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The spatial layout of the coastal forts defense system of the Ming Dynasty of China has been studied in a relatively comprehensive way. Nonetheless, ancient defense mechanisms have not been fully revealed. Previous studies have focused more on the macro and meso levels. Studies into its microscopic construction mechanism need to be enhanced. This research attempts to quantify and validate the rationality of the ancient microscopic defense mechanism, using the ancient defense mechanism of Pu Zhuang Suo-Fort in Zhejiang Province as an instance. This study concentrates on the distribution of firepower strength beyond the walls of coastal defense forts, as well as the effect of wall height on firepower defense capabilities. There is a specific firepower attenuation area near the walls due to the firing blind area in the coastal forts defense system. And the construction of the moat plays an additive role in its defensive capability. Meanwhile, the height of the fort wall will also affect the range of the firing blind zone under Yangmacheng. In theory, there is a reasonable height range of the wall and a proper position of the moat. This height range can meet both good economy and defensive capabilities. In turn, the position of the moats and the height of the walls can verify the rationality of the construction mechanism of the coastal forts’ defense system.

IntroductionAbnormal expression of integrin subunit beta 3 (ITGβ3), a gene-encoding protein, is related to the occurrence and development of cancers; however, the biological role of ITGβ3 in colon adenocarcinoma (COAD) remains unclear.MethodsWe used the Cancer Genome Atlas database to obtain the clinical data of patients with COAD, analyzed the mRNA gene clusters related to ITGβ3, and analyzed the interaction signal pathway and interaction protein network of the differentially expressed gene clusters. The results showed that ITGβ3 expression in COAD tumor tissues was significantly downregulated compared with that in paracancerous tissues. Low ITGβ3 expression in tumor tissues is associated with poor overall survival of patients with COAD. In multivariate analysis, stage IV and ITGβ3 low expression were independent prognostic factors. Gene Ontology analysis showed that differentially expressed genes (DEGs) were significantly enriched in leukocyte migration, cell adhesion, and extracellular matrix (ECM) organization. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were mainly enriched in ECM-receptor interactions, focal adhesion, and the PI3K-Akt signaling pathway. Protein-protein interaction network analysis revealed the hub and seed genes of the key modules related to ITGβ3. Finally, we analyzed the correlation between TGβ3 and immune-related genes and found that ITGβ3 expression was significantly correlated with tumor purity and infiltration level of dominant immune cells.DiscussionThese findings indicate that ITGβ3 downregulation in COAD may profoundly affect genome stability and multiple steps of the cell cycle, alter the tumor immune microenvironment, and be related to the prognosis of patients with COAD.

PurposeTo systematically review the clinical value of three imaging examinations (Magnetic Resonance Imaging, Computed Tomography, and myelography) in the diagnosis of Lumbar Disc Herniation.MethodsDatabases including PubMed, Embase, The Cochrane Library, Web of Science, CBM, CNKI, WanFang Data, and VIP were electronically searched to collect relevant studies on three imaging examinations in the diagnosis of Lumbar Disc Herniation from inception to July 1, 2021. Two reviewers using the Quality Assessment of Diagnostic Accuracy Studies-2 tool independently screened the literature, extracted the data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by using Meta-DiSc 1.4 software and Stata 15.0 software.ResultsA total of 38 studies from 19 articles were included, involving 1,875 patients. The results showed that the pooled Sensitivity, pooled Specificity, pooled Positive Likelihood Ratio, pooled Negative Likelihood Ratio, pooled Diagnostic Odds Ratio, Area Under the Curve of Summary Receiver Operating Characteristic, and Q* were 0.89 (95%CI: 0.87–0.91), 0.83 (95%CI: 0.78–0.87), 4.57 (95%CI: 2.95–7.08), 0.14 (95%CI: 0.09–0.22), 39.80 (95%CI: 18.35–86.32), 0.934, and 0.870, respectively, for Magnetic Resonance Imaging. The pooled Sensitivity, pooled Specificity, pooled Positive Likelihood Ratio, pooled Negative Likelihood Ratio, pooled Diagnostic Odds Ratio, Area Under the Curve of Summary Receiver Operating Characteristic, and Q* were 0.82 (95%CI: 0.79–0.85), 0.78 (95%CI: 0.73–0.82), 3.54 (95%CI: 2.86–4.39), 0.19 (95%CI: 0.12–0.30), 20.47 (95%CI: 10.31–40.65), 0.835, and 0.792, respectively, for Computed Tomography. The pooled Sensitivity, pooled Specificity, pooled Positive Likelihood Ratio, pooled Negative Likelihood Ratio, pooled Diagnostic Odds Ratio, Area Under the Curve of Summary Receiver Operating Characteristic, and Q* were 0.79 (95%CI: 0.75–0.82), 0.75 (95%CI: 0.70–0.80), 2.94 (95%CI: 2.43–3.56), 0.29 (95%CI: 0.21–0.42), 9.59 (95%CI: 7.05–13.04), 0.834, and 0.767 respectively, for myelography.ConclusionThree imaging examinations had high diagnostic value. In addition, compared with myelography, Magnetic Resonance Imaging had a higher diagnostic value.

The limitations of satellite versatility, application dimensions, and wide-area observation efficiency are major issues impeding the development of Chinese spaceborne Synthetic Aperture Radar (SAR). China lacks a satellite system that can realize long-term, stable, and high-performance environmental dynamic monitoring oriented to the world. As the international environment becomes increasingly complex, China urgently needs to develop a SAR satellite system for global dynamic environmental monitoring to achieve large-scale, high-revisit, long-term, stable, and high-precision observations. This paper proposes a SAR Constellation with Dense Time-SEries for MultiDimensional Environmental Monitoring of the Earth (See-Earth) plan. In addition, the system conception, technical architectures, performance analysis, application potential, and new system expansion are discussed.

Automatic Target Recognition (ATR) in Synthetic Aperture Radar (SAR) has been extensively applied in military and civilian fields. However, SAR images are very sensitive to the azimuth of the images, as the same target can differ greatly from different aspects. This means that more reliable and robust multiaspect ATR recognition is required. In this paper, we propose a multiaspect ATR model based on EfficientNet and BiGRU. To train this model, we use island loss, which is more suitable for SAR ATR. Experimental results have revealed that our proposed method can achieve 100% accuracy for 10-class recognition on the Moving and Stationary Target Acquisition and Recognition (MSTAR) database. The SAR targets in three special imaging cases with large depression angles, version variants, and configuration variants reached recognition accuracies of 99.68%, 99.95%, and 99.91%, respectively. In addition, the proposed method achieves satisfactory accuracy even with smaller datasets. Our experimental results show that our proposed method outperforms other state-of-the-art ATR methods on most MSTAR datasets and exhibits a certain degree of robustness.

An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an “all-in-one” vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared via a facile recombinant method. The vaccines induced the maturation of DCs that subsequently primed CD8+ T cells. The TCS-based immunostimulation was associated with the STING pathway. The general applicability of this genetic engineering strategy was demonstrated with various tumor antigens (i.e., legumain and TRP2 antigenic peptides) and tumor models (i.e., colon tumor and melanoma). These findings represent a useful protocol for developing cancer vaccines at low cost and time-saving, and demonstrates the adjuvant application of TCS—an old drug for a new application.

Polyethylene mulching film plays a critical role in agricultural production. To clarify the impact of residual film and microplastics on soil microorganisms, this study examined four cotton fields with different film coverage years in typical areas of Xinjiang and analyzed the changes in soil bacterial and fungal community structure and diversity under residual film and microplastics using high-throughput sequencing technology. The results showed that the residual film in the 0–150 mm soil layers and 150–300 mm soil layers at the same sampling point had spatial distribution characteristics of 60–70% and 30–40%, respectively. The short period of the 0–10 years film mulching treatment increased the soil microbial diversity of the cotton field, whereas continuous film mulching for 25 years significantly decreased the soil microbial diversity, in which Proteobacteria was the dominant bacterial phylum and Ascomycetes was the dominant fungal phylum. The microbial diversity of the film-covered soil was lower than that of the control group. The spatial distribution of the residual film and microplastic changed the distribution of the microbial communities. The diversity of the microbial community structure of the 0–150 mm soil layers was higher than that of the 150–300 mm soil layers. The increase in residual film and microplastics had no significant effect on the diversity of the fungal community but decreased the diversity of the soil bacterial community and decreased the relative abundance of Proteobacteria and Campylobacter. In conclusion, long-term film mulching reduced the soil microbial diversity in cotton fields. This study provides a theoretical basis for understanding the impact of film residues on microorganisms and the ecological environment in typical areas.

