research highlights the flushing effects of TWC/KSSW that will reshape the hypoxia structure and alleviate the hypoxia severity in the south hypoxia area off the Changjiang Estuary.

ObjectiveThis study aims to evaluate the value of contrast-enhanced ultrasound (CEUS), shear wave elastography (SWE), and their combined use in the differentiation of American College of Radiology (ACR) thyroid imaging reporting and data system (TI-RADS) 4 and 5 category thyroid nodules coexisting with Hashimoto’s thyroiditis (HT).Materials and methodsA total of 133 pathologically confirmed ACR TI-RADS 4 and 5 category nodules coexisting with HT in 113 patients were included; CEUS and SWE were performed for all nodules. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and the area under the receiver operating characteristic curve (AUC) of the SWE, CEUS, and the combined use of both for the differentiation of benign and malignant nodules were compared, respectively.ResultsUsing CEUS alone, the sensitivity, specificity, PPV, NPV, and accuracy were 89.2%, 66.0%, 81.3%, 78.6%, and 80.5%, respectively. Using SWE alone, Emax was superior to Emin, Emean, and Eratio for the differentiation of benign and malignant nodules with the best cutoff Emax >46.8 kPa, which had sensitivity of 65.1%, specificity of 90.0%, PPV of 91.5%, NPV of 60.8%, and accuracy of 74.4%, respectively. Compared with the diagnostic performance of qualitative CEUS or/and quantitative SWE, the combination of CEUS and SWE had the best sensitivity, accuracy, and AUC; the sensitivity, specificity, PPV, NPV, accuracy, and AUC were 94.0%, 66.0%, 82.1%, 86.8%, 83.5%, and 0.80 (95% confidence interval: 0.713, 0.886), respectively.ConclusionIn conclusion, CEUS and SWE were useful for the differentiation of benign and malignant ACR TI-RADS 4 and 5 category thyroid nodules coexisting with HT. The combination of CEUS and SWE could improve the sensitivity and accuracy compared with using CEUS or SWE alone. It could be a non-invasive, reliable, and useful method to differentiate benign from malignant ACR TI-RADS 4 and 5 category thyroid nodules coexisting with HT.

This study is the first to use an autologous pericardial patch combined with a 3D carbon fiber stent for the plastic repair of a large trachea defect. Radical surgery is the optimal therapy for primary malignant tracheal tumors. Tracheoplasty or repair is required to guarantee trachea integrity and normal ventilation function after tracheal tumor resection. Here, we present a case of plastic repair of the trachea using an autologous pericardial patch and a 3D custom-made carbon fiber stent. A 4 cm trachea defect was successfully repaired after resecting a malignant schwannoma. The postoperative ventilatory function was normal without obvious symptoms of discomfort. Fiberoptic bronchoscopy showed a smooth mucosal surface of the endotracheal wall and patency of the airway. CT scans performed 3 years after surgery showed no recurrence. Therefore, we can conclude that a 3D carbon fiber stent is feasible for abolishing patch floating and preventing tracheal stenosis.

Additional file 2: Fig S2. Effects of AZI treatment alone on HBECs.

Additional file 1: Fig. S1. Classificationand coefficient of variationvalues for all metabolites detected in apple flesh. Fig. S2. PCA analysis of all metabolite contents detected in other wild, M. sieversii, heirloom, and six apple cultivar groups. Fig. S3. Contents of total tannins and titratable acid in apple accessions among M. sieversii group, low-weight, and high-weight domesticated groups. Fig. S4. Co-mapped regions of soluble tannins identified by GWAS on Chr 16. Fig. S5. Differences between amino acid sequences of MdMyb9 and MD15G1051400. Fig. S6. Whole-genome screen for selective sweeps during apple domestication and improvement. The horizontal gray dotted lines indicate genome-wide thresholds that were estimated based on the top 5% of Fst values. Fig. S7. Co-mapped regions of LPE identified by GWAS on Chr 12.

