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Anisomycin (compound 1), a multifunctional pyrrolidine antibiotic, primarily inhibits protein biosynthesis by binding to the ribosome. Upon binding to the ribosome, the para-phenol moiety of anisomycin inserts completely into the hydrophobic crevice of the A-site and blocks the access of the incoming aminoacyl-tRNAs, disrupting peptide bond formation. Hence, the para-methoxyphenyl group serves as a starting point for developing novel anisomycin analogs with potent antifungal and insecticidal properties. However, the activation and condensation mechanism of phenylpyruvic acid has not yet been elucidated. In this study, genetic manipulations of aniP and its homologue siAniP confirmed their indispensable role in 1 biosynthesis. Bioinformatics analysis suggested that AniP and siAniP function as transketolase. siAniP was found to catalyzed condensation between 4-hydroxyphenylpyruvic acid (3) and glyceraldehyde (GA), initiating pyrrolidine synthesis. siAniP was specific for aromatic keto acids and tolerant of aliphatic and aromatic aldehydes, and was able to catalyze the asymmetric intermolecular condensation of two keto acids, leading to the formation of 24 α-hydroxy ketone. To the best of our knowledge, siAniP is the first TK that catalyzes the transfer of a C2 ketol and symmetrical intermolecular coupling using aromatic keto acids as donor substrates. Structural analysis, docking model construction, and site-directed mutagenesis identified that I220, H275, R322 and W391 were crucial for substrate binding. Moreover, sequence similarity network (SSN)-based genome neighborhood network (GNN) analyses of AniP suggested the widespread occurrence of the AniP-like-mediated reaction in the biosynthesis of 1 and its analogs, particularly in the assembly of benzylpyrrolidine. These findings not only expand the repertoire of TKs but also provide a potent biocatalyst that could be used for the structural innovation of 1 and its derivatives.

Summary: Systemic lupus erythematosus is a remitting relapsing autoimmune disease characterized by autoantibody production and multi-organ involvement. T cell epigenetic dysregulation plays an important role in the pathogenesis of lupus. We have previously demonstrated upregulation of the key epigenetic regulator EZH2 in CD4+ T cells isolated from lupus patients. To further investigate the role of EZH2 in the pathogenesis of lupus, we generated a tamoxifen-inducible CD4+ T cell Ezh2 conditional knockout mouse on the MRL/lpr lupus-prone background. We demonstrate that Ezh2 deletion abrogates lupus-like disease and prevents T cell differentiation. Single-cell analysis suggests impaired T cell function and activation of programmed cell death pathways in EZH2-deficient mice. Ezh2 deletion in CD4+ T cells restricts TCR clonal repertoire and prevents kidney-infiltrating effector CD4+ T cell expansion and tubulointerstitial nephritis, which has been linked to end-stage renal disease in patients with lupus nephritis.

Abstract Aims Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. Methods and results This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5–51.7% vs. 51.1%, 95% CI: 45.3–56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long‐term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91–1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95–1.22, P = 0.260]. Consistently, in time‐varying models, CCB treatment was not linked to long‐term mortality (HR: 0.97, 95% CI: 0.87–1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94–1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity‐matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. Conclusions In patients with LVAD, CCB therapy fails to show benefits in long‐term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.

Remaining useful life (RUL) prediction is widely applied in prognostic and health management (PHM) of turbofan engines. Although some of the existing deep learning-based models for RUL prediction of turbofan engines have achieved satisfactory results, there are still some challenges. For example, the spatial features and importance differences hidden in the raw monitoring data are not sufficiently addressed or highlighted. In this paper, a novel multi-head self-Attention fully convolutional network (MSA-FCN) is proposed for predicting the RUL of turbofan engines. MSA-FCN combines a fully convolutional network and multi-head structure, focusing on the degradation correlation among various components of the engine and extracting spatially characteristic degradation representations. Furthermore, by introducing dual multi-head self-attention modules, MSA-FCN can capture the differential contributions of sensor data and extracted degradation representations to RUL prediction, emphasizing key data and representations. The experimental results on the C-MAPSS dataset demonstrate that, under various operating conditions and failure modes, MSA-FCN can effectively predict the RUL of turbofan engines. Compared with 11 mainstream deep neural networks, MSA-FCN achieves competitive advantages in terms of both accuracy and timeliness for RUL prediction, delivering more accurate and reliable forecasts.