ObjectivesTo assess the lateralization of cerebral blood flow (CBF) in the auditory cortex of idiopathic tinnitus patients and healthy controls (HCs) using 3D pseudocontinuous arterial spin labeling (pcASL).MethodsThirty-six patients with idiopathic tinnitus and 43 sex- and age-matched HCs underwent 3D-pcASL scanning using a 3.0 T MRI system. For both groups, region of interest analysis was performed on the primary auditory cortex (PAC), auditory associative cortex (AAC), and secondary auditory cortex (SAC). The clinical data of all subjects were analyzed.ResultsIn both tinnitus patients and HCs, CBF of the left PAC was significantly higher than that of the right (HCs: P = 0.02; patients: P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left (AAC: HCs, P < 0.001; patients: P < 0.001. SAC: HCs, P < 0.001; patients: P = 0.001). Compared with HCs, tinnitus patients exhibited significantly higher CBF in the bilateral PAC (right: P = 0.008; left: P = 0.022). CBF in the left PAC was positively correlated with tinnitus severity (r = 0.399, P = 0.016).ConclusionThis study confirms the asymmetry of the auditory cortex and investigates the underlying neuropathology of idiopathic tinnitus in terms of CBF.

The senescence-associated secretory phenotype (SASP), which accumulates over the course of normal aging and in age-related diseases, is a crucial driver of chronic inflammation and aging phenotypes. It is also responsible for the pathogenesis of multiple oral diseases. However, the pathogenic mechanism underlying SASP has not yet been fully elucidated. Here, relevant articles on SASP published over the last five years (2017–2022) were retrieved and used for bibliometric analysis, for the first time, to examine SASP composition. More than half of the relevant articles focus on various cytokines (27.5%), growth factors (20.9%), and proteases (20.9%). In addition, lipid metabolites (13.1%) and extracellular vesicles (6.5%) have received increasing attention over the past five years, and have been recognized as novel SASP categories. Based on this, we summarize the evidences demonstrating that SASP plays a pleiotropic role in oral immunity and propose a four-step hypothetical framework for the progression of SASP-related oral pathology—1) oral SASP development, 2) SASP-related oral pathological alterations, 3) pathological changes leading to oral immune homeostasis disruption, and 4) SASP-mediated immune dysregulation escalating oral disease. By targeting specific SASP factors, potential therapies can be developed to treat oral and age-related diseases.

The Kaiser effect is an important phenomenon that occurs in acoustic emission. The estimation of reinforced concrete structures based on acoustic emission is receiving widespread attention. Cumulative acoustic emission parameters were used for the preliminary estimation of Kaiser points through the step loading experiments on four simply supported reinforced concrete beams under bending load. Taking this Kaiser point as the centre, an appropriate interval value was determined. After functional fitting of the “load-acoustic emission parameter” curve, the difference between the estimated value and the measured value was calculated. The Kaiser point was modified in accordance with the “load-difference” curve. The modified Kaiser point was used to calculate the Felicity ratio. The ratio of the maximum load to the ultimate bearing capacity of the beams was calculated. The curves of the ratio and the Felicity ratio were obtained. Fitting of the corresponding relational function was performed. Based on the relational function, the ultimate bearing capacity of the beams was estimated according to the mean of the experiment. The results showed that if there was a significant difference between the preliminarily estimated value and the measured value of the Kaiser point, modifications can be conducted to avoid any significant difference in the Kaiser point caused by human factors. Using the Felicity ratio and based on function fitting, the maximum difference in the ultimate bearing capacity of the beams was estimated to be no more than 10%. Moreover, it was concluded that the estimated ultimate bearing capacity of the beams was characterized by high stability in the case of different sample data. This method will provide a theoretical basis for evaluating the ultimate bearing capacity of reinforced concrete beams under bending load based on the Kaiser effect.

The needs of mitigating COVID-19 epidemic prompt policymakers to make public health-related decision under the guidelines of science. Tremendous unstructured COVID-19 publications make it challenging for policymakers to obtain relevant evidence. Knowledge graphs (KGs) can formalize unstructured knowledge into structured form and have been used in supporting decision-making recently. Here, we introduce a novel framework that can extract the COVID-19 public health evidence knowledge graph (CPHE-KG) from papers relating to a modelling study. We screen out a corpus of 3096 COVID-19 modelling study papers by performing a literature assessment process. We define a novel annotation schema to construct the COVID-19 modelling study-related IE dataset (CPHIE). We also propose a novel multi-tasks document-level information extraction model SS-DYGIE++ based on the dataset. Leveraging the model on the new corpus, we construct CPHE-KG containing 60,967 entities and 51,140 relations. Finally, we seek to apply our KG to support evidence querying and evidence mapping visualization. Our SS-DYGIE++(SpanBERT) model has achieved a F1 score of 0.77 and 0.55 respectively in document-level entity recognition and coreference resolution tasks. It has also shown high performance in the relation identification task. With evidence querying, our KG can present the dynamic transmissions of COVID-19 pandemic in different countries and regions. The evidence mapping of our KG can show the impacts of variable non-pharmacological interventions to COVID-19 pandemic. Analysis demonstrates the quality of our KG and shows that it has the potential to support COVID-19 policy making in public health.

In this article, we draw on the scholarship of feminist communitarianism to develop a critique of the predominant neoliberal qualitative social research collaboration model. We argue that feminist theories and praxis about community building and political activism have the potential to transcend the highly institutionalized, individualistic, and managerialist collaborative culture. Feminist insights can help today's researchers navigate collaborative research and address key issues such as reflexivity, consensus formation, knowledge validation, and group solidarity. We use our own work in the Feminist Research Collective and in the WomenWeLove project to present an alternative orientation and a collective way to enact transformative research. This feminist intervention against the neoliberal research culture contributes to the ongoing reflections of how we produce knowledge via qualitative social research and why we shall do so in the current historical juncture, expands our imaginations of researchers' responsibilities, and engenders new possibilities for resistance and emancipation.

