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Purpose Finite element analysis (FEA) was used to evaluate the effects of different thicknesses, numbers, and positions of the miniplate applied in bilateral sagittal split osteotomy (BSSO) under two occlusal conditions. Methods An FEA model of the mandibles was constructed and combined with different thicknesses (0.6 or 1 mm), number (one or two), positions (upper or lower) of a miniplate and was divided into six models. In addition, external forces were applied to the muscles to simulate the intercuspal position (ICP) and right unilateral molar clench. This study used the reaction force of the temporomandibular joints and the stress of the mandible as observation indexes. Results The results of this study show that, under ICP, the 0.6 mm lower model generated greater TMJ force reaction compared to the 0.6 mm upper model. The same trend was seen in the 1 mm lower model compared to the 1 mm upper model. Regarding the stress of the bone on the screw-implanted sites, under ICP, screw 10 showed greater stress than screw 2, and screw 11 showed greater stress than screw 3. The stress values of the miniplates showed, under ICP, point 1-c was greater than point 3-c, and point 1-b was greater than point 3-b. Conclusion In the case of BSSO mandibular advancement surgery, implanting the miniplate at the upper position can reduce the force on the TMJ and the stress on the distal segment of the mandible. The miniplate can also resist the tensile stress more effectively. In addition, implanting two miniplates with thinner sizes may be an alternative in clinical practice.

Background Resistance to immune checkpoint inhibitor (ICI) therapy narrows the efficacy of cancer immunotherapy. Although 4-1BB is a promising drug target as a costimulatory molecule of immune cells, no 4-1BB agonist has been given clinical approval because of severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy. Methods HK010 was generated by antibody engineering, and the Fab/antigen complex structure was analyzed using crystallography. The affinity and activity of HK010 were detected by multiple in vitro bioassays, including enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), flow cytometry, and luciferase-reporter assays. Humanized mice bearing human PD-L1-expressing MC38 (MC38/hPDL1) or CT26 (CT26/hPDL1) tumor transplants were established to assess the in vivo antitumor activity of HK010. The pharmacokinetics (PK) and toxicity of HK010 were evaluated in cynomolgus monkeys. Results HK010 was generated as an Fc-muted immunoglobulin (Ig)G4 PD-L1x4-1BB bispecific antibody (BsAb) with a distinguished Fab/antigen complex structure, and maintained a high affinity for human PD-L1 (KD: 2.27 nM) and low affinity for human 4-1BB (KD: 493 nM) to achieve potent PD-1/PD-L1 blockade and appropriate 4-1BB agonism. HK010 exhibited synergistic antitumor activity by blocking the PD-1/PD-L1 signaling pathway and stimulating the 4-1BB signaling pathway simultaneously, and being strictly dependent on the PD-L1 receptor in vitro and in vivo. In particular, when the dose was decreased to 0.3 mg/kg, HK010 still showed a strong antitumor effect in a humanized mouse model bearing MC38/hPDL1 tumors. Strikingly, HK010 treatment enhanced antitumor immunity and induced durable antigen-specific immune memory to prevent rechallenged tumor growth by recruiting CD8+ T cells and other lymphocytes into tumor tissue and activating tumor-infiltrating lymphocytes. Moreover, HK010 not only did not induce nonspecific production of proinflammatory cytokines but was also observed to be well tolerated in cynomolgus monkeys in 5 week repeated-dose (5, 15, or 50 mg/kg) and single-dose (75 or 150 mg/kg) toxicity studies. Conclusion We generated an Fc-muted anti-PD-L1x4-1BB BsAb, HK010, with a distinguished structural interaction with PD-L1 and 4-1BB that exhibits a synergistic antitumor effect by blocking the PD-1/PD-L1 signaling pathway and stimulating the 4-1BB signaling pathway simultaneously. It is strictly dependent on the PD-L1 receptor with no systemic toxicity, which may offer a new option for cancer immunotherapy.

In this study, the bacterial diversity of acquired middle ear cholesteatoma (MEC) was evaluated to reveal its pathogenesis and provides a guide for the use of antibiotics. Twenty-nine cases of acquired MEC and eight cases of healthy middle ears undergoing cochlear implantation (CI) were evaluated. Full-length 16S rRNA gene sequencing was performed to profile the bacterial communities in lesions and healthy tissues of the middle ear. ACE (P = 0.043) and Chao1 (P = 0.039) indices showed significant differences in alpha diversity (P < 0.05). Analysis of PERMANOVA/Anosim using the Bray–Curtis distance matrix results suggested that the between-group differences were greater than the within-group differences (R = 0.238, P < 0.05, R2 = 0.066, P < 0.05). Bacterial community analysis revealed that Alphaproteobacteria at the class level and Caulobacterales and Sphingomonadales at the order level were significantly different (P < 0.05). In the LefSe (Linear discriminant analysis effect size) analysis, Porphyromonas bennonis was elevated, and Bryum argenteum and unclassified Cyanobacteriales were reduced at the species level in MEC (P < 0.05). Fifteen metabolic pathways were found to be significantly different between the two groups by analysing the abundance of metabolic pathways in level 2 of the Kyoto Encyclopaedia of Genes and Genomes (KEGG). Seven and eight metabolic pathways were significantly elevated in the MEC and control groups, respectively (P < 0.05). The role of bacteria in the pathogenesis of acquired MEC was further refined through analysis of metabolic pathways. These findings indicate that the acquired MEC and healthy middle ear contain more diverse microbial communities than previously thought.

