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Abstract Objective This study aims to explore the application value of chest wall perforator flaps (CWPF) in oncoplastic breast-conserving surgery. Methods A retrospective review was conducted on 22 early-stage breast cancer patients who underwent oncoplastic breast-conserving surgery using CWPF between January 2021 and December 2022. This included 4 cases (18.2%) utilizing lateral intercostal artery perforator (LICAP) flaps, 10 cases (45.4%) employing lateral thoracic artery perforator (LTAP) flaps, 4 cases (18.2%) combining LICAP and LTAP flaps, and 4 cases (18.2%) using anterior intercostal artery perforator (AICAP) flaps. The perforators used in this study included lateral thoracic artery perforators (LTAP), anterior intercostal artery perforators (AICAP), and lateral intercostal artery perforators (LICAP). In some cases, a combination of LICAP and LTAP was employed to ensure adequate blood supply. All flaps were supplied by dominant perforators, with some cases using multiple perforators to enhance flap perfusion and survival. Our single-center experience with CWPF, including surgical details, complications, aesthetic, and oncological outcomes, is reported. Results Among all patients, tumors were located in the outer quadrant (68.2%), central quadrant (13.6%), and inner quadrant (18.2%) of the excision cavity. In the 22 patients, 15 tumors were located in the outer quadrant: 6 in the left upper outer quadrant (1–2 o’clock), 4 in the right upper outer quadrant (10–11 o’clock), and 5 in the outer quadrants (3 o’clock in 3 cases and 9 o’clock in 2 cases). Four tumors were in the lower inner quadrant: 2 in the left lower inner quadrant (7–8 o’clock) and 2 in the right lower inner quadrant (4–5 o’clock). Three tumors were in the central area extending toward the outer quadrant. All tumors were located more than 2 cm from the nipple-areola complex (NAC), and intraoperative frozen sections confirmed negative margins behind the NAC. All patients had negative surgical margins. The average operative time was 100.5 ± 10.2 min, with flap lengths ranging from 10 to 18 cm and widths from 4 to 10 cm. All flaps survived, with only one instance of surgical site infection, which improved with conservative treatment. Overall patient satisfaction was rated as excellent or good in 85.6%, and physician evaluation was 89.0% excellent or good. In addition to subjective patient and surgeon satisfaction surveys, objective aesthetic outcomes were evaluated using the BCCT.core software. This tool provided a standardized assessment of breast symmetry, contour, and cosmetic outcomes, enhancing the objectivity and reproducibility of the cosmetic evaluation in the study. The median follow-up period was 14.5 months, with one case of tumor recurrence and no patient mortality. Conclusion CWPF can be effectively used in small-to-medium volume, non-ptotic breasts for oncoplastic surgery, yielding high patient satisfaction. In the era of oncoplastic breast surgery, chest wall perforator flaps are a reliable and safe option for partial breast reconstruction with acceptable aesthetic results.

Abstract Background Immune checkpoint blockade (ICB) therapy, including antibodies targeting the programmed cell death protein 1 (PD-1) pathway, has significantly prolonged the overall survival (OS) in patients with advanced cervical cancer (CC). ICB treatment affects both target cells and various components released by immune cells, which can be observed in peripheral blood. However, there has been limited research on the dynamics of peripheral blood immunophenotyping and its association with OS in CC patients receiving ICB therapy. Methods Patients with persistent, recurrent, or metastatic CC treated with ICB were enrolled between December 2019 and September 2022. The dynamic changes in peripheral blood immune cells, immunoglobulins, and complement components were analyzed at baseline (within 30 days prior to the first ICB cycle) and after the second cycle of ICB treatment (4–6 weeks after the first ICB treatment). Associations of the baseline levels of peripheral blood immune cells, immunoglobulins, complement components with OS were analyzed using multivariable Cox regression analysis. Results In this retrospective cohort study, 119 patients who received at least two cycles of ICB were included. Data on peripheral blood immune cells, immunoglobulins, and complement components were available for 70 of these patients. The percentages of suppressor T (Ts) cells and natural killer (NK) cells in peripheral blood increased significantly post-ICB treatment, whereas the Th/Ts ratio and IgM levels decreased. The percentages of cytotoxic T (Tc) cells, Ts cells, the Th/Ts ratio, and levels of IgM, IgA, C3, and C4 were significantly associated with the OS of patients. Furthermore, multivariable Cox regression analysis found that a high level of IgA was associated with poor OS of the patients (HR = 2.918; 95% CI, 1.081–7.877, P = 0.035). Conclusion Our study demonstrated the potential proliferation of peripheral blood anti-tumor T cells in some CC patients undergoing ICB therapy. The observed associations between peripheral blood immunophenotyping and OS suggest that these biomarkers might have potential as prognostic tools.

The microstructural evolution and relaxation strengthening of nano-grained Ni annealed at a temperature range of 493–553 ​K were studied by in situ X-ray diffraction technique, transmission electron microscopy, and microhardness evaluation. Upon low-temperature annealing, the rather limited variations of anisotropic grain size and root-mean-square strain, conforming to an exponential relaxation model, yield a consistent activation energy of approximately 0.5 ​eV, which corresponds to the localized, rapid diffusion of excess vacancies on nonequilibrium surfaces/interfaces and/or defective lattice configurations. Microstructure examinations confirm the grain boundary ordering and excess defect reduction. The relaxation-induced strength enhancement can be attributed to the linear strengthening in the regime of small elastic lattice strains. This study provides an in-depth understanding of low-temperature nanostructural relaxation and its relation to strengthening.

Abstract. Background:. Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. Methods:. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. Results:. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. Conclusion:. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Trial Registration:. Chictr.org.cn: ChiCTR2200059599.

Transmembrane transport remains a significant challenge for nucleic acid vaccine vectors. Promoting the ability of immune cells, such as macrophages, to capture foreign stimuli is also an effective approach to improving cross-presentation. In addition, polyethyleneimine (PEI) has gained attention in the field of nucleic acid vaccine carriers due to its excellent gene transfection efficiency and unique proton buffering effect. However, although high molecular weight PEI exhibits high efficiency, its high-density positive charges make it highly toxic, which limits its application. In this study, mannose/stearyl chloride functionalized polyethylenimine (SA-Man-PEI) was prepared by functionalizing PEI (molecular weight of 25 kDa) with mannose with immunomodulatory and phagocyte targeting effects, and an alkyl hydrophobic chain segment, which could easily promote cell uptake. Moreover, the functionalized-PEI retains a strong proton buffering effect, which helps the carrier escape from the lysosome. The particle sizes of the composite particles formed by SA-Man-PEI and ovalbumin (OVA) were below 200 nm, with good storage stability at both 4 °C and 37 °C. At a drug concentration of 2 μg/mL, the cell survival rate of functionalized-PEI was 19.2% higher than that of unfunctionalized PEI. In vitro macrophage endocytosis experiments showed that SA-Man-PEI could significantly enhance the macrophage uptake of composite particles, compared to unfunctionalized PEI or single-functionalized PEI. This study offers a new approach for developing PEI as a nucleic acid vaccine carrier, which could simultaneously enhance cell targeting and promote cell uptake.

