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Orphans are usually adopted by eligible families or raised by the government and organizations mutually. Although their basic needs are taken care of, the absence of parents in life makes orphans face higher risks of mental health problems, such as anxiety and depression, leading to lower levels of self-esteem and happiness. Previous studies have shown that self-control may have an effect on improving self-esteem; thus, it could become a way to protect mental health. Building on the structural equation model, the current study tested the possible effects of self-control on levels of self-esteem and mental problems among Tibetan orphans.Participants were 143 adolescents from age 16 to 22 years (MSelf-control was negatively associated with psychological illness through improved self-esteem. The present study suggested that self-control was a protective factor for the mental health of adolescent orphans through influencing the levels of self-esteem. Limitations and future directions were discussed.

The additive manufacturing of titanium into porous geometries offers a means to generate low-stiffness endosseous implants with a greater surface area to improve osseointegration. In order to optimize pore size in the scaffolds, it is important to first understand the timeline of osseointegration in pre-clinical models. In this work, selective laser melting was used to produce gyroid-based scaffolds with a uniform pore size of 300 μm or functionally-graded pore size from 600 μm to 300 μm before implantation in New Zealand white rabbit tibiae for 4 and 12 weeks. Initialin vitroassessment with Saos-2 cells showed favourable cell proliferation at pore sizes of 300 and 600 μm. At four weeks, histological observations indicated some residual inflammation alongside neovessel infiltration into the scaffold interior and some early apposition of mineralized bone tissue. At twelve weeks, both scaffolds were filled with a mixture of adipocyte-rich marrow, micro-capillaries, and mineralized bone tissue. X-ray microcomputed tomography showed a higher bone volume fraction (BV/TV) and percentage of bone-implant contact (BIC) in the implants with 300 μm pores than in the functionally-graded specimens, indicating that these smaller pore sizes may be favourable for osseointegration in leporine bone.Graphical Abstract

Autism spectrum disorder (ASD) is a collection of atypical neurodevelopmental conditions characterised by social communication impairments (SCI) and restricted, repetitive behaviours or interests (RRBI), or the autistic dyad. It is worth noting that prior to the release of the Diagnostic and Statistical Manual of Mental Disorders fifth edition, DSM-5, SCI used to include two symptom dimensions: social impairments (SI) and communication impairments (CI), which constituted the autistic triad in earlier studies (American Psychiatric Association, 2013). While a clinical diagnosis of ASD typically requires the manifestation of all autistic symptom dimensions, they often do not co-occur. In fact, ASD can be considered as the quantitative extremes of the more general autistic trait (AST) and they share the same aetiology (Robinson et al., 2011). As a quantitative trait, AST carries an even higher degree of phenotypic heterogeneity. For example, population-based data from the Twins Early Development Study (TEDS) showed that 10% of children (n=6,807) manifested one symptom dimension of the autistic triad; while 0.7% showed symptoms in all three dimensions (Happé & Ronald, 2008). Hence it was not surprising for researchers to identify only modest correlations among the AST dimensions (Ronald, Happé, Price, et al., 2006). Specifically, the phenotypic correlations between parent-rated SI and CI, SI and RRBI, CI and RRBI were only 0.34, 0.23, and 0.38, respectively (Ronald, Happé, Bolton, et al., 2006). This result was replicated by Recruitment of the Western Australian Pregnancy Cohort (Raine) Study and the Child and Adolescent Twin Study in Sweden (CATSS) (Taylor et al., 2017; Whitehouse et al., 2011). However, the developmental pattern of the AST dimension correlations at each age from childhood to adulthood is unclear. That is, whether the correlations get stronger, weaker, or remain the same with age. The Raine study looked at this issue and reported phenotypic correlations between the social and non-social dimensions at ages 2 and 19 of 0.42 and 0.26 for males and 0.31 and 0.25 for females (Whitehouse et al., 2011). Nevertheless, it is worth noting that Raine used caregiver-report data at age 2 but cohort self-report data at age 19, suggesting potential bias induced by different raters when comparing the dimension correlations at different ages. Thus, more systematic analyses with the same rater’s ratings at all ages are needed. Furthermore, three other issues are worth noting: at each age, whether females and males both show modest phenotypic correlations between AST symptom dimensions, whether different raters generate similar correlation results, and whether the quantitative extremes of the AST distribution have similar correlation results to the whole distribution. Previous studies have provided some evidence in answering these questions. A study showed significantly higher phenotypic correlations among SI, CI, and RRBI for males compared to females at age 8 (Ronald, Happé, Price, et al., 2006). The same study also found the dimension correlations higher for the top 5% quantitative extremes (Ronald, Happé, Price, et al., 2006). However, it is unclear whether these findings hold true at other ages and no previous studies have systematically examined the AST dimension correlations across raters. To sum up, the proposed study will investigate how AST symptom dimensions (i.e., SCI and RRBI) correlate at each age from childhood to adulthood as well as to compare the dimension correlation results for females and males, among different raters, and across levels of severity. The proposed study focuses on phenotypic correlations among AST symptom dimensions at each age and for different raters; future work will conduct analogous twin analyses to understand the genetic and environmental underpinnings of these phenotypic correlations.

