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Abstract Objective Thalassemia is among the most common inherited diseases worldwide. We aimed to analyze the genotype and frequency distribution of thalassemia in a general hospital in Beijing and provide a reference for genetic counseling and prenatal diagnosis. Methods A total of 3196 cases of thalassemia screened at Peking Union Medical College Hospital (PUMCH) between January 2018 and January 2022 were collected. Thalassemia genotypes were tested using gap polymerase chain reaction (gap-PCR), PCR, reverse dot blot (RDB), and Sanger sequencing analyses. The pathogenicity of the rare variants was analyzed using bioinformatics approaches. Results Total of 1936 positive routine α/β-thalassemia were detected from 3196 blood samples, including 733 α-thalassemia variants, 1170 β-thalassemia variants, and 33 cases with concurrent α- and β-thalassemia variants. Two novel variants, HBA2:c.300+82G>C and HBB:codon85(-T), were identified in HBA2 and HBB genes, respectively, and were not detected in the ExAC, gnomAD, HbVar, and HGMD databases. Conclusions The genotype distribution of thalassemia in a general hospital in Beijing is complex and heterogeneous. The novel variants in HBA2 and HBB are likely to underlie α/β-thalassemia in these patients.

Abstract Background Activation of pericytes leads to renal interstitial fibrosis, but the regulatory mechanism of pericytes in the progression from AKI to CKD remains poorly understood. CD36 activation plays a role in the progression of CKD. However, the significance of CD36 during AKI-CKD, especially in pericyte, remains to be fully defined. Methods GEO and DISCO database were used to analyze the expression of CD36 in pericyte during AKI-CKD; IRI to conduct AKI-CKD mouse model; Hypoxia/Reoxygenation (H/R) to induce the cell model; RT-qPCR and Western blotting to detect gene expression; IP and confocal-IF to determine the core fucosylation (CF) level of CD36. Flow cytometry (AV/PI staining) to detect the cell apoptosis and JC-1 staining to react to the change of mitochondrial membrane potential. Results During AKI to CKD progression, CD36 expression in pericytes is higher and may be influenced by CF. Moreover, we confirmed the positive association of CD36 expression with pericyte-myofibroblast transition and the progression of AKI-CKD in an IRI mouse model and hypoxia/reoxygenation (H/R) pericytes. Notably, we discovered that FUT8 upregulates both CD36 expression and its CF level, contributing to the activation of the mitochondrial-dependent apoptosis signaling pathway in pericytes, ultimately leading to the progression of AKI-CKD. Conclusion These results further identify FUT8 and CD36 as potential targets for the treatment in the progression of AKI-CKD.

Background The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.Methods This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0–1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0–90 min, 91–180 min and 181–270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment.Results Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0–90 min, 1.23 (95% CI 0.88 to 1.71) for 91–180 min and 1.21 (95% CI 0.88 to 1.65) for 181–270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI −0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI −2.66 to 6.20; p=0.58) for 0–180 min.Conclusions In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Plant irradiation has been used to induce genetic variation in crop germplasm. However, the underlying mechanisms of plant responses to ionizing radiation stress are still unclear. In plants, reactive oxygen species (ROS) are produced with abiotic stress. Respiratory burst oxidative homologs (Rboh) genes are important regulators of plant ROS stress responses, but little is known of their involvement in the response to ionizing radiation stress. In this study, young branches of Ficus carica L. were irradiated with 60Co γ-rays and axillary buds were collected after 3- 48 h after irradiation. The differentially expressed genes (DEGs; p< 0.05) detected included an early (6 h) and sustained increase in member of the MAPK signaling pathway. The activities of superoxide dismutase SOD, POD and CAT in fig axillary buds showed a trend of first decrease and then increase with time, while the contents of MDA and H2O2 maintained an overall upward trend. The analysis of differentially expressed genes (DEGs; p < 0.05) indicated an early (6 h) and sustained increase in member of the MAPK signaling pathway. DEGs for glutathione-s-transferase and genes involved in phenylpropanoid and flavonoid biosynthesis pathways were detected at all time points, indicating that γ-irradiation induced an increased capacity for in ROS-scavenging. Substantial changes in the expression of MYB, NAC and bHLH transcription factor family members were also seen to occur within 6 h after irradiation. Taking Rboh-derived ROS signaling pathway as the entry point, the MYB transcription factor, FcMYB3, was identified as an potential upstream regulator of FcRbohD in a yeast one hybrid assay and this interaction verified by LUC and EMSA experiments. The knock-down and overexpression of FcMYB3 indicated that FcMYB3 is a positive regulator of ROS accumulation in response to γ-ray radiation stress responses in fig. Our results will provide a better understanding of the mechanisms of radiation tolerance in plant materials.