Abstract Conductive gel interface materials are widely employed as reliable agents for electroencephalogram (EEG) recording. However, prolonged EEG recording poses challenges in maintaining stable and efficient capture due to inevitable evaporation in hydrogels, which restricts sustained high conductivity. This study introduces a novel ion‐electron dual‐mode conductive hydrogel synthesized through a cost‐effective and streamlined process. By embedding graphite nanoparticles into ionic hyaluronic acid (HAGN), the hydrogel maintains higher conductivity for over 72 h, outperforming commercial gels. Additionally, it exhibits superior low skin contact impedance, considerable electrochemical capability, and excellent tensile and adhesion performance in both dry and wet conditions. The biocompatibility of the HAGN hydrogel, verified through in vitro cell viability assays and in vivo skin irritation tests, underscores its suitability for prolonged skin contact without eliciting adverse reactions. Furthermore, in vivo EEG tests confirm the HAGN hydrogel's capability to provide high‐fidelity signal acquisition across multiple EEG protocols. The HAGN hydrogel proves to be an effective interface for prolonged high‐quality EEG recording, facilitating high‐performance capture and classification of evoked potentials, thereby providing a reliable conductive medium for EEG‐based systems.

Abstract Objective The macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics. Methods We retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation. Results Among all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5–25%), normal (25–75%), high (75–95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE. Conclusion Machine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.

Riverbed morphology is in dynamic change due to the influences of both natural and human-induced factors. However, there is a knowledge gap in distinguishing the components caused by human activities as well as extreme flooding from the total riverbed evolution. The current study evaluated the water depth variation in the Nandu River (NR) and Wanquan River (WR) in Hainan Island in response to diverse driven factors. The results showed that the average water depth of both rivers significantly increased, but the spatial-temporal variation patterns were different. In the NR, the dominant spatial-temporal water depth variation was driven by extreme flooding, which contributed 59% to the total variance. Then, water–sediment conditions accounted for 30%, followed by direct human activities for 3.6%. However, the main spatial-temporal water depth variation patterns in the WR were 77%, driven by water–sediment conditions, 10% driven by extreme flooding, and 3.9% driven by direct human interventions, respectively. Considering the indirect effects of human activities on the water–sediment process, the total contributions of human activities on the water depth variation were 6.9% and 42.9% in the NR and WR, respectively. Due to the poor riverbed stability and worse resistance, island rivers are more fragile to extreme floods and human interventions. Our findings suggest that extreme floods usually lead to a significant increase in sediment carrying capacity, followed by severe erosion of the riverbed. In addition, combining with the decrease in sediment concentration and grainsize caused by human activities, the rebuilding effect on riverbeds would be magnified. These results highlight the important role of human activities and extreme floods in the evolution of island rivers, which can provide new insights and recommendations for river management and restoration engineering.

Long-time hypoxia induced cardiomyocyte apoptosis is an important mechanism of myocardial ischemia (MI) injury. Interestingly, long noncoding RNA myocardial infarction-associated transcript (LncMIAT) has been involved in the regulation of MI injury; however, the underlying mechanism by which LncMIAT affects the progression of hypoxia-induced cardiomyocyte apoptosis remains unclear. In the present study, hypoxia was found to promote cardiomyocyte apoptosis through an increased expression of LncMIAT in vitro. Biological investigations and dual-luciferase gene reporter assay further revealed that LncMIAT was able to bind with miR-708-5p to upregulate the p53-mediated cell death of the cardiomyocytes. Silencing of LncMIAT or overexpression of miR-708-5p led to a significant reduction in p53-mediated cardiomyocyte apoptosis. The methylated RNA immunoprecipitation (MeRIP)-qPCR results showed that hypoxia exerted its effects on LncMIAT through AKLBH5-N6-methyladenosine (m6A) methylation and therefore hypoxia was shown to trigger HL-1 cardiomyocyte apoptosis via the m6A methylation-mediated LncMIAT/miR-708-5p/p53 axis. Silencing of AKLBH5 significantly alleviated the m6A methylation-mediated LncMIAT upregulation and p53-mediated cardiomyocyte apoptosis, while promoted miR-708-5p expression. Taken together, the present study highlighted that LncMIAT could act as a key biological target during hypoxia-induced cardiomyocyte apoptosis. In addition, it was shown that hypoxia could promote cardiomyocyte apoptosis through regulation of the m6A methylation-mediated LncMIAT/miR-708-5p/p53 signaling axis.

Purpose PIWI-interacting RNAs (piRNAs) are a type of noncoding small RNA that can interact with PIWI-like RNA-mediated gene silencing (PIWIL) proteins to affect biological processes such as transposon silencing through epigenetic effects. Recent studies have found that piRNAs are widely dysregulated in tumors and associated with tumor progression and a poor prognosis. Therefore, this study aimed to investigate the effect of piR-1919609 on the proliferation, apoptosis, and drug resistance of ovarian cancer cells. Methods In this study, we used small RNA sequencing to screen and identify differentially expressed piRNAs in primary ovarian cancer, recurrent ovarian cancer, and normal ovaries. A large-scale verification study was performed to verify the expression of piR-1919609 in different types of ovarian tissue, including ovarian cancer tissue and normal ovaries, by RT–PCR and to analyze its association with the clinical prognosis of ovarian cancer. The expression of PIWILs in ovarian cancer was verified by RT–PCR, Western blotting and immunofluorescence. The effects of piR-1919609 on ovarian cancer cell proliferation, apoptosis and drug resistance were studied through in vitro and in vivo models. Results (1) piR-1919609 was highly expressed in platinum-resistant ovarian cancer tissues (p

Abstract Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross‐linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X‐ray diffraction (XRD), ultraviolet‐visible spectroscopy (UV‐vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram‐negative bacteria (Escherichia coli) and Gram‐positive bacteria (Staphylococcus aureus) for the produced AgNP‐decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP‐decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 μg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP‐decorated vesicles.

Abstract Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.