Yang Yang1,2 *, Yujing Lin1,2 *, Ruogu Xu,1,2 Zhengchuan Zhang,1,2 Wenyi Zeng,1,2 Qiong Xu,1,2 Feilong Deng1,2 1Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong Xu; Feilong Deng, Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, No. 56, Ling Yuan Xi Road, Guangzhou, 510055, People’s Republic of China, Tel +86 20 83862537, Fax +86 20 83822807, Email xqiong@mail.sysu.edu.cn; dengfl@mail.sysu.edu.cnBackground and Purpose: In clinical application of dental implants, the functional state of dendritic cells (DCs) has been suggested to have a close relationship with the implant survival rate or speed of osseointegration. Although microscale surfaces have a stable osteogenesis property, they also incline to trigger unfavorable DCs activation and threaten the osseointegration process. Nanoscale structures have an advantage in regulating cell immune response through orchestrating cell adhesion, indicating the potential of hierarchical micro/nanostructured surface in regulation of DCs’ activation without sacrificing the advantage of microscale topography.Materials and Methods: Two micro/nanostructures were fabricated based on microscale rough surfaces through anodization or alkali treatment, the sand-blasted and acid-etched (SA) surface served as control. The surface characteristics, in vitro and in vivo DC immune reactions and β 2 integrin-FAK signal expression were systematically investigated. The DC responses to different surface topographies after FAK inhibition were also tested.Results: Both micro/nano-modified surfaces exhibited unique composite structures, with higher hydrophilicity and lower roughness compared to the SA surface. The DCs showed relatively immature functional states with round morphologies and significantly downregulated β 2 integrin-FAK levels on micro/nanostructures. Implant surfaces with micro/nano-topographies also triggered lower levels of DC inflammatory responses than SA surfaces in vivo. The inhibited FAK activation effectively reduced the differences in topography-caused DC activation and narrowed the differences in DC activation among the three groups.Conclusion: Compared to the SA surface with solely micro-scale topography, titanium surfaces with hybrid micro/nano-topographies reduced DC inflammatory response by influencing their adhesion states. This regulatory effect was accompanied by the modulation of β 2 integrin-FAK signal expression. The β 2 integrin-FAK-mediated adhesion plays a critical role in topography-induced DC activation, which represents a potential target for material–cell interaction regulation.Graphical Abstract: Keywords: micro/nanostructure, dendritic cell, osteoimmunology, β 2 integrin-FAK signal, surface modification

Background: Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth.Methods: This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed. Results: There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08–1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94–6.30) predicted small nodule interval growth.Conclusions: We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.

Correction for ‘Micro/nano-net guides M2-pattern macrophage cytoskeleton distribution via Src–ROCK signalling for enhanced angiogenesis’ by Yang Yang et al., Biomater. Sci., 2021, DOI: 10.1039/d1bm00116g.

Implant surface topography has been proven to determine the fate of adhered macrophage polarization, which is closely related to the cytoskeletal arrangement during adhesion. Our purpose was to establish a topography that is favourable to M2 macrophage switching by regulating macrophage cytoskeleton distribution. Two micro/nano-net structures with different pore sizes were generated by alkali bathing at medium (SAM) or high (SAH) temperature based on the micro-level surface. Their surface characteristics, in vitro macrophage polarization and impact on endothelial cells were analysed. The in vivo macrophage response and osseointegration were also tested. The results showed that the micro/nano-net has high hydrophilicity and moderate roughness. In the SAH and SAM groups, macrophages exhibited an elongated cytoskeleton with tiny protrusions and had a high M2/M1 polarization ratio with enhanced angiogenic ability, and in vivo studies also showed faster angiogenesis and bone formation in these groups. SAH showed even better results than SAM. For cytoskeleton related pathway explanation, ROCK expression was upregulated and Src expression was downregulated at the early or late adhesion stage in both the SAH and SAM groups. These results indicated that the micro/nano-net structure guides elongated macrophage adhesion states via Src-ROCK signalling and switches macrophages towards the M2 phenotype, which provides a cytoskeleton-oriented topography design for an ideal immune response.