Rainfall data with high spatial and temporal resolutions are essential for urban hydrological modeling. Ubiquitous surveillance cameras can continuously record rainfall events through video and audio, so they have been recognized as potential rain gauges to supplement professional rainfall observation networks. Since video-based rainfall estimation methods can be affected by variable backgrounds and lighting conditions, audio-based approaches could be a supplement without suffering from these conditions. However, most audio-based approaches focus on rainfall-level classification rather than rainfall intensity estimation. Here, we introduce a dataset named Surveillance Audio Rainfall Intensity Dataset (SARID) and a deep learning model for estimating rainfall intensity. First, we created the dataset through audio of six real-world rainfall events. This dataset's audio recordings are segmented into 12,066 pieces and annotated with rainfall intensity and environmental information, such as underlying surfaces, temperature, humidity, and wind. Then, we developed a deep learning-based baseline using Mel-Frequency Cepstral Coefficients (MFCC) and Transformer architecture to estimate rainfall intensity from surveillance audio. Validated from ground truth data, our baseline achieves a root mean absolute error of 0.88 mm h-1 and a coefficient of correlation of 0.765. Our findings demonstrate the potential of surveillance audio-based models as practical and effective tools for rainfall observation systems, initiating a new chapter in rainfall intensity estimation. It offers a novel data source for high-resolution hydrological sensing and contributes to the broader landscape of urban sensing, emergency response, and resilience.

Abstract Background Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. Methods Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. Results The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. Conclusions Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

Tomato spotted wilt virus (TSWV) is an important virus that has rapidly spread throughout the world. TSWV seriously hinders the production of tomato (Solanum lycopersicum) and other plants. In order to discover more new genes and metabolites related to TSWV resistance in tomato plants, the genes and metabolites related to the resistance of tomato plants inoculated with TSWV were identified and studied herein. The tomato TSWV-resistance line YNAU335 (335) and TSWV-susceptible lines NO5 and 96172I (961) were used as the transcriptome and metabolome research materials. Transcriptomic and metabolomic techniques were used to analyze the gene and metabolite response mechanisms to TSWV inoculation. A total of 3 566, 2 951, and 2 674 differentially expressed genes (DEGs) were identified in lines 335, NO5, and 961, respectively. Meanwhile, 208, 228, and 273 differentially accumulated metabolites (DAMs) were identified in lines 335, NO5, and 961, respectively. In line 335, the number of DEGs was the highest, but the number of DAMs was lowest. Furthermore, 903 DEGs and 94 DAMs were common to the response to TSWV in the three inbred lines. The 903 DEGs and 94 DAMs were mainly enriched in the plant hormone signal transduction and flavonoid synthesis pathways. In addition, many nucleotide-binding site-leucine-rich repeat genes and transcription factors were found that might be involved in the TSWV response. These results provide new insights into TSWV resistance mechanisms.

Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4 hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Significant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis.

Exudate management is of significant clinical value for the treatment of acute wound. Various wound dressings have been developed to restore the function of injured tissues and promote wound healing, but proper exploiting the healing factors inside exudate and achieving anti-adhesion wound care remains a challenge. Herein, we present a novel multi-functional composite dressing (MCD) by coupling supernatant lyophilized powder of mesenchymal stem cells (MSC-SLP) with a sandwich-structured wound dressing (SWD). The developed MCDs demonstrated unique unidirectional drainage capability, stable anti-adhesion characteristics, and improved wound healing performance. The designed SWD with both superhydrophobic inner surface and liquid-absorption ability of mid layer enables the dressings exhibit desired anti-adhesion property to neoformative granulation tissues, favorable shielding effect to exogenous bacteria, as well as appropriate exudate-retaining capability and unidirectional exudate-absorption property. The introduction of MSC-SLP in SWD was demonstrated to further improve wound healing quality. Compared to medical gauze, the synergic effect of SWD and MSC-SLP significantly accelerates wound healing rate by over 30%, avoids tissue avulsion when changing dressings, and produces a flat-smooth closure surface. More importantly, the wound treated with MCDs presents more skin accessory organs and blood vessels in regenerated tissues than other groups. In vivo/vitro biocompatibility evaluations indicated little toxicity, demonstrating the biosecurity of the developed dressings. The proposed method offers great potential in clinical applications particularly for chronic wound treatments.

Abstract Background Venous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE. Methods A total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously. Results The TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group. Conclusion The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.

ObjectiveTo investigate the effect of COVID-19 vaccination on plasma D-dimer levels in early pregnant women.MethodsA total of 834 early pregnant women(gestational age ≤ 13 weeks), who visited Northwest Women and Children’s Hospital between December 2020 and April 2022, were selected. There were 696 women in the healthy group (group A) and 138 in the group with a history of adverse pregnancy and childbirth (group B). The plasma D-dimer levels of all participants were tested, and the COVID-19 vaccine history of all participants was collected using a survey questionnaire.ResultsThe plasma D-dimer levels did not differ between group A and the group B (p = 0.1327). In the group A, 470 were vaccinated and 226 were unvaccinated. The D-dimer levels of vaccinated individuals were lower than those of unvaccinated individuals (p = 0.0047). In the group B, 84 were vaccinated and 54 were unvaccinated; no difference in D-dimer levels was found between the vaccinated and unvaccinated individuals (p = 0.0542). In the group A, the D-dimer levels of the unvaccinated group were not different from those of women vaccinated with one dose (p = 0.208), but they were higher than those who received two doses (p = 0.019) or three doses (p = 0.003). And, no significant difference in D-dimer levels was found among women who received different vaccine brands and with different vaccination times.ConclusionThis study preliminarily indicates that COVID-19 vaccination does not increase D-dimer levels in early pregnant women.