Abstract The development of the Internet of things brings exponential growth of wireless traffic, which puts great pressure on the backhaul link. The proactive caching of some contents in the edge device of mobile network can effectively reduce the repeated transmission of the same contents and relieve the burden of the backhaul link. Moreover, the introduction of recommendation mechanisms can reshape user's request and improve cache hit ratio. However, the optimization of recommendation and caching decisions is highly dependent on the users’ preference information for files. Here, a joint optimization algorithm of recommendation and caching based on users’ preference prediction with multiple base stations cooperative caching is proposed. To improve the caching efficiency, the Deep Crossing model is adopted to predict users’ preferences. Under the constraints of cache capacity, recommendation quantity and bandwidth, an optimization problem to minimize the total transmission delay of the system is formulated. Then, the NP‐hardness of the proposed optimization problem is proved and it is decoupled it into three sub‐problems, namely recommendation, user access and caching optimization sub‐problems. Simulation results show that the proposed algorithm can effectively reduce the total transmission delay of the system.

The electrospinning of pure chitosan nanofibers is highly sensitive to environmental humidity, which limits their production consistency and applicability. This study investigates the addition of sodium chloride (NaCl) to chitosan solutions to enhance spinnability and mitigate the effigurefects of low humidity. NaCl was incorporated into the electrospun chitosan solution, leading to increased conductivity and decreased viscosity. These modifications improved the electrospinning process. Comparative analyses between chitosan membranes (CM) and sodium-chloride-added chitosan membranes (SCM) revealed no significant differences in chemical structure, mechanical strength, or in vitro cell proliferation. This indicates that the addition of 1% (w/v) NaCl does not adversely affect the fundamental properties of the chitosan membranes. The findings demonstrate that NaCl addition is a viable strategy for producing electrospun chitosan nanofibers in low-humidity environments, maintaining their physicochemical properties while enhancing spinnability.

Structural and mutagenic analyses reveal the mechanistic basis of azurin-mediated p53 stabilization and tumor suppression, and several affinity-enhancing azurin mutants are designed.

AbstractPost-encapsulation and release of the anticancer drug doxorubicin hydrochloride (DOX·HCl) through cell-like transmission functions of polymeric vesicles were studied using cross-linked pH-responsive polymeric vesicles. The vesicles were fabricated for the first time via the redox-initiated reversible addition-fragmentation chain transfer dispersion polymerization in ethanol-water mixture, using 2-(diisopropylamino)ethyl methacrylate and glycidyl methacrylate, and the vesicle membrane was modified post-cross-linking by using ethylenediamine. A phase diagram was constructed for reproducible fabrication of the polymeric vesicles, and well-shaped vesicles were formed when the target degree of polymerization of the hydrophobic polymer chains was equal to or higher than 50 with solid content in the range of 10–30 wt%. The cross-linked vesicle membrane served as a gate enabling “open” and “closed” states in response to pH stimulation. Up to 50% drug loading efficiency and 39% drug loading content could be achieved, and in vitro release of the DOX-loaded vesicles in aqueous buffer solutions showed a much faster DOX release rate at pH 5.0 than at pH 6.5. The polymeric vesicles were of very low cytotoxicity to A549 cells up to the concentration of 2 mg/mL, and the IC50 of DOX-loaded vesicles were higher than that of the free DOX. The intracellular DOX release study indicated higher cellular uptake capability for DOX-loaded vesicles than that of free DOX.

BackgroundBreast cancer (BC) is one of the females’ most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies.MethodsA combined significance (pcombined) was calculated for each gene by Fisher’s method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a pcombined< 0.01 were subjected to univariate cox and Lasso regression, whereby an RS signature was established. The predicted performance of the RS signature would be assessed in GSE7390 and GSE20685, and emphatically analyzed in triple-negative breast cancer (TNBC) patients, while the expression of immune checkpoints and drug sensitivity were also examined. GSE176078, a single-cell dataset, was used to validate the differences in cellular composition in tumors between TNBC patients with different RS.ResultsThe RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment.ConclusionThe six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.

The rather limited microstructural evolution in electrodeposited nanocrystalline Ni isothermally annealed at 453–493 K is investigated by using in situ X-ray diffraction technique. The nanostructural relaxation features roughly linear lattice contraction, based on which the kinetics analysis yields the activation energy of about 0.57 eV/atom, in good agreement with the fast diffusion of excess vacancies on the nonequilibrium surfaces and/or interfaces for Ni. The lattice contraction of Ni may result from a reduction in the grain boundary excess volume. The integral breadth of diffraction line profiles decreases with annealing time in an exponential manner, implying the gradual improvement of the lattice perfections during nanostructural relaxation. The microhardness evaluation demonstrates the initial invariance or slight softening and subsequent remarkable hardening of nanocrystalline Ni subjected to low-temperature annealing.

Objective To evaluate the immunogenicity, safety and lot-to-lot consistency of an inactivated enterovirus 71 (EV71) vaccine cultured in bioreactors with different specifications after full immunization. Methods A randomized, double-blind trial was performed in 3,000 children aged 6 ~ 35 months with six vaccine batches, which were prepared in 40 L and 150 L bioreactors for three consecutive batches respectively. Children were immunized on day 0 and 28, serum samples were collected on day 0 and 56, and neutralizing antibody titers were determined by the microcytopathic method. Immediate reactions were recorded within 30 min, local and systemic symptoms were recorded within 0 ~ 28 days, and serious adverse events were recorded within 6 months. Results After immunization with two doses of the inactivated EV71 vaccine, the neutralizing antibody GMT was 825.52 ± 4.09, and the positive conversion rate was 96.18%, with no significant difference. The 95% CI of the serum neutralizing antibody GMT ratio between the two groups after immunization with the three vaccine batches produced in the 150 L and 40 L bioreactors ranged from .67 ~ 1.5. The overall incidence of adverse reactions, mainly grade 1 reactions, for all 6 batches from 0 to 28 days after vaccination was 49.62%, with no significant difference (p = .8736). The incidence of systemic adverse reactions, primarily fever and diarrhea, was 45.14%; the incidence of local adverse reactions, primarily erythema and tenderness, was 9.43%. Conclusion The EV71 vaccine was highly immunogenic and safe in children aged 6–35 months, and 6 consecutive batches produced by the two bioreactors with different specifications were consistent.