In order for an electromagnetic acoustic transducer (EMAT) to be able to pick up the out-of-plane vibrations of ultrasonic waves generated by the laser and to facilitate the movement of the system, a new pulse electromagnet EMAT is proposed, which can be combined with a laser to form a new laser–pulse electromagnet EMAT integrated system. Because of the unique structure of the pulse electromagnet EMAT, it can not only generate a uniform transverse magnetic field in the shallow surface of the specimen just below the EMAT receiving coil but also leave enough space above the magnetic field to ensure the smooth radiation of the laser source on the specimen. The optimal parameters of the probe are determined by combining the finite element simulation model and the orthogonal analysis method. The simulation and experimental results show that the pulsed electromagnet can generate at least 0.22 T transverse magnetic field in the specimen when each coil of C-electromagnet, respectively, injects 20 A. The pulsed electromagnet combined with the EMAT coil is used to receive various modes of ultrasonic vibration velocity with the out-of-plane component. It lays a foundation for the research on the simultaneous detection of railhead surface and internal defects by using the new laser–pulse electromagnet EMAT integrated system through one scan.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious viral disease that causes great harm to the pig industry. PRRS virus (PRRSV), the causative agent of PRRS, is characterized by severe reproductive failure and respiratory confusion. This study performed a cross-sectional investigation of PRRSV seroprevalence and collected 14,134 serum samples in pig farms without PRRSV vaccination from 12 provinces and two cities in China from 2017 to 2021 to detect PRRSV antibodies by enzyme-linked immunosorbent assay (ELISA). The apparent and true PRRSV antibody prevalence was estimated and compared based on the Clopper-Pearson method and Pearson chi-square test, respectively. Risk factors associated with the PRRSV serological status of pig farms were analyzed through univariate and multivariable logistic regression analysis. An automatic autoregressive integrated moving average (ARIMA) model procedure was used for time-series analysis for PRRSV seroprevalence. Spatial clusters of high PRRSV seroprevalence were detected by SaTScan software. The total true PRRSV seroprevalence of the animal level was 62.56% (95% confidence interval [CI]: 61.74–63.37%). Additionally, 286 out of 316 pig farms were positive for PRRSV antibodies at the herd level. Pig farms without pseudorabies virus (PRV) infection were 5.413 (95% CI: 1.977–17.435) times more likely to be PRRSV antibody positive than those with PRV. Identically, the possibility of pig farms being PRRSV antibody positive before an African swine fever (ASF) outbreak was 3.104 (95% CI: 1.122–10.326) times more than after ASF. The odd ratio values of medium and large pig farms with PRRSV infection are 3.076 (95% CI: 1.005–9.498) and 6.098 (95% CI: 1.814–21.290). A fluctuant decline pattern for PRRSV prevalence was observed in the temporal analysis. Three significant clusters of high PRRSV seroprevalence were first detected in China, covering a time frame from January 2018 to September 2018, which reveals high PRRSV prevalence before the outbreak of ASF. These findings show the epidemic situation and spatial-temporal distribution of PRRSV infection in China in recent years and could help develop reasonable measures to prevent PRRSV infection.

Abstract The large‐scale application of electric vehicles can lead to new challenges in the operation of the two complex and coupled networks of electricity and transportation systems, thus creating a new concept—a power—traffic network. The purpose is to provide a comprehensive survey of this emerging field. First, both the transportation system and power grid models are briefly introduced in terms of time and space scales. Then, the power traffic network model and applications at long‐term, mid‐term, and short‐term time scales are summarized, and provided a unified view of these achievements. Based on this analysis, recommendations for future research are presented.

Abstract Background SAPHO syndrome is a group of symptoms consisting of synovitis, acne, pustulosis, hyperostosis and osteosis. There is no specific laboratory index assist in the diagnosis of SAPHO because of its highly heterogeneous clinical manifestations. Pathogenic microorganisms had been identified in biopsies of some SAPHO cases and particular gene mutations were also linked to the occurrence of SAPHO. It is largely unknown whether intestinal microbiome plays a role in pathogenesis of SAPHO. To explore the intestinal microbiome structure of SAPHO syndrome, fecal samples from 17 SAPHO patients and 14 healthy controls (HC) were collected for 16S rDNA sequencing. Results Our results showed that there was no significant difference in alpha indexes and beta diversity between SAPHO and HC samples, while there were 14 operational taxonomic units (OTUs) in the Wilcoxon rank-sum test and 42 OTUs in the MetagenomeSeq analysis showed significant difference in distribution between the SAPHO and HC groups, 3 of which in Firmicutes were also observed in the random forest analysis and used to construct a receiver operating characteristic curve to evaluate the diagnostic value, the area under the curve was 0.86. Conclusion Fecal-associated microbiome in the SAPHO samples was characterized by the alteration in abundance of some nondominant species, and the 3 selected OTUs in Firmicutes could serve as candidate biomarkers for SAPHO syndrome diagnosis.

Objective: To clarify the structural and functional characteristics of the gut microbiota in individuals with qi stagnation constitution (QSC) and identify the potential biomarkers related to QSC. Methods: This cross-sectional study involved individuals with QSC and balanced constitution (BC) confirmed by TCM clinicians. The clinical features were recorded, and fecal samples were collected for 16S rDNA sequencing. The structure of the fecal-associated microbiome (FAM) was described by the alpha-diversity indexes, beta-distances, and relative abundances of dominant taxa. The differences in FAM distribution were analyzed by the Wilcoxon rank-sum test, MetagenomeSeq, and LEfSe analysis. The 16S rDNA gene sequences were assigned to the KEGG dataset to predict the functional information of bacterial metabolic pathways by using PICRUSt. Differences in functional pathways between groups were assessed with the Wilcoxon rank-sum test. The ROC curve based on specific operational taxonomic units (OTUs) was constructed, and the AUC was calculated. Results: Twenty-two individuals with BC and 8 with QSC were recruited. Significant differences between the two groups were found in body mass index, health status, and low-density lipoprotein, etc. There was no significant difference in the alpha-diversity index. PCoA showed no evident clustering of bacterial communities according to constitutions. Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, and Prevotellaceae were the four common bacteria with high abundances. Notably, MetagenomeSeq, LEfSe analysis, and the Wilcoxon rank-sum test identified significantly different distributions of 66, 42, and 36 OTUs, respectively. Predictive function analysis showed that 13 metabolic pathways were significantly differentially distributed, including those related to fatty acid synthesis. Five specific OTUs were selected as potential biomarkers of a QSC, and the AUC was 0.94. Conclusion: Individuals with QSC have unique FAM structure and related functional characteristics. Five specific OTUs were identified to serve as potentially effective biomarkers related to QSC.

Sigmoid sinus wall dehiscence (SSWD) is an important etiology of venous pulsatile tinnitus (VPT) and is treated by sigmoid sinus wall reconstruction (SSWR). This study aimed to investigate the therapeutic effects of the different degrees of SSWR and the prognostic effect in patients with VPT. Personalized models of three patients with SSWD (control), 3/4SSWD, 1/2SSWD, 1/4SSWD, and 0SSWD were reconstructed. A multiphysics interaction approach was applied to elucidate the biomechanical and acoustic changes. Results revealed that after SSWR, the average pressure of venous vessel on the SSWD region reduced by 33.70 ± 12.53%, 35.86 ± 12.39%, and 39.70 ± 12.45% (mean ± SD) in three patients with 3/4SSWD, 1/2SSWD, and 1/4SSWD. The maximum displacement of the SSWR region reduced by 25.91 ± 30.20%, 37.20 ± 31.47%, 52.60 ± 34.66%, and 79.35 ± 18.13% (mean ± SD) in three patients with 3/4SSWD, 1/2SSWD, 1/4SSWD, and 0SSWD, with a magnitude approximately 10−3 times that of the venous vessel in the SSWD region. The sound pressure level at the tympanum reduced by 23.72 ± 1.91%, 31.03 ± 14.40%, 45.62 ± 19.11%, and 128.46 ± 15.46% (mean ± SD). The SSWR region was still loaded with high stress in comparison to the surrounding region. The SSWR region of the temporal bone effectively shielded the high wall pressure and blocked the transmission of venous vessel vibration to the inner ear. Patients with inadequate SSWR still had residual VPT symptoms despite the remission of VPT symptoms. Complete SSWR could completely solve VPT issues. High-stress distribution of the SSWR region may be the cause of the recurrence of VPT symptoms.

This study details microwave-absorbing materials made of natural rubber/nitrile butadiene rubber (NR/NBR) blends with multi-walled carbon nanotubes (MWCNTs) and molybdenum disulfide (MoS2). The mechanical blending method and the influences of fabrication on the morphology and microwave-absorbing performance of resulting compounds were logically investigated. It was found that interfacial differences between the fillers and matrix promote the formation of MWCNTs and MoS2 networks in NR/NBR blends, thus improving microwave-absorbing performance. Compared with direct compounding, masterbatch-based two-step blending is more conducive to forming interpenetrating networks of MWCNTs/MoS2, endowing the resulting composite with better microwave attenuation capacity. Composites with MWCNTs in NR and MoS2 in NBR demonstrate the best microwave-absorbing performance, with a minimum reflection loss of −44.54 dB and an effective absorption bandwidth of 3.60 GHz. Exploring the relationship between morphology and electromagnetic loss behavior denotes that such improvement results from the selective distribution of dual fillers, inducing networking and multi-component-derived interfacial polarization enhancement.