Supplementary Material 1

Look-up table(LUT)-based methods have shown the great efficacy in single image super-resolution (SR) task. However, previous methods ignore the essential reason of restricted receptive field (RF) size in LUT, which is caused by the interaction of space and channel features in vanilla convolution. They can only increase the RF at the cost of linearly increasing LUT size. To enlarge RF with contained LUT sizes, we propose a novel Reconstructed Convolution(RC) module, which decouples channel-wise and spatial calculation. It can be formulated as $n^2$ 1D LUTs to maintain $n\times n$ receptive field, which is obviously smaller than $n\times n$D LUT formulated before. The LUT generated by our RC module reaches less than 1/10000 storage compared with SR-LUT baseline. The proposed Reconstructed Convolution module based LUT method, termed as RCLUT, can enlarge the RF size by 9 times than the state-of-the-art LUT-based SR method and achieve superior performance on five popular benchmark dataset. Moreover, the efficient and robust RC module can be used as a plugin to improve other LUT-based SR methods. The code is available at https://github.com/liuguandu/RC-LUT.

We consider a kind of differential equations d/dt y(t) = R(y(t))y(t) + f(y(t)) with energy conservation. Such conservative models appear for instance in quantum physics, engineering and molecular dynamics. A new class of energy-preserving schemes is constructed by the ideas of scalar auxiliary variable (SAV) and splitting, from which the nonlinearly implicit schemes have been improved to be linearly implicit. The energy conservation and error estimates are rigorously derived. Based on these results, it is shown that the new proposed schemes have unconditionally energy stability and can be implemented with a cost of solving a linearly implicit system. Numerical experiments are done to confirm these good features of the new schemes.

Additional file 1.

The complex differentiation hierarchy and cellular heterogeneity of various cell populations in breast cancer (BRCA) were important factors affecting bone metastasis and response to therapy. Nevertheless, there is still lack of a more precise classification system for current therapeutic strategies. UMAP analysis identified nine clusters and three spot types (immune spots, stromal spots and malignant spots), with 11 differentiation states further recapitulated from 2493 malignant spots. We constructed a novel BRCA stratification system (subtype Ⅰ, subtype Ⅱ, subtype Ⅲ and subtype Ⅳ) with prognosis getting worse in order, biological plausibility and clinical significance. Regulation networks were constructed along different development trajectories based on key cell fate-related genes, metastasis-related pathways, transcription factor, immune gene sets, immune cells and RPPA, investigating the relationships between primary and bone metastasis BRCA. Finally, we identified the most significant inhibitors (puromycin, MS-275, megestrol and esculetin) for bone-metastatic BRCA via targeting cell fate-related genes. Validation of large clinical cohort samples confirmed that our molecular/cell-based stratification system had strong translational medical value. In all, we revealed the complex cellular heterogeneity and a differentiated hierarchy of cell subpopulations underlying BRCA bone metastasis. We constructed a novel precise BRCA molecular/cell-based stratification system with potential diagnostic and prognostic cell fate-related markers.

We propose a new strategy to bridge point cloud denoising and surface reconstruction by alternately updating the denoised point clouds and the reconstructed surfaces. In Poisson surface reconstruction, the implicit function is generated by a set of smooth basis functions centered at the octnodes. When the octree depth is properly selected, the reconstructed surface is a good smooth approximation of the noisy point set. Our method projects the noisy points onto the surface and alternately reconstructs and projects the point set. We use the iterative Poisson surface reconstruction (iPSR) to support unoriented surface reconstruction. Our method iteratively performs iPSR and acts as an outer loop of iPSR. Considering that the octree depth significantly affects the reconstruction results, we propose an adaptive depth selection strategy to ensure an appropriate depth choice. To manage the oversmoothing phenomenon near the sharp features, we propose a $\lambda$-projection method, which means to project the noisy points onto the surface with an individual control coefficient $\lambda_{i}$ for each point. The coefficients are determined through a Voronoi-based feature detection method. Experimental results show that our method achieves high performance in point cloud denoising and unoriented surface reconstruction within different noise scales, and exhibits well-rounded performance in various types of inputs.

Reliable pseudo-labels from unlabeled data play a key role in semi-supervised object detection (SSOD). However, the state-of-the-art SSOD methods all rely on pseudo-labels with high confidence, which ignore valuable pseudo-labels with lower confidence. Additionally, the insufficient excavation for unlabeled data results in an excessively low recall rate thus hurting the network training. In this paper, we propose a novel Low-confidence Samples Mining (LSM) method to utilize low-confidence pseudo-labels efficiently. Specifically, we develop an additional pseudo information mining (PIM) branch on account of low-resolution feature maps to extract reliable large-area instances, the IoUs of which are higher than small-area ones. Owing to the complementary predictions between PIM and the main branch, we further design self-distillation (SD) to compensate for both in a mutually-learning manner. Meanwhile, the extensibility of the above approaches enables our LSM to apply to Faster-RCNN and Deformable-DETR respectively. On the MS-COCO benchmark, our method achieves 3.54% mAP improvement over state-of-the-art methods under 5% labeling ratios.