Summary: Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

Abstract Novel Coronavirus disease 2019 (COVID‐19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID‐19 patients hospitalized in 23 centers affiliated to Hubei COVID‐19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID‐19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033,

Abstract Polymer‐protein complexing systems have been extensively studied because of their wide application in biomedicine and industry. Here, we studied the aggregation behavior of the hydrophobically associating water‐soluble polymer poly(acrylic acid‐co‐octadecyl methacrylate) [P(AA‐co‐OMA)] prepared with nonionic surfactant as an emulsifier and bovine serum albumin (BSA) in aqueous solution. We identified the optimal composite conditions of P(AA‐co‐OMA) and BSA aqueous solution. We measured the zeta potential, dynamic light‐scattering particle size, and surface tension of P(AA‐co‐OMA) and BSA mixed aqueous solution. The results showed that the aggregation behavior between the polymer and BSA relied mainly on the hydrophobic interactions between the molecules. In addition, the best compounding condition was 8 wt.% of P(AA‐co‐OMA) content. The structure of hydrophobically associating polymer P(AA‐co‐OMA) and its aggregation with BSA were characterized by Fourier‐transform infrared spectroscopy. The infrared spectroscopy results identified the hydrogen bonding behavior of the amino and carboxyl groups between the polymer and BSA. This behavior was also confirmed using thermogravimetric analysis and differential scanning calorimetry. The thermal decomposition temperature and melting temperature of BSA changed before and after it was combined with the polymer. We measured the morphology of the polymer BSA aggregate with 8 % polymer content by transmission electron microscopy. The binding mechanism was investigated, as well.

Abstract Background Neck pain is prevalent among office workers. This study evaluated the impact of an ergonomic and exercise training (EET) intervention and an ergonomic and health promotion (EHP) intervention on neck pain intensity among the All Workers and a subgroup of Neck Pain cases at baseline. Methods A 12-month cluster-randomized trial was conducted in 14 public and private organisations. Office workers aged ≥18 years working ≥30 h per week (n = 740) received an individualised workstation ergonomic intervention, followed by 1:1 allocation to the EET group (neck-specific exercise training), or the EHP group (health promotion) for 12 weeks. Neck pain intensity (scale: 0–9) was recorded at baseline, 12 weeks, and 12 months. Participants with data at these three time points were included for analysis (n = 367). Intervention group differences were analysed using generalized estimating equation models on an intention-to-treat basis and adjusted for potential confounders. Subgroup analysis was performed on neck cases reporting pain ≥3 at baseline (n = 96). Results The EET group demonstrated significantly greater reductions in neck pain intensity at 12 weeks compared to the EHP group for All Workers (EET: β = − 0.53 points 95% CI: − 0.84– − 0.22 [36%] and EHP: β = − 0.17 points 95% CI: − 0.47–0.13 [10.5%], p-value = 0.02) and the Neck Cases (EET: β = − 2.32 points 95% CI: − 3.09– − 1.56 [53%] and EHP: β = − 1.75 points 95% CI: − 2.35– − 1.16 [36%], p = 0.04). Reductions in pain intensity were not maintained at 12 months with no between-group differences observed in All Workers (EET: β = − 0.18, 95% CI: − 0.53–0.16 and EHP: β = − 0.14 points 95% CI: − 0.49–0.21, p = 0.53) or Neck Cases, although in both groups an overall reduction was found (EET: β = − 1.61 points 95% CI: − 2.36– − 0.89 and EHP: β = − 1.9 points 95% CI: − 2.59– − 1.20, p = 0.26). Conclusion EET was more effective than EHP in reducing neck pain intensity in All Workers and Neck Cases immediately following the intervention period (12 weeks) but not at 12 months, with changes at 12 weeks reaching clinically meaningful thresholds for the Neck Cases. Findings suggest the need for continuation of exercise to maintain benefits in the longer term. Clinical trial registration hACTRN12612001154897 Date of Registration: 31/10/2012.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality. Circular RNAs (CircRNAs) have become a research hotspot in recent years for their vital roles in cancer development and progression. This study aims to clarify the roles of circNTRK2 and its underlying molecular mechanisms in ESCC. Methods The levels of circNTRK2, miR-140-3p, and nuclear receptor-interacting protein 1 (NRIP1) mRNA were examined by qRT-PCR. The cell proliferation ability was detected via CCK-8, EdU and colony formation assays. The invasion capacity was tested by using transwell assay. The apoptotic rate was evaluated through flow cytometry. The protein levels of cleaved PARP, cleaved caspase-3, E-cadherin, vimentin, and NRIP1 were measured by western blot assay. The validation of circular structure was performed by Sanger sequencing, divergent primer PCR, and RNase R treatments. The ceRNA regulatory mechanism of circNTRK2 was observed via dual-luciferase reporter, RIP and RNA pull-down assays. The mice xenograft models were constructed to confirm the oncogenicity of circNTRK2 in ESCC in vivo. Results CircNTRK2 was highly expressed in ESCC tissues and cells. High expression of circNTRK2 was correlated with advanced TNM stage, lymph node metastasis and short survival. Knockdown of circNTRK2 inhibited ESCC cell proliferation, invasion and epithelial-mesenchymal transition (EMT), and accelerated apoptosis in vitro. Mechanistic assays disclosed that circNTRK2 could act as a sponge for miR-140-3p to abate its suppression on target NRIP1 expression. Moreover, miR-140-3p-induced inhibitory effects on ESCC cell malignant phenotypes were attenuated by the overexpression of circNTRK2. In addition, depletion of NRIP1 impeded cell proliferation, invasion and EMT, while enhanced apoptosis. Furthermore, silencing of circNTRK2 suppressed cell proliferation and invasion through regulating NRIP1 expression. Also, knockdown of circNTRK2 slowed ESCC tumor growth in vivo. Conclusion CircNTRK2 promoted ESCC progression by regulating miR-140-3p/NRIP1 pathway. Our findings contribute to a better understanding of circRNAs as miRNA sponges and highlight a promising therapy target in ESCC.