Abstract Hyperglycemia induces chronic low-grade inflammation (inflammaging), which is a newly identified contributor to diabetes-related tissue lesions, including the inflammatory bone loss in periodontitis. It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype (SASP). Macrophage is a key SASP-spreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment. Using a transgenic diabetic model (BLKS/J-Lepr db /lepr db mice) we identified striking senescence of the periodontium in young (18-wk)-diabetic mice accompanied by amassed p16+-macrophages and enhanced early SASP response. Exposed to high glucose in vitro, bone marrow-derived macrophage (BMDM) revealed a strong GLUT1 mRNA response driving the elevated-glucose uptake. GLUT1 is a representative and facilitative glucose transporter in macrophages with potential roles in hyperglycemia-induced inflammation. In this study, both GLUT1 and the downstream GTPase Rheb expression upregulated in the gingiva of diabetic mice with impaired condition. Furthermore, SASP release and p16/p21 signaling were proven to be triggered by mTOR phosphorylation in BMDM and antagonized by restricting glucose uptake in GLUT1 − /− BMDM. Taken together, our findings suggest that elevated-GLUT1 sensor responded to high glucose is important for macrophage senescence and SASP response, generated as a result of hyperglycemia, and it is a potential molecular mechanism for the exacerbation of periodontitis in diabetes.

Driver sleepiness is one of the most important causes of traffic accidents. Efficient and stable algorithms are crucial for distinguishing nonfatigue from fatigue state. Relevance vector machine (RVM) as a leading-edge detection approach allows meeting this requirement and represents a potential solution for fatigue state detection. To accurately and effectively identify the driver’s fatigue state and reduce the number of traffic accidents caused by driver sleepiness, this paper considers the degree of driver’s mouth opening and eye state as multi-source related variables and establishes classification of fatigue and non-fatigue states based on the related literature and investigation. On this basis, an RVM model for automatic detection of the fatigue state is proposed. Twenty male respondents participated in the data collection process and a total of 1000 datasets of driving status (half of non-fatigue and half of fatigue) were obtained. The results of fatigue state recognition were analysed by different RVM classifiers. The results show that the recognition accuracy of the RVM-driven state classifiers with different kernel functions was higher than 90%, which indicated that the mouth-opening degree and the eye state index used in this work were closely related to the fatigue state. Based on the obtained results, the proposed fatigue state identification method has the potential to improve the fatigue state detection accuracy. More importantly, it provides a scientific theoretical basis for the development of fatigue state warning methods.

With the help of accurate parking navigation systems, sharing vacant private parking spaces with public travelers may have the potential of reducing the number of cruising vehicles and contribute to traffic emission reduction. However, the quantitative effects of such a measure are still relatively unknown in traffic management. In this article, we firstly established an optimal allocation model of shared parking spaces, which is a pure integer linear programming model of maximizing the number of served public vehicles to avoid cruising for parking. Further, the parking space allocation model was expanded to an estimation model that quantifies the effect of emission reduction. Secondly, a branch-and-cut algorithm was introduced as the core algorithm to solve the proposed models. Finally, detailed sensitivity analysis, based on empirical data collected by electronic parking toll collections and questionnaire surveys in Beijing, China, evaluated the proposed model and algorithm. The results indicate that shared parking can not only effectively reduce the cruising time and the number of vehicles, but also has significantly a positive effect on emission reduction. This research is helpful to provide theoretical support for alleviating parking pressure and environmental problems.

The Tibetan sheep is an indigenous species on the Tibetan plateau with excellent adaptability to high-altitude hypoxia and is distributed at altitudes of 2500–5000 m. The high-altitude hypoxia adaptation of Tibetan sheep requires adaptive reshaping of multiple tissues and organs, especially the lungs. To reveal the mechanisms of adaptation at the tissue and molecular levels in the lungs of Tibetan sheep under hypoxic conditions at different altitudes, we performed light and electron microscopic observations, transcriptomic sequencing, and enzyme-linked immunosorbent assay studies on the lungs of Tibetan sheep from three altitudes (2500, 3500, and 4500 m). The results showed that in addition to continuous increase in pulmonary artery volume, thickness, and elastic fiber content with altitude, Tibetan sheep increase the hemoglobin concentration at an altitude of 3500 m, while they decrease the Hb concentration and increase the surface area of gas exchange and capacity of the blood at an altitude of 4500 m. Other than that, some important differentially expressed genes related to angiogenesis (FNDC1, HPSE, and E2F8), vasomotion and fibrogenesis (GJA4, FAP, COL1A1, COL1A2, COL3A1, and COL14A1), and gas transport (HBB, HBA1, APOLD1, and CHL1) were also identified; these discoveries at the molecular level explain to some extent the physiological findings. In conclusion, the lungs of Tibetan sheep adopt different strategies when adapting to different altitudes, and these findings are valuable for understanding the basis of survival of indigenous species on the Tibetan plateau.

Objective: To explore the structural and functional characteristics of the fecal-associated microbiome (FAM) in a traditional Chinese medicine (TCM) qi-deficiency constitution (QDC) by comparing with balanced constitution (BC) and screen the related biomarkers. Methods: In this cross-sectional study, the TCM constitutions of subjects were determined based on published the Classification and Determination of constitution in TCM and further confirmed by a TCM clinician. Clinical characteristics were recorded, and fecal samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The FAM structure was described using alpha-diversity indexes, beta-diversity indexes, and the relative abundances of the dominant taxa. Differences in the FAM distribution and function were analyzed with a Wilcoxon rank-sum test, MetagenomeSeq, and LEfSe analysis, after which a receiver operating characteristic curve based on the specific operational taxonomic units (OTUs) was constructed to calculate the area under the curve. Results: Our study population was composed of 22 BCs and 9 QDCs. There were no significant differences between the two groups in the distribution of clinical characteristics or alpha-diversity indexes, except for the sweets preference and blood glucose level. In principal coordinate analysis and partial least squares discriminant analysis, the bacterial communities in the BC group samples and QDC group samples clustered separately. Notably, there were 214 OTUs significantly distributed between groups in the MetagenomeSeq analysis, 200 OTUs identified by the Wilcoxon rank-sum test, and 6 OTUs found by the LEfSe analysis. Predicted function analysis revealed that six metabolic pathways were distinctly distributed between the two groups. The area under the curve for the receiver operating characteristic curve based on the four specific OTUs was 0.88. Conclusion: Unique FAM structural and related functional characteristics are displayed in individuals with a QDC, and four specific OTUs could be used as QDC biomarkers to assist in clinical diagnosis.

To alleviate the problem between parking demand and supply, as well as improving urban traffic environment, shared parking has attracted great interest among researchers, policymakers, and entrepreneurs. Naturally, it is a prerequisite of sharing private parking spaces with public users (P-users) that all of the owners (O-users) providing parking spaces have space to park whenever they come back, with a unified management of all parking resources. However, it remains a challenge both in theory and practice. To solve this problem, firstly, we introduced a management framework of shared parking resource in terms of time and spatial dimension. Under this framework, to control the access to parking spaces of P-users, four phases (preparatory phase, open phase, releasing phase, and reconstructive phase) are divided in time dimension, and two types of parking spaces (the prestored parking spaces, and the shared parking spaces) are classified in spatial dimension. Then, based on the proposed management framework, an intelligent parking management system (IPMS) was developed to simulate the operation of shared parking considering the uncertainties of P-users' and O-users' arrival and departure. Furthermore, detailed sensitivity analysis, based on real-world data and simulations, evaluated the proposed framework and the developed IPMS in a case study concerning parking lots in Beijing, China. The results show that the IPMS can not only realize that there will always be enough available parking spaces satisfying O-users' parking demand, but also bring about vast improvements in both utilization and turnover rate of parking spaces, comparing with the non-shared management strategy.