The survival rate of esophageal squamous carcinoma (ESCC) after surgical resection is estimated to be only 30.3% due to the difficulty in identifying microinfiltration and subtle metastases. In this study, we explored the value of near-infrared fluorescence in the second window (NIR-II) using an epidermal growth factor receptor (EGFR)-targeted probe (cetuximab-IR800) for the intraoperative navigation of ESCC in xenograft mouse models. Immunohistochemical results showed that EGFR was aberrantly expressed in 94.49% (120/127) of ESCC tissues and 90.63% (58/64) of metastatic lymph nodes. Western blot results demonstrated that EGFR protein was highly expressed in ESCC cell lines. Flow cytometry data revealed that cetuximab-IR800 showed a stronger binding specificity in EGFR-positive KYSE-30 cells than in A2780 control cells (

Flavor-imparting volatile chemicals accumulate as fruits ripen, making major contributions to taste. The NAC transcription factor nonripening (NAC-NOR) and DNA demethylase 2 (SlDML2) are essential for tomato fruit ripening, but details of the potential roles and the relationship between these two regulators in the synthesis of volatiles are lacking. Here, we show substantial reductions in fatty acid and carotenoid-derived volatiles in tomato slnor and sldml2 mutants. An unexpected finding is the redundancy and divergence in volatile profiles, biosynthetic gene expression, and DNA methylation in slnor and sldml2 mutants relative to wild-type tomato fruit. Reduced transcript levels are accompanied by hypermethylation of promoters, including the NAC-NOR target gene lipoxygenase (SlLOXC) that is involved in fatty acid-derived volatile synthesis. Interestingly, NAC-NOR activates SlDML2 expression by directly binding to its promoter both in vitro and in vivo. Meanwhile, reduced NAC-NOR expression in the sldml2 mutant is accompanied by hypermethylation of its promoter. These results reveal a relationship between SlDML2-mediated DNA demethylation and NAC-NOR during tomato fruit ripening. In addition to providing new insights into the metabolic modulation of flavor volatiles, the outcome of our study contributes to understanding the genetics and control of fruit ripening and quality attributes in tomato.

Ice accretion on aircraft wings due to Supercooled Large Droplet (SLD) have a significant impact on flight safety. The dynamic behaviours of large droplet, such as deformation, breakup and splashing, have significant effects on icing accretion. The corresponding studies have been carried out experimentally and numerically, and empirical models to predict the dynamic behaviours of large droplets have been proposed. However, few empirical models involve surface roughness effects, especially its effects on the secondary droplets during icing accretion. In this paper, an experimental investigation on the impact of droplets onto surfaces with different roughness was conducted by using the high-speed Digital Inline Holography (DIH). The rapid splashing processes of droplets with Weber number around 570 and Mundo impact parameter K around 240 were captured and reconstructed based on a wavelet-based algorithm. Results show that DIH is suitable to diagnose the secondary droplets with a wide size range and record their velocities and locations. The roughness of the impact surface has a positive effect on the dynamics of splashing droplets, and the parameters including diameter, velocity, splash angle, splash height and mass-loss rate of splashing droplets rise with the increase of roughness. The new empirical correlations of the splashing characteristics of secondary droplets were fitted and developed, which could be used to update the current icing simulation models by taking into account the effect of impact surface roughness on large droplets dynamics. This fundamental study may also be applied to the industrial applications including wind turbine icing, inkjets, sprays, as well as the erosion and formation of ice layers.