The plateau zokor (Myospalax baileyi) is a native species of the Qinghai–Tibet Plateau that spends its entire life underground in sealed burrows with hypoxic conditions. The present study aimed to assess the sequence characteristics of apoptosis-related genes and the response to different oxygen partial pressures (pO2) in plateau zokor and Sprague-Dawley rats. The sequences of the p53-induced protein with a death domain (Pidd), p53-upregulated modulator of apoptosis (Puma), insulin-like growth factor binding protein 3 (Igfbp3), and apoptosis protease-activating factor 1 (Apaf1) were evaluated concerning homology and convergent evolution sites, and their mRNA levels were evaluated in different tissues under 14.13 (3,300 m) and 16.12 kPa (2,260 m) pO2 conditions. Our results showed that, (1) the sequences of the apoptosis-related genes in plateau zokor were highly similar to those of Nannospalax galili, followed by Rattus norvegicus; (2). Pidd, Puma, Igfbp3, and Apaf1 of plateau zokor were found to have five, one, two, and five convergent sites in functional domains with N. galili, respectively. Lastly (3), under low pO2, the expression of Pidd and Puma was downregulated in the lung of plateau zokors. In turn, Igfbp3 and Apaf1 were upregulated in the liver and lung, and Puma was upregulated in the skeletal muscle of plateau zokor under low pO2. In Sprague-Dawley rats, low pO2 downregulated Puma and Apaf1 expression in the liver and downregulated Igfbp3 and Puma in the lung and skeletal muscle separately. In contrast, low pO2 upregulated Pidd expression in the liver and skeletal muscle of Sprague-Dawley rats. Overall, the expression patterns of Apaf1, Igfbp3, and Puma showed the opposite pattern in the liver, lung, and skeletal muscle, respectively, of plateau zokor as compared with Sprague-Dawley rats. In conclusion, for the long-time adaptation to hypoxic environments, Pidd, Puma, Igfbp3, and Apaf1 of plateau zokor underwent convergent evolution, which we believe may have led to upregulation of their levels under low oxygen partial pressures to induce apoptosis, so as to suppress tumorigenesis under hypoxic environments in plateau zokor.

Compositional, functional, and nutritional properties are important for the use-value assessments of wild and cultivated edible plants. The aim of this study was to compare the nutritional composition, bioactive compounds, volatile compounds, and potential biological activities of cultivated and wild Zingiber striolatum. Various substances, such as soluble sugars, mineral elements, vitamins, total phenolics, total flavonoids, and volatiles, were measured and analyzed using UV spectrophotometry, ICP-OES, HPLC, and GC-MS methods. The antioxidant capacity of a methanol extract of Z. striolatum, as well as the hypoglycemic abilities of its ethanol and water extracts, were tested. The results showed that the contents of soluble sugar, soluble protein, and total saponin in the cultivated samples were higher, while the wild samples contained higher amounts of K, Na, Se, vitamin C, and total amino acids. The cultivated Z. striolatum also showed a higher antioxidant potential, while the wild Z. striolatum exhibited a better hypoglycemic activity. Thirty-three volatile compounds were identified using GC-MS in two plants, with esters and hydrocarbons being the main volatile compounds. This study demonstrated that both cultivated and wild Z. striolatum have a good nutritional value and biological activity, and can be used as a source of nutritional supplementation or even in medication.

In recent years, multiple disturbances have significantly altered terrestrial ecosystems in arid and semi-arid regions, particularly on the Mongolian Plateau (MP). Net primary productivity (NPP) of vegetation is an essential component of the surface carbon cycle. As such, it characterizes the state of variation in terrestrial ecosystems and reflects the productive capacity of natural vegetation. This study revealed the complex relationship between the natural environment and NPP in the ecologically fragile and sensitive MP. The modified Carnegie–Ames–Stanford Approach (CASA) model was used to simulate vegetation NPP. Further, the contributions of topography, vegetation, soils, and climate to NPP’s distribution and spatiotemporal variation were explored using the geographic detector model (GDM) and structural equation model (SEM). The study’s findings indicate the following: (1) NPPs for different vegetation types in the MP were in the order of broad-leaved forest > meadow steppe > coniferous forest > cropland > shrub > typical steppe > sandy land > alpine steppe > desert steppe. (2) NPP showed an increasing trend during the growing seasons from 2000 to 2019, with forests providing larger vegetation carbon stocks. It also maintained a more stable level of productivity. (3) Vegetation cover, precipitation, soil moisture, and solar radiation were the key factors affecting NPP’s spatial distribution. NPP’s spatial distribution was primarily explained by the normalized difference vegetation index, solar radiation, precipitation, vegetation type, soil moisture, and soil type (q-statistics = 0.86, 0.71, 0.67, 0.67, 0.57, and 0.57, respectively); the contribution of temperature was small (q-statistics = 0.26), and topographic factors had the least influence on NPP’s distribution, as their contribution amounted to less than 0.20. (4) A SEM constructed based on the normalized difference vegetation index (NDVI), solar radiation, precipitation, temperature, and soil moisture explained 17% to 65% of the MP’s NPP variations. The total effects of the MP’s NPP variations in absolute values were in the order of NDVI (0.47) > precipitation (0.33) > soil moisture (0.16) > temperature (0.14) > solar radiation (0.02), and the mechanisms responsible for NPP variations differed slightly among the relevant vegetation types. Overall, this study can help understand the mechanisms responsible for the MP’s NPP variations and offer a new perspective for regional vegetation ecosystem management.

Wild, edible plants have received increasing attention as an important complement to cultivate vegetables, as they represent an easily accessible source of nutrients, mineral elements, and antioxidants. In this study, the tender stems and leaves of Gonostegia hirta, an edible species for which only scarce data are available in the literature, are thoroughly evaluated for their nutritional profile, chemical characterization, and antioxidant activity. Being considered as an underexploited, potentially edible plant, the nutritional composition of Gonostegia hirta was identified, and several beneficial compounds were highlighted: sugars, potassium, calcium, organic acids, fatty acids, phenolics, and flavonoids. A total of 418 compounds were identified by metabolomic analysis, including phenolic acids, flavonoids, amino acids, lipids, organic acids, terpenoids, alkaloids, nucleotides, tannins, lignans, and coumarin. The plant sample was found to have good antioxidant capacities, presented by DPPH, FRAP, ABTS+, hydroxyl radical scavenging capacity, and its resistance to the superoxide anion radical test. In general, Gonostegia hirta has a good nutritional and phytochemical composition. The health benefits of Gonostegia hirta as a vegetable and herbal medicine is important for both a modern diet and use in medication.

Abstract Background This study uses the RE-AIM framework to provide a process evaluation of a workplace-based cluster randomised trial comparing an ergonomic plus exercise intervention to an ergonomic plus health promotion intervention; and to highlight variations across organisations; and consider the implications of the findings for intervention translation. Method This study applied the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) methodology to examine the interventions’ implementation and to explore the extent to which differences between participating organisations contributed to the variations in findings. Qualitative and quantitative data collected from individual participants, research team observations and organisations were interrogated to report on the five RE-AIM domains. Results Overall reach was 22.7% but varied across organisations (range 9 to 83%). Participants were generally representative of the recruitment pool though more females (n = 452 or 59%) were recruited than were in the pool (49%). Effectiveness measures (health-related productivity loss and neck pain) varied across all organisations, with no clear pattern emerging to indicate the source of the variation. Organisation-level adoption (66%) and staffing level adoption (91%) were high. The interventions were implemented with minimal protocol variations and high staffing consistency, but organisations varied in their provision of resources (e.g. training space, seniority of liaisons). Mean adherence of participants to the EET intervention was 56% during the intervention period, but varied from 41 to 71% across organisations. At 12 months, 15% of participants reported regular EET adherence. Overall mean (SD) adherence to EHP was 56% (29%) across organisations during the intervention period (range 28 to 77%), with 62% of participants reporting regular adherence at 12 months. No organisations continued the interventions after the follow-up period. Conclusion Although the study protocol was implemented with high consistency and fidelity, variations in four domains (reach, effectiveness, adoption and implementation) arose between the 14 participating organisations. These variations may be the source of mixed effectiveness across organisations. Factors known to increase the success of workplace interventions, such as strong management support, a visible commitment to employee wellbeing and participant engagement in intervention design should be considered and adequately measured for future interventions. Trial registration ACTRN12612001154897; 29 October 2012.