Objective: The real-time PCR system is one of the most powerful research tools available in the life sciences field. The aim of this study was to preliminarily evaluate the analytical performance of QuantStudio 1 Plus real-time PCR system (QS 1 plus) for clinical procedures. Methods: The consistency of QS 1 plus with the reference system in terms of various clinical procedures was evaluated. For qualitative data, the Kappa test was used to analyze the agreement of the results. For the quantitative data, Passing-Bablok regression analysis and Bland-Altman plot analysis were used to assess the concordance between QS 1 plus and the reference instrument. Results: Passing-Bablok regression showed an excellent agreement between the QS 1 plus and LC 480 systems for HBV DNA quantification (y = 0.928 + 0.970x), whereas Bland-Altman plot analysis showed very small mean deviations between the two systems. The QS 1 plus yielded perfectly consistent results with the reference instrument for methylenetetrahydrofolate reductase (MTHFR) C677T melting curve genotyping analysis, MTHFR C677T genotyping analysis, Norovirus RNA negative/positive analysis, influenza B virus (Flu B) RNA negative/positive analysis, Mycobacterium tuberculosis (MTB) DNA negative/positive analysis, Human Papillomavirus (HPV) genotyping analysis, epidermal growth factor receptor (EGFR) gene mutation analysis. Both the relative quantitative analysis and the relative quantitative analysis (standard curve) confirmed the satisfactory concordance between the QS 1 plus instrument and the ABI 7500 instrument by Passing-Bablok regression analysis (y = 0.180 + 0.817x and y = 0.012 + 1.000x, respectively) and Bland-Altman plot analysis. Conclusions: Our research has proven that QS 1 plus is adaptable to most test procedures in the clinical laboratory. This may provide the basis for its further application.

Abstract Background and purpose This study assessed the predictive factors for symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) after receiving intravenous thrombolysis (IVT) within 6 h in northern China. Methods We retrospectively analyzed ischemic stroke patients who were treated with IVT between November 2016 and December 2018 in 19 hospitals in Shandong Province, China. Potential predictors of sICH were investigated using univariate and multivariate analyses. Results Of the 1293 enrolled patients (845 men, aged 62 ± 11 years), 33 (2.6%) developed sICH. The patients with sICH had increased coronary heart disease (36.4% vs. 13.7%, P = 0.001), more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score on admission of 14 vs.7, P 50 min, and a white blood cell count ≥9000/mm3 were independent risk factors for sICH in Chinese patients within 6 h after IVT for AIS.

In this study, arc and friction stir hybrid welding (AFSHW) was proposed to weld aluminum-steel dissimilar metals in attempt to realize high quality joining. Firstly, an interlayer was produced on galvanized steel by using bypass current-metal inert gas welding (BC-MIG), and then an aluminium plate was jointed via Friction stir lap welding (FSLW). The effects of tool pin length and FSLW times on the microstructure and mechanical properties of dissimilar joints were fully investigated by means of Optical Microscopy (OM), Scanning Electron Microscope (SEM), Electron Backscatter Diffraction (EBSD), and mechanical testing. The results show that as pin length increased, joint strength tended to increase and then decrease, and the tensile failure partially occurred at aluminium base metal. However, with additional number of FSLW, joint strength would be reduced, which was attributed to attenuated dislocation density and strain concertation in dissimilar joint. The research outcomes will provide a new welding method to obtain sound Al-Fe dissimilar metal joint, and benefit to a better understanding of Al-Fe joining mechanism.

Abstract Background C5aR has been extensively studied in recent years as an essential component of the complement system. However, the role of C5aR in tumors has not been sufficiently investigated and summarized. The aim of this meta-analysis was to investigate the prognostic value of C5aR in solid tumors as well as the correlation between C5aR and clinicopathological features. Methods Relevant study collection was performed in PubMed, Embase, Web of Science, BIOSIS Previews, Cochrane Library until July 10, 2021. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were performed to assess the robustness of this study, while publication bias was tested by Begg’s and Egger’s tests. Results A total of 11 studies involving 1577 patients were included in the study. Our results suggest that the high-level C5aR expression in tumor tissue predicted unsatisfactory overall survival (OS) (HR = 1.92, 95% CI:1.47–2.50, P