We aimed to estimate the burden of UTIs by age, sex, and socioeconomic status in 204 countries and territories from 1990 to 2019.We used data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to analyse the incidence, mortality, and disability-adjusted life-years (DALYs) due to UTIs at the global, regional, and national levels. Estimates are presented as numbers and age-standardised or age-specific rates per 100,000 population, with 95% uncertainty intervals (UIs). We further explored the associations between the incidence, mortality, DALYs, and socio-demographic index (SDI) as a proxy for the development status of regions and countries.In 2019, more than 404.6 million (95% UI 359.4-446.5) individuals had UTIs globally and nearly 236,786 people (198,433-259,034) died of UTIs, contributing to 5.2 million (4.5-5.7) DALYs. The age-standardised incidence rate increased from 4715.0 (4174.2-5220.6) per 100,000 population in 1990 to 5229.3 (4645.3-5771.2) per 100,000 population in 2019. At the GBD regional level, the highest age-standardised incidence rate in 2019 occurred in Tropical Latin America (13,852.9 [12,135.6-15,480.3] per 100,000 population). At the national level, Ecuador had the highest age-standardised incidence rate (15,511.3 [13,685.0-17,375.6] per 100,000 population). The age-standardised death rates were highest in Barbados (19.5 [13.7-23.5] per 100,000 population). In addition, age-standardised incidence, death, and DALY rates generally increased across the SDI.Our study results suggest a globally rising trend of UTI burden between 1990 and 2019.

The Arabidopsis H3K9 methyltransferases KRYPTONITE/SUPPRESSOR OF VARIEGATION 3–9 HOMOLOG 4 (KYP/SUVH4), SUVH5 and SUVH6 are redundantly involved in silencing of transposable elements (TEs). Our recent study indicated that KYP/SUVH5/6 can directly interact with the histone deacetylase HDA6 to synergistically regulate TE expression. However, the function of KYP/SUVH5/6 in plant development is still unclear. The transcriptional factors ASYMMETRIC LEAVES1 (AS1) and AS2 form a transcription complex, which is involved in leaf development by repressing the homeobox genes KNOTTED-LIKE FROM ARABIDOPSIS THALIANA 1 (KNAT1) and KNAT2. In this study, we found that KYP and SUVH5/6 directly interact with AS1-AS2 to repress KNAT1 and KNAT2 by altering histone H3 acetylation and H3K9 dimethylation levels. In addition, KYP can directly target the promoters of KNAT1 and KNAT2, and the binding of KYP depends on AS1. Furthermore, the genome-wide occupancy profile of KYP indicated that KYP is enriched in the promoter regions of coding genes, and the binding of KYP is positively correlated with that of AS1 and HDA6. Together, these results indicate that Arabidopsis H3K9 methyltransferases KYP/SUVH5/6 are involved in leaf development by interacting with AS1-AS2 to alter histone H3 acetylation and H3K9 dimethylation from KNAT1 and KNAT2 loci.

Background To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method. Methods The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time. Results All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into “early phase” and “late phase.” In “late phase” cases, there was less time spent on each step of the operation and less EBL. Conclusions Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.

Conductive carbon structure has been considered as a promising sulfur-hosting material as the cathode of lithium-sulfur batteries. However, the issue of polysulfide shuttling requires an additional component to help restrict and convert sulfur substances. Herein, in this work, hollow and porous carbon nanospheres (HCS) are synthesized by a template method and a high-temperature carbonization treatment. A thin layer of ZnS coating is then deposited on the HCS-based sulfur (ZnS@HCS/S) cathode with controlled thickness, and the overall electrochemical properties are systematically evaluated. Results show that with 30 nm -thick ZnS coating, the cathode reveals an improved capacity of 1411 mA h g−1, and higher capacities from 0.2 to 3 C rate compared with bare HCS/S cathode. Moreover, the ZnS coating also enhances the cycling stability of ZnS@HCS/S cathode over 280 cycles at 0.5 C, with only 0.2% capacity decay per cycle. This work demonstrates potential applications for high-performance lithium-sulfur batteries.