Abstract Background Hybrid exoskeletons are a recent development which combine Functional Electrical Stimulation with actuators to improve both the mental and physical rehabilitation of stroke patients. Hybrid exoskeletons have been shown capable of reducing the weight of the actuator and improving movement precision compared to Functional Electrical Stimulation alone. However little attention has been given towards the ability of hybrid exoskeletons to reduce and manage Functional Electrical Stimulation induced fatigue or towards adapting to user ability. This work details the construction and testing of a novel assist-as-need upper-extremity hybrid exoskeleton which uses model-based Functional Electrical Stimulation control to delay Functional Electrical Stimulation induced muscle fatigue. The hybrid control is compared with Functional Electrical Stimulation only control on a healthy subject. Results The hybrid system produced 24° less average angle error and 13.2° less Root Mean Square Error, than Functional Electrical Stimulation on its own and showed a reduction in Functional Electrical Stimulation induced fatigue. Conclusion As far as the authors are aware, this is the study which provides evidence of the advantages of hybrid exoskeletons compared to use of Functional Electrical Stimulation on its own with regards to the delay of Functional Electrical Stimulation induced muscle fatigue.

Using the first-principles theory, the geometric and electronic properties of the Ru-doped PtTe2 (Ru-PtTe2) monolayer, and its sensing performance for three VOCs biomarkers, namely, 2-propenal (C3H4O), acetone (C3H6O) and isoprene (C5H8), were analyzed, to expound its potential for exhaled breath analysis and diagnosis of lung cancer. It was found that the Ru-substitution on the surface of the pristine PtTe2 surface with a Te atom is energy-favorable, with the formation energy of −1.22 eV. Upon adsorption of the three VOC gas species, chemisorption was identified with the adsorption energies of −1.72, −1.12 and −1.80 eV for C3H4O, C3H6O and C5H8, respectively. The Ru-doping results in a strong magnetic property for the PtTe2 monolayer, whereas the gas adsorption eliminates this magnetic behavior. The electronic properties reveal the sensing mechanism of the Ru-PtTe2 monolayer for gas detection, and the bandgap change indicates its admirable positive sensing response for the three gas species. Therefore, we conclude that the Ru-PtTe2 monolayer is a promising sensing material to realize the diagnosis of lung cancer through exhaled gas detection, with a remarkable decrease in its electrical conductivity. This work paves the way for further exploration of the PtTe2-based gas sensor for early diagnosis of lung cancer, and we hope that more sensing materials can be investigated using the PtTe2 monolayer.

The brain network is one specific type of critical infrastructure networks, which supports the cognitive function of biological systems. With the importance of network reliability in system design, evaluation, operation, and maintenance, we use the percolation methods of network reliability on brain networks and study the network resistance to disturbances and relevant failure modes. In this paper, we compare the brain networks of different species, including cat, fly, human, mouse, and macaque. The differences in structural features reflect the requirements for varying levels of functional specialization and integration, which determine the reliability of brain networks. In the percolation process, we apply different forms of disturbances to the brain networks based on metrics that characterize the network structure. Our findings suggest that the brain networks are mostly reliable against random or k-core-based percolation with their structure design, yet becomes vulnerable under betweenness or degree-based percolation. Our results might be useful to identify and distinguish brain connectivity failures that have been shown to be related to brain disorders, as well as the reliability design of other technological networks.

Vitamin D3 (D3) is produced endogenously from 7-dehydrocholesterol by irradiation and is an important secosteroid for the absorption of calcium and phosphate. Lithocholic acid (LCA) increases intestinal paracellular calcium absorption in a vitamin D receptor-dependent manner in vitamin D-deficient rats. The plateau zokor (Myospalax baileyi), a strictly subterranean species, and plateau pika are endemic to the Qinghai-Tibet Plateau. To verify whether the zokors were deficient in D3 and reveal the effects of hypoxia on D3 metabolism in the zokors and pikas, we measured the levels of 25(OH)D3, calcium, and LCA, and quantified the expression levels of D3 metabolism-related genes. The results showed an undetectable serum level of 25(OH)D3 and a significantly higher concentration of LCA in the serum of plateau zokor, but its calcium concentration was within the normal range compared with that of plateau pika and Sprague-Dawley rats. With increasing altitude, the serum 25(OH)D3 levels in plateau pika decreased significantly, and the mRNA and protein levels of CYP2R1 (in the liver) and CYP27B1 (in the kidney) in plateau pika decreased significantly. Our results indicate that plateau zokors were deficient in D3 and abundant in LCA, which might be a substitution of D3 in the zokor. Furthermore, hypoxia suppresses the metabolism of D3 by down-regulating the expression of CYP2R1 and CYP27B1 in plateau pika.

Directed energy deposition (DED) of Ni-based superalloys has wide applications in the fields of aviation, energy and power. However, for the non-weldable superalloys like Inconel 738, cracking frequently occurs during DED and cannot be thoroughly controlled up to now. We propose a novel method to prevent the cracking during Inconel 738 DED, in which a small amount of Inconel 718 is in-situ doped between the deposited layers of Inconel 738. The obtained layered-gradient-material is found to be free of both macro- and micro-cracks. The microstructure shows that doping Inconel 718 cannot interrupt the epitaxial growth of grains, but can modify the precipitation of γ′. In Inconel 718 layers, nano γ′ particles are intensively precipitated only in the inter-dendrites, while in Inconel 738 layers, they are precipitated in both the inter- and inner-dendrites. This modification on γ′ precipitation can effectively decrease the inner stress and alleviate the stress concentration at the grain boundaries, thus the cracking is prevented. The tensile tests, which were conducted at room temperature, 600 °C and 800 °C respectively, demonstrate that the composite deposited workpieces possess promising strength and plasticity. The proposed method has great potential to improve the printability of un-weldable superalloys in additive manufacturing.