This paper proposed improved measures for the shortest path fare scheme of urban rail transit. Firstly, this paper simulated Beijing rail transit by using Anylogic simulation technology and shortest path algorithm. Then, in order to find the travel time between any originations and destinations, this research measured the inbound time, waiting time, interval time, section running time, transfer time and outbound time. In addition, this paper used big data analysis technology to obtain the actual travel time distribution between any originations and destinations by processing the basic data of passengers entering and leaving the station. Finally, by comparing the valid path travel time calculated by any originations and destinations with the actual travel time distribution of passengers, the path taken by majority of passengers was pushed back to determine the ticket price based on the mileage of the path taken by the majority of passengers. The results reduced the dependence on government subsidies by rail transit operation and made up for the operation and maintenance costs.

Aiming at the defect of low voltage transfer ratio of two-stage matrix converter(TSMC), the proposed topology combines the Y-source network with the TSMC to form the Y-source two-stage matrix converter(YSTSMC) in this paper, and proposes its modulation strategy. The Y-source network is located in the dc-link of TSMC, and uses a tightly coupled inductor with three windings to transfer energy, which can increase voltage transfer ratio. Based on the mathematical model of the Y-source network, a small-signal model is established and dynamic analysis is performed. The analysis result of the impact of the output voltage of the rectifier stage on the output voltage of the system can be obtained. The space vector pulse width modulation (SVPWM) strategy is proposed to control YSTSMC, and according to the fluctuation of dc-link voltage, the modulation ratio of inverter stage is corrected in real time. By analyzing the voltage transfer ratio of YSTSMC, and the calculation expression of the maximum voltage transfer ratio is obtained. Finally, the experimental results are provided to verify the feasibility and validity of the proposed method.

ObjectivesTo simulate hemodynamic changes after extraluminal compression in pulsatile tinnitus (PT) patients with a prominent transverse-sigmoid sinus junction (PTSJ).MethodsOne patient-specific case was reconstructed based on computed tomography venography (CTV) images of a PT patient. The compression degree served as a new index in this study. Cases with 10, 20, 30, 40, 50, 60, 70, 80, and 90% of the compression degree of the control subject were constructed. Steady-state computational fluid dynamics (CFD) were assessed. The wall pressure distribution, wall maximum pressure (Pmax) and flow pattern (velocity streamlines and velocity vector) of the PTSJ were calculated to evaluate hemodynamic differences among all cases.ResultsWith increasing compression, the wall pressure at the compression point and downstream of the PTSJ decreased but increased upstream. When the compression degree exceeded 70%, the upstream pressure increased significantly. Above 50% compression, the blood flow pattern downstream of the sigmoid sinus tended to spiral, especially after 80% compression. Beyond 60% compression, the blood flow pattern under the compression axis became more medial.ConclusionMechanical compression of PTSJ changes wall pressure and blood flow patterns. The degree of compression should be carefully observed to avoid possible complications or reoccurrence.

Abstract Protein–protein interaction (PPI) plays a crucial role in most biological processes, including signal transduction and cell apoptosis. Importantly, the knowledge of PPIs can be useful for identification of multimeric protein complexes and elucidation of uncharacterized protein functions. Arabidopsis thaliana, the best‐characterized dicotyledonous plant, the steadily increasing amount of information on the levels of its proteome and signaling pathways is progressively enabling more researchers to construct models for cellular processes for the plant, which in turn encourages more experimental data to be generated. In this study, we performed an overview analysis of the 10 major organelles and their associated proteins of the dicotyledonous model plant Arabidopsis thaliana via PPI network, and found that PPI may play an important role in organelle communication. Further, multilocation proteins, especially phosphorylation‐related multilocation proteins, can function as a “needle and thread” via PPIs and play an important role in organelle communication. Similar results were obtained in a monocotyledonous model crop, rice. Furthermore, we provide a research strategy for multilocation proteins by LOPIT technique, proteomics, and bioinformatics analysis and also describe their potential role in the field of plant science. The results provide a new view that the phosphorylation‐related multilocation proteins play an important role in organelle communication and provide new insight into PPIs and novel directions for proteomic research. The research of phosphorylation‐related multilocation proteins may promote the development of organelle communication and provide an important theoretical basis for plant responses to external stress.

Pregnancy-induced hypertension (PIH) is common and may affect maternal and children’s healthcare. However, the neurobiological status of neonates born from mothers with PIH has yet to be elucidated. The present study employed physiological imaging to investigate the association between maternal PIH and a number of neonatal health parameters, including cerebral metabolism, hemodynamics, and pathophysiological vulnerabilities. Following the acquisition of ethical approval, we recruited 16 neonates with maternal PIH and 22 normal neonates (non-PIH) as controls. All neonates underwent magnetic resonance imaging (MRI) of the brain. Phase-contrast (PC) MRI and T2-relaxation-under-spin-tagging (TRUST) MRI were performed to determine global cerebral blood flow, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2). These physiological parameters were then compared between PIH neonates and controls. Linear regression analysis was performed to investigate the associations between maternal PIH and each of the physiological parameters. Receiver operating characteristic curves (ROCs) were used to determine whether maternal systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) which could facilitate the diagnosis of neonatal brain injuries. PIH neonates showed significantly lower OEF (25.5 ± 8.8% vs. 32.6 ± 7.3%, P = 0.01) and CMRO2 (29.7 ± 9.4 vs. 40.9 ± 15.0 μmol/100 g/min, P = 0.01) compared to the controls. Maternal blood pressure levels [PIH or non-PIH groups, each one standard deviation (SD) increase in SBP, DBP, and MAP, respectively] were negatively associated with OEF [regression coefficient (β) = −7.9, P = 0.007; β = −4.2, P = 0.004; β = −3.6, P = 0.02; β = −4.0, P = 0.008, respectively). Furthermore, each one SD increase in maternal DBP and MAP was negatively associated with CMRO2 (β = −4.7, P = 0.03; β = −4.4, P = 0.04, respectively). The areas under the curves (AUCs) with 95% confidence intervals (CIs) for maternal SBP, DBP, and MAP were 0.90 (0.80–0.97), 0.85 (0.73–0.97), and 0.89 (0.76–0.99), respectively. The AUC values for maternal SBP, DBP, and MAP indicated good diagnostic ability for identifying neonatal brain injuries. The present study demonstrated that maternal PIH may be associated with a lower oxygen extraction and lower cerebral metabolism in neonates.

ObjectiveAltered cerebral blood flow (CBF) and regional homogeneity (ReHo) have been reported in pulsatile tinnitus (PT) patients. We aimed to explore regional neurovascular coupling changes in PT patients.Materials and MethodsTwenty-four right PT patients and 25 sex- and age-matched normal controls were included in this study. All subjects received arterial spin labeling imaging to measure CBF and functional MRI to compute ReHo. CBF/ReHo ratio was used to assess regional neurovascular coupling between the two groups. We also analyzed the correlation between CBF/ReHo ratio and clinical data from the PT patients.ResultsPT patients exhibited increased CBF/ReHo ratio in left middle temporal gyrus and right angular gyrus than normal controls, and no decreased CBF/ReHo ratio was found. CBF/ReHo ratio in the left middle temporal gyrus of PT patients was positively correlated with Tinnitus Handicap Inventory score (r = 0.433, p = 0.035).ConclusionThese findings indicated that patients with PT exhibit abnormal neurovascular coupling, which provides new information for understanding the neuropathological mechanisms underlying PT.

With the increase in the number of patients and prolongation of their lives after esophagectomy for esophageal cancer, the quality of life after surgery has attracted more and more attention. Although anastomotic stenosis is a common complication, it seriously affects the quality of life and psychological state of patients or even threatens their lives. At present, the exact independent influencing factors of anastomotic stenosis after esophageal cancer surgery have not been determined, and relevant treatment options are still controversial. Here, we analyzed the independent risk factors leading to good postoperative anastomotic stenosis, in order to provide a basis for late prevention. At the same time, we deeply discussed the advantages and safety of stent implantation in the treatment of anastomotic stenosis.