Jijin Yao,1,2,* Ying Wang,3,* Yujing Lin,4 Yingying Yang,5 Jingjing Wan,3 Xiaohua Gong,1 Fanwei Zhang,3 Wangjian Zhang,6 Tia Marks,7 Siyang Wang,1 Hongjun Jin,2 Hong Shan2,8 1The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 3Department of Nuclear Medicine, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 4Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, 519001, People’s Republic of China; 5Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China; 6Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, 12144, USA; 8Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongjun JinGuangdong Provincial Key Laboratory of Biomedical Imaging, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of ChinaEmail jinhj3@mail.sysu.edu.cnHong ShanDepartment of Interventional Medicine, Guangdong Provincial Key Laboratory of Biomedical Imaging, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, People’s Republic of ChinaEmail shanhong@mail.sysu.edu.cnIntroduction: To evaluate the role of maximal standardized uptake values (SUVmax) and total lesion glycolysis (TLG) from serial 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for early prediction of neoadjuvant chemotherapy (NAC) response in locoregionally advanced nasopharyngeal carcinoma (LANPC).Methods: A total of 121 LANPC patients who completed pretreatment 18F-FDG PET/CT between June 2017 and July 2020 were retrospectively included. The median age of all the participants was 50 years old (range: 19– 74 years), with 94 (77.7%) males and 27 (22.3%) females. The SUVmax from the primary tumor site (SUVmax-PT) and the total lesion glycolysis from the primary tumor site (TLG-PT) were recorded. Tumor response was calculated according to the Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 Criteria at two-week post-secondary NAC cycle. Patients who achieved an objectively partial or full reaction after two cycles of NAC were defined as ‘responders’, and patients who obtained stability or progression were classified as ‘non-responders’.Results: After two cycles of NAC, 96 patients were categorized as “responders” and 25 patients as “non-responders”. The optimal thresholds of the SUVmax-PT were 11.8 and 38.5 for the TLG-PT. Non-responders were significantly associated with high SUVmax-PT (HR, 3.49; 95% CI, 1.17– 10.36; p = 0.024) and TLG-PT (HR, 4.45; 95% CI, 1.44– 13.78; p = 0.010) in multivariate analysis. Recursive partitioning analysis (RPA) categorized patients into three prognostic groups based on SUVmax-PT and TLG-PT: high-response group, intermediate-response group, and low-response group, with corresponding favorable response rates of 94%, 80%, and 55%, respectively. Moreover, a nomogram was created based on metabolic parameters that precisely projected an individual’s response of NAC (C-index, 0.787; 95% CI, 0.533– 1.000).Conclusion: Pretreatment 18F-FDG PET/CT to measure SUVmax-PT and TLG-PT could be a useful non-invasive method for early indication of NAC efficacy. The nomogram based on PET/CT parameters may potentially provide direction for treatment decisions based on NAC levels.Keywords: nasopharyngeal carcinoma, neoadjuvant chemotherapy, tumor response, PET/CT, nomogram

A novel tetraploid S. spontaneum with basic chromosome x = 10 was discovered, providing us insights in the origin and evolution in Saccharum species. Sugarcane (Saccharum spp., Poaceae) is a leading crop for sugar production providing 80% of the world's sugar. However, the genetic and genomic complexities of this crop such as its high polyploidy level and highly variable chromosome numbers have significantly hindered the studies in deciphering the genomic structure and evolution of sugarcane. Here, we developed the first set of oligonucleotide (oligo)-based probes based on the S. spontaneum genome (x = 8), which can be used to simultaneously distinguish each of the 64 chromosomes of octaploid S. spontaneum SES208 (2n = 8x = 64) through fluorescence in situ hybridization (FISH). By comparative FISH assay, we confirmed the chromosomal rearrangements of S. spontaneum (x = 8) and S. officinarum (2n = 8x = 80), the main contributors of modern sugarcane cultivars. In addition, we examined a S. spontaneum accession, Np-X, with 2n = 40 chromosomes, and we found that it was a tetraploid with the unusual basic chromosome number of x = 10. Assays at the cytological and DNA levels demonstrated its close relationship with S. spontaneum with basic chromosome number x = 8 (the most common accessions in S. spontaneum), confirming its S. spontaneum identity. Population genetic structure and phylogenetic relationship analyses between Np-X and 64 S. spontaneum accessions revealed that Np-X belongs to the ancient Pan-Malaysia group, indicating a close relationship to S. spontaneum with basic chromosome number of x = 8. This finding of a tetraploid S. spontaneum with basic chromosome number of x = 10 suggested a parallel evolution path of genomes and polyploid series in S. spontaneum with different basic chromosome numbers.