Presently, the environmental pollution problem, especially that of the small and medium-sized enterprises, has become a bottleneck restricting the high-quality development of China’s economy. It is imperative to accelerate the construction of a collaborative governance system with multiple subject participation. The behavior modes of Environmental Non-governmental Organizations (ENGOs), a key player in environmental care, in collaborating with core enterprises to control pollution from small and medium-sized suppliers should be explored. Therefore, we constructed a collaborative governance system consisting of ENGOs, focal firms and small and medium-sized suppliers. Then a two-stage game model was established to analyze the strategies of the governance system. Specifically, we studied the collaborative green cooperation strategy and antagonistic pressure supervision strategy between ENGOs and focal firms, analyzed factors influencing the strategic choices of each subject, and gave the advantages of the cooperation strategies through further comparisons. The results showed that: Under the cooperation strategy, ENGOs provided knowledge of environmental protection to the focal firms, then both the audit efforts of focal firms and the environmental protection efforts of small and medium-sized suppliers were effectively improved. Since ENGOs could not fully obtain the pollution information of small and medium-sized suppliers or accurately trace it from their downstream focal firms, it was difficult to drive the supply chain’s endogenous governance by this external monitoring of ENGOs, making the effect of pressure supervision strategy limited. The effectiveness of green cooperation strategy was positively correlated with the knowledge absorption capacity of focal firms, the unit product revenue, and the focal firms' violation penalties for small and medium-sized suppliers. When ENGOs' violation penalties for small and medium-sized suppliers were higher, or the reputation loss of focal firms was higher, more unfavorable conditions of green cooperation strategy could be achieved. Accordingly, ENGOs should choose to cooperate with focal firms with strong knowledge absorption ability and high profit per product; focal firms should learn environmental protection knowledge to improve the screening standards and review capabilities, and promote the achievement of green cooperation strategy conditions by strengthening active information disclosure; the government should promote the collaboration between ENGOs and focal firms by issuing environmental guidelines.

Abstract Background Bagging can improve the appearance of fruits and increase the food safety and commodification, it also has effects on intrinsic quality of the fruits, which was commonly reported negative changes. Fig can be regarded as a new model fruit with its relatively small genome size and long fruit season. Results In this study, widely targeted metabolomics based on HPLC MS/MS and RNA-seq of the fruit tissue of the ‘Zibao’ fig before and after bagging were analyzed to reveal the metabolites changes of the edible part of figs and the underneath gene expression network changes. A total of 771 metabolites were identified in the metabolome analysis using fig female flower tissue. Of these, 88 metabolites (including one carbohydrate, eight organic acids, seven amino acids, and two vitamins) showed significant differences in fruit tissue before and after bagging. Changes in 16 structural genes, 13 MYB transcription factors, and endogenous hormone (ABA, IAA, and GA) metabolism and signal transduction-related genes in the biosynthesis pathway of flavonoids after bagging were analyzed by transcriptome analysis. KEGG enrichment analysis also determined significant differences in flavonoid biosynthesis pathways in female flower tissue before and after bagging. Conclusions This work provided comprehensive information on the composition and abundance of metabolites in the female flower tissue of fig. The results showed that the differences in flavor components of the fruit before and after bagging could be explained by changes in the composition and abundance of carbohydrates, organic acids, amino acids, and phenolic compounds. This study provides new insights into the effects of bagging on changes in the intrinsic and appearance quality of fruits.

Hepatocellular carcinoma (HCC) is a common malignant tumor. LukS-PV is the S component of Panton-Valetine leukocidin (PVL), which is secreted by Staphylococcus aureus. This study investigated the effects of LukS-PV on the proliferation, apoptosis, and cell-cycle progression of HCC cells and the mechanisms of its activity. The HCC cells were treated with different LukS-PV concentrations in vitro. Cell Counting Kit-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to study cell proliferation. Flow cytometry was used to measure apoptosis and cell-cycle progression. Quantitative reverse transcriptase PCR and western blot assays were used to determine mRNA and protein expression levels. Xenograft experiments were performed to determine the in vivo antitumor effect of LukS-PV. Immunostaining was performed to analyze Ki-67 and HDAC2 (histone deacetylase 2) expression. Our results showed that LukS-PV inhibited cell proliferation and induced apoptosis in a concentration-dependent manner in HCC cell lines. LukS-PV also can induce cell-cycle arrest. Moreover, we discovered that LukS-PV attenuated HDAC2 expression and upregulated PTEN; phosphorylated AKT was also reduced. Further studies demonstrated that LukS-PV treatment significantly reduced tumor growth in nude mice and suppressed Ki-67 and HDAC2 levels. Our data revealed a vital role of LukS-PV in suppressing HCC progression by downregulating HDAC2 and upregulating PTEN.

Streptococcus pneumoniae is a common human pathogen that can cause severe invasive pneumococcal diseases (IPDs). Penicillin-binding proteins (PBPs) are the targets for β-lactam antibiotics (BLAs), which are the common empirical drugs for treatment of pneumococcal infection. This study investigated the serotype distribution and antibiotic resistance patterns of S. pneumoniae strains causing IPD in China, including exploring the association between penicillin (PEN) susceptibility and PBPs variations. A total of 300 invasive S. pneumoniae isolates were collected from 27 teaching hospitals in China (2010-2015). Serotypes were determined by Quellung reaction. Serotypes 23F and 19F were the commonest serotypes in isolates from cerebrospinal fluid (CSF), whilst serotypes 19A and 23F were most commonly seen in non-CSF specimens. Among the 300 invasive S. pneumoniae strains, only one strain (serotype 6A, MIC = 0.25 μg/ml) with PEN MIC value ≤ 0.25 μg/ml did not have any substitutions in the PBPs active sites. All the strains with PEN MIC value ≥ 0.5 μg/ml had different substitutions within PBPs active sites. Substitutions in PBP2b and PBP2x active sites were common in low-level penicillin-resistant S. pneumoniae (PRSP) strains (MIC = 0.5 μg/ml), with or without PBP1a substitution, while all strains with PEN MIC ≥ 1 μg/ml had substitutions in PBP1a active sites, accompanied by PBP2b and PBP2x active site substitutions. Based on the three PBPs substitution combinations, a high degree of diversity was observed amongst the isolates. This study provides some new insights for understanding the serology and antibiotic resistance dynamics of S. pneumoniae causing IPD in China. However, further genomic studies are needed to facilitate a comprehensive understanding of antibiotic resistance mechanisms of S. pneumoniae.