In many congested areas, shared parking has gotten increasing attention because of its potential to alleviate parking resource shortages. However, managing parking resources remains a challenge when simultaneously considering multiple decision-making criteria of public travelers in allocating parking spaces and recommending optimal parking routes. To fill this gap, from four perspectives, i.e., driving, among shared parking lots, at a shared parking lot, between shared parking spaces and destinations, we proposed nine criteria for shared parking space allocations and parking route recommendations, and we also gave the quantitative models for different criteria. Furthermore, an analytic hierarchy process Entropy-TOPSIS grey relational analysis (AHP-Entropy-TOPSIS-GRA) method and an improved ant colony algorithm were proposed to solve the proposed allocation of parking spaces and recommend optimal parking routes, respectively. Finally, the validity of our proposed models and algorithms was tested by empirical parking data and road traffic data collected in Huai’an City, Jiangsu province, China. The research helps provide a theoretical foundation for implementing shared parking initiatives and improving public travelers’ parking satisfaction.

Since carbonate reservoirs develop pores and fractures and have a complex formation pressure system, overflow and even blowout seriously threaten the exploration and development of these kinds of reservoirs. According to the overflow characteristics of fractured-vuggy carbonate reservoirs, a field monitoring and identification method for overflow has been developed. This method is based on the top-down logic framework for early overflow identification, combined with optimized monitoring parameters. The DBSCAN clustering algorithm is used to identify abnormal logging parameters, and thus, a probability weight coefficient of overflow (K) indicated by the abnormal engineering parameters of a gas well can be calculated. K is divided into four early warning response levels of overflow, and the overflow control operation can be made according to the different levels of early warning response. Based on this method, an integrated software system for field monitoring and identification of early overflow is designed. This software system integrates the functions of data collection and management, overflow risk parameter calculation, overflow early warning, and overflow simulation analysis. Finally, according to a case analysis of overflow prediction for a fractured-vuggy carbonate reservoir in Well XX, this method’s prediction stability and accuracy are demonstrated, indicating that it can be used for the overflow early warning in engineering practice.

Volcanic eruptions significantly impact human life. However, real-time high-precision imaging in this context still has limitations. Spatial–temporal interpolation can replace real-time data imaging, in order to obtain the state of a given volcano at any moment. The dispersion curve is interpolated in space as a foreshadowing for subsequent temporal interpolation. In this paper, kriging is applied for the interpolation of dispersion curves, and the feasibility of the process is verified through several tests. Through cross-validation, the “spherical” variogram model and universal kriging were determined. The mean relative error of the predicted dispersion curve is less than 10%, and the mean root mean square error of each predicted dispersion curve is less than 0.1. The results show that the interpolation of dispersion curves based on the kriging method is feasible. In addition, the application of kriging interpolation in ambient noise tomography can expand the imaging area, as well as complement the low ray density area. Taking the ambient noise tomography of the Changbai volcano as an example, in the deep area, the expansion multiple can reach 2.4.

Linear and nonlinear simulations are carried out for the edge coherent mode (ECM) using the global gyrokinetic code GEM based on the EAST experimental parameters. The linear simulation results show that ECM is an electrostatic mode with dominant toroidal mode number n = 18 and frequency about 48 kHz, and propagates along the direction of electron diamagnetic drift, which are consistent with the experimental results. In addition, the density and electron temperature gradients destabilize the mode, while the collision stabilizes the mode. The nonlinear simulation results show that the saturated particle and heat fluxes induced by ECM are mainly due to the perturbed electrostatic ExB drift, and the fluxes of electrons and ions are almost equal. The ECM drives significant outward particle and heat fluxes, thus greatly promoting the maintenance of the long pulse H-mode. The Fourier decomposition of fluxes and potentials demonstrate that the intermediate- n modes of n = 14, 18 grow fastest in the linear phase, while in the nonlinear saturation phase, the low-n modes such as n = 4, 6 dominate and the fluxes are mainly contributed by the mode of n = 10. It is found that zonal flow is not the dominant saturation mechanism of the turbulence. The inverse spectral cascade of turbulence is inevitably observed in the nonlinear saturation process, indicating that it is a more universal turbulence saturation mechanism. It is also found that radial electric field can greatly reduce the turbulence intensity and transport level. From the analyses of frequency and transport channels, it can be concluded that ECM appears to be the collisionless trapped electron mode.

The traditional von Neumann structure computers cannot meet the demands of high-speed big data processing; therefore, neuromorphic computing has received a lot of interest in recent years. Brain-inspired neuromorphic computing has the advantages of low power consumption, high speed and high accuracy. In human brains, the data transmission and processing are realized through synapses. Artificial synaptic devices can be adopted to mimic the biological synaptic functionalities. Nanowire (NW) is an important building block for nanoelectronics and optoelectronics, and many efforts have been made to promote the application of NW-based synaptic devices for neuromorphic computing. Here, we will introduce the current progress of NW-based synaptic memristors and synaptic transistors. The applications of NW-based synaptic devices for neuromorphic computing will be discussed. The challenges faced by NW-based synaptic devices will be proposed. We hope this perspective will be beneficial for the application of NW-based synaptic devices in neuromorphic systems.

Combining the advantages of high efficiency, environmental robustness, and anti-reflection behavior, oscillating-amplifying integrated fiber lasers have become popular for use in high-power laser structures in industrial applications, wherein the size of the laser source matters. Here, an oscillating-amplifying integrated fiber laser in an oval-shaped cylinder package has been proposed and demonstrated, the footprint for which only occupies an area of 0.024 m2 apart from the pump diode, which is much smaller than in traditional planar fiber laser packages. Numerical simulations have been carried out, which have revealed that an oval-shaped cylinder package can effectively suppress the high-order mode in large mode area fiber setups and thereby benefit the integration of fusion points and the unpackaged elements at the same time. Over 3.7 kW of transverse mode instability (TMI)-free output power has been obtained, with a slope efficiency higher than 80%. With a custom-made chirped and tilted fiber Bragg grating (CTFBG), the Raman suppression ratio is improved to reach 38 dB at peak output power. The oval-shaped design has been verified to assist with the realization of TMI suppression and improve the integration of high-power fiber lasers. To the best of our knowledge, this fiber laser has among the smallest footprints of the various fiber sources at such high-power operating levels.

Objective: Transverse sinus stenosis (TSS) is associated with various symptoms, but whether it can lead to pathological brain changes is unclear. This study aimed to investigate brain changes in venous pulsatile tinnitus (PT) patients with TSS.Materials and Methods: In this study, fifty-five consecutive venous PT patients and fifty age- and gender-matched healthy controls (HCs) were investigated. In CT venography, the combined conduit score (CCS) was used to assess the degree of TSS in venous PT patients. Magnetic resonance venography was used to assess TSS in HCs. All the participants had undergone arterial spin labeling and structural MRI scans.Results: Two patients without TSS and ten HCs with TSS were excluded. Fifty-three venous PT patients with TSS and 40 HCs without TSS were included in this study. All the patients had unilateral cases: 16 on the left and 37 on the right. Based on the CCS, the patients were divided into high-degree TSS (a score of 1–2) (n = 30) and low-degree TSS groups (a score of 3–4) (n = 23). In the whole brain and gray matter, the patients with high-degree TSS showed decreased cerebral blood flow (CBF) compared with patients with low-degree TSS as well as HCs (P < 0.05), and no significant difference in CBF was found in patients with low-degree TSS and HCs (P > 0.05). In white matter (WM) regions, the patients with high-degree TSS exhibited decreased CBF relative to the HCs (P < 0.05). The incidence of cloud-like WM hyperintensity was significantly higher in the above two patient groups than in the HC group (P < 0.05).Conclusion: TSS in venous PT patients may lead to decreased CBF and cloud-like WM hyperintensity. These neuroimaging findings may provide new insights into pathological TSS in venous PT.