Hepatocellular carcinoma (HCC) is always accompanied by persistent inflammation of liver tissues, which is considered to exert protumourigenic effects by promoting cancer growth, progression, and metastasis. However, the tumour-promoting roles and predictive value of intratumoural inflammatory cytokines remain unclear. In the present study, we used database analysis, clinical pathological studies, and in vitro biological experiments on human hepatic cancer cell lines to assess the prognostic potential of the primary tumour cytokine mRNA levels and underlying mechanisms in HCC. First, we assessed the prognostic value of several cytokines from the TCGA database and found that IL-8 is a unique cytokine that is associated with poor overall survival of HCC patients. Then, we collected 87 HCC tumour and adjacent non-tumour specimens from patients and confirmed that patients with low IL-8 expression exhibited less intrahepatic invasion or distant metastasis, a lower recurrence rate and longer overall survival time compared to patients with high IL-8 expression. Wound healing, transwell, and western blotting assay results showed that IL-8 promotes the migration and invasion of Huh-7 and HepG2 cells, and the underlying mechanism is that IL-8 induces the EMT of HCC cells via the IL-8/ERK1/2/SNAI1 and IL-8/STAT3/TWIST1 signalling pathways. These results provide valuable biological IL-8 information which needs to be further investigated in liver cancer target therapy research. Furthermore, the intratumoural cytokine expression at the mRNA level may provide insight into hepatocarcinoma prognosis.

BackgroundInsulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2), as a m6A “reader”, is known to be an oncogene, and its expression is elevated in multiple tumors. However, the role of IGF2PB2 in esophageal squamous cell carcinoma (ESCC) is still unclear. MethodsThis study aims to investigate the role of IGF2PB2 expression in ESCC proliferation, invasion and migration as well as the possible mechanism. IGF2BP2 expression was found to be elevated in ESCC tissues by qRT-PCR, western blotting, and immunohistochemical (IHC) staining. ResultsKnocking down IGF2BP2 expression prevented the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of KYSE450 and TE1 cells. Knocking out IGF2BP2 reduced tumorigenesis in vivo. Overexpression of IGF2BP2 was performed, and it was proven that IGF2BP2 had an oncogenic effect in KYSE450 and TE1 cells. Moreover, LY294002, a highly selective inhibitor of PI3K, reversed the effect of IGF2BP2 overexpression on EMT processes. All these results show that the effects of IGF2BP2 on oncogenesis and EMT were clearly exerted via the PI3K/AKT signaling pathway. ConclusionsIn conclusion, this study demonstrates that the oncogenic function of IGF2BP2 is mediated by the PI3K/AKT signaling pathway and is related to EMT in ESCC. In addition, IGF2BP2 can serve as a diagnostic and oncotherapeutic marker in further studies.

Pancreatic ductal adenocarcinoma (PDAC), a fatal malignant tumour, has a high postoperative recurrence rate, mainly due to the difficulty of discerning occult lesions, including those related to perineural invasion (PNI) and lymph node metastasis (LNM). Cellular mesenchymal-epithelial transition factor (c-Met), an excellent imaging marker, is aberrantly expressed in the majority of PDACs. Thus, we plan to utilize a c-Met-targeted near-infrared fluorescent (NIRF) probe for real-time visualization and dissection of PDAC, and corresponding PNI and LNM lesions. Immunohistochemistry showed c-Met expression in PDAC, PNI and LNM reached 94.3% (100/106), 88.3% (53/60), and 71.4% (25/35), respectively, and its expression in PNI and LNM was significantly correlated with that in primary PDAC (r = 0.66, p < 0.0001 and r = 0.44, p < 0.01, respectively). SHRmAb-IR800 was successfully synthesized using an anti-c-Met antibody and a NIRF dye. The in vitro targeting ability of SHRmAb-IR800 was higher in CFPAC1 cells (c-Met positive) than in Miapaca-2 cells (c-Met negative) (p < 0.05). In vivo NIRF imaging of CFPAC1 subcutaneous tumours demonstrated higher accumulation of SHRmAb-IR800 than the control probe (p < 0.05). The signal-to-background ratio (TBR) of an orthotopic PDAC tumour was 3.38 ± 0.46, and imaging with SHRmAb-IR800 facilitated the resection of metastatic lesions with sensitivity and specificity values of 93.3% (56/60) and 87.1% (27/31), respectively. Furthermore, tiny PNI and LNM lesions in xenograft models were detected by NIRF imaging, with TBRs measuring 2.59 ± 0.19 and 2.88 ± 0.72, respectively. Therefore, the clinical translation of this probe might shed new light on NIRF-guided pancreatectomy and improve the surgical prognosis of PDAC patients.