Background TIMM8A is a protein-coding gene located on the X chromosome. There is evidence that TIMM8A plays an important role in mitochondrial morphology and fission. Studies have shown that mitophagy and fission could affect the function of immune cells. However, there is currently no research on this gene’s role in cancer occurrence and progression. Methods TIMM8A expression was analyzed via the Tumor Immune Estimation Resource (TIMER) site and UALCAN database. We evaluated the influence of TIMM8A on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database, and Human Protein Atlas (HPA). The correlations between TIMM8A and cancer immune infiltrates were investigated via TIMER. Tumor Immune Dysfunction and Exclusion (TIDE) was used to evaluate the potential of tumor immune evasion. Functions of TIMM8A mutations and 50 genes significantly associated with TIMM8A mutations in breast cancer (BRCA) and uterine corpus endometrial cancer (UCEC) were analyzed by GO and KEGG in LinkedOmics database. Results We investigated the role of TIMM8A in multiple cancers and found that it was significantly associated with poor prognosis in BRCA and UCEC. After analyzing the effect of TIMM8A on immune infiltration, we found Th2 CD4+ T cells might be a common pathway by which TIMM8A contributed to poor prognosis in BRCA and UCEC. Our results suggested that myeloid-derived suppressor cells (MDSC) and tumor-associated M2 macrophages (TAM M2) might be important factors in immune evasion through T cell rejection in both cancers, and considered TIMM8A as a biomarker to predict the efficacy of this therapy in BRCA and UCEC. The results of TIMM8A enrichment analysis showed us that abnormally expressed TIMM8A might affect the mitochondrial protein in BRCA and UCEC. Conclusions Contributed to illustrating the value of TIMM8A as a prognostic biomarker, our findings suggested that TIMM8A was correlated with prognosis and immune infiltration, including CD8+ T cells, Th2 CD4+ T cells, and macrophages in BRCA and UCEC. In addition, TIMM8A might affect immune infiltration and prognosis in BRCA and UCEC by affecting mitophagy. We believed it could also be a biomarker to predict the efficacy of anti-PD-L1 therapy and proposed to improve the efficacy by eliminating MDSC and TAM M2.

JMCT is a large-scale, high-fidelity, three-dimensional general neutron–photon–electron–proton transport Monte Carlo software system. It was developed based on the combinatorial geometry parallel infrastructure JCOGIN and the adaptive structured mesh infrastructure JASMIN. JMCT is equipped with CAD modeling and visualizes the image output. It supports the geometry of the body and the structured/unstructured mesh. JMCT has most functions, variance reduction techniques, and tallies of the traditional Monte Carlo particle transport codes. Two energy models, multi-group and continuous, are provided. In recent years, some new functions and algorithms have been developed, such as Doppler broadening on-the-fly (OTF), uniform tally density (UTD), consistent adjoint driven importance sampling (CADIS), fast criticality search of boron concentration (FCSBC) domain decomposition (DD), adaptive control rod moving (ACRM), and random geometry (RG) etc. The JMCT is also coupled with the discrete ordinate SN code JSNT to generate source-biasing factors and weight-window parameters. At present, the number of geometric bodies, materials, tallies, depletion zones, and parallel processors are sufficiently large to simulate extremely complicated device problems. JMCT can be used to simulate reactor physics, criticality safety analysis, radiation shielding, detector response, nuclear well logging, and dosimetry calculations etc. In particular, JMCT can be coupled with depletion and thermal-hydraulics for the simulation of reactor nuclear-hot feedback effects. This paper describes the progress in advanced modeling, high-performance numerical simulation of particle transport, multiphysics coupled calculations, and large-scale parallel computing.

In this study, PEF-induced steric configuration changes of the peptide Lys-Asp-His-Cys-His (KDHCH), proposed as the mechanism for its antioxidant activity enhancement induced by PEF treatments, were investigated using spectral and chromatographic methods. While no primary structure changes were observed, the secondary structure of KDHCH changed with a significant decrease in the level of α-helix from 3.1 to 1.7% (P < 0.05). A left chemical shift of the active hydrogen in hydroxyl and changes in connectivity between hydrogen protons were also identified, which may be caused by the steric configuration changes. The PEF treatment also decreased the zeta potential and size distribution which might result from the degradation of the peptide complex by PEF processing. These findings suggest that PEF treatment of the peptide solution led to a structural change, which may have enhanced exposure of active sites responsible for the antioxidant activity of the peptide.

Motivated by the connection with the genus of the corresponding link and its application on DNA polyhedral links, in this paper, we introduce a parameter smax(G), which is the maximum number of circles of states of the link diagram D(G) corresponding to a plane (positive) graph G. We show that smax(G) does not depend on the embedding of G and if G is a 4-edge-connected plane graph then smax(G) is equal to the number of faces of G, which cover the results of S. Y. Liu and H. P. Zhang as special cases.