Objective: To investigate the effect of the blood flow direction and afflux location of emissary veins (EVs) on the hemodynamics of the transverse-sigmoid sinus (TS-SS) junction.Methods: A patient-specific geometric model was constructed using computed tomography venography (CTV) and 4D flow MR data from a venous pulsatile tinnitus (PT) patient. New EV models were assembled with the afflux at the superior, middle and inferior portions of the SS from the original model, and inlet and outlet directions were applied. Computational fluid dynamics (CFD) simulation was performed to analyze the wall pressure and flow pattern of the TS-SS junction in each condition.Results: Compared to the model without EVs, the wall pressure was greatly increased in models with inlet flow and greatly decreased in models with outlet flow. The more closely the EV approached the TS-SS, the larger the pressure in models with inlet flow, and the smaller the pressure in models with outlet flow. The flow streamline in the lateral part of the TS-SS junction was smooth in all models. The streamlines in the medial part were regular spirals in outlet models and chaotic in inlet models. The streamlines showed no obvious changes regardless of afflux location. The velocity at the TS-SS junction of inlet models were uniform, medium-low flow rate, while in control and outlet models were the lateral high flow rate and the central low flow rate.Conclusion: The flow direction and afflux location of EVs affect the hemodynamics of the TS-SS junction, which may influence the severity of PT.

This study aimed to investigate abnormal tinnitus activity by evaluating brain surface-based amplitude of low-frequency fluctuation (ALFF) changes detected by resting-state functional magnetic resonance imaging (RS-fMRI) in patients with idiopathic tinnitus before and after 24 weeks of sound therapy. We hypothesized that sound therapy could gradually return cortical local brain function to a relatively normal range. In this prospective observational study, we recruited thirty-three tinnitus patients who had undergone 24 weeks of sound therapy and 26 matched healthy controls (HCs). For the two groups of subjects, we analyzed the spontaneous neural activity of tinnitus patients by cortical ALFF and detected its correlation with clinical indicators of tinnitus. Patients’ Tinnitus Handicap Inventory (THI) scores were assessed to determine the severity of their tinnitus before and after treatment. Two-way mixed model analysis of variance and Pearson’s correlation analysis were used in the statistical analysis. Student–Newman–Keuls tests were used in the post hoc analysis. Interaction effects between the two groups and between the two scans revealing local neural activity as assessed by ALFF were observed in the bilateral dorsal stream visual cortex (DSVC), bilateral posterior cingulate cortex (PCC), bilateral anterior cingulate and medial prefrontal cortex (ACC and MPC), left temporo-parieto-occipital junction (TPOJ), left orbital and polar frontal cortex (OPFC), left paracentral lobular and mid cingulate cortex (PCL and MCC), right insular and frontal opercular cortex (IFOC), and left early visual cortex (EVC). Importantly, local functional activity in the left TPOJ and right PCC in the patient group was significantly lower than that in the HCs at baseline and was increased to relatively normal levels after treatment. The 24-week sound therapy tinnitus group demonstrated significantly higher ALFF in the left TPOJ and right PCC than in the tinnitus baseline group. Also, compared with the HC baseline group and the 24-week HC group, the 24-week sound therapy tinnitus group demonstrated slightly lower or higher ALFF in the left TPOJ and right PCC, and there were no differences between the 24-week sound therapy tinnitus and HC groups. Decreased THI scores and ALFF changes in the abovementioned brain regions were not correlated. Taken together, surface-based RS-fMRI can provide more subtle local functional activity to explain the mechanism of tinnitus treatment, and long-term sound therapy had a normalizing effect on tinnitus patients.

The sediment microbial community plays a key role in the cycling of organic matter in marine ecosystems. The characteristics of the sediment microbial community are significantly related to changes in the environment. In this study, we analyzed the diversity and distribution of microbial communities in sediments from different geographical regions (the Liao River estuary, Yellow River estuary, hypoxic zone, and offshore zone) of the Bohai Sea using high-throughput sequencing. The results showed that the community richness and diversity (especially the unique diversity) of the Liao River estuary were larger than those of the Yellow River estuary, hypoxic zone, and offshore zone. The phylum Proteobacteria dominated in the Liao River estuary (46.26%), hypoxic zone (76.19%), and offshore zone (69.79%), while the dominant phylum in the Yellow River estuary was the Bacteroidetes phylum. The genus Gillisia was the dominant genus in both the Liao River estuary and Yellow River estuary. The offshore zone and hypoxic zone shared the same dominant Photobacterium genus. The results of Pearson correlation and redundancy analysis showed that environmental parameters such as nitrite, silicate, nitrate, phosphate, ammonia, dissolved oxygen, pH, and salinity interfered significantly with the structure and diversity of the microbial community. The results of this study will provide support for future research on the interaction mechanism of pollutants and microorganisms in the estuaries and a typical hypoxic zone of the Bohai Sea.

A design integrating multiple cladding mode strippers used in fiber laser architectures into a single device is proposed. This approach can increase the compactness of fiber lasers, thus contributing to industrial laser processing applications. By offset-placing the most intense light-stripping parts, for instance, by inversing the laser injection directions or by displacing the beginning of etched sections, multiple cladding mode strippers bundled together into a single housing can have the hottest regions separated and can operate at full power simultaneously, with no evident cross-influence on each other. Two and three cladding-mode-stripper arrays have been implemented, and validation tests have been conducted with ~500-W cladding power being injected into each input port. For both arrayed devices, compared to the scenario in which only a single cladding mode stripper is working, no greater than a 2.1 °C temperature increment is generated when all components are operating concurrently, which demonstrates the effectiveness of the integration method. In this way, one half and two thirds of space/weight reduction can be realized, respectively, for the two and three cladding-mode-stripper arrays, which is meaningful, since cladding mode strippers are among the most bulky and hottest components in fiber lasers. Moreover, this integration provides a valuable reference for the miniaturization of other components, and thus, could contribute to the development fiber lasers with higher power-to-volume ratios, which would be more economical for industrial applications.

Aiming to solve the problems of the poor uniformity of seed flow discharge and serious damage of traditional straight grooved wheels to improve the performance of air-assisted maize high-speed precision seed metering devices, a staggering symmetrical spiral grooved feeding wheel with maize seeds was designed. To explore the influence of the spiral groove inclination angle and the length of the staggered symmetrical spiral groove feed wheel on the uniformity of seed flow discharge, the spiral groove length l and the spiral groove inclination angle ρ were used as the experimental factors, and the variation coefficient of the increase in seed, a full-factor simulation test was carried out for the test indicators, and it was found that both the inclination angle and the length of the spiral groove have an influence on the uniformity of seed flow discharge, and the influence of the inclination angle of the groove is more significant. Comparing the force of a single seed in the traditional straight grooved wheel and that of the spiral feeding wheel, it is found that the staggered symmetrical spiral grooved feeding wheel can reduce the damage of seed fertilizer. Through a bench test, the spiral groove length was found to be 50 mm, and the groove inclination angles are 30°, 45° and 90°. The test results show the variation trend and simulation results of the fluctuating coefficient of variation of the seed flow discharge in the bench test. The trend of change is basically the same. The inclination angle of the spiral groove is 45° and the uniformity of seed flow discharge is the best when the groove length is 50 mm, indicating that this structure can effectively improve the uniformity of material discharge, and the variation coefficient of seed flow discharge fluctuation is 3.12% and the seed breakage rate is 0.69%. Through the seeding performance test, it is verified that the staggered symmetrical spiral grooved feeding wheel can improve the seeding performance of the pneumatic high-speed precision metering device. When the metering device runs smoothly, the qualified rate reaches more than 90%, and the leakage rate is reduced to 0%. Therefore, the results of this study can provide a reference for research on uniform seeding, drill seeding and the uniform application of granular fertilizer.

Due to their high sensitivity to temperature and humidity, the applications of polylactic acid (PLA) products are limited. The stereo-complexation (SC) formed by poly(L-lactic acid) (PLLA) and its enantiomer poly(D-lactic acid) (PDLA) can effectively improve the heat resistance and hydrolysis resistance of PLA products. In this work, the blended melt-spinning process of PLLA/PDLA was carried out using a polyester fiber production line to obtain PLA fiber with a complete SC structure. The effects of high-temperature tension heat-setting on the crystalline structure, thermal properties, mechanical properties, and hydrolysis resistance were discussed. The results indicated that when the tension heat-setting temperature reached 190 °C, the fiber achieved an almost complete SC structure, and its melting point was 222.5 °C. An accelerated hydrolysis experiment in a 95 °C water bath proved that the SC crystallites had better hydrolysis resistance than homocrystallization (HC). The monofilament strength retention rate of SC−190 fiber reached as high as 78.5% after hydrolysis for 24 h, which was significantly improved compared with PLLA/PDLA drawn fiber.