Ethylene is very important in the process of plant development and regulates the biosynthesis of many secondary metabolites. In these regulatory mechanisms, transcription factors (TFs) that mediate ethylene signals play a very important role. Capsaicinoids (CAPs) are only synthesized and accumulated in Capsicum species, causing their fruit to have a special pungent taste, which can protect against attack from herbivores and pathogens. In this study, we identified the TF CcERF2, which is induced by ethylene, and demonstrated its regulatory effect on CAPs biosynthesis. Transcriptome sequencing analysis revealed that the expression patterns of CcERF2 and multiple genes associated with CAPs biosynthesis were basically the same. The spatiotemporal expression results showed CcERF2 was preferentially expressed in the placenta of the spicy fruit. Ethylene can induce the expression of CcERF2 and CAPs biosynthesis genes (CBGs). CcERF2 gene silencing and 1-methylcyclopropene (1-MCP) and pyrazinamide (PZA) treatments caused a decrease in expression of CBGs and a sharp decrease in content of CAPs. The results indicated that CcERF2 was indeed involved in the regulation of structural genes of the CAPs biosynthetic pathway.

The commodity value of fruits is directly affected by fruit flavor and color. Secondary metabolites, such as amino acids, organic acids, esters, and β-carotene, are important synthetic products, which are of great significance in the flavor formation of mango fruits. In this study, a total of 309 different metabolites, consisting of organic acids, amino acids, phenolic acids, and saccharides, and a further 84 types of volatile organic compounds (VOCs) were identified in differential levels in TR vs. MG mango fruit stages. The major volatile compounds found were ester [2(3H)-furanone, 5-ethyldihydro; N-(2,5-ditrifluoromethylbenzoyl)-D-alanine, pentyl ester; and Octanoic acid, ethyl ester], aldehyde (benzaldehyde, 3-ethyl, and nonanal), and phenol [2-(1,1-dimethylethyl)-6-(1-methylethyl) phenol]. The analysis of carotenoid contents identified 68 carotenoids and we report for the first-time significant contents of zeaxanthin palmitate and (E/Z)-phytoene in mango fruits. α-carotene was a further major contributor to carotene contents with lesser contributions from 5,6epoxy-lutein-caprate-palmitate, β-carotene, lutein oleate, and β-cryptoxanthin. What is more, lutein content was significantly decreased in TR vs. MG fruit. RT-qPCR analysis revealed that relative to the MG stage, the expression of carotenogenic genes GGPS, PSY, LCYB, and ZEP was downregulated in TR mango fruit, whereas the transcript levels of PSD, CHYB, and NCED were downregulated. Additionally, the transcription level of some transcription factors (MYB, bHLH, and NAC) was highly correlated with pigment content in the pulp and may be responsible for carotenoid accumulation. The results describe major differences in metabolic pathways during the transition from MG to the TR stage of fruit ripening that are likely to contribute alterations in fruit flavor and provide several associated genes to be further studied in mango fruit.

Background:Streptococcus pneumoniae is an important human pathogen that can cause severe invasive pneumococcal diseases (IPDs). The aim of this multicenter study was to investigate the serotype and sequence type (ST) distribution, antimicrobial susceptibility, and virulence of S. pneumoniae strains causing IPD in China.Methods: A total of 300 invasive S. pneumoniae isolates were included in this study. The serotype, ST, and antimicrobial susceptibility of the strains, were determined by the Quellung reaction, multi-locus sequence typing (MLST) and broth microdilution method, respectively. The virulence level of the strains in the most prevalent serotypes was evaluated by a mouse sepsis model, and the expression level of well-known virulence genes was measured by RT-PCR.Results: The most common serotypes in this study were 23F, 19A, 19F, 3, and 14. The serotype coverages of PCV7, PCV10, PCV13, and PPV23 vaccines on the strain collection were 42.3, 45.3, 73.3 and 79.3%, respectively. The most common STs were ST320, ST81, ST271, ST876, and ST3173. All strains were susceptible to ertapenem, levofloxacin, moxifloxacin, linezolid, and vancomycin, but a very high proportion (>95%) was resistant to macrolides and clindamycin. Based on the oral, meningitis and non-meningitis breakpoints, penicillin non-susceptible Streptococcus pneumoniae (PNSP) accounted for 67.7, 67.7 and 4.3% of the isolates, respectively. Serotype 3 strains were characterized by high virulence levels and low antimicrobial-resistance rates, while strains of serotypes 23F, 19F, 19A, and 14, exhibited low virulence and high resistance rates to antibiotics. Capsular polysaccharide and non-capsular virulence factors were collectively responsible for the virulence diversity of S. pneumoniae strains.Conclusion: Our study provides a comprehensive insight into the epidemiology and virulence diversity of S. pneumoniae strains causing IPD in China.

Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA).Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared.Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group.Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.

Abstract Background Color directly affects fruit quality and consumer preference. In fig syconia, the female flower tissue is contained in a receptacle. Anthocyanin pigmentation of this tissue and the peel differs temporally and spatially. A transcriptome study was carried out to elucidate key genes and transcription factors regulating differences in fig coloring. Results Anthocyanins in the female flower tissue were identified mainly as pelargonidin-3-glucoside and cyanidin-3-rutinoside; in the peel, the major anthocyanins were cyanidin 3-O-glucoside and cyanidin-3-rutinoside. Anthocyanin content was significantly higher in the female flower tissue vs. peel before fig ripening, whereas at ripening, the anthocyanin content in the peel was 5.39 times higher than that in the female flower tissue. Light-deprivation treatment strongly inhibited peel, but not female flower tissue, anthocyanin pigmentation. RNA-Seq revealed 522 differentially expressed genes (recruited with criteria log2 ≥ 2 and P

Abstract Background Fig fruit are highly perishable at the tree-ripe (TR) stage. Commercial-ripe (CR) fruit, which are harvested before the TR stage for their postharvest transportability and shelf-life advantage, are inferior to TR fruit in size, color and sugar content. The succulent urn-shaped receptacle, serving as the protective structure and edible part of the fruit, determines fruit quality. Quantitative iTRAQ and RNA-Seq were performed to reveal the differential proteomic and transcriptomic traits of the receptacle at the two harvest stages. Results We identified 1226 proteins, of which 84 differentially abundant proteins (DAPs) were recruited by criteria of abundance fold-change (FC) ≥1.3 and p

To improve welding efficiency, bypass current hot wire plasma arc welding (BC-PAW) was employed to weld Ti-6Al-4V alloy. The influence of process variables on metal transfer behaviour was explored using high-speed camera, and the material properties were investigated by means of different microscopes and mechanical test. The result shows that the weld seam has a good surface finish without welding defects. The main current, bypass current, and wire feeding speed have a significant influence on the metal transfer behaviour, which further influence the grains’ formation in the weld zone. The microstructure of the weld mainly comprises α martensite and the average tensile strength (UTS) of the as-received joint is 986 MPa, which is larger than that obtained using the conventional PAW method. The fracture occurs in the heat-affected zone (HAZ), which shows a typical ductile fracture surface.

The substitution of slag-based geopolymer materials for cement-stabilized macadam in road bases is in line with the demand for green and sustainable development in the transportation industry. Thus, slag/fly-ash-based geopolymer materials were prepared to stabilize macadam of road bases in this study. The mechanical properties, freeze-thaw resistance, and dry shrinkage durability of slag/fly-ash-based stabilized macadam materials were studied to analyze the influence of geopolymer dosage on these properties of stabilized macadam. Microscopic tests such as XRD, FITR, and SEM were carried out to explore the formation mechanism of strength and the characteristic of interface transition zone (ITZ). Results show that the 28 d compressive strength, compressive elastic modulus, and tensile strength of slag/fly-ash-based stabilized macadam increase linearly with the increase of geopolymer content. When the dosage of slag-based geopolymer is 4%, the 7 d unconfined compressive strength of slag/fly-ash-based stabilized macadam reaches 8.76 MPa, and the strength still reaches 14.84 MPa after five freeze-thaw cycles (28 d), which satisfy the application requirements of expressway and first-class highway base (JTG/T F20-2015). The dry shrinkage property of slag/fly-ash-based stabilized macadam is better than that of cement-fly-ash-stabilized macadam. When the amount of geopolymer is 3%, the dry shrinkage strain of slag/fly-ash-based stabilized macadam is 231.2 με, which is smaller than that of cement-fly-ash-stabilized macadam (261.3 με). No obvious porosity around the ITZ was detected, indicating good binding between the geopolymer and the aggregate.

We report a case of hospital-acquired Legionella pneumonia that was detected by metagenomic next-generation sequencing (mNGS) of blood from a 7-year-old girl after umbilical cord blood stem cell transplantation (UCBT) with myelodysplastic syndrome. UCBT is traditionally associated with an increased risk of infection, particularly during the first 3 months after transplantation. Controlling interstitial pneumonia and severe infection is the key to reducing patient mortality from infection. Legionella pneumophila can cause a mild cough to rapidly fatal pneumonia. After mNGS confirmed that the pathogen was L. pneumophila, azithromycin, cefoperazone sulbactam, and posaconazole were used for treatment, and the patient's temperature decreased and remained normal. The details of this case highlight the benefits of the timely use of metagenomic NGS to identify pathogens for the survival of immunocompromised patients.