Surface imperfections due to manufacturing tolerance, such as steps, gaps, and waviness, can cause early boundary layer transition, thus reduce the practicability of the natural laminar flow (NLF) technology for aircraft drag reduction. In this study, a new numerical methodology is proposed and implemented to predict the effect of backward-facing step (BFS) and forward-facing step (BFS) on boundary layer transition over NLF aircraft body. The method is based on a hypothesis that the effect of surface imperfections on boundary layer flow can be mimicked as that of surface roughness due to the relevant small size of the imperfection compared to the local boundary layer thickness. The predicted transition location on BFS/FFS surface agrees very well with the experimental validation data. It implies the applicability and capability of this approach for transition location prediction over more general surface imperfection arrangements. The study thus provides an efficient, practical prediction tool to determine the manufacturing allowance on surface imperfection dimension on NLF body for aerodynamic engineers.

An accurate computation of near-field unsteady turbulent flow around aerofoil is of outstanding importance for aerofoil trailing edge noise source prediction, which is a representative of main contributor to airframe noise and fan noise in modern commercial aircraft. In this study, an embedded large eddy simulation (ELES) is fully implemented in a separation-induced transitional flow over NACA0012 aerofoil at a moderate Reynolds number. It aims to evaluate the performance of the ELES method in aerodynamics simulation for wall-bounded aerospace flow in terms of accuracy, computational cost and complexity of implementation. Some good practice is presented including the special treatments at RANS-LES interface to provide more realistic turbulence generation in LES inflow. A comprehensive validation of the ELES results is performed by comparing with the experimental data and the wall-resolved large eddy simulation results. It is concluded that the ELES method could provide sufficient accuracy in the transitional flow simulations around aerofoil. It is proved to be a promising alternative to the pure LES for industrial flow applications involving wall boundary layer due to its significant computational efficiency.

The postoperative survival of esophageal squamous cell carcinoma (eSCC) is notably hindered by cancer recurrence due to difficulty in identifying occult metastases. Cellular mesenchymal-epithelial transition factor (c-Met), which is highly expressed in different cancers, including eSCC, has become a target for the development of imaging probes and therapeutic antibodies. In this study, we synthesized an optical probe (SHRmAb-IR800) containing a near-infrared fluorescence (NIRF) dye and c-Met antibody, which may help in NIRF-guided resection of micrometastases derived from eSCC. Cellular uptake of SHRmAb-IR800 was assessed by flow cytometry and confocal microscopy. In vivo accumulation of SHRmAb-IR800 and the potential application of NIRF-guided surgery were evaluated in eSCC xenograft tumor models. c-Met expression in human eSCC samples and lymph node metastases (LNMs) was analyzed via immunohistochemistry (IHC). Cellular accumulation of SHRmAb-IR800 was higher in c-Met-positive EC109 eSCC cells than in c-Met-negative A2780 cells. Infusion of SHRmAb-IR800 produced higher fluorescence intensity and a higher tumor-to-background ratio (TBR) than the control probe in EC109 subcutaneous tumors (P 0.05). The TBRs of orthotopic EC109 tumors and LNMs were 3.01 ± 0.17 and 2.77 ± 0.56, respectively. The sensitivity and specificity of NIRF-guided resection of metastases derived from orthotopic cancers were 92.00% and 89.74%, respectively. IHC results demonstrated positive staining in 97.64% (124/127) of eSCC samples and 91.67% (55/60) of LNMs. Notably, increased c-Met expression was observed in LNMs compared to normal lymph nodes (P 0.0001). Taken together, the results of this study indicated that SHRmAb-IR800 facilitated the resection of micrometastases of eSCC in the xenograft tumor model. This c-Met-targeted probe possesses translational potential in NIRF-guided surgery due to the high positive rate of c-Met protein in human eSCCs.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a poor 5-year survival rate of approximately 6%, mostly due to poor treatment response and early progression. The S100 gene family participates in various pathophysiological processes in various malignancies. S100A16 is a member of the S100 family, which is abnormally expressed in PDAC; however, its biological functions and mechanisms of action remain unclear. We analysed the Gene Expression Omnibus (GEO) public database and the gene ChIP data collected in our previous study of human PDAC cell line PANC-1 cocultured with M2 macrophages to identify differentially expressed genes (DEGs). Twenty-three overexpressed genes were identified by screening. Then, the selected genes were analysed using The Cancer Genome Atlas (TCGA) database to assess whether they have significant impact on the overall survival (OS) of PDAC patients. Of the 14 DEGs identified, S100A16 was associated with poor prognosis and was selected for further investigation; the results indicate that S100A16 is positively correlated with epithelial-mesenchymal transition (EMT)-related genes in the TCGA dataset. Subsequent in vitro and in vivo experiments demonstrated that S100A16 induces the EMT to promote the metastasis of human PDAC cells and that the effect is mediated by the enhanced expression of TWIST1 and activation of the STAT3 signalling pathway. The antitumour effect of gemcitabine (GEM) was enhanced in combination with S100A16 downregulation. In conclusion, our findings suggest that S100A16 is a novel potential therapeutic target for human PDAC treatment.