In the context of carbon neutrality, the low-carbon transition in agriculture is crucial to achieving carbon mitigation through clean production. The provision of agricultural productive services (APS) is pivotal for modernizing farming practices in China. However, the impact of this on the low-carbon transformation has received limited attention. This research examined the non-linear relationship between agricultural productive services and low-carbon development, including verifying a threshold effect with APS as the threshold variable, employing panel data for 31 provinces in China from 2010 to 2021. The results of the study suggested that the effect of services associated with agricultural productivity on the transition of the agricultural sector to low-carbon practices varied across threshold ranges. Specifically, when the APS exceeded the threshold of 2.4396, a significant suppressive effect was observed on carbon emission intensity. Further analysis revealed that APS indirectly influenced the farmland scale and agricultural technological advancements, thereby promoting the low-carbon transition of China’s agriculture. Based on these results, it is recommended to intensify the development of APS in key cereal-producing regions, while emphasizing the harmonious progress of these services in conjunction with large-scale farmland management.

Public discussions on climate change, as a form of social interaction, are widely recognized as effective tools for promoting collective action. However, there is limited research on examining the factors that influence climate change discussions from a social interaction perspective. In the present study, we conducted a large sample (N = 1,169) survey to investigate personal (such as self-efficacy and personal response efficacy) and others' (such as perceived others' response efficacy and social norms) factors influencing climate change discussions from a social interaction perspective. The results showed that (i) for people with high climate change perceptions, personal response efficacy, self-efficacy, and social norms have positive effects on climate change discussions, but the effect of perceived others' response efficacy on climate change discussion is not significant; (ii) for people with low climate change perceptions, self-efficacy and social norms have positive effects on climate change discussions, but the effects of personal response efficacy and perceived others' response efficacy on climate change discussion are not significant; (iii) irrespective of individuals' high or low perceptions of climate change, social norm remains the most important predictor of climate change discussions. These findings make valuable contributions to the theoretical literature and intervention efforts regarding climate change discussions from a social interaction perspective.

Very recently, few certified defense methods have been developed to provably guarantee the robustness of a text classifier to adversarial synonym substitutions. However, all the existing certified defense methods assume that the defenders have been informed of how the adversaries generate synonyms, which is not a realistic scenario. In this study, we propose a certifiably robust defense method by randomly masking a certain proportion of the words in an input text, in which the above unrealistic assumption is no longer necessary. The proposed method can defend against not only word substitution-based attacks, but also character-level perturbations. We can certify the classifications of over 50% of texts to be robust to any perturbation of five words on AGNEWS, and two words on SST2 dataset. The experimental results show that our randomized smoothing method significantly outperforms recently proposed defense methods across multiple datasets under different attack algorithms.

As energy conversion systems continue to grow in complexity, pneumatic control valves may exhibit unexpected anomalies or trigger system shutdowns, leading to a decrease in system reliability. Consequently, the analysis of time-domain signals and the utilization of artificial intelligence, including deep learning methods, have emerged as pivotal approaches for addressing these challenges. Although deep learning is widely used for pneumatic valve fault diagnosis, the success of most deep learning methods depends on a large amount of labeled training data, which is often difficult to obtain. To address this problem, a novel fault diagnosis method based on the attention-weighted relation network (AWRN) is proposed to achieve fault detection and classification with small sample data. In the proposed method, fault diagnosis is performed through the relation network in few-shot learning, and in order to enhance the representativeness of feature extraction, the attention-weighted mechanism is introduced into the relation network. Finally, in order to verify the effectiveness of the method, a DA valve fault dataset is constructed, and experimental validation is performed on this dataset and another benchmark PU rolling bearing fault dataset. The results show that the accuracy of the network on DA is 99.15%, and the average accuracy on PU is 98.37%. Compared with the state-of-the-art diagnosis methods, the proposed method achieves higher accuracy while significantly reducing the amount of training data.