Additional file 1: Fig. S1. Identification of primary bronchial epithelial cells primary bronchial epithelial cells (PBECs).

In this work, we decouple the iterative bi-level offline RL from the offline training phase, forming a non-iterative bi-level paradigm and avoiding the iterative error propagation over two levels. Specifically, this non-iterative paradigm allows us to conduct inner-level optimization in training (for OOD issues), while performing outer-level optimization in testing (for reward maximizing). Naturally, such a paradigm raises three core questions that are \textit{not} fully answered by prior non-iterative offline RL counterparts like reward-conditioned policy: Q1) What information should we transfer from the inner-level to the outer-level? Q2) What should we pay attention to when exploiting the transferred information in the outer-level optimization? Q3) What are the~benefits of concurrently conducting outer-level optimization during testing? Motivated by model-based optimization~{(MBO)}, we propose DROP (\textbf{D}esign f\textbf{RO}m \textbf{P}olicies), which fully answers the above questions. Specifically, in the inner-level, DROP decomposes offline data into multiple subsets and learns an {MBO} score model~(A1). To keep safe exploitation to the score model in the outer-level, we explicitly learn a behavior embedding and introduce a conservative regularization (A2). During testing, we show that DROP permits test-time adaptation, enabling an adaptive inference across states~(A3). Empirically, we find that DROP, compared to prior non-iterative offline RL counterparts, gains an average improvement probability of more than 80\%, and achieves comparable or better performance compared to prior iterative baselines.

Supplemental material, sj-docx-3-tam-10.1177_17588359231167818 for Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients by Zhen Wang, Xu-Chao Zhang, Wei-Neng Feng, Li Zhang, Xiao-Qing Liu, Wei-Bang Guo, Yan-Ming Deng, Qing-Feng Zou, Jin-Ji Yang, Qing Zhou, Bin-Chao Wang, Hua-Jun Chen, Hai-Yan Tu, Hong-Hong Yan and Yi-Long Wu in Therapeutic Advances in Medical Oncology

Preregistration of analysis plan

Additional file 4: Table S2. Differential expressed metabolites involved in MSEA.

Supplemental material, sj-docx-5-tam-10.1177_17588359231167818 for Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients by Zhen Wang, Xu-Chao Zhang, Wei-Neng Feng, Li Zhang, Xiao-Qing Liu, Wei-Bang Guo, Yan-Ming Deng, Qing-Feng Zou, Jin-Ji Yang, Qing Zhou, Bin-Chao Wang, Hua-Jun Chen, Hai-Yan Tu, Hong-Hong Yan and Yi-Long Wu in Therapeutic Advances in Medical Oncology

The cascade of 2D geometric transformations were exploited to model relations between entities in a knowledge graph (KG), leading to an effective KG embedding (KGE) model, CompoundE. Furthermore, the rotation in the 3D space was proposed as a new KGE model, Rotate3D, by leveraging its non-commutative property. Inspired by CompoundE and Rotate3D, we leverage 3D compound geometric transformations, including translation, rotation, scaling, reflection, and shear and propose a family of KGE models, named CompoundE3D, in this work. CompoundE3D allows multiple design variants to match rich underlying characteristics of a KG. Since each variant has its own advantages on a subset of relations, an ensemble of multiple variants can yield superior performance. The effectiveness and flexibility of CompoundE3D are experimentally verified on four popular link prediction datasets.

Tomographic vat photopolymerization offers high speed, auxiliary-free 3D printing. A fundamental limitation to this emerging technology is the non-negativity constraint, i.e., light engines cannot deliver the information carried by the negative values in a tomogram. We introduce binary photoinhibition, which creates a stationary state with controllable stability for every voxel individually. The information carried by negativities is delivered by a second light engine as external stimuli. We employ the oxygen-lophyl radical pair in free radical polymerization to show that removing the non-negativity constraint increases print accuracy, prolongs process window, accelerates printing and enhances property modulation. The result completes the theoretical framework of reversing tomographic reconstruction for ultrafast 3D printing and enables the direct transfer of knowledge associated with computed tomography to improve print accuracy.