Because of technological advancement, human face recognition has been commonly applied in various fields. There are some HCI-related applications, such as camera-ready chatbot and companion robot, require gathering more information from user’s face. In this paper, we developed a system called EAGR for emotion, age, and gender recognition, which can perceive user’s emotion, age and gender based on the face detection. The EAGR system first applies normalized facial cropping (NFC) as a preprocessing method for training data before data augmentation, then uses convolution neural network (CNN) as three training models for recognizing seven emotions (six basics plus one neutral emotion), four age groups, and two genders. For better emotion recognition, the NFC will extract facial features without hair retained. On the other hand, the NFC will extract facial features with hair retained for better age and gender recognition. The experiments were conducted on these three training models of emotion, age and gender recognitions. The recognition performance results from the testing dataset, which has been normalized for tilted head by proposed binocular line angle correction (BLAC), showed that the optimal mean accuracy rates of real-time recognition for seven emotions, four age groups and two genders were 82.4%, 74.95%, and 96.65% respectively. Furthermore, the training time can be substantially reduced via NFC preprocessing. Therefore, we believe that EAGR system is cost-effective in recognizing human emotions, ages, and genders. The EAGR system can be further applied in social applications to help HCI service provide more accurate feedback from pluralistic facial classifications.

Elevated fibrinogen (Fbg) levels contribute to tumor progression and metastasis. However, little is known regarding the association of the clinicopathological characteristics and the prognosis of hilar cholangiocarcinoma (HC) with plasma fibrinogen. Data on the plasma Fbg levels, clinicopathological characteristics, and overall survival were retrospectively collected. Plasma fibrinogen concentrations over 4.0 g/L were classified as hyperfibrinogen, elevated fibrinogen, or abnormal fibrinogen levels. We then analyzed the relationships among plasma fibrinogen level, clinicopathological features, and patient prognosis. A total of 171 HC patients were included. An elevated plasma fibrinogen level was associated with lymph-node metastasis (P

Background Circular RNA (circRNA) is a novel class noncoding RNA (ncRNA) that plays a critical role in various cancers, including prostate cancer (PCa). However, the clinical significance, biological function, and molecular mechanisms of circRNAs in prostate cancer remain to be elucidated. Methods A circRNA array was performed to identified the differentially expressed circRNAs. circPDE5A was identified as a novel circRNA which downregulated in clinical samples. Functionally, the in vitro and in vivo assays were applied to explore the role of circPDE5A in PCa metastasis. Mechanistically, the interaction between circPDE5A and WTAP was verified using RNA pulldown followed by mass spectrometry, RNA Immunoprecipitation (RIP) assays. m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) was then used to identified the downstream target of circPDE5A. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were used to identified transcriptional factor which regulated circPDE5A expression. Results circPDE5A was identified downregulated in PCa tissues compared to adjacent normal tissue and was negatively correlated with gleason score of PCa patients. circPDE5A inhibits PCa cells migration and invasion both in vitro and in vivo. circPDE5A blocks the WTAP-dependent N6-methyladenisine (m6A) methylation of eukaryotic translation initiation factor 3c (EIF3C) mRNA by forming the circPDE5A-WTAP complex, and finally disrupts the translation of EIF3C. Moreover, the circPDE5A-dependent decrease in EIF3C expression inactivates the MAPK pathway and then restrains PCa progression. Conclusions Our findings demonstrate that FOXO4-mediated upregulation of circPDE5A controls PCa metastasis via the circPDE5A-WTAP-EIF3C-MAPK signaling pathway and could serve as a potential therapeutic targer for PCa.

Software-defined networking (SDN) is a state-of-the-art architectural approach to network management that allows more flexible management of a complicated large-scale network. For providing services with high performance, availability, and scalability, server clustering is widely used. This study develops a server cluster based on OpenFlow, which is the most common SDN protocol. To utilize cluster resources effectively, this study focuses on the server-side load-balancing issue and increases the performance for a cluster of servers with different processing capabilities. We have proposed a novel load balancing algorithm, named dynamic weighted random selection (DWRS). DWRS considers the real-time server loads when dispatching requests to servers. Underutilized servers are assigned higher weights, so they have a higher possibility of being selected to process requests. To increase system performance, we modify the flow of packet handling in the Floodlight controller. A multi-threaded technique is used to effectively utilize the parallel processing capability of multiple cores, which speeds up the processing of packet-in messages when selecting the target server. This prevents the controller from becoming overloaded, especially when a large number of packet-in messages arrive. To demonstrate effectiveness and feasibility, we deploy our experimental environment using real hardware, instead of using Mininet to set up a virtual SDN testbed. Experimental results show that the proposed DWRS with multi-threaded implementation outperforms other policies, especially in a heterogeneous environment.