Objectives The aims of this systematic review were to assess the impact of neoadjuvant chemotherapy (NAC) on breast cancer (BC) patients’ quality of life (QOL), to compare the different regimens of NAC on BC patients’ QOL, to compare NAC versus adjuvant chemotherapy on BC patients’ QOL and to identify predictors of QOL on patients with BC receiving NAC.Design The design used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sources Cinahl, Embase, Pubmed, Scopus, Web of Science, Cochrane library and PsycINFO were searched through 27 December 2021.Eligibility criteria for selecting studies The inclusion criteria were included: patients with BC receiving NAC, outcome measures related to QOL and published in English. The exclusion criteria were included: duplicates or overlapping participants, not original research, data or full text not available and qualitative study.Data extraction and synthesis Two independent reviewers used standardised methods to search, screen and code included studies. The risk of bias in individual studies was evaluated with Cochrane collaboration’s tool for assessing risk bias, Newcastle Ottawa Score or Joanna Briggs Institute Critical Appraisal tool. This systematic review performs narrative synthesis based on several different themes.Results The initial search resulted in 2994 studies; 12 of these studies fulfilled inclusion criteria. There was no significant difference in the QOL of BC before and after NAC, but patients experienced adverse reactions and depression during chemotherapy. Different regimens of NAC have different effects on patients’ QOL. Patients with NAC had more severe physical discomfort than those with adjuvant chemotherapy. However, BC patients’ QOL can be improved by intervening on social or family support, and these predictors, including chronotype, QOL before NAC and depression.Conclusions More original research is needed in future to understand the profile and predictors of QOL in patients with BC on NAC, which will help clinicians and patients make decisions and deal with NAC-related issues.

BackgroundInfants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma.ObjectiveTo address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma.MethodsNeonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma.ResultsPVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma.ConclusionProline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.

Naringin (NG), a natural flavanone glycoside, possesses a multitude of pharmacological properties, encompassing anti-inflammatory, sedative, antioxidant, anticancer, anti-osteoporosis, and lipid-lowering functions, and serves as a facilitator for the absorption of other drugs. Despite these powerful qualities, NG’s limited solubility and bioavailability primarily undermine its therapeutic potential. Consequently, innovative solubilization methodologies have received considerable attention, propelling a surge of scholarly investigation in this arena. Among the most promising solutions is the enhancement of NG’s solubility and physiological activity without compromising its inherent active structure, therefore enabling the formulation of non-toxic and benign human body preparations. This article delivers a comprehensive overview of NG and its physiological activities, particularly emphasizing the impacts of structural modification, solid dispersions (SDs), inclusion compound, polymeric micelle, liposomes, and nanoparticles on NG solubilization. By synthesizing current research, this research elucidates the bioavailability of NG, broadens its clinical applicability, and paves the way for further exploration and expansion of its application spectrum.

Abstract Background To evaluate the diagnostic value of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency (VBI) during clinical diagnosis and treatment Methods Eighty patients diagnosed with VBI in our hospital from June 2018 to December 2019 were randomly selected as the observation group, and 80 healthy people who received physical examination in the same period were selected as the control group. The abnormal rate, main performance and results, and the peak velocity of blood flow and vertebrobasilar artery blood flow of the two groups were compared. Results The abnormal rate of EEG and TCD in VBI patients was 38.75% (31/80) and the 93.75% (75/80), respectively. In TCD examination, ACA, PCA, MCA, and VA of both sides of the observation group were higher than those of the control group, while BA was lower than that of the control group (P < 0.05). The Vs, Vd, and Vm on both sides of BA and VA in the observation group were lower than those in the control group, while PI and RI were higher than those in the control group (P < 0.05). Conclusions TCD examination is highly sensitive to the degree and pattern of cerebral ischemia in VBI patients. EEG examination will define the changes of brain cell function after cerebral ischemia. Therefore, EEG and TCD have their own advantages. The application of TCD and EEG can be considered in the early diagnosis, curative effect, and prognosis evaluation of VBI patients, so as to improve the accuracy of diagnosis and prognosis.