Gene expression features that are valuable for pancreatic ductal adenocarcinoma (PDAC) prognosis are still largely unknown. We aimed to explore pivotal molecular signatures for PDAC progression and establish an efficient survival score to predict PDAC prognosis. Overall, 163 overlapping genes were identified from three statistical methods, including differentially expressed genes (DEGs), coexpression network analysis (WGCNA), and target genes for miRNAs that were significantly related to PDAC patients’ overall survival (OS). Then, according to the optimal value of the cross-validation curve (lambda = 0.031), 7 non-zero coefficients (ARNTL2, DSG3, PTPRR, ANLN, S100A14, ANKRD22, and TSPAN7) were selected to establish a prognostic prediction model of PDAC patients. We further confirmed the expression level of 7 genes using RT-PCR, western blot, and immunohistochemistry staining in PDAC patients’ tissues. Our results showed that the ROC curve of the 7-mRNA model indicated good predictive ability for 1- and 2-year OS in three datasets (TCGA: 0.71, 0.69; ICGC: 0.8, 0.74; GEO batch: 0.61, 0.7, respectively). The hazard ratio (HR) of the low-risk group had a similar significant result (TCGA: HR = 0.3723; ICGC: HR = 0.2813; GEO batch: HR = 0.4999; all P < 0.001). Furthermore, Log-rank test results in three cohorts showed that the 7-mRNA assay excellently predicted the prognosis and metastasis, especially in TNM stage I&II subgroups of PDAC. In conclusion, the strong validation of our 7-mRNA signature indicates the promising effectiveness of its clinical application, especially in patients with TNM stages I&II.

A novel surface finish process sequence has been developed with a sequential process employing sol-gel (SG) semi-fixed abrasive polishing tool and gas-liquid assisted chemical mechanical polishing (GLA-CMP) instead of general copper-resin lap or plate (CP) and chemical mechanical polishing (CMP) to enhance the surface finishing efficiency for sapphire wafer. The surface and subsurface quality of sapphire wafer after the SG and GLA-CMP process have been compared with those by CP and CMP, respectively. Results show that the SG polishing can offer a better surface quality in terms of both surface roughness and sub-surface damage for the next fine polishing step. Based on the contact mechanics models, yielding effects of the SG polishing pad are found to be effective to scratch mitigation. This trend is consistent with experimental results. Furthermore, oxygen is applied as catalyst to improve the removal material rate (MRR) of sapphire by GLA-CMP. It is found that oxygen concentration can improve MRR of sapphire polishing. Among four combinations of CP, SG, CMP, and GLA-CMP, the machining by coupling SG and GLA-CMP shows the maximum MRR approximately as high as 77.6 nm/min, more than 10.23% larger than that of CP-machined wafer and traditional CMP. Ultra-smooth wafer surface with damage-free can be achieved by this new process sequence and the sapphire wafer with qualified surface can be obtained within 50 min by GLA-CMP, which is 90 min shorter than the original 140 min polished by the conventional CMP method. Compared to the conventional surface finish process sequence, the proposed sequence shows superior processing efficiency and quality for sapphire wafers.