With the development of technology, the importance of the research on speech emotion recognition and semantic analysis has increased. The research is primarily applied in companion robot, technology products and medical purpose. In this research, a communication system with speech emotion recognition is proposed. The system pre-process speech with sound data enhancing method in speech emotion recognition and transform the sound into spectrogram by MFCC (Mel Frequency Cepstral Coefficient). Then, GoogLeNet of CNN (Convolutional Neural Network) is applied to recognize the five emotions, which are peace, happy, sad, angry and fear, and the top accuracy of recognition is 79.81%. When applying semantic analysis, the training texts are divided into two categories, positive and negative, and the chatting conversations are conducted in the framework Seq2Seq of RNN (Recurrent Neural Network). The systematic framework of this research has two parts, the client and the server. The former one is developed on Android system to be used in Application, and the latter one is established by Ubuntu Linux system and combined with the web server. With the bi-terminal framework system, the users can record voice in APP one his/her cellphone and upload the voice file to the server. Then, the voice undergoes speech emotion recognition by CNN and semantic analysis by RNN to function as a chatting machine that can respond positively or negatively based on the detected emotion and show the results on APP of the user’s cell phone. The main contributions of this research are: 1) This study introduces the Chinese word vector to the robot dialogue system, effectively improving dialogue tolerance and semantic interpretation, 2) The traditional method of emotion identification must first tokenize the Chinese words, analyze the clauses and part of speech, and capture the emotional keywords before being interpreted by the expert system. Different from the traditional method, this study classifies the input directly through the convolutional neural network after the input sentence is converted into a spectrogram by MFCC, and 3) in addition to implementing the companion robot, the user’s emotional index can be collected for analysis by the back-end care organization. In addition, compared with other commercial humanoid companion robots, this study is presented in an App, which is easier to use and economical.

The persistent inflammatory response at the wound site is a cardinal feature of nonhealing wounds. Prolonged neutrophil presence in the wound site due to failed clearance by reduced monocyte-derived macrophages delays the transition from the inflammatory to the proliferative phase of wound healing. Angiopoietin-like 4 protein (Angptl4) is a matricellular protein that has been implicated in many inflammatory diseases. However, its precise role in the immune cell response during wound healing remains unclear. Therefore, we performed flow cytometry and single-cell RNA sequencing to examine the immune cell landscape of excisional wounds from Angptl4+/+ and Angptl4-/- mice. Chemotactic immune cell recruitment and infiltration were not compromised due to Angptl4 deficiency. However, as wound healing progresses, Angptl4-/- wounds have a prolonged neutrophil presence and fewer monocyte-derived macrophages than Angptl4+/+ and Angptl4LysM-/- wounds. The underlying mechanism involves a novel Angptl4-interferon activated gene 202B (ifi202b) axis that regulates monocyte differentiation to macrophages, coordinating neutrophil removal and inflammation resolution. An unbiased kinase inhibitor screen revealed an Angptl4-mediated kinome signaling network involving S6K, JAK, and CDK, among others, that modulates the expression of ifi202b. Silencing ifi202b in Angptl4-/- monocytes, whose endogenous expression was elevated, rescued the impaired monocyte-to-macrophage transition in the in vitro reconstituted wound microenvironment using wound exudate. GSEA and IPA functional analyses revealed that ifi202b-associated canonical pathways and functions involved in the inflammatory response and monocyte cell fate were enriched. Together, we identified ifi202b as a key gatekeeper of monocyte differentiation. By modulating ifi202b expression, Angptl4 orchestrates the inflammatory state, innate immune landscape, and wound healing process. Nanyang Technological University Published version This research is supported by the Nanyang Technological University Singapore StartUp Grant (#001325-00001) to NST. Single-cell RNA sequencing of the wound healing immune landscape was supported by a 10x Genomics Grant awarded to NST.

A facile and efficient mussel-inspired bonding method is developed to improve the interfacial adhesion of polyamide cord/rubber composites by introducing silica coated with polydopamine (PDA). PDA layer is deposited on the silica surface by simply dipping the silica particles into an alkaline dopamine solution. The core–shell structure can endow polyamide cord/rubber high adhesion strength through the strengthening effect of silica on the adhesive transition layer. This new dipping system displays low toxicity, high efficiency and simplicity, which is crucial to rubber industry and human health. Compared with the original cord, the pulled-out force of our developed dipped cord is increased by 63%. In addition, the adhesive property of our developed dipped cord/rubber is characterized, and the adhesive mechanism is also studied in detail. Bionic design of mussels has provided a new way to enhance the adhesion between polyamide cord and rubber in rubber industry.

Using bio-derived cellulose nanocrystals (CNCs) to reinforce the mechanical properties of biodegradable polyurethanes (PUs) is a promising approach especially when attempting to fabricate fully sustainable materials with high performance. However, the way to efficiently improve the dispersion and interfacial strength of CNCs in PU matrices is still an open question. In the current work, poly-l-lactide (PlLA) grafted CNCs (CNC-g-l) and a PU elastomer with poly-d-lactide as partial soft segments (d-PU) were first prepared separately, and then the fully biodegradable PU nanocomposites were fabricated by solution blending of CNC-g-l and d-PU. The surface grafting of PlLA can improve the thermal stability of CNCs, but has marginal effect on that of the nanocomposites. The improved dispersion of CNCs and enhanced interfacial strength, as evidenced by scanning electron microscopy, wide-angle X-ray diffraction and rheology measurements, are achieved by the construction of interfacial polylactide stereocomplexation (sc-PLA). The optimal improvement in mechanical properties of the nanocomposites is realized when only 1 wt% CNC-g-l is incorporated in the d-PU matrix. With the assistance of interfacial sc-PLA, the nanocomposite can gain 40% reduction in oxygen transmission rate at the optimal CNC-g-l content of 5 wt%. This study may provide a new method to improve the dispersion and interfacial strength of CNCs in biodegradable PUs and achieve simultaneously mechanical and barrier performance enhancement.