Abstract Background Thoracolumbar burst fractures can be treated with posterior short-segment fixation. However, no classification can help to estimate whether the healed vertebral body will have sufficient stability after implant removal. We aimed to develop a Healing Pattern Classification (HPC) to evaluate the stability of the healed vertebra based on cavity size and location. Methods Fifty-two thoracolumbar burst fracture patients treated with posterior short-segmental fixation without fusion and followed up for an average of 3.2 years were retrospectively studied. The HPC was divided into 4 types: type I - no cavity; type II - a small cavity with or without the violation of one endplate; type III - a large cavity with or without the violation of one endplate; and type IV - a burst cavity with the violation of both endplates or the lateral cortical shell. The intraobserver and interobserver intraclass correlation coefficients (ICCs) of the HPC were assessed. The demographic characteristics and clinical outcomes of the cohort were compared between the stable group (types I and II) and the unstable group (types III and IV). Logistic regression was conducted to evaluate risk factors for unstable healing. Results The intraobserver and interobserver ICCs of the HPC were 0.86 (95% CI = 0.74–0.90) and 0.77 (95% CI = 0.59–0.86), respectively. While the unstable healing group (types III and IV) accounted for 59.6% of the patients, most of these patients were asymptomatic. The preoperative Load Sharing Classification (LSC) comminution score may predict the occurrence of unstable healing (OR = 8.4, 95% CI = 2.4–29.7). Conclusions A reliable classification for assessing the stability of a healed vertebra was developed. With type I and II healing, the vertebra is considered stable, and the implant can be removed. With type III healing, the vertebra may have healing potential, but the implant should not be removed unless type II healing is achieved. With type IV healing, the vertebra is considered extremely unstable, and instrumentation should be maintained. Assessing the LSC comminution score preoperatively may help to predict unstable healing after surgery.

Due to the lack of an effective overall coordinated treatment method, it is difficult to achieve low cost and efficient removal of pollutants from coal-fired flue gas. This paper establishes a collaborative optimization model for ultralow emission systems, including a system level model of operation cost and three discipline level models for denitration, desulfurization, and dust removal. An improved collaborative optimization method with a dynamic penalty function is proposed to optimize an ultralow emission system. Simulation results show that the improved method achieves better global optimization and effectively reduces the operation cost of the system under ultralow emission constraints.

Automated surface inspection (ASI) is critical to quality control in industrial manufacturing processes. Recent advances in deep learning have produced new ASI methods that automatically learn high-level features from training samples while being robust to changes and capable of detecting different types of surfaces and defects. However, they usually rely heavily on manpower to collect and label training samples. In this paper, a generic semi-supervised deep learning-based approach for ASI that requires a small quantity of labeled training data is proposed. While the approach follows the MixMatch rules to conduct sophisticated data augmentation, we introduce a new loss function calculation method and propose a new convolutional neural network based on a residual structure to achieve accurate defect detection. An experiment on two public datasets (DAGM and NEU) and one industrial dataset (CCL) is carried out. For public datasets, the experimental results are compared against several best benchmarks in the literature. For the industrial dataset, the results are compared against deep learning methods based on benchmark neural networks. The proposed method achieves the best performance in all comparisons. In addition, a comparative experiment of model performance given a different number of labeled samples is conducted, demonstrating that the proposed method can achieve good performance with few labeled training samples.