OBJECTIVES: Using an employer’s perspective, this study aimed to compare the immediate and longer-term impact of workplace ergonomics and neck-specific exercise versus ergonomics and health promotion information on health-related productivity among a general population of office workers and those with neck pain. METHODS: A prospective one-year cluster randomized trial was conducted. Participants received an individualized workstation ergonomics intervention, combined with 12 weeks of either workplace neck-specific exercises or health promotion information. Health-related productivity at baseline, post-intervention and 12-months was measured with the Health and Work Performance Questionnaire. Intention-to-treat analysis was performed using multilevel mixed models. RESULTS: We recruited 763 office workers from 14 organizations and allocated them to 100 clusters. For the general population of office workers, monetized productivity loss at 12 months [AU$1464 (standard deviation [SD] 1318) versus AU$1563 (SD=1039); P=0.023]; and presenteeism at 12 months [2.0 (SD 1.2) versus 2.4 (SD 1.4); P=0.007] was lower in the exercise group compared to those in the health promotion information group. For office workers with neck pain, exercise participants had lower sickness absenteeism at 12 months compared to health promotion information participants [0.7 days (SD 1.0) versus 1.4 days (SD 3.1); P-=0.012], despite a short-term increase in sickness absenteeism post-intervention compared to baseline for the exercise group [1.2 days (SD 2.2) versus 0.6 days (SD 0.9); P

Background: The aim of this study was to investigate the immunogenicity and safety of the enterovirus 71 vaccine (EV71 vaccine) administered alone or simultaneously. Methods: A multi-center, open-label, randomized controlled trial was performed involving 1080 healthy infants aged 6 months or 8 months from Shandong, Shanxi, Shaanxi, and Hunan provinces. These infants were divided into four simultaneous administration groups and EV71 vaccine separate administration group. Blood samples were collected from the infants before the first vaccination and after the completion of the vaccination. This trial was registered in the Clinical Trials Registry (NCT03519568). Results: A total of 895 were included in the per-protocol analysis. The seroconversion rates of antibodies against EV71 in four simultaneous administration groups (98.44% (189/192), 94.57% (122/129), 99.47% (187/188) and 98.45% (190/193)) were non-inferior to EV71 vaccine separate administration group (97.93% [189/193]) respectively. Fever was the most common adverse event, the pairwise comparison tests showed no difference in the incidence rate of solicited, systemic or local adverse events. Three serious adverse events related to the vaccination were reported. Conclusions: The evidence of immunogenicity and safety supports that the EV71 vaccine administered simultaneously with vaccines need to be administered during the same period of time recommended in China.

Okra is a kind of flavonoid-rich food which was reported to have a variety of health functions. Flavonoids are the major polyphenolic compounds in okra and are thought to play a role in reducing the risk of disease. The aim of this study was to isolate and identify the flavonoids composition in okra pods and explore the activity of the main flavonoids components identified on inhibiting tumor cell proliferation in vitro. Six individual flavonoids were identified by HPLC-MS/MS: quercetin-3-gentiobioside (Q3G), quercetin-3-sambubioside (Q3S), rutin, quercetin-7-glucoside (Q7G), isoquercitrin (ISO) and quercetin-3-malonylglucoside (Q3M), which were all separated well within 30 min. The analytical method was validated by the recovery of spiked samples and so on. Moreover, four main flavonoids components, namely Q3G, Q3S, ISO and Q3M, exhibited significant (p < 0.05) inhibition of NCI-N87, A375, A549 cells proliferation (25−100 μmol/L) and of HFLS-RA (200−300 μmol/L) in different levels, according to MTT method, respectively. It is demonstrated that the flavonoids components of okra exhibited a noteworthy development prospect as a possible nutraceutical dietary supplement.

During the gas turbine exploitation the presence of small defects can cause very high vibration amplifications, localized on the components of this rotating machine. For this, a diagnostic process is necessary for decision-making during the monitoring of failures caused by vibration phenomena, which consists in observing the system by comparing its current data with the data coming from a normal operation. These indicators help engineer to determine the symptoms for the failing components of the system. This work deals with problems related to these vibrations, with the aim of developing a system of detection of failures using dynamic neural networks approach. The originality of this contribution is to calculate the various alarms based on this system which used the determined vibration models in order to ensure a reliable and safe operation of the gas compression installation using the examined gas turbine.

Over the past few decades, the topography and river-tide-salt dynamic characteristics of the Pearl River Delta (PRD) have undergone a myriad of changes due to the unnatural evolution process induced by diverse human activities, such as dam construction, land reclamation, sand excavation, and dredging for navigation. To investigate the impact of human activities on hydrodynamic structures in the PRD of the Modaomen Estuary (ME) during the dry season, a three-dimensional river-tide-salt dynamic model was used to simulate the hydrodynamic characteristics of the ME for different historical periods. The model results indicate that large-scale land reclamation weakened the tidal dynamics and mixing effects in the ME, promoting gravity circulation with opposite velocity directions at the surface and bottom within 15 km downstream of the estuary. Additionally, riverbed downcutting enhanced the tidal dynamics, which intensified saltwater intrusion, leading to the spatial scale-of-gravity circulation expanding 1–2 times. The enhancement of riverbed downcutting on the tidal dynamics in the ME was significantly greater than the weakening effect of land reclamation. Hence, due to the comprehensive influence of human activities between the 1970s and 2010, the hydrodynamic structures in the ME changed from a state of atypical gravity circulation, with nonobvious stratification, to a state of highly stratified and large-scale gravity circulation. The pollutant diffusion in the ME under different scenarios is also discussed in this paper. The results show that reclamation results in weakening of tidal dynamics, which is not conducive to the mixing and diffusion of pollutants in the estuary. However, the narrowed estuary due to land reclamation is conducive to the rapid entry of pollutants into the open sea.