Brachypodium distachyon, a new monocotyledonous model plant, has received wide attention in biological research due to its small genome and numerous genetic resources. Codon usage bias is an important feature of genes and genomes, and it can be used in transgenic and evolutionary studies. In this study, the nucleotide compositions and patterns of codon usage bias were calculated using Codon W. Additionally, an ENC plot, Parity rule 2 and correspondence analyses were used to explore the major factors influencing codon usage bias patterns. The numbers of hydrogen bonds and skews were used to analyze the GC trend in the 5′-ends of the coding sequences. The results showed that minor differences in the codon usage bias patterns were revealed by the ENC plot, Parity rule 2 and correspondence analyses. The analyses of the CG-skew and the number of hydrogen bonds showed a declining trend in the number of cytosines at the 5′-ends of the CDSs (from the 5′-ends to the 3′-ends), indicating that GC may play a major role in codon usage bias. In addition, our results laid a foundation for the study of codon usage bias patterns in Brachypodium genus and suggested that the GC plays a major role in determining these patterns.

Perifolliculitis capitis abscedens et suffodiens (PCAS), also known as dissecting cellulitis of the scalp (DCS), is a rare, chronic, suppurative inflammatory disease of the scalp which may evolve into cicatricial alopecia. Its refractory nature has a detrimental impact on patients' quality of life. Here, we report five cases of PCAS treated with 5% 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT), prior to which different methods of surgical intervention were given. The surgical interventions were under local anesthesia. In general, all surgical interventions, pretreatments and PDT were well tolerated. 4 patients showed complete clearance of lesions and 1 patient attained significant improvement of symptoms 1 month after treatment. This suggested that surgical interventions, combined with topical ALA-PDT could be an effective, minimally-invasive, and safe alternative for PCAS, especially for cases recalcitrant to other conventional therapies.

Matrix metalloproteinase‑1 (MMP1) participates in the metastasis of pancreatic cancer, and its expression can be regulated by endogenous microRNAs (miRs/miRNAs) and exogenous inflammatory factors. Whether miRNAs that potentially modulate MMP1 expression can also attenuate the pro‑metastatic effects of its inducer on pancreatic cancer is yet to be completely elucidated. In the present study, a systematic analysis including in silico and bioinformatics analyses, a luciferase reporter assay and an RNA electrophoretic mobility shift assay (EMSA), were used to investigate the interaction between miRNAs and MMP1 mRNA. In addition, wound‑healing assays, Transwell assays and xenograft nude mouse models were implemented to investigate the antitumor activities exerted by candidate miRNAs. As a result, hsa‑miR‑623 was screened as a candidate miRNA that interacts with the MMP1 transcript, and an inverse correlation between the expression of hsa‑miR‑623 and MMP1 was observed in human pancreatic cancer tissue samples. The EMSA confirmed that hsa‑miR‑623 was able to directly bind to its cognate target within the 3'‑untranslated region of the MMP1 transcript. In addition, transfection of hsa‑miR‑623 mimics into PANC‑1 and BXPC‑3 cell lines markedly inhibited the expression of MMP1 at the mRNA and protein levels, and attenuated IL‑8‑induced MMP1 expression. hsa‑miR‑623 also decreased IL‑8‑induced epithelial‑mesenchymal transition in PANC‑1 and BXPC‑3 cells via the underlying mechanism of inhibition of ERK phosphorylation. Consequently, hsa‑miR‑623 inhibited pancreatic cancer cell migration and invasion in vitro and metastasis in vivo. The results of the present study suggest that hsa‑miR‑623 represents a novel adjuvant therapeutic target to prevent metastasis in pancreatic cancer.

In recent years, the LDPC decoder based on stochastic calculation has been becoming a hot topic, and the re-randomization structure based on edge memory for the stochastic LDPC decoder shows great advantages over performance and complexity compared with the traditional decoders. However, latching issue is also the main challenge for the stochastic LDPC decoders with edge memory structure, similar to stochastic LDPC decoders with other structures. Frequent latching state results in a low information updating efficiency, which reduces decoding performance and convergence speed. In order to speed up the information updating efficiency of the stochastic decoder, in this paper, we propose a dual memory parallel update structure for edge memory. Based on the proposed structure, the efficiency of information convergence is greatly accelerated with acceptable hardware cost. And the decoding performance and latency are also improved.