Abstract Background Chlortetracycline (CTC) is one of the commercially important tetracyclines (TCs) family product and is mainly produced by Streptomyces. CTC is still in a great demand due to its broad-spectrum activity against pathogens. Engineering transcriptional control allows the cell to allocate its valuable resources towards protein production and provides an important method for the build-up of desired metabolites. Despite extensive efforts concerning transcriptional regulation for increasing the productivities of TCs, the regulatory mechanisms of the CTC biosynthesis remain poorly understood. Results In this study, the possible regulatory function of CtcS, a potential member of MarR (multiple antibiotic resistance regulator) family of transcriptional regulators in S. aureofaciens F3, was demonstrated. Knockdown of ctcS altered the transcription of several biosynthesis-related genes and reduced the production of tetracycline (TC) and CTC, without obvious effect on morphological differentiation and cell growth. Especially, CtcS directly repressed the transcription of the adjacent divergent gene ctcR (which encodes a putative TC resistance efflux protein). A CtcS-binding site was identified within the promoter region of ctcR by DNase I footprinting and an inverted repeat (5′-CTTGTC-3′) composed of two 6-nt half sites in the protected region was found. Moreover, both CTC and TC could attenuate the binding activity of CtcS with target DNA. Conclusion ctcS regulated the production of TC and CTC in S. aureofaciens F3 and the overexpression of it could be used as a simple approach for the construction of engineering strain with higher productivity. Meanwhile, CtcS was characterized as a TC- and CTC-responsive MarR family regulator. This study provides a previously unrecognized function of CtcS and will benefit the research on the regulatory machinery of the MarR family regulators.

Abstract Background The purpose of this study is to explore the therapeutic effect of percutaneous kyphoplasty (PKP) combined with anti-osteoporosis drug, zoledronic acid, on postmenopausal women with osteoporotic vertebral compression fracture (OVCF) and to perform an analysis of postoperative bone cement leakage risk factors. Methods A total of 112 OVCF patients, according to therapeutic regimens, were divided into control group (n = 52, treated with PKP) and observation group (n = 60, treated with PKP and zoledronic acid injection). Results Postoperative tumor necrosis factor-α and interleukin-6 levels were significantly decreased in the two groups, compared with those before treatment (both P < 0.05); bone mineral density (BMD), serum bone gla protein (BGP), and vertebral height ratio of injured vertebrae were significantly increased, and procollagen type I N-terminal propeptide (PINP), Cobb angle, visual analogue scale/score (VAS), and Oswestry disability index (ODI) were significantly decreased compared with those before treatment (all P < 0.05). There were significantly higher changes in difference value of BMD, PINP, BGP, vertebral height ratio of injured vertebrae, Cobb angle, VAS, and ODI levels and significantly better therapeutic effect in the observation group than those in the control group (all P < 0.05). Multivariate logistic regression analysis showed that the use of zoledronic acid, vertebral height ratio of injured vertebrae, and ODI were independent factors affecting the therapeutic effect, and that the dosage of bone cement, and peripheral vertebrae wall damage were independent risk factors causing postoperative bone cement leakage. There were no significant differences in postoperative bone cement leakage rate between the two groups. Conclusions Peripheral vertebrae wall damage and the dosage of bone cement are independent risk factors causing bone cement leakage in OVCF patients treated with PKP. PKP combined with zoledronic acid has an improvement effect on the condition of postmenopausal women with OVCF and reduces the inflammation and pain in patients, which is beneficial to clinical treatment.