Road hotspots detection method is a key issue in the field of intelligent transportation research. Compared with normal hotspots caused by high traffic flow, abnormal hotspots, which are results of road accidents, perform an occurrence time random behavior and difficult to predict. Deducing from the pulse diagnosis method, in this paper, a region real-time congestion factor is constructed to realize road abnormal hotspots discovery. Taxi’s GPS data of Hangzhou City, China are employed to find abnormal pulse of road segment, while the relationship between proposed congestion factor and the real-time traffic data is discussed. Two accidental scenarios are built to verify the validity of the proposed method. The experiment results show that the proposed method performs well in real-time abnormal hotspot detection and analysis output could be useful in path planning and traffic management.

Orchid mycorrhizal fungi are essential for the seed germination and vegetative growth of orchids. The orchid Bletilla striata has great medical value in China because its tuber is rich in mannan. Some endophytic fungi were isolated from the roots of B. striata. The isolate KB-3 was selected for experiments because it could promote the germination of B. striata seeds. Based on morphological characters and phylogenetic analysis, the isolate KB-3 was identified as Fusarium oxysporum. Co-cultivation experiments of KB-3 with B. striata and Dendrobium candidum were performed to demonstrate orchid mycorrhizal structures. Microscopic examination showed that KB-3 established colonization and produced coiled hyphal structures known as pelotons within the cortical cells of both orchid roots. The results confirm that F. oxysporum KB-3 can behave as an orchid mycorrhizal fungus.

A multidecadal change analysis of the irrigation ponds in Taoyuan, Taiwan, was conducted by using multisource data including digitized ancient maps, declassified single-band CORONA satellite images, and multispectral SPOT images. Ponds and paddy fields are texturally similar but spectrally different, whereas the paddy fields and built-up are texturally different but spectrally similar. In this study, supervised land-use/land-cover classifications were conducted using four textural features derived from the single-band CORONA images and spectral features derived from SPOT images. Post-classification analysis revealed that the number of irrigation ponds in the study area decreased during the post-World War II farmland consolidation period (1945–1965) and the subsequent industrialization period (1970–2000). However, efforts on restoration of irrigation ponds in recent years have resulted in gradual increases in the number (9%) and total area (12%) of irrigation ponds in the study area.

This paper proposes a deep learning network (DLN) as the basis for a bearing fault diagnosis technique, which is constructed by the autoencoders and softmax classifier for the purpose of identifying the various multi-degree bearing fault. Firstly, the ensemble empirical mode decomposition (EEMD) method is used to decompose the original vibration signal into intrinsic mode functions (IMFs). A high-dimensionality feature vector is formed by analyzing the statistical parameters in the time domain and the frequency domain of the first several IMFs. Then, this feature vector serves as the input for DLN to classify the bearing fault pattern. In a DLN, an autoencoder performs the unsupervised feature self-learning phase to generate a final significant feature vector for training the softmax classifier. Finally, the parameters of a complete DLN based on stacking auto-encoders and the softmax classifier together is fine-tuned with respect to supervised learning criterion aiming to optimize the classification error. Experimental results have shown a great effect for bearing fault diagnosis based on the proposed DLN. The identification accuracy result has been achieved in the bearing fault status even with the unpredictable defects tests on the inner race and roller element of bearing. Methodologies in this study offer confidence for complex data classification.

The article “Mineralized manganese dioxide channel as the stent coating for in situ precise tumor navigation” was erroneously originally published electronically on the publisher’s internet portal (currently SpringerLink) on 31 October 2020 with Figs. 1, 3, 4, 5, and Fig. S3 in the ESM.

Higher mortality in asthmatics has been shown previously. However, evidence on different asthma phenotypes on long-term mortality risk is limited. The aim was to evaluate the impact of asthma phenotypes on mortality in general population. Data from the National Health and Nutrition Examination Survey from 2001–2002 to 2013–2014 linked mortality files through December 31, 2015, were used (N = 37,015). Cox proportional hazards regression was used to estimate the risk of all-cause and cause-specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions. During the mean follow-up time of 7.5 years, 4326 participants died from a variety of causes. Current asthma, but not former asthma was associated with increased all-cause mortality (current asthma: HR = 1.37; 95% CI 1.20–1.58; Former asthma: HR = 0.93; 95% CI 0.73–1.18); as well as mortality from cardiovascular disease (HRCurrent = 1.41; 95% CI 1.08–1.85) and chronic lower respiratory diseases (HRCurrent = 3.17; 95% CI 1.96–5.14). In addition, we found that the HR for cardiovascular disease (CVD) mortality was slightly greater in people with childhood-onset asthma than those with adult-onset asthma. The HR for chronic lower respiratory diseases (CLRD) mortality was greater in people with adult-onset asthma than those with childhood-onset asthma. However, the differences were not statistically significant. Our study suggested that current asthma but not former asthma was associated with increased all-cause, CLRD and CVD mortality. Future well-designed studies with larger sample are required to demonstrate the association and clarify the potential mechanisms involved.