Monitoring the work cycles of earthmoving excavators is an important aspect of construction productivity assessment. Currently, the most advanced method for the recognition of work cycles is the “Stretching-Bending” Sequential Pattern (SBSP), which is based on fixed-carrier video monitoring (FC-SBSP). However, the application of this method presupposes the availability of preconstructed installation carriers to act as a surveillance camera as well as installed and commissioned surveillance systems that work in tandem with them. Obviously, this method is difficult to apply to projects with no conditions for a monitoring camera installation or which have a short construction time. This highlights the potential application of Unmanned Aerial Vehicle (UAV) remote sensing, which is flexible and mobile. Unfortunately, few studies have been conducted on the application of UAV remote sensing for the work cycle monitoring of earthmoving excavators. This research is necessary because the use of UAV remote sensing for monitoring the work cycles of earthmoving excavators can improve construction productivity and save time and costs, especially in post-disaster reconstruction projects involving harsh construction environments, and emergency projects with short construction periods. In addition, the challenges posed by UAV shaking may have to be taken into account when using the SBSP for UAV remote sensing. To this end, this study used application experiments in which stabilization processing of UAV video data was performed for UAV shaking. The application experimental results show that the work cycle performance of UAV remote-sensing-based SBSP (UAV-SBSP) for UAV video data was 2.45% and 5.36% lower in terms of precision and recall, respectively, without stabilization processing than after stabilization processing. Comparative experiments were also designed to investigate the applicability of the SBSP oriented toward UAV remote sensing. Comparative experimental results show that the same level of performance was obtained for the recognition of work cycles with the UAV-SBSP as compared with the FC-SBSP, demonstrating the good applicability of this method. Therefore, the results of this study show that UAV remote sensing enables effective monitoring of earthmoving excavator work cycles in construction sites where monitoring cameras are not available for installation, and it can be used as an alternative technology to fixed-carrier video monitoring for onsite proximity monitoring.

Counting the number of work cycles per unit of time of earthmoving excavators is essential in order to calculate their productivity in earthmoving projects. The existing methods based on computer vision (CV) find it difficult to recognize the work cycles of earthmoving excavators effectively in long video sequences. Even the most advanced sequential pattern-based approach finds recognition difficult because it has to discern many atomic actions with a similar visual appearance. In this paper, we combine atomic actions with a similar visual appearance to build a stretching–bending sequential pattern (SBSP) containing only “Stretching” and “Bending” atomic actions. These two atomic actions are recognized using a deep learning-based single-shot detector (SSD). The intersection over union (IOU) is used to associate atomic actions to recognize the work cycle. In addition, we consider the impact of reality factors (such as driver misoperation) on work cycle recognition, which has been neglected in existing studies. We propose to use the time required to transform “Stretching” to “Bending” in the work cycle to filter out abnormal work cycles caused by driver misoperation. A case study is used to evaluate the proposed method. The results show that SBSP can effectively recognize the work cycles of earthmoving excavators in real time in long video sequences and has the ability to calculate the productivity of earthmoving excavators accurately.

Target Tracking (TT) is a fundamental application of wireless sensor networks. TT based on received signal strength indication (RSSI) is by far the cheapest and simplest approach, but suffers from a low stability and precision owing to multiple paths, occlusions, and decalibration effects. To address this problem, we propose an innovative TT algorithm, known as the SVM+KF method, which combines the support vector machine (SVM) and an improved Kalman filter (KF). We first use the SVM to obtain an initial estimate of the target’s position based on the RSSI. This enhances the ability of our algorithm to process nonlinear data. We then apply an improved KF to modify this estimated position. Our improved KF adds the threshold value of the innovation update in the traditional KF. This value changes dynamically according to the target speed and network parameters to ensure the stability of the results. Simulations and real experiments in different scenarios demonstrate that our algorithm provides a superior tracking accuracy and stability compared to similar algorithms.

A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, a nonionic surfactant is employed to minimize the nonspecific adsorption of the biosensor, hence enabling cytokine detection (TNF-α and IFN-γ, significant inflammatory cytokines, are used as representatives) in artificial tears (used as a biofluid representative). The experimental results demonstrate that the biosensor very consistently and sensitively detects TNF-α and IFN-γ, with limits of detection down to 2.75 and 2.89 pM, respectively. The biosensor, which undergoes large deformations, can thus potentially provide a consistent and sensitive detection of cytokines in the human body.

Effective video monitoring systems require optimization of camera and road network coverage, to exploit fully the hardware and software solutions in smart city traffic applications. Monitoring requirements have grown increasingly diverse as scenes are becoming increasingly complex, thereby transforming the camera and road network coverage optimization issue into a nonlinear, high-dimension, and multi-objective problem. Previous research on this topic however, has focused on a single, specific optimization objective, which may result in invalid optimization results in actual applications. To extend this research, we propose a multi-objective scheduling optimization algorithm for a camera network that addresses the problem of directional road network coverage. In this solution, we incorporate an expanding parameter of main optical axes into particle swarm optimization algorithm. Our new strategy divides the range of main optical axes of all the cameras to control the scheduling number, achieving collaborative optimization of multiple objectives. In a simulated camera and road network, an experiment was designed for evaluating the effectiveness of the proposed method, comparing the distribution of optimization results with the global and local optimal solutions of the true value. A second experiment compared the distribution, performance and running time of the optimization results with different values of expanding parameter of main optical axes. A third experiment compared the performance of the optimization solutions with different values of camera parameters. The results showed that the proposed method can adapt to user application preference, and is effective and robust to schedule and allocate monitoring resources in different scenarios.