The protein synthesis inhibitor anisomycin features a unique benzylpyrrolidine system and exhibits potent selective activity against pathogenic protozoa and fungi. It is one of the important effective components in Agricultural Antibiotic120, which has been widely used as naturally-originated agents for treatment of crop decay in China. The chemical synthesis of anisomycin has recently been reported, but the complex process with low productivity made the biosynthesis still to be a vital mainstay in efforts. The biosynthetic gene cluster (BGC) of anisomycin in Streptomyces hygrospinosus var. beijingensis has been identified in our previous work, while poor understanding of the regulatory mechanism limited the yield enhancement via regulation engineering of S. hygrospinosus var. beijingensis. In this study here, we characterized AniF as an indispensable LuxR family transcriptional regulator for the activation of anisomycin biosynthesis. The genetic manipulations of aniF and the real-time quantitative PCR (RT-qPCR) revealed that it positively regulated the transcription of the anisomycin BGC. Moreover, the overexpression of aniF contributed to the improvement of the production of anisomycin and its derivatives. Dissection of the mechanism underlying the function of AniF revealed that it directly activated the transcription of the genes aniR-G involved in anisomycin biosynthesis. Especially, one AniF-binding site in the promoter region of aniR was identified by DNase I footprinting assay and an inverted repeat sequence (5′-GGGC-3′) composed of two 4-nt half sites in the protected region was found. Taken together, our systematic study confirmed the positive regulatory role of AniF and might facilitate the future construction of engineering strains with high productivity of anisomycin and its derivatives. Keywords: Anisomycin, Agricultural Antibiotic120, Biosynthesis, AniF, LuxR regulator, Streptomyces

Abstract Background To examine the epidemiological trends and changes of hepatitis E virus (HEV) infection and the potential risk factors for severe infection in the Zhejiang eastern coastal area of China. Methods We analyzed statutory hepatitis E cases notifications and inpatient data held by the national surveillance and hospital information systems in Wenzhou, Taizhou, Ningbo, and Zhoushan cities of the Zhejiang eastern coastal area of China. Results Nine thousand four hundred sixteen hepatitis E cases were reported from 2004 to 2017, with an average incidence of 2.94 per 100,000. The overall death rate was 0.06% (6/9416). A gradual decline of hepatitis E cases was found in the coastal areas since 2007, while a rise was identified in the non-coastal areas. Annual incidence in non-coastal cities was much higher than that in coastal cities (4.345 vs. 2.945 per 100,000, relative risk = 1.5, P value 0.05). Hepatitis E cases prevalence increased with age, highest among men in their 70s (9.02 vs. 11.33 per 100,000) and women in their 60s (3.94 vs. 4.66 per 100,000) groups for both coastal and noncoastal areas respectively. A clear seasonal pattern was observed, with a peak in March (0.4429 per 100,000) in coastal areas. 202 inpatients were documented, of which 50.50% (102/202) were severe cases. Male individuals with alcohol consumption, alcohol hepatic diseases, and superinfection were the three independent highest risks for severe infections (all with P value

Wireless sensor networks usually suffer from the issue of time synchronization discrepancy due to environmental effects or clock management collapse. This will result in time delays between the dynamic responses collected by wireless sensors. If non-synchronized dynamic response data are directly used for structural modal identification, it leads to the misestimation of modal parameters. To overcome the non-synchronization issue, this study proposes a time synchronization approach to detect and correct asynchronous dynamic responses based on frequency domain decomposition (FDD) with frequency-squeezing processing (FSP). By imposing the expected relationship between modal phase angles extracted from the first-order singular value spectrum, the time lags between different sensors can be estimated, and synchronization can be achieved. The effectiveness of the proposed approach is fully demonstrated by numerical and experimental studies, as well as field measurement of a large-span spatial structure. The results verify that the proposed approach is effective for the time synchronization of wireless accelerometer sensors.

Abstract Background There are no universally accepted protocols for the treatment of late-onset deep surgical site infection. This study retrospectively evaluates the methods of aggressive debridement with instrumentation retention, high vacuum closed-suction drain without irrigation, primary wound closure, and antibiotic therapy for the treatment of late-onset deep surgical site infection after instrumented spinal surgery. Methods A total of 4057 patients who underwent instrumented spinal surgeries were surveyed from January 2010 to June 2014. Surgical debridement was performed immediately after late-onset deep surgical site infection was identified. In addition to extended resection of the devitalized and necrotic tissue, the biofilms adhered to the surface of implants were removed meticulously and thoroughly. Primary wound closure was performed on each patient, and closed suction drains were maintained for about 7–10 days without irrigation. Antibiotic therapy was administered for 3 months according to the results of the pathogenic culture. Results Forty-two patients were identified as having late-onset deep surgical site infection. Staphylococcus aureus was the most common pathogen in this group. Seven patients with late-onset deep surgical site infection had negative bacterial culture results. Infections resolved in all patients. Forty-one patients retained their instrumentation, whereas 1 patient had the implants removed because of Staphylococcus aureus infection, which was found the implants loosening during debridement. Primary wound healing was found in all patients with no recurrence of infection during the follow-up periods. Conclusions A timely diagnosis, aggressive and meticulous debridement, high vacuum closed-suction drain, routine and adequate use of antibacterial agents are the keys to successfully resolving infection and keeping implants retention in the treatment of late-onset deep surgical site infection after instrumented spinal surgery.