Background Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. Results The particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. Conclusions This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

Drug-eluting stent (DES) is a promising strategy for esophageal cancer. However, full-covered drug-loaded stents cause damage to non-tumor tissue in the esophagus, and the development controlled-release system to prevent non-tumor tissue injure is currently a major challenge. Here, in situ mineralized manganese dioxide coating on Ce6 embedded electrospun fibers covered stent was developed for effective tumor therapy via intraluminal photodynamic therapy (PDT), which could reduce phototoxicity to normal esophageal tissue. Oxidation of manganese ions, which was previously swelled between fibers, was used to accomplish mineralization. After implantation, the manganese dioxide coating in situ reacts with tumor endogenous H+ and H2O2, which, on the one hand, could effectively alleviate the hypoxic microenvironment which leads to resistance to PDT, and on the other hand, could expose the Ce6-fibers below the coating for intraluminal PDT. In addition, due to the slow degradation of the coating, this stent could own sustained photodynamic performance for up to one month. Notably, the PDT efficiency of the stent was investigated on orthotopic rabbit esophageal cancer models. Overall, this work suggests that in situ mineralized manganese dioxide coated electrospun fibers covered stent may provide a new strategy for advanced esophageal cancer patients as a functional drug delivery platform.

Background Human enterovirus 71 (EV-A71) is a non-enveloped virus that has a single stranded positive sense RNA genome. In a previous study, we showed that miR-876-5p upregulation was observed in the serum of patients with severe EV-A71 infection. Micro-876-5p (miR-876-5p) is a circulating miRNA that can be identified to modulate EV-A71 infections through both in vitro and in vivo studies. However, the regulatory mechanisms that involve miR-876-5p in the EV-A71 infection cycle remain unclear. Methods We demonstrated that miR-876-5p facilitated EV-A71 replication and expression by overexpression and knocking-down of miR-876-5p through the transfection of miR-876-5p plasmid and miR-876-5p inhibitor. Although miR-876-5p suppressed CREB5 expression, luciferase reporter assay confirmed this. We also evaluated the role of miR-876-5p in the EV-A71 infection cycle by CREB5 mediated by transfection with an anti-miR-876-5P inhibitor or in combination with an si-CREB5 plasmid. Results MicroR-876-5p was upregulated in EV-A71-infected neuroblastoma cells. Overexpression of miR-876-5p or knockdown of cyclic-AMP responsive element binding protein 5 (CREB5) promoted EV-A71 replication. The downregulation of miR-876-5p inhibited the accumulation of viral RNA and the production of viral proteins. Interestingly, CREB5 overexpression also suppressed EV-A71 replication. Our in vitro studies reveal that miR-876-5p directly targets CREB5. Finally, downregulation of CREB5 protein abated the inhibitory effect of anti-miR-876-5p and induced inhibitory effect of EV-A71 replication. Conclusions Our results suggest that intracellular miR-876-5p promotes EV-A71 replication indirectly by targeting the host CREB5 protein.

Construction of stereocomplexation on the interface of cellulose nanocrystal (CNC) and poly(l-lactide) (PLLA) has been proven to be an efficient way to strengthen interfacial interaction of the nanocomposite. However, the surface structure variation of CNC with different types of ionic group after grafting of poly(d-lactide) (PDLA) and its influence on the properties of their PLLA nanocomposites are still unrevealed. In this current work, the sulfonated CNC (SCNC) and phosphorylated CNC (PCNC) are prepared and grafted with PDLA by surface-initiated ring-opening polymerization. The removal of ionic groups is observed on the surface of SCNC and PCNC after modification, but it has an opposite effect on the thermal stability of the grafted CNC particles. The thermal stability of SCNC-g increases compared with SCNC while PCNC-g decreases compared with PCNC. Consequently, the large difference in thermal stability of the pristine CNCs disappears after grafting and PCNC-g only shows slightly higher thermal stability than SCNC-g. Although the average PDLA grafting content is similar, the number and length of grafted chains are different on SCNC-g and PCNC-g. The grafted chain length on SCNC-g is 4 times as large as that on PCNC-g, which facilitates the formation of interfacial stereocomplex (SC) crystallites in the SCNC-g/PLLA nanocomposites. The SC crystallites improve the thermal stability of the nanocomposites and accelerate the matrix crystallization kinetics. PCNC-g/PLLA samples contrarily show earlier decomposition and lower crystallinity due to the absence of SC crystallites. This study could provide some insights into the effects of ionic groups in the surface grafting process of CNC and the influences on interfacial structure and property of the PLLA nanocomposite.