Combined metabolomic and transcriptomic analyses were carried out with fig cultivar Green Peel and its color mutant “Purple Peel.” Five and twenty-two metabolites were identified as having significantly different contents between fruit peels of the two cultivars at young and mature stages, respectively. Cyanidin O-malonylhexoside demonstrated a 3,992-fold increase in the mature purple peel, the first identification of a major cyanidin in fig fruit; cyanidin 3-O-glucoside, cyanidin O-malonylhexoside O-hexoside and cyanidin-3,5-O-diglucoside were upregulated 100-fold, revealing the anthocyanins underlying the purple mutation. Beyond the visible differences, there was very significant accumulation of the colorless flavonoids procyanidin B1, luteolin-3′,7-di-O-glucoside, epicatechin and quercetin-3-O-rhamnoside in the mature “Purple Peel” compared to “Green Peel.” At the young stage, only cyanidin O-malonylhexoside, cyanidin O-malonylhexoside O-hexoside and esculetin were upregulated a few fold in the mutant. Transcriptome analysis revealed a downregulated expression trend of genes encoding phenylpropanoid and flavonoid biosynthetic pathway enzyme in the young “Purple Peel” compared to the young “Green Peel,” whereas significant and simultaneous upregulation was revealed in almost all of the flavonoid and anthocyanin pathway components and relevant transcription factors in the mature-stage mutant. The role of R2R3-MYB transcription factors in the color morph mutation and its possible relation to the activity of retrotransposons are discussed. Moreover, large-scale upregulation of small heat-shock protein genes was found in the mature mutant. This is the first work to reveal comprehensive metabolome and transcriptome network changes underlying a fig mutation in a single horticultural attribute, and its profound effects on fruit nutrition and quality.

Micromagnetic simulations have been performed to investigate the write position shifts in heat-assisted magnetic recording (HAMR) under variation of variables including the thermal profile, write field magnitude, head velocity, media damping, and write field rise time. Simulations reveal that a larger head velocity or a larger media damping tends to shift the write positions towards the heat center. Simulation results are also compared to the predictions of an analytical model based on classical mean-field theory. It is found that, with smaller thermal gradients the analytical model tends to give write positions closer to the heat center; whereas when thermal gradients are larger it tends to shift the write positions away from the heat center. All these effects appear to be dynamic, and can be understood by recognizing the lag between spin temperature and lattice temperature that cannot be captured by the analytical model that assumes equilibrium at all times.

Connected and automated vehicle (CAV) has become an increasingly popular topic recently. As an application, Cooperative Adaptive Cruise Control (CACC) systems are of high interest, allowing CAVs to communicate with each other and coordinating their maneuvers to form platoons, where one vehicle follows another with a constant velocity and/or time headway. In this study, we propose a novel CACC system, where distributed consensus algorithm and protocol are designed for platoon formation, merging maneuvers, and splitting maneuvers. Predecessor following information flow topology is adopted for the system, where each vehicle only communicates with its following vehicle to reach consensus of the whole platoon, making the vehicle-to-vehicle (V2V) communication fast and accurate. Moreover, different from most studies assuming the type and dynamics of all the vehicles in a platoon to be homogenous, we take into account the length, location of GPS antenna on vehicle, and braking performance of different vehicles. A simulation study has been conducted under scenarios including normal platoon formation, platoon restoration from disturbances, and merging and splitting maneuvers. We have also carried out a sensitivity analysis on the distributed consensus algorithm, investigating the effect of the damping gain on convergence rate, driving comfort, and driving safety of the system.

Visual coverage is one of the most important quality indexes for depicting the usability of an individual camera or camera network. It is the basis for camera network deployment, placement, coverage-enhancement, planning, etc. Precision and efficiency are critical influences on applications, especially those involving several cameras. This paper proposes a new method to efficiently estimate superior camera coverage. First, the geographic area that is covered by the camera and its minimum bounding rectangle (MBR) without considering obstacles is computed using the camera parameters. Second, the MBR is divided into grids using the initial grid size. The status of the four corners of each grid is estimated by a line of sight (LOS) algorithm. If the camera, considering obstacles, covers a corner, the status is represented by 1, otherwise by 0. Consequently, the status of a grid can be represented by a code that is a combination of 0s or 1s. If the code is not homogeneous (not four 0s or four 1s), the grid will be divided into four sub-grids until the sub-grids are divided into a specific maximum level or their codes are homogeneous. Finally, after performing the process above, total camera coverage is estimated according to the size and status of all grids. Experimental results illustrate that the proposed method’s accuracy is determined by the method that divided the coverage area into the smallest grids at the maximum level, while its efficacy is closer to the method that divided the coverage area into the initial grids. It considers both efficiency and accuracy. The initial grid size and maximum level are two critical influences on the proposed method, which can be determined by weighing efficiency and accuracy.