Background: Osteoporosis is a systemic bone disease resulting from decreased bone mass and bone microstructure degeneration. Yes-associated protein 1 (YAP1) belongs to YAP family and plays a significant part in controlling bone quality. Aim of the study: Present study aimed to study the function and up-stream mechanism of YAP1 in the differentiation of BMSCs (bone marrow stromal cells) and MC3T3-E1. Methods: ALP staining, alizarin red staining and western blot analysis of osteogenic biomarkers determined osteogenic differentiation in BMSCs and MC3T3-E1. Mechanistic assays including luciferase reporter assay, RIP assay and RNA pull down assay disclosed the interplays between RNAs. Results: YAP1 promoted osteogenic differentiation of BMSCs and MC3T3-E1. Circ_0024097 originated from YAP1 sponged miR-376b-3p to elevate YAP1 expression in BMSCs and MC3T3-E1. Further, YAP1 mediated circ_0024097- promoted effects on osteogenic differentiation. Moreover, circ_0024097 activated Wnt/β-catenin pathway to facilitate osteogenic differentiation. Conclusion: It was firstly uncovered in present study that circ_0024097 attenuated osteoporosis through promoting osteogenic differentiation via miR-376b-3p/YAP1 axis and Wnt/β-catenin pathway.

Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.

Hepatocellular carcinoma (HCC) accounts for most of primary liver cancer, of which five-year survival rate remains low and chemoprevention has become a strategy to reduce disease burden of HCC. We aim to explore the in vivo chemopreventive effect of an organoselenium-containing compound butaselen (BS) against hepatocarcinogenesis and its underlying mechanisms. Pre- and sustained BS treatment (9, 18 and 36 mg/Kg BS) could dose-dependently inhibit chronic hepatic inflammation, fibrosis, cirrhosis and HCC on murine models with 24 weeks treatment scheme. The thioredoxin reductase (TrxR), NF-κB pathway and pro-inflammatory factors were activated during hepatocarcinogenesis, while their expression were decreased by BS treatment. BS treatment could also significantly reduce tumor volume in H22-bearing models and remarkably slow tumor growth. HCC cell lines HepG2, Bel7402 and Huh7 were time- and dose-dependently inhibited by BS treatment. G2/M arrest and apoptosis were observed in HepG2 cells after BS treatment, which were mediated by TrxR/Ref-1 and NF-κB pathways inhibition. BS generated reactive oxygen species (ROS), which could be reduced by antioxidant N-acetyl-L-cysteine (NAC) and NADPH oxidase inhibitor DPI. NAC could markedly increase HepG2 cells viability. TrxR activity of HepG2 cells treated with BS were significantly decreased in parallel with proliferative inhibition. The TrxR1-knockdown HepG2 cells also exhibited low TrxR1 activity, high ROS level, relatively low proliferation rate and increased resistance to BS treatment. In conclusion, BS can prevent hepatocarcinogenesis through inhibiting chronic inflammation, cirrhosis and tumor progression. The underlying mechanisms may include TrxR activity inhibition, leading to ROS elevation, G2/M arrest and apoptosis. Keywords: Chemoprevention, Hepatocellular carcinoma (HCC), Thioredoxin reductase (TrxR), NF-κB, Reactive oxygen species (ROS)