Substrate materials play a significant role in the improvement of electrochemical biosensors. In the present work, NiO nanoflake arrays were fully and uniformly decorated with Mn3O4 nanoparticles by stepwise method. The as-prepared samples were characterized by scanning electron microscopy (SEM), x-ray diffractionmeter (XRD), transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS), energy-dispersive x-ray spectroscopy (EDS), and chronoamperometry. Subsequently, the optimized Mn3O4 nanoparticle/NiO nanoflake arrays were employed as substrate to fabricate electrochemical biosensors for glucose determination. The results demonstrated that as-prepared glucose biosensors could achieve 226.2 μA mM−1 cm−2 of sensitivity and 1.0 μM of detection limit, respectively. In addition, the linear range was between 9.9 and 3665.0 μM. The developed substrate could also be extended to construct electrochemical biosensors based on other oxidase with excellent performance.

Sulfamethoxazole (SMX) has frequently been detected in aquatic environments. In natural environment, not only individual microorganism but also microbial consortia are involved in some biotransformation of pollutants. The competition for space under consortia causing cell–cell contact inhibition changes the cellular behaviors. Herein, the membrane bioreactor system (MBRS) was applied to improve SMX elimination thorough exchanging the cell-free broths (CFB). The removal efficiency of SMX was increased by more than 24% whether under the pure culture of A. faecalis or under the co-culture of A. faecalis and P. denitrificans with MBRS. Meanwhile, MBRS significantly inhibited the formation of HA-SMX, and Ac-SMX from parent compound. Additionally, the cellular growth under MBRS was obviously enhanced, indicating that the increases in the cellular growth under MBRS are possibly related to the decreases in the levels of HA-SMX and Ac-SMX compared to that without MBRS. The intracellular NADH/NAD+ ratios of A. faecalis under MBRS were increased whether thorough itself-recycle of CFB or exchanging CFB between the pure cultures of A. faecalis and P. denitrificans, suggesting that the enhancement in the bioremoval efficiencies of SMX under MBRS by A. faecalis is likely related to the increases in the NADH/NAD+ ratio. Taken together, the regulation of cell-to-cell communication is preferable strategy to improve the bioremoval efficiency of SMX.

Identification of fluorescent biomarkers with peptide ligand-directed receptors for diagnosis or theranostic of pancreatic ductal adenocarcinoma (PDAC) is still challenging. As potential prognostic/predictive bioimaging targets, both aminopeptidase N (APN, known as CD13) and Caveolin-1 are found as upregulation on the cell membrane surface of PDAC, in which APN is the principal receptor of the cyclic peptide cNGR (Asn-Gly-Arg, NGR) and Caveolin-1 can synergistically mediate endocytosis in this receptor-targeted process. Herein, we conjugate cNGR to dicyanomethylene-4 H -pyran (DCM) chromophore to develop a synergistic-targeted near-infrared (NIR) fluorescent probe DCM-cNGR with strongly intrinsic NIR fluorescence, stable optical performance, low cytotoxicity, and rapid accumulation in PANC-1 cells with the synergistic overexpressed APN receptor-targeted and Caveolin-1-mediated endocytosis. As demonstrated, DCM-cNGR can realize noninvasive NIR imaging for targeting PANC-1 tumor in vivo after intravenous injection into PANC-1 xenograft tumor of nude mice, making a great promise to improve the precision diagnosis and therapy of pancreatic cancer with real time tracing and bioimaging of PDAC in vitro and in vivo .

This study developed an adaptive weighted nonlinear least squares (AWNLS) method for solving the problem of high variability in the estimates of the microrate constants of fluorodeoxyglucose (FDG) kinetics caused by measurement noise. In the AWNLS method for adaptive quantitative analysis, the cost function is adjusted according to the characteristics of the tissue time-activity curve (TTAC). Specifically, the average of the early part of the TTAC was used to modify the cost function when fitting the FDG model to the TTAC. A computer simulation study applying different sets of parameter values and noise conditions was conducted. The accuracy and reliability of the parameter estimates obtained using AWNLS were compared with those of nonlinear least squares (NLS), weighted nonlinear least squares (WNLS), linear least squares (LLS), and generalized linear least squares (GLLS). The errors in k1–k3 obtained using NLS indicate this method’s poor precision in the presence of high noise levels. NLS and WNLS were sensitive to the initial values. Moreover, the results of k4 estimated using LLS and GLLS were inaccurate because of large bias. By contrast, the microrate constants (k1–k4), the FDG metabolic rate (K), and the volume of distribution (k1/k2) obtained using AWNLS were stable and accurate regardless of the noise level and initial values. The AWNLS method could estimate the FDG metabolic rate (K) and the microrate constants (k 1–k 4) of the FDG model accurately at various noise levels, irrespective of the initial values.