ObjectivesTo assess a non-invasive means of predicting a venous trans-stenotic pressure gradient (TPG) and intracranial pressure (ICP) as opposed to invasive examinations in unilateral venous pulsatile tinnitus (PT) patients.MethodsThirty patients with unilateral venous PT who presented symptomatic-sided transverse sinus stenosis (TSS) on computed tomography venography (CTV), ipsilateral TPG measured by digital subtraction angiography (DSA) and cerebrospinal fluid (CSF) pressure measured by lumbar puncture were included. The ratio of TSS was calculated by dividing the cross-sectional areas of the maximal stenosed transverse sinus by that of the adjacent normal transverse sinus on CTV. The correlations among and predictive values of TSS, TPG, and ICP were analyzed.ResultsIn patients with unilateral venous PT, the symptomatic-sided and average bilateral TSS values were 78 ± 11 and 77 ± 9%; ICP, 230.50 ± 55.75 mmH2O; and the TPG, 9.51 ± 5.76 mmHg. The symptomatic-sided TSS was linearly and positively correlated with TPG (R2 = 0.400), and the symptomatic-sided and bilateral average TSS both showed weak correlations with ICP (R2 = 0.288, R′2 = 0.156). When the degree of TSS increased by 10%, the TPG and ICP increased by approximately 3.3 mmHg and 25.8 mmH2O, respectively. The receiver operating characteristic curve showed the optimal threshold of ipsilateral TSS for a positive TPG was 0.75, while TSS had no significant predictive value for ICP (p > 0.05). TPG and ICP also exhibited a linear positive correlation (R2 = 0.552). When ICP increased by 10 mmH2O, the TPG increased by approximately 0.77 mmHg, and the optimal threshold of ICP for a positive TPG was 227.5.ConclusionTSS, TPG, and ICP are interrelated. TSS measured by CTV can predict TPG in patients with unilateral venous PT.

Abstract The increasing incidence and mortality of malignant tumors have required the development of diversified innovative therapies. Compared with the new therapeutic molecule invention, it is a more economical and efficient way to reposition old drugs that have been marketed or in clinical trials for tumor treatment. Studies have been carried out for repositioning the old approval drugs that are widely applied clinically with reliable biosafety and effectiveness evidence, including aspirin, artemisinin (and its derivatives, eg, dihydroartemisinin), metformin, and disulfiram (DSF). In addition to the approved pharmacological activity, these old drugs exhibited broad tumor‐suppressive effects. This review summarizes the drug repositioning strategy of DSF through nanotechnology and outlines the DSF nano‐formulations for cancer targeting delivery and therapy.

Abstract Background The long non-coding RNA H19 plays critical roles in cancer occurrence, development, and progression. The present study is for the first time to evaluate the association of genetic variations in the H19 promoter region with advanced colorectal cancer (CRC) susceptibility, environmental factors, and clinical outcomes. Methods 16 single-nucleotide polymorphisms (SNPs) were identified in the H19 gene promoter by DNA sequencing, and 3 SNPs among which including rs4930101, rs11042170, and rs2735970 further expanded samples with 572 advanced CRC patients and 555 healthy controls. Results We found that harboring SNP [rs4930101 (P = 0.009), rs2735970 (P = 0.003), and rs11042170 (P = 0.003)] or carrying more than one combined risk genotypes significantly increased the risk for CRC [P 1 vs. ≤ 1) and family history of cancer demonstrated significant interactions. Furthermore, a remarkably worse clinical outcome was found in combined risk genotypes (> 1 vs. ≤ 1), especially in CRC patients with body weight ≥ 61 kg, smoking, and first-degree family history of cancer (Log-rank test: P = 0.006, P = 0.018, and P = 0.013, respectively). More importantly, the multivariate Cox regression analyses further verified that combined risk genotypes > 1 showed a prognostic risk factor for CRC patients with body weight ≥ 61 kg (P = 0.002), smoking (P = 0.008), and family history of cancer (P = 0.006). In addition, MDR analysis consistently revealed that the combination of selected SNPs and nine known risk factors showed a better prediction prognosis and represented the best model to predict advanced CRC prognosis. Conclusion 3 SNPs of rs4930101, rs11042170, and rs27359703 among 16 identified SNPs of H19 gene remarkably increased CRC risk. Furthermore, the combined risk genotypes had a significant impact on environmental factors and clinical outcomes in the advanced CRC patients with body weight ≥ 61 kg, ever-smoking, and first-degree family history of cancer. These data suggest that H19 promoter SNPs, especially these combined SNPs might be more potentially functional biomarkers in the prediction of advanced CRC risk and prognosis.

Abstract Background SAPHO syndrome is a rare disease characterized by inflammatory lesions on skin and bones. Diversified manifestation and inadequate understanding of etiology has limited its diagnosis and treatment. The co-occurrence of other immune-mediated diseases strongly suggests an involvement of autoimmunity in SAPHO syndrome. However, the role of the largest population of circulating immune cells, neutrophils, is still not well explored. In this study, we performed RNA sequencing to profile the mRNA expression of neutrophils purified from peripheral blood of SAPHO patients to identify key genes associated with SAPHO syndrome, trying to find new functional molecules or biomarkers for this rare disease. Results A total of 442 differentially expressed genes were identified (p 2), in which 294 genes were upregulated and 148 genes were downregulated. Five differentially expressed genes of interest were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), among which S100A12 was upregulated and positively related to high-sensitivity C-reactive protein (hsCRP), while the downregulated gene MYADM was positively related to osteocalcin. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes were enriched in “systemic lupus erythematosus” and “ECM-receptor interaction”. Gene ontology (GO) enrichment showed that differentially expressed genes may participate in biological processes such as “cell migration” and “cell adhesion”. Conclusions In conclusion, this study provides a first insight into transcriptome characteristics of SAPHO syndrome, indicating an over-active neutrophil recruitment in patients and possibly suggesting molecular candidates for further study on diagnosis and pathology of this disease.

Abstract Immunotherapies have led to substantial changes in cancer treatment and have been a persistently popular topic in cancer research because they tremendously improve the efficacy of treatment and survival of individuals with various cancer types. However, only a small proportion of patients are sensitive to immunotherapy, and specific biomarkers are urgently needed to separate responders from nonresponders. Mismatch repair pathways play a vital role in identifying and repairing mismatched bases during DNA replication and genetic recombination in normal and cancer cells. Defects in DNA mismatch repair proteins and subsequent microsatellite instability-high lead to the accumulation of mutation loads in cancer-related genes and the generation of neoantigens, which stimulate the anti-tumor immune response of the host. Mismatch repair deficiency/microsatellite instability-high represents a good prognosis in early colorectal cancer settings without adjuvant treatment and a poor prognosis in patients with metastasis. Several clinical trials have demonstrated that mismatch repair deficiency or microsatellite instability-high is significantly associated with long-term immunotherapy-related responses and better prognosis in colorectal and noncolorectal malignancies treated with immune checkpoint inhibitors. To date, the anti-programmed cell death-1 inhibitor pembrolizumab has been approved for mismatch repair deficiency/microsatellite instability-high refractory or metastatic solid tumors, and nivolumab has been approved for colorectal cancer patients with mismatch repair deficiency/microsatellite instability-high. This is the first time in the history of cancer therapy that the same biomarker has been used to guide immune therapy regardless of tumor type. This review summarizes the features of mismatch repair deficiency/microsatellite instability-high, its relationship with programmed death-ligand 1/programmed cell death-1, and the recent advances in predicting immunotherapy efficacy.