Refilled friction stir spot welding is proposed to replace friction stir spot welding to solve the problem of keyhole in joining of light metals. However, it is rather challenging to ensure the mechanical property of refilled friction stir spot welding joints because of hook defect. In this study, a novel method was proposed to use graphene nanosheets to strengthen the tip of hook defect and improve overall mechanical properties of joint. The joints of AA2014 aluminum alloy with 0.6%wt graphene nanosheets were fabricated by refilled friction stir spot welding. The results show that the tensile/shear strength of joint increases by 31% and the fracture toughness also is improved by nearly 20% with graphene nanosheets. Extension in fatigue life was achieved on joint with graphene nanosheets. Microstructural observations, fracture characteristics and electron back scattered diffraction analysis were systematically investigated to clarify the mechanism for improvement of strength and toughness. The synergetic effect including grain refinement, load transfer, dislocation strengthening and crack bridging, caused by graphene nanosheets, leads to hardening behavior of graphene nanosheets pinned zone and a significant crack deflection during fracture process, which contributes greatly to improving strength and toughness of joint. Keywords: Refilled friction stir spot welding, Graphene nanosheets, Strengthening and toughening mechanism, Hook defect, AA2014 aluminum alloy

Laser Melting Deposition (LMD) of Inconel 738 (IN738) superalloy is a promising process for the remanufacturing of gas turbines and aerospace engines, but the cracking has not been thoroughly understood and controlled. This paper conducts a comprehensive study on the cracking behavior by using optical microscope (OM), scanning electron microscopy (SEM), energy dispersion spectrum (EDS), electron backscatter diffraction (EBSD), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The results indicate that liquation cracking which follows the penetration mechanism is the major origin to those cracks. Whereas, at the propagation stage, ductility-dip cracking (DDC) is an important supplement to liquation cracking, especially at the triple junction points of grain boundaries (GBs) or the bottom of already formed liquation cracks. The cracks are very sensitive to GB morphology, the long-straight GBs which result from higher heat input or unidirectional scanning strategy are very vulnerable to cracking. Moreover, GB oxidation always plays an important role in accelerating crack propagation, the local protection from the cladding head is not enough for the LMD of IN738. For these factors, the test specimens which are bidirectionally deposited in an Argon (Ar) chamber with lower heat input achieve better tensile strengthen reaching 1093 to 1116 MPa. Keywords: Laser melting deposition, Inconel 738 superalloy, Liquation cracking, Ductility-dip cracking, Grain boundary morphology, Grain boundary oxidation

In recent years, auxetic cellular materials such as auxetic reentrant honeycombs were widely studied due to its attractively negative Poisson's ratio. In this manuscript, the structure response of end-clamped sandwich beam with auxetic reentrant hexagonal aluminum honeycomb core locally subjected to foam projectile with high-velocity impact was experimentally and numerically studied. The reentrant honeycomb cores with different cell-wall thicknesses were fabricated by selective laser melting (SLM). According to experiment results, the failure modes of the sandwich beam were investigated. It was found that sandwich beam with different honeycomb cell's thicknesses could fail in different modes. Meanwhile, the local negative Poisson's ratio deformation was observed in the thin honeycomb core. Based on this, a finite element (FE) model was constructed to analysis the dynamic deformation evolution of two face sheets and auxetic reentrant honeycomb core. The local auxetic and expand deformations of honeycomb core were both found. Finally, the residual deflections of sandwich beam under impulsive loadings were discussed. Keywords: Auxetic reentrant honeycomb, Sandwich beam, Structure response, Impulsive loading, Negative Poisson's ratio

The ionic polymer metal composite (IPMC) actuator is a kind of soft actuator that can work for underwater applications. However, IPMC actuator control suffers from high nonlinearity due to the existence of inherent creep and hysteresis phenomena. Furthermore, for underwater applications, they are highly exposed to parametric uncertainties and external disturbances due to the inherent characteristics and working environment. Those factors significantly affect the positioning accuracy and reliability of IPMC actuators. Hence, feedback control techniques are vital in the control of IPMC actuators for suppressing the system uncertainty and external disturbance. In this paper, for the first time an adaptive full-order recursive terminal sliding-mode (AFORTSM) controller is proposed for the IPMC actuator to enhance the positioning accuracy and robustness against parametric uncertainties and external disturbances. The proposed controller incorporates an adaptive algorithm with terminal sliding mode method to release the need for any prerequisite bound of the disturbance. In addition, stability analysis proves that it can guarantee the tracking error to converge to zero in finite time in the presence of uncertainty and disturbance. Experiments are carried out on the IPMC actuator to verify the practical effectiveness of the AFORTSM controller in comparison with a conventional nonsingular terminal sliding mode (NTSM) controller in terms of smaller tracking error and faster disturbance rejection.

With the development of Industry 4.0, additive manufacturing will be widely used to produce customized components. However, it is rather time-consuming and expensive to produce components with sound structure and good mechanical properties using additive manufacturing by a trial-and-error approach. To obtain optimal process conditions, numerous experiments are needed to optimize the process variables within given machines and processes. Digital twins (DT) are defined as a digital representation of a production system or service or just an active unique product characterized by certain properties or conditions. They are the potential solution to assist in overcoming many issues in additive manufacturing, in order to improve part quality and shorten the time to qualify products. The DT system could be very helpful to understand, analyze and improve the product, service system or production. However, the development of genuine DT is still impeded due to lots of factors, such as the lack of a thorough understanding of the DT concept, framework, and development methods. Moreover, the linkage between existing brownfield systems and their data are under development. This paper aims to summarize the current status and issues in DT for additive manufacturing, in order to provide more references for subsequent research on DT systems.

The functionalities of microgrids are detailed and thereby expanded in active distribution systems. A versatile and coordinated operation among multiple microgrids is proposed to facilitate the integration of renewable energy sources (RES) in modern distribution grids. Particularly, to meet the requirements of high penetration level of renewables (e.g., photovoltaics and small hydro), more than one networked controlled microgrids are deployed simultaneously in different locations of a distribution system. Therefore, local RES can be aggregated in each microgrids. In order to satisfy the latest standards in terms of renewable energy integration (i.e., IEEE Std. 1547 Rev), an optimal operation strategy is designed to coordinate the operation of multiple microgrids. A simulation model is implemented in MATLAB to validate the proposed networked microgrids and the corresponding operation strategy.

Point normal calculation and cloud registration are two of the most common operations in point cloud processing. However, both are vulnerable to issues of numerical precision and loss of significance. This paper documents how loss of significance in the open-source Point Cloud Library can create erroneous point normals and cause cloud registration to fail. Several test clouds are used to demonstrate how the loss of significance is caused by tight point spacing and clouds being shifted far from the origin of their coordinate system. The results show that extreme loss of significance can cause point normals to be calculated with a random orientation, and cause meters of error during cloud registration. Depending on the structure of the point cloud, loss of significance can occur when the cloud is at hundreds or even tens of meters from the origin of its coordinate system. Shifting to larger data types (e.g., from 32-bit “floats” to 64-bit “doubles”) can alleviate the problem but will not solve it completely. Several “best practice” recommendations for avoiding this issue are proposed. But the only solution guaranteed to eliminate loss of significance is de-meaning the entire cloud, or clusters of points before processing.